Carrel name: keyword-dna-cord Creating study carrel named keyword-dna-cord Initializing database file: cache/cord-000049-rl7sdzd7.json key: cord-000049-rl7sdzd7 authors: Lee, David; La Mura, Maurizio; Allnutt, Theo R; Powell, Wayne title: Detection of genetically modified organisms (GMOs) using isothermal amplification of target DNA sequences date: 2009-02-02 journal: BMC Biotechnol DOI: 10.1186/1472-6750-9-7 sha: doc_id: 49 cord_uid: rl7sdzd7 file: cache/cord-000104-3b8b8p61.json key: cord-000104-3b8b8p61 authors: McWhirter, Sarah M.; Barbalat, Roman; Monroe, Kathryn M.; Fontana, Mary F.; Hyodo, Mamoru; Joncker, Nathalie T.; Ishii, Ken J.; Akira, Shizuo; Colonna, Marco; Chen, Zhijian J.; Fitzgerald, Katherine A.; Hayakawa, Yoshihiro; Vance, Russell E. title: A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP date: 2009-08-31 journal: J Exp Med DOI: 10.1084/jem.20082874 sha: doc_id: 104 cord_uid: 3b8b8p61 file: cache/cord-000937-8vk89i4h.json key: cord-000937-8vk89i4h authors: Law, John; Jovel, Juan; Patterson, Jordan; Ford, Glenn; O’keefe, Sandra; Wang, Weiwei; Meng, Bo; Song, Deyong; Zhang, Yong; Tian, Zhijian; Wasilenko, Shawn T.; Rahbari, Mandana; Mitchell, Troy; Jordan, Tracy; Carpenter, Eric; Mason, Andrew L.; Wong, Gane Ka-Shu title: Identification of Hepatotropic Viruses from Plasma Using Deep Sequencing: A Next Generation Diagnostic Tool date: 2013-04-17 journal: PLoS One DOI: 10.1371/journal.pone.0060595 sha: doc_id: 937 cord_uid: 8vk89i4h file: cache/cord-000050-tfcerilc.json key: cord-000050-tfcerilc authors: Rao, Srinivas; Kong, Wing-Pui; Wei, Chih-Jen; Yang, Zhi-Yong; Nason, Martha; Styles, Darrel; DeTolla, Louis J.; Sorrell, Erin M.; Song, Haichen; Wan, Hongquan; Ramirez-Nieto, Gloria C.; Perez, Daniel; Nabel, Gary J. title: Multivalent HA DNA Vaccination Protects against Highly Pathogenic H5N1 Avian Influenza Infection in Chickens and Mice date: 2008-06-18 journal: PLoS One DOI: 10.1371/journal.pone.0002432 sha: doc_id: 50 cord_uid: tfcerilc file: cache/cord-003609-p0ydzjre.json key: cord-003609-p0ydzjre authors: Goodman, Danielle E.; Pretto, Carla D.; Krepostman, Tomas A.; Carnahan, Kelly E.; Spindler, Katherine R. title: Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR) date: 2019-04-23 journal: mBio DOI: 10.1128/mbio.00668-19 sha: doc_id: 3609 cord_uid: p0ydzjre file: cache/cord-000269-v4jochbe.json key: cord-000269-v4jochbe authors: Wittekindt, Nicola E.; Padhi, Abinash; Schuster, Stephan C.; Qi, Ji; Zhao, Fangqing; Tomsho, Lynn P.; Kasson, Lindsay R.; Packard, Michael; Cross, Paul; Poss, Mary title: Nodeomics: Pathogen Detection in Vertebrate Lymph Nodes Using Meta-Transcriptomics date: 2010-10-18 journal: PLoS One DOI: 10.1371/journal.pone.0013432 sha: doc_id: 269 cord_uid: v4jochbe file: cache/cord-000403-vzbh457k.json key: cord-000403-vzbh457k authors: Zhang, Weijun; Lin, Yan; Bai, Yu; Tong, Tiegang; Wang, Qun; Liu, Nihong; Liu, Guangliang; Xiao, Yihong; Yang, Tao; Bu, Zhigao; Tong, Guangzhi; Wu, Donglai title: Identification of CD8(+ )cytotoxic T lymphocyte epitopes from porcine reproductive and respiratory syndrome virus matrix protein in BALB/c mice date: 2011-05-30 journal: Virol J DOI: 10.1186/1743-422x-8-263 sha: doc_id: 403 cord_uid: vzbh457k file: cache/cord-000436-k1hwh640.json key: cord-000436-k1hwh640 authors: Amidi, Maryam; de Raad, Markus; Crommelin, Daan J. A.; Hennink, Wim E.; Mastrobattista, Enrico title: Antigen-expressing immunostimulatory liposomes as a genetically programmable synthetic vaccine date: 2010-10-26 journal: Syst Synth Biol DOI: 10.1007/s11693-010-9066-z sha: doc_id: 436 cord_uid: k1hwh640 file: cache/cord-000293-pc4x5e24.json key: cord-000293-pc4x5e24 authors: Yu, Chien-Hung; Noteborn, Mathieu H. M.; Olsthoorn, René C. L. title: Stimulation of ribosomal frameshifting by antisense LNA date: 2010-08-06 journal: Nucleic Acids Res DOI: 10.1093/nar/gkq650 sha: doc_id: 293 cord_uid: pc4x5e24 file: cache/cord-001761-yvd1n42f.json key: cord-001761-yvd1n42f authors: Yoshimura, Takeo; Suzuki, Takamasa; Mineki, Shigeru; Ohuchi, Shokichi title: Controlled Microwave Heating Accelerates Rolling Circle Amplification date: 2015-09-08 journal: PLoS One DOI: 10.1371/journal.pone.0136532 sha: doc_id: 1761 cord_uid: yvd1n42f file: cache/cord-000012-p56v8wi1.json key: cord-000012-p56v8wi1 authors: Bigot, Yves; Samain, Sylvie; Augé-Gouillou, Corinne; Federici, Brian A title: Molecular evidence for the evolution of ichnoviruses from ascoviruses by symbiogenesis date: 2008-09-18 journal: BMC Evol Biol DOI: 10.1186/1471-2148-8-253 sha: doc_id: 12 cord_uid: p56v8wi1 file: cache/cord-000988-79fp75u3.json key: cord-000988-79fp75u3 authors: Al-Siyabi, Turkiya; Binkhamis, Khalifa; Wilcox, Melanie; Wong, Sallene; Pabbaraju, Kanti; Tellier, Raymond; Hatchette, Todd F; LeBlanc, Jason J title: A cost effective real-time PCR for the detection of adenovirus from viral swabs date: 2013-06-07 journal: Virol J DOI: 10.1186/1743-422x-10-184 sha: doc_id: 988 cord_uid: 79fp75u3 file: cache/cord-000452-1gd006zy.json key: cord-000452-1gd006zy authors: Kim, Y. C.; Jarrahian, C.; Zehrung, D.; Mitragotri, S.; Prausnitz, M. R. title: Delivery Systems for Intradermal Vaccination date: 2011-04-07 journal: Intradermal Immunization DOI: 10.1007/82_2011_123 sha: doc_id: 452 cord_uid: 1gd006zy file: cache/cord-000765-r7y1cqou.json key: cord-000765-r7y1cqou authors: Chang, Yu-Ming; Chen, Cammy K. -M.; Chang, Yuan-Chih; Jeng, Wen-Yih; Hou, Ming-Hon; Wang, Andrew H. -J. title: Functional Studies of ssDNA Binding Ability of MarR Family Protein TcaR from Staphylococcus epidermidis date: 2012-09-21 journal: PLoS One DOI: 10.1371/journal.pone.0045665 sha: doc_id: 765 cord_uid: r7y1cqou file: cache/cord-004561-cer5ifac.json key: cord-004561-cer5ifac authors: Astua-Monge, G.; Lyznik, A.; Jones, V.; Mackenzie, S. A.; Vallejos, C. E. title: Evidence for a prokaryotic insertion-sequence contamination in eukaryotic sequences registered in different databases date: 2002 journal: Theor Appl Genet DOI: 10.1007/s001220200005 sha: doc_id: 4561 cord_uid: cer5ifac file: cache/cord-002441-w731ehtz.json key: cord-002441-w731ehtz authors: Jeon, Young Joo; Park, Jong Ho; Chung, Chin Ha title: Interferon-Stimulated Gene 15 in the Control of Cellular Responses to Genotoxic Stress date: 2017-02-28 journal: Mol Cells DOI: 10.14348/molcells.2017.0027 sha: doc_id: 2441 cord_uid: w731ehtz file: cache/cord-002844-jv42o789.json key: cord-002844-jv42o789 authors: Marcos-Villar, Laura; Díaz-Colunga, Juan; Sandoval, Juan; Zamarreño, Noelia; Landeras-Bueno, Sara; Esteller, Manel; Falcón, Ana; Nieto, Amelia title: Epigenetic control of influenza virus: role of H3K79 methylation in interferon-induced antiviral response date: 2018-01-19 journal: Sci Rep DOI: 10.1038/s41598-018-19370-6 sha: doc_id: 2844 cord_uid: jv42o789 file: cache/cord-001537-i34vmfpp.json key: cord-001537-i34vmfpp authors: Lima, Francisco Esmaile de Sales; Cibulski, Samuel Paulo; dos Santos, Helton Fernandes; Teixeira, Thais Fumaco; Varela, Ana Paula Muterle; Roehe, Paulo Michel; Delwart, Eric; Franco, Ana Cláudia title: Genomic Characterization of Novel Circular ssDNA Viruses from Insectivorous Bats in Southern Brazil date: 2015-02-17 journal: PLoS One DOI: 10.1371/journal.pone.0118070 sha: doc_id: 1537 cord_uid: i34vmfpp file: cache/cord-001732-4eyn7pjq.json key: cord-001732-4eyn7pjq authors: Riede, O; Seifert, K; Oswald, D; Endmann, A; Hock, C; Winkler, A; Salguero, F J; Schroff, M; Croft, S L; Juhls, C title: Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine date: 2015-04-30 journal: Gene Ther DOI: 10.1038/gt.2015.35 sha: doc_id: 1732 cord_uid: 4eyn7pjq file: cache/cord-003516-l1lq8yga.json key: cord-003516-l1lq8yga authors: Zhang, Jing; Kang, June; Dehghan, Shoaleh; Sridhar, Siddharth; Lau, Susanna K. 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Y.; Zhang, Qiwei; Seto, Donald title: A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations date: 2019-01-31 journal: Viruses DOI: 10.3390/v11020129 sha: doc_id: 3516 cord_uid: l1lq8yga file: cache/cord-004003-rlgzgyzn.json key: cord-004003-rlgzgyzn authors: Lee, Jeewon; Heo, Sunghoon; Bang, Duhee title: Applying a Linear Amplification Strategy to Recombinase Polymerase Amplification for Uniform DNA Library Amplification date: 2019-11-12 journal: ACS Omega DOI: 10.1021/acsomega.9b02886 sha: doc_id: 4003 cord_uid: rlgzgyzn file: cache/cord-003656-7mzsaz7a.json key: cord-003656-7mzsaz7a authors: Wium, Martha; Jonker, Hester Isabella; Olivier, Adriaan Jacobus; Bellstedt, Dirk Uwe; Botes, Annelise title: DNA Vaccines Against Mycoplasma Elicit Humoral Immune Responses in Ostriches date: 2019-05-14 journal: Front Immunol DOI: 10.3389/fimmu.2019.01061 sha: doc_id: 3656 cord_uid: 7mzsaz7a file: cache/cord-000010-prsvv6l9.json key: cord-000010-prsvv6l9 authors: Qin, Jian; Jones, Robert C.; Ramakrishnan, Ramesh title: Studying copy number variations using a nanofluidic platform date: 2008-08-18 journal: Nucleic Acids Res DOI: 10.1093/nar/gkn518 sha: doc_id: 10 cord_uid: prsvv6l9 file: cache/cord-003674-3ajyr5e4.json key: cord-003674-3ajyr5e4 authors: NAGAO, Konomu; MAKINO, Ryohei; APEGO, Francis Victor; MEKATA, Hirohisa; YAMAZAKI, Wataru title: Development of a fluorescent loop-mediated isothermal amplification assay for rapid and simple diagnosis of bovine leukemia virus infection date: 2019-03-27 journal: J Vet Med Sci DOI: 10.1292/jvms.19-0009 sha: doc_id: 3674 cord_uid: 3ajyr5e4 file: cache/cord-007047-7ty9mxa9.json key: cord-007047-7ty9mxa9 authors: Reller, L. 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F.; Patel, Ami; Ramos, Stephanie; Elwood, Dustin; Zhu, Xizhou; Yan, Jian; Gary, Ebony N.; Walker, Susanne N.; Schultheis, Katherine; Purwar, Mansi; Xu, Ziyang; Walters, Jewell; Bhojnagarwala, Pratik; Yang, Maria; Chokkalingam, Neethu; Pezzoli, Patrick; Parzych, Elizabeth; Reuschel, Emma L.; Doan, Arthur; Tursi, Nicholas; Vasquez, Miguel; Choi, Jihae; Tello-Ruiz, Edgar; Maricic, Igor; Bah, Mamadou A.; Wu, Yuanhan; Amante, Dinah; Park, Daniel H.; Dia, Yaya; Ali, Ali Raza; Zaidi, Faraz I.; Generotti, Alison; Kim, Kevin Y.; Herring, Timothy A.; Reeder, Sophia; Andrade, Viviane M.; Buttigieg, Karen; Zhao, Gan; Wu, Jiun-Ming; Li, Dan; Bao, Linlin; Liu, Jiangning; Deng, Wei; Qin, Chuan; Brown, Ami Shah; Khoshnejad, Makan; Wang, Nianshuang; Chu, Jacqueline; Wrapp, Daniel; McLellan, Jason S.; Muthumani, Kar; Wang, Bin; Carroll, Miles W.; Kim, J. Joseph; Boyer, Jean; Kulp, Daniel W.; Humeau, Laurent M. P. F.; Weiner, David B.; Broderick, Kate E. title: Immunogenicity of a DNA vaccine candidate for COVID-19 date: 2020-05-20 journal: Nat Commun DOI: 10.1038/s41467-020-16505-0 sha: doc_id: 341287 cord_uid: i1hyk962 file: cache/cord-338812-q24jycgk.json key: cord-338812-q24jycgk authors: Zakaryan, H.; Stamminger, T. title: Nuclear remodelling during viral infections date: 2011-04-28 journal: Cell Microbiol DOI: 10.1111/j.1462-5822.2011.01596.x sha: doc_id: 338812 cord_uid: q24jycgk file: cache/cord-344749-omzhhr0k.json key: cord-344749-omzhhr0k authors: Kaya, Sariye Irem; Karadurmus, Leyla; Ozcelikay, Goksu; Bakirhan, Nurgul K.; Ozkan, Sibel A. title: Electrochemical virus detections with nanobiosensors date: 2020-02-14 journal: Nanosensors for Smart Cities DOI: 10.1016/b978-0-12-819870-4.00017-7 sha: doc_id: 344749 cord_uid: omzhhr0k file: cache/cord-345494-8lcdx719.json key: cord-345494-8lcdx719 authors: Chao, Chien-Chung; Belinskaya, Tatyana; Zhang, Zhiwen; Ching, Wei-Mei title: Development of Recombinase Polymerase Amplification Assays for Detection of Orientia tsutsugamushi or Rickettsia typhi date: 2015-07-10 journal: PLoS Negl Trop Dis DOI: 10.1371/journal.pntd.0003884 sha: doc_id: 345494 cord_uid: 8lcdx719 file: cache/cord-342819-p8wp6yvo.json key: cord-342819-p8wp6yvo authors: De Groot, Anne S; Einck, Leo; Moise, Leonard; Chambers, Michael; Ballantyne, John; Malone, Robert W; Ardito, Matthew; Martin, William title: Making vaccines “on demand”: A potential solution for emerging pathogens and biodefense? date: 2013-09-01 journal: Hum Vaccin Immunother DOI: 10.4161/hv.25611 sha: doc_id: 342819 cord_uid: p8wp6yvo file: cache/cord-345144-zvu22n8f.json key: cord-345144-zvu22n8f authors: Compagnone, D.; Van Velzen, K.; Del Carlo, M.; Mascini, Marcello; Visconti, A. title: Chapter 29 Rapid detection of organophosphates, Ochratoxin A, and Fusarium sp. in durum wheat via screen printed based electrochemical sensors date: 2007-12-31 journal: Comprehensive Analytical Chemistry DOI: 10.1016/s0166-526x(06)49029-2 sha: doc_id: 345144 cord_uid: zvu22n8f file: cache/cord-341521-dntkdwkj.json key: cord-341521-dntkdwkj authors: Luo, Yi-Ran; Zhou, Shu-Ting; Yang, Liang; Liu, Yuan-Ping; Jiang, Sheng-Yao; Dawuli, Yeliboli; Hou, Yi-Xuan; Zhou, Tian-Xing; Yang, Zhi-Biao title: Porcine Epidemic Diarrhoea Virus Induces Cell-cycle Arrest through the DNA Damage-signalling Pathway date: 2020-03-24 journal: J Vet Res DOI: 10.2478/jvetres-2020-0024 sha: doc_id: 341521 cord_uid: dntkdwkj file: cache/cord-347221-g98q9cga.json key: cord-347221-g98q9cga authors: Piyush, Ravikant; Rajarshi, Keshav; Chatterjee, Aroni; Khan, Rajni; Ray, Shashikant title: Nucleic acid-based therapy for coronavirus disease 2019 date: 2020-09-19 journal: Heliyon DOI: 10.1016/j.heliyon.2020.e05007 sha: doc_id: 347221 cord_uid: g98q9cga file: cache/cord-345712-gmzue6lj.json key: cord-345712-gmzue6lj authors: Palazzo, Luca; Mikoč, Andreja; Ahel, Ivan title: ADP‐ribosylation: new facets of an ancient modification date: 2017-04-26 journal: FEBS J DOI: 10.1111/febs.14078 sha: doc_id: 345712 cord_uid: gmzue6lj file: cache/cord-341634-mpk8mmp8.json key: cord-341634-mpk8mmp8 authors: Sadana, Ajit; Sadana, Neeti title: Detection of Analytes on Arrays/Microarrays/DNA Chips date: 2010-09-02 journal: Handbook of Biosensors and Biosensor Kinetics DOI: 10.1016/b978-0-444-53262-6.00011-5 sha: doc_id: 341634 cord_uid: mpk8mmp8 file: cache/cord-342782-xty16m8w.json key: cord-342782-xty16m8w authors: Marrugal-Lorenzo, José A.; Serna-Gallego, Ana; Berastegui-Cabrera, Judith; Pachón, Jerónimo; Sánchez-Céspedes, Javier title: Repositioning salicylanilide anthelmintic drugs to treat adenovirus infections date: 2019-01-09 journal: Sci Rep DOI: 10.1038/s41598-018-37290-3 sha: doc_id: 342782 cord_uid: xty16m8w file: cache/cord-346043-8vcvalhp.json key: cord-346043-8vcvalhp authors: Lee, Jong B.; Roh, Young H.; Um, Soong Ho; Funabashi, Hisakage; Cheng, Wenlong; Cha, Judy J.; Kiatwuthinon, Pichamon; Muller, David A.; Luo, Dan title: Multifunctional nanoarchitectures from DNA-based ABC monomers date: 2009-05-03 journal: Nat Nanotechnol DOI: 10.1038/nnano.2009.93 sha: doc_id: 346043 cord_uid: 8vcvalhp file: cache/cord-340503-zwdewiu1.json key: cord-340503-zwdewiu1 authors: Mokhtarzadeh, Ahad; Eivazzadeh-Keihan, Reza; Pashazadeh, Paria; Hejazi, Maryam; Gharaatifar, Nasrin; Hasanzadeh, Mohammad; Baradaran, Behzad; de la Guardia, Miguel title: Nanomaterial-based biosensors for detection of pathogenic virus date: 2017-10-13 journal: Trends Analyt Chem DOI: 10.1016/j.trac.2017.10.005 sha: doc_id: 340503 cord_uid: zwdewiu1 file: cache/cord-347992-coby2m6e.json key: cord-347992-coby2m6e authors: Marton, Soledad; Reyes-Darias, José A.; Sánchez-Luque, Francisco J.; Romero-López, Cristina; Berzal-Herranz, Alfredo title: In Vitro and Ex Vivo Selection Procedures for Identifying Potentially Therapeutic DNA and RNA Molecules date: 2010-06-28 journal: Molecules DOI: 10.3390/molecules15074610 sha: doc_id: 347992 cord_uid: coby2m6e file: cache/cord-345903-ggkn1w5y.json key: cord-345903-ggkn1w5y authors: Revathidevi, Sundaramoorthy; Murugan, Avaniyapuram Kannan; Nakaoka, Hirofumi; Inoue, Ituro; Munirajan, Arasambattu Kannan title: APOBEC: A molecular driver in cervical cancer pathogenesis date: 2020-10-07 journal: Cancer Lett DOI: 10.1016/j.canlet.2020.10.004 sha: doc_id: 345903 cord_uid: ggkn1w5y file: cache/cord-345552-h6fwi0qn.json key: cord-345552-h6fwi0qn authors: Li, Q.-G.; Lindman, K.; Wadell, G. title: Hydropathic characteristics of adenovirus hexons date: 1997-07-01 journal: Arch Virol DOI: 10.1007/s007050050162 sha: doc_id: 345552 cord_uid: h6fwi0qn file: cache/cord-342015-bz2vab6e.json key: cord-342015-bz2vab6e authors: Ouadfeul, Sid-Ali title: Multifractal Analysis of SARS-CoV-2 Coronavirus genomes using the wavelet transform date: 2020-08-16 journal: bioRxiv DOI: 10.1101/2020.08.15.252411 sha: doc_id: 342015 cord_uid: bz2vab6e file: cache/cord-346853-0c1qdjb5.json key: cord-346853-0c1qdjb5 authors: Holmes, E. C.; Drummond, A. J. title: The Evolutionary Genetics of Viral Emergence date: 2007 journal: Wildlife and Emerging Zoonotic Diseases: The Biology, Circumstances and Consequences of Cross-Species Transmission DOI: 10.1007/978-3-540-70962-6_3 sha: doc_id: 346853 cord_uid: 0c1qdjb5 file: cache/cord-346308-9h2fk9qt.json key: cord-346308-9h2fk9qt authors: Kaur, Rajwinder; Yadav, Bhoomika; Tyagi, R.D. title: Microbiology of hospital wastewater date: 2020-05-01 journal: Current Developments in Biotechnology and Bioengineering DOI: 10.1016/b978-0-12-819722-6.00004-3 sha: doc_id: 346308 cord_uid: 9h2fk9qt file: cache/cord-346280-7sw30bsz.json key: cord-346280-7sw30bsz authors: Ramos Venancio, D. B.; Ramos, R. S.; Nascimento Filho, C. B.; Paulino, A. J.; Felix, P. 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cache/cord-356291-0x1jhya6.json key: cord-356291-0x1jhya6 authors: Tang, Liang; Marion, William R; Cingolani, Gino; Prevelige, Peter E; Johnson, John E title: Three-dimensional structure of the bacteriophage P22 tail machine date: 2005-06-02 journal: The EMBO Journal DOI: 10.1038/sj.emboj.7600695 sha: doc_id: 356291 cord_uid: 0x1jhya6 file: cache/cord-010119-t1x9gknd.json key: cord-010119-t1x9gknd authors: nan title: Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 date: 2017-09-04 journal: Transfusion DOI: 10.1111/trf.14286 sha: doc_id: 10119 cord_uid: t1x9gknd Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named keyword-dna-cord parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 93967 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 94353 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 94088 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 94711 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 94974 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 94983 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 94758 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 94865 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 95175 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 95098 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 95142 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 95490 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 95334 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 94979 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 93680 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 96297 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 92689 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 95217 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 96251 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 96126 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 96106 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 94622 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 95268 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 95358 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 96311 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 96802 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 1830 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-003674-3ajyr5e4 author: NAGAO, Konomu title: Development of a fluorescent loop-mediated isothermal amplification assay for rapid and simple diagnosis of bovine leukemia virus infection date: 2019-03-27 pages: extension: .txt txt: ./txt/cord-003674-3ajyr5e4.txt cache: ./cache/cord-003674-3ajyr5e4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-003674-3ajyr5e4.txt' /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 97467 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 96683 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 95641 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 96423 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 96842 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 1740 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === id: cord-000049-rl7sdzd7 author: Lee, David title: Detection of genetically modified organisms (GMOs) using isothermal amplification of target DNA sequences date: 2009-02-02 pages: extension: .txt txt: ./txt/cord-000049-rl7sdzd7.txt cache: ./cache/cord-000049-rl7sdzd7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000049-rl7sdzd7.txt' === file2bib.sh === id: cord-003516-l1lq8yga author: Zhang, Jing title: A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations date: 2019-01-31 pages: extension: .txt txt: ./txt/cord-003516-l1lq8yga.txt cache: ./cache/cord-003516-l1lq8yga.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-003516-l1lq8yga.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 95532 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 97612 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 98254 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 744 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-000575-g1ob16b9 author: Xie, Xiao-li title: Protein sequence analysis based on hydropathy profile of amino acids date: 2012-01-27 pages: extension: .txt txt: ./txt/cord-000575-g1ob16b9.txt cache: ./cache/cord-000575-g1ob16b9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000575-g1ob16b9.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 96754 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 4391 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 85. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-001484-va0teako author: Ahmed, Sarah A. title: Rapid Identification of Black Grain Eumycetoma Causative Agents Using Rolling Circle Amplification date: 2014-12-04 pages: extension: .txt txt: ./txt/cord-001484-va0teako.txt cache: ./cache/cord-001484-va0teako.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001484-va0teako.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-004170-ri5qsarz author: Yashima, Nozomi title: Leukocyte-derived extracellular DNA contributes to abnormal pressure elevation in the extracorporeal circulation circuit date: 2020-01-16 pages: extension: .txt txt: ./txt/cord-004170-ri5qsarz.txt cache: ./cache/cord-004170-ri5qsarz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004170-ri5qsarz.txt' === file2bib.sh === id: cord-004561-cer5ifac author: Astua-Monge, G. title: Evidence for a prokaryotic insertion-sequence contamination in eukaryotic sequences registered in different databases date: 2002 pages: extension: .txt txt: ./txt/cord-004561-cer5ifac.txt cache: ./cache/cord-004561-cer5ifac.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004561-cer5ifac.txt' /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === id: cord-001761-yvd1n42f author: Yoshimura, Takeo title: Controlled Microwave Heating Accelerates Rolling Circle Amplification date: 2015-09-08 pages: extension: .txt txt: ./txt/cord-001761-yvd1n42f.txt cache: ./cache/cord-001761-yvd1n42f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001761-yvd1n42f.txt' === file2bib.sh === id: cord-002441-w731ehtz author: Jeon, Young Joo title: Interferon-Stimulated Gene 15 in the Control of Cellular Responses to Genotoxic Stress date: 2017-02-28 pages: extension: .txt txt: ./txt/cord-002441-w731ehtz.txt cache: ./cache/cord-002441-w731ehtz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002441-w731ehtz.txt' === file2bib.sh === id: cord-000403-vzbh457k author: Zhang, Weijun title: Identification of CD8(+ )cytotoxic T lymphocyte epitopes from porcine reproductive and respiratory syndrome virus matrix protein in BALB/c mice date: 2011-05-30 pages: extension: .txt txt: ./txt/cord-000403-vzbh457k.txt cache: ./cache/cord-000403-vzbh457k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000403-vzbh457k.txt' === file2bib.sh === id: cord-000293-pc4x5e24 author: Yu, Chien-Hung title: Stimulation of ribosomal frameshifting by antisense LNA date: 2010-08-06 pages: extension: .txt txt: ./txt/cord-000293-pc4x5e24.txt cache: ./cache/cord-000293-pc4x5e24.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000293-pc4x5e24.txt' === file2bib.sh === id: cord-001537-i34vmfpp author: Lima, Francisco Esmaile de Sales title: Genomic Characterization of Novel Circular ssDNA Viruses from Insectivorous Bats in Southern Brazil date: 2015-02-17 pages: extension: .txt txt: ./txt/cord-001537-i34vmfpp.txt cache: ./cache/cord-001537-i34vmfpp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001537-i34vmfpp.txt' === file2bib.sh === id: cord-004003-rlgzgyzn author: Lee, Jeewon title: Applying a Linear Amplification Strategy to Recombinase Polymerase Amplification for Uniform DNA Library Amplification date: 2019-11-12 pages: extension: .txt txt: ./txt/cord-004003-rlgzgyzn.txt cache: ./cache/cord-004003-rlgzgyzn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004003-rlgzgyzn.txt' === file2bib.sh === id: cord-007047-7ty9mxa9 author: Reller, L. Barth title: Implications of New Technology for Infectious Diseases Practice date: 2006-11-15 pages: extension: .txt txt: ./txt/cord-007047-7ty9mxa9.txt cache: ./cache/cord-007047-7ty9mxa9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-007047-7ty9mxa9.txt' === file2bib.sh === id: cord-001406-huz0tpmi author: Kersting, Sebastian title: Multiplex isothermal solid-phase recombinase polymerase amplification for the specific and fast DNA-based detection of three bacterial pathogens date: 2014-02-18 pages: extension: .txt txt: ./txt/cord-001406-huz0tpmi.txt cache: ./cache/cord-001406-huz0tpmi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001406-huz0tpmi.txt' === file2bib.sh === id: cord-001090-qg2r691d author: Twin, Jimmy title: The Potential of Metatranscriptomics for Identifying Screening Targets for Bacterial Vaginosis date: 2013-09-27 pages: extension: .txt txt: ./txt/cord-001090-qg2r691d.txt cache: ./cache/cord-001090-qg2r691d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001090-qg2r691d.txt' === file2bib.sh === id: cord-000050-tfcerilc author: Rao, Srinivas title: Multivalent HA DNA Vaccination Protects against Highly Pathogenic H5N1 Avian Influenza Infection in Chickens and Mice date: 2008-06-18 pages: extension: .txt txt: ./txt/cord-000050-tfcerilc.txt cache: ./cache/cord-000050-tfcerilc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000050-tfcerilc.txt' === file2bib.sh === id: cord-000937-8vk89i4h author: Law, John title: Identification of Hepatotropic Viruses from Plasma Using Deep Sequencing: A Next Generation Diagnostic Tool date: 2013-04-17 pages: extension: .txt txt: ./txt/cord-000937-8vk89i4h.txt cache: ./cache/cord-000937-8vk89i4h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000937-8vk89i4h.txt' === file2bib.sh === id: cord-000010-prsvv6l9 author: Qin, Jian title: Studying copy number variations using a nanofluidic platform date: 2008-08-18 pages: extension: .txt txt: ./txt/cord-000010-prsvv6l9.txt cache: ./cache/cord-000010-prsvv6l9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000010-prsvv6l9.txt' === file2bib.sh === id: cord-000436-k1hwh640 author: Amidi, Maryam title: Antigen-expressing immunostimulatory liposomes as a genetically programmable synthetic vaccine date: 2010-10-26 pages: extension: .txt txt: ./txt/cord-000436-k1hwh640.txt cache: ./cache/cord-000436-k1hwh640.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000436-k1hwh640.txt' === file2bib.sh === id: cord-002844-jv42o789 author: Marcos-Villar, Laura title: Epigenetic control of influenza virus: role of H3K79 methylation in interferon-induced antiviral response date: 2018-01-19 pages: extension: .txt txt: ./txt/cord-002844-jv42o789.txt cache: ./cache/cord-002844-jv42o789.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002844-jv42o789.txt' === file2bib.sh === id: cord-000269-v4jochbe author: Wittekindt, Nicola E. title: Nodeomics: Pathogen Detection in Vertebrate Lymph Nodes Using Meta-Transcriptomics date: 2010-10-18 pages: extension: .txt txt: ./txt/cord-000269-v4jochbe.txt cache: ./cache/cord-000269-v4jochbe.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000269-v4jochbe.txt' === file2bib.sh === id: cord-001732-4eyn7pjq author: Riede, O title: Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine date: 2015-04-30 pages: extension: .txt txt: ./txt/cord-001732-4eyn7pjq.txt cache: ./cache/cord-001732-4eyn7pjq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001732-4eyn7pjq.txt' === file2bib.sh === id: cord-007757-4mri8kyq author: van de Sluis, Bart title: Transgene Design date: 2010-10-04 pages: extension: .txt txt: ./txt/cord-007757-4mri8kyq.txt cache: ./cache/cord-007757-4mri8kyq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-007757-4mri8kyq.txt' === file2bib.sh === id: cord-000012-p56v8wi1 author: Bigot, Yves title: Molecular evidence for the evolution of ichnoviruses from ascoviruses by symbiogenesis date: 2008-09-18 pages: extension: .txt txt: ./txt/cord-000012-p56v8wi1.txt cache: ./cache/cord-000012-p56v8wi1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000012-p56v8wi1.txt' === file2bib.sh === id: cord-000765-r7y1cqou author: Chang, Yu-Ming title: Functional Studies of ssDNA Binding Ability of MarR Family Protein TcaR from Staphylococcus epidermidis date: 2012-09-21 pages: extension: .txt txt: ./txt/cord-000765-r7y1cqou.txt cache: ./cache/cord-000765-r7y1cqou.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000765-r7y1cqou.txt' === file2bib.sh === id: cord-000988-79fp75u3 author: Al-Siyabi, Turkiya title: A cost effective real-time PCR for the detection of adenovirus from viral swabs date: 2013-06-07 pages: extension: .txt txt: ./txt/cord-000988-79fp75u3.txt cache: ./cache/cord-000988-79fp75u3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000988-79fp75u3.txt' === file2bib.sh === id: cord-003656-7mzsaz7a author: Wium, Martha title: DNA Vaccines Against Mycoplasma Elicit Humoral Immune Responses in Ostriches date: 2019-05-14 pages: extension: .txt txt: ./txt/cord-003656-7mzsaz7a.txt cache: ./cache/cord-003656-7mzsaz7a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003656-7mzsaz7a.txt' === file2bib.sh === id: cord-000104-3b8b8p61 author: McWhirter, Sarah M. title: A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP date: 2009-08-31 pages: extension: .txt txt: ./txt/cord-000104-3b8b8p61.txt cache: ./cache/cord-000104-3b8b8p61.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000104-3b8b8p61.txt' === file2bib.sh === id: cord-003609-p0ydzjre author: Goodman, Danielle E. title: Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR) date: 2019-04-23 pages: extension: .txt txt: ./txt/cord-003609-p0ydzjre.txt cache: ./cache/cord-003609-p0ydzjre.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003609-p0ydzjre.txt' === file2bib.sh === id: cord-001111-qqmj4v0u author: Liu, Chengyu title: Strategies for Designing Transgenic DNA Constructs date: 2013-03-08 pages: extension: .txt txt: ./txt/cord-001111-qqmj4v0u.txt cache: ./cache/cord-001111-qqmj4v0u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001111-qqmj4v0u.txt' === file2bib.sh === id: cord-009615-xcz8m9a7 author: Stoner, Gerald L. title: Polyomavirus Models of Brain Infection and the Pathogenesis of Multiple Sclerosis date: 2008-01-28 pages: extension: .txt txt: ./txt/cord-009615-xcz8m9a7.txt cache: ./cache/cord-009615-xcz8m9a7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-009615-xcz8m9a7.txt' === file2bib.sh === id: cord-007383-5yb3dxse author: Kang, Jun-Gu title: Vaccination with single plasmid DNA encoding IL-12 and antigens of severe fever with thrombocytopenia syndrome virus elicits complete protection in IFNAR knockout mice date: 2020-03-20 pages: extension: .txt txt: ./txt/cord-007383-5yb3dxse.txt cache: ./cache/cord-007383-5yb3dxse.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-007383-5yb3dxse.txt' === file2bib.sh === id: cord-012473-p66of6kq author: Celniker, Susan E. title: Unlocking the secrets of the genome date: 2009-06-17 pages: extension: .txt txt: ./txt/cord-012473-p66of6kq.txt cache: ./cache/cord-012473-p66of6kq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-012473-p66of6kq.txt' === file2bib.sh === id: cord-010621-d1utt8j3 author: Yamamoto, N. title: Assessing allergenic fungi in house dust by floor wipe sampling and quantitative PCR date: 2011-08-09 pages: extension: .txt txt: ./txt/cord-010621-d1utt8j3.txt cache: ./cache/cord-010621-d1utt8j3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-010621-d1utt8j3.txt' === file2bib.sh === id: cord-010784-khvrklqt author: Waki, Kayoko title: Integrity of plasma DNA is inversely correlated with vaccine-induced antitumor immunity in ovarian cancer patients date: 2020-05-11 pages: extension: .txt txt: ./txt/cord-010784-khvrklqt.txt cache: ./cache/cord-010784-khvrklqt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-010784-khvrklqt.txt' === file2bib.sh === id: cord-003764-141u6ax7 author: Shrestha, Ashish C. title: Cytolytic Perforin as an Adjuvant to Enhance the Immunogenicity of DNA Vaccines date: 2019-04-30 pages: extension: .txt txt: ./txt/cord-003764-141u6ax7.txt cache: ./cache/cord-003764-141u6ax7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003764-141u6ax7.txt' === file2bib.sh === id: cord-010564-7c9h16bi author: Unolt, Marta title: Pathogenic variants in CDC45 on the remaining allele in patients with a chromosome 22q11.2 deletion result in a novel autosomal recessive condition date: 2019-09-02 pages: extension: .txt txt: ./txt/cord-010564-7c9h16bi.txt cache: ./cache/cord-010564-7c9h16bi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-010564-7c9h16bi.txt' === file2bib.sh === id: cord-010056-zfin4bko author: Mejia, Rojelio title: Impact of intestinal parasites on microbiota and cobalamin gene sequences: a pilot study date: 2020-04-19 pages: extension: .txt txt: ./txt/cord-010056-zfin4bko.txt cache: ./cache/cord-010056-zfin4bko.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-010056-zfin4bko.txt' === file2bib.sh === id: cord-014908-jys1y0k9 author: Yadav, Rakesh title: Trends and Perspectives of Biosensors for Food and Environmental Virology date: 2010-05-19 pages: extension: .txt txt: ./txt/cord-014908-jys1y0k9.txt cache: ./cache/cord-014908-jys1y0k9.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 9 resourceName b'cord-014908-jys1y0k9.txt' === file2bib.sh === id: cord-015619-msicix98 author: nan title: Virus Structure & Assembly date: 2009-02-24 pages: extension: .txt txt: ./txt/cord-015619-msicix98.txt cache: ./cache/cord-015619-msicix98.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-015619-msicix98.txt' === file2bib.sh === id: cord-012802-xm2ftrw2 author: Zhao, Wu-li title: The novel quinolizidine derivate IMB-HDC inhibits STAT5a phosphorylation at 694 and 780 and promotes DNA breakage and cell apoptosis via blocking STAT5a nuclear translocation date: 2020-01-13 pages: extension: .txt txt: ./txt/cord-012802-xm2ftrw2.txt cache: ./cache/cord-012802-xm2ftrw2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-012802-xm2ftrw2.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-014674-ey29970v author: nan title: Dreizehnter Bericht nach Inkrafttreten des Gentechnikgesetzes (GenTG) für den Zeitraum vom 1.1.2002 bis 31.12.2002 : Die Arbeit der Zentralen Kommission für die Biologische Sicherheit (ZKBS) im Jahr 2002 date: 2003 pages: extension: .txt txt: ./txt/cord-014674-ey29970v.txt cache: ./cache/cord-014674-ey29970v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-014674-ey29970v.txt' === file2bib.sh === id: cord-008613-tysyq6o4 author: Thomas, Sheila M. title: Two mRNAs that differ by two nontemplated nucleotides encode the amino coterminal proteins P and V of the paramyxovirus SV5 date: 1988-09-09 pages: extension: .txt txt: ./txt/cord-008613-tysyq6o4.txt cache: ./cache/cord-008613-tysyq6o4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-008613-tysyq6o4.txt' === file2bib.sh === id: cord-013223-f43hks44 author: Chronopoulos, Antonios title: Emerging role of bacterial extracellular vesicles in cancer date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-013223-f43hks44.txt cache: ./cache/cord-013223-f43hks44.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-013223-f43hks44.txt' === file2bib.sh === id: cord-012461-v8d91fdo author: Marnissi, Boutheina title: Generation of ssDNA aptamers as diagnostic tool for Newcastle avian virus date: 2020-08-13 pages: extension: .txt txt: ./txt/cord-012461-v8d91fdo.txt cache: ./cache/cord-012461-v8d91fdo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-012461-v8d91fdo.txt' === file2bib.sh === id: cord-011030-o4jn5883 author: Hakki, Morgan title: Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy date: 2020-01-24 pages: extension: .txt txt: ./txt/cord-011030-o4jn5883.txt cache: ./cache/cord-011030-o4jn5883.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-011030-o4jn5883.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-011113-n1yf0o2o author: Chen, Weiye title: A seven-gene-deleted African swine fever virus is safe and effective as a live attenuated vaccine in pigs date: 2020-03-01 pages: extension: .txt txt: ./txt/cord-011113-n1yf0o2o.txt cache: ./cache/cord-011113-n1yf0o2o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-011113-n1yf0o2o.txt' === file2bib.sh === id: cord-015946-biu5zxd1 author: Peng, Daizhi title: Research Advances in Biomarker for Sepsis date: 2016-11-16 pages: extension: .txt txt: ./txt/cord-015946-biu5zxd1.txt cache: ./cache/cord-015946-biu5zxd1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-015946-biu5zxd1.txt' === file2bib.sh === id: cord-011073-uiabpbxd author: Gebrekidan, Hagos title: An appraisal of oriental theileriosis and the Theileria orientalis complex, with an emphasis on diagnosis and genetic characterisation date: 2019-12-06 pages: extension: .txt txt: ./txt/cord-011073-uiabpbxd.txt cache: ./cache/cord-011073-uiabpbxd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-011073-uiabpbxd.txt' === file2bib.sh === id: cord-016808-gy8d8285 author: Agol, Vadim I. title: The Origin and Evolution of Viruses date: 2008 pages: extension: .txt txt: ./txt/cord-016808-gy8d8285.txt cache: ./cache/cord-016808-gy8d8285.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-016808-gy8d8285.txt' === file2bib.sh === id: cord-009376-a35a92gh author: Lovatt, Archie title: Applications of quantitative PCR in the biosafety and genetic stability assessment of biotechnology products date: 2002-01-07 pages: extension: .txt txt: ./txt/cord-009376-a35a92gh.txt cache: ./cache/cord-009376-a35a92gh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-009376-a35a92gh.txt' === file2bib.sh === id: cord-011630-lfm34fsw author: Li, Yan title: Epigenetic inheritance of circadian period in clonal cells date: 2020-05-27 pages: extension: .txt txt: ./txt/cord-011630-lfm34fsw.txt cache: ./cache/cord-011630-lfm34fsw.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-011630-lfm34fsw.txt' === file2bib.sh === id: cord-010511-eoc0ex3i author: Yousefi, Shida title: In vivo evidence for extracellular DNA trap formation date: 2020-04-30 pages: extension: .txt txt: ./txt/cord-010511-eoc0ex3i.txt cache: ./cache/cord-010511-eoc0ex3i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-010511-eoc0ex3i.txt' === file2bib.sh === id: cord-017137-6pmts7ui author: Nema, Vijay title: Microbial Forensics: Beyond a Fascination date: 2018-07-12 pages: extension: .txt txt: ./txt/cord-017137-6pmts7ui.txt cache: ./cache/cord-017137-6pmts7ui.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-017137-6pmts7ui.txt' === file2bib.sh === id: cord-006049-sw1hki4r author: Keefe, Anthony D. title: Aptamers as therapeutics date: 2010 pages: extension: .txt txt: ./txt/cord-006049-sw1hki4r.txt cache: ./cache/cord-006049-sw1hki4r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-006049-sw1hki4r.txt' === file2bib.sh === id: cord-013290-j3assowx author: Guibinga, Ghiabe H. title: Protection against Borreliella burgdorferi infection mediated by a synthetically engineered DNA vaccine date: 2020-08-12 pages: extension: .txt txt: ./txt/cord-013290-j3assowx.txt cache: ./cache/cord-013290-j3assowx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-013290-j3assowx.txt' === file2bib.sh === id: cord-014661-mrh2pbi6 author: Dumitrascu, Georgiana R. title: Critical physiological and pathological functions of Forkhead Box O tumor suppressors date: 2013-12-31 pages: extension: .txt txt: ./txt/cord-014661-mrh2pbi6.txt cache: ./cache/cord-014661-mrh2pbi6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-014661-mrh2pbi6.txt' === file2bib.sh === id: cord-016417-3cwwmyv9 author: Sluijter, J. P. G. title: Quantitative Real-Time PCR date: 2006 pages: extension: .txt txt: ./txt/cord-016417-3cwwmyv9.txt cache: ./cache/cord-016417-3cwwmyv9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-016417-3cwwmyv9.txt' === file2bib.sh === id: cord-016751-g46gs087 author: nan title: DNA, RNA und IHRE Amplifikation date: 2009-12-24 pages: extension: .txt txt: ./txt/cord-016751-g46gs087.txt cache: ./cache/cord-016751-g46gs087.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-016751-g46gs087.txt' === file2bib.sh === id: cord-009261-97qegnlo author: Rieux, Charlotte title: Thiopurine Derivative-Induced Fpg/Nei DNA Glycosylase Inhibition: Structural, Dynamic and Functional Insights date: 2020-03-17 pages: extension: .txt txt: ./txt/cord-009261-97qegnlo.txt cache: ./cache/cord-009261-97qegnlo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-009261-97qegnlo.txt' === file2bib.sh === id: cord-015850-ef6svn8f author: Saitou, Naruya title: Eukaryote Genomes date: 2013-08-22 pages: extension: .txt txt: ./txt/cord-015850-ef6svn8f.txt cache: ./cache/cord-015850-ef6svn8f.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-015850-ef6svn8f.txt' === file2bib.sh === id: cord-016041-427mbaqc author: Hengge, Ulrich R. title: Gentherapie date: 2008 pages: extension: .txt txt: ./txt/cord-016041-427mbaqc.txt cache: ./cache/cord-016041-427mbaqc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-016041-427mbaqc.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-014875-xhzxhwgo author: nan title: Book Reviews date: 2003 pages: extension: .txt txt: ./txt/cord-014875-xhzxhwgo.txt cache: ./cache/cord-014875-xhzxhwgo.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-014875-xhzxhwgo.txt' === file2bib.sh === id: cord-015683-a9a82of4 author: Gupta, Varsha title: Molecular Diagnostics date: 2016-10-23 pages: extension: .txt txt: ./txt/cord-015683-a9a82of4.txt cache: ./cache/cord-015683-a9a82of4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-015683-a9a82of4.txt' === file2bib.sh === id: cord-014368-4nasrbs6 author: nan title: Gene Chip for Viral Discovery date: 2003-11-17 pages: extension: .txt txt: ./txt/cord-014368-4nasrbs6.txt cache: ./cache/cord-014368-4nasrbs6.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-014368-4nasrbs6.txt' === file2bib.sh === id: cord-016144-280kwlev author: Maan, Sushila title: Novel Molecular Diagnostics and Therapeutic Tools for Livestock Diseases date: 2018-04-26 pages: extension: .txt txt: ./txt/cord-016144-280kwlev.txt cache: ./cache/cord-016144-280kwlev.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-016144-280kwlev.txt' === file2bib.sh === id: cord-013614-j6h338qa author: Liu, Xiaojing title: ERCC6L2 promotes DNA orientation-specific recombination in mammalian cells date: 2020-04-30 pages: extension: .txt txt: ./txt/cord-013614-j6h338qa.txt cache: ./cache/cord-013614-j6h338qa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-013614-j6h338qa.txt' === file2bib.sh === id: cord-016628-ljzsg9up author: Bajpai, Bhakti title: High Capacity Vectors date: 2013-10-22 pages: extension: .txt txt: ./txt/cord-016628-ljzsg9up.txt cache: ./cache/cord-016628-ljzsg9up.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-016628-ljzsg9up.txt' === file2bib.sh === id: cord-016309-6mw8okmt author: Bule, Mohammed title: Antivirals: Past, Present and Future date: 2019-06-06 pages: extension: .txt txt: ./txt/cord-016309-6mw8okmt.txt cache: ./cache/cord-016309-6mw8okmt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-016309-6mw8okmt.txt' === file2bib.sh === id: cord-011053-gza05hsv author: Tiew, Pei Yee title: The Mycobiome in Health and Disease: Emerging Concepts, Methodologies and Challenges date: 2020-01-01 pages: extension: .txt txt: ./txt/cord-011053-gza05hsv.txt cache: ./cache/cord-011053-gza05hsv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-011053-gza05hsv.txt' === file2bib.sh === id: cord-013837-x95r6bz8 author: Chai, Qiyao title: New insights into the evasion of host innate immunity by Mycobacterium tuberculosis date: 2020-07-29 pages: extension: .txt txt: ./txt/cord-013837-x95r6bz8.txt cache: ./cache/cord-013837-x95r6bz8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-013837-x95r6bz8.txt' === file2bib.sh === id: cord-017156-ximzvqbm author: Forsdyke, Donald R. title: Chargaff’s GC rule date: 2010-05-18 pages: extension: .txt txt: ./txt/cord-017156-ximzvqbm.txt cache: ./cache/cord-017156-ximzvqbm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-017156-ximzvqbm.txt' === file2bib.sh === id: cord-014397-7b88ycv8 author: Gavora, JS title: Resistance of livestock to viruses: mechanisms and strategies for genetic engineering date: 1996-12-15 pages: extension: .txt txt: ./txt/cord-014397-7b88ycv8.txt cache: ./cache/cord-014397-7b88ycv8.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-014397-7b88ycv8.txt' === file2bib.sh === id: cord-016187-58rqc0cg author: Opal, S. M. title: The Challenge of Emerging Infections and Progressive Antibiotic Resistance date: 2006 pages: extension: .txt txt: ./txt/cord-016187-58rqc0cg.txt cache: ./cache/cord-016187-58rqc0cg.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-016187-58rqc0cg.txt' === file2bib.sh === id: cord-017563-jkhvcjcb author: Holland, Tod D. title: Modeling Brain Tumors Using Avian Retroviral Gene Transfer date: 2008-12-12 pages: extension: .txt txt: ./txt/cord-017563-jkhvcjcb.txt cache: ./cache/cord-017563-jkhvcjcb.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-017563-jkhvcjcb.txt' === file2bib.sh === id: cord-004133-32w6g7qk author: Walker, Faye M. title: Advances in Directly Amplifying Nucleic Acids from Complex Samples date: 2019-09-30 pages: extension: .txt txt: ./txt/cord-004133-32w6g7qk.txt cache: ./cache/cord-004133-32w6g7qk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004133-32w6g7qk.txt' === file2bib.sh === id: cord-001859-d62iuk72 author: Baquero-Pérez, Belinda title: Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments date: 2015-11-20 pages: extension: .txt txt: ./txt/cord-001859-d62iuk72.txt cache: ./cache/cord-001859-d62iuk72.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001859-d62iuk72.txt' === file2bib.sh === id: cord-015941-4fz79wzf author: Hu, Yuan title: Molecular Techniques for Blood and Blood Product Screening date: 2018-11-10 pages: extension: .txt txt: ./txt/cord-015941-4fz79wzf.txt cache: ./cache/cord-015941-4fz79wzf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-015941-4fz79wzf.txt' === file2bib.sh === id: cord-004501-guiy89x8 author: Cojocaru, Florina-Daniela title: Nanomaterials Designed for Antiviral Drug Delivery Transport across Biological Barriers date: 2020-02-18 pages: extension: .txt txt: ./txt/cord-004501-guiy89x8.txt cache: ./cache/cord-004501-guiy89x8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-004501-guiy89x8.txt' === file2bib.sh === id: cord-016588-f8uvhstb author: Sintchenko, Vitali title: Informatics for Infectious Disease Research and Control date: 2009-10-03 pages: extension: .txt txt: ./txt/cord-016588-f8uvhstb.txt cache: ./cache/cord-016588-f8uvhstb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-016588-f8uvhstb.txt' === file2bib.sh === id: cord-013412-gj443yei author: Lebedeva, Natalya Sh. title: The Application of Porphyrins and Their Analogues for Inactivation of Viruses date: 2020-09-23 pages: extension: .txt txt: ./txt/cord-013412-gj443yei.txt cache: ./cache/cord-013412-gj443yei.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-013412-gj443yei.txt' === file2bib.sh === id: cord-017881-5jjlx7ot author: Fulekar, M. H. title: Nanotechnology — In Relation to Bioinformatics date: 2009 pages: extension: .txt txt: ./txt/cord-017881-5jjlx7ot.txt cache: ./cache/cord-017881-5jjlx7ot.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-017881-5jjlx7ot.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-015935-r2wd1yfa author: Sokol, Deborah K. title: The Genetics of Autism date: 2011-02-10 pages: extension: .txt txt: ./txt/cord-015935-r2wd1yfa.txt cache: ./cache/cord-015935-r2wd1yfa.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-015935-r2wd1yfa.txt' === file2bib.sh === id: cord-013415-110b95cg author: Aquino-Martinez, Ruben title: Periodontal Disease and Senescent Cells: New Players for an Old Oral Health Problem? date: 2020-10-09 pages: extension: .txt txt: ./txt/cord-013415-110b95cg.txt cache: ./cache/cord-013415-110b95cg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-013415-110b95cg.txt' === file2bib.sh === id: cord-017838-fbotc479 author: Fagone, Paolo title: Electroporation-Mediated DNA Vaccination date: 2010-12-15 pages: extension: .txt txt: ./txt/cord-017838-fbotc479.txt cache: ./cache/cord-017838-fbotc479.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-017838-fbotc479.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-015677-67md3xox author: Lang, Hans Peter title: Nanomechanical Cantilever Array Sensors date: 2010 pages: extension: .txt txt: ./txt/cord-015677-67md3xox.txt cache: ./cache/cord-015677-67md3xox.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-015677-67md3xox.txt' === file2bib.sh === id: cord-007382-5kb16qb7 author: Hartmann, G. title: Nucleic Acid Immunity date: 2016-12-15 pages: extension: .txt txt: ./txt/cord-007382-5kb16qb7.txt cache: ./cache/cord-007382-5kb16qb7.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-007382-5kb16qb7.txt' === file2bib.sh === id: cord-004995-5jmjejbp author: Hunt, Hamish C. title: Optofluidic integration for microanalysis date: 2007-09-11 pages: extension: .txt txt: ./txt/cord-004995-5jmjejbp.txt cache: ./cache/cord-004995-5jmjejbp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-004995-5jmjejbp.txt' === file2bib.sh === id: cord-010680-lc1onm53 author: Patel, Ami title: In Vivo Delivery of Nucleic Acid-Encoded Monoclonal Antibodies date: 2020-03-10 pages: extension: .txt txt: ./txt/cord-010680-lc1onm53.txt cache: ./cache/cord-010680-lc1onm53.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-010680-lc1onm53.txt' === file2bib.sh === id: cord-016304-uusmg786 author: Lemuth, Karin title: Microarrays as Research Tools and Diagnostic Devices date: 2015-03-11 pages: extension: .txt txt: ./txt/cord-016304-uusmg786.txt cache: ./cache/cord-016304-uusmg786.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-016304-uusmg786.txt' === file2bib.sh === id: cord-017948-fqhl1qb4 author: Hu, Yuan title: Molecular Techniques for Blood and Blood Product Screening date: 2012-04-05 pages: extension: .txt txt: ./txt/cord-017948-fqhl1qb4.txt cache: ./cache/cord-017948-fqhl1qb4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-017948-fqhl1qb4.txt' === file2bib.sh === id: cord-017999-saxwqc2j author: Travers, Andrew A. title: Gene Regulation by HMGA and HMGB Chromosomal Proteins and Related Architectural DNA-Binding Proteins date: 2005 pages: extension: .txt txt: ./txt/cord-017999-saxwqc2j.txt cache: ./cache/cord-017999-saxwqc2j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-017999-saxwqc2j.txt' === file2bib.sh === id: cord-017297-q3qtgrfc author: Rajagopal, Vaishnavi title: Viral Helicases date: 2008-11-01 pages: extension: .txt txt: ./txt/cord-017297-q3qtgrfc.txt cache: ./cache/cord-017297-q3qtgrfc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-017297-q3qtgrfc.txt' === file2bib.sh === id: cord-018039-dw2xblyr author: Norbäck, Dan title: Microbial Agents in the Indoor Environment: Associations with Health date: 2019-08-08 pages: extension: .txt txt: ./txt/cord-018039-dw2xblyr.txt cache: ./cache/cord-018039-dw2xblyr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-018039-dw2xblyr.txt' === file2bib.sh === id: cord-012418-6ralcn8p author: Schwanke, Hella title: Of Keeping and Tipping the Balance: Host Regulation and Viral Modulation of IRF3-Dependent IFNB1 Expression date: 2020-07-07 pages: extension: .txt txt: ./txt/cord-012418-6ralcn8p.txt cache: ./cache/cord-012418-6ralcn8p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-012418-6ralcn8p.txt' === file2bib.sh === id: cord-018526-rz7id5mt author: Braun, Serge title: Non-viral Vector for Muscle-Mediated Gene Therapy date: 2018-12-14 pages: extension: .txt txt: ./txt/cord-018526-rz7id5mt.txt cache: ./cache/cord-018526-rz7id5mt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-018526-rz7id5mt.txt' === file2bib.sh === id: cord-022177-j0qcjbxg author: Markl, Jürgen title: Genome date: 2018-10-12 pages: extension: .txt txt: ./txt/cord-022177-j0qcjbxg.txt cache: ./cache/cord-022177-j0qcjbxg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-022177-j0qcjbxg.txt' === file2bib.sh === id: cord-018133-2otxft31 author: Altman, Russ B. title: Bioinformatics date: 2006 pages: extension: .txt txt: ./txt/cord-018133-2otxft31.txt cache: ./cache/cord-018133-2otxft31.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-018133-2otxft31.txt' === file2bib.sh === id: cord-022336-zqnczjpp author: Robertson, Hugh D. title: Virus Origins: Conjoined RNA Genomes as Precursors to DNA Genomes date: 2007-09-02 pages: extension: .txt txt: ./txt/cord-022336-zqnczjpp.txt cache: ./cache/cord-022336-zqnczjpp.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-022336-zqnczjpp.txt' === file2bib.sh === id: cord-016713-pw4f8asc author: Goyal, Amit K. title: Nanotechnological Approaches for Genetic Immunization date: 2013-05-24 pages: extension: .txt txt: ./txt/cord-016713-pw4f8asc.txt cache: ./cache/cord-016713-pw4f8asc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-016713-pw4f8asc.txt' === file2bib.sh === id: cord-023844-3flfngu0 author: Mülhardt, Cornel title: Was bitte ist denn »Molekularbiologie«? date: 2013 pages: extension: .txt txt: ./txt/cord-023844-3flfngu0.txt cache: ./cache/cord-023844-3flfngu0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-023844-3flfngu0.txt' === file2bib.sh === id: cord-018046-jzoykn0y author: Kumar, Sanjay title: Fabrication of Nanostructures with Bottom-up Approach and Their Utility in Diagnostics, Therapeutics, and Others date: 2017-11-18 pages: extension: .txt txt: ./txt/cord-018046-jzoykn0y.txt cache: ./cache/cord-018046-jzoykn0y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-018046-jzoykn0y.txt' === file2bib.sh === id: cord-019050-a9datsoo author: Ambrogi, Federico title: Bioinformatics and Nanotechnologies: Nanomedicine date: 2014 pages: extension: .txt txt: ./txt/cord-019050-a9datsoo.txt cache: ./cache/cord-019050-a9datsoo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-019050-a9datsoo.txt' === file2bib.sh === id: cord-018897-tceum2m1 author: Zhang, Anqi title: Nanowire Field-Effect Transistor Sensors date: 2016-07-27 pages: extension: .txt txt: ./txt/cord-018897-tceum2m1.txt cache: ./cache/cord-018897-tceum2m1.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-018897-tceum2m1.txt' === file2bib.sh === id: cord-022168-qautse9a author: Liu, Li title: Clinical Use of DNA Vaccines date: 2017-07-25 pages: extension: .txt txt: ./txt/cord-022168-qautse9a.txt cache: ./cache/cord-022168-qautse9a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-022168-qautse9a.txt' === file2bib.sh === id: cord-018437-yjvwa1ot author: Mitchell, Michael title: Taxonomy date: 2013-08-26 pages: extension: .txt txt: ./txt/cord-018437-yjvwa1ot.txt cache: ./cache/cord-018437-yjvwa1ot.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-018437-yjvwa1ot.txt' === file2bib.sh === id: cord-021063-4y8m33ea author: Hug, Peter title: Chapter 18 The advantages of liposome-based gene therapy: A comparison of viral versus liposome-based gene delivery date: 2007-09-02 pages: extension: .txt txt: ./txt/cord-021063-4y8m33ea.txt cache: ./cache/cord-021063-4y8m33ea.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-021063-4y8m33ea.txt' === file2bib.sh === id: cord-018145-kssjdn8y author: Niemann, Heiner title: Transgenic Farm Animals: Current Status and Perspectives for Agriculture and Biomedicine date: 2009 pages: extension: .txt txt: ./txt/cord-018145-kssjdn8y.txt cache: ./cache/cord-018145-kssjdn8y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-018145-kssjdn8y.txt' === file2bib.sh === id: cord-017752-ofzm3x3a author: nan title: Theories of Carcinogenesis date: 2007 pages: extension: .txt txt: ./txt/cord-017752-ofzm3x3a.txt cache: ./cache/cord-017752-ofzm3x3a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-017752-ofzm3x3a.txt' === file2bib.sh === id: cord-010443-4jblod8j author: Meduri, Gianfranco Umberto title: General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections date: 2020-04-22 pages: extension: .txt txt: ./txt/cord-010443-4jblod8j.txt cache: ./cache/cord-010443-4jblod8j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-010443-4jblod8j.txt' === file2bib.sh === id: cord-025232-5itrsfmk author: Yan, Yuqian title: Construction and Characterization of a Novel Recombinant Attenuated and Replication-Deficient Candidate Human Adenovirus Type 3 Vaccine: “Adenovirus Vaccine Within an Adenovirus Vector” date: 2020-05-26 pages: extension: .txt txt: ./txt/cord-025232-5itrsfmk.txt cache: ./cache/cord-025232-5itrsfmk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-025232-5itrsfmk.txt' === file2bib.sh === id: cord-018159-ycg6waay author: Peng, Xiaolei title: Plasmofluidics for Biosensing and Medical Diagnostics date: 2018-01-23 pages: extension: .txt txt: ./txt/cord-018159-ycg6waay.txt cache: ./cache/cord-018159-ycg6waay.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-018159-ycg6waay.txt' === file2bib.sh === id: cord-022037-4ik3jxjy author: Alvarez, Mar title: CANTILEVER BIOSENSORS date: 2008-07-05 pages: extension: .txt txt: ./txt/cord-022037-4ik3jxjy.txt cache: ./cache/cord-022037-4ik3jxjy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-022037-4ik3jxjy.txt' === file2bib.sh === id: cord-018944-du42ho11 author: Shin, Jeong Hwan title: Nucleic Acid Extraction and Enrichment date: 2018-11-10 pages: extension: .txt txt: ./txt/cord-018944-du42ho11.txt cache: ./cache/cord-018944-du42ho11.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-018944-du42ho11.txt' === file2bib.sh === id: cord-023369-xwclh6ih author: Kim, Faith title: Human Herpesvirus-6 Meningitis in a Premature Infant with Fevers: A Case and Literature Review date: 2020-04-18 pages: extension: .txt txt: ./txt/cord-023369-xwclh6ih.txt cache: ./cache/cord-023369-xwclh6ih.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023369-xwclh6ih.txt' === file2bib.sh === id: cord-017188-d3xg05ty author: Swartz, H.M. title: Free Radicals and Medicine date: 2005 pages: extension: .txt txt: ./txt/cord-017188-d3xg05ty.txt cache: ./cache/cord-017188-d3xg05ty.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-017188-d3xg05ty.txt' === file2bib.sh === id: cord-022196-1tionxun author: FENNER, FRANK title: The Nature and Classification of Animal Viruses date: 2013-11-17 pages: extension: .txt txt: ./txt/cord-022196-1tionxun.txt cache: ./cache/cord-022196-1tionxun.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-022196-1tionxun.txt' === file2bib.sh === id: cord-017493-zro9cna3 author: Mcnamee, James P. title: Cytogenetic and Carcinogenic Effects of Exposure to Radiofrequency Radiation date: 2007 pages: extension: .txt txt: ./txt/cord-017493-zro9cna3.txt cache: ./cache/cord-017493-zro9cna3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-017493-zro9cna3.txt' === file2bib.sh === id: cord-022142-d4yxgv83 author: David, Ayelet title: Polymer-Based DNA Delivery Systems for Cancer Immunotherapy date: 2016-05-28 pages: extension: .txt txt: ./txt/cord-022142-d4yxgv83.txt cache: ./cache/cord-022142-d4yxgv83.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-022142-d4yxgv83.txt' === file2bib.sh === id: cord-032220-u5oo7mj2 author: Bao, Mengdi title: Magnetic Bead-Quantum Dot (MB-Qdot) Clustered Regularly Interspaced Short Palindromic Repeat Assay for Simple Viral DNA Detection date: 2020-09-04 pages: extension: .txt txt: ./txt/cord-032220-u5oo7mj2.txt cache: ./cache/cord-032220-u5oo7mj2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-032220-u5oo7mj2.txt' === file2bib.sh === id: cord-026518-xv03vpji author: Xie, Peng title: Immune effect of a Newcastle disease virus DNA vaccine with IL-12 as a molecular adjuvant delivered by electroporation date: 2020-06-09 pages: extension: .txt txt: ./txt/cord-026518-xv03vpji.txt cache: ./cache/cord-026518-xv03vpji.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-026518-xv03vpji.txt' === file2bib.sh === id: cord-016313-n4ewq0pt author: Baranyi, Lajos title: Advances in Lentiviral Vector-based Cell Therapy with Mesenchymal Stem Cells date: 2012-09-27 pages: extension: .txt txt: ./txt/cord-016313-n4ewq0pt.txt cache: ./cache/cord-016313-n4ewq0pt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-016313-n4ewq0pt.txt' === file2bib.sh === id: cord-018737-1h84yi2i author: Kumar, Sudeep title: Live-Attenuated Bacterial Vectors for Delivery of Mucosal Vaccines, DNA Vaccines, and Cancer Immunotherapy date: 2019-01-10 pages: extension: .txt txt: ./txt/cord-018737-1h84yi2i.txt cache: ./cache/cord-018737-1h84yi2i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-018737-1h84yi2i.txt' === file2bib.sh === id: cord-023705-3q9yr6np author: FENNER, FRANK title: Viral Replication date: 2014-06-27 pages: extension: .txt txt: ./txt/cord-023705-3q9yr6np.txt cache: ./cache/cord-023705-3q9yr6np.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-023705-3q9yr6np.txt' === file2bib.sh === id: cord-018371-16zhx0ai author: Schomburg, Dietmar title: DNA helicase 3.6.4.12 date: 2013 pages: extension: .txt txt: ./txt/cord-018371-16zhx0ai.txt cache: ./cache/cord-018371-16zhx0ai.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-018371-16zhx0ai.txt' === file2bib.sh === id: cord-018265-twp33bb6 author: Becker, Pablo D. title: Community-acquired pneumonia: paving the way towards new vaccination concepts date: 2007 pages: extension: .txt txt: ./txt/cord-018265-twp33bb6.txt cache: ./cache/cord-018265-twp33bb6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-018265-twp33bb6.txt' === file2bib.sh === id: cord-020969-lh2ergpm author: STRAUSS, JAMES H. title: Gene Therapy date: 2012-07-27 pages: extension: .txt txt: ./txt/cord-020969-lh2ergpm.txt cache: ./cache/cord-020969-lh2ergpm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-020969-lh2ergpm.txt' === file2bib.sh === id: cord-027654-k0uby99n author: Nabel, Gary J. title: The development of gene-based vectors for immunization date: 2020-06-22 pages: extension: .txt txt: ./txt/cord-027654-k0uby99n.txt cache: ./cache/cord-027654-k0uby99n.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-027654-k0uby99n.txt' === file2bib.sh === id: cord-023698-wvk200j0 author: Hammerschlag, Margaret R. title: Chlamydia pneumoniae date: 2014-10-31 pages: extension: .txt txt: ./txt/cord-023698-wvk200j0.txt cache: ./cache/cord-023698-wvk200j0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-023698-wvk200j0.txt' === file2bib.sh === id: cord-023727-ahbnchj9 author: Low, K. Brooks title: Genetic Recombination: A Brief Overview date: 2012-12-02 pages: extension: .txt txt: ./txt/cord-023727-ahbnchj9.txt cache: ./cache/cord-023727-ahbnchj9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-023727-ahbnchj9.txt' === file2bib.sh === id: cord-020235-stcrozdw author: nan title: Abstracts of Papers Presented at the 38th Meeting of the Deutsche Gesellschaft für Hygiene und Mikrobiologie, Virology Section, Göttingen, 5.–8.10.1981 date: 2012-03-15 pages: extension: .txt txt: ./txt/cord-020235-stcrozdw.txt cache: ./cache/cord-020235-stcrozdw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-020235-stcrozdw.txt' === file2bib.sh === id: cord-016293-pyb00pt5 author: Newell-McGloughlin, Martina title: The flowering of the age of Biotechnology 1990–2000 date: 2006 pages: extension: .txt txt: ./txt/cord-016293-pyb00pt5.txt cache: ./cache/cord-016293-pyb00pt5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-016293-pyb00pt5.txt' === file2bib.sh === id: cord-015933-x5cq4k4x author: Verbrugh, H.A. title: 1 Micro-organismen, de mens en het ontstaan van infectieziekten: algemene principes date: 2011 pages: extension: .txt txt: ./txt/cord-015933-x5cq4k4x.txt cache: ./cache/cord-015933-x5cq4k4x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-015933-x5cq4k4x.txt' === file2bib.sh === id: cord-030295-jlhht2l9 author: Cruz-Flores, Roberto title: Genome reconstruction of white spot syndrome virus (WSSV) from archival Davidson’s-fixed paraffin embedded shrimp (Penaeus vannamei) tissue date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-030295-jlhht2l9.txt cache: ./cache/cord-030295-jlhht2l9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-030295-jlhht2l9.txt' === file2bib.sh === id: cord-025251-evnfvc0l author: Nemunaitis, John title: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection: let the virus be its own demise date: 2020-05-26 pages: extension: .txt txt: ./txt/cord-025251-evnfvc0l.txt cache: ./cache/cord-025251-evnfvc0l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-025251-evnfvc0l.txt' === file2bib.sh === id: cord-021532-6hmn90ac author: Von Seggern, Dan J. title: ADENOVIRAL VECTORS FOR PROTEIN EXPRESSION date: 2007-09-02 pages: extension: .txt txt: ./txt/cord-021532-6hmn90ac.txt cache: ./cache/cord-021532-6hmn90ac.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-021532-6hmn90ac.txt' === file2bib.sh === id: cord-102336-ex3zlq38 author: De Wijngaert, Brent title: Cryo-EM structures reveal transcription initiation steps by yeast mitochondrial RNA polymerase date: 2020-04-14 pages: extension: .txt txt: ./txt/cord-102336-ex3zlq38.txt cache: ./cache/cord-102336-ex3zlq38.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-102336-ex3zlq38.txt' === file2bib.sh === id: cord-018969-0zrnfaad author: Giese, Matthias title: Types of Recombinant Vaccines date: 2015-09-24 pages: extension: .txt txt: ./txt/cord-018969-0zrnfaad.txt cache: ./cache/cord-018969-0zrnfaad.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-018969-0zrnfaad.txt' === file2bib.sh === id: cord-022476-g826uiqx author: nan title: Eosinophils and Anti-Pathogen Host Defense date: 2012-10-12 pages: extension: .txt txt: ./txt/cord-022476-g826uiqx.txt cache: ./cache/cord-022476-g826uiqx.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-022476-g826uiqx.txt' === file2bib.sh === id: cord-029462-jm5qwxhz author: Ouidir, Marion title: Concentrations of persistent organic pollutants in maternal plasma and epigenome-wide placental DNA methylation date: 2020-07-13 pages: extension: .txt txt: ./txt/cord-029462-jm5qwxhz.txt cache: ./cache/cord-029462-jm5qwxhz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-029462-jm5qwxhz.txt' === file2bib.sh === id: cord-023830-w218ogsk author: Perlin, David title: Rapid Detection of Bioterrorism Pathogens date: 2008-09-10 pages: extension: .txt txt: ./txt/cord-023830-w218ogsk.txt cache: ./cache/cord-023830-w218ogsk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023830-w218ogsk.txt' === file2bib.sh === id: cord-023928-9a1w174h author: Thomas, Neal J. title: Genetic Predisposition to Critical Illness in the Pediatric Intensive Care Unit date: 2011-12-16 pages: extension: .txt txt: ./txt/cord-023928-9a1w174h.txt cache: ./cache/cord-023928-9a1w174h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-023928-9a1w174h.txt' === file2bib.sh === id: cord-017208-7oew461e author: Aurigemma, Rosemarie title: Regulatory Aspects in the Development of Gene Therapies date: 2005 pages: extension: .txt txt: ./txt/cord-017208-7oew461e.txt cache: ./cache/cord-017208-7oew461e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-017208-7oew461e.txt' === file2bib.sh === id: cord-033054-qaj1f6qq author: Samad, Abdus title: Computational assessment of MCM2 transcriptional expression and identification of the prognostic biomarker for human breast cancer date: 2020-10-01 pages: extension: .txt txt: ./txt/cord-033054-qaj1f6qq.txt cache: ./cache/cord-033054-qaj1f6qq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-033054-qaj1f6qq.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 31863 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 32989 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-027309-8siz9rb8 author: Paul, Debjani title: Developing a Point-of-Care Molecular Test to Detect SARS-CoV-2 date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-027309-8siz9rb8.txt cache: ./cache/cord-027309-8siz9rb8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-027309-8siz9rb8.txt' === file2bib.sh === id: cord-017817-ztp7w9yh author: Land, Walter Gottlieb title: Cell-Autonomous (Cell-Intrinsic) Stress Responses date: 2018-03-28 pages: extension: .txt txt: ./txt/cord-017817-ztp7w9yh.txt cache: ./cache/cord-017817-ztp7w9yh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-017817-ztp7w9yh.txt' === file2bib.sh === id: cord-103417-2uinislh author: Doi, Hideyuki title: On-site eDNA detection of species using ultra-rapid mobile PCR date: 2020-10-01 pages: extension: .txt txt: ./txt/cord-103417-2uinislh.txt cache: ./cache/cord-103417-2uinislh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103417-2uinislh.txt' === file2bib.sh === id: cord-035173-6974gw6j author: Wang, Zhuo title: Effects of Low-Dose X-Ray on Cell Growth, Membrane Permeability, DNA Damage and Gene Transfer Efficiency date: 2020-10-28 pages: extension: .txt txt: ./txt/cord-035173-6974gw6j.txt cache: ./cache/cord-035173-6974gw6j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-035173-6974gw6j.txt' === file2bib.sh === id: cord-023724-5at0rhqk author: Cann, Alan J. title: Infection date: 2015-07-24 pages: extension: .txt txt: ./txt/cord-023724-5at0rhqk.txt cache: ./cache/cord-023724-5at0rhqk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023724-5at0rhqk.txt' === file2bib.sh === id: cord-024149-qnclsjym author: Gupta, Ankit title: Microbes and Environment date: 2016-10-15 pages: extension: .txt txt: ./txt/cord-024149-qnclsjym.txt cache: ./cache/cord-024149-qnclsjym.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-024149-qnclsjym.txt' === file2bib.sh === id: cord-023120-jcgf2401 author: nan title: Animal virus genetics date: 2004-06-18 pages: extension: .txt txt: ./txt/cord-023120-jcgf2401.txt cache: ./cache/cord-023120-jcgf2401.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-023120-jcgf2401.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 33902 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 33783 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-024058-afgvztwo author: nan title: Engineering a Global Response to Infectious Diseases: This paper presents a more robust, adaptable, and scalable engineering infrastructure to improve the capability to respond to infectious diseases.Contributed Paper date: 2015-02-17 pages: extension: .txt txt: ./txt/cord-024058-afgvztwo.txt cache: ./cache/cord-024058-afgvztwo.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-024058-afgvztwo.txt' === file2bib.sh === id: cord-102504-d840uu3e author: Hass, Kenneth N. title: Integrated Micropillar Polydimethylsiloxane Accurate CRISPR Detection (IMPACT) System for Rapid Viral DNA Sensing date: 2020-03-20 pages: extension: .txt txt: ./txt/cord-102504-d840uu3e.txt cache: ./cache/cord-102504-d840uu3e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-102504-d840uu3e.txt' === file2bib.sh === id: cord-017543-60q9iecq author: Tian, Wei-Chang title: Microfluidic Applications in Biodefense date: 2008-08-23 pages: extension: .txt txt: ./txt/cord-017543-60q9iecq.txt cache: ./cache/cord-017543-60q9iecq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-017543-60q9iecq.txt' === file2bib.sh === id: cord-027865-p1epjn51 author: Sterchi, Diane L. title: Molecular pathology date: 2020-06-22 pages: extension: .txt txt: ./txt/cord-027865-p1epjn51.txt cache: ./cache/cord-027865-p1epjn51.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-027865-p1epjn51.txt' === file2bib.sh === id: cord-048322-5eqdrd52 author: Aigner, Achim title: Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo date: 2006-05-18 pages: extension: .txt txt: ./txt/cord-048322-5eqdrd52.txt cache: ./cache/cord-048322-5eqdrd52.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-048322-5eqdrd52.txt' === file2bib.sh === id: cord-102866-40s64455 author: Bhadra, Sanchita title: One enzyme reverse transcription qPCR using Taq DNA polymerase date: 2020-05-30 pages: extension: .txt txt: ./txt/cord-102866-40s64455.txt cache: ./cache/cord-102866-40s64455.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-102866-40s64455.txt' === file2bib.sh === id: cord-023389-ilrp8vb7 author: Wefer, J. title: Protective DNA Vaccination Against MOG(91‐108)‐Induced Experimental Autoimmune Encephalomyelitis Involves Induction of IFNβ date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-023389-ilrp8vb7.txt cache: ./cache/cord-023389-ilrp8vb7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-023389-ilrp8vb7.txt' === file2bib.sh === id: cord-028729-vhpuvp4g author: Singh, Simranjeet title: Biological Biosensors for Monitoring and Diagnosis date: 2020-07-08 pages: extension: .txt txt: ./txt/cord-028729-vhpuvp4g.txt cache: ./cache/cord-028729-vhpuvp4g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-028729-vhpuvp4g.txt' === file2bib.sh === id: cord-031970-7szpo4zx author: Qiao, Yu title: Tumorigenic and Immunogenic Properties of Induced Pluripotent Stem Cells: a Promising Cancer Vaccine date: 2020-09-16 pages: extension: .txt txt: ./txt/cord-031970-7szpo4zx.txt cache: ./cache/cord-031970-7szpo4zx.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-031970-7szpo4zx.txt' === file2bib.sh === id: cord-026729-hn0q0sbv author: Xu, Jun title: Functional investigation of the chromosomal ccdAB and hipAB operon in Escherichia coli Nissle 1917 date: 2020-06-13 pages: extension: .txt txt: ./txt/cord-026729-hn0q0sbv.txt cache: ./cache/cord-026729-hn0q0sbv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-026729-hn0q0sbv.txt' === file2bib.sh === id: cord-102370-5uy8dq18 author: Marano, Jeffrey M. title: Rolling Circle Amplification is a high fidelity and efficient alternative to plasmid preparation for the rescue of infectious clones date: 2020-06-23 pages: extension: .txt txt: ./txt/cord-102370-5uy8dq18.txt cache: ./cache/cord-102370-5uy8dq18.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-102370-5uy8dq18.txt' === file2bib.sh === id: cord-031565-mos619wp author: Troedsson, Christofer title: Quantification of copepod gut content by differential length amplification quantitative PCR (dla-qPCR) date: 2009-02-01 pages: extension: .txt txt: ./txt/cord-031565-mos619wp.txt cache: ./cache/cord-031565-mos619wp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-031565-mos619wp.txt' === file2bib.sh === id: cord-102511-7zgd45fl author: Khodakov, Dmitriy title: Donut PCR: a rapid, portable, multiplexed, and quantitative DNA detection platform with single-nucleotide specificity date: 2020-05-05 pages: extension: .txt txt: ./txt/cord-102511-7zgd45fl.txt cache: ./cache/cord-102511-7zgd45fl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102511-7zgd45fl.txt' === file2bib.sh === id: cord-102219-d3gkfo7s author: Perzel Mandell, Kira A. title: Characterizing the dynamic and functional DNA methylation landscape in the developing human cortex date: 2019-10-30 pages: extension: .txt txt: ./txt/cord-102219-d3gkfo7s.txt cache: ./cache/cord-102219-d3gkfo7s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102219-d3gkfo7s.txt' === file2bib.sh === id: cord-029957-q7v5gli8 author: Prabhu, D. title: In silico Functional Annotation and Characterization of Hypothetical Proteins from Serratia marcescens FGI94 date: 2020-07-31 pages: extension: .txt txt: ./txt/cord-029957-q7v5gli8.txt cache: ./cache/cord-029957-q7v5gli8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-029957-q7v5gli8.txt' === file2bib.sh === id: cord-104030-eb29t38n author: Morales-Nebreda, Luisa title: Aging imparts cell-autonomous dysfunction to regulatory T cells during recovery from influenza pneumonia date: 2020-06-05 pages: extension: .txt txt: ./txt/cord-104030-eb29t38n.txt cache: ./cache/cord-104030-eb29t38n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-104030-eb29t38n.txt' === file2bib.sh === id: cord-022128-r8el8nqm author: Domingo, Esteban title: Molecular basis of genetic variation of viruses: error-prone replication date: 2019-11-08 pages: extension: .txt txt: ./txt/cord-022128-r8el8nqm.txt cache: ./cache/cord-022128-r8el8nqm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-022128-r8el8nqm.txt' === file2bib.sh === id: cord-103735-nil1vv6h author: Alfano, Niccolo title: Non-invasive surveys of mammalian viruses using environmental DNA date: 2020-03-29 pages: extension: .txt txt: ./txt/cord-103735-nil1vv6h.txt cache: ./cache/cord-103735-nil1vv6h.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103735-nil1vv6h.txt' === file2bib.sh === id: cord-102359-k1xxz4hc author: Klotsa, Daphne title: Electronic Transport in DNA date: 2005-04-04 pages: extension: .txt txt: ./txt/cord-102359-k1xxz4hc.txt cache: ./cache/cord-102359-k1xxz4hc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102359-k1xxz4hc.txt' === file2bib.sh === id: cord-048359-lz37rh82 author: Li, Jin title: s-RT-MELT for rapid mutation scanning using enzymatic selection and real time DNA-melting: new potential for multiplex genetic analysis date: 2007-06-01 pages: extension: .txt txt: ./txt/cord-048359-lz37rh82.txt cache: ./cache/cord-048359-lz37rh82.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-048359-lz37rh82.txt' === file2bib.sh === id: cord-103422-ys846i99 author: Xu, Xinhui title: CRISPR-Assisted DNA Detection, a novel dCas9-based DNA detection technique date: 2020-05-13 pages: extension: .txt txt: ./txt/cord-103422-ys846i99.txt cache: ./cache/cord-103422-ys846i99.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103422-ys846i99.txt' === file2bib.sh === id: cord-103830-pu6v53oy author: Pichon, Fabien title: Analysis and annotation of genome-wide DNA methylation patterns in two nonhuman primate species using the Infinium Human Methylation 450K and EPIC BeadChips date: 2020-05-10 pages: extension: .txt txt: ./txt/cord-103830-pu6v53oy.txt cache: ./cache/cord-103830-pu6v53oy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103830-pu6v53oy.txt' === file2bib.sh === id: cord-000248-zueoyesj author: Berretta, Regina title: Cancer Biomarker Discovery: The Entropic Hallmark date: 2010-08-18 pages: extension: .txt txt: ./txt/cord-000248-zueoyesj.txt cache: ./cache/cord-000248-zueoyesj.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000248-zueoyesj.txt' === file2bib.sh === id: cord-102270-rfhtlodc author: Azhar, Mohd. title: Rapid, field-deployable nucleobase detection and identification using FnCas9 date: 2020-04-21 pages: extension: .txt txt: ./txt/cord-102270-rfhtlodc.txt cache: ./cache/cord-102270-rfhtlodc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-102270-rfhtlodc.txt' === file2bib.sh === id: cord-104272-lczm1z5z author: Yusifov, Taleh N. title: Tear lipocalin is the major endonuclease in tears date: 2008-01-29 pages: extension: .txt txt: ./txt/cord-104272-lczm1z5z.txt cache: ./cache/cord-104272-lczm1z5z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-104272-lczm1z5z.txt' === file2bib.sh === id: cord-021966-5m21bsrw author: Shaw, Alan R. title: Vaccines date: 2009-05-15 pages: extension: .txt txt: ./txt/cord-021966-5m21bsrw.txt cache: ./cache/cord-021966-5m21bsrw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-021966-5m21bsrw.txt' === file2bib.sh === id: cord-103563-7a3wdduq author: Nunez-Bajo, Estefania title: Ultra-Low-Cost Integrated Silicon-based Transducer for On-Site, Genetic Detection of Pathogens date: 2020-03-25 pages: extension: .txt txt: ./txt/cord-103563-7a3wdduq.txt cache: ./cache/cord-103563-7a3wdduq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103563-7a3wdduq.txt' === file2bib.sh === id: cord-010027-r0tl01kq author: nan title: Dublin Pathology 2015. 8th Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland date: 2015-09-15 pages: extension: .txt txt: ./txt/cord-010027-r0tl01kq.txt cache: ./cache/cord-010027-r0tl01kq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-010027-r0tl01kq.txt' === file2bib.sh === id: cord-102206-mb0qcd0b author: Seymour, Elif title: Configurable Digital Virus Counter on Robust Universal DNA Chips date: 2020-10-22 pages: extension: .txt txt: ./txt/cord-102206-mb0qcd0b.txt cache: ./cache/cord-102206-mb0qcd0b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102206-mb0qcd0b.txt' === file2bib.sh === id: cord-252838-av7ducrk author: Lucchi, Naomi W. title: Real-Time Fluorescence Loop Mediated Isothermal Amplification for the Diagnosis of Malaria date: 2010-10-29 pages: extension: .txt txt: ./txt/cord-252838-av7ducrk.txt cache: ./cache/cord-252838-av7ducrk.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-252838-av7ducrk.txt' === file2bib.sh === id: cord-103813-w2sb6h94 author: Schumacher, Garrett J. title: Genetic information insecurity as state of the art date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-103813-w2sb6h94.txt cache: ./cache/cord-103813-w2sb6h94.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103813-w2sb6h94.txt' === file2bib.sh === id: cord-257284-dash9udv author: Decaro, Nicola title: Development and validation of a real-time PCR assay for specific and sensitive detection of canid herpesvirus 1 date: 2010-07-30 pages: extension: .txt txt: ./txt/cord-257284-dash9udv.txt cache: ./cache/cord-257284-dash9udv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-257284-dash9udv.txt' === file2bib.sh === id: cord-189561-jhvwozsn author: Chechetkin, Vladimr R. title: Combining Detection and Reconstruction of Periodic Motifs in Genomic Sequences with Transitional Genome Mapping date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-189561-jhvwozsn.txt cache: ./cache/cord-189561-jhvwozsn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-189561-jhvwozsn.txt' === file2bib.sh === id: cord-255043-uxdsjr39 author: Bustin, Stephen A. title: RT-qPCR Testing of SARS-CoV-2: A Primer date: 2020-04-24 pages: extension: .txt txt: ./txt/cord-255043-uxdsjr39.txt cache: ./cache/cord-255043-uxdsjr39.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-255043-uxdsjr39.txt' === file2bib.sh === id: cord-252871-qfrpuy3t author: Nasir, Arshan title: Investigating the Concept and Origin of Viruses date: 2020-11-03 pages: extension: .txt txt: ./txt/cord-252871-qfrpuy3t.txt cache: ./cache/cord-252871-qfrpuy3t.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-252871-qfrpuy3t.txt' === file2bib.sh === id: cord-017867-8cn4c6cu author: Collántes-Fernández, Esther title: Trichomonas date: 2017-11-08 pages: extension: .txt txt: ./txt/cord-017867-8cn4c6cu.txt cache: ./cache/cord-017867-8cn4c6cu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-017867-8cn4c6cu.txt' === file2bib.sh === id: cord-103892-v6gkubd4 author: Mäkinen, Janne J. title: The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases date: 2020-07-01 pages: extension: .txt txt: ./txt/cord-103892-v6gkubd4.txt cache: ./cache/cord-103892-v6gkubd4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103892-v6gkubd4.txt' === file2bib.sh === id: cord-193910-7p3f3znj author: Zhang, Xiangxie title: Comparing Machine Learning Algorithms with or without Feature Extraction for DNA Classification date: 2020-11-01 pages: extension: .txt txt: ./txt/cord-193910-7p3f3znj.txt cache: ./cache/cord-193910-7p3f3znj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-193910-7p3f3znj.txt' === file2bib.sh === id: cord-257318-jejgkcql author: Jain, K.K. title: Synthetic Biology and Personalized Medicine date: 2012-08-16 pages: extension: .txt txt: ./txt/cord-257318-jejgkcql.txt cache: ./cache/cord-257318-jejgkcql.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-257318-jejgkcql.txt' === file2bib.sh === id: cord-256201-vjzfzshh author: Pereira-Gómez, Marianoel title: Effect of mismatch repair on the mutation rate of bacteriophage ϕX174 date: 2015-09-10 pages: extension: .txt txt: ./txt/cord-256201-vjzfzshh.txt cache: ./cache/cord-256201-vjzfzshh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-256201-vjzfzshh.txt' === file2bib.sh === id: cord-255499-31xmue1g author: Bujarski, J.J. title: Recombination date: 2008-07-30 pages: extension: .txt txt: ./txt/cord-255499-31xmue1g.txt cache: ./cache/cord-255499-31xmue1g.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-255499-31xmue1g.txt' === file2bib.sh === id: cord-252586-fuaoelgb author: Phillips, Sandra title: Alisporivir Inhibition of Hepatocyte Cyclophilins Reduces HBV Replication and Hepatitis B Surface Antigen Production date: 2014-10-08 pages: extension: .txt txt: ./txt/cord-252586-fuaoelgb.txt cache: ./cache/cord-252586-fuaoelgb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-252586-fuaoelgb.txt' === file2bib.sh === id: cord-255536-x1z2o9gs author: Artusi, Sara title: The Herpes Simplex Virus-1 genome contains multiple clusters of repeated G-quadruplex: Implications for the antiviral activity of a G-quadruplex ligand date: 2015-04-03 pages: extension: .txt txt: ./txt/cord-255536-x1z2o9gs.txt cache: ./cache/cord-255536-x1z2o9gs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-255536-x1z2o9gs.txt' === file2bib.sh === id: cord-258035-2tk7maqk author: DeFilippis, Victor title: Functional genomics in virology and antiviral drug discovery date: 2003-10-31 pages: extension: .txt txt: ./txt/cord-258035-2tk7maqk.txt cache: ./cache/cord-258035-2tk7maqk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-258035-2tk7maqk.txt' === file2bib.sh === id: cord-256278-jvfjf7aw author: Feng, Jie title: New method for comparing DNA primary sequences based on a discrimination measure date: 2010-10-21 pages: extension: .txt txt: ./txt/cord-256278-jvfjf7aw.txt cache: ./cache/cord-256278-jvfjf7aw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-256278-jvfjf7aw.txt' === file2bib.sh === id: cord-253295-82ydczid author: Funkhouser, William K. title: Pathology: the clinical description of human disease date: 2020-07-24 pages: extension: .txt txt: ./txt/cord-253295-82ydczid.txt cache: ./cache/cord-253295-82ydczid.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-253295-82ydczid.txt' === file2bib.sh === id: cord-258665-8q3tsggm author: Aydın, Hakan Berk title: Pixelated colorimetric nucleic acid assay date: 2020-03-01 pages: extension: .txt txt: ./txt/cord-258665-8q3tsggm.txt cache: ./cache/cord-258665-8q3tsggm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-258665-8q3tsggm.txt' === file2bib.sh === id: cord-254646-psolkrom author: Matsui, Mary S. title: Vitamin D Update date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-254646-psolkrom.txt cache: ./cache/cord-254646-psolkrom.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-254646-psolkrom.txt' === file2bib.sh === id: cord-252536-gfx4cq03 author: Bieniossek, Christoph title: MultiBac: expanding the research toolbox for multiprotein complexes date: 2011-12-07 pages: extension: .txt txt: ./txt/cord-252536-gfx4cq03.txt cache: ./cache/cord-252536-gfx4cq03.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-252536-gfx4cq03.txt' === file2bib.sh === id: cord-260345-ugd8kkor author: Giles, Ian G. title: A compendium of reviews in biochemistry and molecular biology published in the first half of 1992 date: 1992-12-31 pages: extension: .txt txt: ./txt/cord-260345-ugd8kkor.txt cache: ./cache/cord-260345-ugd8kkor.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-260345-ugd8kkor.txt' === file2bib.sh === id: cord-014712-5u4e00q6 author: nan title: Selected Abstracts from the 100th J Project Meeting, Antalya, Turkey, March 12-14, 2014 date: 2014-08-02 pages: extension: .txt txt: ./txt/cord-014712-5u4e00q6.txt cache: ./cache/cord-014712-5u4e00q6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-014712-5u4e00q6.txt' === file2bib.sh === id: cord-253894-4u5yt7b7 author: Senkevich, Tatiana G. title: Vaccinia virus F16 protein, a predicted catalytically inactive member of the prokaryotic serine recombinase superfamily, is targeted to nucleoli date: 2011-09-01 pages: extension: .txt txt: ./txt/cord-253894-4u5yt7b7.txt cache: ./cache/cord-253894-4u5yt7b7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-253894-4u5yt7b7.txt' === file2bib.sh === id: cord-260050-9ex70e1k author: Zhang, Y. Q. title: Inhibition of herpes simplex virus type 1 by small interfering RNA date: 2007-11-02 pages: extension: .txt txt: ./txt/cord-260050-9ex70e1k.txt cache: ./cache/cord-260050-9ex70e1k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-260050-9ex70e1k.txt' === file2bib.sh === id: cord-016095-jop2rx61 author: Vignais, Pierre V. title: Challenges for Experimentation on Living Beings at the Dawn of the 21(st) Century date: 2010-06-08 pages: extension: .txt txt: ./txt/cord-016095-jop2rx61.txt cache: ./cache/cord-016095-jop2rx61.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-016095-jop2rx61.txt' === file2bib.sh === id: cord-253115-ekgdsv4f author: Mehta, Meenu title: Oligonucleotide therapy: An emerging focus area for drug delivery in chronic inflammatory respiratory diseases date: 2019-08-01 pages: extension: .txt txt: ./txt/cord-253115-ekgdsv4f.txt cache: ./cache/cord-253115-ekgdsv4f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-253115-ekgdsv4f.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-254942-g51mjj2b author: Touati, Rabeb title: New methodology for repetitive sequences identification in human X and Y chromosomes date: 2020-10-19 pages: extension: .txt txt: ./txt/cord-254942-g51mjj2b.txt cache: ./cache/cord-254942-g51mjj2b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-254942-g51mjj2b.txt' === file2bib.sh === id: cord-260653-5qwtvm9x author: Chikhlikar, Priya title: DNA Encoding an HIV-1 Gag/Human Lysosome-Associated Membrane Protein-1 Chimera Elicits a Broad Cellular and Humoral Immune Response in Rhesus Macaques date: 2006-12-27 pages: extension: .txt txt: ./txt/cord-260653-5qwtvm9x.txt cache: ./cache/cord-260653-5qwtvm9x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-260653-5qwtvm9x.txt' === file2bib.sh === id: cord-259929-02765q5j author: Stanley, Philip M. title: Decoding DNA data storage for investment date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-259929-02765q5j.txt cache: ./cache/cord-259929-02765q5j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-259929-02765q5j.txt' === file2bib.sh === id: cord-263134-0p4zy5t2 author: de Paz, Hector David title: Molecular isothermal techniques for combating infectious diseases: towards low-cost point-of-care diagnostics date: 2014-07-23 pages: extension: .txt txt: ./txt/cord-263134-0p4zy5t2.txt cache: ./cache/cord-263134-0p4zy5t2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-263134-0p4zy5t2.txt' === file2bib.sh === id: cord-261134-zarq507s author: Pulford, David title: Amplification refractory mutation system PCR assays for the detection of variola and Orthopoxvirus date: 2004-02-13 pages: extension: .txt txt: ./txt/cord-261134-zarq507s.txt cache: ./cache/cord-261134-zarq507s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-261134-zarq507s.txt' === file2bib.sh === id: cord-259738-yuqc6dk0 author: Tang, Mengjun title: Enhancement of the immunogenicity of an infectious bronchitis virus DNA vaccine by a bicistronic plasmid encoding nucleocapsid protein and interleukin-2 date: 2008-03-07 pages: extension: .txt txt: ./txt/cord-259738-yuqc6dk0.txt cache: ./cache/cord-259738-yuqc6dk0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-259738-yuqc6dk0.txt' === file2bib.sh === id: cord-258623-9evwcs32 author: Roembke, Benjamin T. title: Nucleic acid detection using G-quadruplex amplification methodologies date: 2013-12-15 pages: extension: .txt txt: ./txt/cord-258623-9evwcs32.txt cache: ./cache/cord-258623-9evwcs32.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-258623-9evwcs32.txt' === file2bib.sh === id: cord-014685-ihh30q6f author: nan title: Posters P788 - P999 date: 2005-09-21 pages: extension: .txt txt: ./txt/cord-014685-ihh30q6f.txt cache: ./cache/cord-014685-ihh30q6f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-014685-ihh30q6f.txt' === file2bib.sh === id: cord-257802-vgizgq2y author: Uttamchandani, Mahesh title: Applications of microarrays in pathogen detection and biodefence date: 2008-11-12 pages: extension: .txt txt: ./txt/cord-257802-vgizgq2y.txt cache: ./cache/cord-257802-vgizgq2y.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-257802-vgizgq2y.txt' === file2bib.sh === id: cord-262733-icnkx1rx author: Daneluz, Larissa O. title: Efficiency and cell viability implications using tip type electroporation in zebrafish sperm cells date: 2020-07-13 pages: extension: .txt txt: ./txt/cord-262733-icnkx1rx.txt cache: ./cache/cord-262733-icnkx1rx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-262733-icnkx1rx.txt' === file2bib.sh === id: cord-258014-lzzi4rnz author: Chorna, Nataliya title: A Protocol for the Multi-Omic Integration of Cervical Microbiota and Urine Metabolomics to Understand Human Papillomavirus (HPV)-Driven Dysbiosis date: 2020-04-08 pages: extension: .txt txt: ./txt/cord-258014-lzzi4rnz.txt cache: ./cache/cord-258014-lzzi4rnz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-258014-lzzi4rnz.txt' === file2bib.sh === id: cord-262660-t1ndfn2l author: Hass, Kenneth N. title: Integrated Micropillar Polydimethylsiloxane Accurate CRISPR Detection System for Viral DNA Sensing date: 2020-10-13 pages: extension: .txt txt: ./txt/cord-262660-t1ndfn2l.txt cache: ./cache/cord-262660-t1ndfn2l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262660-t1ndfn2l.txt' === file2bib.sh === id: cord-014462-11ggaqf1 author: nan title: Abstracts of the Papers Presented in the XIX National Conference of Indian Virological Society, “Recent Trends in Viral Disease Problems and Management”, on 18–20 March, 2010, at S.V. University, Tirupati, Andhra Pradesh date: 2011-04-21 pages: extension: .txt txt: ./txt/cord-014462-11ggaqf1.txt cache: ./cache/cord-014462-11ggaqf1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-014462-11ggaqf1.txt' === file2bib.sh === id: cord-259412-l8uta7du author: Mattossovich, Rosanna title: O(6)-alkylguanine-DNA Alkyltransferases in Microbes Living on the Edge: From Stability to Applicability date: 2020-04-20 pages: extension: .txt txt: ./txt/cord-259412-l8uta7du.txt cache: ./cache/cord-259412-l8uta7du.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-259412-l8uta7du.txt' === file2bib.sh === id: cord-265237-sxh2nqre author: Weile, Jan title: Current applications and future trends of molecular diagnostics in clinical bacteriology date: 2009-04-18 pages: extension: .txt txt: ./txt/cord-265237-sxh2nqre.txt cache: ./cache/cord-265237-sxh2nqre.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-265237-sxh2nqre.txt' === file2bib.sh === id: cord-015678-9b3eazd4 author: Merzendorfer, Hans title: Chitin/Chitosan: Versatile Ecological, Industrial, and Biomedical Applications date: 2019-03-07 pages: extension: .txt txt: ./txt/cord-015678-9b3eazd4.txt cache: ./cache/cord-015678-9b3eazd4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-015678-9b3eazd4.txt' === file2bib.sh === id: cord-263570-6notzm6s author: Elia, Gabriella title: Detection of infectious canine parvovirus type 2 by mRNA real-time RT-PCR date: 2007-08-10 pages: extension: .txt txt: ./txt/cord-263570-6notzm6s.txt cache: ./cache/cord-263570-6notzm6s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-263570-6notzm6s.txt' === file2bib.sh === id: cord-030028-s6sxi8uj author: Rubio, Luis title: Detection of Plant Viruses and Disease Management: Relevance of Genetic Diversity and Evolution date: 2020-07-17 pages: extension: .txt txt: ./txt/cord-030028-s6sxi8uj.txt cache: ./cache/cord-030028-s6sxi8uj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-030028-s6sxi8uj.txt' === file2bib.sh === id: cord-260705-huyyw5z6 author: Moshe, Adi title: Virus-Induced Aggregates in Infected Cells date: 2012-10-17 pages: extension: .txt txt: ./txt/cord-260705-huyyw5z6.txt cache: ./cache/cord-260705-huyyw5z6.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-260705-huyyw5z6.txt' === file2bib.sh === id: cord-265173-70wyecwj author: Trujillo-Uscanga, Adrian title: Host cell p53 associates with the feline calicivirus major viral capsid protein VP1, the protease-polymerase NS6/7, and the double-stranded RNA playing a role in virus replication date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-265173-70wyecwj.txt cache: ./cache/cord-265173-70wyecwj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-265173-70wyecwj.txt' === file2bib.sh === id: cord-257046-er5orx8s author: Ladekjær-Mikkelsen, A.-S title: Reproduction of postweaning multisystemic wasting syndrome (PMWS) in immunostimulated and non-immunostimulated 3-week-old piglets experimentally infected with porcine circovirus type 2 (PCV2) date: 2002-10-22 pages: extension: .txt txt: ./txt/cord-257046-er5orx8s.txt cache: ./cache/cord-257046-er5orx8s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-257046-er5orx8s.txt' === file2bib.sh === id: cord-253826-63dgq551 author: Kim, Jisung title: State of diagnosing infectious pathogens using colloidal nanomaterials date: 2017-08-17 pages: extension: .txt txt: ./txt/cord-253826-63dgq551.txt cache: ./cache/cord-253826-63dgq551.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-253826-63dgq551.txt' === file2bib.sh === id: cord-254115-hwy962a4 author: Reslova, Nikol title: xMAP Technology: Applications in Detection of Pathogens date: 2017-01-25 pages: extension: .txt txt: ./txt/cord-254115-hwy962a4.txt cache: ./cache/cord-254115-hwy962a4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-254115-hwy962a4.txt' === file2bib.sh === id: cord-256130-zhlvvuj4 author: Nordén, Rickard title: Quantification of Torque Teno Virus and Epstein-Barr Virus Is of Limited Value for Predicting the Net State of Immunosuppression After Lung Transplantation date: 2018-03-06 pages: extension: .txt txt: ./txt/cord-256130-zhlvvuj4.txt cache: ./cache/cord-256130-zhlvvuj4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-256130-zhlvvuj4.txt' === file2bib.sh === id: cord-256320-zocunore author: Liao, Bo title: Coronavirus phylogeny based on triplets of nucleic acids bases date: 2006-04-15 pages: extension: .txt txt: ./txt/cord-256320-zocunore.txt cache: ./cache/cord-256320-zocunore.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-256320-zocunore.txt' === file2bib.sh === id: cord-009571-mygj2nd4 author: nan title: Proceedings of the 42nd annual meeting of the american rheumatism association a section of the arthritis foundation june 1 & 2, 1978 new york city abstracts of papers presented date: 2005-11-23 pages: extension: .txt txt: ./txt/cord-009571-mygj2nd4.txt cache: ./cache/cord-009571-mygj2nd4.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-009571-mygj2nd4.txt' === file2bib.sh === id: cord-265764-h4zg0q8x author: Singh, Kamaljit title: Synthesis of 4-aminoquinoline–pyrimidine hybrids as potent antimalarials and their mode of action studies date: 2013-06-10 pages: extension: .txt txt: ./txt/cord-265764-h4zg0q8x.txt cache: ./cache/cord-265764-h4zg0q8x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-265764-h4zg0q8x.txt' === file2bib.sh === id: cord-261417-4pf5nsw2 author: Harwig, Alex title: The Battle of RNA Synthesis: Virus versus Host date: 2017-10-21 pages: extension: .txt txt: ./txt/cord-261417-4pf5nsw2.txt cache: ./cache/cord-261417-4pf5nsw2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-261417-4pf5nsw2.txt' === file2bib.sh === id: cord-258363-gmgbus9i author: Kolla, Venkatadri title: Synthesis of a bacteriophage MB78 late protein by novel ribosomal frameshifting() date: 2000-08-22 pages: extension: .txt txt: ./txt/cord-258363-gmgbus9i.txt cache: ./cache/cord-258363-gmgbus9i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-258363-gmgbus9i.txt' === file2bib.sh === id: cord-267714-ji88tvsl author: JAKUPCIAK, JOHN P. title: Biological agent detection technologies date: 2009-04-21 pages: extension: .txt txt: ./txt/cord-267714-ji88tvsl.txt cache: ./cache/cord-267714-ji88tvsl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-267714-ji88tvsl.txt' === file2bib.sh === id: cord-268549-2lg8i9r1 author: Dai, Qi title: Sequence comparison via polar coordinates representation and curve tree date: 2012-01-07 pages: extension: .txt txt: ./txt/cord-268549-2lg8i9r1.txt cache: ./cache/cord-268549-2lg8i9r1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-268549-2lg8i9r1.txt' === file2bib.sh === id: cord-272943-q09i8fqu author: Dalhoff, A. title: Antiviral, antifungal, and antiparasitic activities of fluoroquinolones optimized for treatment of bacterial infections: a puzzling paradox or a logical consequence of their mode of action? date: 2014-12-17 pages: extension: .txt txt: ./txt/cord-272943-q09i8fqu.txt cache: ./cache/cord-272943-q09i8fqu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-272943-q09i8fqu.txt' === file2bib.sh === id: cord-263282-a7emso89 author: Coghlan, Megan L. title: Egg forensics: An appraisal of DNA sequencing to assist in species identification of illegally smuggled eggs date: 2011-07-07 pages: extension: .txt txt: ./txt/cord-263282-a7emso89.txt cache: ./cache/cord-263282-a7emso89.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-263282-a7emso89.txt' === file2bib.sh === id: cord-261028-sxux2ujo author: Vatner, Ralph E. title: STING, DCs and the link between innate and adaptive tumor immunity date: 2017-12-20 pages: extension: .txt txt: ./txt/cord-261028-sxux2ujo.txt cache: ./cache/cord-261028-sxux2ujo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-261028-sxux2ujo.txt' === file2bib.sh === id: cord-260422-z22t57ju author: Godet, Julien title: Comparative nucleic acid chaperone properties of the nucleocapsid protein NCp7 and Tat protein of HIV-1 date: 2012-06-26 pages: extension: .txt txt: ./txt/cord-260422-z22t57ju.txt cache: ./cache/cord-260422-z22t57ju.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-260422-z22t57ju.txt' === file2bib.sh === id: cord-252147-bvtchcbt author: Domingo-Espín, Joan title: Engineered Biological Entities for Drug Delivery and Gene Therapy: Protein Nanoparticles date: 2011-11-15 pages: extension: .txt txt: ./txt/cord-252147-bvtchcbt.txt cache: ./cache/cord-252147-bvtchcbt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-252147-bvtchcbt.txt' === file2bib.sh === id: cord-267928-dflkggjt author: Kantola, Kalle title: Merkel cell polyomavirus DNA in tumor-free tonsillar tissues and upper respiratory tract samples: Implications for respiratory transmission and latency date: 2009-05-22 pages: extension: .txt txt: ./txt/cord-267928-dflkggjt.txt cache: ./cache/cord-267928-dflkggjt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-267928-dflkggjt.txt' === file2bib.sh === id: cord-269352-0o3mryu1 author: Dhama, K. title: DNA vaccines and their applications in veterinary practice: current perspectives date: 2008-04-19 pages: extension: .txt txt: ./txt/cord-269352-0o3mryu1.txt cache: ./cache/cord-269352-0o3mryu1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-269352-0o3mryu1.txt' === file2bib.sh === id: cord-260042-cs0wp99n author: Khan, Samiullah title: Genes involved in mitochondrial biogenesis and function may not show synchronised responses to mitochondria in shell gland of laying chickens under infectious bronchitis virus challenge date: 2019-04-01 pages: extension: .txt txt: ./txt/cord-260042-cs0wp99n.txt cache: ./cache/cord-260042-cs0wp99n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-260042-cs0wp99n.txt' === file2bib.sh === id: cord-264746-gfn312aa author: Muse, Spencer title: GENOMICS AND BIOINFORMATICS date: 2012-03-29 pages: extension: .txt txt: ./txt/cord-264746-gfn312aa.txt cache: ./cache/cord-264746-gfn312aa.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-264746-gfn312aa.txt' === file2bib.sh === id: cord-273993-rkqijcxn author: Menchaca, A. title: CRISPR in livestock: From editing to printing date: 2020-01-29 pages: extension: .txt txt: ./txt/cord-273993-rkqijcxn.txt cache: ./cache/cord-273993-rkqijcxn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-273993-rkqijcxn.txt' === file2bib.sh === id: cord-262870-r3w44mg0 author: Duval, R.-E. title: Interest of designed cyclodextrin-tools in gene delivery date: 2012-11-30 pages: extension: .txt txt: ./txt/cord-262870-r3w44mg0.txt cache: ./cache/cord-262870-r3w44mg0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-262870-r3w44mg0.txt' === file2bib.sh === id: cord-271635-tydlyc1q author: Abdel-Hamid, Nabil M. title: Herbal management of hepatocellular carcinoma through cutting the pathways of the common risk factors date: 2018-11-30 pages: extension: .txt txt: ./txt/cord-271635-tydlyc1q.txt cache: ./cache/cord-271635-tydlyc1q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-271635-tydlyc1q.txt' === file2bib.sh === id: cord-264456-wjpc6zgq author: Bütepage, Mareike title: Intracellular Mono-ADP-Ribosylation in Signaling and Disease date: 2015-09-25 pages: extension: .txt txt: ./txt/cord-264456-wjpc6zgq.txt cache: ./cache/cord-264456-wjpc6zgq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-264456-wjpc6zgq.txt' === file2bib.sh === id: cord-264880-0tmd9knh author: Li, Zhao title: Picoliter Well Array Chip-Based Digital Recombinase Polymerase Amplification for Absolute Quantification of Nucleic Acids date: 2016-04-13 pages: extension: .txt txt: ./txt/cord-264880-0tmd9knh.txt cache: ./cache/cord-264880-0tmd9knh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-264880-0tmd9knh.txt' === file2bib.sh === id: cord-266670-jxgywvwx author: Wong, Mark title: Chapter 13 Recent Advances and Future Needs in Environmental Virology date: 2007-09-06 pages: extension: .txt txt: ./txt/cord-266670-jxgywvwx.txt cache: ./cache/cord-266670-jxgywvwx.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-266670-jxgywvwx.txt' === file2bib.sh === id: cord-273347-eyxc4rt0 author: Mohammadinejad, Reza title: In vivo gene delivery mediated by non-viral vectors for cancer therapy date: 2020-07-04 pages: extension: .txt txt: ./txt/cord-273347-eyxc4rt0.txt cache: ./cache/cord-273347-eyxc4rt0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-273347-eyxc4rt0.txt' === file2bib.sh === id: cord-269124-oreg7rnj author: Spyrou, Maria A. title: Ancient pathogen genomics as an emerging tool for infectious disease research date: 2019-04-05 pages: extension: .txt txt: ./txt/cord-269124-oreg7rnj.txt cache: ./cache/cord-269124-oreg7rnj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-269124-oreg7rnj.txt' === file2bib.sh === id: cord-272579-aenuyht0 author: Emmett, Stevan R. title: The Cell Cycle and Virus Infection date: 2005 pages: extension: .txt txt: ./txt/cord-272579-aenuyht0.txt cache: ./cache/cord-272579-aenuyht0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-272579-aenuyht0.txt' === file2bib.sh === id: cord-269839-jxqs51o5 author: Bitome-Essono, Paul-Yannick title: Tracking zoonotic pathogens using blood-sucking flies as 'flying syringes' date: 2017-03-28 pages: extension: .txt txt: ./txt/cord-269839-jxqs51o5.txt cache: ./cache/cord-269839-jxqs51o5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-269839-jxqs51o5.txt' === file2bib.sh === id: cord-274644-gr1eaj6k author: Chen, Zhao-Chi title: Thermally stable and uniform DNA amplification with picosecond laser ablated graphene rapid thermal cycling device date: 2019-12-15 pages: extension: .txt txt: ./txt/cord-274644-gr1eaj6k.txt cache: ./cache/cord-274644-gr1eaj6k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-274644-gr1eaj6k.txt' === file2bib.sh === id: cord-279084-bbae1qyx author: Liu, Bin title: Free DNA, a reason for severe COVID-19 infection? date: 2020-05-05 pages: extension: .txt txt: ./txt/cord-279084-bbae1qyx.txt cache: ./cache/cord-279084-bbae1qyx.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 1 resourceName b'cord-279084-bbae1qyx.txt' === file2bib.sh === id: cord-276101-quis0c6e author: Hamula, Camille L.A. title: Selection and analytical applications of aptamers binding microbial pathogens date: 2011-09-09 pages: extension: .txt txt: ./txt/cord-276101-quis0c6e.txt cache: ./cache/cord-276101-quis0c6e.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-276101-quis0c6e.txt' === file2bib.sh === id: cord-270637-4zphlpks author: Van Rompay, An R title: Substrate specificity and phosphorylation of antiviral and anticancer nucleoside analogues by human deoxyribonucleoside kinases and ribonucleoside kinases date: 2003-11-04 pages: extension: .txt txt: ./txt/cord-270637-4zphlpks.txt cache: ./cache/cord-270637-4zphlpks.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-270637-4zphlpks.txt' === file2bib.sh === id: cord-274707-mxh38hwd author: Laureano, Ana Flávia Santarine title: The different tests for the diagnosis of COVID-19 - A review in Brazil so far date: 2020 pages: extension: .txt txt: ./txt/cord-274707-mxh38hwd.txt cache: ./cache/cord-274707-mxh38hwd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-274707-mxh38hwd.txt' === file2bib.sh === id: cord-275232-0sg0hv9w author: Yeung, Siu-Wai title: A DNA biochip for on-the-spot multiplexed pathogen identification date: 2006-09-25 pages: extension: .txt txt: ./txt/cord-275232-0sg0hv9w.txt cache: ./cache/cord-275232-0sg0hv9w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-275232-0sg0hv9w.txt' === file2bib.sh === id: cord-262353-iips79vo author: Veltkamp, Henk-Willem title: Disposable DNA Amplification Chips with Integrated Low-Cost Heaters † date: 2020-02-25 pages: extension: .txt txt: ./txt/cord-262353-iips79vo.txt cache: ./cache/cord-262353-iips79vo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-262353-iips79vo.txt' === file2bib.sh === id: cord-267733-fuz8r3vj author: Al Ali, Sally title: Use of Reporter Genes in the Generation of Vaccinia Virus-Derived Vectors date: 2016-05-21 pages: extension: .txt txt: ./txt/cord-267733-fuz8r3vj.txt cache: ./cache/cord-267733-fuz8r3vj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-267733-fuz8r3vj.txt' === file2bib.sh === id: cord-274049-3gw65kpu author: Zhang, Han title: CRISPR Editing in Biological and Biomedical Investigation date: 2017-05-31 pages: extension: .txt txt: ./txt/cord-274049-3gw65kpu.txt cache: ./cache/cord-274049-3gw65kpu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-274049-3gw65kpu.txt' === file2bib.sh === id: cord-275886-502es8qm author: Chailapakul, Orawon title: Paper-based sensors for the application of biological compound detection date: 2020-06-05 pages: extension: .txt txt: ./txt/cord-275886-502es8qm.txt cache: ./cache/cord-275886-502es8qm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-275886-502es8qm.txt' === file2bib.sh === id: cord-272357-fxe49zen author: Campolongo, Michael J. title: DNA nanomedicine: Engineering DNA as a polymer for therapeutic and diagnostic applications() date: 2010-04-30 pages: extension: .txt txt: ./txt/cord-272357-fxe49zen.txt cache: ./cache/cord-272357-fxe49zen.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-272357-fxe49zen.txt' === file2bib.sh === id: cord-279503-w4tn03w0 author: Kim, Hanbi title: Development of Label-Free Colorimetric Assay for MERS-CoV Using Gold Nanoparticles date: 2019-05-07 pages: extension: .txt txt: ./txt/cord-279503-w4tn03w0.txt cache: ./cache/cord-279503-w4tn03w0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-279503-w4tn03w0.txt' === file2bib.sh === id: cord-276271-3nz3169p author: Deborggraeve, Stijn title: T. cruzi OligoC-TesT: A Simplified and Standardized Polymerase Chain Reaction Format for Diagnosis of Chagas Disease date: 2009-06-02 pages: extension: .txt txt: ./txt/cord-276271-3nz3169p.txt cache: ./cache/cord-276271-3nz3169p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-276271-3nz3169p.txt' === file2bib.sh === id: cord-254527-zddwajzg author: Junter, Guy-Alain title: Polysaccharide-based chromatographic adsorbents for virus purification and viral clearance date: 2020-01-13 pages: extension: .txt txt: ./txt/cord-254527-zddwajzg.txt cache: ./cache/cord-254527-zddwajzg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-254527-zddwajzg.txt' === file2bib.sh === id: cord-271241-w1q46y63 author: Ruggiero, Emanuela title: Viral G-quadruplexes: New frontiers in virus pathogenesis and antiviral therapy date: 2020-05-18 pages: extension: .txt txt: ./txt/cord-271241-w1q46y63.txt cache: ./cache/cord-271241-w1q46y63.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-271241-w1q46y63.txt' === file2bib.sh === id: cord-279229-2226jnfl author: Savan, R title: Loop‐mediated isothermal amplification: an emerging technology for detection of fish and shellfish pathogens date: 2005-11-22 pages: extension: .txt txt: ./txt/cord-279229-2226jnfl.txt cache: ./cache/cord-279229-2226jnfl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-279229-2226jnfl.txt' === file2bib.sh === id: cord-276335-e1xlwcvc author: Poh, W.P. title: Characterization of cytotoxic T‐lymphocyte epitopes and immune responses to SARS coronavirus spike DNA vaccine expressing the RGD‐integrin‐binding motif date: 2009-05-27 pages: extension: .txt txt: ./txt/cord-276335-e1xlwcvc.txt cache: ./cache/cord-276335-e1xlwcvc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-276335-e1xlwcvc.txt' === file2bib.sh === id: cord-273716-vv3pyft4 author: Khosravi-Darani, Kianoush title: The role of high-resolution imaging in the evaluation of nanosystems for bioactive encapsulation and targeted nanotherapy date: 2007-07-03 pages: extension: .txt txt: ./txt/cord-273716-vv3pyft4.txt cache: ./cache/cord-273716-vv3pyft4.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-273716-vv3pyft4.txt' === file2bib.sh === id: cord-278249-vvhq9vgp author: Blot, Mathieu title: CXCL10 could drive longer duration of mechanical ventilation during COVID-19 ARDS date: 2020-11-02 pages: extension: .txt txt: ./txt/cord-278249-vvhq9vgp.txt cache: ./cache/cord-278249-vvhq9vgp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-278249-vvhq9vgp.txt' === file2bib.sh === id: cord-280249-kfon0l9h author: Granstrom, David E. title: Recent Advances in the Laboratory Diagnosis of Equine Parasitic Diseases date: 1995-12-31 pages: extension: .txt txt: ./txt/cord-280249-kfon0l9h.txt cache: ./cache/cord-280249-kfon0l9h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280249-kfon0l9h.txt' === file2bib.sh === id: cord-277054-eq4obbte author: Kaur, Manpreet title: Rabies DNA vaccine: No impact of MHC Class I and Class II targeting sequences on immune response and protection against lethal challenge date: 2009-03-26 pages: extension: .txt txt: ./txt/cord-277054-eq4obbte.txt cache: ./cache/cord-277054-eq4obbte.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-277054-eq4obbte.txt' === file2bib.sh === id: cord-277318-cwuls6xs author: Visscher, Koen title: −1 Programmed Ribosomal Frameshifting as a Force-Dependent Process date: 2016-02-02 pages: extension: .txt txt: ./txt/cord-277318-cwuls6xs.txt cache: ./cache/cord-277318-cwuls6xs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-277318-cwuls6xs.txt' === file2bib.sh === id: cord-259748-x7dq1sy4 author: Wan, Dongshan title: Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response date: 2020-04-28 pages: extension: .txt txt: ./txt/cord-259748-x7dq1sy4.txt cache: ./cache/cord-259748-x7dq1sy4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-259748-x7dq1sy4.txt' === file2bib.sh === id: cord-269426-82g5eiyg author: Holman, David H. title: Viral Vectors date: 2009-01-30 pages: extension: .txt txt: ./txt/cord-269426-82g5eiyg.txt cache: ./cache/cord-269426-82g5eiyg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-269426-82g5eiyg.txt' === file2bib.sh === id: cord-279267-iyobsuvz author: Hacker, David L. title: Polyethyleneimine-based transient gene expression processes for suspension-adapted HEK-293E and CHO-DG44 cells date: 2013-11-30 pages: extension: .txt txt: ./txt/cord-279267-iyobsuvz.txt cache: ./cache/cord-279267-iyobsuvz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-279267-iyobsuvz.txt' === file2bib.sh === id: cord-278397-u33x4jaw author: Abe, Takayuki title: Negative Regulation of Cytosolic Sensing of DNA date: 2018-10-29 pages: extension: .txt txt: ./txt/cord-278397-u33x4jaw.txt cache: ./cache/cord-278397-u33x4jaw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-278397-u33x4jaw.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55578 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55377 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 27048 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-278081-tk7vn1v1 author: Brooks, Wesley H. title: Viral Impact in Autoimmune Diseases: Expanding the “X Chromosome–Nucleolus Nexus” Hypothesis date: 2017-11-28 pages: extension: .txt txt: ./txt/cord-278081-tk7vn1v1.txt cache: ./cache/cord-278081-tk7vn1v1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-278081-tk7vn1v1.txt' === file2bib.sh === id: cord-281565-v8s2ski3 author: Belmonte-Reche, Efres title: Exploring G and C-quadruplex structures as potential targets against the severe acute respiratory syndrome coronavirus 2 date: 2020-08-20 pages: extension: .txt txt: ./txt/cord-281565-v8s2ski3.txt cache: ./cache/cord-281565-v8s2ski3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-281565-v8s2ski3.txt' === file2bib.sh === id: cord-281883-l9yshyc7 author: Alekseeva, Ekaterina title: Enhancement of the expression of HCV core gene does not enhance core-specific immune response in DNA immunization: advantages of the heterologous DNA prime, protein boost immunization regimen date: 2009-06-08 pages: extension: .txt txt: ./txt/cord-281883-l9yshyc7.txt cache: ./cache/cord-281883-l9yshyc7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-281883-l9yshyc7.txt' === file2bib.sh === id: cord-278250-dwok857k author: Li, Heng title: The altered gut virome community in rhesus monkeys is correlated with the gut bacterial microbiome and associated metabolites date: 2019-08-19 pages: extension: .txt txt: ./txt/cord-278250-dwok857k.txt cache: ./cache/cord-278250-dwok857k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-278250-dwok857k.txt' === file2bib.sh === id: cord-283807-4yo27web author: Ashtari, Parviz title: An efficient method for recovery of target ssDNA based on amino-modified silica-coated magnetic nanoparticles date: 2005-09-15 pages: extension: .txt txt: ./txt/cord-283807-4yo27web.txt cache: ./cache/cord-283807-4yo27web.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-283807-4yo27web.txt' === file2bib.sh === id: cord-264814-v4wnmg03 author: Flanagan, Katie L. title: Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-264814-v4wnmg03.txt cache: ./cache/cord-264814-v4wnmg03.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-264814-v4wnmg03.txt' === file2bib.sh === id: cord-271504-t3y1w9ef author: Luo, Zichao title: Combating the Coronavirus Pandemic: Early Detection, Medical Treatment, and a Concerted Effort by the Global Community date: 2020-06-16 pages: extension: .txt txt: ./txt/cord-271504-t3y1w9ef.txt cache: ./cache/cord-271504-t3y1w9ef.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-271504-t3y1w9ef.txt' === file2bib.sh === id: cord-279827-921kvrrz author: Murata, Takayuki title: Growth behavior of bovine herpesvirus-1 in permissive and semi-permissive cells date: 1999-06-11 pages: extension: .txt txt: ./txt/cord-279827-921kvrrz.txt cache: ./cache/cord-279827-921kvrrz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-279827-921kvrrz.txt' === file2bib.sh === id: cord-270082-byxd4o4m author: Doheny, Kimberly Floy title: Identification of essential components of the S. cerevisiae kinetochore date: 1993-05-21 pages: extension: .txt txt: ./txt/cord-270082-byxd4o4m.txt cache: ./cache/cord-270082-byxd4o4m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-270082-byxd4o4m.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58230 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58813 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-282062-h9smg0w9 author: Takano, Tomomi title: Novel single-stranded, circular DNA virus identified in cats in Japan date: 2018-09-14 pages: extension: .txt txt: ./txt/cord-282062-h9smg0w9.txt cache: ./cache/cord-282062-h9smg0w9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-282062-h9smg0w9.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 56796 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58649 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 59780 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-277293-eo3bei9x author: Fondong, Vincent N. title: Geminivirus protein structure and function date: 2013-04-25 pages: extension: .txt txt: ./txt/cord-277293-eo3bei9x.txt cache: ./cache/cord-277293-eo3bei9x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-277293-eo3bei9x.txt' === file2bib.sh === id: cord-280429-4fota9rl author: Medvedev, Kirill E. title: Functional and evolutionary analysis of viral proteins containing a Rossmann‐like fold date: 2018-06-13 pages: extension: .txt txt: ./txt/cord-280429-4fota9rl.txt cache: ./cache/cord-280429-4fota9rl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280429-4fota9rl.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 58949 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 43792 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-282106-7k088cqv author: Yang, Zhi-yong title: A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice date: 2004 pages: extension: .txt txt: ./txt/cord-282106-7k088cqv.txt cache: ./cache/cord-282106-7k088cqv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-282106-7k088cqv.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 55854 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 59710 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-283249-pk5sc2ca author: Yoshida, Wataru title: Homogeneous DNA sensing using enzyme-inhibiting DNA aptamers date: 2006-09-15 pages: extension: .txt txt: ./txt/cord-283249-pk5sc2ca.txt cache: ./cache/cord-283249-pk5sc2ca.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-283249-pk5sc2ca.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 61710 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60951 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64448 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 59918 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-286684-2xmd3jfo author: Stefanetti, Valentina title: Retrospective Biomolecular Investigation of Coxiella burnetii and Leptospira spp. DNA in Cases of Abortion, Stillbirth and Neonatal Mortality in Dogs and Cats date: 2018-08-20 pages: extension: .txt txt: ./txt/cord-286684-2xmd3jfo.txt cache: ./cache/cord-286684-2xmd3jfo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-286684-2xmd3jfo.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64996 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64727 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-288390-p1q3v1ie author: Habjan, Matthias title: Cytoplasmic sensing of viral nucleic acids date: 2015-02-07 pages: extension: .txt txt: ./txt/cord-288390-p1q3v1ie.txt cache: ./cache/cord-288390-p1q3v1ie.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-288390-p1q3v1ie.txt' === file2bib.sh === id: cord-274128-kgtr77e7 author: Hochstetter, Axel title: Lab-on-a-Chip Technologies for the Single Cell Level: Separation, Analysis, and Diagnostics date: 2020-04-29 pages: extension: .txt txt: ./txt/cord-274128-kgtr77e7.txt cache: ./cache/cord-274128-kgtr77e7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-274128-kgtr77e7.txt' === file2bib.sh === id: cord-282618-tjvjlyn9 author: Luke, J M title: Improved antibiotic-free plasmid vector design by incorporation of transient expression enhancers date: 2010-11-25 pages: extension: .txt txt: ./txt/cord-282618-tjvjlyn9.txt cache: ./cache/cord-282618-tjvjlyn9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-282618-tjvjlyn9.txt' === file2bib.sh === id: cord-281404-5a8au32c author: Gastaldello, Stefano title: Caspase-1 Promotes Epstein-Barr Virus Replication by Targeting the Large Tegument Protein Deneddylase to the Nucleus of Productively Infected Cells date: 2013-10-10 pages: extension: .txt txt: ./txt/cord-281404-5a8au32c.txt cache: ./cache/cord-281404-5a8au32c.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-281404-5a8au32c.txt' === file2bib.sh === id: cord-285982-1a5u7uux author: Moss, Ronald B title: Prospects for control of emerging infectious diseases with plasmid DNA vaccines date: 2009-09-07 pages: extension: .txt txt: ./txt/cord-285982-1a5u7uux.txt cache: ./cache/cord-285982-1a5u7uux.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-285982-1a5u7uux.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66290 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-283880-lrrkuist author: Kumar, Arvind title: Evolution of selective-sequencing approaches for virus discovery and virome analysis date: 2017-07-15 pages: extension: .txt txt: ./txt/cord-283880-lrrkuist.txt cache: ./cache/cord-283880-lrrkuist.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-283880-lrrkuist.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66240 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66312 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-291174-rym84kni author: Yang, Yazhi title: A label-free electrochemical assay for coronavirus IBV H120 strain quantification based on equivalent substitution effect and AuNPs-assisted signal amplification date: 2020-10-23 pages: extension: .txt txt: ./txt/cord-291174-rym84kni.txt cache: ./cache/cord-291174-rym84kni.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-291174-rym84kni.txt' === file2bib.sh === id: cord-253466-7gpije5d author: Netherton, Christopher title: A Guide to Viral Inclusions, Membrane Rearrangements, Factories, and Viroplasm Produced During Virus Replication date: 2007-08-31 pages: extension: .txt txt: ./txt/cord-253466-7gpije5d.txt cache: ./cache/cord-253466-7gpije5d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-253466-7gpije5d.txt' === file2bib.sh === id: cord-291749-revhbd0q author: Mongan, Arthur Elia title: Portable sequencer in the fight against infectious disease date: 2019-10-03 pages: extension: .txt txt: ./txt/cord-291749-revhbd0q.txt cache: ./cache/cord-291749-revhbd0q.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-291749-revhbd0q.txt' === file2bib.sh === id: cord-281188-0cql96hu author: Baquero, Fernando title: Proximate and ultimate causes of the bactericidal action of antibiotics date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-281188-0cql96hu.txt cache: ./cache/cord-281188-0cql96hu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-281188-0cql96hu.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66760 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66906 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66987 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66975 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64327 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-288131-dwhfrgje author: Zhao, Guodong title: Aberrant DNA Methylation of SEPT9 and SDC2 in Stool Specimens as an Integrated Biomarker for Colorectal Cancer Early Detection date: 2020-06-18 pages: extension: .txt txt: ./txt/cord-288131-dwhfrgje.txt cache: ./cache/cord-288131-dwhfrgje.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-288131-dwhfrgje.txt' === file2bib.sh === id: cord-285077-okwck5sv author: Sayahi, Tofigh title: Airborne Aerosolized Mouse Cytomegalovirus From Common Otolaryngology Procedures: Implications for COVID-19 Infection date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-285077-okwck5sv.txt cache: ./cache/cord-285077-okwck5sv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-285077-okwck5sv.txt' === file2bib.sh === id: cord-288444-0vv4neq6 author: Cotrone, Serafina title: Microcantilevers and organic transistors: two promising classes of label-free biosensing devices which can be integrated in electronic circuits date: 2011-12-22 pages: extension: .txt txt: ./txt/cord-288444-0vv4neq6.txt cache: ./cache/cord-288444-0vv4neq6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-288444-0vv4neq6.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 7557 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67636 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-292794-okh6i4l1 author: Wang, Bin title: Protective efficacy of a broadly cross-reactive swine influenza DNA vaccine encoding M2e, cytotoxic T lymphocyte epitope and consensus H3 hemagglutinin date: 2012-06-27 pages: extension: .txt txt: ./txt/cord-292794-okh6i4l1.txt cache: ./cache/cord-292794-okh6i4l1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-292794-okh6i4l1.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67627 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67945 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-280605-2i4gk7et author: Bachmann, María Consuelo title: The Challenge by Multiple Environmental and Biological Factors Induce Inflammation in Aging: Their Role in the Promotion of Chronic Disease date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-280605-2i4gk7et.txt cache: ./cache/cord-280605-2i4gk7et.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-280605-2i4gk7et.txt' === file2bib.sh === id: cord-279346-7del8d2p author: Callendret, Benoît title: Heterologous viral RNA export elements improve expression of severe acute respiratory syndrome (SARS) coronavirus spike protein and protective efficacy of DNA vaccines against SARS date: 2007-07-05 pages: extension: .txt txt: ./txt/cord-279346-7del8d2p.txt cache: ./cache/cord-279346-7del8d2p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-279346-7del8d2p.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67503 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-284582-xwedgllw author: Korabecna, M. title: Cell-free DNA in plasma as an essential immune system regulator date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-284582-xwedgllw.txt cache: ./cache/cord-284582-xwedgllw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-284582-xwedgllw.txt' === file2bib.sh === id: cord-280691-nzc8ir0n author: Guo, Sun-Wei title: China’s “Gene War of the Century” and Its Aftermath: The Contest Goes On date: 2013-08-30 pages: extension: .txt txt: ./txt/cord-280691-nzc8ir0n.txt cache: ./cache/cord-280691-nzc8ir0n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-280691-nzc8ir0n.txt' === file2bib.sh === id: cord-030369-4dn02a35 author: Peng, Liang title: Clinical Manifestations and Laboratory Tests of AECHB and Severe Hepatitis (Liver Failure) date: 2019-05-21 pages: extension: .txt txt: ./txt/cord-030369-4dn02a35.txt cache: ./cache/cord-030369-4dn02a35.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-030369-4dn02a35.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66888 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68115 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68816 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68569 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68621 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-264884-ydkigome author: Villarreal, Luis P. title: The Widespread Evolutionary Significance of Viruses date: 2008-07-05 pages: extension: .txt txt: ./txt/cord-264884-ydkigome.txt cache: ./cache/cord-264884-ydkigome.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-264884-ydkigome.txt' === file2bib.sh === id: cord-277665-ac8txr3h author: Grichko, Varvara P. title: 15 Nanodiamond Designing the Bio-Platform date: 2006-12-31 pages: extension: .txt txt: ./txt/cord-277665-ac8txr3h.txt cache: ./cache/cord-277665-ac8txr3h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-277665-ac8txr3h.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68671 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68574 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68359 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68658 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68243 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69136 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68932 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69818 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69872 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70789 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69780 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 69790 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70304 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-296967-qiil3gqk author: Tatlow, Dean title: A novel concept for treatment and vaccination against Covid‐19 with an inhaled chitosan‐coated DNA vaccine encoding a secreted spike protein portion date: 2020-08-08 pages: extension: .txt txt: ./txt/cord-296967-qiil3gqk.txt cache: ./cache/cord-296967-qiil3gqk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-296967-qiil3gqk.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 71004 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-296197-ohfhnpma author: Deborggraeve, Stijn title: A Simplified and Standardized Polymerase Chain Reaction Format for the Diagnosis of Leishmaniasis date: 2008-11-15 pages: extension: .txt txt: ./txt/cord-296197-ohfhnpma.txt cache: ./cache/cord-296197-ohfhnpma.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-296197-ohfhnpma.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68098 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-293072-giakcaki author: Xu, Wan-Xiang title: A simpler and more cost-effective peptide biosynthetic method using the truncated GST as carrier for epitope mapping date: 2017-10-12 pages: extension: .txt txt: ./txt/cord-293072-giakcaki.txt cache: ./cache/cord-293072-giakcaki.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-293072-giakcaki.txt' === file2bib.sh === id: cord-296356-qkvafy69 author: Garman, Elspeth title: SARS Proteomics Reveals Viral Secrets date: 2005-11-30 pages: extension: .txt txt: ./txt/cord-296356-qkvafy69.txt cache: ./cache/cord-296356-qkvafy69.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-296356-qkvafy69.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70832 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70012 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70413 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-032183-yqqqe325 author: Ning, Qin title: Antiviral Therapy for AECHB and Severe Hepatitis B (Liver Failure) date: 2019-05-21 pages: extension: .txt txt: ./txt/cord-032183-yqqqe325.txt cache: ./cache/cord-032183-yqqqe325.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-032183-yqqqe325.txt' === file2bib.sh === id: cord-282251-r4on3lpr author: Veggiani, Gianluca title: Emerging drug development technologies targeting ubiquitination for cancer therapeutics date: 2019-03-07 pages: extension: .txt txt: ./txt/cord-282251-r4on3lpr.txt cache: ./cache/cord-282251-r4on3lpr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-282251-r4on3lpr.txt' === file2bib.sh === id: cord-274080-884x48on author: Rumlová, Michaela title: In vitro methods for testing antiviral drugs date: 2018-06-30 pages: extension: .txt txt: ./txt/cord-274080-884x48on.txt cache: ./cache/cord-274080-884x48on.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-274080-884x48on.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 71170 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 834 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70798 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 71671 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-294712-kvvxmvqo author: Pelosse, Martin title: MultiBac: from protein complex structures to synthetic viral nanosystems date: 2017-10-30 pages: extension: .txt txt: ./txt/cord-294712-kvvxmvqo.txt cache: ./cache/cord-294712-kvvxmvqo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-294712-kvvxmvqo.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 71794 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 72177 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-286877-0h5vgi5c author: Dahiya, Shyam S. title: Immunogenicity of a DNA-launched replicon-based canine parvovirus DNA vaccine expressing VP2 antigen in dogs date: 2012-10-31 pages: extension: .txt txt: ./txt/cord-286877-0h5vgi5c.txt cache: ./cache/cord-286877-0h5vgi5c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-286877-0h5vgi5c.txt' === file2bib.sh === id: cord-020010-q58x6xb0 author: nan title: 19th ICAR Abstracts: date: 2006-03-13 pages: extension: .txt txt: ./txt/cord-020010-q58x6xb0.txt cache: ./cache/cord-020010-q58x6xb0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-020010-q58x6xb0.txt' === file2bib.sh === id: cord-300040-rvrp5zvv author: Dutta, Noton Kumar title: Search for potential target site of nucleocapsid gene for the design of an epitope-based SARS DNA vaccine date: 2008-06-15 pages: extension: .txt txt: ./txt/cord-300040-rvrp5zvv.txt cache: ./cache/cord-300040-rvrp5zvv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-300040-rvrp5zvv.txt' === file2bib.sh === id: cord-305024-343l2ha7 author: Sonntag, Michael title: New Adenovirus in Bats, Germany date: 2009-12-17 pages: extension: .txt txt: ./txt/cord-305024-343l2ha7.txt cache: ./cache/cord-305024-343l2ha7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-305024-343l2ha7.txt' === file2bib.sh === id: cord-298514-l2hs1h9c author: Ghosh, Soma title: Central Role of Ubiquitination in Genome Maintenance: DNA Replication and Damage Repair date: 2012-02-08 pages: extension: .txt txt: ./txt/cord-298514-l2hs1h9c.txt cache: ./cache/cord-298514-l2hs1h9c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-298514-l2hs1h9c.txt' === file2bib.sh === id: cord-292757-d03byeee author: Zhou, Xianfeng title: Enhance immune response to DNA vaccine based on a novel multicomponent supramolecular assembly date: 2007-08-07 pages: extension: .txt txt: ./txt/cord-292757-d03byeee.txt cache: ./cache/cord-292757-d03byeee.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-292757-d03byeee.txt' === file2bib.sh === id: cord-014597-66vd2mdu author: nan title: Abstracts from the 25th European Society for Animal Cell Technology Meeting: Cell Technologies for Innovative Therapies: Lausanne, Switzerland. 14-17 May 2017 date: 2018-03-15 pages: extension: .txt txt: ./txt/cord-014597-66vd2mdu.txt cache: ./cache/cord-014597-66vd2mdu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-014597-66vd2mdu.txt' === file2bib.sh === id: cord-292031-weiwksh6 author: Ramírez-Castillo, Flor Yazmín title: Waterborne Pathogens: Detection Methods and Challenges date: 2015-05-21 pages: extension: .txt txt: ./txt/cord-292031-weiwksh6.txt cache: ./cache/cord-292031-weiwksh6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-292031-weiwksh6.txt' === file2bib.sh === id: cord-298697-v1qdizwx author: Chang, Jia Jin Marc title: Takeaways from Mobile DNA Barcoding with BentoLab and MinION date: 2020-09-24 pages: extension: .txt txt: ./txt/cord-298697-v1qdizwx.txt cache: ./cache/cord-298697-v1qdizwx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-298697-v1qdizwx.txt' === file2bib.sh === id: cord-301167-101lnq4f author: Liu, Quanjun title: Microarray-in-a-Tube for Detection of Multiple Viruses date: 2007-02-01 pages: extension: .txt txt: ./txt/cord-301167-101lnq4f.txt cache: ./cache/cord-301167-101lnq4f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-301167-101lnq4f.txt' === file2bib.sh === id: cord-292569-h8fe0zio author: Lee, Si-Hyeong title: Preferential production of IgM-secreting hybridomas by immunization with DNA vaccines coding for Ebola virus glycoprotein: use of protein boosting for IgG-secreting hybridoma production date: 2017-07-26 pages: extension: .txt txt: ./txt/cord-292569-h8fe0zio.txt cache: ./cache/cord-292569-h8fe0zio.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-292569-h8fe0zio.txt' === file2bib.sh === id: cord-280549-bsnz24jx author: Fan, Ying title: Breaking Bad: How Viruses Subvert the Cell Cycle date: 2018-11-19 pages: extension: .txt txt: ./txt/cord-280549-bsnz24jx.txt cache: ./cache/cord-280549-bsnz24jx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-280549-bsnz24jx.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 73847 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 75684 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-311023-4ge4glq9 author: Hsieh, Yi-Fan title: A Lego(®)-like swappable fluidic module for bio-chem applications date: 2014-12-01 pages: extension: .txt txt: ./txt/cord-311023-4ge4glq9.txt cache: ./cache/cord-311023-4ge4glq9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-311023-4ge4glq9.txt' === file2bib.sh === id: cord-306754-qohrnpgq author: Lee, Justin S. title: Targeted Enrichment for Pathogen Detection and Characterization in Three Felid Species date: 2017-05-23 pages: extension: .txt txt: ./txt/cord-306754-qohrnpgq.txt cache: ./cache/cord-306754-qohrnpgq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-306754-qohrnpgq.txt' === file2bib.sh === id: cord-312517-b24zlaqt author: Kim, Denny title: The Brighton collaboration standardized template for collection of key information for benefit-risk assessment of nucleic acid (RNA and DNA) vaccines date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-312517-b24zlaqt.txt cache: ./cache/cord-312517-b24zlaqt.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-312517-b24zlaqt.txt' === file2bib.sh === id: cord-320501-xqgqq55q author: Theobald, Nigel title: Emerging vaccine delivery systems for COVID-19: Functionalised silica nanoparticles offer a potentially safe and effective alternative delivery system for DNA/RNA vaccines and may be useful in the hunt for a COVID-19 vaccine date: 2020-06-24 pages: extension: .txt txt: ./txt/cord-320501-xqgqq55q.txt cache: ./cache/cord-320501-xqgqq55q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-320501-xqgqq55q.txt' === file2bib.sh === id: cord-298051-ej8qxkce author: Louten, Jennifer title: Detection and Diagnosis of Viral Infections date: 2016-05-06 pages: extension: .txt txt: ./txt/cord-298051-ej8qxkce.txt cache: ./cache/cord-298051-ej8qxkce.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-298051-ej8qxkce.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-291349-tq2n4mx3 author: Smith, Kevin R title: Gene transfer in higher animals: theoretical considerations and key concepts date: 2002-10-09 pages: extension: .txt txt: ./txt/cord-291349-tq2n4mx3.txt cache: ./cache/cord-291349-tq2n4mx3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-291349-tq2n4mx3.txt' === file2bib.sh === id: cord-289535-srrfr1es author: Tregoning, J. S. title: Vaccines for COVID‐19 date: 2020-10-18 pages: extension: .txt txt: ./txt/cord-289535-srrfr1es.txt cache: ./cache/cord-289535-srrfr1es.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-289535-srrfr1es.txt' === file2bib.sh === id: cord-312757-58p5b2vw author: Pérez-Montoto, Lázaro G. title: Scoring function for DNA–drug docking of anticancer and antiparasitic compounds based on spectral moments of 2D lattice graphs for molecular dynamics trajectories date: 2009-11-30 pages: extension: .txt txt: ./txt/cord-312757-58p5b2vw.txt cache: ./cache/cord-312757-58p5b2vw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-312757-58p5b2vw.txt' === file2bib.sh === id: cord-314415-yr0uxok2 author: Guo, Zijing title: Identification and genomic characterization of a novel CRESS DNA virus from a calf with severe hemorrhagic enteritis in China date: 2018-08-15 pages: extension: .txt txt: ./txt/cord-314415-yr0uxok2.txt cache: ./cache/cord-314415-yr0uxok2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-314415-yr0uxok2.txt' === file2bib.sh === id: cord-315616-pvt0amth author: Poole, Anthony title: Methyl-RNA: an evolutionary bridge between RNA and DNA? date: 2004-06-17 pages: extension: .txt txt: ./txt/cord-315616-pvt0amth.txt cache: ./cache/cord-315616-pvt0amth.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-315616-pvt0amth.txt' === file2bib.sh === id: cord-317591-qa6oxy4j author: Fukushima, Akiko title: Development of a Chimeric DNA-RNA Hammerhead Ribozyme Targeting SARS Virus date: 2009-05-07 pages: extension: .txt txt: ./txt/cord-317591-qa6oxy4j.txt cache: ./cache/cord-317591-qa6oxy4j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-317591-qa6oxy4j.txt' === file2bib.sh === id: cord-306780-9xelf8oh author: Dale, Timothy D. title: Enhancement of wildlife disease surveillance using multiplex quantitative PCR: development of qPCR assays for major pathogens in UK squirrel populations date: 2016-07-28 pages: extension: .txt txt: ./txt/cord-306780-9xelf8oh.txt cache: ./cache/cord-306780-9xelf8oh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-306780-9xelf8oh.txt' === file2bib.sh === id: cord-308687-wrzzb9cy author: Brunner, Jesse L. title: Pooled samples and eDNA-based detection can facilitate the “clean trade” of aquatic animals date: 2020-06-24 pages: extension: .txt txt: ./txt/cord-308687-wrzzb9cy.txt cache: ./cache/cord-308687-wrzzb9cy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-308687-wrzzb9cy.txt' === file2bib.sh === id: cord-310268-8q4tk6fd author: Zhu, Qinchang title: DNA Aptamers in the Diagnosis and Treatment of Human Diseases date: 2015-11-25 pages: extension: .txt txt: ./txt/cord-310268-8q4tk6fd.txt cache: ./cache/cord-310268-8q4tk6fd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-310268-8q4tk6fd.txt' === file2bib.sh === id: cord-316096-3fnwosst author: Jin, Huali title: Induction of Th1 type response by DNA vaccinations with N, M, and E genes against SARS-CoV in mice date: 2005-03-25 pages: extension: .txt txt: ./txt/cord-316096-3fnwosst.txt cache: ./cache/cord-316096-3fnwosst.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-316096-3fnwosst.txt' === file2bib.sh === id: cord-315541-tirod4t6 author: Henriques, Ana Margarida title: Development and validation of a real-time PCR for the detection and quantification of porcine circovirus type 2 date: 2018-07-17 pages: extension: .txt txt: ./txt/cord-315541-tirod4t6.txt cache: ./cache/cord-315541-tirod4t6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-315541-tirod4t6.txt' === file2bib.sh === id: cord-307909-7vbxyns0 author: Ronda, Luca title: Rational Design of a User-Friendly Aptamer/Peptide-Based Device for the Detection of Staphylococcus aureus date: 2020-09-02 pages: extension: .txt txt: ./txt/cord-307909-7vbxyns0.txt cache: ./cache/cord-307909-7vbxyns0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-307909-7vbxyns0.txt' === file2bib.sh === id: cord-312522-mymgnf8z author: Nelson, Megan M. title: Rapid molecular detection of macrolide resistance date: 2019-02-12 pages: extension: .txt txt: ./txt/cord-312522-mymgnf8z.txt cache: ./cache/cord-312522-mymgnf8z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-312522-mymgnf8z.txt' === file2bib.sh === id: cord-314642-oobbdgzh author: Campbell, Allan title: The future of bacteriophage biology date: 2003 pages: extension: .txt txt: ./txt/cord-314642-oobbdgzh.txt cache: ./cache/cord-314642-oobbdgzh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-314642-oobbdgzh.txt' === file2bib.sh === id: cord-318276-so5jooj0 author: Bertholet, Christine title: Vaccinia virus produces late mRNAs by discontinuous synthesis date: 1987-07-17 pages: extension: .txt txt: ./txt/cord-318276-so5jooj0.txt cache: ./cache/cord-318276-so5jooj0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-318276-so5jooj0.txt' === file2bib.sh === id: cord-316434-mz4y5am2 author: Yang, Benjamin title: Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination date: 2015-06-25 pages: extension: .txt txt: ./txt/cord-316434-mz4y5am2.txt cache: ./cache/cord-316434-mz4y5am2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-316434-mz4y5am2.txt' === file2bib.sh === id: cord-322240-z8zkl2xh author: Maeda, Ken title: Isolation of Novel Adenovirus from Fruit Bat (Pteropus dasymallus yayeyamae) date: 2008-02-17 pages: extension: .txt txt: ./txt/cord-322240-z8zkl2xh.txt cache: ./cache/cord-322240-z8zkl2xh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-322240-z8zkl2xh.txt' === file2bib.sh === id: cord-318609-211m5b79 author: Yang, Chen title: Accurate, rapid and low-cost diagnosis of Mycoplasma pneumoniae via fast narrow-thermal-cycling denaturation bubble-mediated strand exchange amplification date: 2020-10-11 pages: extension: .txt txt: ./txt/cord-318609-211m5b79.txt cache: ./cache/cord-318609-211m5b79.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-318609-211m5b79.txt' === file2bib.sh === id: cord-314503-u1y1bznk author: Jaluria, Pratik title: A perspective on microarrays: current applications, pitfalls, and potential uses date: 2007-01-25 pages: extension: .txt txt: ./txt/cord-314503-u1y1bznk.txt cache: ./cache/cord-314503-u1y1bznk.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-314503-u1y1bznk.txt' === file2bib.sh === id: cord-286719-1xjmlwqr author: Draz, Mohamed Shehata title: Applications of gold nanoparticles in virus detection date: 2018-02-15 pages: extension: .txt txt: ./txt/cord-286719-1xjmlwqr.txt cache: ./cache/cord-286719-1xjmlwqr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-286719-1xjmlwqr.txt' === file2bib.sh === id: cord-315164-nidgnvvi author: Medkour, Hacène title: Adenovirus Infections in African Humans and Wild Non-Human Primates: Great Diversity and Cross-Species Transmission date: 2020-06-18 pages: extension: .txt txt: ./txt/cord-315164-nidgnvvi.txt cache: ./cache/cord-315164-nidgnvvi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-315164-nidgnvvi.txt' === file2bib.sh === id: cord-312001-8p7scli8 author: Majzoub, Karim title: The Innate Antiviral Response in Animals: An Evolutionary Perspective from Flagellates to Humans date: 2019-08-16 pages: extension: .txt txt: ./txt/cord-312001-8p7scli8.txt cache: ./cache/cord-312001-8p7scli8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312001-8p7scli8.txt' === file2bib.sh === id: cord-310734-6v7oru2l author: Bolatti, Elisa M. title: A Preliminary Study of the Virome of the South American Free-Tailed Bats (Tadarida brasiliensis) and Identification of Two Novel Mammalian Viruses date: 2020-04-09 pages: extension: .txt txt: ./txt/cord-310734-6v7oru2l.txt cache: ./cache/cord-310734-6v7oru2l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-310734-6v7oru2l.txt' === file2bib.sh === id: cord-312336-784izxqd author: Fouret, Julien title: Sequencing the Genome of Indian Flying Fox, Natural Reservoir of Nipah Virus, Using Hybrid Assembly and Conservative Secondary Scaffolding date: 2020-07-29 pages: extension: .txt txt: ./txt/cord-312336-784izxqd.txt cache: ./cache/cord-312336-784izxqd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312336-784izxqd.txt' === file2bib.sh === id: cord-320628-uc97t0ea author: Huguenin, Antoine title: Broad respiratory virus detection in infants hospitalized for bronchiolitis by use of a multiplex RT‐PCR DNA microarray system date: 2012-04-12 pages: extension: .txt txt: ./txt/cord-320628-uc97t0ea.txt cache: ./cache/cord-320628-uc97t0ea.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-320628-uc97t0ea.txt' === file2bib.sh === id: cord-319884-d8n0aokl author: Natesan, Mohan title: Protein Microarrays and Biomarkers of Infectious Disease date: 2010-12-16 pages: extension: .txt txt: ./txt/cord-319884-d8n0aokl.txt cache: ./cache/cord-319884-d8n0aokl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-319884-d8n0aokl.txt' === file2bib.sh === id: cord-303265-v6ci69n0 author: Domingo, Esteban title: Introduction to virus origins and their role in biological evolution date: 2019-11-08 pages: extension: .txt txt: ./txt/cord-303265-v6ci69n0.txt cache: ./cache/cord-303265-v6ci69n0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-303265-v6ci69n0.txt' === file2bib.sh === id: cord-313161-07iwwsfz author: Lundstrom, Kenneth title: Alphavirus-Based Vaccines date: 2014-06-16 pages: extension: .txt txt: ./txt/cord-313161-07iwwsfz.txt cache: ./cache/cord-313161-07iwwsfz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-313161-07iwwsfz.txt' === file2bib.sh === id: cord-307768-xx46w6dc author: Ding, Yun title: From single-molecule detection to next-generation sequencing: microfluidic droplets for high-throughput nucleic acid analysis date: 2017-03-10 pages: extension: .txt txt: ./txt/cord-307768-xx46w6dc.txt cache: ./cache/cord-307768-xx46w6dc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-307768-xx46w6dc.txt' === file2bib.sh === id: cord-304424-048xo7jn author: Greninger, Alexander L. title: A decade of RNA virus metagenomics is (not) enough date: 2018-01-15 pages: extension: .txt txt: ./txt/cord-304424-048xo7jn.txt cache: ./cache/cord-304424-048xo7jn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-304424-048xo7jn.txt' === file2bib.sh === id: cord-311839-61djk4bs author: Wei, Dan title: A novel hierarchical clustering algorithm for gene sequences date: 2012-07-23 pages: extension: .txt txt: ./txt/cord-311839-61djk4bs.txt cache: ./cache/cord-311839-61djk4bs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-311839-61djk4bs.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-311328-k751tehv author: Rabti, Amal title: DNA markers and nano-biosensing approaches for tuberculosis diagnosis date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-311328-k751tehv.txt cache: ./cache/cord-311328-k751tehv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-311328-k751tehv.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-309642-wwaa6ls0 author: Potgieter, Leon N.D. title: Pathogenesis of Viral Infections date: 1986-11-30 pages: extension: .txt txt: ./txt/cord-309642-wwaa6ls0.txt cache: ./cache/cord-309642-wwaa6ls0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-309642-wwaa6ls0.txt' === file2bib.sh === id: cord-317021-o30zylrq author: Zhai, Yujia title: SmartBac, a new baculovirus system for large protein complex production date: 2019-02-10 pages: extension: .txt txt: ./txt/cord-317021-o30zylrq.txt cache: ./cache/cord-317021-o30zylrq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-317021-o30zylrq.txt' === file2bib.sh === id: cord-304869-l6a68tqn author: Bielińska-Wąż, Dorota title: Graphical and numerical representations of DNA sequences: statistical aspects of similarity date: 2011-08-28 pages: extension: .txt txt: ./txt/cord-304869-l6a68tqn.txt cache: ./cache/cord-304869-l6a68tqn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-304869-l6a68tqn.txt' === file2bib.sh === id: cord-309083-ew9cwiw0 author: Su, Hang title: Cyprinid viral diseases and vaccine development date: 2018-09-07 pages: extension: .txt txt: ./txt/cord-309083-ew9cwiw0.txt cache: ./cache/cord-309083-ew9cwiw0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-309083-ew9cwiw0.txt' === file2bib.sh === id: cord-319116-2ts6zpdb author: Ruggiero, Emanuela title: G-quadruplexes and G-quadruplex ligands: targets and tools in antiviral therapy date: 2018-04-20 pages: extension: .txt txt: ./txt/cord-319116-2ts6zpdb.txt cache: ./cache/cord-319116-2ts6zpdb.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-319116-2ts6zpdb.txt' === file2bib.sh === id: cord-324094-23kzr8rq author: Parida, M. M. title: Rapid and real-time detection technologies for emerging viruses of biomedical importance date: 2008-11-01 pages: extension: .txt txt: ./txt/cord-324094-23kzr8rq.txt cache: ./cache/cord-324094-23kzr8rq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-324094-23kzr8rq.txt' === file2bib.sh === id: cord-323691-5s5almd2 author: Mishin, Vasiliy P title: A ‘minimal’ approach in design of flavivirus infectious DNA date: 2001-12-04 pages: extension: .txt txt: ./txt/cord-323691-5s5almd2.txt cache: ./cache/cord-323691-5s5almd2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-323691-5s5almd2.txt' === file2bib.sh === id: cord-315570-khm1veuv author: González-Mora, Alejandro title: Bacteriophage-Based Vaccines: A Potent Approach for Antigen Delivery date: 2020-09-04 pages: extension: .txt txt: ./txt/cord-315570-khm1veuv.txt cache: ./cache/cord-315570-khm1veuv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-315570-khm1veuv.txt' === file2bib.sh === id: cord-320015-lbr2q4qh author: Chinchar, V. Gregory title: The Molecular Biology of Frog Virus 3 and other Iridoviruses Infecting Cold-Blooded Vertebrates date: 2011-10-20 pages: extension: .txt txt: ./txt/cord-320015-lbr2q4qh.txt cache: ./cache/cord-320015-lbr2q4qh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-320015-lbr2q4qh.txt' === file2bib.sh === id: cord-316534-ep7ezoko author: Gamble, Lena J title: Current progress in the development of a prophylactic vaccine for HIV-1 date: 2010-12-22 pages: extension: .txt txt: ./txt/cord-316534-ep7ezoko.txt cache: ./cache/cord-316534-ep7ezoko.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-316534-ep7ezoko.txt' === file2bib.sh === id: cord-319799-h9kot3og author: Schäfer, Alexandra title: Epigenetic Landscape during Coronavirus Infection date: 2017-02-15 pages: extension: .txt txt: ./txt/cord-319799-h9kot3og.txt cache: ./cache/cord-319799-h9kot3og.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-319799-h9kot3og.txt' === file2bib.sh === id: cord-321640-kx3t81yh author: Patrone, Paul N. title: Affine analysis for quantitative PCR measurements date: 2020-09-20 pages: extension: .txt txt: ./txt/cord-321640-kx3t81yh.txt cache: ./cache/cord-321640-kx3t81yh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-321640-kx3t81yh.txt' === file2bib.sh === id: cord-316033-xg8eb2nm author: Easton, Alice title: Molecular evidence of hybridization between pig and human Ascaris indicates an interbred species complex infecting humans date: 2020-11-06 pages: extension: .txt txt: ./txt/cord-316033-xg8eb2nm.txt cache: ./cache/cord-316033-xg8eb2nm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-316033-xg8eb2nm.txt' === file2bib.sh === id: cord-009664-kb9fnbgy author: nan title: Oral presentations date: 2014-12-24 pages: extension: .txt txt: ./txt/cord-009664-kb9fnbgy.txt cache: ./cache/cord-009664-kb9fnbgy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 8 resourceName b'cord-009664-kb9fnbgy.txt' === file2bib.sh === id: cord-328518-umvk59dc author: Lee, Dana N. title: Two novel adenoviruses found in Cave Myotis bats (Myotis velifer) in Oklahoma date: 2019-12-03 pages: extension: .txt txt: ./txt/cord-328518-umvk59dc.txt cache: ./cache/cord-328518-umvk59dc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-328518-umvk59dc.txt' === file2bib.sh === id: cord-321386-u1imic5l author: Li, Chun title: Protein Sequence Comparison and DNA-binding Protein Identification with Generalized PseAAC and Graphical Representation date: 2018-02-17 pages: extension: .txt txt: ./txt/cord-321386-u1imic5l.txt cache: ./cache/cord-321386-u1imic5l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-321386-u1imic5l.txt' === file2bib.sh === id: cord-327170-rv0efgg2 author: Decaro, Nicola title: Tissue distribution of the antigenic variants of canine parvovirus type 2 in dogs date: 2007-03-31 pages: extension: .txt txt: ./txt/cord-327170-rv0efgg2.txt cache: ./cache/cord-327170-rv0efgg2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-327170-rv0efgg2.txt' === file2bib.sh === id: cord-311349-145kwny3 author: Mariani, Stefano title: Surface plasmon resonance applications in clinical analysis date: 2014-02-25 pages: extension: .txt txt: ./txt/cord-311349-145kwny3.txt cache: ./cache/cord-311349-145kwny3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-311349-145kwny3.txt' === file2bib.sh === id: cord-323973-wszo9s3d author: Zhu, Hanliang title: The vision of point-of-care PCR tests for the COVID-19 pandemic and beyond date: 2020-07-20 pages: extension: .txt txt: ./txt/cord-323973-wszo9s3d.txt cache: ./cache/cord-323973-wszo9s3d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-323973-wszo9s3d.txt' === file2bib.sh === id: cord-306798-f28264k3 author: Walsh, Geraldine M. title: Blood-Borne Pathogens: A Canadian Blood Services Centre for Innovation Symposium date: 2016-02-23 pages: extension: .txt txt: ./txt/cord-306798-f28264k3.txt cache: ./cache/cord-306798-f28264k3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306798-f28264k3.txt' === file2bib.sh === id: cord-303978-z3888e3g author: Hong, Ka Lok title: Single-Stranded DNA Aptamers against Pathogens and Toxins: Identification and Biosensing Applications date: 2015-06-23 pages: extension: .txt txt: ./txt/cord-303978-z3888e3g.txt cache: ./cache/cord-303978-z3888e3g.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-303978-z3888e3g.txt' === file2bib.sh === id: cord-328206-iylw1bvw author: Yu, Daojun title: Simultaneous Detection and Differentiation of Human Papillomavirus Genotypes 6, 11, 16 and 18 by AllGlo Quadruplex Quantitative PCR date: 2012-11-09 pages: extension: .txt txt: ./txt/cord-328206-iylw1bvw.txt cache: ./cache/cord-328206-iylw1bvw.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328206-iylw1bvw.txt' === file2bib.sh === id: cord-325280-4whzcmqv author: Takizawa, Naoki title: Current landscape and future prospects of antiviral drugs derived from microbial products date: 2017-10-11 pages: extension: .txt txt: ./txt/cord-325280-4whzcmqv.txt cache: ./cache/cord-325280-4whzcmqv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325280-4whzcmqv.txt' === file2bib.sh === id: cord-324321-y96x8x3h author: Cai, Yingyun title: Down-regulation of transcription of the proapoptotic gene BNip3 in cultured astrocytes by murine coronavirus infection date: 2003-11-10 pages: extension: .txt txt: ./txt/cord-324321-y96x8x3h.txt cache: ./cache/cord-324321-y96x8x3h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-324321-y96x8x3h.txt' === file2bib.sh === id: cord-317213-vhprfb1o author: Tram, Dai Thien Nhan title: Advances in nanomaterials and their applications in point of care (POC) devices for the diagnosis of infectious diseases date: 2016-09-26 pages: extension: .txt txt: ./txt/cord-317213-vhprfb1o.txt cache: ./cache/cord-317213-vhprfb1o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-317213-vhprfb1o.txt' === file2bib.sh === id: cord-324137-nau83mjv author: Saranathan, Nandhini title: G-Quadruplexes: More Than Just a Kink in Microbial Genomes date: 2018-09-14 pages: extension: .txt txt: ./txt/cord-324137-nau83mjv.txt cache: ./cache/cord-324137-nau83mjv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-324137-nau83mjv.txt' === file2bib.sh === id: cord-324811-yjwavea5 author: Kidgell, Claire title: Elucidating genetic diversity with oligonucleotide arrays date: 2005 pages: extension: .txt txt: ./txt/cord-324811-yjwavea5.txt cache: ./cache/cord-324811-yjwavea5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324811-yjwavea5.txt' === file2bib.sh === id: cord-331641-u27ohm5p author: Liu, Xiaonan title: A direct isothermal amplification system adapted for rapid SNP genotyping of multifarious sample types date: 2018-09-15 pages: extension: .txt txt: ./txt/cord-331641-u27ohm5p.txt cache: ./cache/cord-331641-u27ohm5p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-331641-u27ohm5p.txt' === file2bib.sh === id: cord-306904-8iteddug author: Uversky, Vladimir N title: Unreported intrinsic disorder in proteins: Building connections to the literature on IDPs date: 2014-12-12 pages: extension: .txt txt: ./txt/cord-306904-8iteddug.txt cache: ./cache/cord-306904-8iteddug.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306904-8iteddug.txt' === file2bib.sh === id: cord-026025-xqj877en author: PETRAS, ROBERT E. title: Large Intestine (Colon) date: 2009-10-30 pages: extension: .txt txt: ./txt/cord-026025-xqj877en.txt cache: ./cache/cord-026025-xqj877en.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-026025-xqj877en.txt' === file2bib.sh === id: cord-321762-7kiahjyy author: Nandy, Ashesh title: Chapter 5 The GRANCH Techniques for Analysis of DNA, RNA and Protein Sequences date: 2015-12-31 pages: extension: .txt txt: ./txt/cord-321762-7kiahjyy.txt cache: ./cache/cord-321762-7kiahjyy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-321762-7kiahjyy.txt' === file2bib.sh === id: cord-324829-0nz0qioh author: Carabineiro, Sónia Alexandra Correia title: Applications of Gold Nanoparticles in Nanomedicine: Recent Advances in Vaccines † date: 2017-05-22 pages: extension: .txt txt: ./txt/cord-324829-0nz0qioh.txt cache: ./cache/cord-324829-0nz0qioh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324829-0nz0qioh.txt' === file2bib.sh === id: cord-326228-9x1233q6 author: Holley, Caroline L title: The rOX‐stars of inflammation: links between the inflammasome and mitochondrial meltdown date: 2020-02-10 pages: extension: .txt txt: ./txt/cord-326228-9x1233q6.txt cache: ./cache/cord-326228-9x1233q6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-326228-9x1233q6.txt' === file2bib.sh === id: cord-336636-xgfw21hk author: Spezia, Pietro Giorgio title: Redondovirus DNA in human respiratory samples date: 2020-08-15 pages: extension: .txt txt: ./txt/cord-336636-xgfw21hk.txt cache: ./cache/cord-336636-xgfw21hk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336636-xgfw21hk.txt' === file2bib.sh === id: cord-330581-g5r2b043 author: Marini, Elena title: HIV‐1 matrix protein p17 binds to monocytes and selectively stimulates MCP‐1 secretion: role of transcriptional factor AP‐1 date: 2007-10-26 pages: extension: .txt txt: ./txt/cord-330581-g5r2b043.txt cache: ./cache/cord-330581-g5r2b043.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-330581-g5r2b043.txt' === file2bib.sh === id: cord-332844-2se4d1yp author: Yun, Sang-Im title: Bacterial Artificial Chromosomes: A Functional Genomics Tool for the Study of Positive-strand RNA Viruses date: 2015-12-29 pages: extension: .txt txt: ./txt/cord-332844-2se4d1yp.txt cache: ./cache/cord-332844-2se4d1yp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-332844-2se4d1yp.txt' === file2bib.sh === id: cord-332654-nav15g8k author: Paniri, Alireza title: Molecular effects and retinopathy induced by hydroxychloroquine during SARS-CoV-2 therapy: Role of CYP450 isoforms and epigenetic modulations date: 2020-08-04 pages: extension: .txt txt: ./txt/cord-332654-nav15g8k.txt cache: ./cache/cord-332654-nav15g8k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-332654-nav15g8k.txt' === file2bib.sh === id: cord-331718-rjggiklf author: Kubota, Takeo title: Epigenetic Effect of Environmental Factors on Autism Spectrum Disorders date: 2016-05-14 pages: extension: .txt txt: ./txt/cord-331718-rjggiklf.txt cache: ./cache/cord-331718-rjggiklf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-331718-rjggiklf.txt' === file2bib.sh === id: cord-328633-c31xsyeo author: Moser, Michael J. title: Thermostable DNA Polymerase from a Viral Metagenome Is a Potent RT-PCR Enzyme date: 2012-06-04 pages: extension: .txt txt: ./txt/cord-328633-c31xsyeo.txt cache: ./cache/cord-328633-c31xsyeo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328633-c31xsyeo.txt' === file2bib.sh === id: cord-333914-c150ki1n author: Koba, Ryota title: Identification and characterization of a novel bat polyomavirus in Japan date: 2020-08-20 pages: extension: .txt txt: ./txt/cord-333914-c150ki1n.txt cache: ./cache/cord-333914-c150ki1n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-333914-c150ki1n.txt' === file2bib.sh === id: cord-321697-yua3apfi author: Crigna, Adriana Torres title: Cell-free nucleic acid patterns in disease prediction and monitoring—hype or hope? date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-321697-yua3apfi.txt cache: ./cache/cord-321697-yua3apfi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-321697-yua3apfi.txt' === file2bib.sh === id: cord-307914-lgprrwee author: Bartok, Eva title: Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids date: 2020-07-14 pages: extension: .txt txt: ./txt/cord-307914-lgprrwee.txt cache: ./cache/cord-307914-lgprrwee.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-307914-lgprrwee.txt' === file2bib.sh === id: cord-328940-8vtcochx author: Lee, Jeong Yoon title: Bacterial RecA Protein Promotes Adenoviral Recombination during In Vitro Infection date: 2018-06-20 pages: extension: .txt txt: ./txt/cord-328940-8vtcochx.txt cache: ./cache/cord-328940-8vtcochx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-328940-8vtcochx.txt' === file2bib.sh === id: cord-335490-p63qlcnx author: Schenk, Thomas title: Disseminated Bocavirus Infection after Stem Cell Transplant date: 2007-09-17 pages: extension: .txt txt: ./txt/cord-335490-p63qlcnx.txt cache: ./cache/cord-335490-p63qlcnx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-335490-p63qlcnx.txt' === file2bib.sh === id: cord-328460-thx9zh11 author: Zanoli, Laura Maria title: Isothermal Amplification Methods for the Detection of Nucleic Acids in Microfluidic Devices date: 2012-12-27 pages: extension: .txt txt: ./txt/cord-328460-thx9zh11.txt cache: ./cache/cord-328460-thx9zh11.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328460-thx9zh11.txt' === file2bib.sh === id: cord-331916-n744pymd author: Liu, Jue title: Inhibition of porcine circovirus type 2 replication in mice by RNA interference date: 2006-04-10 pages: extension: .txt txt: ./txt/cord-331916-n744pymd.txt cache: ./cache/cord-331916-n744pymd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-331916-n744pymd.txt' === file2bib.sh === id: cord-331557-8axi74nn author: Raoult, Didier title: What does the future hold for clinical microbiology? date: 2004 pages: extension: .txt txt: ./txt/cord-331557-8axi74nn.txt cache: ./cache/cord-331557-8axi74nn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-331557-8axi74nn.txt' === file2bib.sh === id: cord-328899-kog99kk5 author: Ferrari, Stefano title: Barriers to and new approaches for gene therapy and gene delivery in cystic fibrosis date: 2002-12-05 pages: extension: .txt txt: ./txt/cord-328899-kog99kk5.txt cache: ./cache/cord-328899-kog99kk5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-328899-kog99kk5.txt' === file2bib.sh === id: cord-333220-tcvs4beg author: Lee, Szu-Yuan title: Compact optical diagnostic device for isothermal nucleic acids amplification date: 2008-08-12 pages: extension: .txt txt: ./txt/cord-333220-tcvs4beg.txt cache: ./cache/cord-333220-tcvs4beg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-333220-tcvs4beg.txt' === file2bib.sh === id: cord-323029-7hqp8xuq author: Bognár, Zsófia title: Aptamers against Immunoglobulins: Design, Selection and Bioanalytical Applications date: 2020-08-11 pages: extension: .txt txt: ./txt/cord-323029-7hqp8xuq.txt cache: ./cache/cord-323029-7hqp8xuq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-323029-7hqp8xuq.txt' === file2bib.sh === id: cord-342629-mzi0krja author: Wu, Q. title: An Activated GOPS‐poly‐L‐Lysine‐ Coated Glass Surface for the Immobilization of 60mer Oligonucleotides date: 2005-11-16 pages: extension: .txt txt: ./txt/cord-342629-mzi0krja.txt cache: ./cache/cord-342629-mzi0krja.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-342629-mzi0krja.txt' === file2bib.sh === id: cord-329155-ddpfox68 author: Mindikoglu, Ayse L. title: Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome date: 2020-10-27 pages: extension: .txt txt: ./txt/cord-329155-ddpfox68.txt cache: ./cache/cord-329155-ddpfox68.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-329155-ddpfox68.txt' === file2bib.sh === id: cord-339915-8j04y50s author: Deng, Wei title: DV-Curve Representation of Protein Sequences and Its Application date: 2014-05-08 pages: extension: .txt txt: ./txt/cord-339915-8j04y50s.txt cache: ./cache/cord-339915-8j04y50s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-339915-8j04y50s.txt' === file2bib.sh === id: cord-337867-hqmf6r7t author: Shim, Byoung-Shik title: Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses date: 2010-12-31 pages: extension: .txt txt: ./txt/cord-337867-hqmf6r7t.txt cache: ./cache/cord-337867-hqmf6r7t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-337867-hqmf6r7t.txt' === file2bib.sh === id: cord-331698-rwow1ydx author: Latorre-Pérez, Adriel title: A lab in the field: applications of real-time, in situ metagenomic sequencing date: 2020-08-20 pages: extension: .txt txt: ./txt/cord-331698-rwow1ydx.txt cache: ./cache/cord-331698-rwow1ydx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-331698-rwow1ydx.txt' === file2bib.sh === id: cord-339522-jm2xpn1w author: Sharma, Nidhi title: Recombinase‐Based Isothermal Amplification of Nucleic Acids with Self‐Avoiding Molecular Recognition Systems (SAMRS) date: 2014-09-10 pages: extension: .txt txt: ./txt/cord-339522-jm2xpn1w.txt cache: ./cache/cord-339522-jm2xpn1w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-339522-jm2xpn1w.txt' === file2bib.sh === id: cord-325750-x7jpsnxg author: Mokili, John L title: Metagenomics and future perspectives in virus discovery date: 2012-01-20 pages: extension: .txt txt: ./txt/cord-325750-x7jpsnxg.txt cache: ./cache/cord-325750-x7jpsnxg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-325750-x7jpsnxg.txt' === file2bib.sh === id: cord-338633-pxxon1ni author: Zuo, Yu title: Neutrophil extracellular traps and thrombosis in COVID-19 date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-338633-pxxon1ni.txt cache: ./cache/cord-338633-pxxon1ni.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-338633-pxxon1ni.txt' === file2bib.sh === id: cord-336659-qddjqiw9 author: Ramos, Jheneffer Sonara Aguiar title: Multi-biomarker responses to pesticides in an agricultural population from Central Brazil date: 2020-08-21 pages: extension: .txt txt: ./txt/cord-336659-qddjqiw9.txt cache: ./cache/cord-336659-qddjqiw9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-336659-qddjqiw9.txt' === file2bib.sh === id: cord-327883-s9nbr5y8 author: nan title: Section Virology date: 1990-03-31 pages: extension: .txt txt: ./txt/cord-327883-s9nbr5y8.txt cache: ./cache/cord-327883-s9nbr5y8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-327883-s9nbr5y8.txt' === file2bib.sh === id: cord-328947-3l9ydspz author: Webb, L. G. title: Chikungunya virus antagonizes cGAS-STING mediated type-I interferon responses by degrading cGAS date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-328947-3l9ydspz.txt cache: ./cache/cord-328947-3l9ydspz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-328947-3l9ydspz.txt' === file2bib.sh === id: cord-334082-fyxn0g3v author: O’Carroll, I.P. title: Viral Nucleic Acids date: 2015-08-20 pages: extension: .txt txt: ./txt/cord-334082-fyxn0g3v.txt cache: ./cache/cord-334082-fyxn0g3v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-334082-fyxn0g3v.txt' === file2bib.sh === id: cord-336749-qbko22vf author: Kalisch, Thomas title: New readers and interpretations of poly(ADP-ribosyl)ation date: 2012-09-30 pages: extension: .txt txt: ./txt/cord-336749-qbko22vf.txt cache: ./cache/cord-336749-qbko22vf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-336749-qbko22vf.txt' === file2bib.sh === id: cord-339419-b6tr2zyx author: Lee, Thomas Ming-Hung title: DNA-based bioanalytical microsystems for handheld device applications date: 2006-01-18 pages: extension: .txt txt: ./txt/cord-339419-b6tr2zyx.txt cache: ./cache/cord-339419-b6tr2zyx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-339419-b6tr2zyx.txt' === file2bib.sh === id: cord-338942-q4neat3x author: Zhang, Haoqing title: LAMP-on-a-chip: Revising microfluidic platforms for loop-mediated DNA amplification date: 2019-01-31 pages: extension: .txt txt: ./txt/cord-338942-q4neat3x.txt cache: ./cache/cord-338942-q4neat3x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-338942-q4neat3x.txt' === file2bib.sh === id: cord-330800-s91zfzfi author: Reta, Daniel Hussien title: Molecular and Immunological Diagnostic Techniques of Medical Viruses date: 2020-09-04 pages: extension: .txt txt: ./txt/cord-330800-s91zfzfi.txt cache: ./cache/cord-330800-s91zfzfi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-330800-s91zfzfi.txt' === file2bib.sh === id: cord-335839-wgdqu1s1 author: Singh, Meharban title: Pediatrics in 21(st) Century and Beyond date: 2016-08-10 pages: extension: .txt txt: ./txt/cord-335839-wgdqu1s1.txt cache: ./cache/cord-335839-wgdqu1s1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-335839-wgdqu1s1.txt' === file2bib.sh === id: cord-335607-gv96hlw6 author: Yang, Dayong title: Novel DNA materials and their applications date: 2010-08-20 pages: extension: .txt txt: ./txt/cord-335607-gv96hlw6.txt cache: ./cache/cord-335607-gv96hlw6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-335607-gv96hlw6.txt' === file2bib.sh === id: cord-332379-340wczmq author: Pennington, Matthew R. title: Disparate Entry of Adenoviruses Dictates Differential Innate Immune Responses on the Ocular Surface date: 2019-09-13 pages: extension: .txt txt: ./txt/cord-332379-340wczmq.txt cache: ./cache/cord-332379-340wczmq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-332379-340wczmq.txt' === file2bib.sh === id: cord-325915-dw989txm author: Wolf, Michael W title: Downstream processing of cell culture-derived virus particles date: 2014-01-09 pages: extension: .txt txt: ./txt/cord-325915-dw989txm.txt cache: ./cache/cord-325915-dw989txm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-325915-dw989txm.txt' === file2bib.sh === id: cord-342737-hhs3owvr author: Jula, Alma title: Primary and Secondary Human Bocavirus 1 Infections in a Family, Finland date: 2013-08-17 pages: extension: .txt txt: ./txt/cord-342737-hhs3owvr.txt cache: ./cache/cord-342737-hhs3owvr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342737-hhs3owvr.txt' === file2bib.sh === id: cord-004948-ad3i9wgj author: nan title: 7th International Congress on Amino Acids and Proteins : Vienna, Austria, August 6–10, 2001 date: 2001 pages: extension: .txt txt: ./txt/cord-004948-ad3i9wgj.txt cache: ./cache/cord-004948-ad3i9wgj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 9 resourceName b'cord-004948-ad3i9wgj.txt' === file2bib.sh === id: cord-338164-pyam9yn3 author: Livingston, Andrew D title: Biochip sensors for the rapid and sensitive detection of viral disease date: 2005-05-26 pages: extension: .txt txt: ./txt/cord-338164-pyam9yn3.txt cache: ./cache/cord-338164-pyam9yn3.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-338164-pyam9yn3.txt' === file2bib.sh === id: cord-336219-xndxn1r3 author: Chuang, Chi-Mu title: Treatment with Imiquimod enhances antitumor immunity induced by therapeutic HPV DNA vaccination date: 2010-04-28 pages: extension: .txt txt: ./txt/cord-336219-xndxn1r3.txt cache: ./cache/cord-336219-xndxn1r3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336219-xndxn1r3.txt' === file2bib.sh === id: cord-343029-85ga6r7d author: Haghpanah, Abdolreza title: Potential mechanisms of SARS‐CoV‐2 action on male gonadal function and fertility: Current status and future prospects date: 2020-10-27 pages: extension: .txt txt: ./txt/cord-343029-85ga6r7d.txt cache: ./cache/cord-343029-85ga6r7d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343029-85ga6r7d.txt' === file2bib.sh === id: cord-341062-k3vjqumq author: Pruitt, Hawley C. title: Roles of N‐Myc and STAT interactor in cancer: From initiation to dissemination date: 2016-03-11 pages: extension: .txt txt: ./txt/cord-341062-k3vjqumq.txt cache: ./cache/cord-341062-k3vjqumq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-341062-k3vjqumq.txt' === file2bib.sh === id: cord-333524-a6p6ma8r author: Khan, Pavana title: Isothermal SARS-CoV-2 Diagnostics: Tools for Enabling Distributed Pandemic Testing as a Means of Supporting Safe Reopenings date: 2020-09-23 pages: extension: .txt txt: ./txt/cord-333524-a6p6ma8r.txt cache: ./cache/cord-333524-a6p6ma8r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-333524-a6p6ma8r.txt' === file2bib.sh === id: cord-339369-9z30nksl author: Chiappetta, Catarina Marcon title: Molecular Detection of Circovirus and Adenovirus in Feces of Fur Seals (Arctocephalus spp.) date: 2016-11-01 pages: extension: .txt txt: ./txt/cord-339369-9z30nksl.txt cache: ./cache/cord-339369-9z30nksl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-339369-9z30nksl.txt' === file2bib.sh === id: cord-340781-z348xbn0 author: Namvar, Ali title: In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine date: 2019-10-23 pages: extension: .txt txt: ./txt/cord-340781-z348xbn0.txt cache: ./cache/cord-340781-z348xbn0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-340781-z348xbn0.txt' === file2bib.sh === id: cord-343775-tcljwdlo author: Tiee, Madeline S. title: Ghosts of infections past: using archival samples to understand a century of monkeypox virus prevalence among host communities across space and time date: 2018-01-31 pages: extension: .txt txt: ./txt/cord-343775-tcljwdlo.txt cache: ./cache/cord-343775-tcljwdlo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343775-tcljwdlo.txt' === file2bib.sh === id: cord-342015-bz2vab6e author: Ouadfeul, Sid-Ali title: Multifractal Analysis of SARS-CoV-2 Coronavirus genomes using the wavelet transform date: 2020-08-16 pages: extension: .txt txt: ./txt/cord-342015-bz2vab6e.txt cache: ./cache/cord-342015-bz2vab6e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342015-bz2vab6e.txt' === file2bib.sh === id: cord-338812-q24jycgk author: Zakaryan, H. title: Nuclear remodelling during viral infections date: 2011-04-28 pages: extension: .txt txt: ./txt/cord-338812-q24jycgk.txt cache: ./cache/cord-338812-q24jycgk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-338812-q24jycgk.txt' === file2bib.sh === id: cord-023055-ntbvmssh author: nan title: Immunogenicity date: 2004-02-19 pages: extension: .txt txt: ./txt/cord-023055-ntbvmssh.txt cache: ./cache/cord-023055-ntbvmssh.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-023055-ntbvmssh.txt' === file2bib.sh === id: cord-346043-8vcvalhp author: Lee, Jong B. title: Multifunctional nanoarchitectures from DNA-based ABC monomers date: 2009-05-03 pages: extension: .txt txt: ./txt/cord-346043-8vcvalhp.txt cache: ./cache/cord-346043-8vcvalhp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-346043-8vcvalhp.txt' === file2bib.sh === id: cord-338582-o976nab9 author: Dahlhausen, Bob title: Future Veterinary Diagnostics date: 2010-09-19 pages: extension: .txt txt: ./txt/cord-338582-o976nab9.txt cache: ./cache/cord-338582-o976nab9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-338582-o976nab9.txt' === file2bib.sh === id: cord-345552-h6fwi0qn author: Li, Q.-G. title: Hydropathic characteristics of adenovirus hexons date: 1997-07-01 pages: extension: .txt txt: ./txt/cord-345552-h6fwi0qn.txt cache: ./cache/cord-345552-h6fwi0qn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-345552-h6fwi0qn.txt' === file2bib.sh === id: cord-341521-dntkdwkj author: Luo, Yi-Ran title: Porcine Epidemic Diarrhoea Virus Induces Cell-cycle Arrest through the DNA Damage-signalling Pathway date: 2020-03-24 pages: extension: .txt txt: ./txt/cord-341521-dntkdwkj.txt cache: ./cache/cord-341521-dntkdwkj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-341521-dntkdwkj.txt' === file2bib.sh === id: cord-342819-p8wp6yvo author: De Groot, Anne S title: Making vaccines “on demand”: A potential solution for emerging pathogens and biodefense? date: 2013-09-01 pages: extension: .txt txt: ./txt/cord-342819-p8wp6yvo.txt cache: ./cache/cord-342819-p8wp6yvo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342819-p8wp6yvo.txt' === file2bib.sh === id: cord-341287-i1hyk962 author: Smith, Trevor R. F. title: Immunogenicity of a DNA vaccine candidate for COVID-19 date: 2020-05-20 pages: extension: .txt txt: ./txt/cord-341287-i1hyk962.txt cache: ./cache/cord-341287-i1hyk962.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-341287-i1hyk962.txt' === file2bib.sh === id: cord-347221-g98q9cga author: Piyush, Ravikant title: Nucleic acid-based therapy for coronavirus disease 2019 date: 2020-09-19 pages: extension: .txt txt: ./txt/cord-347221-g98q9cga.txt cache: ./cache/cord-347221-g98q9cga.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-347221-g98q9cga.txt' === file2bib.sh === id: cord-324944-ixh3ykrc author: Mitsakakis, Konstantinos title: Diagnostic tools for tackling febrile illness and enhancing patient management date: 2018-12-05 pages: extension: .txt txt: ./txt/cord-324944-ixh3ykrc.txt cache: ./cache/cord-324944-ixh3ykrc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-324944-ixh3ykrc.txt' === file2bib.sh === id: cord-342782-xty16m8w author: Marrugal-Lorenzo, José A. title: Repositioning salicylanilide anthelmintic drugs to treat adenovirus infections date: 2019-01-09 pages: extension: .txt txt: ./txt/cord-342782-xty16m8w.txt cache: ./cache/cord-342782-xty16m8w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342782-xty16m8w.txt' === file2bib.sh === id: cord-346280-7sw30bsz author: Ramos Venancio, D. B. title: Biomathematical models for genetic diversity analyses in complete genomes of SARS-CoV-2 date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-346280-7sw30bsz.txt cache: ./cache/cord-346280-7sw30bsz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-346280-7sw30bsz.txt' === file2bib.sh === id: cord-345494-8lcdx719 author: Chao, Chien-Chung title: Development of Recombinase Polymerase Amplification Assays for Detection of Orientia tsutsugamushi or Rickettsia typhi date: 2015-07-10 pages: extension: .txt txt: ./txt/cord-345494-8lcdx719.txt cache: ./cache/cord-345494-8lcdx719.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-345494-8lcdx719.txt' === file2bib.sh === id: cord-345712-gmzue6lj author: Palazzo, Luca title: ADP‐ribosylation: new facets of an ancient modification date: 2017-04-26 pages: extension: .txt txt: ./txt/cord-345712-gmzue6lj.txt cache: ./cache/cord-345712-gmzue6lj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-345712-gmzue6lj.txt' === file2bib.sh === id: cord-335864-392xmrq0 author: Sun, Yu-Meng title: Principles and innovative technologies for decrypting noncoding RNAs: from discovery and functional prediction to clinical application date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-335864-392xmrq0.txt cache: ./cache/cord-335864-392xmrq0.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-335864-392xmrq0.txt' === file2bib.sh === id: cord-351197-xv6ymc4l author: Cibulski, Samuel title: A plate of viruses: Viral metagenomics of supermarket chicken, pork and beef from Brazil date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-351197-xv6ymc4l.txt cache: ./cache/cord-351197-xv6ymc4l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-351197-xv6ymc4l.txt' === file2bib.sh === id: cord-339152-wfakzb6w author: Trovato, Maria title: Viral Emerging Diseases: Challenges in Developing Vaccination Strategies date: 2020-09-03 pages: extension: .txt txt: ./txt/cord-339152-wfakzb6w.txt cache: ./cache/cord-339152-wfakzb6w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-339152-wfakzb6w.txt' === file2bib.sh === id: cord-343470-w215pzdc author: Tsai, Kevin title: Epigenetic and epitranscriptomic regulation of viral replication date: 2020-06-12 pages: extension: .txt txt: ./txt/cord-343470-w215pzdc.txt cache: ./cache/cord-343470-w215pzdc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343470-w215pzdc.txt' === file2bib.sh === id: cord-346853-0c1qdjb5 author: Holmes, E. C. title: The Evolutionary Genetics of Viral Emergence date: 2007 pages: extension: .txt txt: ./txt/cord-346853-0c1qdjb5.txt cache: ./cache/cord-346853-0c1qdjb5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-346853-0c1qdjb5.txt' === file2bib.sh === id: cord-347472-n6811ens author: Rosebrock, Adam P. title: Patient DNA cross-reactivity of the CDC SARS-CoV-2 extraction control leads to an inherent potential for false negative results date: 2020-05-15 pages: extension: .txt txt: ./txt/cord-347472-n6811ens.txt cache: ./cache/cord-347472-n6811ens.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-347472-n6811ens.txt' === file2bib.sh === id: cord-345903-ggkn1w5y author: Revathidevi, Sundaramoorthy title: APOBEC: A molecular driver in cervical cancer pathogenesis date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-345903-ggkn1w5y.txt cache: ./cache/cord-345903-ggkn1w5y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-345903-ggkn1w5y.txt' === file2bib.sh === id: cord-346450-x1u567ss author: del Fresno, Carlos title: Myeloid cells in sensing of tissue damage date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-346450-x1u567ss.txt cache: ./cache/cord-346450-x1u567ss.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-346450-x1u567ss.txt' === file2bib.sh === id: cord-345144-zvu22n8f author: Compagnone, D. title: Chapter 29 Rapid detection of organophosphates, Ochratoxin A, and Fusarium sp. in durum wheat via screen printed based electrochemical sensors date: 2007-12-31 pages: extension: .txt txt: ./txt/cord-345144-zvu22n8f.txt cache: ./cache/cord-345144-zvu22n8f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-345144-zvu22n8f.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 98111 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-349042-u9svz7pf author: Li, Jifen title: The successes and future prospects of the linear antisense RNA amplification methodology date: 2018-03-29 pages: extension: .txt txt: ./txt/cord-349042-u9svz7pf.txt cache: ./cache/cord-349042-u9svz7pf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-349042-u9svz7pf.txt' === file2bib.sh === id: cord-350890-ajxvjkmq author: Hsieh, Yi-Fan title: A real-time convective PCR machine in a capillary tube instrumented with a CCD-based fluorometer date: 2013-07-05 pages: extension: .txt txt: ./txt/cord-350890-ajxvjkmq.txt cache: ./cache/cord-350890-ajxvjkmq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-350890-ajxvjkmq.txt' === file2bib.sh === id: cord-350807-qdq96723 author: Reckziegel, Maria title: Viruses and atypical bacteria in the respiratory tract of immunocompromised and immunocompetent patients with airway infection date: 2020-05-27 pages: extension: .txt txt: ./txt/cord-350807-qdq96723.txt cache: ./cache/cord-350807-qdq96723.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-350807-qdq96723.txt' === file2bib.sh === id: cord-344749-omzhhr0k author: Kaya, Sariye Irem title: Electrochemical virus detections with nanobiosensors date: 2020-02-14 pages: extension: .txt txt: ./txt/cord-344749-omzhhr0k.txt cache: ./cache/cord-344749-omzhhr0k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-344749-omzhhr0k.txt' === file2bib.sh === id: cord-351295-4toxlskr author: Lanave, Gianvito title: Identification of hepadnavirus in the sera of cats date: 2019-07-23 pages: extension: .txt txt: ./txt/cord-351295-4toxlskr.txt cache: ./cache/cord-351295-4toxlskr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351295-4toxlskr.txt' === file2bib.sh === id: cord-350004-o151wwcf author: An, D. J. title: A DNA miniarray system for simultaneous visual detection of porcine circovirus type 1 (PCV1) and 2 (PCV2) in pigs date: 2008-07-24 pages: extension: .txt txt: ./txt/cord-350004-o151wwcf.txt cache: ./cache/cord-350004-o151wwcf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350004-o151wwcf.txt' === file2bib.sh === id: cord-346104-18x8u2oe author: Black, Wendy title: Identification of gammaherpesvirus infection in free-ranging black bears (Ursus americanus) date: 2019-01-02 pages: extension: .txt txt: ./txt/cord-346104-18x8u2oe.txt cache: ./cache/cord-346104-18x8u2oe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-346104-18x8u2oe.txt' === file2bib.sh === id: cord-354990-2hx7f6ny author: ZAKIAN, VIRGINIA A. title: Telomere formation in yeast date: 1989 pages: extension: .txt txt: ./txt/cord-354990-2hx7f6ny.txt cache: ./cache/cord-354990-2hx7f6ny.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-354990-2hx7f6ny.txt' === file2bib.sh === id: cord-347992-coby2m6e author: Marton, Soledad title: In Vitro and Ex Vivo Selection Procedures for Identifying Potentially Therapeutic DNA and RNA Molecules date: 2010-06-28 pages: extension: .txt txt: ./txt/cord-347992-coby2m6e.txt cache: ./cache/cord-347992-coby2m6e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-347992-coby2m6e.txt' === file2bib.sh === id: cord-340503-zwdewiu1 author: Mokhtarzadeh, Ahad title: Nanomaterial-based biosensors for detection of pathogenic virus date: 2017-10-13 pages: extension: .txt txt: ./txt/cord-340503-zwdewiu1.txt cache: ./cache/cord-340503-zwdewiu1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-340503-zwdewiu1.txt' === file2bib.sh === id: cord-348860-zaimorg0 author: Ratra, Ruchi title: Functional genomics as a tool in virus research date: 2008-06-01 pages: extension: .txt txt: ./txt/cord-348860-zaimorg0.txt cache: ./cache/cord-348860-zaimorg0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-348860-zaimorg0.txt' === file2bib.sh === id: cord-352619-s2x53grh author: Payne, Natalie title: Novel Circoviruses Detected in Feces of Sonoran Felids date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-352619-s2x53grh.txt cache: ./cache/cord-352619-s2x53grh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-352619-s2x53grh.txt' === file2bib.sh === id: cord-348104-7662q8dg author: Yang, Xiaoyun title: Molecular basis for the MacroD1-mediated hydrolysis of ADP-ribosylation date: 2020-06-22 pages: extension: .txt txt: ./txt/cord-348104-7662q8dg.txt cache: ./cache/cord-348104-7662q8dg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-348104-7662q8dg.txt' === file2bib.sh === id: cord-353389-5dtwje1b author: Han, Guojun title: Absolute and Relative Quantification of Multiplex DNA Assays Based on an Elemental Labeling Strategy date: 2013-01-28 pages: extension: .txt txt: ./txt/cord-353389-5dtwje1b.txt cache: ./cache/cord-353389-5dtwje1b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-353389-5dtwje1b.txt' === file2bib.sh === id: cord-341634-mpk8mmp8 author: Sadana, Ajit title: Detection of Analytes on Arrays/Microarrays/DNA Chips date: 2010-09-02 pages: extension: .txt txt: ./txt/cord-341634-mpk8mmp8.txt cache: ./cache/cord-341634-mpk8mmp8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-341634-mpk8mmp8.txt' === file2bib.sh === id: cord-353297-jizitnfl author: Meyer, R.F. title: Viruses and Bioterrorism date: 2008-07-30 pages: extension: .txt txt: ./txt/cord-353297-jizitnfl.txt cache: ./cache/cord-353297-jizitnfl.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-353297-jizitnfl.txt' === file2bib.sh === id: cord-352891-ljmkqdzx author: Parang, Keykavous title: Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs against Human Coronavirus 229E (HCoV-229E) date: 2020-05-17 pages: extension: .txt txt: ./txt/cord-352891-ljmkqdzx.txt cache: ./cache/cord-352891-ljmkqdzx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-352891-ljmkqdzx.txt' === file2bib.sh === id: cord-015348-qt0worsl author: nan title: Abstract date: 2010-07-30 pages: extension: .txt txt: ./txt/cord-015348-qt0worsl.txt cache: ./cache/cord-015348-qt0worsl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 7 resourceName b'cord-015348-qt0worsl.txt' === file2bib.sh === id: cord-326785-le2t1l8g author: nan title: Pathological Society of Great Britain and Ireland. 163rd meeting, 3–5 July 1991 date: 2005-06-15 pages: extension: .txt txt: ./txt/cord-326785-le2t1l8g.txt cache: ./cache/cord-326785-le2t1l8g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-326785-le2t1l8g.txt' === file2bib.sh === id: cord-004879-pgyzluwp author: nan title: Programmed cell death date: 1994 pages: extension: .txt txt: ./txt/cord-004879-pgyzluwp.txt cache: ./cache/cord-004879-pgyzluwp.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-004879-pgyzluwp.txt' === file2bib.sh === id: cord-354000-jxqskt4k author: Warren, Cody J. title: The Antiviral Restriction Factors IFITM1, 2 and 3 Do Not Inhibit Infection of Human Papillomavirus, Cytomegalovirus and Adenovirus date: 2014-05-14 pages: extension: .txt txt: ./txt/cord-354000-jxqskt4k.txt cache: ./cache/cord-354000-jxqskt4k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-354000-jxqskt4k.txt' === file2bib.sh === id: cord-347569-9fvbshz2 author: Balakrishnan, Krishnan Nair title: Multiple gene targeting siRNAs for down regulation of Immediate Early-2 (Ie2) and DNA polymerase genes mediated inhibition of novel rat Cytomegalovirus (strain All-03) date: 2020-10-27 pages: extension: .txt txt: ./txt/cord-347569-9fvbshz2.txt cache: ./cache/cord-347569-9fvbshz2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-347569-9fvbshz2.txt' === file2bib.sh === id: cord-349672-2kt7xw8i author: Dasgupta, Tumpa title: Mechanism of Type IA Topoisomerases date: 2020-10-17 pages: extension: .txt txt: ./txt/cord-349672-2kt7xw8i.txt cache: ./cache/cord-349672-2kt7xw8i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-349672-2kt7xw8i.txt' === file2bib.sh === id: cord-341029-49360l2a author: Nasir, Arshan title: A phylogenomic data-driven exploration of viral origins and evolution date: 2015-09-25 pages: extension: .txt txt: ./txt/cord-341029-49360l2a.txt cache: ./cache/cord-341029-49360l2a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-341029-49360l2a.txt' === file2bib.sh === id: cord-356291-0x1jhya6 author: Tang, Liang title: Three-dimensional structure of the bacteriophage P22 tail machine date: 2005-06-02 pages: extension: .txt txt: ./txt/cord-356291-0x1jhya6.txt cache: ./cache/cord-356291-0x1jhya6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-356291-0x1jhya6.txt' === file2bib.sh === id: cord-352172-g0jiaenw author: Stoevesandt, Oda title: Protein microarrays: high-throughput tools for proteomics date: 2014-01-09 pages: extension: .txt txt: ./txt/cord-352172-g0jiaenw.txt cache: ./cache/cord-352172-g0jiaenw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-352172-g0jiaenw.txt' === file2bib.sh === id: cord-350212-448mv4lt author: Chiuppesi, Flavia title: Development of a Multi-Antigenic SARS-CoV-2 Vaccine Using a Synthetic Poxvirus Platform date: 2020-07-17 pages: extension: .txt txt: ./txt/cord-350212-448mv4lt.txt cache: ./cache/cord-350212-448mv4lt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350212-448mv4lt.txt' === file2bib.sh === id: cord-355913-fhvt1ht1 author: Burrell, Christopher J. title: Virus Replication date: 2016-11-11 pages: extension: .txt txt: ./txt/cord-355913-fhvt1ht1.txt cache: ./cache/cord-355913-fhvt1ht1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-355913-fhvt1ht1.txt' === file2bib.sh === id: cord-346308-9h2fk9qt author: Kaur, Rajwinder title: Microbiology of hospital wastewater date: 2020-05-01 pages: extension: .txt txt: ./txt/cord-346308-9h2fk9qt.txt cache: ./cache/cord-346308-9h2fk9qt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-346308-9h2fk9qt.txt' === file2bib.sh === id: cord-350019-4nlbu54e author: Robinson, Elektra K. title: The how and why of lncRNA function: An innate immune perspective() date: 2019-09-02 pages: extension: .txt txt: ./txt/cord-350019-4nlbu54e.txt cache: ./cache/cord-350019-4nlbu54e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-350019-4nlbu54e.txt' === file2bib.sh === id: cord-346890-4vozhns4 author: Prajapati, Deepak G. title: Progress in the Development of Intrinsically Conducting Polymer Composites as Biosensors date: 2019-04-23 pages: extension: .txt txt: ./txt/cord-346890-4vozhns4.txt cache: ./cache/cord-346890-4vozhns4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-346890-4vozhns4.txt' === file2bib.sh === id: cord-346965-0oq2n0af author: Liu, Zhi-Ping title: Bridging protein local structures and protein functions date: 2008-04-18 pages: extension: .txt txt: ./txt/cord-346965-0oq2n0af.txt cache: ./cache/cord-346965-0oq2n0af.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-346965-0oq2n0af.txt' === file2bib.sh === id: cord-344321-fjer281d author: Ning, Yi title: Aptamers used for biosensors and targeted therapy date: 2020-10-20 pages: extension: .txt txt: ./txt/cord-344321-fjer281d.txt cache: ./cache/cord-344321-fjer281d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-344321-fjer281d.txt' === file2bib.sh === id: cord-023225-5quigar4 author: nan title: Posters date: 2012-08-21 pages: extension: .txt txt: ./txt/cord-023225-5quigar4.txt cache: ./cache/cord-023225-5quigar4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 18 resourceName b'cord-023225-5quigar4.txt' === file2bib.sh === id: cord-023592-w96h4rir author: nan title: Abstracts cont. date: 2015-12-28 pages: extension: .txt txt: ./txt/cord-023592-w96h4rir.txt cache: ./cache/cord-023592-w96h4rir.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 8 resourceName b'cord-023592-w96h4rir.txt' === file2bib.sh === id: cord-004675-n8mlxe7p author: nan title: 2019 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference date: 2019-02-26 pages: extension: .txt txt: ./txt/cord-004675-n8mlxe7p.txt cache: ./cache/cord-004675-n8mlxe7p.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 7 resourceName b'cord-004675-n8mlxe7p.txt' === file2bib.sh === id: cord-015368-a0qz4tb9 author: nan title: 48th Annual Meeting of the Austrian Society of Surgery, Graz, June 7–9, 2007 date: 2007 pages: extension: .txt txt: ./txt/cord-015368-a0qz4tb9.txt cache: ./cache/cord-015368-a0qz4tb9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 8 resourceName b'cord-015368-a0qz4tb9.txt' === file2bib.sh === id: cord-006466-e1phpqes author: nan title: 2018 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference date: 2018-04-23 pages: extension: .txt txt: ./txt/cord-006466-e1phpqes.txt cache: ./cache/cord-006466-e1phpqes.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 9 resourceName b'cord-006466-e1phpqes.txt' === file2bib.sh === id: cord-347710-ff64y6ef author: Wan, Qianya title: Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development date: 2020-07-13 pages: extension: .txt txt: ./txt/cord-347710-ff64y6ef.txt cache: ./cache/cord-347710-ff64y6ef.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-347710-ff64y6ef.txt' === file2bib.sh === id: cord-267671-ys43n672 author: Whary, Mark T. title: Biology and Diseases of Mice date: 2015-07-10 pages: extension: .txt txt: ./txt/cord-267671-ys43n672.txt cache: ./cache/cord-267671-ys43n672.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 7 resourceName b'cord-267671-ys43n672.txt' === file2bib.sh === id: cord-000083-3p81yr4n author: nan title: Poster Exhibition date: 2009-01-31 pages: extension: .txt txt: ./txt/cord-000083-3p81yr4n.txt cache: ./cache/cord-000083-3p81yr4n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 22 resourceName b'cord-000083-3p81yr4n.txt' === file2bib.sh === id: cord-006229-7yoilsho author: nan title: Abstracts of the 82(nd) Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and the 18(th) Annual Meeting of the Network Clinical Pharmacology Germany (VKliPha) in cooperation with the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e.V. (AGAH) date: 2016-02-06 pages: extension: .txt txt: ./txt/cord-006229-7yoilsho.txt cache: ./cache/cord-006229-7yoilsho.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 12 resourceName b'cord-006229-7yoilsho.txt' === file2bib.sh === id: cord-023209-un2ysc2v author: nan title: Poster Presentations date: 2008-10-07 pages: extension: .txt txt: ./txt/cord-023209-un2ysc2v.txt cache: ./cache/cord-023209-un2ysc2v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 9 resourceName b'cord-023209-un2ysc2v.txt' === file2bib.sh === id: cord-001835-0s7ok4uw author: nan title: Abstracts of the 29th Annual Symposium of The Protein Society date: 2015-10-01 pages: extension: .txt txt: ./txt/cord-001835-0s7ok4uw.txt cache: ./cache/cord-001835-0s7ok4uw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 10 resourceName b'cord-001835-0s7ok4uw.txt' === file2bib.sh === id: cord-023346-8sqbqjm1 author: nan title: MONDAY: POSTERS date: 2005-06-08 pages: extension: .txt txt: ./txt/cord-023346-8sqbqjm1.txt cache: ./cache/cord-023346-8sqbqjm1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 13 resourceName b'cord-023346-8sqbqjm1.txt' === file2bib.sh === id: cord-023364-ut56gczm author: nan title: EDUCATION DAY MONDAY: PLENARY SESSION 1 MONDAY: PARALLEL SESSIONS date: 2005-06-08 pages: extension: .txt txt: ./txt/cord-023364-ut56gczm.txt cache: ./cache/cord-023364-ut56gczm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 21 resourceName b'cord-023364-ut56gczm.txt' === file2bib.sh === id: cord-023354-f2ciho6o author: nan title: TUESDAY PLENARY SESSION 3 TUESDAY: POSTERS date: 2005-06-08 pages: extension: .txt txt: ./txt/cord-023354-f2ciho6o.txt cache: ./cache/cord-023354-f2ciho6o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 12 resourceName b'cord-023354-f2ciho6o.txt' === file2bib.sh === id: cord-006230-xta38e7j author: nan title: Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date: 2012-02-22 pages: extension: .txt txt: ./txt/cord-006230-xta38e7j.txt cache: ./cache/cord-006230-xta38e7j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 13 resourceName b'cord-006230-xta38e7j.txt' === file2bib.sh === id: cord-004534-jqm1hxps author: nan title: Abstract date: 2009-06-09 pages: extension: .txt txt: ./txt/cord-004534-jqm1hxps.txt cache: ./cache/cord-004534-jqm1hxps.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 24 resourceName b'cord-004534-jqm1hxps.txt' === file2bib.sh === id: cord-008777-i2reanan author: nan title: ECB12: 12th European Congess on Biotechnology date: 2005-07-19 pages: extension: .txt txt: ./txt/cord-008777-i2reanan.txt cache: ./cache/cord-008777-i2reanan.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 23 resourceName b'cord-008777-i2reanan.txt' === file2bib.sh === id: cord-023095-4dannjjm author: nan title: Research Abstract Program of the 2011 ACVIM Forum Denver, Colorado, June 15–18, 2011 date: 2011-05-03 pages: extension: .txt txt: ./txt/cord-023095-4dannjjm.txt cache: ./cache/cord-023095-4dannjjm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 9 resourceName b'cord-023095-4dannjjm.txt' === file2bib.sh === id: cord-022501-9wnmdvg5 author: nan title: P1460 – P1884 date: 2015-12-28 pages: extension: .txt txt: ./txt/cord-022501-9wnmdvg5.txt cache: ./cache/cord-022501-9wnmdvg5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 10 resourceName b'cord-022501-9wnmdvg5.txt' === file2bib.sh === id: cord-014794-yppi30a0 author: nan title: 19th European Congress of Pathology, Ljubljana, Slovenia, September 6-11, 2003 date: 2003-07-31 pages: extension: .txt txt: ./txt/cord-014794-yppi30a0.txt cache: ./cache/cord-014794-yppi30a0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 13 resourceName b'cord-014794-yppi30a0.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 41900 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-000718-7whai7nr author: nan title: ESP Abstracts 2012 date: 2012-08-22 pages: extension: .txt txt: ./txt/cord-000718-7whai7nr.txt cache: ./cache/cord-000718-7whai7nr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 15 resourceName b'cord-000718-7whai7nr.txt' === file2bib.sh === id: cord-023211-kt5gt26t author: nan title: Poster Session Abstracts date: 2007-08-29 pages: extension: .txt txt: ./txt/cord-023211-kt5gt26t.txt cache: ./cache/cord-023211-kt5gt26t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 28 resourceName b'cord-023211-kt5gt26t.txt' === file2bib.sh === id: cord-031907-ilhr3iu5 author: nan title: ISEV2020 Abstract Book date: 2020-07-15 pages: extension: .txt txt: ./txt/cord-031907-ilhr3iu5.txt cache: ./cache/cord-031907-ilhr3iu5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 15 resourceName b'cord-031907-ilhr3iu5.txt' === file2bib.sh === id: cord-010092-uftc8inx author: nan title: Abstract of 29th Regional Congress of the ISBT date: 2019-06-07 pages: extension: .txt txt: ./txt/cord-010092-uftc8inx.txt cache: ./cache/cord-010092-uftc8inx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 29 resourceName b'cord-010092-uftc8inx.txt' === file2bib.sh === id: cord-022940-atbjwpo5 author: nan title: Poster Sessions date: 2016-09-07 pages: extension: .txt txt: ./txt/cord-022940-atbjwpo5.txt cache: ./cache/cord-022940-atbjwpo5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 25 resourceName b'cord-022940-atbjwpo5.txt' === file2bib.sh === id: cord-015394-uj7fe5y6 author: nan title: Scientific Abstracts date: 2008-12-23 pages: extension: .txt txt: ./txt/cord-015394-uj7fe5y6.txt cache: ./cache/cord-015394-uj7fe5y6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 14 resourceName b'cord-015394-uj7fe5y6.txt' === file2bib.sh === id: cord-010119-t1x9gknd author: nan title: Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 date: 2017-09-04 pages: extension: .txt txt: ./txt/cord-010119-t1x9gknd.txt cache: ./cache/cord-010119-t1x9gknd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 11 resourceName b'cord-010119-t1x9gknd.txt' Que is empty; done keyword-dna-cord === reduce.pl bib === id = cord-000049-rl7sdzd7 author = Lee, David title = Detection of genetically modified organisms (GMOs) using isothermal amplification of target DNA sequences date = 2009-02-02 pages = extension = .txt mime = text/plain words = 2899 sentences = 141 flesch = 55 summary = Here we have applied the loop-mediated isothermal amplification (LAMP) method to amplify GMO-related DNA sequences, 'internal' commonly-used motifs for controlling transgene expression and event-specific (plant-transgene) junctions. Moreover, the sensitivity and ability to amplify targets, even with a high background of DNA, here demonstrated, highlights the advantages of this isothermal amplification when applied for GMO detection. Here we assess the LAMP protocol for the detection of GMOs using primers that target event-specific sequences for transgenic MS8 and RF3 oilseed rape (Brassica napus L.) and generic GMO sequences such as the cauliflower mosaic virus 35S promoter (P-35S) and the promoter and terminator for the nopaline synthase gene (P-nos and T-nos, respectively) from Agrobacterium spp. LAMP sensitivity was assessed by the detection of ten RoundUp Ready™ GMO targets in a background of 100 ng of genomic oilseed rape DNA (Figure 3 ). cache = ./cache/cord-000049-rl7sdzd7.txt txt = ./txt/cord-000049-rl7sdzd7.txt === reduce.pl bib === id = cord-000104-3b8b8p61 author = McWhirter, Sarah M. title = A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP date = 2009-08-31 pages = extension = .txt mime = text/plain words = 8572 sentences = 499 flesch = 56 summary = The potency of cytosolic signaling induced by c-di-GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, nuclear factor κB, and MAP kinases. Cell type-specific responses to cytosolic DNA and c-di-GMP Collectively, these results suggest that there are strong similarities in the signaling pathways triggered by the cytosolic presence of c-di-GMP and other nucleic acids, such as DNA and RNA. These results suggest that at least one component of the host signaling pathway responding to c-di-GMP is distinct from that used for responses to cytosolic RNA or DNA, and is differentially expressed in different cell types. cache = ./cache/cord-000104-3b8b8p61.txt txt = ./txt/cord-000104-3b8b8p61.txt === reduce.pl bib === id = cord-000937-8vk89i4h author = Law, John title = Identification of Hepatotropic Viruses from Plasma Using Deep Sequencing: A Next Generation Diagnostic Tool date = 2013-04-17 pages = extension = .txt mime = text/plain words = 6644 sentences = 332 flesch = 50 summary = RNA and DNA libraries were sequenced from plasma filtrates enriched in viral particles to catalog virus populations. Seven RNA libraries (aihP01, hbvP02, hcvP02, hcvP03, hcvP05, nshP01, norP01) and seven DNA libraries (aihP01D, hbvP02D, hcvP02D, hcvP03D, hcvP05D, nshP01D, norP01D) were constructed from patients with autoimmune hepatitis (AIH), hepatitis B virus (HBV) chronic infection, hepatitis C virus (HCV) chronic infection, non-alcoholic steatohepatitis (NASH), and healthy subjects (NOR). Plasma samples were obtained from patients with autoimmune hepatitis (AIH), chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, non-alcoholic steatohepatitis (NASH), and healthy subjects (NOR); each RNA library was named by diagnosis (e.g. aihP01) and a suffix 'D' was added for each DNA library (e.g. aihP01D). To a lesser extent (about one read per million), we also detected sequences resembling RNA viruses in our DNA libraries (Supplemental Tables S15-S28 ). Assembly of viral sequences was also possible for all viruses shown in Figure 2 as the most abundant virus in each library (data not shown). cache = ./cache/cord-000937-8vk89i4h.txt txt = ./txt/cord-000937-8vk89i4h.txt === reduce.pl bib === id = cord-000050-tfcerilc author = Rao, Srinivas title = Multivalent HA DNA Vaccination Protects against Highly Pathogenic H5N1 Avian Influenza Infection in Chickens and Mice date = 2008-06-18 pages = extension = .txt mime = text/plain words = 5605 sentences = 256 flesch = 44 summary = METHODOLOGY / PRINCIPAL FINDINGS: The ability of DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. After optimization of injection conditions, alternative multivalent DNA vaccine regimens were analyzed and compared for magnitude and breadth of neutralizing antibodies, as well as protective efficacy after challenge in mouse and chicken models of HPAI H5N1 infection. The ability of chickens to generate specific antibodies was assessed with three strains that showed broad cross protection in mouse studies (A/Vietnam/1203/2004, A/Anhui/ 1/2005 and A/Indonesia/05/2005), administered individually or in combination, by different injection methods. cache = ./cache/cord-000050-tfcerilc.txt txt = ./txt/cord-000050-tfcerilc.txt === reduce.pl bib === id = cord-003609-p0ydzjre author = Goodman, Danielle E. title = Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR) date = 2019-04-23 pages = extension = .txt mime = text/plain words = 8894 sentences = 487 flesch = 55 summary = RNA was purified from fractions containing monosomes MAV-1 Degrades PKR during Infection ® and polysomes and then used to generate cDNA, which we assayed for PKR mRNA by qPCR (Fig. 4C) . Thus, the 18-hpi time point is considered an early time point during MAV-1 infection of CMT93 cells, prior to DNA replication, suggesting the involvement of an early viral protein in PKR depletion. We examined PKR protein levels during MAV-1 infection and found that PKR was depleted from the cells as early as 12 hpi (Fig. 7) . While the PKR mRNAs in C57BL/6 MEFs were depleted 33% at 48 hpi and 40% at 72 hpi compared to mock-infected lysates, this was not sufficient to explain the 84% and 94% reductions, respectively, in PKR protein levels at those time points (Fig. 2B ). cache = ./cache/cord-003609-p0ydzjre.txt txt = ./txt/cord-003609-p0ydzjre.txt === reduce.pl bib === id = cord-000436-k1hwh640 author = Amidi, Maryam title = Antigen-expressing immunostimulatory liposomes as a genetically programmable synthetic vaccine date = 2010-10-26 pages = extension = .txt mime = text/plain words = 5886 sentences = 313 flesch = 47 summary = To show proof-of-concept for this artificial cell-based platform, a bacterial in vitro transcription and translation system together with a gene construct encoding the model antigen β-galactosidase were entrapped inside multilamellar liposomes. Vaccination studies in mice showed that such antigen-expressing immunostimulatory liposomes (AnExILs) elicited higher specific humoral immune responses against the produced antigen (β-galactosidase) than control vaccines (i.e. AnExILs without genetic input, liposomal β-galactosidase or pDNA encoding β-galactosidase). Here, we show that AnExILs expressing b-galactosidase are well tolerated after i.m. injection and were capable of inducing strong systemic immune responses, which were superior to that of liposomal DNA or protein vaccines encoding the same antigen. Characterization of AnExILs and liposomes loaded with b-galactosidase and/or pDNA Cell-free protein synthesis was used to transcribe and translate the lacZ gene encoding for E. AnExILs combine antigen-production, delivery and adjuvanticity in one system, making them more potent in inducing antibody responses compared to liposomal DNA vaccines as shown here. cache = ./cache/cord-000436-k1hwh640.txt txt = ./txt/cord-000436-k1hwh640.txt === reduce.pl bib === id = cord-000269-v4jochbe author = Wittekindt, Nicola E. title = Nodeomics: Pathogen Detection in Vertebrate Lymph Nodes Using Meta-Transcriptomics date = 2010-10-18 pages = extension = .txt mime = text/plain words = 5886 sentences = 314 flesch = 44 summary = cDNA libraries from five individuals and two pools of samples were prepared from retropharyngeal lymph node RNA enriched for polyadenylated RNA and sequenced using Roche-454 Life Sciences technology. Representatives of all bacterial phyla were detected in the seven libraries based on protein-coding transcripts indicating that viable microbiota were present in lymph nodes. Based on detection of both rRNA and protein-coding transcripts, we identified two new proteobacterial species; a Helicobacter closely related to Helicobacter cetorum in the Helicobacter pylori/Helicobacter acinonychis complex and an Acinetobacter related to Acinetobacter schindleri. The microbial community of mule deer lymph nodes Detection of protein-coding and ribosomal RNA transcripts provides strong support for the presence of viable and replicating microorganisms. As an alternative approach to identifying bacterial microorganisms present in lymph node tissue, we utilized amplicon DNA library sequencing technology. cache = ./cache/cord-000269-v4jochbe.txt txt = ./txt/cord-000269-v4jochbe.txt === reduce.pl bib === id = cord-000403-vzbh457k author = Zhang, Weijun title = Identification of CD8(+ )cytotoxic T lymphocyte epitopes from porcine reproductive and respiratory syndrome virus matrix protein in BALB/c mice date = 2011-05-30 pages = extension = .txt mime = text/plain words = 4247 sentences = 206 flesch = 51 summary = Twenty-seven nanopeptides derived from the matrix (M) protein of porcine reproductive and respiratory syndrome virus (PRRSV) were screened for their ability to elicit a recall interferon-γ (IFN-γ) response from the splenocytes of BALB/c mice following DNA vaccination and a booster vaccination with recombinant vaccinia virus rWR-PRRSV-M. We screened peptides derived from the PRRSV M protein for their ability to induce interferon (IFN)-γ in splenocytes harvested from BALB/ c mice following DNA vaccination and a booster vaccination with recombinant vaccinia virus expressing M protein. In contrast, control mice vaccinated with pVAX1-only or PBS-only did not show significant increases in M protein-specific antibody titers after the booster vaccination with rWR-PRRSV-M (P > 0.05, Additional file 5, Fig. S5 ). Specific increases in the number of cells producing IFN-γ following stimulation with the peptides "K 93 FITSRCRL" and "F 57 GYMTFVHF" was observed by day 3 after the booster vaccination with rWR-PRRSV-M (Figure 1 and 2) . cache = ./cache/cord-000403-vzbh457k.txt txt = ./txt/cord-000403-vzbh457k.txt === reduce.pl bib === id = cord-000293-pc4x5e24 author = Yu, Chien-Hung title = Stimulation of ribosomal frameshifting by antisense LNA date = 2010-08-06 pages = extension = .txt mime = text/plain words = 3901 sentences = 194 flesch = 49 summary = The requirements for À1 ribosomal frameshifting are the presence of a slippery heptanucleotide sequence X XXY YYZ (where X can be A, U, G or C; Y can be A or U; and Z does not equal Y; the spaces indicate the original reading frame) (8) followed by a downstream structural element, such as a pseudoknot, a hairpin or an antisense oligonucleotide duplex [for reviews, see (9) ]. We and others have demonstrated that small RNA oligonucleotides are able to mimic the function of frameshifter pseudoknots or hairpins by redirecting ribosomes into new reading frames (27, 28) . These results demonstrate that LNA modifications indeed enhance the antisense-induced frameshifting efficiency probably due to higher thermodynamic stability and RNA-like structural properties. In addition to RNA oligonucleotides, we demonstrated that LNA/DNA mix-mers are also capable of stimulating efficient À1 ribosomal frameshifting in contrast to DNA oligonucleotides. Triplex structures in an RNA pseudoknot enhance mechanical stability and increase efficiency of À1 ribosomal frameshifting cache = ./cache/cord-000293-pc4x5e24.txt txt = ./txt/cord-000293-pc4x5e24.txt === reduce.pl bib === id = cord-001761-yvd1n42f author = Yoshimura, Takeo title = Controlled Microwave Heating Accelerates Rolling Circle Amplification date = 2015-09-08 pages = extension = .txt mime = text/plain words = 4411 sentences = 223 flesch = 48 summary = Analysis of the temperature profiles of each RCA component subjected to microwave heating revealed the selectivity heating of buffer components compared with primers, template DNA, dNTP, and RNase-free water. To determine the component of RCA by microwave selectivity heating, we measured the temperatures of the five components (circularized template with primers, dNTPs, ThermoPol Buffer, Bst-LF, and RNase-free water) of the RCA and MW-RCA mixtures for 10 min from 13°C to 60°C. To reveal the effect of the selectivity heating in MW-RCA, we compared the efficiency of DNA amplification in the RCA and MW-RCA reactions mixtures containing a 4-fold excess concentration of each RCA component (dNTP, template-primers, Bst-LF, Tris-HCl, KCl, (NH 4 ) 2 SO 4 , and MgSO 4 ). We performed MW-RCA reactions containing a four-fold higher concentration of each RCA component [dNTP, template-primers, Bst DNA polymerase-LF, Tris-HCl, KCl, (NH 4 ) 2 SO 4 , and MgSO 4 ] to identify a link between microwave selective heating and DNA amplification. cache = ./cache/cord-001761-yvd1n42f.txt txt = ./txt/cord-001761-yvd1n42f.txt === reduce.pl bib === id = cord-000012-p56v8wi1 author = Bigot, Yves title = Molecular evidence for the evolution of ichnoviruses from ascoviruses by symbiogenesis date = 2008-09-18 pages = extension = .txt mime = text/plain words = 6419 sentences = 293 flesch = 44 summary = CONCLUSION: Our results provide molecular evidence supporting the origin of ichnoviruses from ascoviruses by lateral transfer of ascoviral genes into ichneumonid wasp genomes, perhaps the first example of symbiogenesis between large DNA viruses and eukaryotic organisms. With respect to both species number and mechanisms that lead to successful parasitism, endoparasitic wasps are known to inject secretions at oviposition, but only a few lineages use viruses or virus-like particles (VLPs) to evade or to suppress host defences. Extending our investigations to proteins encoded by open reading frames of certain ascoviruses and bracoviruses, hosts and bacteria, in the light of recent analyses about the involvement of the replication machinery of virus groups related to ascoviruses in lateral gene transfer [29] , we discuss the robustness and the limits of the molecular evidence supporting an ascovirus origin for ichnovirus lineages. cache = ./cache/cord-000012-p56v8wi1.txt txt = ./txt/cord-000012-p56v8wi1.txt === reduce.pl bib === id = cord-000988-79fp75u3 author = Al-Siyabi, Turkiya title = A cost effective real-time PCR for the detection of adenovirus from viral swabs date = 2013-06-07 pages = extension = .txt mime = text/plain words = 6247 sentences = 327 flesch = 43 summary = Twentyseven virus culture-positive specimens and 169 virus culture-negative specimens were randomly selected and tested for the presence of HAdV using a well established in-house real-time PCR assay [18] following recovery of viral DNA was recovered by homogenization with heat treatment or automated nucleic acid extraction. This internally controlled quantitative real-time PCR assay targets the hexon gene of adenovirus, and is validated for detection Table 1 Nucleotide sequences of primers and probes used in this study The analytical sensitivity (or limit of detection, LoD) of the homogenization with heat treatment or nucleic acid extraction, in combination with the real-time PCR, was determined using 10-fold serial dilutions (in UTM) of a cultured HAdV-C type 6. Virus stock dilutions were quantified using commercial real-time PCR assay, and the LoD for homogenization or nucleic acid extraction-based protocols were shown to be approximately equivalent (Figure 2) . cache = ./cache/cord-000988-79fp75u3.txt txt = ./txt/cord-000988-79fp75u3.txt === reduce.pl bib === === reduce.pl bib === id = cord-000765-r7y1cqou author = Chang, Yu-Ming title = Functional Studies of ssDNA Binding Ability of MarR Family Protein TcaR from Staphylococcus epidermidis date = 2012-09-21 pages = extension = .txt mime = text/plain words = 5770 sentences = 317 flesch = 54 summary = title: Functional Studies of ssDNA Binding Ability of MarR Family Protein TcaR from Staphylococcus epidermidis However, the detailed mechanism of multiple antibiotic resistance regulator (MarR) family proteins such as TcaR is unclear and only restricted on the binding ability of double-strand DNA (dsDNA). Here we show by electrophoretic mobility shift assay (EMSA), electron microscopy (EM), circular dichroism (CD), and Biacore analysis that TcaR can interact strongly with single-stranded DNA (ssDNA), thereby identifying a new role in MarR family proteins. IcaR DNA1 probe duplex of 1 mM was pre-incubated with 2 mM TcaR (dimer) at room temperature for 15 min before mixing with increasing concentration of GC33 ssDNA, followed by the same procedure as described in the legend to Figure 1B . In the EMSA analysis, 1 mM IcaR DNA1 probe duplex was pre-incubated with 1 mM GC33 ssDNA fragment for 15 min at room temperature before mixing with TcaR protein of increasing concentration. cache = ./cache/cord-000765-r7y1cqou.txt txt = ./txt/cord-000765-r7y1cqou.txt === reduce.pl bib === id = cord-004561-cer5ifac author = Astua-Monge, G. title = Evidence for a prokaryotic insertion-sequence contamination in eukaryotic sequences registered in different databases date = 2002 pages = extension = .txt mime = text/plain words = 3807 sentences = 200 flesch = 52 summary = An insertion-sequence of prokaryotic origin was detected in a genomic clone obtained from a Phaseolus vulgaris bacterial artificial chromosome (BAC) library. Southern hybridization of EcoRI-digested BnBAC25 and BnBAC55 clones vulgaris BAC clones resulting from the insertion of the prokaryotic transposable element IS10R. C A southern-blot of several BAC clones showing that only the mutant BnBAC55::IS10R has a 4.1-kb fragment that hybridizes to a probe derived from the IS10R sequence. The presence of the 2.3-kb EcoRV fragment in all clones after prolonged subculturing suggested that IS10R Fig. 2 Sample BAC filter-hybridization results with the IS10R sequence as a probe. BAC DNA prepared from the intensely hybridizing clones possesses a common restriction fragment that contains part of the IS10R sequence database sequence entries from diverse eukaryotic sources that include humans, Arabidopsis, yeast and Drosophila, among others. cache = ./cache/cord-004561-cer5ifac.txt txt = ./txt/cord-004561-cer5ifac.txt === reduce.pl bib === id = cord-002441-w731ehtz author = Jeon, Young Joo title = Interferon-Stimulated Gene 15 in the Control of Cellular Responses to Genotoxic Stress date = 2017-02-28 pages = extension = .txt mime = text/plain words = 4141 sentences = 227 flesch = 44 summary = The expression of interferon-stimulated gene 15 (ISG15), the first identified ubiquitin-like protein, has recently been shown to be induced under various DNA damage conditions, such as exposure to UV, camptothecin, and doxorubicin. Here we overview the recent findings on the role of ISG15 and its conjugation to target proteins (e.g., p53, ΔNp63α, and PCNA) in the control of cellular responses to genotoxic stress, such as the inhibition of cell growth and tumorigenesis. Accordingly, treatment with DNA-damaging agents, such as UV, camptothecin, and doxorubicin, markedly induces both the mRNA and protein further accelerates p53 ISGylation and subsequent processes for suppression of cell growth and tumor development by forming a positive feedback loop. Thus, it appears clear that ISG15 and its conjugation to target proteins play a crucial function in the control of cellular responses to genotoxic stresses and in turn in suppression of DNA damage-mediated tumorigenesis. cache = ./cache/cord-002441-w731ehtz.txt txt = ./txt/cord-002441-w731ehtz.txt === reduce.pl bib === id = cord-002844-jv42o789 author = Marcos-Villar, Laura title = Epigenetic control of influenza virus: role of H3K79 methylation in interferon-induced antiviral response date = 2018-01-19 pages = extension = .txt mime = text/plain words = 6091 sentences = 308 flesch = 43 summary = These results indicate that epigenetic modifications induced by influenza virus infection mainly target the histone component of host cell chromatin, with H3K79 residue methylation the most frequently modified. Dot1L inhibition caused an increase in viral replication, higher in cells infected with the natural isolates, which suggests a general role of H3K79 methylation in control of the influenza virus life cycle. At 8 h, we found a weak increase on IFNβ, IFN-stimulated gene 56 (ISG56) and interferon-induced protein Mx1 (Mx1) RNA levels after IFNαβ addition or influenza virus infection, and Dot1L inhibitor treatment did not significantly decreased their accumulation (Fig. 6B,C) . Given the role of H3K79 methylation in the control of IFN signaling, we analyzed the effect of Dot1L inhibitor on influenza virus replication in cells with normal or deficient IFN responses. Since H3K79 methylation does not affect influenza virus replication in cells with impaired IFN signaling, we analyzed the effect of Dot1L inhibitor in subsequent stages of viral infection. cache = ./cache/cord-002844-jv42o789.txt txt = ./txt/cord-002844-jv42o789.txt === reduce.pl bib === id = cord-001732-4eyn7pjq author = Riede, O title = Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine date = 2015-04-30 pages = extension = .txt mime = text/plain words = 6339 sentences = 336 flesch = 49 summary = Evaluation of single-dose and repeated-dose toxicity of the vaccine candidate after i.d. administration to naive, non-infected mice did not reveal any safety concerns. To assess toxicity of LEISHDNAVAX in naive mice, sterile phosphate-buffered saline (PBS, placebo) and ascending doses of the vaccine were injected either once or five times in weekly intervals (Table 1) . Twenty-four hour after single or repeated injection, MIDGE-Th1 vector DNA was detected in almost all organs and tissues examined, suggesting that it was distributed systemically, most likely via the lymphatic system and the blood stream. Groups of 10 BALB/c mice (5 male, 5 female) were immunized i.d. at the tail base five times in weekly intervals with either PBS or LEISHDNAVAX (10, 50 or 100 μg per dose). In summary, we have shown here that LEISHDNAVAX, a novel DNA vaccine candidate against leishmaniasis is safe and well tolerated in both naive and Leishmania-infected mice. cache = ./cache/cord-001732-4eyn7pjq.txt txt = ./txt/cord-001732-4eyn7pjq.txt === reduce.pl bib === id = cord-001537-i34vmfpp author = Lima, Francisco Esmaile de Sales title = Genomic Characterization of Novel Circular ssDNA Viruses from Insectivorous Bats in Southern Brazil date = 2015-02-17 pages = extension = .txt mime = text/plain words = 3874 sentences = 195 flesch = 53 summary = The predicted protein sequences encoded by ORF2 (cap) and ORF1 (rep) of BatCV I-VI genomes were used for phylogenetic analysis with representative and recently discovered circoviruses/cycloviruses; Pepper golden mosaic virus was used as outgroup, as they are somewhat related to other members in the Circoviridae family (Fig. 3A, 3B and 3C ). The phylogenetic analysis constructed based on the alignments of the complete REP and CAP protein confirms that BatCV POA/II and VI cluster into the genus Cyclovirus along with the Chinese cycloviruses sequences clade detected in bat feces [18] and sharing less than 65% of identity at the CAP/REP amino acid level. BatCV POA I and V had a low amino acid identity with CAP (<20%) and REP (<10%) sequences of two other sequences detected in bat feces in this study with known circoviruses/cycloviruses (Table 2) . cache = ./cache/cord-001537-i34vmfpp.txt txt = ./txt/cord-001537-i34vmfpp.txt === reduce.pl bib === id = cord-003516-l1lq8yga author = Zhang, Jing title = A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations date = 2019-01-31 pages = extension = .txt mime = text/plain words = 2357 sentences = 133 flesch = 38 summary = title: A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations A signature of these "old" HAdV-E4 is the absence of a critical replication motif, NF-I, which is found in all HAdV respiratory pathogens and most HAdVs. However, our recent survey of flu-like disease in children in Hong Kong reveals that the emergent HAdV-E4 pathogens circulating in civilian populations contain NF-I, indicating recombination and reflecting host-adaptation that enables the "new" HAdV-E4 to replicate more efficiently in human cells and foretells more potential HAdV-E4 outbreaks in immune-naïve civilian populations. Recent isolates are recombinants containing this HAdV replication motif [1] , presumably permitting an expansion of the virus range into the immune-naïve populations [5] [6] [7] [21] [22] [23] , and should be noted as a molecular evolution example of a post-zoonotic, host-adaptation of a "novel" and "emergent" human pathogen. cache = ./cache/cord-003516-l1lq8yga.txt txt = ./txt/cord-003516-l1lq8yga.txt === reduce.pl bib === id = cord-004003-rlgzgyzn author = Lee, Jeewon title = Applying a Linear Amplification Strategy to Recombinase Polymerase Amplification for Uniform DNA Library Amplification date = 2019-11-12 pages = extension = .txt mime = text/plain words = 3386 sentences = 200 flesch = 51 summary = Thus, to amplify the size-variable DNA library uniformly, we introduced a linear amplification strategy with RPA and successfully improved the uniformity. Also, the average percentages of bases in the uniform range (uniformity value between 0.5 and 1.5) about the triplet experiment was improved from 56.3 and 49.2% by two-primer RPA to 73.6 and 75.7% by linear RPA for the small and large DNA libraries, respectively (Figures 2b and S5) . Taken together, the data show that RPA uniformly amplifies DNA libraries of the same size and has different amplification preferences than PCR. However, during the experiment, an accelerated small-sized DNA amplification by two-primer RPA reaction caused lower uniformity compared to PCR. It was noted that during the analysis, different amplification preferences were found between the PCR and RPA amplified oligo library sequencing data. Taken together, we show that single-primer linear RPA can be one of the alternative methods to PCR for DNA library amplification. cache = ./cache/cord-004003-rlgzgyzn.txt txt = ./txt/cord-004003-rlgzgyzn.txt === reduce.pl bib === id = cord-003656-7mzsaz7a author = Wium, Martha title = DNA Vaccines Against Mycoplasma Elicit Humoral Immune Responses in Ostriches date = 2019-05-14 pages = extension = .txt mime = text/plain words = 5575 sentences = 308 flesch = 53 summary = Currently there are no commercially available vaccines against ostrich-infecting mycoplasmas and this study therefore set out to develop and evaluate the use of a DNA vaccine against mycoplasma infections in ostriches using an OppA protein as antigen. The ability of the DNA vaccines to elicit an anti-OppA antibody response was evaluated by ELISA using the recombinant OppA protein of Ms03 as coating antigen. In this study we report, for the first time, that a DNA vaccine can elicit a humoral immune response in ostriches using OppA as antigen. The controls were serum samples representing the week 0, 3, 6, and 9 sampling points of a single ostrich, randomly selected from the pCI-neo_oppA 1,200 µg group based on high titers produced after vaccination. In this study, DNA vaccines were developed for ostriches using the oppA gene of an ostrich-infecting mycoplasma (Ms03) as vaccine antigen. cache = ./cache/cord-003656-7mzsaz7a.txt txt = ./txt/cord-003656-7mzsaz7a.txt === reduce.pl bib === id = cord-007047-7ty9mxa9 author = Reller, L. Barth title = Implications of New Technology for Infectious Diseases Practice date = 2006-11-15 pages = extension = .txt mime = text/plain words = 4095 sentences = 190 flesch = 38 summary = Problems with currently available molecular assays include a lack of knowledge about the extent of microbial nucleic acid in "normal" hosts, concentration of agent material in small volume samples, lack of microbiologist expertise, lack of adequate reimbursement, and difficulty with validation based on conventional methods. Infectious diseases clinicians have relied on these expert workers, and Reliable molecular diagnostic tests are not readily available for many infectious agents Commercial tests should only be used for validated specimen types Transportation problems, low concentrations of infectious agent, primer binding site genetic changes, final assay volume, inhibition, contamination, nonspecific amplification, and operator error lead to false-negative and false-positive amplification results Genomic bacterial sequencing is subject to error because of sequence homology among different bacteria, database problems, and mutations A number of nucleic acid hybridization and amplification methods are now in use, including direct probe hybridization (AdvanDx FISH for Staphylococcus aureus [AdvanDx] and GenProbe for group A streptococci [GenProbe]), hybrid capture (Digene for human papillomavirus; Digene), PCR, branched-chain DNA (bDNA; Bayer Diagnostics), and transcription-mediated amplification (Probe-Tec for Chlamydia and N. cache = ./cache/cord-007047-7ty9mxa9.txt txt = ./txt/cord-007047-7ty9mxa9.txt === reduce.pl bib === id = cord-000010-prsvv6l9 author = Qin, Jian title = Studying copy number variations using a nanofluidic platform date = 2008-08-18 pages = extension = .txt mime = text/plain words = 4986 sentences = 250 flesch = 51 summary = Copy number variations (CNVs) in the human genome are conventionally detected using high-throughput scanning technologies, such as comparative genomic hybridization and high-density single nucleotide polymorphism (SNP) microarrays, or relatively low-throughput techniques, such as quantitative polymerase chain reaction (PCR). We have developed a new technology to study copy numbers using a platform known as the digital array, a nanofluidic biochip capable of accurately quantitating genes of interest in DNA samples. Other existing technologies, such as quantitative polymerase chain reaction (PCR), are limited because of their inability to reliably distinguish less than a twofold difference in copy number of a particular gene in DNA samples (11) (12) (13) . In this study we demonstrate the use of a unique integrated nanofluidic system, the digital array, in the study of CNVs. The digital array (14, 15) is able to accurately quantitate DNA samples based on the fact that single DNA molecules are randomly distributed in more than 9000 reaction chambers and then PCR amplified. cache = ./cache/cord-000010-prsvv6l9.txt txt = ./txt/cord-000010-prsvv6l9.txt === reduce.pl bib === id = cord-003674-3ajyr5e4 author = NAGAO, Konomu title = Development of a fluorescent loop-mediated isothermal amplification assay for rapid and simple diagnosis of bovine leukemia virus infection date = 2019-03-27 pages = extension = .txt mime = text/plain words = 2565 sentences = 130 flesch = 53 summary = title: Development of a fluorescent loop-mediated isothermal amplification assay for rapid and simple diagnosis of bovine leukemia virus infection A fluorescent loop-mediated isothermal amplification (fLAMP) assay targeting BLV env sequences was developed and used to evaluate 100 bovine blood samples. Fluorescent (fLAMP) reagents are commercially available, and this real-time amplification approach allows extremely rapid and accurate diagnosis through the use of an improved chain replacement enzyme and annealing analysis compared with tLAMP [4, 6, 17] . Here we used 100 bovine blood samples obtained from farms in the Kagoshima, Miyazaki and Oita prefectures in Japan to develop an fLAMP assay that we compared with a published real-time PCR assay. We used 100 bovine clinical blood samples, comprising 80 ELISA-positive and 20 ELISA-negative samples, to evaluate the performance of the BLV specific fLAMP assay. Development of loop-mediated isothermal amplification method for diagnosis of bovine leukemia virus infection cache = ./cache/cord-003674-3ajyr5e4.txt txt = ./txt/cord-003674-3ajyr5e4.txt === reduce.pl bib === id = cord-001406-huz0tpmi author = Kersting, Sebastian title = Multiplex isothermal solid-phase recombinase polymerase amplification for the specific and fast DNA-based detection of three bacterial pathogens date = 2014-02-18 pages = extension = .txt mime = text/plain words = 4671 sentences = 255 flesch = 41 summary = title: Multiplex isothermal solid-phase recombinase polymerase amplification for the specific and fast DNA-based detection of three bacterial pathogens The isothermal RPA was applied to amplify specific target sequences from the pathogens Neisseria gonorrhoeae, Salmonella enterica and methicillin-resistant Staphylococcus aureus (MRSA) using genomic DNA. A possible alternative to the PCR are isothermal nucleic acid amplification techniques which are carried out at a single temperature throughout the entire reaction using different mechanisms e.g. the strand-displacement activity of certain polymerases or the addition of further proteins used in the natural replication processes [4] . To our knowledge this highly multiplex pathogen detection is the first combination of isothermal RPA and microarray technology and offers new possibilities for the development of point-of-care testing devices for nucleic acids. (i) The excess of reverse primer in the reaction and the subsequent polymerase elongation leads to a preferred amplification of a single strand antisense DNA strand which can hybridize to the target specific probe structure on the surface. cache = ./cache/cord-001406-huz0tpmi.txt txt = ./txt/cord-001406-huz0tpmi.txt === reduce.pl bib === id = cord-001484-va0teako author = Ahmed, Sarah A. title = Rapid Identification of Black Grain Eumycetoma Causative Agents Using Rolling Circle Amplification date = 2014-12-04 pages = extension = .txt mime = text/plain words = 2922 sentences = 165 flesch = 48 summary = A rapid, simple, and highly efficient molecular based method for identification of agents of black grain eumycetoma is introduced, aiming to improve diagnostic in endemic areas. Rolling circle amplification (RCA) is a powerful diagnostic method based on detection of specific nucleic-acid sequences and enzymatic amplification of circularized oligonucleotide probes under isothermal conditions [10] . The specificity of the 8 RCA probes was tested using strains of black-grain mycetoma causative species listed in table 1. Identification of mycetoma agent with phenotypic features is too limited, and physiological and biochemical techniques are laborious, time-consuming and nonspecific, whereas the currently available molecular methods based on DNA sequencing are specific but extremely expensive. We describe rolling circle amplification method for identification of black grain eumycetoma using species-specific padlock probes. In the present study we developed a simple, fast and highly specific molecular method for the identification of agents of black grain mycetoma. cache = ./cache/cord-001484-va0teako.txt txt = ./txt/cord-001484-va0teako.txt === reduce.pl bib === === reduce.pl bib === id = cord-001111-qqmj4v0u author = Liu, Chengyu title = Strategies for Designing Transgenic DNA Constructs date = 2013-03-08 pages = extension = .txt mime = text/plain words = 8122 sentences = 382 flesch = 47 summary = Finally, the strategies for conducting each of the major types of transgenic research are discussed, including gene overexpression, promoter characterization, cell-lineage tracing, mutant complementation, expression of double or multiple transgenes, siRNA knockdown, and conditional and inducible systems. Generating a typical transgenic construct involves assembling three basic DNA elements: (1) a promoter and/or enhancer which confers the desired spatial and temporal pattern of transgene expression; (2) the gene to be transcribed, which may or may not encode a protein; and (3) a transcription termination or polyadenylation signal sequence to stop transcription and enable 3 ¢ end processing. BACs can be used for driving expression of Cre and FLP recombinase genes in desired tissues, but as will be discussed in Subheading 4.6 , the commonly used BAC vectors already contain loxP sites, which can be problematic when crossbred to fl oxed mouse lines. cache = ./cache/cord-001111-qqmj4v0u.txt txt = ./txt/cord-001111-qqmj4v0u.txt === reduce.pl bib === id = cord-001090-qg2r691d author = Twin, Jimmy title = The Potential of Metatranscriptomics for Identifying Screening Targets for Bacterial Vaginosis date = 2013-09-27 pages = extension = .txt mime = text/plain words = 3944 sentences = 201 flesch = 44 summary = BACKGROUND: The ribosomal RNA content of a sample collected from a woman with bacterial vaginosis (BV) was analysed to determine the active microbial community, and to identify potential targets for further screening. Prevotella amnii was chosen as an example target, being the most metabolically active species present in the single patient with BV, and was found to be detected at a high concentration by qPCR in 31% of cohort with BV, with an association with both oral and penile-vaginal sex. An amplicon-based metagenomic library was generated from the extracted DNA using the universal bacterial PCR primers 27F and 338R that target the V1-V2 hypervariable regions of the 16S rRNA gene as previously described [15] . Comparison of cDNA to DNA from Nugent 10 patient All of the predominant bacteria with .1% total abundance identified in the cDNA library were also detected using the 16S rRNA gene amplicon-based approach on extracted DNA. cache = ./cache/cord-001090-qg2r691d.txt txt = ./txt/cord-001090-qg2r691d.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-007757-4mri8kyq author = van de Sluis, Bart title = Transgene Design date = 2010-10-04 pages = extension = .txt mime = text/plain words = 3791 sentences = 205 flesch = 43 summary = Size constraints, inherent to particular cloning systems, may limit the use of native regulatory elements: if a transgene becomes too large for regular plasmid or cosmid-based vectors, or when genetic complementation is desired (e.g., with DNA fragments spanning large genomic deletions), one can switch to systems that allow cloning of very large DNA segments (see Subheading 1.3; Chapter 9). In addition, some endogenous introns appear to harbor regulatory elements with structural and functional similarities to enhancers, Locus control regions (LCRs), or Matrix attachment regions (MARs) (see Subheading 2.2) which direct transgene expression in a position-independent or cell type-specific fashion (9-17). The experimenter has a certain degree of freedom to tailor transgene design to specific requirements ((3); see also The choice of regulatory elements that drive transgene expression is broad (Fig. 2) , and is primarily determined by the aim of the model. cache = ./cache/cord-007757-4mri8kyq.txt txt = ./txt/cord-007757-4mri8kyq.txt === reduce.pl bib === id = cord-004170-ri5qsarz author = Yashima, Nozomi title = Leukocyte-derived extracellular DNA contributes to abnormal pressure elevation in the extracorporeal circulation circuit date = 2020-01-16 pages = extension = .txt mime = text/plain words = 3584 sentences = 234 flesch = 44 summary = title: Leukocyte-derived extracellular DNA contributes to abnormal pressure elevation in the extracorporeal circulation circuit Abnormal in-circuit elevation in pressure was associated with deposition of extracellular DNA on the outlet surface of the filter. In-circuit pressure was elevated at the oxygenator if heparin was administered in whole blood that was stored for 7 days (Fig. S1B) . Then, we examined whether leukocyte stimulation results in elevation of in-circuit pressure since previous studies have suggested that stimulated leukocytes are prone to releasing DNA into the extracellular space 13 . Our study showed that leukocyte-derived extracellular DNA induced an elevation of in-circuit pressure. Our study suggested that extracellular DNA from disrupted leukocytes contributed to elevation of in-circuit pressure. In conclusion, our study shows that leukocyte-derived extracellular DNA contributes to abnormal in-circuit elevation of pressure in an ex vivo circuit. cache = ./cache/cord-004170-ri5qsarz.txt txt = ./txt/cord-004170-ri5qsarz.txt === reduce.pl bib === id = cord-000575-g1ob16b9 author = Xie, Xiao-li title = Protein sequence analysis based on hydropathy profile of amino acids date = 2012-01-27 pages = extension = .txt mime = text/plain words = 2178 sentences = 116 flesch = 48 summary = A new method to analyze the similarity/dissimilarity of protein sequence was proposed based on the conditional probability of the protein sequence. Based on the graphical representation, it is possible to numerically characterize DNA sequence and further quantitatively measure similarity of different DNA sequences. This is mainly because extension of DNA graphical representation to protein sequences would enormously increase the number of possible alternative assignments for the 20 amino acids. The graphical representation of protein sequence cannot only describe amino acid sequence, but also measure similarity/ dissimilarity of different protein sequences. In this paper, we converted a protein sequence into three-letter sequence based on hydropathy profile of amino acid and defined the three curves to represent different hydropathy features. The method is based on the graphical representation and conditional probability taken as the numerical characterization of the protein sequence. Similarity/dissimilarity studies of protein sequences based on a new 2D graphical representation cache = ./cache/cord-000575-g1ob16b9.txt txt = ./txt/cord-000575-g1ob16b9.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-000248-zueoyesj author = Berretta, Regina title = Cancer Biomarker Discovery: The Entropic Hallmark date = 2010-08-18 pages = extension = .txt mime = text/plain words = 33594 sentences = 1678 flesch = 43 summary = These authors cite, for example, ''mitochondrial dysfunction'' [5, 6] (including, but not limited to ''glucose avidity'' [7] and ''a shift in glucosemetabolism from oxidative phosphorylation to glycolysis'' [6, 8] , ''altered glycolysis'' [9] , ''altered bioenergetic function of mitochondria'' [10] ), ''dysregulation of cell cycle and defective genome-integrity checkpoints'' [11] , ''aberrant DNA methylation'' [12] (''promoter hypermethylation of hallmark cancer genes'' [13] and ''CpG island hypermethylation and global genomic hypomethylation'' [14] ), ''shift in cellular metabolism'' [15, 16, 17] , ''regional hypoxia'' [18] , ''microenviroment acidosis'' [19] , ''abnormal microRNA regulation'' [20, 21] , ''aneuploidy'' and ''chromosome aberrations'' [22, 23, 24, 25, 26] , ''disruption of cellular junctions'' [27] , ''avoidance of the immune response'' [28] , ''pre-existing chronic inflammatory conditions'' [29, 30] , ''cancerrelated inflammation'' [29] , ''disabled autophagy'' [28] , ''impaired cellular senescence'' [31] , ''altered NF-kappaB signalling'' [32] , ''altered growth patterns, not altered growth per se'' [33] , ''disregulated DNA methylation and histone modifications'' [34] , ''tissue dedifferentiation'' [35, 36] , and ''somatically heritable molecular alterations'' [37] . cache = ./cache/cord-000248-zueoyesj.txt txt = ./txt/cord-000248-zueoyesj.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-004995-5jmjejbp author = Hunt, Hamish C. title = Optofluidic integration for microanalysis date = 2007-09-11 pages = extension = .txt mime = text/plain words = 17310 sentences = 797 flesch = 42 summary = Integration of waveguides from which light emerges into a microfluidic channel is an attractive advance upon the use of external lenses or the hybrid integration of individual optical fibres to realise dual-beam traps, in terms of robustness, alignment and potential for mass production. Detection and analysis of chemical and biochemical species in microfluidic systems is challenging due to short optical path-lengths, small sample volumes, and the need to analyse individual particles or molecules. This section reviews optical detection schemes for chemical analysis in microfluidic systems, divided according to the principal optical phenomena employed: scattering, absorption, refractive index, fluorescence, Raman spectroscopy, and thermal lensing. Kamei and Wada (2006) built upon earlier work (Kamei et al 2005) demonstrating microfluidic separation of biomolecules, and realised a detection platform shown in Fig. 11 , which included a 2 mm diameter half-ball lens for fluorescence collection, a microstructured interference filter deposited directly on a pin photodiode, and an aperture through the centre of the detector and filter via which excitation light from a 488 nm frequency-doubled VCSEL was introduced. cache = ./cache/cord-004995-5jmjejbp.txt txt = ./txt/cord-004995-5jmjejbp.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-001859-d62iuk72 author = Baquero-Pérez, Belinda title = Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments date = 2015-11-20 pages = extension = .txt mime = text/plain words = 15958 sentences = 876 flesch = 50 summary = Similar Hsc70 localization was seen during early lytic replication (12 h reactivation), when RTA protein was diffuse in the nucleus, Successful enrichment of the nuclear envelope region and associated KSHV RTCs in HEK-293T rKSHV.219 cells. These results clearly demonstrate that KSHV specifically redistributes the molecular chaperones, Hsc70 and iHsp70, from the cytoplasm to the nucleus, in contrast to Grp78, which coincides with the initial formation of KSHV RTCs. Treatment with the small molecule inhibitor VER-155008 abrogated viral protein synthesis at non-cytotoxic concentrations Members of the HSP70 chaperone family possess an N-terminal nucleotide binding domain with ATPase activity which is essential for their function. Therefore to ascertain whether Hsp70 isoforms could stabilise the essential KSHV lytic proteins RTA and ORF57, TREx BCBL1-RTA cells were reactivated for 24 h to allow sufficient viral protein expression followed by addition of DMSO control or VER-155008 in conjunction with cycloheximide (CHX) at 50 μg/ml to block de novo protein synthesis. cache = ./cache/cord-001859-d62iuk72.txt txt = ./txt/cord-001859-d62iuk72.txt === reduce.pl bib === id = cord-006049-sw1hki4r author = Keefe, Anthony D. title = Aptamers as therapeutics date = 2010 pages = extension = .txt mime = text/plain words = 9789 sentences = 510 flesch = 42 summary = Nucleic acid aptamers can be selected from pools of random-sequence oligonucleotides to bind a wide range of biomedically relevant proteins with affinities and specificities that are comparable to antibodies. Although this is true for biological nucleic acids [1] [2] [3] [4] , it was only recently that a series of technological advances allowed the development of in vitro evolutionary methods for the discovery of additional, non-biological oligonucleotides that can bind to protein targets. Since the invention of the SELEX process around 1990 (REfS 5, 6) , researchers have identified high-affinity aptamers that target a broad cross-section of protein families including cytokines, proteases, kinases, cell-surface receptors and cell-adhesion molecules (TABLE 1) . In particular, the site-specific placement of functional groups for conjugation means that the modification of aptamers after the solid-phase step (for example with high molecular mass PEG 46 ) leads to products with discrete stoichiometries and defined chemical structures. Selection of a RNA aptamer that binds to human activated protein C and inhibits its protease function cache = ./cache/cord-006049-sw1hki4r.txt txt = ./txt/cord-006049-sw1hki4r.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-004501-guiy89x8 author = Cojocaru, Florina-Daniela title = Nanomaterials Designed for Antiviral Drug Delivery Transport across Biological Barriers date = 2020-02-18 pages = extension = .txt mime = text/plain words = 13993 sentences = 673 flesch = 37 summary = According to the literature data results, namomaterials designed with different shapes and morphologies display numerous advantages for use in antiviral therapy, namely: nanometric size that permits drug delivery through impermeable barriers [88] , large surface area to volume ratios for large drug payloads incorporation [117] and improved efficacy, surface modification and/or backbone functionalization versatility that facilitates cellular membranes passage [118] or enhancing stability and bioavailability [119] , virucidal activity against a series of viruses (HIV, HSV, HBV, etc.) due to biomimetic properties [120] , increased specificity, improved antiviral delivery and controlled drug release to the target [121] through engineered moieties, decrease the emergence of drug resistance, personalized therapy possibility, protection of the drugs and low adverse drug side effects mainly due to the composition. cache = ./cache/cord-004501-guiy89x8.txt txt = ./txt/cord-004501-guiy89x8.txt === reduce.pl bib === === reduce.pl bib === id = cord-009261-97qegnlo author = Rieux, Charlotte title = Thiopurine Derivative-Induced Fpg/Nei DNA Glycosylase Inhibition: Structural, Dynamic and Functional Insights date = 2020-03-17 pages = extension = .txt mime = text/plain words = 11719 sentences = 574 flesch = 52 summary = Among forty compounds, four TXn were better inhibitors than 2TX for Fpg. Unexpectedly, but very interestingly, two dithiolated derivatives more selectively and efficiently inhibit the zincless finger (ZnLF)-containing enzymes (human and mimivirus Neil1 DNA glycosylases hNeil1 and MvNei1, respectively). The crystal structure of LlFpg bound to 14-mer [8-oxoG:C] DNA duplex (which differs from that used in this study only by the damaged nature present in the duplex: an 8-oxoG lesion in place of THF) revealed that the second Fpg molecule can bind to the overhanging base positioned at the 5 end of the damaged strand ( Figure S5b ) [38] . Similar to the 2TX-containing crystal structure, the intramolecular disulfide bridge Cys245-S-S-Cys265 is also formed in the presence of TXn. Not observed previously, one 2TX molecule that is non-covalently bound to the enzyme is inserted at the protein-DNA interface in the vicinity of the ZnF loop and the H2TH motif (Figure 10a,b) , the two DNA binding domains that characterize the Fpg/Nei DNA glycosylase superfamily [29] . cache = ./cache/cord-009261-97qegnlo.txt txt = ./txt/cord-009261-97qegnlo.txt === reduce.pl bib === id = cord-003764-141u6ax7 author = Shrestha, Ashish C. title = Cytolytic Perforin as an Adjuvant to Enhance the Immunogenicity of DNA Vaccines date = 2019-04-30 pages = extension = .txt mime = text/plain words = 6292 sentences = 309 flesch = 42 summary = The ability of a DNA vaccine to elicit T cell immunity is thus dependent on activating APCs to present antigen: MHC complexes to T cells [31] and adjuvants can serve as an important costimulatory factor to enhance this process. The use of fusogenic membrane glycoprotein (FMG) gene from VSV vaccine encoding the H7 protein of human papillomavirus type 16 was shown to enhance ell responses and effectively control growth of tumors [87] . The use of fusogenic membrane glycoprotein (FMG) gene from VSV in a DNA vaccine encoding the H7 protein of human papillomavirus type 16 was shown to enhance CD8 + T cell responses and effectively control growth of tumors [87] . This cytolytic DNA vaccine is unique as it is based on a bicistronic plasmid with the ability to coexpress antigen and PRF in a balanced mechanism causing necrosis of vaccine-transduced cells, followed by increased activation of immune cells and cross presentation of vaccine immunogen. cache = ./cache/cord-003764-141u6ax7.txt txt = ./txt/cord-003764-141u6ax7.txt === reduce.pl bib === id = cord-004133-32w6g7qk author = Walker, Faye M. title = Advances in Directly Amplifying Nucleic Acids from Complex Samples date = 2019-09-30 pages = extension = .txt mime = text/plain words = 13585 sentences = 664 flesch = 42 summary = Studies were included if they involved direct amplification and detection of genetic material from one of six representative sample types: blood, dried blood spot, serum and plasma, saliva and sputum, swabs, urine, and stool. However, it is important to note that the sensitivity does not necessarily suffer in much more concentrated samples-in Liu et al.'s highly robust two-step amplification process with direct hairpin assembly and HCR-based detection of SNP DNA sequences in 50% (v/v) serum, they achieved a very low LOD of 100 pg [119] . However, it is important to note that the sensitivity does not necessarily suffer in much more concentrated samples-in Liu et al.'s highly robust two-step amplification process with direct hairpin assembly and HCR-based detection of SNP DNA sequences in 50% (v/v) serum, they achieved a very low LOD of 100 pg [119] . cache = ./cache/cord-004133-32w6g7qk.txt txt = ./txt/cord-004133-32w6g7qk.txt === reduce.pl bib === id = cord-008613-tysyq6o4 author = Thomas, Sheila M. title = Two mRNAs that differ by two nontemplated nucleotides encode the amino coterminal proteins P and V of the paramyxovirus SV5 date = 1988-09-09 pages = extension = .txt mime = text/plain words = 8410 sentences = 433 flesch = 60 summary = Simian virus 5 (SV5), a prototype paramyxovirus, has a single-stranded, negative sense genomic RNA (vRNA) approximately 15,000 nucleotides in chain length that is transcribed in infected cells by the virion-associated RNA transcriptase to yield virus-specific mRNAs. The SV5 "P" gene has been shown to encode both the P protein (Mr = 44,000), and protein V (Mr = 24,000) by the arrest of translation in vitro of both P and V using a cDNA clone derived from SV5-specific mRNAs (Paterson et al., 1984) . Antigenic Region Mapping of the P and V Monoclonal Antibodies on the P and V Gene Using T7 RNA Polymerase Runoff Transcripts, In Vitro Translation, and Immunoprecipitation The full-length P203-1 DNA insert cloned using Xbal linkers (XX) and a Hindlll to Xbal fragment (HX) containing the 3' two-thirds of the P203-1 DNA were placed under the control of the T7 promoter in the plasmid pGEM-2. cache = ./cache/cord-008613-tysyq6o4.txt txt = ./txt/cord-008613-tysyq6o4.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-009615-xcz8m9a7 author = Stoner, Gerald L. title = Polyomavirus Models of Brain Infection and the Pathogenesis of Multiple Sclerosis date = 2008-01-28 pages = extension = .txt mime = text/plain words = 6395 sentences = 329 flesch = 44 summary = Animal models of viral demyelination and studies showing that JC virus (JCV), the polyomavirus which causes progressive multifocal leukoencephalopathy (PML), may be latent in some normal human brains suggest another possibility. It is thought that an MS virus could be one of two basic types: 1) A rare agent which infects relatively few individuals but is frequently pathogenic, or 2) A common agent which infects a majority of the population and perhaps a significant number of normal brains, but, in which the virus expression and the host response to the infection ( Immunocytochemical studies in our laboratory indicate that perivascular cellular infiltration, apparently due to immunological reactivity to SV40 antigens, occurs in this model (Fig. 1) . Thus, simian immunodeficiency virus (S1V)-infected macaques should be observed regularly for the possible occurrence of MS-like signs with demyelination attributable to mononuclear cell infiltration in response to abortively infected glial cells, rather twa-stage process of deletion and duplication known as "brain adaptation" to generate the progressive multifocal leukoencephalopathy (PML)-type viral genome capable of replicating in glial cells of the human brain. cache = ./cache/cord-009615-xcz8m9a7.txt txt = ./txt/cord-009615-xcz8m9a7.txt === reduce.pl bib === id = cord-010027-r0tl01kq author = nan title = Dublin Pathology 2015. 8th Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland date = 2015-09-15 pages = extension = .txt mime = text/plain words = 36299 sentences = 2004 flesch = 47 summary = Further profiling of other T cell populations may help to further understand this expression which may act as a biomarker or provide a therapeutic target Biomarkers that are able to distinguish stage II and III colon cancer patients at high risk of developing disease recurrence, who may benefit from adjuvant chemotherapy, are still lacking. *AM supported by the NIHR and the Academy of Medical Sciences ABSTRACTS S·17 Assessment of HER2 Status on Needle Core Biopsy of Breast Cancer: Impact of Histopathological Concordance P M Pigera; AHS Lee; IO Ellis; EA Rakha; Z Hodi Nottingham City Hospital, Nottingham, UK One of the key recommendations introduced in the ASCO/CAP update guideline recommendation on HER2 testing is the novel concept of "histopathological concordance." It is proposed that certain tumour morphological features such as histologic type and grade should trigger repeating a molecular test in cases of "discordance". cache = ./cache/cord-010027-r0tl01kq.txt txt = ./txt/cord-010027-r0tl01kq.txt === reduce.pl bib === === reduce.pl bib === id = cord-007382-5kb16qb7 author = Hartmann, G. title = Nucleic Acid Immunity date = 2016-12-15 pages = extension = .txt mime = text/plain words = 16155 sentences = 915 flesch = 47 summary = With the additions of RNAi and the CRISPR/Cas system, specific nucleases including the restriction-modification (R-M) systems, and antiviral effector proteins partially discovered only recently in the context of rare hereditary inflammatory diseases, the new concept of nucleic acid immunity evolves. While innate nucleic acid immune-sensing receptors elicit antiviral signaling pathways, a number of nucleic acid-detecting effector proteins (viral restriction factors, e.g., PKR, ADAR1, IFIT1) directly detect and restrict nucleic acid function and replication. Another member of the RIG-I-like helicase family of receptors is MDA5 which was found to be responsible for the long sought after type I IFN-inducing activity of cytosolic long double-stranded RNA including poly(I:C) . Extrinsic effects inside the same cell include degradation of the nucleic acid (e.g., RNase L activated by 2 0 -5 0 -OA generated by OAS1 upon binding of long double-stranded RNA). cache = ./cache/cord-007382-5kb16qb7.txt txt = ./txt/cord-007382-5kb16qb7.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-007383-5yb3dxse author = Kang, Jun-Gu title = Vaccination with single plasmid DNA encoding IL-12 and antigens of severe fever with thrombocytopenia syndrome virus elicits complete protection in IFNAR knockout mice date = 2020-03-20 pages = extension = .txt mime = text/plain words = 5369 sentences = 272 flesch = 49 summary = title: Vaccination with single plasmid DNA encoding IL-12 and antigens of severe fever with thrombocytopenia syndrome virus elicits complete protection in IFNAR knockout mice Immunization of NS antigen with Freund's adjuvant in C57BL/6 mice, which are naturally resistant to SFTSV but partially mimic human infections [12] , failed to enhance viral clearance, although it induced high titer of anti-NS antibodies and significantly elevated IFN-γ levels in sera upon viral challenge [9] . Vaccination of pSFTSV-IL12 provided complete protection of IFNAR KO mice upon lethal SFTSV challenge, whereas immunization with pSFTSV elicits only partial protection, indicating that antigen-specific cellular immune responses enhanced by co-expression of IL-12 could play a significant role in protection against lethal SFTSV infection. Since we observed significant elevation of T cell responses specific to the viral antigens in IFNAR KO mice immunized with pSFTSV-IL12 DNA vaccine, we tested whether it could provide protective immunity against lethal SFTSV infection. cache = ./cache/cord-007383-5yb3dxse.txt txt = ./txt/cord-007383-5yb3dxse.txt === reduce.pl bib === id = cord-004948-ad3i9wgj author = nan title = 7th International Congress on Amino Acids and Proteins : Vienna, Austria, August 6–10, 2001 date = 2001 pages = extension = .txt mime = text/plain words = 73534 sentences = 3588 flesch = 45 summary = Specific CTL were derived by immunization of HHD mice with tumor peptide extracts loaded on antigen presenting cells and with HHD transfected human tumor cell lines CTL induced against peptides from various tumors recognized tumor peptides more effectively than peptides extracted from normal tissues and also reacted with a serie of peptides derived from overexpressed candidate proteins, identified by differential display methods (SAGE, Microarrays) Comparison of CTL derived from HHD mice to CTL induced from patient's PBMC showed overlapping recognition of many candidate peptides. By comparison of pro-teomic cell maps from normal controls and individuals affected with lysosomal transport disorders we have selected and identified several candidate disease-causing proteins, which have to be further studied by mutation analysis and functional expression. The results of the in vitro studies available to date strongly suggest that its effects on neuronal amino acid transport processes is mediated via some novel extracellular mechanism controlling the H ϩ (and/or other ionic) concentrations of neurones. cache = ./cache/cord-004948-ad3i9wgj.txt txt = ./txt/cord-004948-ad3i9wgj.txt === reduce.pl bib === id = cord-009664-kb9fnbgy author = nan title = Oral presentations date = 2014-12-24 pages = extension = .txt mime = text/plain words = 71112 sentences = 3948 flesch = 47 summary = Because of the conflicting reports and lack of published data from paediatric patients, we sought to assess possible MIC change over time and to compare results generated by using different methodologies including Etest, agar dilution, and broth microdilution (MicroScan) methods. Recently, in vitro and in vivo studies have shown that NO plays a key role in the eradication of the leishmania parasite Objective: To determine whether a NO donor patch (developed by electrospinning technique) is as effective as meglumine antimoniate in the treatment of CL while causing less adverse events Methods: A double-blind, randomised, placebo-controlled clinical trial was conducted with 178 patients diagnosed with CL in Santander, Colombia, South-America. To follow the development and spread of the resistance among these strains is difficult, as antibiotic susceptibility testing of clinically relevant anaerobes in different routine laboratories in Europe is less and less frequently carried out due to the fact, that clinicians treat many presumed anaerobic infections empirically. cache = ./cache/cord-009664-kb9fnbgy.txt txt = ./txt/cord-009664-kb9fnbgy.txt === reduce.pl bib === id = cord-009376-a35a92gh author = Lovatt, Archie title = Applications of quantitative PCR in the biosafety and genetic stability assessment of biotechnology products date = 2002-01-07 pages = extension = .txt mime = text/plain words = 9214 sentences = 523 flesch = 48 summary = Applications of Q-PCR within biotechnology are discussed with particular emphasis on the following areas of biosafety and genetic stability testing: (a) determination of the biodistribution of gene therapy vectors in animals; (b) quantification of the residual DNA in final product therapeutics; (c) detection of viral and bacterial nucleic acid in contaminated cell banks and final products; (d) quantification of the level of virus removal in process validation viral clearance studies; (e) specific detection of retroviral RT activity in vaccines with high sensitivity; and (f) transgene copy number determination for monitoring genetic stability during production. We are developing Q-PCR assays for these repeat regions for rodent and primate residual DNA to obtain sensitivity in the fg range, however, one advantage of using a gene such as ␤-actin is gene stability, as this target should not undergo copy number changes within a stable cell line. cache = ./cache/cord-009376-a35a92gh.txt txt = ./txt/cord-009376-a35a92gh.txt === reduce.pl bib === id = cord-004675-n8mlxe7p author = nan title = 2019 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference date = 2019-02-26 pages = extension = .txt mime = text/plain words = 86427 sentences = 5050 flesch = 46 summary = However, the mean infusion rate per site was similar between patients aged <18 years ( XMEN disease (X-linked Immunodeficency with Magnesium defect, Epstein-Barr virus infection and Neoplasia) is a primary immune deficiency caused by mutations in MAGT1 and characterized by chronic infection with Epstein-Barr virus (EBV), EBV-driven lymphoma, CD4 T-cell lymphopenia, and dysgammaglobulinemia. We present the case of a 1-year old Hispanic infant with a pathogenic variant in MAGT1 gene that clinically manifested with early Pneumocystis jirovecii and cytomegalovirus (CMV) interstitial pneumonia, and EBV chronic infection with good response to intravenous immunoglobulins supplementation without hematopoietic stem cell transplantation or gene therapy. Chief, Laboratory of Clinical Immunology and Microbiology, IDGS, DIR, NIAID, NIH, Bethesda, MD, USA Hypomorphic Recombination Activating Gene 1 (RAG1) mutations result in residual T-and B-cell development in both humans and mice and have been found in patients presenting with delayed-onset combined immune deficiency with granulomas and/or autoimmunity (CID-G/AI). cache = ./cache/cord-004675-n8mlxe7p.txt txt = ./txt/cord-004675-n8mlxe7p.txt === reduce.pl bib === id = cord-004879-pgyzluwp author = nan title = Programmed cell death date = 1994 pages = extension = .txt mime = text/plain words = 81677 sentences = 4465 flesch = 51 summary = Furthermore kinetic experiments after complementation of HIV=RT p66 with KIV-RT pSl indicated that HIV-RT pSl can restore rate and extent of strand displacement activity by HIV-RT p66 compared to the HIV-RT heterodimer D66/D51, suggesting a function of the 51 kDa polypeptide, The mouse mammary tumor virus proviral DNA contains an open reading frame in the 3' long terminal repeat which can code for a 36 kDa polypeptide with a putative transmembrane sequence and five N-linked glycosylation sites. To this end we used constructs encoding the c-fos (and c-jun) genes fused to the hormone-binding domain of the human estrogen receptor, designated c-FosER (and c-JunER), We could show that short-term activation (30 mins.) of c-FosER by estradiole (E2) led to the disruption of epithelial cell polarity within 24 hours, as characterized by the expression of apical and basolateral marker proteins. cache = ./cache/cord-004879-pgyzluwp.txt txt = ./txt/cord-004879-pgyzluwp.txt === reduce.pl bib === === reduce.pl bib === id = cord-009571-mygj2nd4 author = nan title = Proceedings of the 42nd annual meeting of the american rheumatism association a section of the arthritis foundation june 1 & 2, 1978 new york city abstracts of papers presented date = 2005-11-23 pages = extension = .txt mime = text/plain words = 46150 sentences = 2284 flesch = 49 summary = Levels of Ty cells as well as total T lymphocytes were measured in 19 patients with systemic lupus erythematosus (SLE), 11 with active and 8 with inactive disease, and in 47 normal subjects. The diagnosis of GC arthritis were studied for the presence of GC antigen (AG) and anti-in all seven patients was made by typical clinical presentation, body (AB) in serum and synovial fluid by counter-positive local culture for Ngonorrhoeae (NG) , and response to treatment. A retrospective study was instituted on 10 patients in the UCLA lupus nephritis clinic in an attempt to determine the ability of three serologic indicators-specifically immune complexes (IC), anti-DNA antibodies (DNA-ab), and C3-to predict the activity of SLE renal disease as indicated by changes in 24 hour proteinuria, serum creatinine, and creatinine clearance. cache = ./cache/cord-009571-mygj2nd4.txt txt = ./txt/cord-009571-mygj2nd4.txt === reduce.pl bib === === reduce.pl bib === id = cord-001835-0s7ok4uw author = nan title = Abstracts of the 29th Annual Symposium of The Protein Society date = 2015-10-01 pages = extension = .txt mime = text/plain words = 138514 sentences = 6150 flesch = 40 summary = Altogether, these results indicate that, although PHDs might be more selective for HIF as a substrate as it was initially thought, the enzymatic activity of the prolyl hydroxylases is possibly influenced by a number of other proteins that can directly bind to PHDs. Non-natural aminoacids via the MIO-enzyme toolkit Alina Filip 1 , Judith H Bartha-V ari 1 , Gergely B an oczy 2 , L aszl o Poppe 2 , Csaba Paizs 1 , Florin-Dan Irimie 1 1 Biocatalysis and Biotransformation Research Group, Department of Chemistry, UBB, 2 Department of Organic Chemistry and Technology An attractive enzymatic route to enantiomerically pure to the highly valuable a-or b-aromatic amino acids involves the use of aromatic ammonia lyases (ALs) and aminomutases (AMs). Continuing our studies of the effect of like-charged residues on protein-folding mechanisms, in this work, we investigated, by means of NMR spectroscopy and molecular-dynamics simulations, two short fragments of the human Pin1 WW domain [hPin1(14-24); hPin1(15-23)] and one single point mutation system derived from hPin1(14-24) in which the original charged residues were replaced with non-polar alanine residues. cache = ./cache/cord-001835-0s7ok4uw.txt txt = ./txt/cord-001835-0s7ok4uw.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-004534-jqm1hxps author = nan title = Abstract date = 2009-06-09 pages = extension = .txt mime = text/plain words = 139023 sentences = 6450 flesch = 42 summary = HIV-1 to efficiently complete a replication cycle has to integrate its genome into the host cellular DNA.After HIV-1 enters target cells,neosynthesized viral DNA forms along with other proteins the pre-integration complex (PIC).PICs are then transported into the nucleus where integration,catalyzed by the viral integrase,takes place.HIV-1 viral particles engineered to incorporate integrase fused to EGFP have proven effective to study PICs within nuclei of infected cells.In this study we report the live imaging analysis of nuclear PIC dynamics obtained by time-lapse microscopy.Intranuclear trajectories of IN-EGFP-labeled PIC were collected in three dimensions and examined by both mean squared displacement (MSD) and cage diameter (CD) analysis.In CD the maximum distances measured between two positions occupied by a PIC in a time window of 2 minutes were calculated while in our MSD analysis 5-minute long trajectory segments were considered.Remarkably,MSD revealed the presence of an underlying active transport mechanism.To test the possible role of actin filaments,PIC nuclear trafficking was analyzed in cells treated with latrunculin B (actin polymerization inhibitor).Preliminary results suggest that the disruption of actin function impairs the active nuclear movement of PICs. Second harmonic generation microscopy reveals sarcomere contractile dynamics of cardiomyocytes N. cache = ./cache/cord-004534-jqm1hxps.txt txt = ./txt/cord-004534-jqm1hxps.txt === reduce.pl bib === id = cord-011053-gza05hsv author = Tiew, Pei Yee title = The Mycobiome in Health and Disease: Emerging Concepts, Methodologies and Challenges date = 2020-01-01 pages = extension = .txt mime = text/plain words = 10936 sentences = 561 flesch = 30 summary = In this state-of-the-art review, we discuss current diagnostic and therapeutic challenges associated with fungal disease and provide key examples where the application of sequencing technologies has potential diagnostic application in assessing the human 'mycobiome'. Despite their natural environmental abundance, few fungi are human pathogens, and while fulminant fungal infection is uncommon in the healthy individuals, invasive fungal disease is a concern in the immuno-compromised host with significant associated morbidity and mortality [2] . Increasing numbers of patients are at risk of invasive fungal disease including those with human immunodeficiency virus (HIV), malignancy and transplant recipients on immunosuppressive or immunomodulatory therapies, each contributing to the rising global trend of fungal infections among susceptible populations. Despite treatment, mortality rates for invasive fungal disease remain high with factors contributing to poor prognosis including delayed diagnosis and initiation of antifungal treatment, host factors, site of infection, emerging antifungal resistance and drug toxicity. cache = ./cache/cord-011053-gza05hsv.txt txt = ./txt/cord-011053-gza05hsv.txt === reduce.pl bib === id = cord-012802-xm2ftrw2 author = Zhao, Wu-li title = The novel quinolizidine derivate IMB-HDC inhibits STAT5a phosphorylation at 694 and 780 and promotes DNA breakage and cell apoptosis via blocking STAT5a nuclear translocation date = 2020-01-13 pages = extension = .txt mime = text/plain words = 7536 sentences = 330 flesch = 50 summary = Our research reveals a novel DNA response mechanism different from general DNA-damaging agents, and that sophoridine derivate inhibits the phosphorylation of Tyr694 and Ser780 of STAT5a to induce the lessened shuttle from the cytoplasm to the nucleus, and leads to the decreased nuclear STAT5a and subsequently inhibits the expression of STAT5a target gene RAD51 that contributes to the checkpoint activation, thus inhibiting ATR activation. All the above-mentioned results demonstrated that IMB-HDC depressed STAT5a nuclear translocation, transcriptional activity, and triggers DNA breakage and apoptosis via blocking 694 and 780 phosphorylation IMB-HDC-induced proliferation inhibition depends on the decreased phosphorylation of 694 and 780 in vivo Next, in a tumor xenograft nude mouse model, we examined IMB-HDC anticancer efficacy. Our previous chip assay analysis showed that the level of several STAT5a target genes decreased; thus, we speculated that STAT5a might be implicated in IMB-HDC-induced apoptosis and DNA breakage in tumor cells. cache = ./cache/cord-012802-xm2ftrw2.txt txt = ./txt/cord-012802-xm2ftrw2.txt === reduce.pl bib === id = cord-010511-eoc0ex3i author = Yousefi, Shida title = In vivo evidence for extracellular DNA trap formation date = 2020-04-30 pages = extension = .txt mime = text/plain words = 9212 sentences = 461 flesch = 32 summary = The formation of extracellular DNA traps by neutrophils, eosinophils, and basophils, but also lymphocytes, has been observed in various infections of humans, mice, and additional species. The circulating autoantibodies such as anti-damaged-DNA/RNA ribonucleoprotein antibody immune complexes (RNP-ICs-Ab) can further activate neutrophils, including NET formation (not shown) 13, 73, 74 , leading to vicious cycle of chronic inflammation in genetically susceptible individuals 68, 74 , causing autoimmune diseases such as systemic lupus erythematous (SLE). Upon stimulation with antimicrobial 72 or antiribonucleoprotein (RNP) antibodies 13, 73, 74 , neutrophils from SLE patients have been shown to release self-DNA associated with antimicrobial peptides able to trigger innate plasmocytoid dendritic cell (pDC) activation via TLR9 to produce IFN-Ι (Fig. 1) . Deep vein thrombosis (DVT) has been linked to neutrophil activation and release of NETs based on studies investigating the pathogenic role of NETs in the pathogenesis of venous thromboembolism (VT) using genetically modified mice, various large animal models and human material assessing plasma markers or thrombi species 126 . cache = ./cache/cord-010511-eoc0ex3i.txt txt = ./txt/cord-010511-eoc0ex3i.txt === reduce.pl bib === id = cord-010621-d1utt8j3 author = Yamamoto, N. title = Assessing allergenic fungi in house dust by floor wipe sampling and quantitative PCR date = 2011-08-09 pages = extension = .txt mime = text/plain words = 5414 sentences = 250 flesch = 48 summary = Abstract In the present study, we modified an existing surface wipe sampling method for lead and other heavy metals to create a protocol to collect fungi in floor dust followed by real‐time quantitative PCR (qPCR)‐based detection. Combined field and laboratory results suggested this modified new wipe sampling method, in conjunction with growth‐independent qPCR, shows potential to improve human exposure and health studies for fungal pathogens and allergens in dust in homes of susceptible, vulnerable population subgroups. Abstract In the present study, we modified an existing surface wipe sampling method for lead and other heavy metals to create a protocol to collect fungi in floor dust followed by real-time quantitative PCR (qPCR)-based detection. Combined field and laboratory results suggested this modified new wipe sampling method, in conjunction with growth-independent qPCR, shows potential to improve human exposure and health studies for fungal pathogens and allergens in dust in homes of susceptible, vulnerable population subgroups. cache = ./cache/cord-010621-d1utt8j3.txt txt = ./txt/cord-010621-d1utt8j3.txt === reduce.pl bib === === reduce.pl bib === id = cord-014368-4nasrbs6 author = nan title = Gene Chip for Viral Discovery date = 2003-11-17 pages = extension = .txt mime = text/plain words = 10009 sentences = 438 flesch = 49 summary = As they report in this paper, Miguel Nicolelis and colleagues have helped clarify some of the fundamental issues surrounding the programming and use of BMIs. Presenting results from a series of long-term studies in monkeys, they demonstrate that the same set of brain cells can control two distinct movements, the reaching and grasping of a robotic arm. RAG genes regulate the genetic recombination and ultimate cell surface expression of TCRs. Using chemical inhibitors and mutant human T cell lines deficient in critical signaling components involved in antigen receptor-dependent pathways, the researchers found that the loss of specific functions or specific proteins affected an unexpected set of target genes. But these studies also establish a model for investigating other signaling systems, to determine whether biologically functional basal signaling is a rare phenomenon or whether it is a fundamental cell process needed to control the profile of gene expression in the quiescent state. cache = ./cache/cord-014368-4nasrbs6.txt txt = ./txt/cord-014368-4nasrbs6.txt === reduce.pl bib === id = cord-011030-o4jn5883 author = Hakki, Morgan title = Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy date = 2020-01-24 pages = extension = .txt mime = text/plain words = 7454 sentences = 384 flesch = 39 summary = A subset of patients were categorized as CMV high-risk, including HLA-A, B, or DR mismatch related donor, HLA-A, B, C, and DRB1 mismatch unrelated Excludes overlapping toxicities with agents commonly used after HCT 3 Approved by the US FDA (year of approval) for prevention and/or treatment 4 ND, not determined donor, haploidentical donor, cord blood transplant, ex vivo T cell-depleted graft, or graft-versus-host disease (GVHD) of grade 2 or greater requiring ≥ 1 mg/kg/day prednisone (or equivalent). A subsequent phase 3 study evaluated maribavir at 100 mg twice daily compared with placebo for the prevention of CMV infection and disease in allogeneic HCT recipients [64] . Maribavir for refractory or resistant cytomegalovirus infections in hematopoietic-cell or solid-organ transplant recipients: a randomized, dose-ranging, double-blind, phase 2 study Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem-cell transplant recipients: a multicenter, randomized, double-blind, placebo-controlled, doseranging study cache = ./cache/cord-011030-o4jn5883.txt txt = ./txt/cord-011030-o4jn5883.txt === reduce.pl bib === id = cord-010443-4jblod8j author = Meduri, Gianfranco Umberto title = General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections date = 2020-04-22 pages = extension = .txt mime = text/plain words = 18827 sentences = 815 flesch = 23 summary = In critical illness, NF-κB-driven systemic inflammation, also known as a "cytokine storm" (14) , activates a multi-system response that includes at least three major domains: (i) the stress system composed by the hypothalamic-pituitary-adrenal (HPA) axis and the locus caeruleus-norepinephrine/sympathetic nervous system activated to provide sufficient energy and hemodynamic stability to overcome the initial phase of critical illness (15) ; (ii) the acute-phase reaction (APR), which has several adaptive functions, including increasing the production of procoagulant factors in preparation for possible tissue damage (16) ; and (iii) the tissue defense response (TDR) of the target organs [ Figure 1 ; (11, 17) ]. In patients with septic shock (170, 171) or ARDS (172, 173) , prolonged glucocorticoid (hydrocortisone or methylprednisolone) treatment resulted in the following: (i) increased plasma activated protein C levels (173); (ii) reduction in markers of endothelial injury such as sICAM-1 (35); (iii) rapid and consistent improvement in capillary perfusion, independently of the cortisol response to ACTH (170) ; and (iv) improvement in alveolar-capillary (172) and renal (171) endothelial permeability. cache = ./cache/cord-010443-4jblod8j.txt txt = ./txt/cord-010443-4jblod8j.txt === reduce.pl bib === id = cord-014908-jys1y0k9 author = Yadav, Rakesh title = Trends and Perspectives of Biosensors for Food and Environmental Virology date = 2010-05-19 pages = extension = .txt mime = text/plain words = 5113 sentences = 259 flesch = 32 summary = Unluckily, the PCR-based tools do not persistently amplify nucleic acids if viruses are found in infected food or environmental samples at critically low level. Another successful innovative biosensor with combined microfluidics and biosensing capabilities, furnish real time and automated affinity bioanalysis (e.g. for antigen-antibody assays) through surface plasmon resonance (SPR)-based original optical transduction mechanism. Since molecular recognition trait is central in the biosensing systems, all the structural components can be targeted to device a biosensor for detection of the specific virion particles present in food and environment samples. Molecular nanotechnology-based new nanostructures/nanomaterials such as aptamers are capable for developing highly specific biosensor for target elements detection. DNA-based biosensors have great applications in food and environmental analysis including determination of the pathogenic bacteria , and virus DNA sequence such as that of SARS virus (Abad-Valle et al. Quartz crystal microbalance (QCM)-based piezoelectric sensors can detect the hybridized viral DNA and also the capsid protein-ligand interactions. cache = ./cache/cord-014908-jys1y0k9.txt txt = ./txt/cord-014908-jys1y0k9.txt === reduce.pl bib === id = cord-014661-mrh2pbi6 author = Dumitrascu, Georgiana R. title = Critical physiological and pathological functions of Forkhead Box O tumor suppressors date = 2013-12-31 pages = extension = .txt mime = text/plain words = 9235 sentences = 419 flesch = 38 summary = FOXO proteins are considered unique cellular targets, regulating a wide variety of critical cellular processes, such as: apoptosis, oxidative stress, DNA damage repair, cell cycle, stem cell proliferation and maintenance, metabolism, angiogenesis, vascular tone, cardiovascular development, fertility, immune response and neuronal survival 4, 20 . Hence, the FOXO transcription factors control the expression of a wide spectrum of genes that regulate essential physiological cellular processes, such as cell death/cell survival, cell cycle, cell proliferation, cell differentiation/development, angiogenesis, cell metabolism, stress response and stem cell maintenance 33,34,35,36,37,38 (Figure 2) . Moreover, the consensus FOXO recognition element (FRE) -(G/C)(T/A)AA(C/T)AA -which differs from that of other forkhead proteins, seems to have a very important role in both apoptotic pathways, since matching functional FRE sites have been identified in the promoters of FOXO target genes encoding Fas ligand (FasL), insulin like growth factorbinding protein 1 (IGFBP1), the apoptotic regulator Bcl-2 interacting mediator of cell death (Bim) and others 30 . cache = ./cache/cord-014661-mrh2pbi6.txt txt = ./txt/cord-014661-mrh2pbi6.txt === reduce.pl bib === id = cord-010564-7c9h16bi author = Unolt, Marta title = Pathogenic variants in CDC45 on the remaining allele in patients with a chromosome 22q11.2 deletion result in a novel autosomal recessive condition date = 2019-09-02 pages = extension = .txt mime = text/plain words = 4682 sentences = 274 flesch = 44 summary = Based on the clinical presentation of these patients and on the recurrent phenotype of the patients with pathogenic variants in the CDC45 gene (Table 1) , reported by Fenwick et al., 5 we further expanded the atypical findings spectrum, to include rare gastrointestinal anomalies, such as intestinal malrotation, imperforate/anteriorly displaced anus and congenital diaphragmatic hernia and short stature (in absence of any endocrine or metabolic cause) and patellar anomalies. 5 identified biallelic pathogenic variants in the CDC45 gene in patients with a recurrent phenotype ( Table 1 ) they reported to be consistent with Meier-Gorlin syndrome (MGS, MIM 224690), a rare autosomal recessive primordial dwarfism disorder, characterized by microtia, short stature, and absent or hypoplastic patellae. Importantly, we suggest that a pathogenic variant in CDC45 should now be considered in every patient with a 22q11.2 deletion who presents with the following findings: craniosynostosis, anorectal anomalies/intestinal malrotation, short stature, upper limb anomalies, and cleft lip and palate. cache = ./cache/cord-010564-7c9h16bi.txt txt = ./txt/cord-010564-7c9h16bi.txt === reduce.pl bib === id = cord-013837-x95r6bz8 author = Chai, Qiyao title = New insights into the evasion of host innate immunity by Mycobacterium tuberculosis date = 2020-07-29 pages = extension = .txt mime = text/plain words = 11189 sentences = 603 flesch = 31 summary = In this review, we describe the emerging role of cytosolic nucleic acid-sensing pathways at the host–Mtb interface and summarize recently revealed mechanisms by which Mtb circumvents host cellular innate immune strategies such as membrane trafficking and integrity, cell death and autophagy. [19] [20] [21] The involvement of the cGAS-mediated DNA-sensing pathway in host anti-Mtb immunity is indicated by the findings that cGAS expression is upregulated and that cGAS is colocalized with mycobacteria in human TB lesions, and its deficiency impairs the induction of type I IFN responses and autophagy in Mtb-infected macrophages. 23 Therefore, specifically targeting mycobacterial ESX-1 products or host regulatory factors might enable the selective regulation of inflammasome and cGAS/STING pathway activation and, hence, contribute to the recovery of the equilibrium between Th1-type cytokine and type I IFN responses in TB patients to improve their anti-Mtb immunity. cache = ./cache/cord-013837-x95r6bz8.txt txt = ./txt/cord-013837-x95r6bz8.txt === reduce.pl bib === id = cord-014397-7b88ycv8 author = Gavora, JS title = Resistance of livestock to viruses: mechanisms and strategies for genetic engineering date = 1996-12-15 pages = extension = .txt mime = text/plain words = 11583 sentences = 528 flesch = 41 summary = Thus introduction of new mechanisms of disease resistance in livestock by gene transfer may be viewed as a logical continuation of the creative influence of humans on the evolution of farm animals and birds that could benefit mankind by improvements in food safety and production efficiency. As background for the discussion of the subject, the article deals briefly with coevolution of hosts and parasites and principal elements of virus-host interactions, and reviews past improvement of disease resistance in plants and livestock by conventional breeding and genetic engineering, as well as the potential 'biological cost' of genetic manipulation. Basic understanding of the parallel evolution of viruses and their hosts provides a useful starting point for the consideration of strategies for genetic engineering of new mechanisms of resistance. Genetic engineering strategies that prevent entry of viruses into host cells would be effective against all three types of viral infection. cache = ./cache/cord-014397-7b88ycv8.txt txt = ./txt/cord-014397-7b88ycv8.txt === reduce.pl bib === id = cord-012461-v8d91fdo author = Marnissi, Boutheina title = Generation of ssDNA aptamers as diagnostic tool for Newcastle avian virus date = 2020-08-13 pages = extension = .txt mime = text/plain words = 6108 sentences = 304 flesch = 54 summary = Top aptameric sequences were used to develop a sandwich enzymatic linked aptamer assay (ELAA) for rapid and sensitive detection of NDV in farm samples. Following optimization of the sandwich ELAA method, the results demonstrated that both selected aptamers Apt_NDV01 and Apt_NDV03 with dissociation constant values of 31 nM and 78.1 nM, respectively, showed the highest specificity and affinity for NDV detection. The output of the SELEX was amplified by symmetric (S1 Fig in S1 File) and asymmetric PCR, and the final PCR products were incubated with the virus immobilized on a nitrocellulose membrane, using an immune-blot test to monitor the enrichment of target-binding aptamers. The specificity of the five selected aptamers, Apt_NDV01-05, against NDV was evaluated by testing their affinities against various avian viruses besides NDV-LaSota vaccine strain, including H120-IBV, IBDV-Gomboro, 1133 reovirus, avian influenza-H9N2, and a naïve library which was used as a negative control. cache = ./cache/cord-012461-v8d91fdo.txt txt = ./txt/cord-012461-v8d91fdo.txt === reduce.pl bib === id = cord-010784-khvrklqt author = Waki, Kayoko title = Integrity of plasma DNA is inversely correlated with vaccine-induced antitumor immunity in ovarian cancer patients date = 2020-05-11 pages = extension = .txt mime = text/plain words = 3076 sentences = 173 flesch = 50 summary = Here, we investigated the potential utility of the circulating cell-free DNA (cfDNA) integrity—a ratio of necrotic cell-derived, longer DNA fragments versus apoptotic cell-derived shorter fragments of Alu gene—as a biomarker of vaccine therapy for patients with ovarian cancer. We analyzed plasma samples from 39 patients with advanced or recurrent ovarian cancer enrolled in clinical trials for personalized peptide vaccinations. We conducted the present study to investigate the possibility of using the circulating cfDNA integrity as a biomarker of vaccine therapy for patients with ovarian cancer. Frozen plasma samples from 39 patients with advanced or recurrent ovarian cancer who were enrolled in clinical trials of the personalized peptide vaccination during the period from January 2009 to July 2012 were used in this study [6] . We analyzed the circulating cfDNA integrity of 39 patients with advanced or recurrent ovarian cancer who were treated with a personalized peptide vaccination in a clinical trial [6] . cache = ./cache/cord-010784-khvrklqt.txt txt = ./txt/cord-010784-khvrklqt.txt === reduce.pl bib === id = cord-011630-lfm34fsw author = Li, Yan title = Epigenetic inheritance of circadian period in clonal cells date = 2020-05-27 pages = extension = .txt mime = text/plain words = 5694 sentences = 306 flesch = 43 summary = By examining large-scale phenotype-associated gene expression profiles in hundreds of mouse clonal cell lines, we identified and validated multiple novel candidate genes involved in circadian period determination in the absence of significant genomic variants. Here, by examining phenotype-associated high-throughput multi-omics profiles in clonal cell populations, we identified and validated a pool of novel candidate genes regulating circadian period length and uncovered complex gene co-expression networks highly enriched in stress response and metabolic pathways. Using weighted gene co-expression network analysis (WGCNA), we generated 31 modules from the 10 clonal cell lines RNA-seq data ( Figure 4A , Figure 4 -source data 1). Dnmt1 and Dnmt3a knockdown in the ten clonal cell lines showed the same overall results, suggesting that DNA methylation affects circadian periodicity in the same way in all clones tested ( Figure 7C ). cache = ./cache/cord-011630-lfm34fsw.txt txt = ./txt/cord-011630-lfm34fsw.txt === reduce.pl bib === id = cord-012473-p66of6kq author = Celniker, Susan E. title = Unlocking the secrets of the genome date = 2009-06-17 pages = extension = .txt mime = text/plain words = 2556 sentences = 119 flesch = 37 summary = T he primary objective of the Human Genome Project was to produce highquality sequences not just for the human genome but also for those of the chief model organisms: Escherichia coli, yeast (Saccharomyces cerevisiae), worm (Caenorhabditis elegans), fly (Drosophila melanogaster) and mouse (Mus musculus). Free access to the resultant data has prompted much biological research, including development of a map of common human genetic variants (the International HapMap Project) 1 , expression profiling of healthy and diseased cells 2 and in-depth studies of many individual genes. On the basis of this experience, the NHGRI launched two complementary programmes in 2007: an expansion of the human ENCODE project to the whole genome (www.genome.gov/ENCODE) and the model organism ENCODE (modENCODE) project to generate a comprehensive annotation of the functional elements in the C. The research communities that study these two organisms will rapidly make use of the modENCODE results, deploying powerful experimental approaches that are often not possible or practical in mammals, including genetic, genomic, transgenic, biochemical and RNAi assays. cache = ./cache/cord-012473-p66of6kq.txt txt = ./txt/cord-012473-p66of6kq.txt === reduce.pl bib === id = cord-010680-lc1onm53 author = Patel, Ami title = In Vivo Delivery of Nucleic Acid-Encoded Monoclonal Antibodies date = 2020-03-10 pages = extension = .txt mime = text/plain words = 13044 sentences = 659 flesch = 41 summary = Some of these hurdles may be overcome through transient in vivo gene delivery platforms, such as non-viral synthetic plasmid DNA and messenger RNA vectors that are engineered to encode optimized mAb genes. In this review, we focus on nucleic acid delivery of antibody employing synthetic plasmid DNA vector platforms, and RNA delivery, these being important approaches that are advancing simple, rapid, in vivo expression and having an impact in animal models of infectious diseases and cancer, among others. The original studies surrounding in vivo antibody gene delivery focused primarily on gene delivery using recombinant viral vectors such as AAV and adenovirus (Ad), which were advanced clinically, building on work in the traditional gene therapy-based field. Additional studies to help evaluate fully human pDNA-mAbs in mouse models would be highly informative for both non-viral and viral delivery and provide an important path forward for preclinical evaluation of in vivo-delivered antibodies [109] . cache = ./cache/cord-010680-lc1onm53.txt txt = ./txt/cord-010680-lc1onm53.txt === reduce.pl bib === id = cord-013412-gj443yei author = Lebedeva, Natalya Sh. title = The Application of Porphyrins and Their Analogues for Inactivation of Viruses date = 2020-09-23 pages = extension = .txt mime = text/plain words = 13428 sentences = 626 flesch = 46 summary = The purpose of this review paper is to summarize the main approaches developed to date in the chemical and photodynamic inactivation of human and animal viruses using porphyrins and their analogues and to analyze and discuss the information on viral targets and antiviral activity of porphyrins, chlorins, of their conjugates with organic/inorganic compounds obtained in the last 10–15 years in order to identify the most promising areas. A cationic substituent is necessary to increase the solubility of porphyrins and their analogues in aqueous media, and three nitro groups provide linking of the gp120 protein with the glycoprotein ( Figure 3 ) and thereby inhibit fusion between the virus and the cell membrane. A cationic substituent is necessary to increase the solubility of porphyrins and their analogues in aqueous media, and three nitro groups provide linking of the gp120 protein with the glycoprotein ( Figure 3 ) and thereby inhibit fusion between the virus and the cell membrane. cache = ./cache/cord-013412-gj443yei.txt txt = ./txt/cord-013412-gj443yei.txt === reduce.pl bib === id = cord-010056-zfin4bko author = Mejia, Rojelio title = Impact of intestinal parasites on microbiota and cobalamin gene sequences: a pilot study date = 2020-04-19 pages = extension = .txt mime = text/plain words = 4092 sentences = 260 flesch = 41 summary = RESULTS: For Giardia-only infected children compared to uninfected children, DNA sequencing data showed a decrease in microbiota biodiversity that correlated with increasing Giardia burden and was statistically significant using Shannon's alpha diversity (Giardia-only > 1 fg/µl 2.346; non-infected group 3.253, P = 0.0317). CONCLUSION: The study results may provide evidence for an effect of parasitic infections enabling the permissive growth of anaerobic bacteria such as Prevotella, suggesting an altered capacity of vitamin B12 (cobalamin) biosynthesis and potential impact on growth and development in children [Image: see text]. There are few studies attributing gut microbiome changes to giardiasis [17] [18] [19] and no published studies showing the impact on the human intestinal microbiome using multi-parallel real-time quantitative (qPCR) to detect the presence of Giardia and quantitating the burden of infection [20] . In this pilot study, parasite qPCR and next-generation DNA sequencing was used to explore whether quantitative burden of specific parasites (Giardia duodenalis and soil-transmitted helminths) influence the composition of intestinal microbial communities. cache = ./cache/cord-010056-zfin4bko.txt txt = ./txt/cord-010056-zfin4bko.txt === reduce.pl bib === id = cord-011073-uiabpbxd author = Gebrekidan, Hagos title = An appraisal of oriental theileriosis and the Theileria orientalis complex, with an emphasis on diagnosis and genetic characterisation date = 2019-12-06 pages = extension = .txt mime = text/plain words = 7011 sentences = 406 flesch = 46 summary = Oriental theileriosis, a tick-borne disease of bovids caused by members of the Theileria orientalis complex, has a worldwide distribution. orientalis complex, including conventional polymerase chain reaction (PCR), nested-PCR, reverse line blot hybridisation assay (RLB), loop-mediated isothermal amplification (LAMP), real-time/quantitative PCR (qPCR) using hydrolysis probes and multiplexed tandem PCR (MT-PCR) assays (Table 2) . nPCR Members of the Theileria orientalis complex have been detected in cattle blood samples in Brazil, Iran, South Africa, Uganda and the USA using semi-nested or nested PCR (nPCR) assay employing the SSU or ITS loci (Chae et al. orientalis allow for a rapid and accurate diagnosis (mainly for the two pathogenic genotypes chitose and ikeda), some assays can be expensive for routine use due to individual testing of blood samples, particularly when outbreaks of oriental theileriosis occur in cattle herds. Development and evaluation of a real-time PCR assay for the quantitative detection of Theileria annulata in cattle cache = ./cache/cord-011073-uiabpbxd.txt txt = ./txt/cord-011073-uiabpbxd.txt === reduce.pl bib === id = cord-013614-j6h338qa author = Liu, Xiaojing title = ERCC6L2 promotes DNA orientation-specific recombination in mammalian cells date = 2020-04-30 pages = extension = .txt mime = text/plain words = 8200 sentences = 576 flesch = 55 summary = To identify potentially new NHEJ factors, we combined chemical perturbation screens on 36 compounds with focused CRISPRknockout screens on 414 genes in the CH12 B cell line ( Fig. 1a ; Supplementary information, Table S1 , see Materials and Methods for details). ERCC6L2 clusters with other NHEJ factors Next, we clustered all 414 DNA repair genes by their z-scores across the 36 chemicals used, which categorized genes into three major groups depending on their impact on cell growth (Supplementary information, Fig. S1a ). Furthermore, the helicase catalytic-dead (DEAH > AAAH) mutant did not promote CSR ( Fig. 3a ; Supplementary information, Fig. S4b ), indicating that ERCC6L2's predicted catalytic activity is required for DNA end-joining. To bypass the B cell development defect of core-NHEJ factor deficiencies and quickly access the directional CSR, we deleted the non-productive IgH allele in CH12F3 cells as previous described 18 (Supplementary information, Fig. S8c , named CH12-NCDel cells) and perform HTGTS assay with endogenous AID Sμ baits. cache = ./cache/cord-013614-j6h338qa.txt txt = ./txt/cord-013614-j6h338qa.txt === reduce.pl bib === id = cord-013223-f43hks44 author = Chronopoulos, Antonios title = Emerging role of bacterial extracellular vesicles in cancer date = 2020-10-15 pages = extension = .txt mime = text/plain words = 5793 sentences = 264 flesch = 29 summary = The increasing appreciation that microbiota-derived EV can enter the systemic circulation and be detected in human body fluids is likely to stimulate completely new areas of investigation in microbiome research, biomarkers and liquid biopsies, BEV-based therapeutics, onco-immunology, as well as fundamental microbial EV biology. In addition to potentially modulating the innate immune response via or more cytosolic DNA sensors, the possibility that pathogenic BEV-derived DNA can be transferred and detected in the nucleus of non-phagocytic cells (e.g. epithelial cells) [30] , raises the intriguing possibility that bacterial genetic material could be transferred to human somatic cells and integrated into the host genome. BEVs released by bacteria in the gut lumen can cross the epithelial barrier to gain access into the underlying submucosa enabling them to interact with various resident immune cell populations (dendritic cells, neutrophils and macrophages) as well as potentially disseminate more widely around the body via the systemic or lymphatic circulation to reach distant tissues and organs or even the brain (Fig. 2) . cache = ./cache/cord-013223-f43hks44.txt txt = ./txt/cord-013223-f43hks44.txt === reduce.pl bib === id = cord-015946-biu5zxd1 author = Peng, Daizhi title = Research Advances in Biomarker for Sepsis date = 2016-11-16 pages = extension = .txt mime = text/plain words = 5100 sentences = 242 flesch = 40 summary = Most commonly proposed sepsis and infection biomarkers including C-reactive protein (CRP), procalcitonin (PCT) [5, 6] , cytokines (TNF-α, IL-1, IL-6, IL-10, osteopontin) [7, 8] , chemokines [macrophage migration inhibitory factor (MIF), high-mobility-group box 1 (HMGB1)] [9, 10] , soluble receptor [soluble triggering receptor expressed on myeloid cells 1 (sTREM-1), soluble urokinase-type plasminogen activator receptor (suPAR)] [11, 12] etc. When it comes to sepsis, by using genome-wide miRNA profiling with microarray in peripheral blood leukocytes and quantitative RT-PCR, Vasilescu [71] found that miR-150 levels were significantly reduced in both leukocytes and plasma of sepsis patients and had a negative correlation with the level of disease severity measured by the Sequential Organ Failure Assessment (SOFA) score, which made it a biomarker of early sepsis. As they were significantly correlated with disease severity, classical markers of inflammation and bacterial infection, as well as organ failure, high miR-133a levels were considered as independent biomarkers for unfavorable prognosis of critically ill patients. cache = ./cache/cord-015946-biu5zxd1.txt txt = ./txt/cord-015946-biu5zxd1.txt === reduce.pl bib === id = cord-015850-ef6svn8f author = Saitou, Naruya title = Eukaryote Genomes date = 2013-08-22 pages = extension = .txt mime = text/plain words = 7424 sentences = 484 flesch = 53 summary = General overviews of eukaryote genomes are first discussed, including organelle genomes, introns, and junk DNAs. We then discuss the evolutionary features of eukaryote genomes, such as genome duplication, C-value paradox, and the relationship between genome size and mutation rates. Most of the protein coding genes of melon mitochondrial DNAs are highly similar to those of its congeneric species, which are watermelon and squash whose mitochondrial genome sizes are 119 kb and 125 kb, respectively. There are various genomic features that are specifi c to eukaryotes other than existence of introns and junk DNAs, such as genome duplication, RNA editing, C-value paradox, and the relationship between genome size and mutation rates. The Perigord black truffl e ( Tuber melanosporum ), shown as A i n Fig. 8.9 , has the largest genome size (~125 Mb) among the 88 fungi species whose genome sequences were so far determined, yet the number of genes is only ~7,500 [ 81 ] . cache = ./cache/cord-015850-ef6svn8f.txt txt = ./txt/cord-015850-ef6svn8f.txt === reduce.pl bib === id = cord-014875-xhzxhwgo author = nan title = Book Reviews date = 2003 pages = extension = .txt mime = text/plain words = 7144 sentences = 338 flesch = 46 summary = The last chapter in the second focused area is by Pumpens and Grens, who provide an in-depth discussion of the use of viral vectors for delivering a desirable gene into target cells for protein production. The chapters don't cover material in great depth (and if they did, this book will be many times larger) but they provide enough information to cover what someone new to the area would need to know to get started. As described above, this book does not intend to summarize transporters related to drugs rather tried to introduce many technologies to be used in future studies for molecular cloning, structure, functionality, regulation, and sorting in various point of views by using typical experimental results on physiologically important transporter molecules. Each chapter provides a polymer-based step-bystep description of not only basic information including various classification, application, and structure-property relationships, but also very practical descriptions of synthetic and analytic techniques that are believed to be good references in research laboratories. cache = ./cache/cord-014875-xhzxhwgo.txt txt = ./txt/cord-014875-xhzxhwgo.txt === reduce.pl bib === id = cord-015677-67md3xox author = Lang, Hans Peter title = Nanomechanical Cantilever Array Sensors date = 2010 pages = extension = .txt mime = text/plain words = 10409 sentences = 597 flesch = 42 summary = In addition to application of such sensors for gas and chemical-vapor sensing, for example as an artificial nose, they have also been employed to measure physical properties of tiny amounts of materials in miniaturized versions of conventional standard techniques such as calorimetry, thermogravimetry, weighing, photothermal spectroscopy, as well as for monitoring chemical reactions such as catalysis on small surfaces. In addition to application of such sensors for gas and chemicalvapor sensing, for example as an artificial nose, they have also been employed to measure physical properties of tiny amounts of materials in miniaturized versions of conventional standard techniques such as calorimetry, thermogravimetry, weighing, photothermal spectroscopy, as well as for monitoring chemical reactions such as catalysis on small surfaces. Besides chemical and biochemical sensing, microcantilevers can also detect changes in physical properties of surrounding media, such as gas or liquid, or of layers deposited on the cantilever itself. cache = ./cache/cord-015677-67md3xox.txt txt = ./txt/cord-015677-67md3xox.txt === reduce.pl bib === id = cord-011113-n1yf0o2o author = Chen, Weiye title = A seven-gene-deleted African swine fever virus is safe and effective as a live attenuated vaccine in pigs date = 2020-03-01 pages = extension = .txt mime = text/plain words = 5944 sentences = 283 flesch = 60 summary = As shown in Figure 4A , the pigs that were inoculated with one dose of 10 5 TCID 50 vaccine and challenged i.m. with 200 PLD 50 of HLJ/18 on day 28 post-vaccination all survived the 3-week observation period, but viral DNA was detected in the blood, tonsil, and two lymph nodes of one of the five pigs that were euthanized at the end of the observation period ( Figure 4A ), indicating that HLJ/18-7GD provides similar protection in both farmed and SPF pigs. cache = ./cache/cord-011113-n1yf0o2o.txt txt = ./txt/cord-011113-n1yf0o2o.txt === reduce.pl bib === id = cord-015935-r2wd1yfa author = Sokol, Deborah K. title = The Genetics of Autism date = 2011-02-10 pages = extension = .txt mime = text/plain words = 11276 sentences = 598 flesch = 45 summary = Another offshoot of microarray technology is submicroscopic chromosome copy number variation (CNV) analysis, in which deletions or duplications involving > 1-kb DNA have been detected in patients with mental retardation, autism, and multiple congenital anomalies. Technology compatible with this approach includes cytogenetics (including karyotyping and FISH), gene association studies (analysis of genes and protein system from less complex genetic syndromes similar to autism such as Rett and fragile X syndromes), linkage studies (including genome screens in affected sibling pairs), microarray technology, and CNV analysis. Cytogenetic approaches provided the first evidence for an autism gene 40 years ago when Lubs (1969) identified an abnormal or "fragile" site on the long arm of chromosome X in four males with mental retardation, leading to the recognition of fragile X syndrome (FXS). As chromosome 7q has been discussed in section "Cytogenetics: Rare Mutations," chromosome 2 and then 17q11 will follow the description of how linkage studies led to the discovery of the gene loci for a syndromic form of autism: tuberous sclerosis complex (TSC). cache = ./cache/cord-015935-r2wd1yfa.txt txt = ./txt/cord-015935-r2wd1yfa.txt === reduce.pl bib === id = cord-013290-j3assowx author = Guibinga, Ghiabe H. title = Protection against Borreliella burgdorferi infection mediated by a synthetically engineered DNA vaccine date = 2020-08-12 pages = extension = .txt mime = text/plain words = 5081 sentences = 281 flesch = 50 summary = We describe the development of a novel synthetically engineered DNA vaccine, pLD1 targeting the outer-surface protein A (OspA) of Borreliella burgdorferi. Immunization of C3 H/HeN mice with pLD1 elicits robust humoral and cellular immune responses that confer complete protection against a live Borreliella burgdorferi bacterial challenge. The data show that pDL1 DNA vaccine elicits robust humoral and cellular immune responses in mice against the OspA antigen that confers protection against Borreliella burgdorferi spirochete tissue colonization following a live bacterial challenge. We show that a synthetically engineered vaccine pLD1 elicits robust and durable anti-OspA IgG levels, and confers protection against Borreliella burgdorferi infection in a C3 H/HeN mouse needle challenge model. These data indicate the immune response elicited by pLD1 can generate antibodies which can bind to the same OspA epitopes as mAbs which have been shown to prevent transmission of Lyme disease spirochetes. cache = ./cache/cord-013290-j3assowx.txt txt = ./txt/cord-013290-j3assowx.txt === reduce.pl bib === id = cord-013415-110b95cg author = Aquino-Martinez, Ruben title = Periodontal Disease and Senescent Cells: New Players for an Old Oral Health Problem? date = 2020-10-09 pages = extension = .txt mime = text/plain words = 10333 sentences = 522 flesch = 27 summary = Although the host immune response rapidly protects against bacterial invasion, oxidative stress generated during inflammation can indirectly deteriorate periodontal tissues through the damage to vital cell macromolecules, including DNA. In contrast to transient DNA damage, persistent genomic lesions promote constitutive DNA damage signaling and cellular senescence, which is correlated with increased secretion of inflammatory signals [26, 30] In agreement with this observation, several studies have reported that premature senescence can also be induced by exposing human cells to subtoxic H 2 O 2 concentrations [31, 32] . As a consequence of chronological aging, the burden of senescent cells increases in different tissues in humans, mice, and other species, where they contribute to the development of chronic pathologies including arthritis, osteoporosis, Alzheimer's disease, atherosclerosis, cancer, and diabetes [58, 59] Similar to other agerelated pathologies, the etiology of diabetes may be the result of the impact of different aging mechanism, including stem cell exhaustion, chronic low-grade inflammation, macromolecular damage, and cellular senescence. cache = ./cache/cord-013415-110b95cg.txt txt = ./txt/cord-013415-110b95cg.txt === reduce.pl bib === id = cord-012418-6ralcn8p author = Schwanke, Hella title = Of Keeping and Tipping the Balance: Host Regulation and Viral Modulation of IRF3-Dependent IFNB1 Expression date = 2020-07-07 pages = extension = .txt mime = text/plain words = 15685 sentences = 761 flesch = 38 summary = Due to its key role during the induction of the initial IFN response, the activity of the transcription factor interferon regulatory factor 3 (IRF3) is tightly regulated by the host and fiercely targeted by viral proteins at all conceivable levels. The crucial role of IRF3 and the posttranslational changes it undergoes upon viral infection were first reported more than 20 years ago: Upon stimulation, IRF3 gets phosphorylated and accumulates in the nucleus where it interacts with the coactivators CREB-binding protein (CBP)/p300 to specifically bind to virus-inducible enhancer elements and exerts transcriptional activation of the IFNB1 gene [21, [36] [37] [38] (Figure 2 ). The crucial role of IRF3 and the posttranslational changes it undergoes upon viral infection were first reported more than 20 years ago: Upon stimulation, IRF3 gets phosphorylated and accumulates in the nucleus where it interacts with the coactivators CREB-binding protein (CBP)/p300 to specifically bind to virus-inducible enhancer elements and exerts transcriptional activation of the IFNB1 gene [21, [36] [37] [38] (Figure 2 ). cache = ./cache/cord-012418-6ralcn8p.txt txt = ./txt/cord-012418-6ralcn8p.txt === reduce.pl bib === id = cord-016309-6mw8okmt author = Bule, Mohammed title = Antivirals: Past, Present and Future date = 2019-06-06 pages = extension = .txt mime = text/plain words = 8200 sentences = 405 flesch = 36 summary = Those included usage restricted to a single virus and specific animal species, problems with high spectrum activity and low cytotoxicity, high costs of development of new chemical compounds and absence of rapid diagnostic techniques allowing prompt use of a specific antiviral agent in the course of an acute infection (Rollinson 1992a, b) . Nevertheless, several licensed human antiviral agents are being used with cascade principle for treatment of animal diseases (e.g. acyclovir, idoxuridine and trifluridine against feline herpesvirus-1 ocular infection in cats) (Thiry et al. The discovery of PAA (Fig. 22.4) as an antiviral drug gave rise to intense research on its biological activities, which demonstrated PAA and its derivatives' ability to inhibit the replication of a number of viruses such as immunodeficiency, hepatitis and herpes viruses. To conclude with, equine herpesvirus type 1 (EHV-1) infection causes outbreak of respiratory and various neurological diseases in horses, against which acyclovir and valacyclovir are the most common drugs, but also IFN targeting IFNGR complex as a key mediator of virus-specific cellular immunity (Poelaert et al. cache = ./cache/cord-016309-6mw8okmt.txt txt = ./txt/cord-016309-6mw8okmt.txt === reduce.pl bib === id = cord-014462-11ggaqf1 author = nan title = Abstracts of the Papers Presented in the XIX National Conference of Indian Virological Society, “Recent Trends in Viral Disease Problems and Management”, on 18–20 March, 2010, at S.V. University, Tirupati, Andhra Pradesh date = 2011-04-21 pages = extension = .txt mime = text/plain words = 35453 sentences = 1711 flesch = 49 summary = Molecular diagnosis based on reverse transcription (RT)-PCR s.a. one step or nested PCR, nucleic acid sequence based amplification (NASBA), or real time RT-PCR, has gradually replaced the virus isolation method as the new standard for the detection of dengue virus in acute phase serum samples. Non-genetic methods of management of these diseases include quarantine measures, eradication of infected plants and weed hosts, crop rotation, use of certified virus-free seed or planting stock and use of pesticides to control insect vector populations implicated in transmission of viruses. The results of this study indicate that NS1 antigen based ELISA test can be an useful tool to detect the dengue virus infection in patients during the early acute phase of disease since appearance of IgM antibodies usually occur after fifth day of the infection. The studies showed high level of expression in case of constructed vector as compared to infected virus for the specific protein. cache = ./cache/cord-014462-11ggaqf1.txt txt = ./txt/cord-014462-11ggaqf1.txt === reduce.pl bib === id = cord-016144-280kwlev author = Maan, Sushila title = Novel Molecular Diagnostics and Therapeutic Tools for Livestock Diseases date = 2018-04-26 pages = extension = .txt mime = text/plain words = 6526 sentences = 364 flesch = 45 summary = Further, modifications in PCR-based molecular detection techniques have generated a vast array of fast, reliable and specific assays which have widespread applications in veterinary diagnostics. The sensitivity of any genome detection-based method can be enhanced to a very high degree by manipulating any of the three pillars of the assay, i.e. by amplification of target, signal and probe. Common real-time PCRs include (1) SYBR green method where the fluorescent dye SYBR green binds to random dsDNA and can also give nonspecific amplification and (2) dual dyelabelled probe method which involves the use of sequence-specific DNA probes that are labelled with a fluorescent reporter, permitting specific detection after hybridization of the probe with its complementary sequence. To overcome these limitations and to increase efficiency comparable to symmetric PCRs, linear after the exponential (LATE)-PCR was developed based on primer pairs purposely designed for use at unequal concentrations to yield specific single-stranded DNA products in a robust way (Pierce et al. cache = ./cache/cord-016144-280kwlev.txt txt = ./txt/cord-016144-280kwlev.txt === reduce.pl bib === id = cord-006466-e1phpqes author = nan title = 2018 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference date = 2018-04-23 pages = extension = .txt mime = text/plain words = 92230 sentences = 5516 flesch = 46 summary = Whole exome sequencing revealed a heterozygous mutation, previously reported (c.1425+1G>T) Conclusions: In summary, this report emphasizes the suspicion of a combined immunodeficiency in the presence of multiple abscesses by Mycoplasma, the usefulness of rDNA 16s in order to achieve proper Objectives: We describe a 15-year-old male patient with novel heterozygous mutation of EP300 gene; his first manifestations were initially characterized by infections, cytopenia and hypogammaglobulinemia suggesting a Common Variable Immunodeficiency (CVID), but later on, persisting lymphopenia was suggestive of a combined immunodeficiency. Conclusions: Close monitoring of immune function in early life for patients with CHH and CID as well as the availability of suitable donors assists in determining management, including HSCT Introduction/Background: Leukocyte Adhesion Deficiency (LAD) represents a group of distinct inherited disorders, which inhibit the normal extravasation of neutrophils and their recruitment to sites of infection or inflammation. cache = ./cache/cord-006466-e1phpqes.txt txt = ./txt/cord-006466-e1phpqes.txt === reduce.pl bib === === reduce.pl bib === id = cord-016041-427mbaqc author = Hengge, Ulrich R. title = Gentherapie date = 2008 pages = extension = .txt mime = text/plain words = 7287 sentences = 824 flesch = 46 summary = Die somatische Gentherapie befasst sich mit der Behandlung von somatischen (Körper-)Zellen (>Tab. 4.1.1), wobei das therapeutische Gen ein im Organismus benötigtes Protein kodiert. Die somatische Gentherapie befasst sich mit der Behandlung von somatischen (Körper-)Zellen (>Tab. 4.1.1), wobei das therapeutische Gen ein im Organismus benötigtes Protein kodiert. Neue Verfahren des Vektor-Targetings sowie interessante Techniken wie Elektroporation und hydrodynamische Injektion konnten die Transgenexpression in vivo verbessern, indem eine verbesserte Verteilung der Plasmid-DNA im Zielorgan erreicht wurde (Wolff u. Bei einer weiteren Zytokin-Gentherapie wurde Melanompatienten intratumoral ein Canarypox-Virus-Vektor injiziert, der das IL-12-Gen exprimierte, und zur T-Zell-Akkumulation in injizierten Melanomen führte (Triozzi et al. Es ist jedoch schwierig, einen Zusammenhang zwischen Tumorregression und der Existenz einer durch die Vakzinierung induzierten zytotoxischen T-Zell-Antwort unzweifelhaft festzustellen, da nicht alle Patienten mit zellulären Immunantworten auf den Tumor eine Regression desselben zeigen. Ein Paradebeispiel hierfür ist das p53-Protein, das erst nach einem aufgetretenen DNA-Schaden den Zellzyklus blockiert und die Zellen der Apoptose unterwirft (Roth 2006) . cache = ./cache/cord-016041-427mbaqc.txt txt = ./txt/cord-016041-427mbaqc.txt === reduce.pl bib === id = cord-014712-5u4e00q6 author = nan title = Selected Abstracts from the 100th J Project Meeting, Antalya, Turkey, March 12-14, 2014 date = 2014-08-02 pages = extension = .txt mime = text/plain words = 36900 sentences = 2254 flesch = 49 summary = Ege University Faculty of Medicine, Dept of Pediatric Immunology, Izmir, Turkey Ig class switch recombination deficiencies are rare PIDs (1:500,000 births) with normal or elevated serum IgM and low IgG, IgA and IgE levels, defective or normal somatic hypermutation, defective T/B cooperation (50%), intrinsic B cell defect (50%), susceptibility to bacterial infections begining from the first year of age (impaired B cell immunity) and lack of germinal centres in secondary lymphoid organs. Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, and Primary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK Even following the introduction of biologic disease modifying antirheumatic drugs (DMARDs), a small number of children suffering from severe, refractory autoimmune (AI), rheumatic and/or autoinflammatory disorders will not get into clinical remission (CR) and will potentially further suffer from multiple side-effects of combined and long-term immunosuppressive and anti-inflammatory therapies, in particular severe infections (Marodi L, Casanova JL. cache = ./cache/cord-014712-5u4e00q6.txt txt = ./txt/cord-014712-5u4e00q6.txt === reduce.pl bib === id = cord-015619-msicix98 author = nan title = Virus Structure & Assembly date = 2009-02-24 pages = extension = .txt mime = text/plain words = 3302 sentences = 164 flesch = 45 summary = The studies were performed with nanoindentation techniques using an Atomic Force Microscope (AFM), an approach which is becoming a standard method to measure the mechanical properties of viral particles (1, 2) . Using molecular dynamics simulations of the connector in complex with DNA, and aiming at distinguishing between these three models, we calculated mechanical properties of this system. The bacteriophage lambda is composed of an icosahedral capsid, into which a 48.5 kbp double-stranded DNA genome is packaged, and a long non-contractile tail consisting of 34 disk-like structures. The relative probabilities of fusion and endocytosis of a virus particle initially nonspecifically adsorbed on the host cell membrane are computed as functions of receptor concentration, binding strength, and number of spikes. As revealed by techniques of structural biology and single-molecule experimentation, the capsids of viruses are some of nature's best examples of highly symmetric multiscale self-assembled structures with impressive mechanical properties of strength and elasticity. cache = ./cache/cord-015619-msicix98.txt txt = ./txt/cord-015619-msicix98.txt === reduce.pl bib === id = cord-014597-66vd2mdu author = nan title = Abstracts from the 25th European Society for Animal Cell Technology Meeting: Cell Technologies for Innovative Therapies: Lausanne, Switzerland. 14-17 May 2017 date = 2018-03-15 pages = extension = .txt mime = text/plain words = 50613 sentences = 2624 flesch = 46 summary = Irrespective of the cell culture-based system and production scale, PEIpro® and PEIpro®-HQ have led to efficient viral vector yields superior to 10 7 IG/mL and 10 9 VG/mL, respectively for lentiviruses and AAVs Background Continuous perfusion process is making a comeback as a competing upstream manufacturing technology for the production of Biopharmaceuticals compared to the standard fed batch processes. To evaluate the impact of feed-spiking compared with cultivation in basal medium only, the cell line was grown in bioreactors under controlled conditions to determine cellspecific metabolic rates, nutrient consumption, and byproduct accumulation over the process time. Through the interchangeability of signal peptides between products and even species, a large variety can be used to enhance protein expression in already existing production systems Materials and methods At first the influence of four different natural SPs (SP (7), (8), (9) and (10)) was compared on the secreted amount of an IgG4 model antibody (product A) in fed batches using a CHO DG44 host cell line. cache = ./cache/cord-014597-66vd2mdu.txt txt = ./txt/cord-014597-66vd2mdu.txt === reduce.pl bib === id = cord-014674-ey29970v author = nan title = Dreizehnter Bericht nach Inkrafttreten des Gentechnikgesetzes (GenTG) für den Zeitraum vom 1.1.2002 bis 31.12.2002 : Die Arbeit der Zentralen Kommission für die Biologische Sicherheit (ZKBS) im Jahr 2002 date = 2003 pages = extension = .txt mime = text/plain words = 2522 sentences = 181 flesch = 62 summary = title: Dreizehnter Bericht nach Inkrafttreten des Gentechnikgesetzes (GenTG) für den Zeitraum vom 1.1.2002 bis 31.12.2002 : Die Arbeit der Zentralen Kommission für die Biologische Sicherheit (ZKBS) im Jahr 2002 We have closely examined the experimental data and the analyses of the nucleotide sequences presented in the report.We find that aside from problematic details of the experimental design and some erratic presentations of the data the results of the study do not provide evidence for the introgression of recombinant DNA from transgenic crop plants into the genomes of 'criollo' maize. 3. We characterized with the help of BLAST searches those parts of the sequences of the iPCR amplification products that were denoted by Quist and Chapela in their Fig.2 as regions flanking the CMV p-35S sequence.We find that the sequence of AF434754 denoted adh1 in the K1 source of Fig. 2 does not match with the maize adh1 gene. We examined whether the identified regions in the maize genomic DNA from which PCR amplification products were obtained by the authors would perhaps be flanked by primer binding sites. cache = ./cache/cord-014674-ey29970v.txt txt = ./txt/cord-014674-ey29970v.txt === reduce.pl bib === id = cord-017156-ximzvqbm author = Forsdyke, Donald R. title = Chargaff’s GC rule date = 2010-05-18 pages = extension = .txt mime = text/plain words = 9179 sentences = 467 flesch = 55 summary = The model predicts that, for preventing recombination (i.e. creating reproductive isolation), a non-complementarity between the sequences of potentially pairing strands, in itself, might be less important than a noncomplementarity associated with sequence differences that change the pattern of stem-loops. By continuous backcrossing to sylvestris the chromosomes deriv ed from sylvestris can be tested because they form tetrads with the sylvestrisThe surv ival of a duplicate copy of a gene depends on a var iety of factors , including (i) natural selection favouring organisms where a function encoded by the gene is either increased or changed (i.e . Each isochore would have arisen as a random fluctuation in the base composition of a genomic region such that a copy of a duplicated gene that had transposed to that region was able to survive without recombination with the original gene for a sufficient number of generations to allow differentiation between the copy and its original to occur. cache = ./cache/cord-017156-ximzvqbm.txt txt = ./txt/cord-017156-ximzvqbm.txt === reduce.pl bib === id = cord-016293-pyb00pt5 author = Newell-McGloughlin, Martina title = The flowering of the age of Biotechnology 1990–2000 date = 2006 pages = extension = .txt mime = text/plain words = 22402 sentences = 943 flesch = 47 summary = In the course of the project, especially in the early years, the plan stated that "much new technology will be developed that will facilitate biomedical and a broad range of biological research, bring down the cost of many experiments (mapping and sequencing), and finding applications in numerous other fields." The plan built upon the 1988 reports of the Office of Technology Assessment and the National Research Council on mapping and sequencing the human genome. These DNA chips have broad commercial applications and are now used in many areas of basic and clinical research including the detection of drug resistance mutations in infectious organisms, direct DNA sequence comparison of large segments of the human genome, the monitoring of multiple human genes for disease associated mutations, the quantitative and parallel measurement of mRNA expression for thousands of human genes, and the physical and genetic mapping of genomes. cache = ./cache/cord-016293-pyb00pt5.txt txt = ./txt/cord-016293-pyb00pt5.txt === reduce.pl bib === id = cord-014685-ihh30q6f author = nan title = Posters P788 - P999 date = 2005-09-21 pages = extension = .txt mime = text/plain words = 38354 sentences = 1784 flesch = 45 summary = This study has attempted to analyse the structural properties of membrane peptides and proteins through the use of model systems that have been designed to mimic their natural counterparts: Podlubnaya 2 1 Institute of Theoretical and Experimental Biophysics RAS, 2 Pushchino State University Amyloid brils are formed by proteins or their peptides in the result of a conformational transition from alpha helix into beta-sheet structure. Analysis of the results of such studies indicate that folding of SNase fragments is dominated by developing the local and non-local nucleation sites from native-like secondary structures and by intensifying the longrange interactions of residues at nucleation sites with residues further removed in sequence. The results show that at different pH values the aggregation processes of both proteins follow different pathways determined by the variations in the native structure and by the details of the involved conformational changes. cache = ./cache/cord-014685-ihh30q6f.txt txt = ./txt/cord-014685-ihh30q6f.txt === reduce.pl bib === id = cord-016588-f8uvhstb author = Sintchenko, Vitali title = Informatics for Infectious Disease Research and Control date = 2009-10-03 pages = extension = .txt mime = text/plain words = 8186 sentences = 393 flesch = 36 summary = The goal of infectious disease informatics is to optimize the clinical and public health management of infectious diseases through improvements in the development and use of antimicrobials, the design of more effective vaccines, the identification of biomarkers for life-threatening infections, a better understanding of host-pathogen interactions, and biosurveillance and clinical decision support. "New Age" infectious disease informatics rests on advances in microbial genomics, the sequencing and comparative study of the genomes of pathogens, and proteomics or the identification and characterization of their protein related properties and reconstruction of metabolic and regulatory pathways (Bansal 2005) . The figure was produced using Artemis software (The Wellcome Trust Sanger Institute, UK) 1 Informatics for Infectious Disease Research and Control evidence-based gene calling or translating alignments of the DNA sequence to known proteins; and (3) aligning cDNAs from the same or related species. cache = ./cache/cord-016588-f8uvhstb.txt txt = ./txt/cord-016588-f8uvhstb.txt === reduce.pl bib === id = cord-017137-6pmts7ui author = Nema, Vijay title = Microbial Forensics: Beyond a Fascination date = 2018-07-12 pages = extension = .txt mime = text/plain words = 4463 sentences = 227 flesch = 42 summary = When leftover microbes in the biological material or objects used by the culprit or the person in question are used to correlate the identity of the individual, it takes us to the new field of science—"microbial forensics." Technological advances in the field of forensics, molecular biology, and microbiology have all helped to refine the techniques of collecting and processing of the samples for microbiological identification using DNA-based methods followed by its inference in the form of evidence. Herein the microbial forensics could be defined as "the discipline of applying scientific methods to the analysis of evidence related to bioterrorism, biocrimes, hoaxes, or the accidental release of a biological agent or toxin for attribution purposes" [21] . Microbial forensics has a role in such cases by applying scientific methods for the analysis of evidence from such a bioterrorism attack. The most reliable technique till date for microbial forensics is metagenomics-a culture-independent approach for identifying and enumerating microbes. cache = ./cache/cord-017137-6pmts7ui.txt txt = ./txt/cord-017137-6pmts7ui.txt === reduce.pl bib === id = cord-016808-gy8d8285 author = Agol, Vadim I. title = The Origin and Evolution of Viruses date = 2008 pages = extension = .txt mime = text/plain words = 3255 sentences = 172 flesch = 44 summary = Modern hypotheses of viral origin are based on two major developments of the molecular biology: discovery of ribozymes (RNA-based enzymes) and formulation of the "RNA World" theory (RNA had been "invented" before proteins and DNA), on the one hand, and achievements of genomics (determination of the nucleotide sequences of a great number of cellular and viral genomes), on the other. Three distinct DNA viruses, which had infected RNA genome-containing cells, gave rise to the three distinct domains of life, bacteria, archea, and eukarya (Forterre, 2006) . To infect a human, an avian flu virus should change its receptor specificity, which depends on the interaction of viral hemagglutinin (HA) with a cellular membrane glycoprotein receptor. Such a change in the host range may be achieved by either mutations in the avian HA or acquisition by an avian virus of the HA gene from human influenza virus as a result of genetic exchange (reassortment) between these viruses during mixed infections. Three RNA cells for ribosomal lineages and three DNA viruses to replicate their genomes: A hypothesis for the origin of cellular domain cache = ./cache/cord-016808-gy8d8285.txt txt = ./txt/cord-016808-gy8d8285.txt === reduce.pl bib === id = cord-016187-58rqc0cg author = Opal, S. M. title = The Challenge of Emerging Infections and Progressive Antibiotic Resistance date = 2006 pages = extension = .txt mime = text/plain words = 6617 sentences = 330 flesch = 37 summary = Community and nosocomial outbreaks of multidrug resistant pathogens as evidenced by methicillin and vancomycin resistance [17] in Staphylococcus aureus and resistance to the new anti-viral neuraminidase inhibitors [18, 19] by recent infl uenza isolates are cause for real concern. Beta-lactam antibiotics have been known for almost 80 years and their widespread use has created selection pressures on bacterial pathogens to resist their inhibitory actions. These investigators discovered that the resistant strain had acquired a new methylase gene that blocked the binding site for inhibition by aminoglycosides on a specifi c sequence on 16S ribosomal RNA. Mutations resulting in the loss of specifi c porins can occur in clinical isolates and determine increased resistance to beta-lactam antibiotics. If we could discover new targets for future antimicrobial drugs it may be possible to keep pace or even exceed the rate of antibiotic resistance gene development by microbial pathogens. cache = ./cache/cord-016187-58rqc0cg.txt txt = ./txt/cord-016187-58rqc0cg.txt === reduce.pl bib === id = cord-015348-qt0worsl author = nan title = Abstract date = 2010-07-30 pages = extension = .txt mime = text/plain words = 74085 sentences = 4714 flesch = 45 summary = However, the application of the compounds in clinical trials has revealed promising results only when predictive procedures have been available for determining which patients will benefit from targeting therapy, so-called eligibility or predictive tests, e.g. Her2 in breast cancer, KRAS and EGFR mutations in colorectal cancer and non-small cell lung cancer. Conclusion: We report on the development of a quantitative tissue-based immunohistochemical (IHC) methodology employing activation-specific antibodies against multiple components of the BCR signaling pathway that will assess the activity of the BCR pathway in formalin-fixed paraffinembedded primary DLBCLs. This approach will identify the subset of patient tumors that are actively signaling through the BCR pathway and, therefore, will predict therapeutic responsiveness to targeted inhibition of BCR signaling. Method: In our study, we investigate 120 cases diagnosed with invasive breast carcinoma in which we established microscopic characterization, immunohistochemical profiles (expression of proliferation markers, steroid receptors and Her2) and computer-assisted morphometric profiles by determining the mean values for nuclear area, cellular area and N/C ratio with Lucia Net Software. cache = ./cache/cord-015348-qt0worsl.txt txt = ./txt/cord-015348-qt0worsl.txt === reduce.pl bib === id = cord-016095-jop2rx61 author = Vignais, Pierre V. title = Challenges for Experimentation on Living Beings at the Dawn of the 21(st) Century date = 2010-06-08 pages = extension = .txt mime = text/plain words = 42843 sentences = 1503 flesch = 43 summary = Instead of setting out to discover unknown mechanisms by analyzing effects that are dependent on specific causes, with some uncertainty as to the possible success of the enterprise being undertaken, which is the foundation stone of the Bernardian paradigm of the experimental method, many current research projects give themselves achievable and programmable objectives that depend upon the means available to them: sequencing of genomes with a view to comparing them, recognition of sequence similarities in proteins coded for by genes belonging to different species, with the aim of putting together phylogenetic trees, synthesis of interesting proteins in transgenic animals and plants, analysis of the three-dimensional structure of proteins, in order to find sites that are likely to fix medicinal substances, and synthesis of molecular species able to recognize pathogenic targets. cache = ./cache/cord-016095-jop2rx61.txt txt = ./txt/cord-016095-jop2rx61.txt === reduce.pl bib === id = cord-015933-x5cq4k4x author = Verbrugh, H.A. title = 1 Micro-organismen, de mens en het ontstaan van infectieziekten: algemene principes date = 2011 pages = extension = .txt mime = text/plain words = 19354 sentences = 1625 flesch = 54 summary = Virussen vormen een geheel aparte groep biologische agentia die ziekte bij de mens kunnen veroorzaken; hun meest karakteristieke eigenschap is dat zij voor hun vermeerdering afhankelijk zijn van levende gastheercellen. Dit duidt er dus tevens op dat een micro-organisme over een complex geheel van genetische eigenschappen moet beschikken, wil het pathogene betekenis voor de mens krijgen; dergelijke eigenschappen worden ook wel virulentiefactoren genoemd. Een aantal virussen staat bekend als tumorvirus omdat zij een permanente maligne transformatie in hun gastheercel kunnen teweegbrengen; het virus beïnvloedt dan de transcriptie van specifieke cellulaire oncogenen of andere gastheergenen, genen die betrokken zijn bij de regulatie van celdeling of spontane celdood (apoptose). Hoewel sommige micro-organismen (stafylokokken) zich direct aan dergelijke kunststoffen kunnen hechten, is het in de praktijk zo dat het oppervlak ervan snel door neerslag met bovengenoemde matrixeiwitten als fibronectine wordt bedekt, een proces dat ook wel conditionering van het biomateriaal wordt genoemd. cache = ./cache/cord-015933-x5cq4k4x.txt txt = ./txt/cord-015933-x5cq4k4x.txt === reduce.pl bib === id = cord-008777-i2reanan author = nan title = ECB12: 12th European Congess on Biotechnology date = 2005-07-19 pages = extension = .txt mime = text/plain words = 151383 sentences = 7577 flesch = 43 summary = Mollerup Department of Chemical Engineering, Building 229, DTU, 2800 Lyngby, Denmark A variety of factors that govern the properties of proteins are utilized in the development of chromatographic processes for the recovery of biological products including the binding and release of protons, the non-covalent association with non-polar groups (often hydrophobic interactions), the association of small ions (ion exchange) and the highly specific antigen-antibody interaction (affinity interactions). Such fermenters will be needed in order to meet the increasing pressure on costs for low price commodity type products such as single cell protein or food and technical grade enzymes, and to meet the demands of the new wave of white biotech, in which bio-produced chemicals must be made at prices competitive with those of the traditional chemical industry. The presentation will focus on use of the sensitive sandwich hybridization technology for the quantitative analysis of process relevant marker genes in different kind of microbial cell cultures with a focus on the production of recombinant proteins. cache = ./cache/cord-008777-i2reanan.txt txt = ./txt/cord-008777-i2reanan.txt === reduce.pl bib === id = cord-015683-a9a82of4 author = Gupta, Varsha title = Molecular Diagnostics date = 2016-10-23 pages = extension = .txt mime = text/plain words = 4774 sentences = 294 flesch = 52 summary = Molecular diagnostics such as Western blot , ELISA , PCR , DNA, and protein microarrays are 7 revolutionizing the clinical practice of infectious diseases. Molecular diagnostics such as Western blot , ELISA , PCR , DNA, and protein microarrays are 7 revolutionizing the clinical practice of infectious diseases. Binding of another antigen-specifi c antibody linked with enzyme results in color formation upon addition of the substrate 9.2 Diagnosis of Bacterial, Viral, and Parasitic Diseases peptide may react in some assays but not in others as some regions of a peptide may be more immunogenic than others. Because of the specifi city, homogeneity, and unlimited availability of the MAbs, vast amount of work has been carried out on the production/development The immuno-diagnoses of protozoan and parasitic diseases have signifi cantly been improved by MAb technology because the tests involving MAb as diagnostic reagents overcome the limitations of polyclonal antibodies. The sensitivity and specifi city of a PCR assay is dependent on target genes, primer sequences, PCR techniques, DNA extraction procedures, and PCR product detection methods. cache = ./cache/cord-015683-a9a82of4.txt txt = ./txt/cord-015683-a9a82of4.txt === reduce.pl bib === id = cord-016313-n4ewq0pt author = Baranyi, Lajos title = Advances in Lentiviral Vector-based Cell Therapy with Mesenchymal Stem Cells date = 2012-09-27 pages = extension = .txt mime = text/plain words = 20575 sentences = 824 flesch = 39 summary = The field of possible application of mesenchymal stem cells in medicine and research expanded tremendously with the advent of improved Lentiviral-vectors capable of inserting stable copies of genes of interest and expressing proteins or biologically active RNA species ad libitum, performing delicate gene editing or active gene silencing or serving as advanced drug delivery systems utilized in ex vivo cell therapy. Implantation of Lentiviral vector-transduced human bone marrow mesenchymal cells using collagen scaffolds into immunode fi cient mice resulted in ef fi cient engraftment of gene-engineered cells and provided sites for transgene-expression in vivo. Moreover, it did not alter the differentiation potential of either HSCs or MSCs. In addition, the therapeutic potential of CD133+ and MSC progenitor cells transduced ex vivo with Lentiviral vector encoding the mature form of vascular endothelial growth factor D (VEGF-D ) or the enhanced green fl uorescent protein (eGFP) marker gene achieved permanent gene expression. cache = ./cache/cord-016313-n4ewq0pt.txt txt = ./txt/cord-016313-n4ewq0pt.txt === reduce.pl bib === id = cord-016751-g46gs087 author = nan title = DNA, RNA und IHRE Amplifikation date = 2009-12-24 pages = extension = .txt mime = text/plain words = 3437 sentences = 491 flesch = 63 summary = Die lange Suche nach dem Träger der Vererbung kulminierte ein erstes Mal 1944, als Avery, MacLeod und McCarty am Rockefeller Institut eindeutig nachweisen konnten, dass die bakterielle Erbinformation in hochgereinigter DNA, nicht aber in Proteinfraktionen, enthalten ist. Indem man diese Abstammungslinien zurückverfolgt, kann man sich ein Bild darüber machen, wie sich kleine Volksstämme des modernen Menschen in Afrika vor Zehntausenden von Jahren auseinanderentwickelt und in die ganze Welt ausgebreitet haben. Ihre Angehörigen haben sich vielleicht dem Clan des Mittleren Ostens (mit dem Marker M89) angeschlossen, als sie den Herden der großen Säugetiere nach Norden durch die Grasländer und Savannen des Sahara-Korridors folgten. Für einen Afro-Amerikaner aus der Haplogruppe L2 -wahrscheinlich ein Nachkomme von Westafrikanern, die im Zuge des Sklavenhandels nach Amerika gelangten -kann man nicht mit Sicherheit sagen, wo genau in Afrika die Linie entstanden ist. cache = ./cache/cord-016751-g46gs087.txt txt = ./txt/cord-016751-g46gs087.txt === reduce.pl bib === id = cord-016417-3cwwmyv9 author = Sluijter, J. P. G. title = Quantitative Real-Time PCR date = 2006 pages = extension = .txt mime = text/plain words = 3110 sentences = 174 flesch = 53 summary = In this chapter, we focus on the newest advancements in reverse transcription polymerase chain reaction (rt-pcr) technology, the real-time PCR or quantitative PCR, using small amounts of RNA to determine expression levels.We discuss the technique in general and describe two different approaches. Traditional methods to quantify mRNA expression levels are Northern blotting, in situ hybridization, ribonuclease protection, cDNA arrays, and reverse transcription polymerase chain reaction (rt-pcr). PCR amplification of your target DNA will increase the number of probes that hybridize with the complementary template. Accumulation of the released reporter molecules during the amplification cycles results in an increasing fluorescent signal and is correlated to the amount of the target DNA present. When the probe binds to the target sequence this will result in a separation of the reporter and quencher molecule and the fluorescent signal can be monitored. Amplification in a real-time PCR will increase the target DNA and therefore also the observed fluorescent signal. cache = ./cache/cord-016417-3cwwmyv9.txt txt = ./txt/cord-016417-3cwwmyv9.txt === reduce.pl bib === id = cord-015678-9b3eazd4 author = Merzendorfer, Hans title = Chitin/Chitosan: Versatile Ecological, Industrial, and Biomedical Applications date = 2019-03-07 pages = extension = .txt mime = text/plain words = 29015 sentences = 1474 flesch = 35 summary = A plethora of chemical chitosan derivatives have been synthesized yielding improved materials with suggested or effective applications in water treatment, biosensor engineering, agriculture, food processing and storage, textile additives, cosmetics fabrication, and in veterinary and human medicine. Chitosan and its derivatives have many desirable properties such as antioxidative and antimicrobial effects, mucoadhesiveness, biodegradability, and biocompatibility and can be manufactured in various formulations including hydrogels, films, membranes, porous sponges, nanoparticles, and nanofibers. Recyclable composite microspheres composed of cross-linked chitosan grafted with glutamic acid and having a core of Fe 3 O 4 nanoparticles coated with silica adsorb cationic dyes like methylene blue, crystal violet, and light yellow 7GL (Yan et al. While chitosan-based materials have been commercially launched as packaging and coating material in food industry, as an ingredient in cosmetics, and as ion exchanger in water treatment and are approved for human dietary use and wound dressing, their commercial applications in medicine as drug delivery systems or scaffold for tissue engineering are pending. cache = ./cache/cord-015678-9b3eazd4.txt txt = ./txt/cord-015678-9b3eazd4.txt === reduce.pl bib === id = cord-015941-4fz79wzf author = Hu, Yuan title = Molecular Techniques for Blood and Blood Product Screening date = 2018-11-10 pages = extension = .txt mime = text/plain words = 7210 sentences = 381 flesch = 50 summary = Through the application of molecular biology, biological and biochemical analyses have been revolutionized, and nucleic acid, gene-based techniques have been developed to screen blood and plasma donations for evidence of very recent and earlier viral infections that might otherwise be missed by conventional serologic testing. Because NAT detects a virus's genetic material instead of waiting for the body's response, the formation of antibodies, as with many current tests, it offers the opportunity to reduce the window period during which an infecting agent is undetectable by traditional tests [21] , thus further improving blood safety. One reason for this is that currently available blood screening technologies detect core antibodies or surface antigens, which appear up to 8 weeks after infection. The anti-HBc test developed in 1987 detects an antibody to the hepatitis B virus that is produced during and after infection. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-amplification testing cache = ./cache/cord-015941-4fz79wzf.txt txt = ./txt/cord-015941-4fz79wzf.txt === reduce.pl bib === id = cord-017297-q3qtgrfc author = Rajagopal, Vaishnavi title = Viral Helicases date = 2008-11-01 pages = extension = .txt mime = text/plain words = 11546 sentences = 654 flesch = 52 summary = In a recent study on HSV-1 UL9 helicase, mutational analysis of the residues in the Ia motif implicated in DNA binding resulted in moderate to severe defects in single-stranded nucleic-acids binding and ssNA stimulated ATPase activity, while retaining the intrinsic ATPase activity similar to that of wildtype enzyme (Marintcheva and Weller 2003) . Thus, in order to understand the mechanism of helicase catalyzed unwinding reactions, it is important to understand all the individual steps to it, namely: nucleic-acid binding, NTP binding and hydrolysis, single-stranded translocation, and then finally the strand-separation function. Two early genes of bacteriophage T5 encode proteins containing an NTP-binding sequence motif and probably involved in DNA replication, recombination and repair Bacteriophage T7 helicase/primase proteins form rings around single-stranded DNA that suggest a general structure for hexameric helicases A functional interaction of ICP8, the herpes simplex virus single-stranded DNA-binding protein, and the helicase-primase complex that is dependent on the presence of the UL8 subunit cache = ./cache/cord-017297-q3qtgrfc.txt txt = ./txt/cord-017297-q3qtgrfc.txt === reduce.pl bib === id = cord-016713-pw4f8asc author = Goyal, Amit K. title = Nanotechnological Approaches for Genetic Immunization date = 2013-05-24 pages = extension = .txt mime = text/plain words = 16034 sentences = 814 flesch = 34 summary = The use of nonviral particulate carriers for DNA-based vaccination could provide better and safe delivery of encapsulated genetic material, circumvent the need for muscle involvement and facilitate instead the uptake of the Fig. 4 Schematic representation of immunological response greeted by novel DNA-loaded nanocarrier DNA by APCs. However, transfection of APCs with encapsulated DNA into particulate carrier systems will be dependent upon choice of carrier surface charge, size, and lipid/polymer composition, or presence of other biological [e.g., interleukin 2 and interferon-γ (IFN-γ)]. Modification of lipid/DNA complexes by the polymer poly(D,L-lactic acid) was found to be consistently and significantly more effective than either unmodified liposomal DNA or naked DNA in eliciting transgene-specific immune responses to plasmid-encoded antigen when administered by the s.c. route (Bramwell et al. cache = ./cache/cord-016713-pw4f8asc.txt txt = ./txt/cord-016713-pw4f8asc.txt === reduce.pl bib === id = cord-016628-ljzsg9up author = Bajpai, Bhakti title = High Capacity Vectors date = 2013-10-22 pages = extension = .txt mime = text/plain words = 4070 sentences = 215 flesch = 52 summary = An ideal cloning vehicle would have the following four properties: • Low-molecular weight • Ability to confer readily selectable phenotypic traits on host cells • Single sites for a large number of restriction endonucleases, preferably in genes with a scorable phenotype • Ability to replicate within the host cell, so that numerous copies of the recombinant DNA molecule can be produced and passed to daughter cells. The examples of naturally occurring or artificially constructed vectors include vectors based on Escherichia coli plasmids, bacteriophages (e.g., k, M13, P1), viruses (e.g., animal viruses-retrovirus, adenovirus, adeno-associated virus, Herpes Simplex virus, Vaccinia virus, etc.; insect viruses-baculo virus; plant viruses-cauliflower mosaic virus, potato virus X, Gemini virus, etc.), Agrobacterium tumefaciens based vectors, chimeric plasmids (e.g., cosmid, phagemid, phasmid, and fosmid), artificial chromosomes [e.g., YAC, BAC, PAC, MAC and HAC], and non-E. cache = ./cache/cord-016628-ljzsg9up.txt txt = ./txt/cord-016628-ljzsg9up.txt === reduce.pl bib === id = cord-017563-jkhvcjcb author = Holland, Tod D. title = Modeling Brain Tumors Using Avian Retroviral Gene Transfer date = 2008-12-12 pages = extension = .txt mime = text/plain words = 4703 sentences = 213 flesch = 51 summary = Mice bearing RCAS/tv-a-induced brain tumors are currently being used for preclinical trials to understand the biology of therapeutic response in the various cell types that make up gliomas and medulloblastomas. These oncogenes appeared to be stolen from the host genome and then expressed either in the wrong cell type or in an unregulated manner by the virus leading to the formation of cancer (Kurth, 1983) . Gliomas probably form from stem cells or progenitors and are driven by the signaling pathways that drive normal development in the CNS such as PDGF and downstream effectors such as RAS and Akt. The most potent oncogene in the formation of gliomas is the PDGFB ligand . Then SHH gene transfer with RCAS vectors into nestin-expressing cells of the rhombic lip created medulloblastomas in a minority of mice (Rao et al., 2004) . cache = ./cache/cord-017563-jkhvcjcb.txt txt = ./txt/cord-017563-jkhvcjcb.txt === reduce.pl bib === id = cord-015368-a0qz4tb9 author = nan title = 48th Annual Meeting of the Austrian Society of Surgery, Graz, June 7–9, 2007 date = 2007 pages = extension = .txt mime = text/plain words = 86620 sentences = 6042 flesch = 51 summary = Surgical treatment and evaluation, complications, short and long term patency of our patients were compared to interventional techniques and international literature. The aim of the study was to investigate: i) relevant and combined determinants of the development, management and outcome of a representative patient cohort (n ¼ 9.991) with acute appendicitis enrolled in a prospective unicenter study through a time period of 27 years (middle Europe), and ii) the frequency and impact of specific categories (e.g., characteristics of the medical history, clinical and intraoperative findings, complications), correlation and relative risk factors of the disease and its prognosis. From 01=1997 until 12=2006 198 TEM procedures were performed in 194 patients, 104 males, 90 females, mean age was 68.9 years (38-91), the median hospital stay was 8 days . No conversion to open technique had to be performed, no postoperative surgical complications were observed, one patient died 4 weeks postoperative due to liver failure following esophageal varices bleeding. cache = ./cache/cord-015368-a0qz4tb9.txt txt = ./txt/cord-015368-a0qz4tb9.txt === reduce.pl bib === id = cord-000083-3p81yr4n author = nan title = Poster Exhibition date = 2009-01-31 pages = extension = .txt mime = text/plain words = 112815 sentences = 7542 flesch = 56 summary = R. China Background: The objective of this study was to evaluate the early virologic response for prediction of achievement of HBeAg seroconversion and hepatitis B virus (HBV) DNA negativity after two years of lamivudine treatment in chronic hepatitis B (CHB) patients. Methods: A total of 620 patients who tested positive for hepatitis B surface antigen and were referred to Chiba University Hospital between February 1985 and March 2008 were included in the study, and their following characteristics were analyzed: age, gender, the status of HBeAg, ALT, HBV-DNA level, and PLT. Methods: A total of 60 patients with chronic hepatitis B, 32 (53.3%) were HBeAg positive (group A) while 28(46.7%) were HBeAg negative (group B) were included in this study after meeting the following criteria: age 18 to 60 years, HBsAg positive for more than 6 months, serum HBV-DNA was >5 log(10) copies/mL and ALT more than two times the upper normal limit. cache = ./cache/cord-000083-3p81yr4n.txt txt = ./txt/cord-000083-3p81yr4n.txt === reduce.pl bib === id = cord-006229-7yoilsho author = nan title = Abstracts of the 82(nd) Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and the 18(th) Annual Meeting of the Network Clinical Pharmacology Germany (VKliPha) in cooperation with the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e.V. (AGAH) date = 2016-02-06 pages = extension = .txt mime = text/plain words = 133493 sentences = 6804 flesch = 42 summary = It directly activates Protein Kinase A (PKA) or the Exchange protein directly activated by cAMP (Epac) which is a guanine exchange factor (GEF) for the small monomeric GTPase Rap. As Human umbilical vein endothelial cells (HUVEC) express both cAMP effectors (Epac1 and PKA), we investigated the role of cAMP-signaling using a spheroid based sprouting assay as an in vitro model for angiogenesis. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration Methods and Results: Here we demonstrate that dexamethasone treatment lowered S1P 1 mRNA and protein expression levels in rat mesangial cells measured by TaqMan® and Western blot analyses. The aim of this study was to investigate the relevance of IGFBP5 in cardiogenesis and cardiac remodeling and its role as a potential target for ameliorating stress-induced cardiac remodeling Methods and Results: We investigated the expression of Igfbp5 in murine cardiac tissue at different developmental stages by qPCR normalized to Tpt1 (Tumor Protein, Translationally-Controlled 1). cache = ./cache/cord-006229-7yoilsho.txt txt = ./txt/cord-006229-7yoilsho.txt === reduce.pl bib === id = cord-016304-uusmg786 author = Lemuth, Karin title = Microarrays as Research Tools and Diagnostic Devices date = 2015-03-11 pages = extension = .txt mime = text/plain words = 8577 sentences = 457 flesch = 41 summary = Starting from mono-parametric tests within the last years, technologies have evolved that allow for the detection of many parameters in parallel, e.g., by using multiplex nucleic acid amplification techniques, microarrays, or next-generation sequencing technologies. Further, closed lab-on-a-chip devices that use DNA microarrays as detection tools are discussed, and additionally, an outlook toward applications of next-generation sequencing tools in diagnostics will be given. First used for multiparametric transcriptional profiling, the technology rapidly developed toward a tool for the detection of all kinds of biological targets (DNA, RNA, proteins, cells, nucleic acids, carbohydrates, etc.) or their modifications (methylation, phosphorylation, etc.) within the last 20 years. This 70-gene signature has been validated in several clinical trials, in general using fresh biopsy tissue for preparation of the transcriptional profiles during the last years and is now commercially available via Agendia as MammaPrint ® (using Microarrays based on Agilent technology) for guided therapy of early-stage breast cancer (Exner et al. cache = ./cache/cord-016304-uusmg786.txt txt = ./txt/cord-016304-uusmg786.txt === reduce.pl bib === id = cord-017752-ofzm3x3a author = nan title = Theories of Carcinogenesis date = 2007 pages = extension = .txt mime = text/plain words = 12289 sentences = 692 flesch = 47 summary = Others attributed the simplified enzyme patterns of cancerous cells to a regression of the tumor tissues to early embryonal stages of development. Viral DNA is frequently integrated into the cancer cells, but additional agents or factors may be involved at various stages of the progression to invasive carcinoma. The encounter with a family, in which many members developed breast or liver cancer, led Pierre Paul Broca to hypothesize, in 1866, that an inherited abnormality within the affected tissue caused the tumor development [Broca 1866 Theodor Boveri (1862 Boveri ( -1915 then proposed that defects in chromosomes lead to malignancy [Boveri 1914 ]. Any mutation of cancer associated genes can be handed on to following generations and predispose the affected cells to malignant transformation in the case of additional DNA damage. Further developments in tumor immunology have led to models of selection and evolution of cancer cells. cache = ./cache/cord-017752-ofzm3x3a.txt txt = ./txt/cord-017752-ofzm3x3a.txt === reduce.pl bib === id = cord-017838-fbotc479 author = Fagone, Paolo title = Electroporation-Mediated DNA Vaccination date = 2010-12-15 pages = extension = .txt mime = text/plain words = 5279 sentences = 221 flesch = 31 summary = Thus, electroporation-mediated DNA vaccination represents a promising new strategy for the elicitation of strong immune responses directed against the expressed antigen(s) and not the vector, and ongoing studies are currently underway to optimize the working parameters of this technique. [26] demonstrated in mice that upon electroporative treatment, the delivery of a weakly immunogenic hepatitis B virus (HBV) surface antigen (Hbs Ag) DNA vaccine resulted in an increased humoral immune response, characterized by rapid onset and higher titers of anti-Hbs Ag antibodies. In addition, the authors observed in the same study that the potency of an HIV gag pDNA vaccine was increased as shown by the lower dosage of DNA required to induce higher antigen-specific antibody levels and increased CD8 + T cell responses. [31] have demonstrated that gene electrotransfer efficiently increased the cellular immune response both in mice and rhesus macaques vaccinated with a plasmid encoding a nonstructural region of hepatitis C virus (HCV). cache = ./cache/cord-017838-fbotc479.txt txt = ./txt/cord-017838-fbotc479.txt === reduce.pl bib === id = cord-017948-fqhl1qb4 author = Hu, Yuan title = Molecular Techniques for Blood and Blood Product Screening date = 2012-04-05 pages = extension = .txt mime = text/plain words = 7304 sentences = 372 flesch = 54 summary = Currently, nucleic acid testing techniques have been developed to screen blood and plasma products for evidence of very recent viral infections that could be missed by conventional serologic tests. Through the application of molecular biology, biological and biochemical analyses have been revolutionized, and nucleic acid, gene-based techniques have been developed to screen blood and plasma donations for evidence of very recent and earlier viral infections that might otherwise be missed by conventional serologic testing. Because NAT detects a virus's genetic material instead of waiting for the body's response, the formation of antibodies, as with many current tests, it offers the opportunity to reduce the window period during which an infecting agent is undetectable by traditional tests [ 19 ] , thus further improving blood safety. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-ampli fi cation testing cache = ./cache/cord-017948-fqhl1qb4.txt txt = ./txt/cord-017948-fqhl1qb4.txt === reduce.pl bib === id = cord-017188-d3xg05ty author = Swartz, H.M. title = Free Radicals and Medicine date = 2005 pages = extension = .txt mime = text/plain words = 15533 sentences = 799 flesch = 45 summary = Examples described include pulmonary free radical damage, free radicals and sickle cell disease, free radicals in amyotrophic lateral sclerosis, melanin and free radicals and the potential role of oxidative stress in the induction of cancer. The potential limiting factors for such studies include the technical problems of carrying out EPR measurements in human subjects and‚ for techniques that involve the administration of spin traps or other substances‚ the complex and difficult process for obtaining permission to administer substances to human subjects (Swartz‚ 2003) . The first in vivo spin trapping evidence for increased free radical formation was provided using the SOD1-G93A transgenic mouse model for FALS (Gurney et al.‚ 1998) . In conclusion‚ in vitro and in vivo experiments suggest that nitrone spin traps can potentially mitigate oxidative stress in FALS mutant overexpressing cells and mice and protect against progressive motor neuron death. cache = ./cache/cord-017188-d3xg05ty.txt txt = ./txt/cord-017188-d3xg05ty.txt === reduce.pl bib === id = cord-017817-ztp7w9yh author = Land, Walter Gottlieb title = Cell-Autonomous (Cell-Intrinsic) Stress Responses date = 2018-03-28 pages = extension = .txt mime = text/plain words = 17727 sentences = 855 flesch = 40 summary = Autophagy is an evolutionarily highly conserved self-digestive process in response to environmental stress to eukaryotic cells, by which cytoplasmic components such as defective/damaged or redundant organelles or protein aggregates are delivered to the lysosome for recycling and degradation. More recent studies then revealed that these transcription factors, notably Nrf2, are activated by Keap1 as the primary negative regulator of Nrf2, that is, a molecule that simultaneously operates as a sensor protein able to perceive dyshomeostatic Subclass IIC-4 DAMPs, for example, in terms of redox changes reflecting electrophilic stress. Strikingly, a complex relationship reportedly exists between autophagy and DAMPs in cellular adaption to stress and injury and cell death characterized by a crosstalk between autophagy induction and secretion or release of DAMPs. In fact, growing evidence indicates that autophagic mechanisms are involved in regulating release and degradation of DAMPs including CALR, HMGB1, ATP, and DNA in several cell types [37, 148, 175] . cache = ./cache/cord-017817-ztp7w9yh.txt txt = ./txt/cord-017817-ztp7w9yh.txt === reduce.pl bib === id = cord-017881-5jjlx7ot author = Fulekar, M. H. title = Nanotechnology — In Relation to Bioinformatics date = 2009 pages = extension = .txt mime = text/plain words = 2668 sentences = 150 flesch = 49 summary = Eric Drexler, in 1986, published book "Engines of Creation" in which he described his ideas of molecular nanotechnology used to build miniature machines and devices from the bottom up using self-assembly. National Science and Technology Council (US) (2000) has defined Nanotechnology as: "Research and Technology development at the atomic, molecular, or macromolecular levels in the length of approximately 1-100 nm range, to provide fundamental understanding of phenomena and materials at the nanoscale, and to create and use structures, devices and systems that have novel properties and functions because of their small size. Nanotechnology research and development includes integration of nanoscale structure into larger material components, systems, and architectures. Nanotechnology will complement genomic and proteomic research and accelerate the ability of scientist to prevent, detect and treat cancer. The development of tools in genomics, proteomics, molecular imaging, bioinformatics, nanotechnology and other advanced technologies is a critical step. cache = ./cache/cord-017881-5jjlx7ot.txt txt = ./txt/cord-017881-5jjlx7ot.txt === reduce.pl bib === id = cord-018039-dw2xblyr author = Norbäck, Dan title = Microbial Agents in the Indoor Environment: Associations with Health date = 2019-08-08 pages = extension = .txt mime = text/plain words = 7024 sentences = 396 flesch = 44 summary = Keywords Mould · Bacteria · Endotoxin · Beta-1-3-glucan · Muramic acid Fungal DNA · Microbial volatile organic compounds (MVOC) · Mycotoxins Asthma · Respiratory symptoms Endotoxin: A cell-wall compound found in gram-negative bacteria (endotoxin can have different chain length of the 3-hydroxy acids in the molecule) Muramic acid (MuA): A cell-wall compound found mainly in gram-positive bacteria Ergosterol: A cell-wall compound found in mould (but also in plant materials) Beta 1-3 glucans: A group of cell-wall compounds in mould (but also in pollen)t Fungal DNA: DNA sequences specific for mould (general or species specific sequences) Bacterial DNA: DNA sequences specific for bacteria (general or species specific sequences) MVOC: Volatile organic compounds produced by microorganisms (but can have non-microbial sources as well) Secondary microbial metabolites: Chemical compounds produced by the secondary metabolism of microorganisms Mycotoxins: Chemical compounds with toxic properties produced by mould (a subgroup of secondary microbial metabolites) They concluded that there is sufficient evidence of a causal association between outdoor culturable fungal exposure and exacerbation in asthmatics sensitised to fungi. cache = ./cache/cord-018039-dw2xblyr.txt txt = ./txt/cord-018039-dw2xblyr.txt === reduce.pl bib === id = cord-017999-saxwqc2j author = Travers, Andrew A. title = Gene Regulation by HMGA and HMGB Chromosomal Proteins and Related Architectural DNA-Binding Proteins date = 2005 pages = extension = .txt mime = text/plain words = 6332 sentences = 294 flesch = 48 summary = The eukaryotic abundant high mobility group HMGA and HMGB proteins can act as architectural transcription factors by promoting the assembly of higher-order protein-DNA complexes which can either activate or repress gene expression. Similarly rat SSRPl has been shown to facilitate the DNA binding of serum response factor and human SSRPl is associated with the y isoform of p63 in vivo at the endogenous MDM22inAp2nfl'"^^ promoters.^^ In most of these cases, the interaction of the HMG protein with the transcription factor has been detected in vitro and could, in principle, serve as the mechanism for recruitment of HMGB 1 or 2 to particular DNA sites. cache = ./cache/cord-017999-saxwqc2j.txt txt = ./txt/cord-017999-saxwqc2j.txt === reduce.pl bib === id = cord-017867-8cn4c6cu author = Collántes-Fernández, Esther title = Trichomonas date = 2017-11-08 pages = extension = .txt mime = text/plain words = 24060 sentences = 1231 flesch = 48 summary = In addition, the OIE Terrestrial Manual also provides recommendations for PCR analyses, which can be applied in combination either with or after culture as an ancillary test or-more often-direct as the primary test to examine bovine samples-i.e., preputial material, uterine or vaginal secretions, or abomasal content of aborted fetuses. In bovine tritrichomonosis cultivation became an important diagnostic tool, because parasite numbers in bovine samples-e.g., preputial smegma or cervico-vaginal mucus-are usually too low to be detected by direct microscopy and a multiplication of parasites after a few days of cultivation increases the chance to find infected bulls. Sensitivity and specificity of culture and PCR of smegma samples of bulls experimentally infected with Tritrichomonas foetus Evaluation of a PCR test for the diagnosis of Tritrichomonas foetus infection in bulls: effects of sample collection method, storage and transport medium on the test Comparison of sampling and culture methods for the diagnosis of Tritrichomonas foetus infection in bulls cache = ./cache/cord-017867-8cn4c6cu.txt txt = ./txt/cord-017867-8cn4c6cu.txt === reduce.pl bib === id = cord-017493-zro9cna3 author = Mcnamee, James P. title = Cytogenetic and Carcinogenic Effects of Exposure to Radiofrequency Radiation date = 2007 pages = extension = .txt mime = text/plain words = 12182 sentences = 514 flesch = 48 summary = (2004b) found no evidence of increased DNA damage, as determined by the alkaline comet assay, in either mouse C3H 10T1/2 fibroblasts or human glioblastoma U87MG cells following in vitro exposure for 2-24 h to 835 MHz-2.45 GHz RFR at a variety of modulations in the SAR range of 0.6-5.1 W/kg. This was followed by a series of highly publicized studies by Lai and Singh (1995 , who reported increased levels of primary DNA damage (which may have included DNA single-strand and double-strand breaks, alkali-labile sites and DNA cross-links) in rat brain cells at 0-4 h after a 2-h in vivo exposure to 2.45 GHz CW or pulse-modulated RFR at SARs of 0.6-1.2 W/kg. More recently, Paulraj and Behari (2006) reported increased DNA damage in brain cells of Wistar rats following exposure to 2.45 or 16.5 GHz RFR for 35 days at 2 h/day at SARs of approximately 1.0 and 2.0 W/kg, respectively. cache = ./cache/cord-017493-zro9cna3.txt txt = ./txt/cord-017493-zro9cna3.txt === reduce.pl bib === id = cord-018133-2otxft31 author = Altman, Russ B. title = Bioinformatics date = 2006 pages = extension = .txt mime = text/plain words = 9592 sentences = 462 flesch = 46 summary = Experimentation and bioinformatics have divided the research into several areas, and the largest are: (1) genome and protein sequence analysis, (2) macromolecular structure-function analysis, (3) gene expression analysis, and (4) proteomics. With the completion of the human genome and the abundance of sequence, structural, and gene expression data, a new field of systems biology that tries to understand how proteins and genes interact at a cellular level is emerging. The Entrez system from the National Center for Biological Information (NCBI) gives integrated access to the biomedical literature, protein, and nucleic acid sequences, macromolecular and small molecular structures, and genome project links (including both the Human Genome Project and sequencing projects that are attempting to determine the genome sequences for organisms that are either human pathogens or important experimental model organisms) in a manner that takes advantages of either explicit or computed links between these data resources. cache = ./cache/cord-018133-2otxft31.txt txt = ./txt/cord-018133-2otxft31.txt === reduce.pl bib === id = cord-018145-kssjdn8y author = Niemann, Heiner title = Transgenic Farm Animals: Current Status and Perspectives for Agriculture and Biomedicine date = 2009 pages = extension = .txt mime = text/plain words = 9160 sentences = 503 flesch = 40 summary = Guidelines developed by the Food and Drug Administration (FDA) of the USA require monitoring the animals' health in a specific pathogen free (SPF) facility, sequence validation of the gene construct, characterization of the isolated recombinant protein, and monitoring the genetic stability of the transgenic animals over several generations. Some gene constructs have failed to produce economically significant amounts of protein in the milk of transgenic animals indicating that the technology needs further refinement to insure consistent high-level expression. The use of somatic nuclear transfer will accelerate production of transgenic animals for mammary gland specific synthesis of recombinant proteins. In the pig, increased transgenic expression of a bovine lactalbumin construct in the mammary gland resulted in increased lactose content and increased milk production which resulted in improved survival and development of the piglets (Wheeler et al. cache = ./cache/cord-018145-kssjdn8y.txt txt = ./txt/cord-018145-kssjdn8y.txt === reduce.pl bib === id = cord-017208-7oew461e author = Aurigemma, Rosemarie title = Regulatory Aspects in the Development of Gene Therapies date = 2005 pages = extension = .txt mime = text/plain words = 18290 sentences = 816 flesch = 37 summary = Table 1 Beyond a Good Idea: What the Successful Investigator Has Already Done With a Project Leading to Commercial Development Defined candidate biologic (or molecule) Made comparisons with similar products Characteristics of product are consistent with pharmaceutical requirements Production scale is adequate Product characterization is adequate Laboratory reference standard exists In vitro potency assay has been developed Stability studies develop confidence product is a "drug" Reproducible model systems have confirmed in vivo activity with clinical product Early animal work includes some toxicology Scale-up requirements practical for initial clinical trials In general, reflects experience and scientific maturity of investigator In addition to the US agencies that develop the regulations that govern drug development and licensing, the International Conference on Harmonization (ICH) was formed in April 1990 involving the United States, the European Union, and Japan to address the issue of globalizing such regulations. cache = ./cache/cord-017208-7oew461e.txt txt = ./txt/cord-017208-7oew461e.txt === reduce.pl bib === id = cord-017543-60q9iecq author = Tian, Wei-Chang title = Microfluidic Applications in Biodefense date = 2008-08-23 pages = extension = .txt mime = text/plain words = 16557 sentences = 831 flesch = 37 summary = Sections cover microscale sample preparation methods; immunomagnetic separations and immunoassays; proteomics; polymerase chain reaction (PCR), quantitative PCR (qPCR) and other nucleic acid amplification methods; DNA microarrays, microelectrophoresis, and finally integrated Lab-on-a-Chip systems. The intent of JBAIDS Block III, Next Generation Diagnostics (NGD), is to establish a new system incorporating the capabilities of Block I and Block II capabilities (Table 10 .1) and adding immunoassay capabilities and the ability to identify up to 50 agents including toxins in 15 minutes using automated, miniaturized sample preparation integrated with analysis for nucleic acids and proteins, in a hand held or smaller format. They will need to be completely automated or simple to use; incorporate advanced technologies including sample preparation starting from primary samples (aerosols, blood, etc.), molecular detection, automation, microfluidics, and bioinformatics; reduce reagent consumption and space requirements; and provide cost and performance advantages compared to present systems. cache = ./cache/cord-017543-60q9iecq.txt txt = ./txt/cord-017543-60q9iecq.txt === reduce.pl bib === id = cord-018046-jzoykn0y author = Kumar, Sanjay title = Fabrication of Nanostructures with Bottom-up Approach and Their Utility in Diagnostics, Therapeutics, and Others date = 2017-11-18 pages = extension = .txt mime = text/plain words = 7643 sentences = 456 flesch = 42 summary = Nanofabrication has been a critical area of research in the last two decades and has found wide-ranging application in improvising material properties, sensitive clinical diagnostics, and detection, improving the efficiency of electron transport processes within materials, generating high energy densities leading to pulse power, novel therapeutic mechanisms, environmental remediation and control. It also covers the recent advancements in fabrication of ZnO-based nanostructures, DNA-based nanostructures, polymer-based nanostructures, and metal-based nanostructures and their widespread applications in the field of diagnostics, therapeutics, and others. Some of the methods used in bottom-up approach include plasma arcing, chemical vapor deposition process, metal organic decomposition, laser pyrolysis, molecular beam epitaxy, solgel method, wet synthesis, and self-assembly processes. Several fabrication techniques have been described in the literature for fabrication of ZnO nanostructures, such as sputtering, laser ablation, molecular beam epitaxy, physical vapor deposition, thermal evaporation, electrochemical deposition, template-based synthesis, and solgel methods (Yao et al. cache = ./cache/cord-018046-jzoykn0y.txt txt = ./txt/cord-018046-jzoykn0y.txt === reduce.pl bib === id = cord-018371-16zhx0ai author = Schomburg, Dietmar title = DNA helicase 3.6.4.12 date = 2013 pages = extension = .txt mime = text/plain words = 13038 sentences = 1289 flesch = 67 summary = The enzyme utilizes the energy of ATP hydrolysis to translocate along one strand of the duplex and unwind the complementary strand [43] ; <3,48> gonadotropin-regulated testicular he-licase (GRTH/DDX25), a target of gonadotropin and androgen action, is a post-transcriptional regulator of key spermatogenesis genes [36] ; <20> helicase UvrD protein plays an important role in nucleotide excision repair, mismatch repair, rolling circular plasmid replication, and in DNA replication [16] ; <39> helicases play an essential role in nearly all the nucleic acid metabolic processes, catalyzing the transient opening of the duplex nucleic acids in an ATP-dependent manner [18] ; <32> involved in DNA recombination, repair and genome stability maintenance [56] ; <22> meiosis-specific MER3 protein is required for crossing over, which ensures faithful segregation of homologous chromosomes at the first meiotic division [30] ; <41> PcrA is a chromosomally encoded DNA helicase of gram-positive bacteria involved in replication of rolling circle replicating plasmids [21] ; <43> the ability of CeWRN-1 to unwind DNA structures may improve the access for DNA repair and replication proteins that are important for preventing the accumulation of abnormal structures, contributing to genomic stability [9] ; <12> the C-terminal portion of hepatitis C virus nonstructural protein 3 (NS3) forms a three domain polypeptide that possesses the ability to travel along RNA or single-stranded DNA (ssDNA) in a 3' to 5' direction. cache = ./cache/cord-018371-16zhx0ai.txt txt = ./txt/cord-018371-16zhx0ai.txt === reduce.pl bib === id = cord-018265-twp33bb6 author = Becker, Pablo D. title = Community-acquired pneumonia: paving the way towards new vaccination concepts date = 2007 pages = extension = .txt mime = text/plain words = 14121 sentences = 697 flesch = 36 summary = A live vaccine based on a master virus strain developed at the Institute of Applied Microbiology (Austria) by growing wild influenza virus in Vero cells at 25°C was also demonstrated to be safe, well-tolerated and immunogenic after intranasal immunization in young adults [18]. Candidate vaccines should be able to replicate and induce a protective immune response in young infants, even in the presence of maternally acquired antibodies. This demonstrates that antibodies play a major role in protection against this disease, whereas T-cell immunity targeted to internal viral proteins appears to contribute to clearance. The second generation of PS-based conjugate vaccines stimulates stronger antibody responses, even in infants, young children and immune deficient individuals, as well as immunological memory. The resulting proteins are then used to perform immunological and/or functional studies to select the most promising candidates (e.g., able to induce the production of microbicidal or neutralizing antibodies, capacity to confer protective immunity). cache = ./cache/cord-018265-twp33bb6.txt txt = ./txt/cord-018265-twp33bb6.txt === reduce.pl bib === id = cord-006230-xta38e7j author = nan title = Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date = 2012-02-22 pages = extension = .txt mime = text/plain words = 135419 sentences = 7042 flesch = 43 summary = Here, we will present our analysis of Ca 2+ signaling following stimulation of the FcεRI receptor and application of secretagogues that are supposed to affect Ca 2+ -dependent mast cell activation such as adenosine, endothelin-1, substance P and compound 48/80 in BMMCs and PMCs derived from mouse lines with inactivation of TRPC1, TRPC3, TRPC4, TRPC5 or TRPC6 since specific antagonists are still lacking for these TRP channels. These data indicate that increased PP2A activity is associated with modified gene expression in TG hearts possibly affecting stress response and regulation of cell signalling. As demonstrated by qPCR and Western blot experiments, mesangial cells showed a marked time-and dose-dependent upregulation of CSE mRNA and protein levels after treatment with platelet-derived growth factor (PDGF-BB). The transcription factor cAMP response element (CRE)-binding protein (CREB) plays a critical role in regulating gene expression in response to activation of the cAMPdependent signaling pathway, which is implicated in the pathophysiology of heart failure. cache = ./cache/cord-006230-xta38e7j.txt txt = ./txt/cord-006230-xta38e7j.txt === reduce.pl bib === id = cord-018159-ycg6waay author = Peng, Xiaolei title = Plasmofluidics for Biosensing and Medical Diagnostics date = 2018-01-23 pages = extension = .txt mime = text/plain words = 9124 sentences = 499 flesch = 40 summary = With their capability of controlling light at the nanoscale beyond the diffraction limit, surface plasmons such as surface plasmon polaritons (SPPs) and localized surface plasmon resonances (LSPRs) [8] are effective at optically manipulating, sensing, and analyzing biological cells and molecules [9] [10] [11] . Using simple optics to create the trapping force, plasmonic tweezers can be readily incorporated into microfluidic systems to design novel plasmofluidic chips with functionalities such as single-particle trapping [57, 62] , parallel trapping [58] , co-trapping [63] , and kinetic detection of biological objects [61, 64] . Plasmonic nanotechnologies such as plasmonic arrays [87, 88, [101] [102] [103] and SPRI [104, 105] and innovative microfluidic techniques such as integrated concentration gradient generator [104] and multi-well fluidic measurement [106] have been intensely pursued to detect and quantify cancer biomarkers with enhanced sensitivity, robustness, integrity, high throughput, and multiplexity. achieved label-free imaging, detection, and mass/size measurement of single viral particles with high-resolution surface plasmon resonance spectroscopy [121] . cache = ./cache/cord-018159-ycg6waay.txt txt = ./txt/cord-018159-ycg6waay.txt === reduce.pl bib === id = cord-018526-rz7id5mt author = Braun, Serge title = Non-viral Vector for Muscle-Mediated Gene Therapy date = 2018-12-14 pages = extension = .txt mime = text/plain words = 5181 sentences = 228 flesch = 37 summary = Nevertheless, the local production of therapeutic proteins that may act distantly from the injected site and/or the hydrodynamic perfusion of safe plasmids remains a viable basis for the non-viral gene therapy of muscle disorders, cachexia, as well as peripheral neuropathies. In humans, intramuscular injections of naked plasmid encoding angiogenic factors (such as VEGF165 or HGF) were used in small numbers of patients with critical limb ischemia and did demonstrate promising clinical efficacy for the treatment of peripheral arterial disease. A meta-analysis of 12 clinical trials (1494 patients total) of local administration of pro-angiogenic growth factors (VEGF, FGF, HGF, Del-1, HIF-1alpha) using plasmid or viral gene transfer by intra-arterial or intramuscular injections showed that, despite promising results in single studies, no clear benefit could be identified in peripheral artery disease patients, irrespective of disease severity [51] . cache = ./cache/cord-018526-rz7id5mt.txt txt = ./txt/cord-018526-rz7id5mt.txt === reduce.pl bib === id = cord-018737-1h84yi2i author = Kumar, Sudeep title = Live-Attenuated Bacterial Vectors for Delivery of Mucosal Vaccines, DNA Vaccines, and Cancer Immunotherapy date = 2019-01-10 pages = extension = .txt mime = text/plain words = 10719 sentences = 586 flesch = 34 summary = Activation of antigen-presenting cells by live-attenuated bacterial vectors leads to adaptive immune response: Various pathogen-associated molecular patterns present in the liveattenuated bacterial vectors interact with Toll-like receptors expressed on the surface or in endosomal membranes. Live-attenuated microbes exhibit superior ability to deliver vaccine antigens to the mucosal immune system, as many of them are derived from natural mucosal pathogens, including Salmonella spp., Lm, E. Adaptation of the endogenous Salmonella enterica serovar Typhi clyA-encoded hemolysin for antigen export enhances the immunogenicity of anthrax protective antigen domain 4 expressed by the attenuated live-vector vaccine strain CVD 908-htrA Immune responses to recombinant pneumococcal PspA antigen delivered by live attenuated Salmonella enterica serovar typhimurium vaccine Regulated delayed expression of rfc enhances the immunogenicity and protective efficacy of a heterologous antigen delivered by live attenuated Salmonella enterica vaccines Attenuated deltaguaBA Salmonella typhi vaccine strain CVD 915 as a live vector utilizing prokaryotic or eukaryotic expression systems to deliver foreign antigens and elicit immune responses cache = ./cache/cord-018737-1h84yi2i.txt txt = ./txt/cord-018737-1h84yi2i.txt === reduce.pl bib === id = cord-018437-yjvwa1ot author = Mitchell, Michael title = Taxonomy date = 2013-08-26 pages = extension = .txt mime = text/plain words = 9283 sentences = 561 flesch = 48 summary = Classifi cation is based on the genomic nucleic acid used by the virus (DNA or RNA), strandedness (single or double stranded), and method of replication. The nucleocapsids of some viruses are surrounded by envelopes composed of lipid bilayers and host-or viral-encoded proteins. The sequence of negative-sense ssRNA is complementary to the coding sequence for translation, so mRNA must be synthesized by RNA polymerase, typically carried within the virion, before translation into viral proteins. Among the families of viruses able to infect humans and other vertebrate hosts, there are many species that target and cause disease in the lung. The nucleocapsid is surrounded by an envelope derived from host-cell membrane and viral envelope proteins, including hepatitis B surface antigen. The genome of human parainfl uenza viruses is ~15 kb in length with an organization and six reading frames (N, P, M, F, HN, L) typical of the Paramyxoviridae (Karron and Collins 2007 ) . cache = ./cache/cord-018437-yjvwa1ot.txt txt = ./txt/cord-018437-yjvwa1ot.txt === reduce.pl bib === id = cord-018969-0zrnfaad author = Giese, Matthias title = Types of Recombinant Vaccines date = 2015-09-24 pages = extension = .txt mime = text/plain words = 14221 sentences = 811 flesch = 48 summary = New vaccines and vaccination strategies are being developed including the use of attenuated live mycobacteria, recombinant microorganisms, and subunits, prime-boost strategies based on the successive administration of a certain mycobacterial antigen under two different vaccine vectors, and DNA vaccines [ 1 ] . However, several animal models have been developed to study the pathogenesis of Shigella , the resulting immune response against Shigella antigens, and the protection efficacy of candidate vaccines against shigellosis: [ 31 ] . The GAS M protein is the major protective antigen and an ideal target for vaccine development; however it contains heart tissue cross-reactive epitopes particularly in the conserved region [ 98 ] . Immunization of mice with a C-region peptide GAS vaccine candidate called J8 conjugated to the carrier protein diphtheria toxoid (dT) and co-delivery with an appropriate adjuvant led to protection against systemic and mucosal GAS infection [ 104 ] (Fig. 9.29 ). cache = ./cache/cord-018969-0zrnfaad.txt txt = ./txt/cord-018969-0zrnfaad.txt === reduce.pl bib === id = cord-000718-7whai7nr author = nan title = ESP Abstracts 2012 date = 2012-08-22 pages = extension = .txt mime = text/plain words = 166497 sentences = 12847 flesch = 49 summary = Method: We analyzed consecutive gastric cancer cases in terms of AMACR immunohistochemical expression and clinical/pathological characteristics and followed patients' postoperative history. Results: Histological, immunohistochemical and molecular examination revealed non-neoplastic lymphadenopathy with atypical paracortical T-cell hyperplasia with immunoblastic reaction in the former and burnt-out histiocytic pattern in the latter, both falling into a broad spectrum of reactive lymph node changes associated with Still's disease. Method: We have thus collected, from our two Institutions a large number (45 cases) of cancers showing the histological definition of adenosquamous carcinomas according to the WHO criteria and performed gene analysis for k-RAS (codons 12, 13) and EGFR (codons 18, 19 and 21) mutations. Objective: We previously identified amplified fibroblast growth factor 1 (FGFR1) as a therapeutic target for small molecule inhibitor (SMI) therapy in squamous cell lung cancer (L-SCC), resulting in currently running clinical trials treating patients with stage III disease. cache = ./cache/cord-000718-7whai7nr.txt txt = ./txt/cord-000718-7whai7nr.txt === reduce.pl bib === id = cord-019050-a9datsoo author = Ambrogi, Federico title = Bioinformatics and Nanotechnologies: Nanomedicine date = 2014 pages = extension = .txt mime = text/plain words = 8851 sentences = 367 flesch = 31 summary = In this chapter we focus on the bioinformatics strategies for translating genome-wide expression analyses into clinically useful cancer markers with a specific focus on breast cancer with a perspective on new diagnostic device tools coming from the field of nanobiotechnology and the challenges related to high-throughput data integration, analysis, and assessment from multiple sources. In this chapter we focus on the bioinformatics strategies for translating genome-wide expression analyses into clinically useful cancer markers with a specific focus on breast cancer with a perspective on new diagnostic device tools coming from the field of nanobiotechnology and the challenges related to high-throughput data integration, analysis, and assessment from multiple sources. In particular, DNA microarray-based technology, with the simultaneous evaluation of thousands of genes, has provided researchers with an opportunity to perform comprehensive molecular and genetic profiling of breast cancer able to classify it into some clinically relevant subtypes and in the attempt to predict the prognosis or the response to treatment [32.5-8]. cache = ./cache/cord-019050-a9datsoo.txt txt = ./txt/cord-019050-a9datsoo.txt === reduce.pl bib === id = cord-022196-1tionxun author = FENNER, FRANK title = The Nature and Classification of Animal Viruses date = 2013-11-17 pages = extension = .txt mime = text/plain words = 9588 sentences = 406 flesch = 46 summary = With most isometric particles and in all complex virions, the capsid encloses another protein structure containing the viral genome, called the core. All animal viruses with tubular nucleocapsids are enveloped, and in these the lipid layer from which glycoprotein peplomers project is probably applied to a protein shell (the membrane protein; see Fig. 1 -1), which may be relatively rigid, as in Rhabdovirus, or readily distorted (as in the myxoviruses) so that in negatively stained electron micrographs the virions appear to be pleomorphic. The RNA viruses that have the largest (single-stranded) genomes, those of the Leukovirus genus, also have a highly complex structure with an envelope enclosing an icosahedral capsid that, in turn, surrounds a tubular nucleocapsid. The conventional physicochemical criteria [(a) nucleic acid: type, strandedness, fragmentation, and molecular weight; (b) virion: shape, size, and symmetry] are suitable for classification at this level of family/genus, perhaps assisted by the serological cross-reactivity of "group" antigens where these have been recognized. cache = ./cache/cord-022196-1tionxun.txt txt = ./txt/cord-022196-1tionxun.txt === reduce.pl bib === id = cord-018897-tceum2m1 author = Zhang, Anqi title = Nanowire Field-Effect Transistor Sensors date = 2016-07-27 pages = extension = .txt mime = text/plain words = 6316 sentences = 301 flesch = 42 summary = Research advances exploiting SiNWs configured as FETs for biomolecule analysis have emerged as one of the most promising and powerful platforms for label-free, real-time, and sensitive electrical detection of proteins as well as many other biological species. Since the NW diameters can be similar to biomolecules such as proteins and nucleic acids, these binding events can be sensitively detected by the NW-FETs. Furthermore, incorporation of a number of NW-FET elements in a single sensor chip where the NWs are functionalized with different surface receptors allows for multiplexed electrical detection in the same assay, enabling a unique and powerful platform for chemical/biological recognition [6] . Furthermore, several methods for improving the sensitivity and/or capabilities of NW-FET sensors, including the use of branched NWs to enhance the capture efficiency of molecular analytes, operation of the FET in the subthreshold regime, increasing the analyte concentration by electrokinetic effects, and detection in physiological fluids, are briefly illustrated. cache = ./cache/cord-018897-tceum2m1.txt txt = ./txt/cord-018897-tceum2m1.txt === reduce.pl bib === id = cord-022168-qautse9a author = Liu, Li title = Clinical Use of DNA Vaccines date = 2017-07-25 pages = extension = .txt mime = text/plain words = 7120 sentences = 321 flesch = 38 summary = Specifically, the strategies that allow DNA vaccines to overcome antigenic diversity for viral infection and break immune tolerance for cancer therapy are explored. To overcome these obstacles, several approaches focusing on augmenting DNA uptake, maximizing protein expression, and enhancing antigen immunogenicity have been developed and tested in clinical trials. Therefore, one key element to improve DNA vaccine efficacy is to formulate a vaccine with an immunogenic cancer antigen so that it can prime T cells for immune responses. To date, the most successful and encouraging outcomes of using DNA vaccine in the clinical setting were obtained from treatment of malignant diseases where the etiological agent is of foreign viral origin, such as the human papillomavirus (HPV), as these viral agents can readily induce a strong immune response against cancerous cells harboring viral antigens. cache = ./cache/cord-022168-qautse9a.txt txt = ./txt/cord-022168-qautse9a.txt === reduce.pl bib === id = cord-021063-4y8m33ea author = Hug, Peter title = Chapter 18 The advantages of liposome-based gene therapy: A comparison of viral versus liposome-based gene delivery date = 2007-09-02 pages = extension = .txt mime = text/plain words = 6270 sentences = 341 flesch = 51 summary = Potential problems associated with the use of viral vectors include: (i) the possibility of recombination events that could convert a replication-defective vector into an infectious agent, (ii) the possibility that superinfection with another retrovirus may allow unwanted transfer of the introduced gene between individuals, (iii) a 7-13 kb limit on the amount of DNA that can be packaged, (iv) potential problems in targeting the virus to specific cells, and (v) difficulty in maintaining high-level expression of the exogenous gene. While both cationic liposomes and retroviral gene delivery vectors lack the ability to target specific cells, the lack of length constraints makes tissue-specific expression easier to achieve using DNA-lipid complexes as compared to retroviruses. Second, limiting the number of cells that are transfected reduces the amount of DNA, lipid, and other proteins needed to perform the gene therapy. The central problem of any liposome-based gene therapy system is that DNA must be introduced into the cytoplasm of the target cell. cache = ./cache/cord-021063-4y8m33ea.txt txt = ./txt/cord-021063-4y8m33ea.txt === reduce.pl bib === id = cord-022336-zqnczjpp author = Robertson, Hugh D. title = Virus Origins: Conjoined RNA Genomes as Precursors to DNA Genomes date = 2007-09-02 pages = extension = .txt mime = text/plain words = 6163 sentences = 229 flesch = 47 summary = The chapter also outlines the significance of work on viroid-like pathogens, circular RNA replication, and their potential relation to early RNA; and relates the early emergence of RNA mosaics to developments leading to today's DNA-based systems of viral gene expression. Recent work to be reviewed below shows that there is one class of primitive life forms-the viroid-like pathogens -whose properties today could help us to understand how primitive RNA-based self-replication may have been compatible with expansion to produce more complex RNAs. In summary, the causative agent for human hepatitis delta contains two specialized domains, one concerned with replication and the other encoding a single protein (Branch et al., 1989; Purcell and Gerin, 1996; Taylor, 1996) . It is evident that if RNA conjunction leading to delta-like RNA mosaics with both replicating and functionally translatable protein-coding domains has taken place, we need to consider the consequences both for the evolution of primitive RNA systems, yielding today's DNA-based cellular information system, and for presentday RNA-level events. cache = ./cache/cord-022336-zqnczjpp.txt txt = ./txt/cord-022336-zqnczjpp.txt === reduce.pl bib === id = cord-020235-stcrozdw author = nan title = Abstracts of Papers Presented at the 38th Meeting of the Deutsche Gesellschaft für Hygiene und Mikrobiologie, Virology Section, Göttingen, 5.–8.10.1981 date = 2012-03-15 pages = extension = .txt mime = text/plain words = 13494 sentences = 843 flesch = 58 summary = Hepatitis A virus (HAV) was isolated directly from human stool in diploid human fibroplasrs, Viral antigen was expressed only after 210 days of incubation of the infected cultures. Univ., 0-8700 Wiirzburg Effect of Measles (SSPE) Antiserum on Viral Surface Proteins and Hormone Receptor Activity in C6/SSPE Persistently Infected Cells BARRETT, P. Inst, of Genetics, Univ., 0-5000 Co logne Virus-Cell DNA Recombinants in Human Cells Lytically Infected by Ad2 NEUMANN, R., WEYER, U., and DOERFLER, W. In vitro, however, the gag-specific peptide sequences are cleaved off upon addition of the purified viral piS protease; in the case of the replication-defective, transforming avian sarcoma virus PRC II the cleaved nongag part has a ryrosine-phosphorylaring kinase activity similar to that described for the RSV src-gene product pp60 src . f. Virologie, Univ., D·6300 Giefen, 3 A protein of a molecular weight of about 38.000 d has been found to be phosphorylated 1 h after the onset of cell transformation by Rous sarcoma virus (RSV). cache = ./cache/cord-020235-stcrozdw.txt txt = ./txt/cord-020235-stcrozdw.txt === reduce.pl bib === id = cord-020969-lh2ergpm author = STRAUSS, JAMES H. title = Gene Therapy date = 2012-07-27 pages = extension = .txt mime = text/plain words = 11793 sentences = 597 flesch = 52 summary = Together with methods for cloning and manipulating viral genomes, this information has made possible the use of viruses as vectors to express foreign genes. The use of minus-strand RNA viruses as vectors was delayed because the virion RNA itself is not infectious, but recent developments has made it possible to rescue virus from cloned DNA by using coexpression of the appropriate viral proteins in a transfected cell. It is also possible to transfect cells with the E1 or E3 expression cassette together with DNA clones encoding the rest of the adenovirus genome, in which case homologous recombination results in the production of virus. Because the poliovirus replicon lacks a full complement of the structural genes (it is a suicide vector), packaging to produce particles requires infection of a cell that expresses the polioviral structural proteins by some mechanism. cache = ./cache/cord-020969-lh2ergpm.txt txt = ./txt/cord-020969-lh2ergpm.txt === reduce.pl bib === id = cord-023120-jcgf2401 author = nan title = Animal virus genetics date = 2004-06-18 pages = extension = .txt mime = text/plain words = 17801 sentences = 1474 flesch = 67 summary = We suggest that, (1) c regions contain promotors for viral RNA synthesis, (2) cx contains a more efficient promotor than c" and (3) non-acute disease foliows the formation of critical viral-cell recombinants in which ( 2 ) The r e s u l t i n g CDNA i s f r a c t i o n a t e d and a l l fragments having a length g r e a t e r than 300 nucleotides are i s o l a t e d and c u t with a r e s t r i c t i o n endonuclease capable of d i g e s t i n g single-stranded DNA. Studies of the synthesis and processing of viral proteins in simian sarcoma associated virus (SSAV)infected and SSV(SSAV)transformed marmoset and human cell lines has demonstrated polyprotein precursors precipitable by anti-SSAV p30 and anti-SSAV gp70. cache = ./cache/cord-023120-jcgf2401.txt txt = ./txt/cord-023120-jcgf2401.txt === reduce.pl bib === id = cord-022128-r8el8nqm author = Domingo, Esteban title = Molecular basis of genetic variation of viruses: error-prone replication date = 2019-11-08 pages = extension = .txt mime = text/plain words = 17663 sentences = 798 flesch = 39 summary = In the case of viral genomes, mutations can result from different mechanisms: (i) template miscopying (direct incorporation of an incorrect nucleotide); (ii) primer-template misalignments that include miscoding followed by realignment, and misalignment of the template relative to the growing chain (polymerase "slippage" or "stuttering"); (iii) activity of cellular enzymes (i.e., deaminases), or (iv) chemical damage to the viral nucleic acids (deamination, depurination, depyrimidination, reactions with oxygen radicals, direct and indirect effects of ionizing radiation, photochemical reactions, etc.) (Naegeli, 1997; Bloomfield et al., 2000; Friedberg et al., 2006) . In addition to the general environmental and sequence context consequences for templatecopying fidelity that may affect any genome type, mutation rates for DNA viruses will also be influenced by: (i) whether the DNA polymerase that catalyzes viral DNA synthesis includes or lacks a functional proofreading-repair activity. cache = ./cache/cord-022128-r8el8nqm.txt txt = ./txt/cord-022128-r8el8nqm.txt === reduce.pl bib === id = cord-021532-6hmn90ac author = Von Seggern, Dan J. title = ADENOVIRAL VECTORS FOR PROTEIN EXPRESSION date = 2007-09-02 pages = extension = .txt mime = text/plain words = 12536 sentences = 580 flesch = 43 summary = Many features of this viral system, including the ability to infect a wide variety of nondividing cells, a large capacity for insertion of DNA, ease of production and stability of the viral particles, and the high viral titers that can be produced, make Ad-based vectors especially useful in gene transfer. Recombinant adenoviruses have been used to express foreign proteins for a number of years, and the recent explosion of interest in gene therapy has led to the development both of improved adenoviral vectors and of more efficient techniques for generating them. Once constructed, a single vector can be used for in vitro protein expression and purification, studies of the effect of the gene product on cell biology, or in vivo studies in many tissue types and a number of different species. Viral vectors deleted for the corresponding sequences will have a higher capacity for insertion of DNA and should be useful for expressing large proteins such as dystrophin or combinations of genes (perhaps multisubunit enzyme complexes). cache = ./cache/cord-021532-6hmn90ac.txt txt = ./txt/cord-021532-6hmn90ac.txt === reduce.pl bib === id = cord-022177-j0qcjbxg author = Markl, Jürgen title = Genome date = 2018-10-12 pages = extension = .txt mime = text/plain words = 3467 sentences = 425 flesch = 51 summary = Das Projekt profitierte von der Entwicklung vieler neuer und bahnbrechender Methoden, die zuerst bei der Sequenzierung kleinerer Genome angewendet wurden -von Prokaryoten und einfach gebauten Eukaryoten, etwa von den Modellorganismen, denen Sie in vorangegangenen Kapiteln dieses Buches bereits begegnet sind. RNA-Gene, etwa für rRNA, tRNA und kleine nucleäre RNA (snRNA) und mikroRNA andere nichtcodierende Sequenzen, die verschiedenen Kategorien zugeordnet werden können, beispielsweise Centromer-oder Telomerregionen, Transposons und weitere Sequenzwiederholungen Sequenzinformationen werden auch in der vergleichenden Genomik genutzt, also für den Vergleich eines neu sequenzierten Genoms (oder von Teilen daraus) mit den Sequenzen von anderen Organismen. Wenn man die Genome von Prokaryoten und Eukaryoten vergleicht, drängt sich eine interessante Schlussfolgerung auf: Bestimmte Gene sind universell, also bei allen Lebewesen vorhanden. Mithilfe der DNA-Sequenzierung kann man die Genome von Prokaryoten untersuchen, von denen viele für den Menschen und bestimmte Ökosysteme von Bedeutung sind. cache = ./cache/cord-022177-j0qcjbxg.txt txt = ./txt/cord-022177-j0qcjbxg.txt === reduce.pl bib === id = cord-018944-du42ho11 author = Shin, Jeong Hwan title = Nucleic Acid Extraction and Enrichment date = 2018-11-10 pages = extension = .txt mime = text/plain words = 6857 sentences = 355 flesch = 41 summary = [6, 7] as follows: (1) extraction should be simple and rapid and should show high sensitivity and specificity; (2) it is preferred that there be no requirements for specialized equipment or special knowledge and skills; (3) the final nucleic acid should be pure and easy to modify for various amplification techniques; (4) the reagents and their product should be harmless; and (5) the process of preparation should resist contamination with other specimens. Although the phenolchloroform method is relatively easy compared with the CsCl/EtBr gradient and is very useful for the extraction of nucleic acids, it also is problematic for the clinical microbiology laboratory because phenol has important limitations due to its being toxic, caustic, and flammable [5, 15, 16] . In recent years, it has become possible to extract viral nucleic acid from clinical specimens having cellular components, and there have been trials of these commercially available kits to detect various clinically important viruses [30] [31] [32] . cache = ./cache/cord-018944-du42ho11.txt txt = ./txt/cord-018944-du42ho11.txt === reduce.pl bib === id = cord-021966-5m21bsrw author = Shaw, Alan R. title = Vaccines date = 2009-05-15 pages = extension = .txt mime = text/plain words = 21170 sentences = 897 flesch = 33 summary = Because a number of proteins produced in isolation by recombinant methods have been observed to elicit lower immune responses than do natural infections or live attenuated vaccines, the development and use of adjuvants to optimize recombinant vaccine immunogenicity represent an important parallel area for future exploration. Modern molecular biology and biochemistry have provided numerous options for vaccine immunogen presentation, including recombinant proteins (and recombinant virus-like particles (VLPs)), synthetic proteins, protein-polysaccharide conjugates, and gene delivery systems (recombinant viral vectors, or DNA vaccines) >> Is the antigen of interest sufficiently immunogenic on its own, or is augmentation of the desired immune response by conjugation to a specific carrier or addition of an adjuvant necessary to elicit a sufficient and sufficiently durable immune response in individuals in the target population for vaccination? cache = ./cache/cord-021966-5m21bsrw.txt txt = ./txt/cord-021966-5m21bsrw.txt === reduce.pl bib === id = cord-022142-d4yxgv83 author = David, Ayelet title = Polymer-Based DNA Delivery Systems for Cancer Immunotherapy date = 2016-05-28 pages = extension = .txt mime = text/plain words = 7778 sentences = 367 flesch = 43 summary = A number of polymer-based nanomedicines have been developed to deliver genes into DCs, primarily by incorporating tumor-specific, antigen-encoding plasmid DNA with polycationic molecules to facilitate DNA loading and intracellular trafficking. Direct in vivo targeting of plasmid DNA to DC surface receptors can induce high transfection efficiency and long-term gene expression, essential for antigen loading onto major histocompatibility complex molecules and stimulation of T-cell responses. This chapter highlights the repertoire of non-viral, nanosized polymeric DNA delivery systems (polyplexes) available to achieve effi cient gene transfer into DCs for immunotherapeutic applications in cancer therapy. With respect to clinical translation, effi cacious non-viral gene delivery into DCs will depend on the combination of intelligent material design, the appropriate tumor specifi c antigen-encoding DNA and immuno-stimulatory molecules to promote DC maturation and activation. cache = ./cache/cord-022142-d4yxgv83.txt txt = ./txt/cord-022142-d4yxgv83.txt === reduce.pl bib === id = cord-022476-g826uiqx author = nan title = Eosinophils and Anti-Pathogen Host Defense date = 2012-10-12 pages = extension = .txt mime = text/plain words = 12501 sentences = 638 flesch = 36 summary = Similarly, although the weight of evidence suggests that eosinophils contribute to the pathophysiology of allergy and asthma, a chronic respiratory disease in which bronchoconstriction in response to environmental triggers is typically associated with production of T h 2 cytokines and recruitment of eosinophils to the airways, asthmatic responses are obviously negative sequelae of eosinophil function that alone cannot represent a direct evolutionary advantage to the host organism. Although respiratory virus infections are not among the diseases typically associated with T h 2 lymphocyte activation and profound pulmonary eosinophilia, eosinophils and/or eosinophil granule secretory proteins have been detected in lung washings or systemically in infants in need of supplemental oxygen secondary to severe RSV infection. 55 A number of studies suggest potential detrimental roles for eosinophils and fungi in T h 2-mediated airway diseases, such as allergic bronchopulmonary aspergillosis (ABPA), severe asthma associated with fungal sensitivity (SAFS), and CRS. cache = ./cache/cord-022476-g826uiqx.txt txt = ./txt/cord-022476-g826uiqx.txt === reduce.pl bib === id = cord-023389-ilrp8vb7 author = Wefer, J. title = Protective DNA Vaccination Against MOG(91‐108)‐Induced Experimental Autoimmune Encephalomyelitis Involves Induction of IFNβ date = 2008-06-28 pages = extension = .txt mime = text/plain words = 16845 sentences = 866 flesch = 46 summary = We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. cache = ./cache/cord-023389-ilrp8vb7.txt txt = ./txt/cord-023389-ilrp8vb7.txt === reduce.pl bib === id = cord-023705-3q9yr6np author = FENNER, FRANK title = Viral Replication date = 2014-06-27 pages = extension = .txt mime = text/plain words = 8331 sentences = 424 flesch = 51 summary = Many important biochemical phenomena such as the splicing and other types of posttranscriptional processing of RNA, the posttranslational cleavage and glycosylation of proteins, the replication of RNA, reverse transcription, integration, and the transposition of viral genes and cellular oncogenes were first elucidated by virologists and have general application in cell biology. Many important biochemical phenomena, such as splicing and other types of posttranscriptional processing of RNA, posttranslational cleavage and glycosylation of proteins, replica tion of RNA, reverse transcription, integration, and transposition of viral genes and cellular oncogenes, were first elucidated by virologists and have general application in cell biology. The proteins translated from the early transcripts of DNA viruses include enzymes and other proteins required for the replication of viral nucleic acid, as well as proteins that suppress host cell RNA and protein synthesis. cache = ./cache/cord-023705-3q9yr6np.txt txt = ./txt/cord-023705-3q9yr6np.txt === reduce.pl bib === id = cord-022037-4ik3jxjy author = Alvarez, Mar title = CANTILEVER BIOSENSORS date = 2008-07-05 pages = extension = .txt mime = text/plain words = 6805 sentences = 310 flesch = 41 summary = Nanomechanical sensors are derived from the microfabricated cantilevers used in atomic force microscopy (AFM) and are based on the bending or resonance change induced in the cantilever when, for example, a biomolecular interaction takes place on one of its surfaces. The sensitivity of microcantilevers for measuring intermolecular forces, the commercial availability of cantilevers, and their fabrication using standard microelectronic technology resulted, around 1994, in a new type of sensor where the transducer system is based on a silicon microcantilever with a tipless free end (Figure 10 .6) (Gimzewski et al., 1994; Chen et al., 1995) . Biochemical applications for this type of sensor have been specifically developed for bending-based modes of measurement, with an optical read-out, due to the complexity required for working with the dynamic mode in liquids. Currently, there are many different and alternative ways to increase the sensitivity of cantilever-based biosensors, depending on the sensor working mode. cache = ./cache/cord-022037-4ik3jxjy.txt txt = ./txt/cord-022037-4ik3jxjy.txt === reduce.pl bib === id = cord-020010-q58x6xb0 author = nan title = 19th ICAR Abstracts: date = 2006-03-13 pages = extension = .txt mime = text/plain words = 46663 sentences = 2181 flesch = 44 summary = In the present study we reported the antiviral activity of neuraminidase inhibitor oseltamivir against lethal H5N1 influenza virus infection in ferrets, an appropriate animal model that closely resembles clinical signs of human influenza. Earl Kern 1 , Kathy Keith 2 , Robert Jordan 2 , Dennis Hruby 2 , Debra Quenelle 2 1 Department of Pediatrics, University of Alabama School of Medicine, Birmingham, AL, USA; 2 SIGA Technologies, Inc., Corvallis, OR, USA Although cidofovir (CDV) has been approved as an investigational new drug for emergency treatment of smallpox, its lack of oral activity and dose limiting toxicity dictates a need for continued development of better therapeutic agents for this potential bioterror disease. The in vitro antiviral activity of one of the most selective compounds, i.e. CHI-033, was assessed by (i) MTS-based cytopathic effect assays, (ii) virus yield reduction assays, (iii) real-time quantitative PCR (RT-QPCR) and (iv) by monitoring viral antigen expression. cache = ./cache/cord-020010-q58x6xb0.txt txt = ./txt/cord-020010-q58x6xb0.txt === reduce.pl bib === id = cord-023698-wvk200j0 author = Hammerschlag, Margaret R. title = Chlamydia pneumoniae date = 2014-10-31 pages = extension = .txt mime = text/plain words = 10016 sentences = 533 flesch = 38 summary = Because the organism has been difficult to grow and because of the lack of a commercially available other diagnostic assay, most original associations with respiratory diseases have been use of serology with the microimmunofluorescence (MIF) test. 38, 39 For an example of the complexity of this issue, consider that two multicenter pneumonia treatment studies in children showed that although 7% to 13% of the patients in the study had positive culture results and 7% to 18% met the serologic criteria with the MIF test for acute infection, they were not the same patients. pneumoniae infection is that the MIF method used to detect serum antibodies is not standardized; recent studies have shown substantial interlaboratory variation in the performance of these tests. Multicenter comparison trial of DNA extraction methods and PCR assays for detection of Chlamydia pneumoniae in endarterectomy specimens Multicenter comparison trial of DNA extraction methods and PCR assays for detection of Chlamydia pneumoniae in endarterectomy specimens cache = ./cache/cord-023698-wvk200j0.txt txt = ./txt/cord-023698-wvk200j0.txt === reduce.pl bib === id = cord-023844-3flfngu0 author = Mülhardt, Cornel title = Was bitte ist denn »Molekularbiologie«? date = 2013 pages = extension = .txt mime = text/plain words = 2802 sentences = 358 flesch = 69 summary = Der Molekularbiologe, auch Molli genannt, hantiert die meiste Zeit mit winzigen Mengen zumeist klarer, farbloser Lösungen -keine Spur vom wildgewordenen Forscher, wie man ihn aus den Filmen kennt, der inmitten von wabernden, dampfenden, knallbunten Flüssigkeiten steht und dabei offensichtlich viel Spaß hat. Die Natur -wen immer man sich darunter vorstellen mag -hat aus einer seltsamen Laune heraus die Eigenschaften von Nucleinsäuren optimal genutzt, um daraus eine verwirrende Vielfalt von Leben zu schaffen, und das geht so: Weil sich die Basen paaren, kann man zu einer einzelsträngigen DNA einen komplementären Strang synthetisieren, zu dem man ebenfalls wieder einen komplementären Strang synthetisieren kann, der mit dem ersten Strang identisch ist. Sie liegen wie eine zweite Haut an, sind aber leider allergen, vor allem die gepuderte Variante, von der man entschieden abraten muss, weil sich im Laufe der Monate und Jahre bei den meisten Leuten Hautprobleme einstellen. cache = ./cache/cord-023844-3flfngu0.txt txt = ./txt/cord-023844-3flfngu0.txt === reduce.pl bib === id = cord-025232-5itrsfmk author = Yan, Yuqian title = Construction and Characterization of a Novel Recombinant Attenuated and Replication-Deficient Candidate Human Adenovirus Type 3 Vaccine: “Adenovirus Vaccine Within an Adenovirus Vector” date = 2020-05-26 pages = extension = .txt mime = text/plain words = 5669 sentences = 312 flesch = 45 summary = The strategy of using a clinically approved and replication-defective HAdV-5 vector provides a novel approach to develop universal adenovirus vaccine candidates against all the other types of adenoviruses causing ARDs and perhaps other adenovirus-associated diseases. In this study, the commercially-available and gene therapy use approved replication-defective HAdV-5 vector was used to construct a recombinant attenuated human adenovirus type 3 vaccine (Ginn et al. The complete hexon gene of HAdV-3 GZ01 was cloned into the AdEasy TM Adenoviral Vector, and this type-specific antigen was expressed when the recombinant adenovirus vaccine was inoculated into mice. The recombinant vaccine is expected to be used in the prevention of ARD outbreaks caused by HAdV-3 infections, and to serve as a model using adenovirus vectors for the construction of other vaccines against additional important serotypes of adenoviral respiratory pathogens. Mice were either inoculated with HAdV-3 wild-type strain GZ01 or immunized with the rAd3H recombinant vaccine by either the intranasal route or intramuscular route, respectively, to assess the antibody titer. cache = ./cache/cord-025232-5itrsfmk.txt txt = ./txt/cord-025232-5itrsfmk.txt === reduce.pl bib === id = cord-023724-5at0rhqk author = Cann, Alan J. title = Infection date = 2015-07-24 pages = extension = .txt mime = text/plain words = 14979 sentences = 755 flesch = 48 summary = The problems plant viruses face in initiating infections of host cells have already been described (Chapter 4), as has the fact that no known plant virus employs a specific cellular receptor of the types that animal and bacterial viruses use to attach to cells. There are probably many different mechanisms involved in systemic resistance, but in general terms there is a tendency of these processes to increase local necrosis when substances such as proteases and peroxidases are produced by the plant to destroy the virus and to prevent its spread and subsequent systemic infection. Virus-resistant plants have been created by the production of transgenic plants expressing recombinant virus proteins or nucleic acids which interfere with virus replication without producing the pathogenic consequences of infection, for example: I Virus coat proteins, which have a variety of complex effects, including inhibition of virus uncoating and interference of expression of the virus at the level of RNA ("gene silencing" by "untranslatable" RNAs), I Intact or partial virus replicases which interfere with genome replication, I Antisense RNAs, I Defective virus genomes, I Satellite sequences (see Chapter 8), I Catalytic RNA sequences (ribozymes), I Modified movement proteins. cache = ./cache/cord-023724-5at0rhqk.txt txt = ./txt/cord-023724-5at0rhqk.txt === reduce.pl bib === id = cord-023225-5quigar4 author = nan title = Posters date = 2012-08-21 pages = extension = .txt mime = text/plain words = 70251 sentences = 3367 flesch = 43 summary = To further explore the structure-function relationship, a viable synthesis strategy for pseudodesmin A analogues was developed, based on side-chain attachment of the first amino acid to the solid support, followed by stepwise Fmoc solid-phase synthesis of the linear peptide precursor and on-resin head-to-tail cyclization. The cases when the amino acid sequence of a fragment coincided with part of the primary structure of a natural oligopeptide were recorded in the Total protein chemical synthesis requires a case by case design and optimization which is governed by factors such as the solubility of the individual peptide segments, their primary sequence and in particular the presence of "difficult" amino acid residues at ligation junctions such as proline or the location of cysteines. In this study we present synthesis of two series of peptide libraries, which were designed by substitution of Leu in the P5, P6 position of our control peptide (Ac-LLLLRVKR-AMBA) with each of nineteen amino acid residues in order to verifying its influence on activity and selectivity of the resulting analogues. cache = ./cache/cord-023225-5quigar4.txt txt = ./txt/cord-023225-5quigar4.txt === reduce.pl bib === id = cord-023369-xwclh6ih author = Kim, Faith title = Human Herpesvirus-6 Meningitis in a Premature Infant with Fevers: A Case and Literature Review date = 2020-04-18 pages = extension = .txt mime = text/plain words = 4890 sentences = 219 flesch = 43 summary = They both had IgM antibodies in the acute phase and PCR detection of HHV-6 DNA in the serum at high copy numbers suggestive of a primary infection despite presence of preexisting maternal antibodies, which the authors isolated from both mothers. 18 Infants with congenital infection due to ciHHV6 had evidence of high viral loads in the cord blood and detection of HHV-6 DNA in hair follicles in both the infants and at least one parent. In summary, we present a case of a premature infant with multiple anomalies who acquired acute HHV-6 viral meningitis in the setting of intermittent high fevers, elevated inflammatory markers, and diagnostic testing from her CSF that confirmed the diagnosis. Transplacental human herpesvirus 6 (HHV-6) congenital infection caused by maternal chromosomally integrated virus cache = ./cache/cord-023369-xwclh6ih.txt txt = ./txt/cord-023369-xwclh6ih.txt === reduce.pl bib === id = cord-023928-9a1w174h author = Thomas, Neal J. title = Genetic Predisposition to Critical Illness in the Pediatric Intensive Care Unit date = 2011-12-16 pages = extension = .txt mime = text/plain words = 12255 sentences = 510 flesch = 46 summary = authors: Thomas, Neal J.; Dahmer, Mary K.; Quasney, Michael W. Examples of the infl uence of genetic variations in proteins involved in recognition of pathogens on the severity of infections include polymorphisms in the genes coding for mannose binding Individual variability in the susceptibility to and outcome from critical care diseases has long been observed, and advances in genomic medicine now gives an opportunity to understand these differences. cache = ./cache/cord-023928-9a1w174h.txt txt = ./txt/cord-023928-9a1w174h.txt === reduce.pl bib === id = cord-027865-p1epjn51 author = Sterchi, Diane L. title = Molecular pathology date = 2020-06-22 pages = extension = .txt mime = text/plain words = 13228 sentences = 841 flesch = 54 summary = ISH is a method of localizing and detecting specific mRNA sequences in preserved tissue sections or cell preparations by hybridizing the complementary strand of a nucleotide probe to the sequence of interest. (See Data Sheet Kappa and Lambda Probe ISH Kit, Novacastra.) (Fig. 21.3.) Chromogenic in situ hybridization (CISH) is a method 'that enables the detection of gene expression in the nucleus using a conventional histochemical reaction' (White 2005) ; it is used for the detection of abnormal genes and to identify a gene therapy treatment direction. However, FISH still has an advantage over chromogenic methods for labeling specific nucleic acid sequences in cells and tissues. This may be done by using the normal detection procedure for the ISH method on dots of labeled nucleic acid sequence and a labeled control applied at matching descending concentrations on a positively charged nylon membrane. cache = ./cache/cord-027865-p1epjn51.txt txt = ./txt/cord-027865-p1epjn51.txt === reduce.pl bib === id = cord-027654-k0uby99n author = Nabel, Gary J. title = The development of gene-based vectors for immunization date = 2020-06-22 pages = extension = .txt mime = text/plain words = 6550 sentences = 321 flesch = 37 summary = The advantages of their ability to induce cellular immunity, immunogenicity, safety, mode of antigen presentation, and other attractive features are countered by limitations in knowledge about clinical effi cacy, production methodologies, DNA vaccination as the initial vaccine constituent and replication-defective viral vectors, including modifi ed vaccinia Ankara virus (MVA), 21,28 rAd 22,23,27,29 or proteins to boost the initial response. 31, 32 In addition, the development of improved enhancer/ promoter regions can allow for even higher expression 5 and these vaccines have advanced into multiple human Phase I studies, alone or in combination with other gene-based vectors. Depending on their ability to target antigen presenting cells, ability to develop packaging lines, inherent immunogenicity of both the vector and insert, and other factors (Table 62 -2), these viral vectors are helping to improve vaccine effi cacy in a variety of infectious disease models. Comparative immunogenicity in rhesus monkeys of DNA plasmid, recombinant vaccinia virus, and replication-defective adenovirus vectors expressing a human immunodefi ciency virus type 1 gag gene cache = ./cache/cord-027654-k0uby99n.txt txt = ./txt/cord-027654-k0uby99n.txt === reduce.pl bib === id = cord-025251-evnfvc0l author = Nemunaitis, John title = Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection: let the virus be its own demise date = 2020-05-26 pages = extension = .txt mime = text/plain words = 7308 sentences = 397 flesch = 38 summary = Herein we describe the rationale and potential of repurposing a dual plasmid, Vigil (pbi-shRNA(furin)-GM-CSF), now in Phase III cancer trials, for the treatment of and, in certain circumstances, enhancement of the immune response to SARS-CoV-2. A recent publication from Nankai University (Tianjin, China) on SARS-CoV-2 reported that genome sequence analysis revealed a section of genes that was not present in SARS-CoV that had a cleavage site similar to HIV and Ebola which carry viral proteins necessary for fusogenic activity of viral species to the human cell membrane. Another immunotherapeutic intervention would be to increase the pulmonary expression of GM-CSF, which, in vivo, redirects macrophages from an M1 state of activation to an M2 activation state and enhances expression of anti-inflammatory mediators and perhaps allow more time for patients to mount an effective immune response against SARS-CoV-2 [25] . Similar to SARS-CoV-2, alveolar epithelial cells are the primary target of influenza virus (IV) and are the first site of entry and support for viral propagation and replication. cache = ./cache/cord-025251-evnfvc0l.txt txt = ./txt/cord-025251-evnfvc0l.txt === reduce.pl bib === id = cord-014794-yppi30a0 author = nan title = 19th European Congress of Pathology, Ljubljana, Slovenia, September 6-11, 2003 date = 2003-07-31 pages = extension = .txt mime = text/plain words = 158059 sentences = 9041 flesch = 44 summary = These parts were in a high percentage associated with fibrosis and lymphocyte rich areas and showed a higher mitotic activity than usual PTCs. Discussion The differences in the occurrence of TCV and TCmorphology between the presented series and previously reported cases might result from until now not clearly defined tall cell morphology as well as from similarities to PTCs, such as the oxyphilic variant, which is extremely rare in our series, and maybe also from often described squamous changes within PTCs. Due to these data it is not clear which tumor parts have relevance for prognosis and which tumors should be treated more aggressively than others. The aims of this study were to characterize the group of patients with BSOT and evaluate the significance of various molecular markers expression versus serous papillary ovarian carcinomas (SPOC) Material and methods We analyzed a total of 102 cases including: 64 cystadenoma, 10 borderline and 28 cystadenocarcinoma. cache = ./cache/cord-014794-yppi30a0.txt txt = ./txt/cord-014794-yppi30a0.txt === reduce.pl bib === id = cord-026518-xv03vpji author = Xie, Peng title = Immune effect of a Newcastle disease virus DNA vaccine with IL-12 as a molecular adjuvant delivered by electroporation date = 2020-06-09 pages = extension = .txt mime = text/plain words = 5771 sentences = 280 flesch = 52 summary = An additional 52 14-day-old SPF chickens were randomly divided into four equal groups (N = 13) to investigate the effect of chIL-12 used as an adjuvant to the F gene DNA vaccine. Two weeks after booster vaccination, the birds were challenged with NDV and mortality for 14 days was evaluated the two delivery methods might induce different immune responses in chickens. Oladele and colleagues constructed a DNA vaccine based on the HA gene of H5N1 avian influenza virus and found that EP delivery could enhance the antibody response, significantly reduce morbidity, and protect chickens from fatal NDV attack [25] . However, although all of the chickens in the pCAG-F/EP group survived, they did not all have detectable neutralizing antibodies, indicating that antibodies may not be essential for protection and that cell mediated immunity might play an important role in plasmid DNA-induced protection against NDV challenge. cache = ./cache/cord-026518-xv03vpji.txt txt = ./txt/cord-026518-xv03vpji.txt === reduce.pl bib === id = cord-032220-u5oo7mj2 author = Bao, Mengdi title = Magnetic Bead-Quantum Dot (MB-Qdot) Clustered Regularly Interspaced Short Palindromic Repeat Assay for Simple Viral DNA Detection date = 2020-09-04 pages = extension = .txt mime = text/plain words = 4825 sentences = 300 flesch = 52 summary = [Image: see text] We have developed a novel detection system that couples clustered regularly interspaced short palindromic repeat-Cas recognition of target sequences, Cas-mediated nucleic acid probe cleavage, and quantum dots as highly sensitive reporter molecules for simple detection of viral nucleic acid targets. 18, 19 However, most of the CRISPR-Cas detection systems utilize reporter probes with organic dyes and quenchers that require external instruments and possess a high fluorescence background, which limits overall sensitivity. 20 In this study, we develop a novel probe system for CRISPR-Cas nucleic acid assays that use quantum dots (Qdots) as a reporter. After magnetic isolation, a high fluorescence intensity (∼14 counts) was detected, indicating that the MB-Qdot conjugate is mainly achieved by DNA complementary hybridization rather than non-specific absorption (control, blue). To avoid bulky and complicated sensing instruments, in this work, we developed a simple visual detection system coupled with quantum dots as an ultra-brightness indicator and CRISPR-Cas12a assay for isothermal viral DNA target sensing. cache = ./cache/cord-032220-u5oo7mj2.txt txt = ./txt/cord-032220-u5oo7mj2.txt === reduce.pl bib === id = cord-024149-qnclsjym author = Gupta, Ankit title = Microbes and Environment date = 2016-10-15 pages = extension = .txt mime = text/plain words = 11674 sentences = 625 flesch = 39 summary = Genome sequencing of a free-living heterotroph bacteria found in aerobic soil, e.g., Chthoniobacter flavus, suggests that it is able to metabolize plant polysaccharides but not amino acids except pyruvate. Sphingobacteria are known to be involved in aerobic degradation of plant materials present in soil and complex organic molecules, e.g., starch, proteins, cellulose, and chitin. Other microbes such as green and purple sulfur bacteria participate in carbon cycle by degrading hydrogen sulfide (H 2 S) into compounds having carbon during energy production (see in reaction). In rhizosphere different microbes colonize around growing roots, which may either result in symbiotic, neutralistic, or parasitic interactions depending upon nutritional status of soil, soil environment, plant defense mechanism, and the type of microbial proliferation in the rhizosphere zone. Numerous fungi, bacteria, viruses, and nematodes are pathogenic in nature and caused many plant and animal diseases (Tables 3.4 and 3.5). cache = ./cache/cord-024149-qnclsjym.txt txt = ./txt/cord-024149-qnclsjym.txt === reduce.pl bib === === reduce.pl bib === id = cord-023055-ntbvmssh author = nan title = Immunogenicity date = 2004-02-19 pages = extension = .txt mime = text/plain words = 64563 sentences = 3952 flesch = 59 summary = Antigen is internalized into acidic vesicles, proteolyzed, and peptides containing T ceU antigenic determinants are transported to the APC surface where they are recognized by the antigen-specific T cell in conjunction with Ia. Most Ia-"pressing cells are competent APC, however, only B cells have antigen-specilic receptors on their surface aUowing bound antigen to be processed and presented at 1/lW the antigen concentration required by nonspecific APC Little is known about B cell antigen processing function during differentiation, or if Ig-mediated APC function is altered at different maturational stages, thus allowing regulation of B cell-helper T cell interactions. These results indicate that the poor response of murine CTL to human class I antigens is not determined by selection in the thymus, but by species-specific constraints on the interaction of MHC antigens with T-cell recognition structures. cache = ./cache/cord-023055-ntbvmssh.txt txt = ./txt/cord-023055-ntbvmssh.txt === reduce.pl bib === id = cord-029462-jm5qwxhz author = Ouidir, Marion title = Concentrations of persistent organic pollutants in maternal plasma and epigenome-wide placental DNA methylation date = 2020-07-13 pages = extension = .txt mime = text/plain words = 6383 sentences = 353 flesch = 45 summary = We performed an epigenome-wide association study (EWAS) to identify placental DNA methylation associated with maternal plasma concentration of POPs in early gestation (10 weeks 0 days to 13 weeks 6 days) among 260 pregnant women participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development's (NICHD) Fetal Growth Studies-Singletons cohort (which comprised 2802 pregnant women from 12 clinic sites within the USA). In total, maternal early pregnancy plasma concentrations of POPs were significantly associated with placental DNA methylation at 214 CpG sites annotated to 205 genes (BACON-corrected false discovery rate (FDR) p values < 0.05, nominal p values ranging from 2.61 × 10 −21 to 2.11 10 −7 , Supplementary Table S3 ). The correlations between DNA methylation at the POPs-associated CpG sites and neonatal anthropometry suggest that placental epigenetic mechanisms may underlie the influence of specific maternal plasma POP concentrations on fetal growth. cache = ./cache/cord-029462-jm5qwxhz.txt txt = ./txt/cord-029462-jm5qwxhz.txt === reduce.pl bib === id = cord-023830-w218ogsk author = Perlin, David title = Rapid Detection of Bioterrorism Pathogens date = 2008-09-10 pages = extension = .txt mime = text/plain words = 6048 sentences = 292 flesch = 38 summary = The inadequacy of phenotypic-based diagnostic assays is illustrated graphically by the ''gold standard'' public health laboratory-testing algorithm that was in place for positive identification of Bacillus anthracis from environmental samples during the October 2001 anthrax outbreak (Fig. 16.1a) . Genomic differences between microbes offer an alternative to culturing for detection and identification of pathogens by providing species-specific DNA targets that can be accurately resolved by molecular methodology. Polymerase chain reaction (PCR)-based amplification of highly conserved ribosomal RNA (rRNA) genes, intergenic sequences, and specific toxin genes is currently the most reliable approach for identification of bacterial, fungal and many viral pathogenic agents. Most importantly, these genetic probing systems offer rapid turn around time (1-6 h) and are suitable for high throughput, automated multiplex operations critical for use in clinical diagnostic laboratories. Rapid diagnostic assays in the genomic biology era: detection and identification of infectious disease and biological weapon agents cache = ./cache/cord-023830-w218ogsk.txt txt = ./txt/cord-023830-w218ogsk.txt === reduce.pl bib === id = cord-023727-ahbnchj9 author = Low, K. Brooks title = Genetic Recombination: A Brief Overview date = 2012-12-02 pages = extension = .txt mime = text/plain words = 4931 sentences = 290 flesch = 46 summary = In rare instances, rearrangements of DNA molecules have been observed to result from an apparent end-to-end fusion process or else a chromosomal crossover which does not appear to involve extensive homology or site-specificity. Examples of irregular recombination events include apparent end-toend fusion events in bacteria (Guyer et ai, 1977; Horowitz and Deonier, 1985) ; recombination involving an origin of replication (Kilbane and Malamy, 1980; Michel and Ehrlich, 1986) ; nonrandom crossovers involving extremely small (if any) regions of homology (e.g., 5-10 base pairs) (King et al, 1982d; Linn et ai, 1979; Mertz and Berg, 1974; Nakano et al., 1984; Schmid and Roth, 1983) ; end-joining of DNA transfected into animal cells Wilson, 1985, 1986) ; and nonhomologous joining of phage λ and plasmid pBR322 (Ikeda, 1986) . cache = ./cache/cord-023727-ahbnchj9.txt txt = ./txt/cord-023727-ahbnchj9.txt === reduce.pl bib === id = cord-026729-hn0q0sbv author = Xu, Jun title = Functional investigation of the chromosomal ccdAB and hipAB operon in Escherichia coli Nissle 1917 date = 2020-06-13 pages = extension = .txt mime = text/plain words = 8851 sentences = 494 flesch = 54 summary = Biofilm and persister formation of EcN controlled by the ccdAB and hipAB were associated with the expression of genes involved in DNA synthesis, SOS response, and stringent response. coli, more than ten kinds of type II TASs have been studied, of which the F-plasmid-based ccdAB and high persistence allele hipAB are two of the best characterized and identified that are mainly responsible for the plasmid maintenance and persister formation, respectively (Ogura and Hiraga 1983; Semanjski et al. The results showed that the inhibited expression of either ccdAB or hipAB significantly reduced the biofilm formation of EcN compared with that of control groups (wildtype and non-induced group), with the value of OD 540 /OD 620 decreased from 1.87 to 1.49, and 1.94 to 1.62, Fig. 3 Comparative and phylogenetic analysis of HipAB among different E. By CRISPRi, ccdAB and hipAB were shown to be involved in the formation of biofilm and persister cells in EcN. cache = ./cache/cord-026729-hn0q0sbv.txt txt = ./txt/cord-026729-hn0q0sbv.txt === reduce.pl bib === id = cord-033054-qaj1f6qq author = Samad, Abdus title = Computational assessment of MCM2 transcriptional expression and identification of the prognostic biomarker for human breast cancer date = 2020-10-01 pages = extension = .txt mime = text/plain words = 5008 sentences = 247 flesch = 42 summary = Therefore, we aimed to analyze the MCM2 expression and the associated outcome in breast cancer (BC) patients based on the publicly available online databases. In this study, server-based gene expression analyses indicate the upregulation of MCM2 (p < 10(−6); fold change>2.0) in various BC subtypes as compared to the respective normal tissues. The GEPIA2 database contains data from 1,085 tumors and 291 normal tissues related to BC where the type of cancers can be predicted by the query sample based on the intensity of gene expression. The mRNA expression of the MCM2 gene in BC patients was analyzed based on their clinicopathological characteristics in TCGA datasets with the UALCAN server [29, 30] . The results exhibit enhanced expression of MCM2 irrespective of individual cancer stages, patient's race, gender, age, major subclass with and without different TNBC-type, menopause status, tumor histology, and nodal metastasis depicted in Figure 3 and listed in Table 2 . cache = ./cache/cord-033054-qaj1f6qq.txt txt = ./txt/cord-033054-qaj1f6qq.txt === reduce.pl bib === id = cord-030295-jlhht2l9 author = Cruz-Flores, Roberto title = Genome reconstruction of white spot syndrome virus (WSSV) from archival Davidson’s-fixed paraffin embedded shrimp (Penaeus vannamei) tissue date = 2020-08-10 pages = extension = .txt mime = text/plain words = 4004 sentences = 209 flesch = 49 summary = title: Genome reconstruction of white spot syndrome virus (WSSV) from archival Davidson's-fixed paraffin embedded shrimp (Penaeus vannamei) tissue In this study, the complete genome of white spot syndrome virus (WSSV) was reconstructed from ~ 2-year-old archived Davidson's-fixed paraffin-embedded (DFPE) shrimp tissue using Next Generation Sequencing (NGS). Archived Davidson's-fixed paraffin-embedded (DFPE) tissues in the Aquaculture Pathology Laboratory of The University of Arizona are an untapped invaluable resource for pathogen discovery, metagenomic and evolutionary studies to understand the origin, evolution and spread of shrimp pathogens worldwide. Our results confirm that NGS from DNA extracted from DFPE tissue is also a viable approach to detect know viral sequences. The ability to reconstruct DNA viral genomes as large as 300 kbp size from DFPE tissues shows the feasibility to generate baseline genetic data from archived tissue and determine how pathogens have evolved over time. cache = ./cache/cord-030295-jlhht2l9.txt txt = ./txt/cord-030295-jlhht2l9.txt === reduce.pl bib === id = cord-048322-5eqdrd52 author = Aigner, Achim title = Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo date = 2006-05-18 pages = extension = .txt mime = text/plain words = 7333 sentences = 363 flesch = 41 summary = The antitumorigenic effects of PEI/siRNA-mediated in vivo gene-targeting of tumor-relevant proteins like in mouse tumor xenograft models are described. The efficient protection against enzymatic or nonenzymatic degradation is particularly important for RNA molecules including siRNAs. In fact, while the therapeutic potential of siRNAs for the treatment of various diseases is in principle very promising, limitations of transfer vectors may turn out to be rate-limiting in the development of RNAi-based therapeutic strategies. Their ultimate success, however, will Figure 4 : Systemic treatment of mice with PEI-complexed HER-2-specific siRNAs leads to reduced growth of subcutaneous SKOV-3 tumor xenografts due to decreased HER-2 expression. RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo Atelocollagenmediated synthetic small interfering RNA delivery for effective gene silencing in vitro and in vivo cache = ./cache/cord-048322-5eqdrd52.txt txt = ./txt/cord-048322-5eqdrd52.txt === reduce.pl bib === id = cord-024058-afgvztwo author = nan title = Engineering a Global Response to Infectious Diseases: This paper presents a more robust, adaptable, and scalable engineering infrastructure to improve the capability to respond to infectious diseases.Contributed Paper date = 2015-02-17 pages = extension = .txt mime = text/plain words = 5592 sentences = 294 flesch = 38 summary = Examples of innovative leveraging of infrastructure, technologies to enhance existing disease management strategies, engineering approaches to accelerate the rate of discovery and application of scientific, clinical, and public health information, and ethical issues that need to be addressed for implementation are presented. Because engineers contribute to the design and implementation of infrastructure, there are opportunities for innovative solutions to infectious disease response within existing systems that have utility, and therefore resources, before a public health emergency. Moving forward, addressing privacy issues will be critical so that geographic tracking of a phone's location could be used to help inform an individual of potential contact with infected persons or animals and support automated, anonymous, electronic integration of those data to accelerate the epidemiological detective work of identifying and surveying those same individuals for public health benefit. cache = ./cache/cord-024058-afgvztwo.txt txt = ./txt/cord-024058-afgvztwo.txt === reduce.pl bib === id = cord-035173-6974gw6j author = Wang, Zhuo title = Effects of Low-Dose X-Ray on Cell Growth, Membrane Permeability, DNA Damage and Gene Transfer Efficiency date = 2020-10-28 pages = extension = .txt mime = text/plain words = 5527 sentences = 262 flesch = 56 summary = title: Effects of Low-Dose X-Ray on Cell Growth, Membrane Permeability, DNA Damage and Gene Transfer Efficiency BACKGROUND: We aimed to reveal if low dose X-rays would induce harmful or beneficial effect or dual response on biological cells and whether there are conditions the radiation can enhance gene transfer efficiency and promote cell growth but without damage to the cells. METHOD: A systematic study was performed on the effects of Kilo-V and Mega-V X-rays on the cell morphology, viability, membrane permeability, DNA damage, and gene transfection of 293 T and CHO cells. RESULTS: The Kilo-V X-rays of very low doses from 0.01 to 0.04 Gray in principle didn't induce any significant change in cell morphology, growth, membrane permeability, and cause DNA damage. We have shown that the very low doses KV X-ray irradiation (doses from 0.01-0.04 Gy) didn't induce any significant change in CHO cells on cell morphology, cell viability, membrane permeability, DNA structure, and GFP transfection. cache = ./cache/cord-035173-6974gw6j.txt txt = ./txt/cord-035173-6974gw6j.txt === reduce.pl bib === id = cord-031970-7szpo4zx author = Qiao, Yu title = Tumorigenic and Immunogenic Properties of Induced Pluripotent Stem Cells: a Promising Cancer Vaccine date = 2020-09-16 pages = extension = .txt mime = text/plain words = 6938 sentences = 377 flesch = 39 summary = Finally, the review will discuss the expanding application of iPSC technology in cancer immunotherapy as a potential cancer vaccine and its advantages in auxiliary treatment compared with oncofetal antigen-based and embryonic stem cell (ESC)-based vaccines. While the core pluripotent factors like Oct4, Sox2, Klf4, c-Myc, Nanog and Lin28 are promoting the somatic reprogramming process, one of the vital tumor suppressor gene -P53 acts like a barrier to impede this. Abnormal epigenetic modification accumulated in the iPSCs from reprogramming to prolonged culture also contributes to the risk of tumorigenic potential colon cancer cell line reduced colony formation not because of apoptosis induction, but due to its role in mediating p53dependent cell cycle arrest [66] . Another parallel study demonstrated that iPSC had similar gene expression patterns with lung adenocarcinoma stem cells and could provoke anti-tumor immunity in humanized mice model [154] . Humanized mice reveal differential immunogenicity of cells derived from autologous induced pluripotent stem cells cache = ./cache/cord-031970-7szpo4zx.txt txt = ./txt/cord-031970-7szpo4zx.txt === reduce.pl bib === id = cord-102336-ex3zlq38 author = De Wijngaert, Brent title = Cryo-EM structures reveal transcription initiation steps by yeast mitochondrial RNA polymerase date = 2020-04-14 pages = extension = .txt mime = text/plain words = 2266 sentences = 127 flesch = 60 summary = Cryo-EM structures of transcription pre-initiation complex (PIC) and initiation complex (IC) of yeast mitochondrial RNA polymerase show fully resolved transcription bubbles and explain promoter melting, template alignment, DNA scrunching, transition into elongation, and abortive synthesis. Hence, the structural basis for promoter melting, DNA scrunching, and transcription initiation remains largely unknown for the mtRNAPs. RPO41 (∆N100) and MTF1 were assembled on a pre-melted promoter (-21 to +12, 15S yeast mtDNA promoter; Fig. 1A ) to generate the yeast mitochondrial transcription preinitiation complex (y-mtPIC) (Fig. S1 ). The 3.7 Å density map of IC locates many previously uncharacterized structural elements, including the C-tail of MTF1 and the scrunched DNA ( Fig. 2B-C) , and reveals the mechanism of template alignment and RNA synthesis during initiation. During the transition, the upstream DNA from position -1 onward is locked in the MTF1 NT-groove while the template strand undergoes a large conformational switching to align with the 2-mer RNA and the incoming UTPaS at the active site ( Fig. 2C; Movie S2). cache = ./cache/cord-102336-ex3zlq38.txt txt = ./txt/cord-102336-ex3zlq38.txt === reduce.pl bib === id = cord-102504-d840uu3e author = Hass, Kenneth N. title = Integrated Micropillar Polydimethylsiloxane Accurate CRISPR Detection (IMPACT) System for Rapid Viral DNA Sensing date = 2020-03-20 pages = extension = .txt mime = text/plain words = 4432 sentences = 285 flesch = 57 summary = This miniaturized and fully packed IMPACT chip demonstrates rapid, sensitive, and simple nucleic acid detection and is an ideal candidate for the next generation molecular diagnostic platform for point-of-care (POC) applications, responding to emerging and deadly pathogen outbreaks. On the solid surface, reporter probes do not require a quencher since they are only measured in the liquid phase after degradation, thus no fluorescent signal will be detected without the target DNA present in the assay. Leveraging the high activity of CRISPR-Cas12a enzyme and the ability of micropillars to bind more reporter probes, we successfully detect double-stranded DNA target without background issues. As shown in Fig. 3 , for streptavidin coated surface, the number of DNA immobilized on the surface does not show significant change with an incubation time between 10 to 60 min as the integrated fluorescence intensity of the retrieved DNA ranges between 50,000 to 60,000 counts. The extended surface provided by high-aspect ratio micropillars significantly increases the reporter probe binding capacity. cache = ./cache/cord-102504-d840uu3e.txt txt = ./txt/cord-102504-d840uu3e.txt === reduce.pl bib === id = cord-028729-vhpuvp4g author = Singh, Simranjeet title = Biological Biosensors for Monitoring and Diagnosis date = 2020-07-08 pages = extension = .txt mime = text/plain words = 4791 sentences = 291 flesch = 34 summary = It also has immense applications in the detection of different contaminants in the food industry, environmental monitoring, disease diagnosis, etc. Biosensors are devices comprising of a biological and physicochemical component to detect an analyte by producing a signal which can be measured (Mishra et al. It is used for the detection of a pathogen in water and food by measuring the change in optical density or color of the test sample upon a chemical reaction (Park et al. Biosensors exhibit numerous promising applications in various fields such as environmental monitoring, molecular diagnostics, pathogen detection, food industries, etc. Majority of the biosensors developed for detecting pathogens involved in causing infectious disease are based on the principle of electrochemical reaction. On the other hand, different electrochemical biosensors have also been developed to detect the microbes in contaminated food. Electrochemical DNA sensors based on the use of gold nanoparticles: a review on recent developments cache = ./cache/cord-028729-vhpuvp4g.txt txt = ./txt/cord-028729-vhpuvp4g.txt === reduce.pl bib === id = cord-102359-k1xxz4hc author = Klotsa, Daphne title = Electronic Transport in DNA date = 2005-04-04 pages = extension = .txt mime = text/plain words = 6669 sentences = 412 flesch = 62 summary = In most models of electronic transport [13, 60] it has been assumed that the transmission channels are along the long axis of the DNA molecule [61] and that the conduction path is due to π-orbital overlap between consecutive bases [52] ; density-functional calculations [37] have shown that the bases, especially Guanine, are rich in π-orbitals. The main advantage of both methods is that they work reliably (i) for short DNA strands ranging from 13 (DFT studies [37] ) base pairs up to 30 base pairs length which are being used in the nanoscopic transport measurements [15] as well as (ii) for somewhat longer DNA sequences as modelled in the electron transfer results and (iii) even for complete DNA sequences which contain, e.g. for human chromosomes up to 245 million base pairs [2] . The fishbone and ladder models studied in the present paper give qualitatively similar results, i.e. a gap in the DOS on the order of the hopping energies to the backbone, extended states for periodic DNA sequences and localised states for any non-zero disorder strength. cache = ./cache/cord-102359-k1xxz4hc.txt txt = ./txt/cord-102359-k1xxz4hc.txt === reduce.pl bib === id = cord-029957-q7v5gli8 author = Prabhu, D. title = In silico Functional Annotation and Characterization of Hypothetical Proteins from Serratia marcescens FGI94 date = 2020-07-31 pages = extension = .txt mime = text/plain words = 5796 sentences = 311 flesch = 42 summary = Two proteins AGB81206.1 and AGB83112.1 were predicted as a member of the exonuclease-endonuclease-phosphate domain super family which plays a crucial role in the intracellular signaling activities in bacteria (Dlakic, 2000) . The observed function of the HPs helps to understand the crucial role of new proteins in bacterial growth and can be targeted as a potential targets for drug discovery. The protein AGB80728.1 was predicted as Translocation and Assembly Module (TAM), which plays a major role in outer membrane biogenesis and virulence mechanisms in bacterial kingdom (Josts et al., 2017) . This kind of proteins are found in wide variety of prokaryotic and eukaryotic organisms and plays an vital role in cell processes and associated with virulence mechanisms of bacterial pathogens (Cerveny et al., 2013) . Various types of enzymes, transporters, cell division, binding proteins were characterized which play an essential role in the growth, survival virulence and pathogenesis of S. cache = ./cache/cord-029957-q7v5gli8.txt txt = ./txt/cord-029957-q7v5gli8.txt === reduce.pl bib === id = cord-027309-8siz9rb8 author = Paul, Debjani title = Developing a Point-of-Care Molecular Test to Detect SARS-CoV-2 date = 2020-06-19 pages = extension = .txt mime = text/plain words = 2269 sentences = 136 flesch = 51 summary = The recent pandemic of COVID-19 caused by the novel coronavirus (SARS-CoV-2) has drawn attention to the need for developing rapid and accurate diagnostic tests. The widespread use of these immunodiagnostic tests in clinical settings, in spite of their shortcomings, emphasizes the need for developing rapid and point-of-care (POC) tests that are based on molecular diagnostics (i.e., tests that detect the viral RNA directly in a manner similar to RT-PCR). We believe we can build on our past experience with isothermal DNA amplification techniques and paperfluidic devices to develop an isothermal amplification-based molecular diagnostic test for COVID-19 that can be deployed more easily. The ID NOW COVID-19 assay from Abbott, which recently got an emergency use authorization (EUA) from the US government for clinical use, detects SARS-CoV-2 RNA using an isothermal amplification test and can enable a clinical decision in as early as 13 min (ID NOWTM Covid-19 2020). cache = ./cache/cord-027309-8siz9rb8.txt txt = ./txt/cord-027309-8siz9rb8.txt === reduce.pl bib === id = cord-030369-4dn02a35 author = Peng, Liang title = Clinical Manifestations and Laboratory Tests of AECHB and Severe Hepatitis (Liver Failure) date = 2019-05-21 pages = extension = .txt mime = text/plain words = 35858 sentences = 1603 flesch = 38 summary = Once pulmonary infection is present, the disease condition will likely deteriorate, directly causing death; (3) a majority of infections are nosocomial infection, and pathogens are usually resistant to common antibiotics, making therapy challenging; (4) the pathogens causing infection are diverse but mainly Gram-negative bacteria, although the incidence of Gram-positive and fungal infections is increasing; (5) infection is closely related to the prognosis for liver failure patients. Although their clinical manifestation differ significantly, the "coexistence of acute and chronic failures" is shared by failures of all those organs; (2) CLF classification has been generally recognized at home and abroad, and the necessity of classification are further proved by the difference between CLF and the other three types; (3) CLF cases are relatively large in proportion (nearly 30%), which is still increasing (since the proportion of ALF/SALF are lowering); (4) Complications of CLF are common and are found in various forms, with bad prognosis; (5) In CLF patients with correlation to HBV, virus replication are commonly found, which is closely related to decompensation. cache = ./cache/cord-030369-4dn02a35.txt txt = ./txt/cord-030369-4dn02a35.txt === reduce.pl bib === id = cord-102511-7zgd45fl author = Khodakov, Dmitriy title = Donut PCR: a rapid, portable, multiplexed, and quantitative DNA detection platform with single-nucleotide specificity date = 2020-05-05 pages = extension = .txt mime = text/plain words = 4279 sentences = 214 flesch = 44 summary = Here, we present the Donut PCR platform that features high multiplexing, rapid turnaround times, single nucleotide discrimination, and precise quantitation of DNA targets in a portable, affordable, and battery-powered instrument using closed consumables that minimize contamination. Here, we present the Donut PCR platform for DNA detection that combines scalable and massive multiplexing, rapid turnaround times, single nucleotide discrimination, and precise quantitation in a portable, affordable, and batterypowered instrument using closed consumables that minimize contamination risks ( Table 1 ). By engineering a donut-shaped reaction chamber in the PCR chip, we remove most of the dead volume, and are able to achieve similar PCR specificity on human genomic DNA as the commercial Bio-Rad CFX96 instrument (Fig. 2a) . The Donut PCR platform presented here achieves rapid, sensitive, and quantitative detection of many DNA targets from a single sample using a closed, portable, and affordable instrument. cache = ./cache/cord-102511-7zgd45fl.txt txt = ./txt/cord-102511-7zgd45fl.txt === reduce.pl bib === id = cord-026025-xqj877en author = PETRAS, ROBERT E. title = Large Intestine (Colon) date = 2009-10-30 pages = extension = .txt mime = text/plain words = 48309 sentences = 3034 flesch = 42 summary = 27, 28 These guidelines consider colonoscopic polypectomy definitive treatment for a patient with a malignant polyp if the following criteria are fulfilled: (1) the polyp is considered completely excised at endoscopy, (2) the specimen is properly processed by the pathology laboratory, (3) the cancer is not poorly differentiated, (4) no histologic evidence of vascular or lymphatic involvement exists, and (5) the resection margin is not involved by carcinoma. Pathologic features of colorectal cancer that suggest MSI/Lynch's syndrome include right-sided location, synchronous or metachronous large bowel cancers, large and bulky polypoid tumors with circumscribed pushing margins, tumors showing prominent lymphoid infiltrate, and cancers of poor differentiation (medullary or undifferentiated carcinoma) or mucinous and signet ring cell histologic pattern (Figs. [352] [353] [354] [355] The trauma-type histologic features can be seen in the solitary rectal ulcer syndrome, localized colitis cystica profunda, inflammatory cloacogenic polyp, the mucosa adjacent to orifices of colonic diverticula, 356 and inflammatory cap polyposis 357 and are frequent findings adjacent to neoplasia and in the vicinity of the ileocecal valve. cache = ./cache/cord-026025-xqj877en.txt txt = ./txt/cord-026025-xqj877en.txt === reduce.pl bib === id = cord-032183-yqqqe325 author = Ning, Qin title = Antiviral Therapy for AECHB and Severe Hepatitis B (Liver Failure) date = 2019-05-21 pages = extension = .txt mime = text/plain words = 32675 sentences = 1658 flesch = 43 summary = Patients awaiting liver transplantation because of HBV-related end-stage liver disease or liver cancer should be given nucleoside analogues with strong HBV inhibition and low drug-resistance, or nucleotides analogues combination treatment, in order to reduce viral load and prevent graft re-infection. The objective of antiviral treatment for HBV-ACLF is to reduce viral load at an appreciably high rate, thereby promoting reduction in hepatocyte cell death and improved survival outcomes by prevention of decompensation related multiorgan complications in this group of severely ill patients. Response-Guided Therapy 4006 study [126] suggested continuous treatment with LAM (10 years) delayed clinical progression in patients with chronic hepatitis and advanced fibrosis by significantly reducing the incidence of the risk of hepatocellular carcinoma and hepatic decompensation. cache = ./cache/cord-032183-yqqqe325.txt txt = ./txt/cord-032183-yqqqe325.txt === reduce.pl bib === id = cord-103417-2uinislh author = Doi, Hideyuki title = On-site eDNA detection of species using ultra-rapid mobile PCR date = 2020-10-01 pages = extension = .txt mime = text/plain words = 1507 sentences = 91 flesch = 50 summary = Our method reduced the measurement time to 30 min and provided high detectability of aquatic organisms compared to the national observation surveys using multiple fishing nets and laboratory extraction/detection using a benchtop qPCR platform. Ultra-rapid methods from DNA collection to detection are still not well developed (1), especially for environmental DNA (eDNA) analysis, which uses water or soil samples to track the presence of target species (2, 3) . Here, we developed a new innovative method for the field processing of eDNA samples and measurements using an ultra-rapid mobile PCR platform (hereafter, mobile PCR) to reduce the measurement time to 30 min and maintain high detectability of aquatic organisms. We compared the on-site eDNA measurement to the laboratory extraction and detection using a benchtop qPCR platform and the national survey to confirm the performance. Our ultra-rapid on-site eDNA extraction and measurement method using mobile PCR successfully detected the eDNA of H. cache = ./cache/cord-103417-2uinislh.txt txt = ./txt/cord-103417-2uinislh.txt === reduce.pl bib === id = cord-048359-lz37rh82 author = Li, Jin title = s-RT-MELT for rapid mutation scanning using enzymatic selection and real time DNA-melting: new potential for multiplex genetic analysis date = 2007-06-01 pages = extension = .txt mime = text/plain words = 6258 sentences = 299 flesch = 49 summary = Subsequently, melting curve analysis, on conventional or nano-technology real-time PCR platforms, detects the samples that contain mutations in a high-throughput and closed-tube manner. Following denaturation and re-annealing of PCR products that leads to formation of cross-hybridized sequences at the positions of mutations ( Figure 1A ) the sample is exposed to Surveyor TM endonuclease that recognizes base pair mismatches or small loops with high specificity (28) and generates a break on both DNA strands 3 0 to the mismatch. Finally, because the amplified mutated sequences contain defined primers at their ends, direct sequencing of enzymatically selected PCR products is readily possible following the real-time melting step, enabling sequencing of low-level mutations identified by Surveyor TM . Here we enabled Surveyor TM , an endonuclease that recognizes selectively mismatches formed by mutations and small deletions following 'cross-hybridized sequence' formation, to generate mutation-specific DNA fragments that are amplified and screened via differential melting curve analysis. cache = ./cache/cord-048359-lz37rh82.txt txt = ./txt/cord-048359-lz37rh82.txt === reduce.pl bib === id = cord-102866-40s64455 author = Bhadra, Sanchita title = One enzyme reverse transcription qPCR using Taq DNA polymerase date = 2020-05-30 pages = extension = .txt mime = text/plain words = 2863 sentences = 161 flesch = 58 summary = To verify this activity and to determine whether Taq polymerasemediated reverse transcription might be leveraged for single enzyme RNA detection, we carried out the CDC-approved SARS-CoV-2-specific N1 TaqMan RT-qPCR assay using only Taq DNA polymerase and its accompanying commercial reaction buffer, ThermoPol, (New England Biolabs) seeded with different copies of N gene armored RNA (Asuragen), a commercial template preparation that is devoid of DNA. Even though the only polymerase present in these reactions was Taq DNA polymerase (NEB), and no dedicated reverse transcriptase was added, amplification curves were generated in response to 3 x 10 5 , 3 x 10 4 , and 3 x 10 3 copies of the SARS-CoV-2 N gene armored RNA templates (Figure 1 ). Similar to our results with armored N gene RNA, the NEB Taq DNA polymerase was able to perform TaqMan RT-qPCR analysis of SARS-CoV-2 viral genomic RNA with all three CDC assays (Figure 2 ). cache = ./cache/cord-102866-40s64455.txt txt = ./txt/cord-102866-40s64455.txt === reduce.pl bib === id = cord-103735-nil1vv6h author = Alfano, Niccolo title = Non-invasive surveys of mammalian viruses using environmental DNA date = 2020-03-29 pages = extension = .txt mime = text/plain words = 5829 sentences = 373 flesch = 53 summary = Using a curated set of RNA oligonucleotides based on the ViroChip microarray assay [7] as baits in a hybridization capture system, multiple mammalian RNA and DNA viruses were detected from both eDNA and iDNA samples. Highlights Environmental DNA (water and blood-sucking leeches) provided a non-invasive method of screening wildlife for viruses A comprehensive viral RNA oligonucleotide bait set was developed to capture known and unknown mammalian virus diversity Leech blood meal host determination and viruses identified were congruent Viruses determined from water correlated with known and observed species visiting the water sources In brief Alfano, Dayaram, et al. In filtered water and sediment samples collected from the same waterhole, only one virus per sample was generally identified and in one location (WM20 and SM20) contigs from different viral families were isolated based on sample type. We provide evidence that environmental and invertebrate-derived DNA samples including waterhole water, sediment and wild haematophagous terrestrial leeches can be used to survey known and unknown viruses. cache = ./cache/cord-103735-nil1vv6h.txt txt = ./txt/cord-103735-nil1vv6h.txt === reduce.pl bib === id = cord-023209-un2ysc2v author = nan title = Poster Presentations date = 2008-10-07 pages = extension = .txt mime = text/plain words = 111878 sentences = 5398 flesch = 45 summary = Site-specifi c PEGylation of human IgG1-Fab using a rationally designed trypsin variant In the present contribution we report on a novel, highly selective biocatalytic method enabling C-terminal modifi cations of proteins with artifi cial functionalities under native state conditions. Recently, our group report a novel approach to a totally synthetic vaccine which consists of FMDV (Foot and Mouth Disease Virus) VP1 peptides, prepared by covalent conjugation of peptide biomolecules with membrane active carbochain polyelectrolytes In the present study, peptide epitops of VP1 protein both 135-161(P1) amino acid residues (Ser-Lys-Tyr-Ser-Thr-Thr-Gly-Glu-Arg-Thr-Arg-Thr-Arg-Gly-Asp-Leu-Gly-Ala-Leu-Ala-Ala-Arg-Val-Ala-Thr-Gln-Leu-Pro-Ala) and triptophan (Trp) containing on the N terminus 135-161 amino acid residues (Trp-135-161) (P2) were synthesized by using the microwave assisted solid-phase methods. Using as a template a peptide, already identifi ed, with agonist activity against PTPRJ(H-[Cys-His-His-Asn-Leu-Thr-His-Ala-Cys]-OH), here we report a structure-activity study carried out through endocyclic modifi cations (Ala-scan, D-substitutions, single residue deletions, substitutions of the disulfi de bridge) and the preliminary biological results of this set of compounds. cache = ./cache/cord-023209-un2ysc2v.txt txt = ./txt/cord-023209-un2ysc2v.txt === reduce.pl bib === id = cord-102370-5uy8dq18 author = Marano, Jeffrey M. title = Rolling Circle Amplification is a high fidelity and efficient alternative to plasmid preparation for the rescue of infectious clones date = 2020-06-23 pages = extension = .txt mime = text/plain words = 4116 sentences = 225 flesch = 53 summary = The traditional approach to rescuing virus from an infectious cDNA clone requires propagating large amounts of plasmids in bacteria, which can result in unwanted mutations in the viral genome due to bacterial toxicity or recombination and requires specialized equipment and knowledge to propagate the bacteria. We have developed an alternative method of preparing large quantities of DNA that can be directly transfected to recover infectious virus without the need for bacteria by amplifying the infectious cDNA clone plasmid using rolling circle amplification (RCA). Typically, the propagation of infectious cDNA clones before viral rescue requires the generation of high concentration plasmid stocks from bacteria, which is not only cumbersome and time-consuming but also presents an opportunity for the introduction of unwanted mutations during amplification in bacteria. To ensure that the above results were not restricted to a specific RCA kit, Vero cells were transfected in triplicate in two independent replicates with RCA product produced using both the Evomics SuperPhi Kit and the GE GenomiPhi Kit or plasmid DNA (Fig. 4) . cache = ./cache/cord-102370-5uy8dq18.txt txt = ./txt/cord-102370-5uy8dq18.txt === reduce.pl bib === id = cord-031565-mos619wp author = Troedsson, Christofer title = Quantification of copepod gut content by differential length amplification quantitative PCR (dla-qPCR) date = 2009-02-01 pages = extension = .txt mime = text/plain words = 4215 sentences = 211 flesch = 47 summary = Recently, molecular based methods have demonstrated that DNA from prey species can be used to identify zooplankton gut contents, and further, quantitative gut content estimates by quantitative PCR (qPCR) assays targeted to the 18S rRNA gene have been used to estimate feeding rates in appendicularians and copepods. The assay utilizes multiple primer sets that amplify different sized fragments of the prey 18S rRNA gene and, based on the differential amplification of these fragments, the degree of digestion is estimated and corrected for. Recently, our group developed a PCR based assay for detection of prey content in the gut of the calanoid copepod Calanus finmarchicus (Nejstgaard et al. We refer to this method as ''differential length amplification quantitative polymerase chain reaction'' (dla-qPCR), and by amplifying different sized fragments of the same prey target gene extracted from copepod guts, we hypothesize that it would be possible to generate a digestion profile of a target prey species consumed by a copepod. cache = ./cache/cord-031565-mos619wp.txt txt = ./txt/cord-031565-mos619wp.txt === reduce.pl bib === id = cord-102219-d3gkfo7s author = Perzel Mandell, Kira A. title = Characterizing the dynamic and functional DNA methylation landscape in the developing human cortex date = 2019-10-30 pages = extension = .txt mime = text/plain words = 5038 sentences = 231 flesch = 47 summary = In the present report, we describe the use of whole genome bisulfite sequencing (WGBS) to capture an unbiased map of the DNAm landscape, and to characterize both CpG and CpH methylation during prenatal brain development. We performed whole genome bisulfite sequencing (WGBS) to better characterize the shifting DNAm landscape in the developing human dorsolateral prefrontal cortex (DLPFC) in 20 prenatal samples during the second trimester in utero (Table S1 ). We found that DNAm changes were abundant even during this relatively restricted period in prenatal development, with 36,546 CpG sites differentially methylated across the ages of 14-20 post-conception weeks (PCW, at FDR < 0.05, Table S3 ). The top biological processes associated with genes containing differentially methylated CpGs across age were related to axon development and guidance, and regulation of neuron projection ( Figure S4 , Table S8 ). cache = ./cache/cord-102219-d3gkfo7s.txt txt = ./txt/cord-102219-d3gkfo7s.txt === reduce.pl bib === id = cord-104030-eb29t38n author = Morales-Nebreda, Luisa title = Aging imparts cell-autonomous dysfunction to regulatory T cells during recovery from influenza pneumonia date = 2020-06-05 pages = extension = .txt mime = text/plain words = 3960 sentences = 175 flesch = 36 summary = Using heterochronic (age-mismatched) adoptive Treg cell transfer experiments and molecular profiling in mice, we sought to determine whether the age-related impairment in repair following influenza-induced lung injury is intrinsic to Treg cells. Our data support a paradigm in which aged Treg cells fail to upregulate youthful reparative programs, activate maladaptive responses and consequently exhibit a cell-autonomous impairment in pro-recovery function, which delays resolution from viralinduced lung injury in aged hosts. Gene set enrichment analysis of these genes demonstrated that this methylation-regulated gene expression program was associated with pro-recovery processes and was significantly skewed toward young Treg cells ( Figure 6C) . Combined, these results show that age-related DNA methylation regulates the pro-reparative transcriptional regulatory network during recovery from influenza-induced lung injury. What are the molecular mechanisms underpinning the age-associated Treg cell gain or loss-of pro-reparative function in the lung following influenza infection? cache = ./cache/cord-104030-eb29t38n.txt txt = ./txt/cord-104030-eb29t38n.txt === reduce.pl bib === id = cord-103422-ys846i99 author = Xu, Xinhui title = CRISPR-Assisted DNA Detection, a novel dCas9-based DNA detection technique date = 2020-05-13 pages = extension = .txt mime = text/plain words = 4258 sentences = 308 flesch = 60 summary = In this detection, DNA sample is incubated with a pair of capture sgRNAs (sgRNAa and sgRNAb) specific to a target DNA, dCas9, a signal readout-related probe, and an oligo-coated solid support beads or microplate at room temperature for 15 min. When target DNA is bound by a pair of dCas9-sgRNA complexes, the dCas9-sgRNA-DNA complex will be captured on surface of beads or microplate via annealing between an oligonucleotide coupled on solid supports and capture sequence of sgRNAa. Then the captured dCas9-sgRNA-DNA complex is reported by a kind of signal reporter captured by the capture sequence of sgRNAb. This method was validated by detecting DNA of bacteria, cancer cell and virus. We compared the HPV detection results of these 31 clinical samples tested by Beads-HCR CADD and PCR-reverse dot hybridization method that was performed by Jinling Hospital (Fig. 4C ). These results indicate that Beads-HCR CADD can be used to detect hrHPV infections in clinical samples with high sensitivity and specificity. cache = ./cache/cord-103422-ys846i99.txt txt = ./txt/cord-103422-ys846i99.txt === reduce.pl bib === id = cord-103830-pu6v53oy author = Pichon, Fabien title = Analysis and annotation of genome-wide DNA methylation patterns in two nonhuman primate species using the Infinium Human Methylation 450K and EPIC BeadChips date = 2020-05-10 pages = extension = .txt mime = text/plain words = 5439 sentences = 225 flesch = 47 summary = In the present study, we evaluated the use of the Infinium 450K and Infinium EPIC BeadChips for genome-wide DNA methylation analyses in samples from Chlorocebus sabaeus and Macaca mulatta and conducted an in-depth analysis of the available probes for these two old world monkey genomes. We provide for each species and each microarray a list of annotated probes that can be used by the scientific community for genome-wide DNA methylation studies in Chlorocebus sabaeus or Macaca mulatta. We then mapped all the 50 bp probe sequences targeting CpG positions in the human genome from the Infinium 450K and EPIC arrays to Chlorocebus sabaeus (CS) and Macaca mulatta (MM) genomes, consecutively, using Bowtie [39], allowing only a unique position on the respective genome and up to 3 mismatches. cache = ./cache/cord-103830-pu6v53oy.txt txt = ./txt/cord-103830-pu6v53oy.txt === reduce.pl bib === id = cord-103892-v6gkubd4 author = Mäkinen, Janne J. title = The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases date = 2020-07-01 pages = extension = .txt mime = text/plain words = 8442 sentences = 418 flesch = 51 summary = Overall, these data demonstrated that the enhanced or diminished capabilities of the variant RNAPs to utilize 2'dGTP in the SNA assays reflected, in qualitative terms, their capabilities to utilize all four 2'dNTPs. The role of the β'Arg425 in selectively promoting the binding of NTPs was easy to explain because the β'Arg425 interacts with the 2'OH of the NTP analogues in several RNAP structures (Supplementary Table 5 , Fig. 1c, 4a, b) . We further hypothesized and demonstrated by in silico docking experiments that the 3'OH could move to within the hydrogen bond distance of the β'Arg425 if the deoxyribose moiety adopted a 2'-endo conformation (Supplementary Fig. 8 To test this hypothesis in crystallo, we solved the X-ray crystal structure of the initially transcribing complexes containing T. Overall, the comparative analysis of RNAP structures with CMPCPP, 2'dCTP and 3'dCTP suggested that the β'Arg425 inhibited the incorporation of 2'dNTPs by interacting with their 3'OH group and favoring the 2'-endo conformation of the deoxyribose moiety. cache = ./cache/cord-103892-v6gkubd4.txt txt = ./txt/cord-103892-v6gkubd4.txt === reduce.pl bib === id = cord-103563-7a3wdduq author = Nunez-Bajo, Estefania title = Ultra-Low-Cost Integrated Silicon-based Transducer for On-Site, Genetic Detection of Pathogens date = 2020-03-25 pages = extension = .txt mime = text/plain words = 4535 sentences = 211 flesch = 44 summary = Unlike other silicon-based technologies, TriSilix can be produced at wafer-scale in a standard laboratory; we have developed a series of methodologies based on metal-assisted chemical (wet) etching, electroplating, thermal bonding and laser-cutting to enable a cleanroom-free low-cost fabrication that does not require processing in an advanced semiconductor foundry. To create an ultra-low-cost device, the architecture proposed exploits the intrinsic properties of silicon and integrates three modes of operation in a single chip: i) electrical (Joule) heater, ii) temperature sensor (i.e. thermistor) with a negative temperature coefficient that can provide the precise temperature of the sample solution during reaction and iii) electrochemical sensor for detecting target NA. Using TriSilix, the sample solution can be maintained at a single, specific temperature (needed for isothermal amplification of NA such as Recombinase Polymerase Amplification (RPA) or cycled between different temperatures (with a precision of ±1.3°C) for Polymerase Chain Reaction (PCR) while the exact concentration of amplicons is measured quantitatively and in real-time electrochemically. cache = ./cache/cord-103563-7a3wdduq.txt txt = ./txt/cord-103563-7a3wdduq.txt === reduce.pl bib === === reduce.pl bib === id = cord-103813-w2sb6h94 author = Schumacher, Garrett J. title = Genetic information insecurity as state of the art date = 2020-07-10 pages = extension = .txt mime = text/plain words = 6459 sentences = 358 flesch = 35 summary = Therefore, human genetic information is a uniquely confidential form of data that requires increased security controls and scrutiny. Sensitive genetic information, which includes both biological material and digital genetic data, is the primary asset of concern, and associated assets, such as metadata, electronic health records and intellectual property, are also vulnerable within this ecosystem. ❖ Private Sensitive Genetic Information can be expected to cause a moderate level of risk to a nation, ethnic group, individual, or stakeholder if it is disclosed, modified, or destroyed without authorization. The genetic information ecosystem is a distributed cyber-physical system containing numerous stakeholders (Supplementary Material, Appendix 1), personnel, and devices for computing and networking purposes. Genetic information security is a shared responsibility between sequencing laboratories and device vendors, as well as all other involved stakeholders. Examples include biorepositories, DNA sequencing laboratories, researchers, cloud and other service providers, and supply chain entities responsible for devices, software and materials. cache = ./cache/cord-103813-w2sb6h94.txt txt = ./txt/cord-103813-w2sb6h94.txt === reduce.pl bib === id = cord-102270-rfhtlodc author = Azhar, Mohd. title = Rapid, field-deployable nucleobase detection and identification using FnCas9 date = 2020-04-21 pages = extension = .txt mime = text/plain words = 3971 sentences = 217 flesch = 50 summary = We then fixed the position of this mutation with respect to PAM and changed every other base in the sgRNA sequence to identify which combination led to complete loss of cleavage of a wild type substrate in an in vitro cleavage (IVC) assay with FnCas9 ( Figure 1B, Supplementary Figure 1A ). Taken together, these experiments suggest that FELUDA design can be universally used for detection of SNVs and and would not require extensive optimization or validation steps for new SNVs. To aid users for quick design and implementation of FELUDA for a target SNV, we have developed a webtool JATAYU (Junction for Analysis and Target Design for Your FELUDA assay) that incorporates the above features and generates primer sequences for amplicon and sgRNA synthesis (https:// jatayu.igib.res.in, Supplementary Figure 2 ). cache = ./cache/cord-102270-rfhtlodc.txt txt = ./txt/cord-102270-rfhtlodc.txt === reduce.pl bib === id = cord-102206-mb0qcd0b author = Seymour, Elif title = Configurable Digital Virus Counter on Robust Universal DNA Chips date = 2020-10-22 pages = extension = .txt mime = text/plain words = 5898 sentences = 284 flesch = 52 summary = Here, we demonstrate real-time multiplexed virus detection by applying DNA-directed antibody immobilization technique to a single-particle interferometric reflectance imaging sensor (SP-IRIS). We also show that this method can be modified to produce a single-step, homogeneous assay format by mixing the antibody-DNA conjugates with the virus sample in solution phase prior to flowing in the microfluidic cartridge, eliminating the antibody immobilization step. 16 SP-IRIS has been utilized for detecting viruses in complex media using antibody microarrays by imaging chips both dry (dried after sample incubation and wash steps) and in liquid using disposable microfluidic cartridges. To demonstrate the feasibility of using the homogeneous assay in combination with the passive flow cartridge and to compare its performance to the directly immobilized antibody assay, an SP-IRIS chip was printed with anti-EBOV mAb, A' probe, and a negative DNA sequence, and washed as described previously. cache = ./cache/cord-102206-mb0qcd0b.txt txt = ./txt/cord-102206-mb0qcd0b.txt === reduce.pl bib === id = cord-030028-s6sxi8uj author = Rubio, Luis title = Detection of Plant Viruses and Disease Management: Relevance of Genetic Diversity and Evolution date = 2020-07-17 pages = extension = .txt mime = text/plain words = 14687 sentences = 698 flesch = 40 summary = This technique has been used to differentiate isolates of some plant viruses, such as prunus necrotic ringspot virus (PNRSV), TYLCV and CTV (Gillings et al., 1993; Hammond et al., 1998; Font et al., 2007) ; iii) Single-strand conformation polymorphism (SSCP) analysis is based on electrophoresis of denatured dsDNA in non-denaturing gels so migration of single-stranded DNA depends on its conformation determined by its nucleotide sequence and the electrophoretic conditions. This technique followed by sequencing of the different haplotypes detected has been used to evaluate the genetic variation of some plant viruses, such as cucumber mosaic virus (CMV), citrus psorosis virus (CPsV) and CTV (Rubio et al., 1996; Rubio et al., 1999; Vives et al., 2002; Lin et al., 2003; Martıń et al., 2006) . Procedures to detect and identify various viruses or virus strains in a single assay simultaneously reduce time and cost of the analysis (see Pallaś et al., 2018 for a comprehensive review), and are especially suitable for evaluating mixed infections in individual plants. cache = ./cache/cord-030028-s6sxi8uj.txt txt = ./txt/cord-030028-s6sxi8uj.txt === reduce.pl bib === === reduce.pl bib === id = cord-104272-lczm1z5z author = Yusifov, Taleh N. title = Tear lipocalin is the major endonuclease in tears date = 2008-01-29 pages = extension = .txt mime = text/plain words = 4121 sentences = 244 flesch = 54 summary = To determine the mode of hydrolysis, the cleaved ends of the DNA digested by tear DNases were analyzed by 3′ and 5′ end labeling using either terminal deoxynucleotidyl transferase or polynucleotide kinase with or without pretreatment with alkaline phosphatase. Both are Mg(2+) dependent enzyme endonucleases that are enhanced by Ca(2+), active at physiologic pH, inhibited by aurintricarboxylic acid, and catalyze hydrolysis of DNA to produce 3′-OH/5′P ends. Both endonucleases in tears show maximal activity in hydrolyzing plasmid DNA in 50 mM NaCl (Figure 4 ). To compare the DNA fragment sizes remaining after hydrolysis by TL and the minor endonuclease, dideoxy sequencing gel electrophoresis was performed on the digestion products ( Figure 9 ). The size variation of the final single strand hydrolysis products observed in sequencing gels for DNase I, TL, and the minor endonuclease may reflect mechanistic interactions of the DNA substrate with unique binding and cleavage sites. cache = ./cache/cord-104272-lczm1z5z.txt txt = ./txt/cord-104272-lczm1z5z.txt === reduce.pl bib === id = cord-193910-7p3f3znj author = Zhang, Xiangxie title = Comparing Machine Learning Algorithms with or without Feature Extraction for DNA Classification date = 2020-11-01 pages = extension = .txt mime = text/plain words = 7724 sentences = 436 flesch = 59 summary = In the experiments, the performances of feature extraction using primers and random DNA sequences will be compared to several other machine learning approaches. Finally, three state-of-the-art methods, namely a con-volutional neural network (CNN), a deep neural network (DNN), and an N-gram probabilistic model, which were fed the unprocessed DNA sequences without prior feature extraction, were tested. Different machine learning algorithms will be trained and tested using each set of feature vectors in the experiments. For each data set, the results of all six machine learning algorithms using the random DNA sequence feature extraction method are presented in Table ( 8) containing mean accuracy and standard deviation over the ten folds of the cross-validation. It can be concluded that the Levenshtein distance feature extraction yields the best and most consistent results across the six different machine learning algorithms when the distance between a primer and a DNA sequence is taken. cache = ./cache/cord-193910-7p3f3znj.txt txt = ./txt/cord-193910-7p3f3znj.txt === reduce.pl bib === id = cord-023592-w96h4rir author = nan title = Abstracts cont. date = 2015-12-28 pages = extension = .txt mime = text/plain words = 67857 sentences = 4136 flesch = 52 summary = Conclusions: Although the risk of developing more serious gastric lesions increased as the number of virulence factor genes are accumulated in a given Hp strain, we did not find any significant differences or relationship in the cagA, vacA or babA2 status between the Hp isolates from patients with gastritis or peptic ulcer in this study. pneumophila at the serogroup level, it was used in two different outbreaks to demonstrate rapidly the identity of the sequences between strains responsible for severe human infection and those isolated in the hot water reservoir, suggesting a common origin. To determine the antimicrobial resistance in Salmonella and Shigella strains isolated from stool specimens during a 2-year period, from patients admitted to our clinics with a diagnosis of diarrhoea. In our study the susceptibility of 65 bacterial strains isolated in hospital environment (colonising or infecting patients or carried by German cockroaches) to antibiotics and chemical disinfectants was determined. cache = ./cache/cord-023592-w96h4rir.txt txt = ./txt/cord-023592-w96h4rir.txt === reduce.pl bib === id = cord-252838-av7ducrk author = Lucchi, Naomi W. title = Real-Time Fluorescence Loop Mediated Isothermal Amplification for the Diagnosis of Malaria date = 2010-10-29 pages = extension = .txt mime = text/plain words = 4913 sentences = 250 flesch = 52 summary = In this study, we attempted to improve this method for malaria diagnosis by using a simple and portable device capable of performing both the amplification and detection (by fluorescence) of LAMP in one platform. reported a species specific LAMP diagnostic method; using clinical samples and a conventional DNA extraction method, they demonstrated sensitivity and specificity of 98.5% and 94.3% respectively compared to microscopy and a nested PCR [14] . We refer to this method as RealAmp. We demonstrate the utility of this method for the diagnosis of malaria by using published Plasmodium genus specific primers and comparing it to microscopy and a nested PCR method as described by Singh et al [18] . As summarized in Table 5 , results from the RealAmp method were comparable to the previously reported malaria LAMP assays [13] [14] [15] [16] [17] demonstrating reasonable sensitivity and specificity profiles when compared to microscopy and nested PCR. cache = ./cache/cord-252838-av7ducrk.txt txt = ./txt/cord-252838-av7ducrk.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-252147-bvtchcbt author = Domingo-Espín, Joan title = Engineered Biological Entities for Drug Delivery and Gene Therapy: Protein Nanoparticles date = 2011-11-15 pages = extension = .txt mime = text/plain words = 17193 sentences = 888 flesch = 39 summary = Modular protein engineering, virus-like particles (VLPs), and other self-assembling entities are envisioned as modulatable novel protein nanoparticles able to include many desirable properties in the correct delivery of drugs and nucleic acids. 120 Modular fusion proteins that combine distinct functions required for cell type-specific uptake and intracellular delivery of DNA or drugs present an attractive approach for the development of self-assembling vectors for targeted gene or drug delivery. 215, 216 Although VLP-based vaccines have been primarily developed for their use against the corresponding virus, in the last decades genetic engineering or chemical modifications have been applied in order to generate chimeric VLPs. Thus, on the one hand, commonly short heterologous peptide epitopes or full proteins that are unable to form VLPs or that are unsafe for vaccination have been presented on surface-exposed loops or fused to N-or C-exposed termini of structural viral capsid proteins on VLPs. 154, 161, 210 Different HPV, 217-219 HBV, 220,221 parvovirus, 222, 223 and chimeric polyoma VLPs have been engineered 170, 175 and tested for different applications including vaccination against viral or bacterial diseases, against virus-induced tumors, and more recently, for immunotherapy of nonviral cancer. cache = ./cache/cord-252147-bvtchcbt.txt txt = ./txt/cord-252147-bvtchcbt.txt === reduce.pl bib === id = cord-252871-qfrpuy3t author = Nasir, Arshan title = Investigating the Concept and Origin of Viruses date = 2020-11-03 pages = extension = .txt mime = text/plain words = 5153 sentences = 298 flesch = 46 summary = We propose a new definition of viruses that is not restricted to the presence or absence of any genetic or physical feature, detail a scenario for how viruses likely originated from ancient cells, and explain technical and conceptual biases that limit our understanding of virus evolution. We propose a new definition of viruses that is not restricted to the presence or absence of any genetic or physical feature, detail a scenario for how viruses likely originated from ancient cells, and explain technical and conceptual biases that limit our understanding of virus evolution. In turn, the origin of archaeoviruses from Archaea, bacterioviruses from Bacteria, and eukaryoviruses from Eukarya also seems less likely as these viruses share several conserved protein folds involved in virion synthesis and other functions, indicating that they may have evolved prior to the diversification of LUCA into modern cells. cache = ./cache/cord-252871-qfrpuy3t.txt txt = ./txt/cord-252871-qfrpuy3t.txt === reduce.pl bib === id = cord-253295-82ydczid author = Funkhouser, William K. title = Pathology: the clinical description of human disease date = 2020-07-24 pages = extension = .txt mime = text/plain words = 8864 sentences = 396 flesch = 34 summary = Patient workup uses present illness history with reference to past medical history, review of other organ systems for other abnormalities, review of family history, physical examination, radiographic studies, clinical laboratory studies (for example, peripheral blood or CSF specimens), and anatomic pathology laboratory studies (for example, tissue biopsy or pleural fluid cytology specimens). Obviously, arrival at the correct diagnosis is a function of the examining physician and pathologist (fund of knowledge, experience, alertness), the prevalence of the disease in question in the particular patient (age, race, sex, site), and the sensitivity/ specificity of the screening tests used (physical exam, vital signs, blood solutes, tissue stains, genetic assays). However, understanding the molecular and cellular pathogenesis of a disease allows development of screening methods to determine risk for clinically unaffected individuals, as well as mechanistic approaches to specific therapy. cache = ./cache/cord-253295-82ydczid.txt txt = ./txt/cord-253295-82ydczid.txt === reduce.pl bib === id = cord-257284-dash9udv author = Decaro, Nicola title = Development and validation of a real-time PCR assay for specific and sensitive detection of canid herpesvirus 1 date = 2010-07-30 pages = extension = .txt mime = text/plain words = 3138 sentences = 149 flesch = 52 summary = The detection limit was 10(1) and 1.20 × 10(1) DNA copies per 10 μl(−1) of template for standard DNA and a CHV-1-positive kidney sample, respectively: about 1-log higher than a gel-based PCR assay targeting the thymidine kinase gene. Unlike other CHV-1-specific diagnostic methods, this quantitative assay permits simultaneous detection and quantitation of CHV-1 DNA in a wide range of canine tissues and body fluids, thus providing a useful tool for confirmation of a clinical diagnosis, for the study of viral pathogenesis and for evaluation of the efficacy of vaccines and antiviral drugs. To evaluate the detection limits of the real-time PCR assay, 10fold dilutions of the plasmid DNA, ranging from 10 9 to 10 0 copies, were made in a CHV-1-negative kidney homogenate and tested subsequently. The development and validation of a real-time PCR assay for detection and absolute quantitation of CHV-1 DNA in tissue samples and body fluids of dogs are described. cache = ./cache/cord-257284-dash9udv.txt txt = ./txt/cord-257284-dash9udv.txt === reduce.pl bib === id = cord-257318-jejgkcql author = Jain, K.K. title = Synthetic Biology and Personalized Medicine date = 2012-08-16 pages = extension = .txt mime = text/plain words = 6096 sentences = 285 flesch = 33 summary = Methods based on synthetic biology enable the design of novel strategies for the treatment of cancer, immune diseases metabolic disorders and infectious diseases as well as the production of cheap drugs [2] . Whereas genetic engineering focuses on individual genes, synthetic biology strings together a series of molecular components, such as DNA, RNA, proteins and cells, into circuits and networks. Synthetic gene network design and prototype therapeutic circuits will have an impact on future gene-and cell-based therapies and usher a new era of drug discovery that may enable treatment of complex diseases in a personalized manner. Among new technologies, synthetic biology will contribute by the introduction of therapeutic systems based on a synthetic genome, using an expanded genetic code, and designed for specific personalized drug synthesis as well as delivery and activation by a pathological signal. cache = ./cache/cord-257318-jejgkcql.txt txt = ./txt/cord-257318-jejgkcql.txt === reduce.pl bib === id = cord-256201-vjzfzshh author = Pereira-Gómez, Marianoel title = Effect of mismatch repair on the mutation rate of bacteriophage ϕX174 date = 2015-09-10 pages = extension = .txt mime = text/plain words = 6108 sentences = 284 flesch = 54 summary = Finally, the mutation rate reduction afforded by GATC sites is fully reverted under stress conditions, which up-regulate repair pathways and expression of error-prone host polymerases such as heat and treatment with the base analog 5-fluorouracil, suggesting that access to repair renders the phage sensitive to stress-induced mutagenesis. Finally, we found that the mutation rate reduction afforded by the twenty GATC motifs was fully reverted at 42 C and in the presence of the base analog 5-fluorouracil (5-FU), two stress factors that promote overexpression of repair-associated error prone polymerases (Layton and Foster 2005; Malkova and Haber 2012) , thus suggesting that addition of GATC motifs renders the phage sensitive to stress-induced mutagenesis. We have shown that introduction of GATC sites in the /X174 genome can reduce the spontaneous mutation rate of the phage by up to fiftyfold, indicating that phage DNA can undergo MMR if the required sequence motifs are present. cache = ./cache/cord-256201-vjzfzshh.txt txt = ./txt/cord-256201-vjzfzshh.txt === reduce.pl bib === id = cord-252536-gfx4cq03 author = Bieniossek, Christoph title = MultiBac: expanding the research toolbox for multiprotein complexes date = 2011-12-07 pages = extension = .txt mime = text/plain words = 7120 sentences = 354 flesch = 39 summary = It consists of an array of small synthetic DNA plasmids, an engineered baculovirus genome derived from the Autographa californica nuclear polyhedrosis virus (AcNPV; see Glossary) that is used to infect cells of the caterpillar Spodoptera frugiperda, and a set of protocols detailing every step from gene insertion into the plasmids to production of protein complexes in cultured insect cells [19, 20] . Donors and acceptors contain a resistance marker, a short imperfect inverted repeat (LoxP), an expression cassette consisting of a baculoviral promoter (p10 or polh), a DNA segment for inserting heterologous genes, and an efficient signal for eukaryotic polyadenylation (Figure 1a ). Two outstanding examples of the utility of MultiBac are the elegant production of the entire anaphase promoting complex, APC/Ca large (1.1 MDa) 13-subunit multiprotein assembly that regulates defined cell cycle transitions [34] and the recent crystal structure elucidation of the Mediator head modulea transcription factor complex that is essential for the expression of class II genes in eukaryotes [35] . cache = ./cache/cord-252536-gfx4cq03.txt txt = ./txt/cord-252536-gfx4cq03.txt === reduce.pl bib === id = cord-255499-31xmue1g author = Bujarski, J.J. title = Recombination date = 2008-07-30 pages = extension = .txt mime = text/plain words = 4852 sentences = 253 flesch = 41 summary = In general, homologous recombination events occur much more often and they are most commonly known as genetic crossing-over that happens in every DNA-based organism during meiosis. The mechanism may involve either homologous crossing-over events or copy-choice processes that rely on template switching by DNA replicase. Aberrant homologous recombination involves crossovers between related RNAs, but the crosses occur at not-corresponding sites leading to sequences insertions or deletions. A double-stranded RNA Pseudomonas phage Phi6 was hypothesized to recombine its RNA based on a copy-choice template switching mechanism, where the crossovers would have occurred inside the virus capsid structures at regions with almost no sequence similarity. In some cases, the base pairing between a partial nascent strand and the acceptor template can lead to the appearance of the rearranged regions in DI RNAs. In addition to rearranged DI RNAs, some RNA viruses accumulate defective RNAs due to a single internal deletion in the genomic RNA of the helper virus. cache = ./cache/cord-255499-31xmue1g.txt txt = ./txt/cord-255499-31xmue1g.txt === reduce.pl bib === id = cord-023364-ut56gczm author = nan title = EDUCATION DAY MONDAY: PLENARY SESSION 1 MONDAY: PARALLEL SESSIONS date = 2005-06-08 pages = extension = .txt mime = text/plain words = 130049 sentences = 7334 flesch = 54 summary = • enhancement of automation/computerisation; • process control to provide an 'error-free pathway'; • (national) surveillance and trend analysis of results, preferably based on national working standards; • significantly increased sensitivity, especially from development of antigen/antibody 'combi' assays (e.g. for HIV, and recently, for HCV); • awareness of HBsAg vaccine-escape mutants and design of assays to cope with this; • extension of range of agents and markers tested for (varies in different countries); • increasing range of assays available for testing donors with a relevant history of exposure to malaria or Chagas' disease infection (for retrieval of otherwise wasted blood); • European Union's in vitro diagnostics directive: this has caused some problems and reduced flexibility. cache = ./cache/cord-023364-ut56gczm.txt txt = ./txt/cord-023364-ut56gczm.txt === reduce.pl bib === id = cord-189561-jhvwozsn author = Chechetkin, Vladimr R. title = Combining Detection and Reconstruction of Periodic Motifs in Genomic Sequences with Transitional Genome Mapping date = 2020-10-14 pages = extension = .txt mime = text/plain words = 4184 sentences = 268 flesch = 54 summary = A method of transitional automorphic mapping of the genome on itself (TAMGI) is aimed at combining detection and reconstruction of periodic motifs in the genomic RNA/DNA sequences. Generally, TAMGI provides a convenient tool for the study of numerous molecular mechanisms with participation of both quasi-periodic motifs and complete repeats, the genome organization, contextual analysis of cis/trans regulatory elements, data mining, and correlations in the genomic sequences. f The distribution of k-mer lengths after TAMGI for the steps within interval 1-500 for the genome of SARS-CoV-2 (shown by crosses) and its comparison with the counterpart distribution for a random reshuffled sequence (shown by circles). The correspondence should be searched between the (generally multiple) elements of icosahedral symmetry and the character of large-scale quasi-periodic segmentation induced by weakly specific cooperative interactions between genomic RNA/DNA and capsid proteins. To sum up, TAMGI method developed in this article is quite general and can be applied to the combined detection/reconstruction of quasi-periodic motifs in the genomic RNA/DNA sequences. cache = ./cache/cord-189561-jhvwozsn.txt txt = ./txt/cord-189561-jhvwozsn.txt === reduce.pl bib === id = cord-252586-fuaoelgb author = Phillips, Sandra title = Alisporivir Inhibition of Hepatocyte Cyclophilins Reduces HBV Replication and Hepatitis B Surface Antigen Production date = 2014-10-08 pages = extension = .txt mime = text/plain words = 5530 sentences = 296 flesch = 47 summary = METHODS: Liver-derived cell lines producing full-length HBV and HBsAg particles, owing to stable (HepG2215) or transient (HuH-7) transfection, or infected with HBV (HepaRG cells; Invitrogen [Carlsbad, CA]), were incubated with alisporivir or NIM811 alone, or alisporivir in combination with a direct antiviral (telbivudine). Alisporivir treatment of HepG2215 cells resulted in a progressive reduction of secreted and intracellular, nucleocapsid-associated HBV DNA dependent on both drug concentration and time of drug exposure ( Figure 1A and B). NIM811 treatment of HepG2215 and of HepaRG cells also reduced the secreted and intracellular nucleocapsidassociated HBV DNA, however, its antiviral effect was lower than alisporivir (Supplementary Figure 3) . As stated earlier, alisporivir at 5 mg/mL reduced intracellular HBV-DNA levels by 73% and 58% in HuH-7 and HepG2215 cells, respectively, after 72 hours of treatment ( Figure 1B and D) . cache = ./cache/cord-252586-fuaoelgb.txt txt = ./txt/cord-252586-fuaoelgb.txt === reduce.pl bib === id = cord-023346-8sqbqjm1 author = nan title = MONDAY: POSTERS date = 2005-06-08 pages = extension = .txt mime = text/plain words = 130043 sentences = 7330 flesch = 54 summary = • enhancement of automation/computerisation; • process control to provide an 'error-free pathway'; • (national) surveillance and trend analysis of results, preferably based on national working standards; • significantly increased sensitivity, especially from development of antigen/antibody 'combi' assays (e.g. for HIV, and recently, for HCV); • awareness of HBsAg vaccine-escape mutants and design of assays to cope with this; • extension of range of agents and markers tested for (varies in different countries); • increasing range of assays available for testing donors with a relevant history of exposure to malaria or Chagas' disease infection (for retrieval of otherwise wasted blood); • European Union's in vitro diagnostics directive: this has caused some problems and reduced flexibility. cache = ./cache/cord-023346-8sqbqjm1.txt txt = ./txt/cord-023346-8sqbqjm1.txt === reduce.pl bib === id = cord-255043-uxdsjr39 author = Bustin, Stephen A. title = RT-qPCR Testing of SARS-CoV-2: A Primer date = 2020-04-24 pages = extension = .txt mime = text/plain words = 4552 sentences = 201 flesch = 46 summary = The only reliable test in current use for testing acute infection targets the genome of SARS-CoV-2, and the most widely used method is quantitative fluorescence-based reverse transcription polymerase chain reaction (RT-qPCR). Given that on 9th January 2020 SARS-CoV-2 was definitively identified by the Chinese CDC as the causative agent for COVID-19 pneumonia and that its genomic sequence (GenBank accession number MN908947) was made available on 10th January, it is extraordinary that by the time the earliest documented transmission within the UK appeared on 28th February, no definitive action plan, stockpile of assays and required consumables, RNA extraction robots or high throughput qPCR instruments had been assembled to allow immediate and widespread RT-qPCR testing. This involves designing assays that generate PCR products of 60-80 bp, using fast RNA-and DNA-dependent DNA polymerases such as Superscript IV and KAPA Taq polymerase, respectively, and selecting instruments capable of rapid cycling, for example Eco from PCRMax. This allows the RT step to be limited to 2 min or less, with the denaturation and annealing/polymerisation steps limited to 1 s each ( Figure 3) . cache = ./cache/cord-255043-uxdsjr39.txt txt = ./txt/cord-255043-uxdsjr39.txt === reduce.pl bib === id = cord-254646-psolkrom author = Matsui, Mary S. title = Vitamin D Update date = 2020-10-14 pages = extension = .txt mime = text/plain words = 5106 sentences = 236 flesch = 42 summary = This review will briefly summarize fundamental, well-established aspects of vitamin D and human health and then will also discuss (a) some of the most recent work related to vitamin D and non-skeletal-associated health issues; (b) the complexity of establishing meaningful vitamin D measurement metrics and assessing vitamin D status; c)decisionmaking for obtaining vitamin D through diet, supplements, or sun exposure; (d) the impact of skin type, pigmentation, and sunscreen on vitamin D levels; and (e) evidence for a potential influence of vitamin D on the mortality and morbidity of COVID-19 through modulation of the pro-inflammatory cytokine response and respiratory response to the virus. To some extent, this is because relevant factors vary: vitamin D food fortification regulations, the strength of ambient ultraviolet radiation (UVR), levels of smog, culture and ethnicity, skin phototype, chronological age, and ease and accuracy of specific clinical laboratory measurements. cache = ./cache/cord-254646-psolkrom.txt txt = ./txt/cord-254646-psolkrom.txt === reduce.pl bib === id = cord-258035-2tk7maqk author = DeFilippis, Victor title = Functional genomics in virology and antiviral drug discovery date = 2003-10-31 pages = extension = .txt mime = text/plain words = 4769 sentences = 255 flesch = 39 summary = Given that virus replication involves use and manipulation of multiple host proteins and molecular processes, cellular pathways related to transcription and translation, signal transduction, metabolism, host defense and cell cycle control are Review commonly altered in response to, or as a result of, infection with diverse virus types. A special case of virus modulation of host cell gene expression in which functional genomics will reveal novel targets and treatments is viral oncogenesis. The most recent method for analyzing gene inhibition studies has been RNAi or siRNA, where small 21 -23-nucleotide (nt) RNA duplexes interfere with the transcription program by directing degradation of homologous mRNA [34] [35] [36] [37] . Both new-generation antisense oligomers and siRNA can be used to knockdown expression of genes that were found by DNA microarrays to be upregulated in virally infected cells or organisms. RNA interference directed against viral and cellular targets inhibits human immunodeficiency virus type 1 replication cache = ./cache/cord-258035-2tk7maqk.txt txt = ./txt/cord-258035-2tk7maqk.txt === reduce.pl bib === id = cord-022501-9wnmdvg5 author = nan title = P1460 – P1884 date = 2015-12-28 pages = extension = .txt mime = text/plain words = 128256 sentences = 7808 flesch = 51 summary = Methods: Using published data on (1) the prevalence of MRSA and other bacterial pathogens causing cSSSI in the US, (2) the in-vitro susceptibility rates of commonly used regimens in cSSSI in the US in relation to the most pervasive pathogens identified above, and (3) estimated costs of failure of initial, empiric treatment from a recent study of a large US multi-hospital database, we developed a model to predict the expected clinical and economic impact of increasing prevalence of MRSA. Small outbreaks of VEB-1 ESBL producing Acinetobacter baumannii in Belgian nursing homes and hospitals through cross-border transfer of patients from northern France Methods: From 01/04 to 03/05, all Belgian acute hospitals were invited to report cases of nosocomial infections/colonisations due to MDR Ab isolates presenting a resistance profile similar to the French epidemic strain (resistance to all agents except carbapenems and colistin) and to send such isolates to the reference laboratory for phenotypic confirmation and for genotypic characterization (PCR of VEB-1 and class 1 Integron, PFGE typing). cache = ./cache/cord-022501-9wnmdvg5.txt txt = ./txt/cord-022501-9wnmdvg5.txt === reduce.pl bib === id = cord-253466-7gpije5d author = Netherton, Christopher title = A Guide to Viral Inclusions, Membrane Rearrangements, Factories, and Viroplasm Produced During Virus Replication date = 2007-08-31 pages = extension = .txt mime = text/plain words = 26372 sentences = 1363 flesch = 45 summary = Significantly, Poliovirus infection causes enrichment of GEFs in membranes containing replicase proteins, and this would provide a mechanism for increasing levels of Arf1-GTP at sites of virus replication. There is evidence that Tobacco mosaic virus also uses the ER as a site of replication because the replicase enzyme and viral RNA are located on the ER of infected cells, and infection causes major changes in ER morphology (Reichel and Beachy, 1998) , including ER aggregation and formation of lamella structures. Even though these viruses infect a diverse range of hosts from different phyla, including vertebrates [poxviruses, African swine fever virus (ASFV)], arthropods (entomopox, ASFV, chloriridoviruses), amphibians and fish (Ranavirus, Megalocytivirus, and Lymphocystivirus genera of the Iridoviridae family), marine algae (phycodnaviruses), and protozoa (mimivirus), they all generate cytoplasmic factories as major sites of virus assembly and replication (illustrated in Fig. 4 ). Formation of DNA replication structures in herpes virus-infected cells requires a viral DNA binding protein cache = ./cache/cord-253466-7gpije5d.txt txt = ./txt/cord-253466-7gpije5d.txt === reduce.pl bib === id = cord-254942-g51mjj2b author = Touati, Rabeb title = New methodology for repetitive sequences identification in human X and Y chromosomes date = 2020-10-19 pages = extension = .txt mime = text/plain words = 7712 sentences = 513 flesch = 52 summary = In this paper, we propose an efficient algorithm based on the signal and image processing tools to localize repetitive DNA sequences. Fig. 3 shows an example of the FCGS 2 signal, the correspondent scalogram in a 3D representation and the energy wavelet of a sequence located in chromosome X of the human genome. For each DNA image into the repeat-Data database, we aim to identify a DNA-reference sequence, to which corresponds the existing repetitive pattern in the scalogram. In the first result block, we provide the scalogram representation of the DNA sequence we have located at the X chromosome of the human genome (Xp22.33, position: [321001:322000bp]). Location of repetitive intronic satellites sequence "Rseq7" and the corresponding exonic modified sequences in different chromosomes of the human genome. These repetitive sequences are also located at the same position in intronic region within the DHRSX gene in the Y chromosome of the human genome. cache = ./cache/cord-254942-g51mjj2b.txt txt = ./txt/cord-254942-g51mjj2b.txt === reduce.pl bib === id = cord-254115-hwy962a4 author = Reslova, Nikol title = xMAP Technology: Applications in Detection of Pathogens date = 2017-01-25 pages = extension = .txt mime = text/plain words = 11354 sentences = 530 flesch = 40 summary = xMAP multiplex assays are currently available in various nucleic acid and immunoassay formats, enabling simultaneous detection and typing of pathogenic viruses, bacteria, parasites and fungi and also antigen or antibody interception. High-throughput multiplex detection techniques are designed for the rapid, sensitive and specific testing of large numbers of analytes (nucleic acid assays, immunoassays, enzyme assays, or receptor-ligands) in a single biological sample. Although PCR allows multiplex amplification of several targets in a single run xMAP as a methodology represents a significant step forward, and was designed with the aim of creating a high-throughput bioassay platform, enabling rapid, cost-effective, and simultaneous analysis of multiple analytes within a single biological sample. In direct DNA hybridization (DDH), allele-specific primer extension (ASPE), single base chain extension (SBCE), and Oligonucleotide ligation assay (OLA) all the target DNA sequences are amplified in multiplex PCR prior to hybridization to microspheres. cache = ./cache/cord-254115-hwy962a4.txt txt = ./txt/cord-254115-hwy962a4.txt === reduce.pl bib === id = cord-255536-x1z2o9gs author = Artusi, Sara title = The Herpes Simplex Virus-1 genome contains multiple clusters of repeated G-quadruplex: Implications for the antiviral activity of a G-quadruplex ligand date = 2015-04-03 pages = extension = .txt mime = text/plain words = 4823 sentences = 261 flesch = 55 summary = The remarkably high guanine content of the Herpes Simplex Virus-1 (HSV-1) genome prompted us to investigate both the presence of G-quadruplex forming sequences in the viral genome and the possibility to target them with G-quadruplex ligands to obtain anti-HSV-1 effects with a novel mechanism of action. BRACO-19 was able to inhibit Taq polymerase processing at G-quadruplex forming sequences in the HSV-1 genome, and decreased intracellular viral DNA in infected cells. In the Epstein-Barr herpes virus (EBV), G-quadruplexes modulate EBV nuclear antigen 1 (EBNA1) activity and translation (Murat et al., 2014) ; in particular, BRACO-19 inhibited EBNA1-dependent stimulation of viral DNA replication http://dx.doi.org/10.1016/j.antiviral.2015.03.016 0166-3542/Ó 2015 Elsevier B.V. All rights reserved. We demonstrate that treatment with the G-quadruplex ligand BRACO-19 greatly stabilizes these sequences resulting in decrease of infectious viral particles, reduction of late viral transcripts, inhibition of Taq polymerase processing at the HSV-1 genome, specifically affecting viral DNA replication at G-quadruplex regions. cache = ./cache/cord-255536-x1z2o9gs.txt txt = ./txt/cord-255536-x1z2o9gs.txt === reduce.pl bib === id = cord-260345-ugd8kkor author = Giles, Ian G. title = A compendium of reviews in biochemistry and molecular biology published in the first half of 1992 date = 1992-12-31 pages = extension = .txt mime = text/plain words = 5327 sentences = 701 flesch = 45 summary = 203, sodium dodecyl-sulfate.; ted blood-cells; phosphoenolpyruvate carboxylase activity; nucleotide-linked dehydrogenases; alkaline-phosphatase isoenzymes; pathogenesis-related proteins; cr-L-fucosidase; polyactylamide-gel; produce phosphate; general-method. low-density~l&protein; high-performance liquid; chrcmatogmphy mass spectmmetry; chicken vitellogam gene; thin-layer chmmatography; apolipoprotein-VLDL-II; fatty-acid composition; laying turkey hens; egg-yolk; plasma-lipoproteins. human-skin fibroblests; IGF binding-protein; messenger ribonucleic-acid; cooh-teminal truncation; monoclonal-antibody; endothelial-cells; factor receptoc amniotic-fluid; DNA-synthesis; rat-heart. factor-binding-protein; erythroid colony formation; cultured human-tibroblasts; factor messenger-RNA, N-terminal sequence; fetal bovine serum; IGF-I; somatomedin C, clinical-applicstians; stimulating factors. shon-hved protein; dependent pmteolytic system; ubiquitin-conjugating enzyme; repair gene ra&, Escherichia coli; transfer RNA; Sacclurroqces cercvisiue; endoplasmic-reticulum; cell-cycle; amino-acid. polymense chain-reaction; fragment length polymorphisms; dependent diabetes-mellitus; sickle-cell anemia; factor-M gene; enzymatic AMPlificatiat; genomic DNA; mutations; sequence; diagnosis; predisposition; genetics. T-cell receptor; messenger-RNA degradation; gamma-delta; stress proteins; antigen-receptor, lymphocytes-T; ~ycobactcrium fuberc&arir. Wiskott-Aldrich syndrome; heat-shock proteins; receptor-delta; ataxia telangiectasia; transgenic mice; lymphocytes T; bearing cells; recognition; expression; incmase. human granulocyte-macmphage; protein kinase-c; recombinant human interleukin-3; cell growth-factor, murine bone-marrow; express functional receptors; acute lymphocytic-leukemia; GTPase-activating pm&n; factor-independent growth. cache = ./cache/cord-260345-ugd8kkor.txt txt = ./txt/cord-260345-ugd8kkor.txt === reduce.pl bib === id = cord-253826-63dgq551 author = Kim, Jisung title = State of diagnosing infectious pathogens using colloidal nanomaterials date = 2017-08-17 pages = extension = .txt mime = text/plain words = 10488 sentences = 535 flesch = 39 summary = This review article discusses current advances of diagnostic systems using colloidal nanomaterials (e.g., gold nanoparticles, quantum dots, magnetic nanoparticles) for identifying and differentiating infectious pathogens. Similarly, Raman dye labeled oligonucleotide probes have been conjugated to GNPs in a scanometric assay to generate spectroscopic codes for individual target DNA and demonstrate a multiplexed detection (Fig. 6C ). While this technology is still early in development, these results show that thermal contrast may enhance the analytical sensitivity to enable detection of infectious pathogens, which are normally done with more complex molecular diagnostics. For detection of nucleic acids, none of the nanodiagnostic approaches were as sensitive as PCR (zM), except for the Mirkin's bio-barcode assay that utilized magnetic separation, and two levels of signal amplification. As we discussed in this review article, nanoparticles have been exploited to improve the analytical sensitivity of diagnostic assays, provide various readout signals, simultaneously detect multiple targets, and simplify diagnostic procedures. cache = ./cache/cord-253826-63dgq551.txt txt = ./txt/cord-253826-63dgq551.txt === reduce.pl bib === id = cord-258665-8q3tsggm author = Aydın, Hakan Berk title = Pixelated colorimetric nucleic acid assay date = 2020-03-01 pages = extension = .txt mime = text/plain words = 4056 sentences = 225 flesch = 45 summary = Herein, we report a pixelated analysis approach for correlating colorimetric responses of CPE with nucleic acid concentrations down to 1 nM, in plasma samples, utilizing a smart phone with an algorithm that can perform analytical testing and data processing. A smart phone application is developed to capture and digitize the colorimetric response of the individual pixels of the digital images of CPE on the PVDF membrane, followed by an analysis using the algorithm. The proposed pixelated approach enables precise quantification of nucleic acid assay concentrations, thereby eliminating the margin of error involved in conventional methodologies adopted for interpretation of colorimetric responses, for instance, RGB analysis. Herein, we propose a smart phone application algorithm that evaluates the colorimetric responses based on a pixel level analysis approach, enabling quantification of nucleic acids with high precision at clinically relevant concentration ranges. A cartridge-based point of care assay for colorimetric detection of nucleic acids has been developed using a smart phone algorithm. cache = ./cache/cord-258665-8q3tsggm.txt txt = ./txt/cord-258665-8q3tsggm.txt === reduce.pl bib === id = cord-023354-f2ciho6o author = nan title = TUESDAY PLENARY SESSION 3 TUESDAY: POSTERS date = 2005-06-08 pages = extension = .txt mime = text/plain words = 130046 sentences = 7333 flesch = 54 summary = • enhancement of automation/computerisation; • process control to provide an 'error-free pathway'; • (national) surveillance and trend analysis of results, preferably based on national working standards; • significantly increased sensitivity, especially from development of antigen/antibody 'combi' assays (e.g. for HIV, and recently, for HCV); • awareness of HBsAg vaccine-escape mutants and design of assays to cope with this; • extension of range of agents and markers tested for (varies in different countries); • increasing range of assays available for testing donors with a relevant history of exposure to malaria or Chagas' disease infection (for retrieval of otherwise wasted blood); • European Union's in vitro diagnostics directive: this has caused some problems and reduced flexibility. cache = ./cache/cord-023354-f2ciho6o.txt txt = ./txt/cord-023354-f2ciho6o.txt === reduce.pl bib === id = cord-259412-l8uta7du author = Mattossovich, Rosanna title = O(6)-alkylguanine-DNA Alkyltransferases in Microbes Living on the Edge: From Stability to Applicability date = 2020-04-20 pages = extension = .txt mime = text/plain words = 7475 sentences = 352 flesch = 42 summary = The reaction mechanism of AGTs is based on the recognition of the damaged nucleobase on DNA [5] , followed by a one-step SN 2 -like mechanism, in which the alkyl group of the damaged guanine is irreversibly transferred to a cysteine residue in its active site [5] [6] [7] [8] (Figure 1 , blue path). These compounds mimic damaged guanine on DNA and react with the protein by the covalent transfer of the alkyl adduct to the active site cysteine residue, thus irreversibly inactivating the enzyme (Figure 1 , red path). Concerning biotechnology, the use of a modified hMGMT as protein tag opened the possibility to generalise this method-a targeted mutagenesis on a thermostable OGT by following a rational approach led to the characterization of SsOGT-H 5 , applicable to in vitro harsh reaction conditions and to in vivo (hyper)thermophilic model organisms. cache = ./cache/cord-259412-l8uta7du.txt txt = ./txt/cord-259412-l8uta7du.txt === reduce.pl bib === id = cord-253115-ekgdsv4f author = Mehta, Meenu title = Oligonucleotide therapy: An emerging focus area for drug delivery in chronic inflammatory respiratory diseases date = 2019-08-01 pages = extension = .txt mime = text/plain words = 7317 sentences = 457 flesch = 39 summary = Commonly used drug delivery systems for respiratory diseases are polymer-based, lipid-based and peptide-based, and among these three, the lipid-based carriers are the most commonly used vectors for delivering RNAi. They include solid lipid nanoparticles, cationic liposomes, lipidoids, solid nanostructured lipid carriers and pH-responsive lipids [26] . The effective delivery of the drug and siRNA induced cell death of lung tumor cells by targeted gene silencing [56] . Glud et al., investigated pulmonary gene silencing effect of small interfering locked nucleic acid (siLNAs), targeting enhanced-greenfluorescent-protein (EGFP) in lung bronchoepithelium upon intravenous delivery of naked siLNAs and intranasal delivery of naked siLNA or chitosan based siLNA mucoadhesive nanoparticles. This study demonstrated that SAMiRNA nanoparticle is a stable siRNA silencing platform with less toxicity for effective in vivo targeting of genes involved in the pathogenesis of respiratory diseases [96] . Overcoming cisplatin resistance in non-small cell lung cancer with Mad2 silencing siRNA delivered systemically using EGFR-targeted chitosan nanoparticles cache = ./cache/cord-253115-ekgdsv4f.txt txt = ./txt/cord-253115-ekgdsv4f.txt === reduce.pl bib === id = cord-253894-4u5yt7b7 author = Senkevich, Tatiana G. title = Vaccinia virus F16 protein, a predicted catalytically inactive member of the prokaryotic serine recombinase superfamily, is targeted to nucleoli date = 2011-09-01 pages = extension = .txt mime = text/plain words = 6253 sentences = 286 flesch = 44 summary = VACV, by far the most intensively studied poxvirus, replicates entirely in the cytoplasm of infected cells and encodes many of the proteins required for its growth as well as numerous proteins modulating virus-host interactions. Here we provide a detailed computational analysis of the F16 protein indicating that it is unlikely to have serine recombinase activity, and experimental data showing that the F16L gene is not required for virus growth in cell culture. F16-3xflag was detected by Western blotting at 2 h after infection, only slightly increased in amount between 4 and 24 h, and accumulated in the presence of cytosine arabinoside (araC), an inhibitor of DNA synthesis that prevents VACV intermediate and late gene expression. Two other VAC proteins, I3 and B1, containing a C-terminal 3xflag tag and expressed from a transfected plasmid under the control of the CMV promoter were analyzed in parallel with F16-3xflag, and no nucleolar or nuclear membrane staining was detected (not shown). cache = ./cache/cord-253894-4u5yt7b7.txt txt = ./txt/cord-253894-4u5yt7b7.txt === reduce.pl bib === id = cord-256278-jvfjf7aw author = Feng, Jie title = New method for comparing DNA primary sequences based on a discrimination measure date = 2010-10-21 pages = extension = .txt mime = text/plain words = 2864 sentences = 186 flesch = 53 summary = title: New method for comparing DNA primary sequences based on a discrimination measure Three years after, Blaisdell (1989) proved that the dissimilarity values observed by using distance measures based on word frequencies are directly related to the ones requiring sequence alignment. In Table 2 , we present the similarity/dissimilarity matrix for the full DNA sequences of bÀglobin gene from 10 species listed in Table 1 by our new method. In Fig. 2, we show the phylogenetic tree of 10 bÀglobin gene sequences based on the distance matrix DM, using NJ method. In this paper, we propose a new method for the similarity analysis of DNA sequences. Our algorithm is not necessarily an improvement as compared to some existing methods, but an alternative for the similarity analysis of DNA sequences. Analysis of similarity/ dissimilarity of DNA sequences based on novel 2-D graphical representation A measure of DNA sequence dissimilarity based on Mahalanobis distance between frequencies of words cache = ./cache/cord-256278-jvfjf7aw.txt txt = ./txt/cord-256278-jvfjf7aw.txt === reduce.pl bib === id = cord-259929-02765q5j author = Stanley, Philip M. title = Decoding DNA data storage for investment date = 2020-09-28 pages = extension = .txt mime = text/plain words = 5978 sentences = 308 flesch = 47 summary = Moving forward, the concerted efforts of academia, large corporates, innovative startup companies together with venture capital investment will be required to propel DNA data storage to commercial scale. Interdisciplinary efforts spanning molecular biology, computer science, and information technology are required to reach a complete DNA data storage workflow and in the following paragraphs, several of these approaches are discussed in more depth. First, the past seven years have seen a rapid increase in total capital invested in companies developing DNA data storage-enabling technologies (Figure 3a) , averaging a 44% compound annual growth rate (CAGR). Given DNA data storage"s technology maturity time-scale, venture capital firms companies investing in this space (see 4.) would already be operating with a long-term view and longer timelines than are typical for other fields of investment. cache = ./cache/cord-259929-02765q5j.txt txt = ./txt/cord-259929-02765q5j.txt === reduce.pl bib === id = cord-257802-vgizgq2y author = Uttamchandani, Mahesh title = Applications of microarrays in pathogen detection and biodefence date = 2008-11-12 pages = extension = .txt mime = text/plain words = 6568 sentences = 305 flesch = 35 summary = Advances in miniaturizing this initial PCR step, for instance the development of Review Glossary Biodefence: defensive measures against biological threats, including natural/ emerging pathogens and bioterror agents, that have significant potential to endanger public health Detection: identifying the presence of target pathogen(s) from clinical or environmental samples. (b) Antibody microarrays can be used to detect pathogen proteins or antigens that might be present in environmental samples as an indication of contamination or for diagnostic purposes to determine pathogen infection in human tissues. fabricated a customized Affymetrix microarray containing 53 660 probes to detect DNA amplified from 18 different pathogenic microorganisms simultaneously, including pathogens from the US CDC's list of bioterrorism agents, such as Bacillus anthracis (which causes anthrax), Clostridium botulinum (which generates the botulinum toxin), Yersinia pestis (which causes bubonic plague) and the Ebola virus [17] . cache = ./cache/cord-257802-vgizgq2y.txt txt = ./txt/cord-257802-vgizgq2y.txt === reduce.pl bib === id = cord-260653-5qwtvm9x author = Chikhlikar, Priya title = DNA Encoding an HIV-1 Gag/Human Lysosome-Associated Membrane Protein-1 Chimera Elicits a Broad Cellular and Humoral Immune Response in Rhesus Macaques date = 2006-12-27 pages = extension = .txt mime = text/plain words = 6117 sentences = 278 flesch = 49 summary = Thomas; Marques, Ernesto T.A. title: DNA Encoding an HIV-1 Gag/Human Lysosome-Associated Membrane Protein-1 Chimera Elicits a Broad Cellular and Humoral Immune Response in Rhesus Macaques Previous studies of HIV-1 p55Gag immunization of mice have demonstrated the usefulness of targeting antigens to the cellular compartment containing the major histocompatibility complex type II (MHC II) complex molecules by use of a DNA antigen formulation encoding Gag as a chimera with the mouse lysosome-associated membrane protein (mLAMP/gag). In the present study, we have analyzed the magnitude and breadth of Gag-specific T-lymphocyte and antibody responses elicited in Rhesus macaques after immunization with DNA encoding a human LAMP/gag (hLAMP/gag) chimera. This study demonstrates that Rhesus macaques immunized with a DNA plasmid vaccine-encoding gag as an hLAMP/gag chimera develops strong antigen-specific humoral responses as well as CD4 + and CD8 + T-cell responses. cache = ./cache/cord-260653-5qwtvm9x.txt txt = ./txt/cord-260653-5qwtvm9x.txt === reduce.pl bib === id = cord-263134-0p4zy5t2 author = de Paz, Hector David title = Molecular isothermal techniques for combating infectious diseases: towards low-cost point-of-care diagnostics date = 2014-07-23 pages = extension = .txt mime = text/plain words = 6474 sentences = 304 flesch = 34 summary = This review describes the landscape of molecular isothermal diagnostic techniques for infectious diseases, their characteristics, current state of development, and available products, with a focus on new directions towards point-of-care applications. Advances in microfluidics and miniaturization of signal detectors have allowed the integration of molecular diagnostics into microscale lab-on-achip devices that perform all necessary PCR steps automatically, from sample intake to cell lysis, DNA extraction, purification and amplification. This review describes the state-ofthe-art and new directions in the development of isothermal amplification technologies for diagnosis of infectious diseases with particular focus on those susceptible to be integrated in inexpensive molecular POC tests. • Loop-mediated isothermal amplification, smart amplification process & signal mediated amplification of RNA technology, helicasedependent amplification, strand displacement amplification, recombinase polymerase amplification and nicking and extension amplification reaction are isothermal techniques with mid/high tolerance to inhibitory compounds that allow the use of raw samples without any pretreatment step, which may be an interesting feature for PCR-based point-of-care (POC) testing. cache = ./cache/cord-263134-0p4zy5t2.txt txt = ./txt/cord-263134-0p4zy5t2.txt === reduce.pl bib === id = cord-254527-zddwajzg author = Junter, Guy-Alain title = Polysaccharide-based chromatographic adsorbents for virus purification and viral clearance date = 2020-01-13 pages = extension = .txt mime = text/plain words = 16940 sentences = 907 flesch = 42 summary = Table 2 gathers a variety of packed-bed column chromatography procedures applied to viral particle purification in which the stationary phase consists of AG -essentially Sepharose® ("Separation-Pharmacia-AG"; GE Healthcare, Chicago, Ill.) (Seph) -or CELe.g., Cellufine™ (JNC Corporation, Tokyo, Japan) -gel beads, modified to fulfill varying separation modes, i.e., ion exchange, size exclusion and affinity (Table 3 [77] [78] [79] [80] [81] ). For instance, the purification process for Nuwiq®, a recombinant coagulation factor VIII (a blood-clotting protein whose deficiency is associated with hemophilia A) patented by Octapharma AG (Lachen, Switzerland) [195] , includes solvent/detergent (S/D) treatment, Planova NF, and five chromatography steps using PS-based stationary phases, i.e., MMC (Capto MMC), CEC (SP Seph FF), AFC (VIIISelect, a Capto matrix with factor VIIIselective ligand), AEC (Q Seph FF) and SEC (Superdex 200). cache = ./cache/cord-254527-zddwajzg.txt txt = ./txt/cord-254527-zddwajzg.txt === reduce.pl bib === id = cord-258014-lzzi4rnz author = Chorna, Nataliya title = A Protocol for the Multi-Omic Integration of Cervical Microbiota and Urine Metabolomics to Understand Human Papillomavirus (HPV)-Driven Dysbiosis date = 2020-04-08 pages = extension = .txt mime = text/plain words = 6060 sentences = 394 flesch = 47 summary = This methods article suggests detailed sample collection and laboratory processes of metabolomics, DNA extraction for microbiota, HPV typing, and the bioinformatic analyses of the data, both to characterize the metabolome, the microbiota, and joint multi-omic analyses, useful for the development of new point-of-care diagnostic tests based on these approaches. Recent studies have indicated that changes of the cervicovaginal microbiome [5] [6] [7] , such as bacterial vaginosis [8, 9] , cervical inflammation [10, 11] and vaginal pH [12, 13] , play a role in the susceptibility to cervical Human Papillomavirus (HPV) infection and the development of cervical intraepithelial neoplasia due to the profound shifts in the relative abundances of protective bacteria [10] . Derivatization solution without the sample only, and empty vials, must also be included as quality controls in the analysis to ensure that identified metabolites 11. cache = ./cache/cord-258014-lzzi4rnz.txt txt = ./txt/cord-258014-lzzi4rnz.txt === reduce.pl bib === id = cord-260050-9ex70e1k author = Zhang, Y. Q. title = Inhibition of herpes simplex virus type 1 by small interfering RNA date = 2007-11-02 pages = extension = .txt mime = text/plain words = 2120 sentences = 131 flesch = 51 summary = Aim. To investigate the antiviral effects of siRNA on herpes simplex virus type 1 (HSV‐1) replication in Vero cells. These results indicate that siRNA can potently inhibit HSV‐1 replication in vitro, suggesting that siRNA‐based antiviral therapy may be a potential effective therapeutic alternative for patients with HSV‐1 infection. In our experiments, we showed that the siRNA duplexes targeting VP16 and DNA polymerase genes potently inhibited HSV-1 replication. However, this is not a universal finding as no additive or synergistic effect on antiviral activity was observed in a study when using any combination between the specific siRNA targeting viral protease 2A and any other siRNAs targeting the 5¢ untranslated region, start codon and RNA polymerase 3D of coxsackie virus B3. Short interfering RNA-mediated inhibition of herpes simplex virus type 1 gene expression and function during infection of human keratinocytes cache = ./cache/cord-260050-9ex70e1k.txt txt = ./txt/cord-260050-9ex70e1k.txt === reduce.pl bib === id = cord-258623-9evwcs32 author = Roembke, Benjamin T. title = Nucleic acid detection using G-quadruplex amplification methodologies date = 2013-12-15 pages = extension = .txt mime = text/plain words = 4218 sentences = 235 flesch = 58 summary = Willner and co-workers also reported nucleic acid detection using a symmetric split G-quadruplex probe but instead of DAB, the Willner group used luminol as a reductant for a luminescent readout (Fig. 3 ) [22] . Wang and co-workers have described an interesting ''split'' molecular beacon G-quadruplex probe that can be used to detect DNA or thrombin (a dual probe, Fig. 12 ) [31] . When there is no target DNA, and both molecular beacons are intact, the probe can form a complete G-quadruplex, resulting in an active DNAzyme peroxidase. To create a turn on probe the authors used the blocker DNA in a twostep amplification process, in which the blocker DNA would lose affinity for the MB and bind the DNA analyte of interest resulting in the molecular beacon refolding and forming an active G-quadruplex peroxidase. Willner and co-workers showed that upon binding of a target to a MB G-quadruplex probe that was attached to a gold electrode, a G-quadruplex forms. cache = ./cache/cord-258623-9evwcs32.txt txt = ./txt/cord-258623-9evwcs32.txt === reduce.pl bib === id = cord-260705-huyyw5z6 author = Moshe, Adi title = Virus-Induced Aggregates in Infected Cells date = 2012-10-17 pages = extension = .txt mime = text/plain words = 5063 sentences = 265 flesch = 39 summary = During infection, many viruses induce cellular remodeling, resulting in the formation of insoluble aggregates/inclusions, usually containing viral structural proteins. The aggregates are utilized by viruses to house a large complex of proteins of both viral and host origin to promote virus replication, translation, intraand intercellular transportation. In plant cells, both RNA and DNA viruses are associated with large inclusions detected in the cytoplasm and nucleus, however, their role in virus propagation or oppositely in virus restraint is less investigated than in infected mammalian cells. In general, mammalian and plant viruses make use of aggregates as scaffolds for anchoring the replication complex, increasing the local concentration of viral and host components required for replication and assembly, and shielding the process of replication from host defense. cache = ./cache/cord-260705-huyyw5z6.txt txt = ./txt/cord-260705-huyyw5z6.txt === reduce.pl bib === id = cord-259738-yuqc6dk0 author = Tang, Mengjun title = Enhancement of the immunogenicity of an infectious bronchitis virus DNA vaccine by a bicistronic plasmid encoding nucleocapsid protein and interleukin-2 date = 2008-03-07 pages = extension = .txt mime = text/plain words = 3841 sentences = 209 flesch = 49 summary = title: Enhancement of the immunogenicity of an infectious bronchitis virus DNA vaccine by a bicistronic plasmid encoding nucleocapsid protein and interleukin-2 A DNA vaccine against infectious bronchitis virus (IBV) can induce specific humoral and cell-mediated immunity. When chickens were challenged with a virulent strain of IBV, the protective efficacy could be enhanced significantly after immunization with bicistronic DNA vaccine. In the present study, a bicistronic plasmid encoding the nucleocapsid protein and immune-stimulatory interleukin-2 has been constructed and its immunogenicity and protective effect in chickens has been evaluated. These recombinant plasmids were inoculated in chickens and tested in a protection-challenge experiment, demonstrating that vaccination with the co-expression plasmid pIRES-N/IL2 can induce stronger immune response than vaccination with pIRES-N. These results suggested that vaccination with the co-expression plasmid of N protein gene and IL-2 may have increased the protection rate against challenge. Partial protection against infectious bursal disease virus through DNA-mediated vaccination with the VP2 capsid protein and chicken IL-2 genes cache = ./cache/cord-259738-yuqc6dk0.txt txt = ./txt/cord-259738-yuqc6dk0.txt === reduce.pl bib === id = cord-262660-t1ndfn2l author = Hass, Kenneth N. title = Integrated Micropillar Polydimethylsiloxane Accurate CRISPR Detection System for Viral DNA Sensing date = 2020-10-13 pages = extension = .txt mime = text/plain words = 5219 sentences = 317 flesch = 54 summary = This miniaturized and fully packed IMPACT chip demonstrates sensitive and accurate DNA detection within 120 min and paves ways to the next-generation point-of-care diagnostics, responding to emerging and deadly pathogen outbreaks. On the solid surface, reporter probes do not require a quencher since they are only measured in the liquid phase after degradation; thus, the fluorescent signal will be largely reduced without the target DNA present in the assay. 19, 20 Here, we present a fully enclosed Integrated Micropillar Polydimethylsiloxane Accurate CRISPR deTection (IMPACT) system for nucleic acid target detection on the solid-surface of polydimethylsiloxane (PDMS) utilizing CRISPR-Cas12a. Leveraging the high activity of CRISPR-Cas12a enzyme and the ability of micropillars to bind more reporter probes, we successfully detected a double-stranded DNA target without background issues. The extended surface provided by high-aspect ratio micropillars significantly increases the reporter probe binding capacity. cache = ./cache/cord-262660-t1ndfn2l.txt txt = ./txt/cord-262660-t1ndfn2l.txt === reduce.pl bib === id = cord-265173-70wyecwj author = Trujillo-Uscanga, Adrian title = Host cell p53 associates with the feline calicivirus major viral capsid protein VP1, the protease-polymerase NS6/7, and the double-stranded RNA playing a role in virus replication date = 2020-08-27 pages = extension = .txt mime = text/plain words = 5671 sentences = 282 flesch = 53 summary = title: Host cell p53 associates with the feline calicivirus major viral capsid protein VP1, the protease-polymerase NS6/7, and the double-stranded RNA playing a role in virus replication Viruses modulate p53 functions in different manners: single-stranded RNA viruses such as the human coronavirus NL63 (HCoV-NL63) induces its degradation of p53 (Yuan et al., 2015) to ensure viral growth in infected cells (Ma-Lauer et al., 2016) , Zika (ZIKV) and West Nile (WNV) activate p53 to facilitate their replication (El Ghouzzi et al., 2016) (Teng et al., 2017) (Yang et al., 2008) while Adenovirus Even though p53 is implicated in the induction of apoptosis and in many viral infections, its role during calicivirus infection has not been studied. Here we found that p53 interacts with FCV dsRNA, the protease-polymerase NS6/7, and VP1 in the RC; moreover, knockdown of p53 resulted in a significant reduction of the NS viral protein synthesis and virus production, indicating its role for efficient viral replication. cache = ./cache/cord-265173-70wyecwj.txt txt = ./txt/cord-265173-70wyecwj.txt === reduce.pl bib === id = cord-261134-zarq507s author = Pulford, David title = Amplification refractory mutation system PCR assays for the detection of variola and Orthopoxvirus date = 2004-02-13 pages = extension = .txt mime = text/plain words = 3799 sentences = 215 flesch = 50 summary = PCR assays that can identify the presence of variola virus (VARV) sequences in an unknown DNA sample were developed using principles established for the amplification refractory mutation system (ARMS). When a variola virus specific primer was used with a consensus primer in an ARMS assay with different Orthopoxvirus genomes, a PCR product was only amplified from variola virus DNA. Incorporating a second consensus primer into the assay produced a multiplex PCR that provided Orthopoxvirus generic and variola-specific products with variola virus DNA. The variola virus specific primers did not produce amplicons with either assay format when tested with 50 other Orthopoxvirus DNA samples. These multiplex assays employ three primers; two consensus primers generate an amplicon diagnostic of an Old World Orthopoxvirus and the third primer simultaneously binds to a variola-specific polymorphism and initiates extension of a shorter PCR product to detect the presence of variola virus. cache = ./cache/cord-261134-zarq507s.txt txt = ./txt/cord-261134-zarq507s.txt === reduce.pl bib === id = cord-265237-sxh2nqre author = Weile, Jan title = Current applications and future trends of molecular diagnostics in clinical bacteriology date = 2009-04-18 pages = extension = .txt mime = text/plain words = 4555 sentences = 226 flesch = 35 summary = Improvements and new approaches in technology now open the possibility for the development of multiparameter assays using microarrays, multiplex nucleic acid amplification techniques, or mass spectrometry, while the introduction of closed-tube systems has resulted in rapid microbial diagnostics with a subsequently reduced contamination risk. We mainly focus this review on nucleic-acid-based molecular techniques for identification and resistance determination in clinical bacteriology, giving a brief overview of currently used modern bacterial diagnostics and providing an outlook on future technologies, especially dealing with the multiparametric detection of infectious disease-related determinants. With exception of molecular tests such as nucleic acid amplification techniques (NAT), direct microscopy of the specimen, culturing, and direct antigen detection represent the sole possibilities to detect an acute infection as early as possible, facing either a lack of sensitivity, specificity or long time periods until results are available. cache = ./cache/cord-265237-sxh2nqre.txt txt = ./txt/cord-265237-sxh2nqre.txt === reduce.pl bib === id = cord-262733-icnkx1rx author = Daneluz, Larissa O. title = Efficiency and cell viability implications using tip type electroporation in zebrafish sperm cells date = 2020-07-13 pages = extension = .txt mime = text/plain words = 4961 sentences = 254 flesch = 46 summary = Sperm kinetics parameters were assessed using Computer Assisted Semen Analysis (CASA) and cell integrity, reactive oxygen species (ROS), mitochondrial functionality and transfection rate were evaluated by flow cytometry. increased DNA uptake by sperm cells, some problems are associated with the conventional cuvette type electroporation, such as low transfection rate, mosaic gene expression, and negative effects on cell viability [9] . The objective of this study was to demonstrate the feasibility of tip type electroporation in Danio rerio sperm, allowing its further use in SMGT, showing a protocol that provide high transfection efficiency, with minimal sideeffects on sperm cells. Cell integrity, membrane fluidity, mitochondrial functionality, concentration of reactive oxygen species (ROS) and total of sperm-bound exogenous DNA were evaluated by flow cytometry (Attune® Acoustic Focusing Cytometer, Applied Biosystems, USA) as previously described [30] . Here, transfection rate of fish spermatozoa was positively affected for tip type electroporation, increasing the number of cells containing exogenous DNA. cache = ./cache/cord-262733-icnkx1rx.txt txt = ./txt/cord-262733-icnkx1rx.txt === reduce.pl bib === id = cord-260422-z22t57ju author = Godet, Julien title = Comparative nucleic acid chaperone properties of the nucleocapsid protein NCp7 and Tat protein of HIV-1 date = 2012-06-26 pages = extension = .txt mime = text/plain words = 9180 sentences = 486 flesch = 49 summary = Today's view is that RNA chaperones are nucleic acid binding proteins present in all living organisms, including viruses, where they Abbreviations: HIV-1, human immunodeficiency virus-type I; NCp7, nucleocapsid protein of HIV-1; ZF, zinc finger; NA, nucleic acid; TAR, transactivation response element; PBS, primer binding site; AA, amino acids. The substantial nucleic acid chaperone properties exhibited by Tat may account for its ability to promote the annealing of the primer tRNA to the viral RNA (Kameoka et al., 2002) and intervene in the first strand transfer (Boudier et al., 2010) and by this way, to stimulate RTion as does NCp7 (Harrich et al., 1997; Ulich et al., 1999; Apolloni et al., 2007) . Human immunodeficiency virus Type 1 nucleocapsid protein (NCp7) directs specific initiation of minusstrand DNA synthesis primed by human tRNA(Lys3) in vitro: studies of viral RNA molecules mutated in regions that flank the primer binding site cache = ./cache/cord-260422-z22t57ju.txt txt = ./txt/cord-260422-z22t57ju.txt === reduce.pl bib === id = cord-261028-sxux2ujo author = Vatner, Ralph E. title = STING, DCs and the link between innate and adaptive tumor immunity date = 2017-12-20 pages = extension = .txt mime = text/plain words = 10018 sentences = 475 flesch = 44 summary = Dendritic cells (DCs) are a heterogeneous population of professional antigen-presenting cells (APCs) from hematopoietic origin that serve as a key link between the innate and adaptive immune systems, and are the lynchpin in generating anti-tumor immunity (Steinman and Idoyaga, 2010) . More recently, type I IFN production and signaling through the STING pathway has been identified as having an essential role in the development of anti-tumor immunity in response to tumor derived DNA. DNA sensing by STING is the upstream link that triggers type I IFN production by DCs and facilitates effective cross-priming of tumor specific CD8+ T cells. This DNA is likely derived from stressed and dying cancer cells, and is introduced into the DC cytosol through a yet unknown mechanism where it binds to cGAS, which initiates STING mediated type I IFN transcription (Fig. 2) . cache = ./cache/cord-261028-sxux2ujo.txt txt = ./txt/cord-261028-sxux2ujo.txt === reduce.pl bib === id = cord-261417-4pf5nsw2 author = Harwig, Alex title = The Battle of RNA Synthesis: Virus versus Host date = 2017-10-21 pages = extension = .txt mime = text/plain words = 7864 sentences = 443 flesch = 53 summary = Why the virus prefers to use these snRNAs as targets has yet to be experimentally established, but it has been proposed that the selective de-capping of U1 and U2 RNAs in combination with the binding of the viral NS1 protein to U6 snRNA may serve to inhibit host pre-mRNA splicing [66] . The folding of the TAR hairpin is key to the regulation of HIV-1 transcription [94] as it is used as a scaffold to recruit essential transcription factors, including the 86-101 amino acid (aa) viral trans-activator protein (Tat) [83] ( Figure 3C ). Interestingly, the human T-lymphotropic virus type 1 transcriptional activator Tax also utilizes P-TEFb for viral transcription and displaces P-TEFb from 7SK snRNP through binding CycT1 [101, 102] , suggesting that P-TEFb liberation from 7SK snRNP could be a common theme developed by different viruses to support their replication in host cells. cache = ./cache/cord-261417-4pf5nsw2.txt txt = ./txt/cord-261417-4pf5nsw2.txt === reduce.pl bib === id = cord-263570-6notzm6s author = Elia, Gabriella title = Detection of infectious canine parvovirus type 2 by mRNA real-time RT-PCR date = 2007-08-10 pages = extension = .txt mime = text/plain words = 3990 sentences = 224 flesch = 58 summary = The load and distribution of CPV-2 mRNA in samples from infected dogs were estimated in comparison with the load of virus DNA, as evaluated by real-time PCR. The analytic specificity of spliced CPV-2 mRNA detection by real-time RT-PCR was assessed by testing RNA and DNA preparations of other canine pathogens, including canine coronavirus types I and II (CCoVI, CCoVII) (Decaro et al., 2005d) , canine distemper virus (CDV) (Elia et al., 2006) , canine adenovirus (CAdV) (Decaro et al., 2006a) , reoviruses (Decaro et al., 2005b) and rotaviruses . To compare the amount of viral DNA in the tissue samples and in the infected cell cultures, a real-time PCR assay was used as described previously (Decaro et al., 2005c) . The newly developed real-time RT-PCR assay was applied to determine the viral mRNA loads in different tissues of CPV-2 naturally infected dogs. A real-time PCR assay for rapid detection and quantitation of canine parvovirus type 2 DNA in the feces of dogs cache = ./cache/cord-263570-6notzm6s.txt txt = ./txt/cord-263570-6notzm6s.txt === reduce.pl bib === id = cord-257046-er5orx8s author = Ladekjær-Mikkelsen, A.-S title = Reproduction of postweaning multisystemic wasting syndrome (PMWS) in immunostimulated and non-immunostimulated 3-week-old piglets experimentally infected with porcine circovirus type 2 (PCV2) date = 2002-10-22 pages = extension = .txt mime = text/plain words = 6752 sentences = 360 flesch = 49 summary = title: Reproduction of postweaning multisystemic wasting syndrome (PMWS) in immunostimulated and non-immunostimulated 3-week-old piglets experimentally infected with porcine circovirus type 2 (PCV2) Reproduction of postweaning multisystemic wasting syndrome (PMWS) in immunostimulated and non-immunostimulated 3-week-old piglets experimentally infected with porcine circovirus type 2 (PCV2) PCV1 is considered to be a non-pathogenic virus (Tischer et al., 1986; Allan et al., 1995) , whereas infection of swine with PCV2 is causally associated with development of postweaning multisystemic wasting syndrome (PMWS) in weaned 5-to 12-week-old piglets (Allan et al., 1998; Ellis et al., 1998) . In contrast, dual infection with PCV2 and porcine parvovirus (PPV) or porcine reproductive and respiratory syndrome virus (PRRSV) potentiates the replication and distribution of PCV2 and induces clinical disease in addition to more severe histopathological lesions Kennedy et al., 2000; Krakowka et al., 2000; Harms et al., 2001) . cache = ./cache/cord-257046-er5orx8s.txt txt = ./txt/cord-257046-er5orx8s.txt === reduce.pl bib === id = cord-264746-gfn312aa author = Muse, Spencer title = GENOMICS AND BIOINFORMATICS date = 2012-03-29 pages = extension = .txt mime = text/plain words = 10976 sentences = 583 flesch = 58 summary = The success of this project (it came in almost 3 years ahead of time and 10% under budget, while at the same time providing more data than originally planned) depended on innovations in a variety of areas: breakthroughs in basic molecular biology to allow manipulation of DNA and other compounds; improved engineering and manufacturing technology to produce equipment for reading the sequences of DNA; advances in robotics and laboratory automation; development of statistical methods to interpret data from sequencing projects; and the creation of specialized computing hardware and software systems to circumvent massive computational barriers that faced genome scientists. Although the list of important biotechnologies changes on an almost daily basis, there are three prominent data types in today's environment: (1) genome sequences provide the starting point that allows scientists to begin understanding the genetic underpinnings of an organism; (2) measurements of gene expression levels facilitate studies of gene regulation, which, among other things, help us to understand how an organism's genome interacts with its environment; and (3) genetic polymorphisms are variations from individual to individual within species, and understanding how these variations correlate with phenotypes such as disease susceptibility is a crucial element of modern biomedical research. cache = ./cache/cord-264746-gfn312aa.txt txt = ./txt/cord-264746-gfn312aa.txt === reduce.pl bib === id = cord-256130-zhlvvuj4 author = Nordén, Rickard title = Quantification of Torque Teno Virus and Epstein-Barr Virus Is of Limited Value for Predicting the Net State of Immunosuppression After Lung Transplantation date = 2018-03-06 pages = extension = .txt mime = text/plain words = 4853 sentences = 230 flesch = 47 summary = Here, we evaluated quantification of torque teno virus (TTV) and Epstein-Barr virus (EBV) as biomarkers for defining the net state of immunosuppression in lung-transplanted patients. The aim of the present study was to evaluate levels of TTV and EBV in relation to the frequency of infectious events and acute rejections over time in a prospective manner in a single-center cohort of lung-transplanted patients. The total nucleic acid content was isolated from serum or whole blood samples and analyzed for TTV-, EBV-, and CMV-DNA load by real-time PCR. Comparison of TTV-and EBV-DNA levels in lung transplant recipients who received either Tacrolimus-or Cyclosporinebased therapy revealed that Cyclosporine-treated patients had significantly lower TTV-DNA levels in serum at month 6 post-LTx and onwards, compared with the Tacrolimustreated patients (Figure 1 ). However, we found no association between either TTV-or EBV-DNA load and infectious events or acute rejections, which suggests a limited clinical applicability as biomarkers predicting short-term outcomes related to the net state of immunosuppression. cache = ./cache/cord-256130-zhlvvuj4.txt txt = ./txt/cord-256130-zhlvvuj4.txt === reduce.pl bib === id = cord-264456-wjpc6zgq author = Bütepage, Mareike title = Intracellular Mono-ADP-Ribosylation in Signaling and Disease date = 2015-09-25 pages = extension = .txt mime = text/plain words = 10307 sentences = 575 flesch = 46 summary = inactive mRNA regulation and miRNA silencing [36] Component of stress granules [17] Viral defense [36] ARTD14 (PARP7, TiPARP) MAR AHR signaling [37] [38] [39] [40] Translation [31] TCCD-induced hepatotoxicity [40] Inhibition of viral replication [31, 41] ARTD15 (PARP16) MAR Unfolded protein response [42] Not reported ARTD16 (PARP8) MAR Unclear Not reported ARTD17 (PARP6) MAR Regulates cell cycle progression [43] Inhibits cell proliferation, survival benefit in colorectal cancer [43] SIRT4 MAR Glutamine metabolism [44, 45] Tumor-suppressive [45, 46] SIRT6 MAR DNA repair [47] [48] [49] Retrotransposon silencing [50] Tumor suppressive [50] [51] [52] [53] [54] [55] [56] [57] and oncogenic functions [58, 59] MACROD1 (LRP16) Hydrolase ERα signaling [60, 61] AR signaling [62] Promotes cell proliferation [60, 62] Metastasis, invasion and survival in gastric and colorectal cancer [63, 64] . cache = ./cache/cord-264456-wjpc6zgq.txt txt = ./txt/cord-264456-wjpc6zgq.txt === reduce.pl bib === id = cord-269124-oreg7rnj author = Spyrou, Maria A. title = Ancient pathogen genomics as an emerging tool for infectious disease research date = 2019-04-05 pages = extension = .txt mime = text/plain words = 11932 sentences = 518 flesch = 42 summary = Examples of tools that have shown their effectiveness with ancient metagenomic DNA include the widely used Basic Local Alignment Search Tool (BLAST) 68 ; the MEGAN Alignment Tool (MALT) 41 , which involves a taxonomic binning algorithm that can use whole genome databases (such as the National Center for Biotechnical Information (NCBI) Reference Sequence (RefSeq) database 69 ); Metagenomic Phylogenetic Analysis (MetaPhlAn) 70 , which is also integrated into the metagenomic pipeline MetaBIT 71 and uses thousands (or millions) of marker genes for the distinction of specific microbial clades; or Kraken 72 , an alignment free sequence classifier that is based on k-mer matching of a query to a constructed database. Similar limitations can arise when the evolutionary history of a microorganism is vastly affected by recombination, as observed for HBV 44, 53 , although HBV molecular dating was recently attempted using a different genomic data set and suggested that the currently explored diversity of Old and New World pri mate lineages (including all human genotypes) may have emerged within the last 20,000 years 43 . cache = ./cache/cord-269124-oreg7rnj.txt txt = ./txt/cord-269124-oreg7rnj.txt === reduce.pl bib === id = cord-270637-4zphlpks author = Van Rompay, An R title = Substrate specificity and phosphorylation of antiviral and anticancer nucleoside analogues by human deoxyribonucleoside kinases and ribonucleoside kinases date = 2003-11-04 pages = extension = .txt mime = text/plain words = 11595 sentences = 702 flesch = 47 summary = (2001) , there are 3 general mechanisms of resistance to NAs that have been described in cell lines and clinical samples: (1) insufficient intracellular concentrations of NA-TPs, which might be due to inefficient cellular uptake, decreased levels of activating enzymes, increased catabolism by elevated levels of 5V -NT or deaminases, or expansion of dNTP pools; (2) inability to achieve sufficient alterations in DNA strands or dNTP pools, which might result from altered interactions with DNA polymerases, lack of inhibition of RR, or inadequate p53 exonuclease activity; and (3) defective induction of apoptosis. In human leukemia cell lines is CAFdA, a more efficient substrate for dCK, and the active form is more stable due to higher phosphorylation and longer retention time compared with CdA, but the mechanisms leading to acquired resistance to CAFdA seem to be similar to those for CdA (Lotfi et al., 1999; Månsson et al., 2003) . cache = ./cache/cord-270637-4zphlpks.txt txt = ./txt/cord-270637-4zphlpks.txt === reduce.pl bib === id = cord-256320-zocunore author = Liao, Bo title = Coronavirus phylogeny based on triplets of nucleic acids bases date = 2006-04-15 pages = extension = .txt mime = text/plain words = 1972 sentences = 171 flesch = 72 summary = Abstract We considered the fully overlapping triplets of nucleotide bases and proposed a 2D graphical representation of protein sequences consisting of 20 amino acids and a stop code. Based on this 2D graphical representation, we outlined a new approach to analyze the phylogenetic relationships of coronaviruses by constructing a covariance matrix. Based on these graphical representation, several authors outlined some approaches to make comparison of DNA sequences [21] [22] [23] [24] [25] . In this Letter, we proposed a 2D graphical representation of the protein sequences consisting of 20 amino acids and a stop code. Using the translate tool, we can obtain three protein sequences consisting of 20 amino acids and a stop code. Using the translate tool, one can obtain three protein sequences consisting of 20 amino acids and a stop code corresponding three reading frame start at position 1, 2 and 3. The current two-dimensional graphical representation of DNA sequences provides different approach for constructing phylogenetic tree. cache = ./cache/cord-256320-zocunore.txt txt = ./txt/cord-256320-zocunore.txt === reduce.pl bib === id = cord-259748-x7dq1sy4 author = Wan, Dongshan title = Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response date = 2020-04-28 pages = extension = .txt mime = text/plain words = 14147 sentences = 850 flesch = 41 summary = Double-stranded DNA (dsDNA) sensor cyclic-GMP-AMP synthase (cGAS) along with the downstream stimulator of interferon genes (STING) acting as essential immune-surveillance mediators have become hot topics of research. The intrinsic function of the cGAS-STING pathway facilitates type-I interferon (IFN) inflammatory signaling responses and other cellular processes such as autophagy, cell survival, senescence. In 2008, several research teams discovered a new protein on the endoplasmic reticulum (ER) which can be activated by immune-stimulatory DNA (ISD) and initiate type-I interferon (IFN) responses, which was named "stimulator of interferon genes" (STING, also known as MITA, ERIS) (2) (3) (4) . Mitochondrial outer membrane permeabilization (MOMP) activation, which is executed by BCL-2-associated X protein (BAX) and BCL-2 antagonist or killer (BAK), is a highly controlled conserved process in regulated cell FIGURE 3 | Interaction of the cGAS-STING pathway with other DNA-sensing pathways and its role in cell survival. Human plasmacytoid dentritic cells elicit a Type I interferon response by sensing DNA via the cGAS-STING signaling pathway cache = ./cache/cord-259748-x7dq1sy4.txt txt = ./txt/cord-259748-x7dq1sy4.txt === reduce.pl bib === id = cord-271635-tydlyc1q author = Abdel-Hamid, Nabil M. title = Herbal management of hepatocellular carcinoma through cutting the pathways of the common risk factors date = 2018-11-30 pages = extension = .txt mime = text/plain words = 10051 sentences = 543 flesch = 36 summary = They can inhibit the liver cancer development and progression in several ways as protecting against liver carcinogens, enhancing effects of chemotherapeutic drugs, inhibiting tumor cell growth and metastasis, and suppression of oxidative stress and chronic inflammation. The co-treatment with LPP, orally, in NAFLD in rats, showed a significant improvement in the hepatic histology, reduction in the fibrosis, oxidative stress, inflammation, accumulation of fats and apoptosis, through modulating the transcriptional factors NF-κB and activator protein-1 (AP-1). The major polyphenol of green tea, epigallocatechin-3-gallate (EGCG), was used in CCl 4 -treated mice and showed a significant therapeutic potential in hepatic damage, inflammation and oxidative stress induced by CCl 4 in a dose-dependent manner at both biochemical and histological levels [34] . It was also reported that co-treatment of the whole green tea extract with alcohol administration showed an effective reduction of the hepatic oxidative stress and reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase systems in experimental alcohol-induced liver injury [35] . cache = ./cache/cord-271635-tydlyc1q.txt txt = ./txt/cord-271635-tydlyc1q.txt === reduce.pl bib === id = cord-265764-h4zg0q8x author = Singh, Kamaljit title = Synthesis of 4-aminoquinoline–pyrimidine hybrids as potent antimalarials and their mode of action studies date = 2013-06-10 pages = extension = .txt mime = text/plain words = 4082 sentences = 219 flesch = 49 summary = On the other hand, pyrimidine-based compounds are well known for their wide range of promising antiviral [22] , antitubercular [23] , anti-AIDS [24] , antinociceptive [25] , antifungal [26] , antitumor [27] and antimalarial activities [28] apart from their role in the nucleic acid synthesis. The in vitro antimalarial screening of the new synthesized compounds 5aeg revealed good to moderate activities in nM range against both the tested Dd2 (CQ S ) and D10 strains (CQ R ) of P. Analysis of the activity of the compounds recorded in Table 1 reveals that replacing C-5 ethyl ester of the previously reported [29] decrease in antimalarial activity against both the chloroquine sensitive and chloroquine resistant strains of P. In this study, we have evaluated the mechanism of antimalarial activity of the most potent compound 5b of the series by studying its binding with heme (Fig. 4) . cache = ./cache/cord-265764-h4zg0q8x.txt txt = ./txt/cord-265764-h4zg0q8x.txt === reduce.pl bib === id = cord-258363-gmgbus9i author = Kolla, Venkatadri title = Synthesis of a bacteriophage MB78 late protein by novel ribosomal frameshifting() date = 2000-08-22 pages = extension = .txt mime = text/plain words = 4578 sentences = 279 flesch = 63 summary = In vitro transcription-translation yields a major protein that migrates as 28 kDa, whereas in vivo expression using pET expression vectors yields two equally expressed proteins of molecular sizes 28 and 26 kDa. A putative slippery sequence TTTAAAG and a pseudoknot structure, two essential cis elements required for the classical ribosomal frameshifting, are identified in the reading frame. The chelating agent EDTA is an effective It is now known that two proteins can be expressed inhibitor of its DNA synthesis, whereas EGTA and from a single open reading frame through 'ribosomal orthophenanthroline have practically no effect on the frameshifting'. During the process of 'ribosomal frameshifting', two or more proteins can result, starting from a single initiation codon Abbreviations: bp, base pairs; IPTG, isopropyl b-thiogalactosidase; ( Farabaugh and Vimaladithan, 1998 direction (+1 frame shift) has been described in the k The nucleotide sequence reported in this paper has been deposited yeast retrotransposon TY (Belcourt and Farabaugh, in the EMBL/GenBank database under Accession No. X87092. cache = ./cache/cord-258363-gmgbus9i.txt txt = ./txt/cord-258363-gmgbus9i.txt === reduce.pl bib === id = cord-263282-a7emso89 author = Coghlan, Megan L. title = Egg forensics: An appraisal of DNA sequencing to assist in species identification of illegally smuggled eggs date = 2011-07-07 pages = extension = .txt mime = text/plain words = 4869 sentences = 245 flesch = 51 summary = Clearly the lack of validated DNA reference sequences is hindering our ability to accurately assign a species identity, and accordingly, we advocate that more attention needs to be paid to establishing validated, multi locus mtDNA reference databases for exotic birds that can both assist in genetic identifications and withstand legal scrutiny. Clearly the lack of validated DNA reference sequences is hindering our ability to accurately assign a species identity, and accordingly, we advocate that more attention needs to be paid to establishing validated, multi locus mtDNA reference databases for exotic birds that can both assist in genetic identifications and withstand legal scrutiny. In wildlife forensics, DNA species identification is commonly carried out by amplifying and sequencing fragments of the mitochondrial DNA (mtDNA) genes cytochrome oxidase I (COI), cytochrome b (Cytb), or 12S ribosomal RNA (12S) [15, 17, 20, 21] . cache = ./cache/cord-263282-a7emso89.txt txt = ./txt/cord-263282-a7emso89.txt === reduce.pl bib === id = cord-272943-q09i8fqu author = Dalhoff, A. title = Antiviral, antifungal, and antiparasitic activities of fluoroquinolones optimized for treatment of bacterial infections: a puzzling paradox or a logical consequence of their mode of action? date = 2014-12-17 pages = extension = .txt mime = text/plain words = 4715 sentences = 256 flesch = 36 summary = Surprisingly, the use of fluoroquinolones in indications other than bacterial infections has never been exploited, although not only nalidixic acid and its congener chloroquine exerts pleiotropic actions but, e.g., β-lactams and aminoglycosides are characterized by a broad range of biological activities too [47, 48] , so that a multitude of antimicrobial effects would not have been unusual. Fluoroquinolones inhibit not only enzymic activity of viral topoisomerases/helicases, but inhibit in vitro human immunodeficiency virus (HIV) reverse transcriptase as well; complete inhibition was observed at concentrations of ciprofloxacin and ofloxacin of 3 μM and norfloxacin of 1 μM, respectively [71] [72] [73] . Fluoroquinolones like ciprofloxacin, amifloxacin, enoxacin, norfloxacin, ofloxacin, pefloxacin, grepafloxacin, trovafloxacin, and 16 additional commercially available quinolones exhibit marked in vitro activity and in vivo efficacy against Plasmodium spp. cache = ./cache/cord-272943-q09i8fqu.txt txt = ./txt/cord-272943-q09i8fqu.txt === reduce.pl bib === id = cord-269352-0o3mryu1 author = Dhama, K. title = DNA vaccines and their applications in veterinary practice: current perspectives date = 2008-04-19 pages = extension = .txt mime = text/plain words = 6856 sentences = 339 flesch = 41 summary = Inoculation of plasmid DNA, encoding an immunogenic protein gene of an infectious agent, stands out as a novel approach for developing new generation vaccines for prevention of infectious diseases of animals. As an effective vaccine, plasmid DNA have a gene encoding a protective antigen of a pathogen, which when injected into host, is transcribed and translated, to induce a specific immune response. Regarding veterinary practice, the last few years have seen numerous trials of DNA vaccines against various animal diseases like foot and mouth disease (FMD) and herpes virus infection in cattle, Aujeszky's disease and classical swine fever in swine, rabies and canine distemper in canines, and avian influenza, infectious bronchitis, infectious bursal disease and coccidiosis in birds (Oshop et al. Besides, DNA vaccines have been developed against major viral infections of poultry like avian influenza, utilizing the HA gene of the virus (Kodihalli et al. cache = ./cache/cord-269352-0o3mryu1.txt txt = ./txt/cord-269352-0o3mryu1.txt === reduce.pl bib === id = cord-273993-rkqijcxn author = Menchaca, A. title = CRISPR in livestock: From editing to printing date = 2020-01-29 pages = extension = .txt mime = text/plain words = 6877 sentences = 331 flesch = 42 summary = When applied in large animals, CRISPR involves timeand cost-consuming projects, and it is mandatory not only to choose the best approach for genome editing, but also for embryo production, zygote microinjection or electroporation, cryopreservation and embryo transfer. In addition, we discuss some CRISPR applications to enhance livestock production in the context of a growing global demand of food, in terms of increasing efficiency, reducing the impact of farming on the environment, enhancing pest control, animal welfare and health. The wide range of CRISPR applications in large animals include improving productive traits, enhancing animal welfare through adaptation and resilience, conferring resistance to infectious and transmissible diseases, generating animal models for biomedical research, and suppressing other species considered as pests for livestock. Genome editing mediated by SCNT is applied by some laboratories in some kind of projects (e.g., multiplex editing), but the high efficiency of CRISPR after direct microinjection into zygotes has allowed an easier approach (sheep: [6, 7, 15, 16] ; goats: [9, 17] ; pigs: [11, 13] ). cache = ./cache/cord-273993-rkqijcxn.txt txt = ./txt/cord-273993-rkqijcxn.txt === reduce.pl bib === id = cord-267714-ji88tvsl author = JAKUPCIAK, JOHN P. title = Biological agent detection technologies date = 2009-04-21 pages = extension = .txt mime = text/plain words = 3526 sentences = 175 flesch = 35 summary = PCR-based methods have critical limitations, since they depend on a priori knowledge of what sequence to detect in a sample further complicated by recent demonstrations of greater variability in genomic sequence than expected. A platform for genome identification of a specimen from any source must not only be sensitive and specific, but must also detect a variety of pathogens with high accuracy, including modified or previously uncharacterized agents, and this challenge is daunting when identification must be achieved using nucleic acids in a complex sample matrix. The build-out of genome identification DNA sequencing technology in the form of practical instrumentation will be achieved by incorporating the critical requirements for accurate long reads, without dependency for template amplification, capable of manipulating terabytes of data to provide reliable and useful identification of genetic sequences within any unknown sample, whether clinical, environmental, or other type of specimen. cache = ./cache/cord-267714-ji88tvsl.txt txt = ./txt/cord-267714-ji88tvsl.txt === reduce.pl bib === id = cord-268549-2lg8i9r1 author = Dai, Qi title = Sequence comparison via polar coordinates representation and curve tree date = 2012-01-07 pages = extension = .txt mime = text/plain words = 4360 sentences = 272 flesch = 59 summary = It considers whole distribution of dual bases and employs polar coordinates method to map a biological sequence into a closed curve. First, many graphical representations were designed by assigning the single bases or dual nucleotides to corresponding direction/points/cells in Cartesian coordinates, so little attention has been paid to the whole distribution of the single nucleotide or dual nucleotides in biological sequences. Based on the whole distribution of the dual bases, we proposed a polar coordinates representation that maps a biological sequence into a closed curve. Here, we propose a novel graphical representation of DNA sequence in polar coordinates based on the distribution of the dual nucleotides. In contrast to the existing graphical representations, we used the whole distribution of the dual bases to map a biological sequence into a closed curve in polar coordinates. Analysis of similarity/dissimilarity of DNA sequences based on novel 2-D graphical representation cache = ./cache/cord-268549-2lg8i9r1.txt txt = ./txt/cord-268549-2lg8i9r1.txt === reduce.pl bib === id = cord-260042-cs0wp99n author = Khan, Samiullah title = Genes involved in mitochondrial biogenesis and function may not show synchronised responses to mitochondria in shell gland of laying chickens under infectious bronchitis virus challenge date = 2019-04-01 pages = extension = .txt mime = text/plain words = 6931 sentences = 362 flesch = 47 summary = The present study aimed to: a) determine mitochondrial counts in the cells of oviduct segments in laying hens at different time-points of egg formation in relation to the requirement of energy for egg production during IBV challenge; b) to determine the expression of nuclear DNA encoded genes in the shell gland to gain insights into their responses to IBV infection and time-points of egg-shell formation. Based on the lack of significant differences in mitochondrial count in the cells between the challenged and control groups for the magnum and isthmus, we focused further on shell gland tissue and studied the expression level of genes involved in mitochondrial density, biogenesis and fission. The lack of any significant difference in the relative expression levels of all of the genes except SDHA, between the control and IBV T challenged groups, may indicate that mitochondrial function may have been enhanced and thus overall egg quality may not have been affected by fewer mitochondria in the shell gland cells of IBV T infected hens. cache = ./cache/cord-260042-cs0wp99n.txt txt = ./txt/cord-260042-cs0wp99n.txt === reduce.pl bib === id = cord-273347-eyxc4rt0 author = Mohammadinejad, Reza title = In vivo gene delivery mediated by non-viral vectors for cancer therapy date = 2020-07-04 pages = extension = .txt mime = text/plain words = 7777 sentences = 485 flesch = 39 summary = We will also highlight the in vivo gene delivery mediated by non-viral vectors to treat cancer in different tissue and organs including brain, breast, lung, liver, stomach, and prostate. Since various routes of administration have been used to transfer non-viral delivery systems for gene therapy, it seems that the route is highly dependent on the characteristics of the carrier and nucleic acids as well the prepared complex and the final formulation. Synthesis and Application of a Novel Gene Delivery Vector for Non-Small-Cell Lung Cancer Therapy Chloroquine in combination with aptamer-modified nanocomplexes for tumor vessel normalization and efficient erlotinib/Survivin shRNA co-delivery to overcome drug resistance in EGFR-mutated non-small cell lung cancer Enhanced delivery of siRNA to triple negative breast cancer cells in vitro and in vivo through functionalizing lipid-coated calcium phosphate nanoparticles with dual target ligands Highly efficient cationic hydroxyethylated cholesterol-based nanoparticle-mediated gene transfer in vivo and in vitro in prostate carcinoma PC-3 cells cache = ./cache/cord-273347-eyxc4rt0.txt txt = ./txt/cord-273347-eyxc4rt0.txt === reduce.pl bib === id = cord-271504-t3y1w9ef author = Luo, Zichao title = Combating the Coronavirus Pandemic: Early Detection, Medical Treatment, and a Concerted Effort by the Global Community date = 2020-06-16 pages = extension = .txt mime = text/plain words = 14361 sentences = 795 flesch = 42 summary = A confirmed case should have at least one of the following criteria: (i) a positive result for 2019-nCoV nucleic acid, using real-time PCR tests from respiratory or blood samples; (ii) a high homogeneity between viral gene sequencing from respiratory or blood samples and known 2019-nCoV; and (iii) serum samples positive for IgM or IgG to 2019-nCoV, or seroconversion in IgG, or a fourfold or more significant increase in IgG antibody titer to 2019-nCoV in the recovery phase than in the acute phase [25] . Using blood samples taken from alleged COVID-19 patients, the researchers detected antibodies targeting the spike protein that prevented the virus from killing cells in laboratory tests. showed a promising in vitro inhibitory effect of this serine protease inhibitor in SARS-CoV and 2019-nCoV on human lung cells, showing potential as a viable option for COVID-19 treatment [113] . Given that antiviral drugs have previously demonstrated reasonable inhibition of coronaviruses and therapeutic efficacy against coronavirus outbreaks, umifenovir, chloroquine, hydroxychloroquine, lopinavir-ritonavir, and ribavirin have been recommended in the latest guidelines for diagnosis and treatment of COVID-19, updated on 17 February 2020 [189] . cache = ./cache/cord-271504-t3y1w9ef.txt txt = ./txt/cord-271504-t3y1w9ef.txt === reduce.pl bib === === reduce.pl bib === id = cord-264884-ydkigome author = Villarreal, Luis P. title = The Widespread Evolutionary Significance of Viruses date = 2008-07-05 pages = extension = .txt mime = text/plain words = 23138 sentences = 1203 flesch = 47 summary = For example, common structural motifs from phage to eukaryotic DNA viruses (T4 and herpesvirus) suggest very ancient links in virus evolution that span all domains of life (see below). On an evolutionary time-scale, the majority of viral lineages tend to exist as species-specifi c persistent (aka temperate, latent, and chronic) infections in which individual hosts will be colonized by mostly silent (asymptomatic) viruses for the duration of their life . It has distinct genetic, fi tness, and evolutionary characteristics that require intimate, host (tissue)-specifi c viral strategies and precise gene functions to attain stable maintenance in the presence of immunity and to allow biologically controlled reactivation. Thus, the phycodnaviruses appear to represent a basal but diverse viral lineage that has both acute and persistent lifestyle and have some clear relationships to most large eukaryotic DNA viruses and many phage. cache = ./cache/cord-264884-ydkigome.txt txt = ./txt/cord-264884-ydkigome.txt === reduce.pl bib === id = cord-264814-v4wnmg03 author = Flanagan, Katie L. title = Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines date = 2020-10-02 pages = extension = .txt mime = text/plain words = 15130 sentences = 700 flesch = 44 summary = Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. Comprehensive safety studies are particularly critical because some candidate vaccines use platform technologies that have not been examined extensively in human subjects to date, including some of the viral vectors, mRNA and nanoparticle constructs, and because of the potential for enhanced disease and adverse events related to aberrant immune responses to be seen upon infection pre-and post-licensure. cache = ./cache/cord-264814-v4wnmg03.txt txt = ./txt/cord-264814-v4wnmg03.txt === reduce.pl bib === id = cord-023095-4dannjjm author = nan title = Research Abstract Program of the 2011 ACVIM Forum Denver, Colorado, June 15–18, 2011 date = 2011-05-03 pages = extension = .txt mime = text/plain words = 134226 sentences = 6834 flesch = 51 summary = The purpose of this study was to determine the short-term effects of ivabradine on heart rate (HR), blood pressure, left ventricular (LV) systolic and diastolic function, left atrial (LA) performance, and clinical tolerance in healthy cats after repeated oral doses. The goal of this study was to investigate the relationship between heart rate and ECG time intervals to body mass in apparently healthy horses and ponies and to calculate normal ranges for different weight groups. This study aimed to investigate the prevalence of hypercoagulability in PLN dogs based on thromboelastography (TEG), and to determine whether hypercoagulability in these patients could be predicted by clinical assessments that identify systemic hypertension (systolic blood pressure 4 160 mmHg), hypoalbuminemia (serum albumin o 2.7 mg/dl), antithrombin activity (o 70%), and degree of proteinuria (urine protein:creatinine ratio [UPC] ! cache = ./cache/cord-023095-4dannjjm.txt txt = ./txt/cord-023095-4dannjjm.txt === reduce.pl bib === id = cord-267928-dflkggjt author = Kantola, Kalle title = Merkel cell polyomavirus DNA in tumor-free tonsillar tissues and upper respiratory tract samples: Implications for respiratory transmission and latency date = 2009-05-22 pages = extension = .txt mime = text/plain words = 2731 sentences = 162 flesch = 58 summary = STUDY DESIGN: Altogether 1390 samples from immunocompetent or immunocompromised patients, including (i) tonsillar tissues and sera from tonsillectomy patients; (ii) nasopharyngeal aspirates (NPAs) and sera from wheezing children and (iii) nasal swabs, sera and stools from febrile leukemic children were studied for MCPyV. RESULTS: MCPyV DNA was detected in 14 samples altogether; 8 of 229 (3.5%) tonsillar tissues, 3 of 140 (2.1%) NPAs, 2 of 106 (1.9%) nasal swabs and 1 of 840 (0.1%) sera. In this study MCPyV DNA was detected in clinical samples of many different types: nasal swabs and nasopharyngeal aspirates, tumor-free tonsillar tissues and sera. Among immunocompetent children, the absence of MCPyV from the 496 serum samples tested is in accordance with our recent study (in submission) in which the two other polyomaviruses KIPyV and WUPyV were absent from all of these sera. cache = ./cache/cord-267928-dflkggjt.txt txt = ./txt/cord-267928-dflkggjt.txt === reduce.pl bib === id = cord-264880-0tmd9knh author = Li, Zhao title = Picoliter Well Array Chip-Based Digital Recombinase Polymerase Amplification for Absolute Quantification of Nucleic Acids date = 2016-04-13 pages = extension = .txt mime = text/plain words = 5347 sentences = 260 flesch = 46 summary = We developed a picoliter well array (PWA) chip with 27,000 consistently sized picoliter reactions (314 pL) for isothermal DNA quantification using digital RPA (dRPA) at 39°C. To avoid thermal cycling, different isothermal amplification methods have been developed that rapidly amplify nucleic acids to detectable levels at a single temperature [42, 43] , such as loop-mediated amplification (LAMP) [44] , rolling circle amplification (RCA) [45] , helicasedependent amplification (HDA) [46] , nucleic acid sequence-based amplification (NASBA) [47] , recombinase polymerase amplification (RPA) [48] , transcription-mediated amplification (TMA) [49] , multiple displacement amplification (MDA) [50] , and strand-displacement amplification (SDA) [51] . Finally, we sealed the PWA chip in a homemade copper chamber filled with oil and successfully performed real-time dRPA on an isothermal incubation setup for the absolute quantification of serial dilutions of a Listeria monocytogenes gDNA stock solution. cache = ./cache/cord-264880-0tmd9knh.txt txt = ./txt/cord-264880-0tmd9knh.txt === reduce.pl bib === id = cord-266670-jxgywvwx author = Wong, Mark title = Chapter 13 Recent Advances and Future Needs in Environmental Virology date = 2007-09-06 pages = extension = .txt mime = text/plain words = 5842 sentences = 333 flesch = 39 summary = The standard method of detection of viral pathogens in environmental samples uses assays in mammalian cell culture. The standard method of detection of viral pathogens in environmental samples uses assays in mammalian cell culture. When realtime PCR quantitative results for adenoviruses in environmental samples were compared with conventional cell culture results, it was concluded that the real-time PCR method demonstrated higher quantities of adenoviruses in comparison with conventional techniques. Detection of astroviruses, enteroviruses, and adenovirus types 40 and 41 in surface waters collected and evaluated by the information collection rule and an integrated cell culture-nested PCR procedure Application of Real-Time PCR and Tissue Culture Assay for Adenovirus Detection in Two Southern California Urban Rivers Rapid and quantitative detection of human adenovirus DNA by real-time PCR Use of cell culture-PCR assay based on combination of A549 and BGMK cell lines and molecular identification as a tool to monitor infectious adenoviruses and enteroviruses in river water cache = ./cache/cord-266670-jxgywvwx.txt txt = ./txt/cord-266670-jxgywvwx.txt === reduce.pl bib === id = cord-273716-vv3pyft4 author = Khosravi-Darani, Kianoush title = The role of high-resolution imaging in the evaluation of nanosystems for bioactive encapsulation and targeted nanotherapy date = 2007-07-03 pages = extension = .txt mime = text/plain words = 10230 sentences = 514 flesch = 34 summary = This review will focus on nanoscale bioactive delivery and targeting mechanisms and the role of high-resolution imaging techniques in the evaluation and development of nanocarriers. Applications of nanotechnology in medicine are particularly promising and areas such as molecular imaging, disease diagnosis, bioactive encapsulation and targeted delivery at specific sites in the body are being intensively investigated and some products undergoing clinical trials (Moghimi et al., 2005; Shaffer, 2005; Wilkinson, 2003) . Usefulness of high-resolution scanning probe imaging in the study of lipidic gene transfer vectors and the interaction between liposomes and DNA molecules have recently been reviewed by Mozafari et al. Modern nanocarrier systems such as nanoliposomes, niosomes, solid lipid nanoparticles (Saupe and Rades, 2006) , as well as silicon-, carbon-and polymer-based nanocarriers play an important role in controlled delivery of the bioactive agents to the desired site of action, limiting the side effects at nontarget sites (Ruozi et al., 2007) . cache = ./cache/cord-273716-vv3pyft4.txt txt = ./txt/cord-273716-vv3pyft4.txt === reduce.pl bib === id = cord-262353-iips79vo author = Veltkamp, Henk-Willem title = Disposable DNA Amplification Chips with Integrated Low-Cost Heaters † date = 2020-02-25 pages = extension = .txt mime = text/plain words = 9618 sentences = 540 flesch = 57 summary = Based on the analysis of the milling process, metal adhesion studies, and COMSOL MultiPhysics heat transfer simulations, the first batch of chips has been fabricated and successful multiple displacement amplification reactions are performed inside these chips. The work presented at the 4th Microfluidic Handling Systems conference and which is extended in this paper aims at the development of a disposable, polymer-based DNA amplification lab-on-chip system with integrated resistive heater based on the World Health Organization (WHO) Sexually Transmitted Diseases Diagnostics Initiative (SDI) ASSURED criteria. The aim of this study was to fabricate biocompatible, low-cost, and disposable chips with integrated heater, which should be able to perform DNA amplification, and possible in situ fluorescence detection in the near future. The integrated resistive heaters on the chips were characterized and showed a temperature stability of ±2 • C over a time period of 25 h, which is at least twelve-fold longer than the required operating times for DNA amplification reactions [6, [8] [9] [10] [11] . cache = ./cache/cord-262353-iips79vo.txt txt = ./txt/cord-262353-iips79vo.txt === reduce.pl bib === id = cord-272579-aenuyht0 author = Emmett, Stevan R. title = The Cell Cycle and Virus Infection date = 2005 pages = extension = .txt mime = text/plain words = 6456 sentences = 388 flesch = 60 summary = A number of different viruses interact with the cell cycle in order to subvert host-cell function and increase the efficiency of virus replication; examples can be found from DNA, retro, and RNA viruses. The majority of studies have been conducted on DNA and retroviruses whose primary site of replication is the nucleus, but increasingly a number of researchers are demonstrating that RNA viruses, whose primary site of replication is normally the cytoplasm, also interfere with the cell cycle. Viral interference with the cell cycle can have a myriad of different effects to improve virus infection, for example to promote replication of viral DNA genomes, or to delay the cell cycle to allow sufficient time for RNA virus assembly. Increasingly we have found that proteomic approaches allow the rapid analysis of a whole plethora of cell cycle proteins that may be affected by virus infection. cache = ./cache/cord-272579-aenuyht0.txt txt = ./txt/cord-272579-aenuyht0.txt === reduce.pl bib === id = cord-271241-w1q46y63 author = Ruggiero, Emanuela title = Viral G-quadruplexes: New frontiers in virus pathogenesis and antiviral therapy date = 2020-05-18 pages = extension = .txt mime = text/plain words = 8912 sentences = 495 flesch = 45 summary = Since the genomes of viruses are remarkably variable, high conservation rates strongly suggest a crucial role of G4s in the viral replication cycle and evolution, emphasizing the possibility of targeting viral G4s as a new pharmacological approach in antiviral therapy. 1 In the past few decades, pharmaceutical and biotechnological advance has succeeded in developing new therapeutics for the management of different viral diseases: for example, anti-retroviral therapy against the human immunodeficiency virus (HIV), or the pan-genotypic direct-acting antiviral drugs used for hepatitis C (HCV) management. In addition, such PQSs are highly conserved, despite the high recombination rates that characterize viruses, suggesting a crucial role for G4s in viral evolution and replication, and corroborating their targeting as a valid pharmacological approach for antiviral therapy. cache = ./cache/cord-271241-w1q46y63.txt txt = ./txt/cord-271241-w1q46y63.txt === reduce.pl bib === id = cord-275886-502es8qm author = Chailapakul, Orawon title = Paper-based sensors for the application of biological compound detection date = 2020-06-05 pages = extension = .txt mime = text/plain words = 7032 sentences = 365 flesch = 40 summary = Other venerable methods such as complex formation [12] and Griess test [13] were reported in the early development of PADs. The surface of nanoparticles can be modified with specific probe using precious metal and sulphur formation [14] which increases the selectivity of the materials towards target analytes. In 2009, our group reported for the first time an enzymatic electrochemical method based on paper based analytical device (PADs) for the simultaneous determination of uric acid, glucose and lactate in biological fluids. In order to improve the DNA based sensor to be an alternative sensor designed for point-of-care (POC) application, it has been quickly integrated into paper-based analytical devices (PADs) providing a low cost, simple and rapid diagnostic platform especially for developing countries and resourcelimited areas. [39] developed a paper-based electrochemical DNA biosensor using the acpcPNA probe labelled with anthroquinone (AQ) for detecting highrisk human papillomavirus (HPV) type 16 (Fig. 12) . cache = ./cache/cord-275886-502es8qm.txt txt = ./txt/cord-275886-502es8qm.txt === reduce.pl bib === id = cord-262870-r3w44mg0 author = Duval, R.-E. title = Interest of designed cyclodextrin-tools in gene delivery date = 2012-11-30 pages = extension = .txt mime = text/plain words = 3768 sentences = 189 flesch = 42 summary = Among them, Capillary electrophoresis (CE) was used to perfectly characterize our CyD-siRNA and CyD-DNA complexes and shown to be a very attractive method with advantages of low sample consumption, rapid analysis speed, and high efficiency that make this technology a major tool for association constant measurement. Finally, we present the different biological methods that can be used, in vitro, to study gene delivery, and more precisely ones we have performed to evaluate the capability of our original model bis-guanidinium-tetrakis-β-cyclodextrin dendrimeric tetrapod, to deliver efficiently DNA or siRNA in eukaryotic cells. In this part, we present the different biological methods that can be used, in vitro, to study gene delivery, and more precisely ones we have performed to evaluate the capability of our original model, i.e. bis-guanidiniumtetrakis-␤-cyclodextrin dendrimeric tetrapod, to deliver efficiently DNA or siRNA [18, 20] . cache = ./cache/cord-262870-r3w44mg0.txt txt = ./txt/cord-262870-r3w44mg0.txt === reduce.pl bib === id = cord-269839-jxqs51o5 author = Bitome-Essono, Paul-Yannick title = Tracking zoonotic pathogens using blood-sucking flies as 'flying syringes' date = 2017-03-28 pages = extension = .txt mime = text/plain words = 5875 sentences = 319 flesch = 57 summary = This study demonstrates that using hematophagous flies as 'flying syringes' constitutes an interesting approach to investigate blood-borne pathogen diversity in wild vertebrates and could be used as an early detection tool of zoonotic pathogens. The omnipresence of hematophagous flies in certain habitats and their opportunistic blood-feeding behaviour (Muturi et al., 2011; Muzari et al., 2010; Späth, 2000) make of them compelling candidates to obtain blood meals from different vertebrate hosts for pathogen detection. In the present study, we investigated the possibility of using hematophagous flies as 'flying syringes' to explore the diversity of extant malaria parasites (Haemosporida) infecting wild vertebrates living in the forests of Gabon (Central Africa). Overall, the blood meal origin was successfully identified in 428 fly samples (35%) using a PCR system amplifying long fragments of Cytb (450 bp) or COI genes (330 bp or 660 bp). In this study, we tested whether hematophagous flies could be used as 'flying syringes' to identify blood-borne pathogens circulating in the wild vertebrate fauna of Gabon. cache = ./cache/cord-269839-jxqs51o5.txt txt = ./txt/cord-269839-jxqs51o5.txt === reduce.pl bib === id = cord-267733-fuz8r3vj author = Al Ali, Sally title = Use of Reporter Genes in the Generation of Vaccinia Virus-Derived Vectors date = 2016-05-21 pages = extension = .txt mime = text/plain words = 7966 sentences = 392 flesch = 41 summary = This broad host range allows infection of cell lines with recombinant viruses for large-scale expression of heterologous proteins, which reduces its cost This broad host range allows infection of cell lines with recombinant viruses for large-scale expression of heterologous proteins, which reduces its cost in comparison to other production systems [21, 24] . This reporter gene system has been widely used in transgenic plants, and it has also been successfully used in mammalian cells for VACV recombinant virus selection [54] . Reporter-gene assays have helped the pox virologists in basic research, for example for the study of the location, structure and function of many VACV proteins during the infection cycle and their interaction with proteins of the host cell [44, 70] . The main limitation of using VACV as a vector is the short-term gene expression, since it is a lytic virus killing the infected cells. Insertion sites for recombinant vaccinia virus construction: Effects on expression of a foreign protein cache = ./cache/cord-267733-fuz8r3vj.txt txt = ./txt/cord-267733-fuz8r3vj.txt === reduce.pl bib === id = cord-272357-fxe49zen author = Campolongo, Michael J. title = DNA nanomedicine: Engineering DNA as a polymer for therapeutic and diagnostic applications() date = 2010-04-30 pages = extension = .txt mime = text/plain words = 7365 sentences = 419 flesch = 43 summary = Nanomedicine, the application of nanotechnology to medicine, encompasses a broad spectrum of fields including molecular detection, diagnostics, drug delivery, gene regulation and protein production. There are a variety of systems that take advantage of the hybridisation of linear DNA for nanomedicine applications, including oligonucleotide sensing, multiplexed pathogen detection, aptameric drug delivery and diagnostics, as well as stimuli-responsive hydrogels. Notably, a nanoparticle-based biobarcode assay was developed for the ultrasensitive detection of biomolecules, such as proteins [44] [45] [46] [47] [48] , messenger RNA (mRNA) [49] and the human immunodeficiency virus (HIV)-1 antigen [50] , as well as for the multiplexed detection with high selectivity but without the need for enzymatic target amplification and labelling [28, 47] (Fig. 2B) . Over the past 17 years, aptamers have been generated against a wide array of molecular targets, including many known proteins, carbohydrates, lipids, nucleotides and other small molecules, as well as highly complex structures such as viruses [64] [65] [66] . cache = ./cache/cord-272357-fxe49zen.txt txt = ./txt/cord-272357-fxe49zen.txt === reduce.pl bib === id = cord-269426-82g5eiyg author = Holman, David H. title = Viral Vectors date = 2009-01-30 pages = extension = .txt mime = text/plain words = 8734 sentences = 420 flesch = 40 summary = Abstract Traditional vaccine development platforms such as live-attenuated virus, killed virus, or recombinant subunit-based vaccines are often effective in eliciting long-term immunity to a number of infectious human pathogens. Finally, it is suggested that vaccination by alternate routes of administration (such as oral or intranasal) rather than injection can overcome pre-existing vector immunity ( Appaiahgari et al., 2006 ; Xiang et al., 2003 ) , which is supported by data from a human clinical trial ( Van Kampen et al., 2005 Lusky et al., 1998 ; Moorhead et al., 1999 ) or the E4 region ( Dedieu et al., 1997 ; Gao et al., 1996 ) of the Ad genome, which reduced or eliminated the expression of E2 or E4 proteins. High-level primary CD8( ϩ ) T-cell response to human immunodeficiency virus type 1 gag and env generated by vaccination with recombinant vesicular stomatitis viruses cache = ./cache/cord-269426-82g5eiyg.txt txt = ./txt/cord-269426-82g5eiyg.txt === reduce.pl bib === id = cord-274644-gr1eaj6k author = Chen, Zhao-Chi title = Thermally stable and uniform DNA amplification with picosecond laser ablated graphene rapid thermal cycling device date = 2019-12-15 pages = extension = .txt mime = text/plain words = 5152 sentences = 265 flesch = 59 summary = This study reports a straightforward fabrication technique for patterning an on-chip graphene-based device with hole arrays, in which the mechanism of surface structures can achieve stable and uniform thermal control for the amplification of DNA fragments. Our results demonstrated that the proposed integration of a graphene-based device and a laser-pulse ablation process to form a thin-film PCR device has cost benefits in a small-volume reagent and holds great promise for practical medical use of DNA amplification. DNA amplification is performed using thermal cycling, with a high degree of control of stable and uniform temperature distribution being attributed to array structures (Bigham et al., 2017; Seo et al., 2018) , microchannel heat exchangers (Riera et al., 2013) , membrane-based microfluidics (Chen and Shen, 2017) , and doped hybrid materials (Seo et al., 2016) . cache = ./cache/cord-274644-gr1eaj6k.txt txt = ./txt/cord-274644-gr1eaj6k.txt === reduce.pl bib === id = cord-274049-3gw65kpu author = Zhang, Han title = CRISPR Editing in Biological and Biomedical Investigation date = 2017-05-31 pages = extension = .txt mime = text/plain words = 6583 sentences = 333 flesch = 40 summary = © 2017 Wiley Periodicals, Inc. nucleases (ZFN) and transcription activator-like effector nucleases (TALEN), have enabled the manipulation of genes by targeting DNA double-stranded breaks (DSBs) via non-homologous end-joining (NHEJ) or homology-directed repair (HDR) pathways [Rudin et al., 1989; Rouet et al., 1994; Choulika et al., 1995; Bibikova et al., 2002; Moscou and Bogdanove, 2009 ]. Overall, these studies empower a broader range of disease modeling applications via CRISPR-Cas9-mediated genome engineering, allowing researchers to uncover fundamental mechanisms in disease initiation, maintenance and procession, and explore the therapeutic potential of the CRISPR-Cas9 system to correct disease-causing mutations. Owing to its ability to completely disrupt target genes and the simplicity of designing potent sgRNAs, the CRISPR-Cas9 system has been extended to large-scale loss-of-function (LOF) genome screens in human cells [Koike-Yusa et al., 2014; Shalem et al., 2014; Wang et al., 2014; Zhou et al., 2014] . Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease cache = ./cache/cord-274049-3gw65kpu.txt txt = ./txt/cord-274049-3gw65kpu.txt === reduce.pl bib === id = cord-274128-kgtr77e7 author = Hochstetter, Axel title = Lab-on-a-Chip Technologies for the Single Cell Level: Separation, Analysis, and Diagnostics date = 2020-04-29 pages = extension = .txt mime = text/plain words = 14656 sentences = 748 flesch = 49 summary = Given the vast adaptability of microfluidics to any kind of single or multi-cellular assay [63] , the ability to combine it with various light microscopy techniques [64] , image processing [65] , optical or acoustic traps [53] , generation of chemical gradients [66] , and even cell culture [4, [67] [68] [69] [70] [71] [72] [73] [74] [75] [76] [77] [78] [79] [80] [81] [82] [83] , any cellular or subcellular target seems to be possible for future on-chip diagnostics. If the sample is in the continuous phase, we can separate the target cells either using deterministic lateral displacement (DLD), ratchets, dean-flow, di-electrophoresis, surface acoustic waves (SAW), optical and acoustic tweezers or by using optical density/refractive index. cache = ./cache/cord-274128-kgtr77e7.txt txt = ./txt/cord-274128-kgtr77e7.txt === reduce.pl bib === id = cord-276101-quis0c6e author = Hamula, Camille L.A. title = Selection and analytical applications of aptamers binding microbial pathogens date = 2011-09-09 pages = extension = .txt mime = text/plain words = 4741 sentences = 259 flesch = 51 summary = This article describes recent advances in the development of aptamers targeting specific pathogens (e.g., live bacteria, whole viral particles, and virally-infected mammalian cells). Specific aptamers against pathogens have been used as affinity reagents to develop sandwich assays, to label and to image cells, to bind with cells for flow-cytometry analysis, and to act as probes for development of whole-cell biosensors. Aptamers can be chemically modified and incorporated into a variety of simple assays for pathogen detection, as well as more complex assay formats, including flow cytometry, cell imaging, and aptamerbased biosensors. Aptamers binding to the cell surface can be used to purify and to identify their respective target molecules post-SELEX. The aptamers were shown to bind different cell-surface targets via a competitive flow-cytometry experiment; using five aptamers combined, rather than individually, was superior at detecting bacteria in pyogenic fluid. cache = ./cache/cord-276101-quis0c6e.txt txt = ./txt/cord-276101-quis0c6e.txt === reduce.pl bib === id = cord-277318-cwuls6xs author = Visscher, Koen title = −1 Programmed Ribosomal Frameshifting as a Force-Dependent Process date = 2016-02-02 pages = extension = .txt mime = text/plain words = 8568 sentences = 455 flesch = 48 summary = 13 A recent single-molecule experiment indicates that ribosome helicase action during the translational elongation cycle may be twofold: it destabilizes the helical junction at the mRNA entry site favoring an open conformation, and it appears to pull mRNA strands apart during the translocation step when relatively large structural rearrangements occur on the ribosome. 26 We will review methods and experiments that apply force to the single molecules to determine the mechanical properties of codon-anticodon interaction at the slippery site, the stability of downstream mRNA structure motifs that give rise to −1 PRF, and elastic properties of the ssRNA elasticity bridging those elements. 104, 105 Single-molecule assays that probe the codon-anticodon dynamics at the slippery sequence and investigate the force dependence of the translation elongational cycle (discussed later in the chapter; see Fig. 8 ) should be fit to answer these questions and allow unfolding of −1 PRF mRNA structure motifs held at the ribosome's entry site. cache = ./cache/cord-277318-cwuls6xs.txt txt = ./txt/cord-277318-cwuls6xs.txt === reduce.pl bib === === reduce.pl bib === id = cord-267671-ys43n672 author = Whary, Mark T. title = Biology and Diseases of Mice date = 2015-07-10 pages = extension = .txt mime = text/plain words = 63666 sentences = 3678 flesch = 40 summary = Clinical Signs MCMV causes subclinical infection in adult immunocompetent mice, but experimental inoculation of neonates can cause lethal disease due to multisystemic necrosis and inflammation. Diagnosis Because infected mice do not manifest signs or lesions and the virus is very difficult to propagate in cell culture, detection and diagnosis rely on serology and molecular methods. Differential Diagnosis Reovirus infection must be differentiated from other diarrheal diseases of infant mice, including those caused by mouse coronaviruses, EDIM virus, Salmonella spp., or Clostridium piliforme. Epizootiology EDIM virus appears to be infectious only for mice and occurs episodically in mouse colonies, and infection is probably widespread geographically (Livingston and Riley, 2003; Pritchett-Corning LABORATORY ANIMAL MEDICINE et al., 2009) . Sentinel mouse surveillance, using soiled bedding, is an effective strategy for detecting MNV (Manuel et al., 2008) Differential Diagnosis The mild change in fecal consistency associated with MNV in adult mice may mimic rotavirus, coronavirus, Helicobacter spp., Citrobacter rodentium, or other enteric diseases. cache = ./cache/cord-267671-ys43n672.txt txt = ./txt/cord-267671-ys43n672.txt === reduce.pl bib === id = cord-276335-e1xlwcvc author = Poh, W.P. title = Characterization of cytotoxic T‐lymphocyte epitopes and immune responses to SARS coronavirus spike DNA vaccine expressing the RGD‐integrin‐binding motif date = 2009-05-27 pages = extension = .txt mime = text/plain words = 6046 sentences = 326 flesch = 52 summary = Significant cell‐mediated immune responses were characterized by cytotoxic T‐lymphocyte (51)Cr release assay and interferon‐gamma secretion ELISPOT assay against RMA‐S target cells presenting predicted MHC class I H2‐Kb epitopes, including those spanning residues 884–891 and 1116–1123 within the S2 subunit of SARS‐CoV spike protein. The production of antigen-specific antibody induced by the SARS-CoV spike DNA vaccinations was assessed For the MHC-peptide binding assay, the mean fluorescence increase (MFI) was calculated as the ratio of the fluorescence of peptide-loaded RMA-S cells to the fluorescence of unloaded RMA-S cells. Mouse IFN-g ELISPOT for splenocytes of C57BL/6 mice immunized with selected S-His and S-RGD/His DNA vaccines to confirm T-cell epitopes of spike protein. This study demonstrated that prime-boost immunization of mice with SARS-CoV spike DNA vaccine constructs S-His and S-RGD/His induced significant antigen-specific cellular immune responses, IFN-g stimulation, and CTL activation. cache = ./cache/cord-276335-e1xlwcvc.txt txt = ./txt/cord-276335-e1xlwcvc.txt === reduce.pl bib === id = cord-270082-byxd4o4m author = Doheny, Kimberly Floy title = Identification of essential components of the S. cerevisiae kinetochore date = 1993-05-21 pages = extension = .txt mime = text/plain words = 9918 sentences = 556 flesch = 54 summary = Readthrough Assay and Secondary Screen of the ctf Collection When transcription from a strong promoter is initiated toward a CEN DNA sequence, the mitotic segregational function of the centromere is destroyed (Hill and Bloom, 1987) without disruption of its 180-220 bp nuclease protected region (Bloom et al., 1984; Hill and Bloom, 1987) , indicating that at least some of the kinetochore complex remains intact. To test the hypothesis that a CfN DNA-protein complex was responsible for the transcriptional block, we replaced the wild-type CENG sequence with a CEN6 sequence containing a single-nucleotide point mutation (CDEIII-15C) in the central element of the palindrome of CDEIII (CCG). Of 34 cff mutants screened (see Experimental Procedures for list), 7 were identified as putative kinetochore mutants because they produced an intermediate level of blue colony color between the levels of the CTF+ strains carrying the wild-type and mutant CEN reporters. cache = ./cache/cord-270082-byxd4o4m.txt txt = ./txt/cord-270082-byxd4o4m.txt === reduce.pl bib === id = cord-274707-mxh38hwd author = Laureano, Ana Flávia Santarine title = The different tests for the diagnosis of COVID-19 - A review in Brazil so far date = 2020 pages = extension = .txt mime = text/plain words = 3736 sentences = 204 flesch = 50 summary = The virus is now widespread and causing the current pandemic of COVID-19, a highly pathogenic viral pneumonia, commonly presented with fever and cough, which frequently lead to lower respiratory tract disease with poor clinical outcomes associated with older age and underlying health conditions. Most rapid tests use colloidal gold particles in a technique known as immunochromatography, also called lateral flow immunoassay, a type of sandwich assay that relies on a pair of antibodies used to recognize two independent epitopes of a protein, and therefore it can achieve high specificity (Zhou et al., 2012) . One of the first rapid tests (lateral flow immunoassay) for SARS-CoV-2 IgG and IgM immune responses was developed by professor's Feng Ye group at the National Clinical Research Centre for Respiratory Disease in Guangzhou, China. Development and Clinical Application of A Rapid IgM-IgG Combined Antibody Test for SARS-CoV-2 Infection Diagnosis cache = ./cache/cord-274707-mxh38hwd.txt txt = ./txt/cord-274707-mxh38hwd.txt === reduce.pl bib === id = cord-276271-3nz3169p author = Deborggraeve, Stijn title = T. cruzi OligoC-TesT: A Simplified and Standardized Polymerase Chain Reaction Format for Diagnosis of Chagas Disease date = 2009-06-02 pages = extension = .txt mime = text/plain words = 4732 sentences = 261 flesch = 52 summary = cruzi OligoC-TesT: A Simplified and Standardized Polymerase Chain Reaction Format for Diagnosis of Chagas Disease The specificity and sensitivity of the assay were evaluated on blood samples from 60 Chagas non-endemic and 48 endemic control persons and on biological samples from 33 patients, 7 reservoir animals, and 14 vectors collected in Chile. We assessed the diagnostic accuracy of the assay on a broad spectrum of biological samples from Chagas non-endemic and endemic control persons, infected children, adults, reservoir animals and vectors. DNA from 25 different Trypanosoma rangeli isolates (Table 1) and from Leishmania donovani, Trypanosoma brucei gambiense, Mycobacterium tuberculosis, Schistosoma mansoni and Plasmodium falciparum was obtained from other research groups. cruzi OligoC-TesT, a simple and standardized dipstick format for detection of PCR amplified T. cruzi OligoC-TesT, a simple and standardized dipstick format for detection of PCR amplified T. cache = ./cache/cord-276271-3nz3169p.txt txt = ./txt/cord-276271-3nz3169p.txt === reduce.pl bib === id = cord-275232-0sg0hv9w author = Yeung, Siu-Wai title = A DNA biochip for on-the-spot multiplexed pathogen identification date = 2006-09-25 pages = extension = .txt mime = text/plain words = 3241 sentences = 162 flesch = 41 summary = The DNA-based identification of the two model pathogens involved a number of steps including a thermal lysis step, magnetic particle-based isolation of the target genomes, asymmetric PCR, and electrochemical sequence-specific detection using silver-enhanced gold nanoparticles. The assay involves the following steps: (i) sample preparation using thermal cell lysis and magnetic particle-based target genome isolation; (ii) target DNA amplification by the PCR; (iii) hybridization of the amplicons to their complementary oligonucleotide capture probes immobilized onto individual detection electrode surfaces and (iv) electrochemical transduction of the recognition event via gold nanoparticles with signal amplification using electrocatalytic silver deposition (10) . The three main steps were (A) sample preparation: thermal cell lysis and magnetic particle-based isolation of specific genomic DNAs; (B) target DNA amplification: generation of single-stranded rich amplicons by asymmetric PCR; (C) product detection: gold nanoparticle labeling, electrocatalytic silver deposition, and electrochemical silver dissolution. cache = ./cache/cord-275232-0sg0hv9w.txt txt = ./txt/cord-275232-0sg0hv9w.txt === reduce.pl bib === id = cord-278249-vvhq9vgp author = Blot, Mathieu title = CXCL10 could drive longer duration of mechanical ventilation during COVID-19 ARDS date = 2020-11-02 pages = extension = .txt mime = text/plain words = 6238 sentences = 346 flesch = 45 summary = In addition, since most patients need to undergo mechanical ventilation in this context, ventilator-induced lung injury (VILI) could exacerbate tissue damage as well as local and systemic inflammation, thus acting as a "second hit." Our team has previously shown that mitochondrial alarmins (i.e., mitochondrial DNA) are released by human epithelial cells submitted to cyclic stretch, and these alarmins are also recovered from bronchoalveolar lavage (BAL) fluid obtained from either ventilated rabbits or ARDS patients. This comprehensive evaluation of systemic and pulmonary immune response showed that the higher CXCL10 concentrations in both the systemic and alveolar compartments of patients with COVID-19 ARDS were associated with a longer duration of mechanical ventilation. Finally, in both COVID-19 and non-COVID-19 patients, higher mitochondrial DNA concentrations in the plasma and ELF compartment were highly correlated with alveolar inflammation, as assessed by BALF cell count and ELF IL-8 and IL-1β concentrations. cache = ./cache/cord-278249-vvhq9vgp.txt txt = ./txt/cord-278249-vvhq9vgp.txt === reduce.pl bib === id = cord-277054-eq4obbte author = Kaur, Manpreet title = Rabies DNA vaccine: No impact of MHC Class I and Class II targeting sequences on immune response and protection against lethal challenge date = 2009-03-26 pages = extension = .txt mime = text/plain words = 6906 sentences = 378 flesch = 45 summary = The potency of modified DNA vaccines assessed by total antibody response, antibody isotypes, cytokine profile, neutralizing antibody titer and protection conferred against in vivo challenge; was enhanced in comparison to native unmodified vaccine, but the response elicited did not pertain to the type of target sequence and the directed arm of immunity. The ability of these DNA vaccines to elicit protective responses in immunized mice was assessed by intracerebral challenge with 20 LD 50 of virulent rabies virus CVS strain. In an effort to develop an optimal DNA vaccine against rabies virus, this study was aimed at evaluating the immune enhancement potential of different antigen targeting strategies to selectively improve responses mediated by CD8 + and CD4 + T lymphocytes and by antibodies, induced after intramuscular immunization with DNA plasmids. also reported that DNA vaccine encoding rabies virus glycoprotein lacking transmembrane domain though enhances antibody response but does not confer protection [35] . cache = ./cache/cord-277054-eq4obbte.txt txt = ./txt/cord-277054-eq4obbte.txt === reduce.pl bib === id = cord-279503-w4tn03w0 author = Kim, Hanbi title = Development of Label-Free Colorimetric Assay for MERS-CoV Using Gold Nanoparticles date = 2019-05-07 pages = extension = .txt mime = text/plain words = 3541 sentences = 185 flesch = 49 summary = In this study, we propose a colorimetric assay based on an extended form of double-stranded DNA (dsDNA) self-assembly shielded gold nanoparticles (AuNPs) under positive electrolyte (e.g., 0.1 M MgCl(2)) for detection of Middle East respiratory syndrome coronavirus (MERS-CoV). This assay could be highly reliable for MERS-CoV diagnosis as we have followed WHO updated recommendations for infectious disease laboratory testing, which targets the two regions on MERS-CoV considered for potential preclinical screening and high sensitivity 20 The developed assay platform was able to detect the target DNA through optical properties of the gold nanoparticles such as color changes with the naked eye and spectral shifts on UV− vis wavelength. We proposed a colorimetric assay using disulfide bonds formed by hybridizing with thiolated probes and a target; this method inhibited the aggregation of AuNPs by salt and limits the color change for diagnosis of MERS. cache = ./cache/cord-279503-w4tn03w0.txt txt = ./txt/cord-279503-w4tn03w0.txt === reduce.pl bib === id = cord-274080-884x48on author = Rumlová, Michaela title = In vitro methods for testing antiviral drugs date = 2018-06-30 pages = extension = .txt mime = text/plain words = 17989 sentences = 941 flesch = 41 summary = For the majority of animal viruses, the activation of these fusion or penetration mechanisms occurs through conformational changes and structural rearrangements in viral surface proteins and/or the whole virion shell that may destabilize the capsid core. D: Three mechanisms (I.-III.) of DNA viruses replication are shown: (I): Following entry and uncoating, the DNA genome is transported to the nucleus; products of early genes (regulatory proteins, transcription factors) regulate the synthesis of viral enzymes (e.g. DNA polymerase) required for genome replication; expression of late genes encoding structural capsid proteins in the cytosol, they are then transported into nucleus where packaging and pre-assembly take place; preassembled procapsids exit the nucleus and leave the cell (e.g. Herpesviruses). Here, we provide an overview of in vitro methods, including cell-based assays, that may be suitable for screening of antivirotics that interfere with the key steps of viral life cycles and target either virus or cell-encoded proteins required for the infectivity. cache = ./cache/cord-274080-884x48on.txt txt = ./txt/cord-274080-884x48on.txt === reduce.pl bib === id = cord-278081-tk7vn1v1 author = Brooks, Wesley H. title = Viral Impact in Autoimmune Diseases: Expanding the “X Chromosome–Nucleolus Nexus” Hypothesis date = 2017-11-28 pages = extension = .txt mime = text/plain words = 9823 sentences = 457 flesch = 42 summary = Here is presented new details to the hypothesis, explaining how the disrupted chromatin can lead to subsequent disruption of the nucleolus, even nucleolar fragmentation, which results in ineffective nucleolar functioning, misfolded RNAs, misassembled or incompletely assembled ribonucleoprotein (RNP) complexes, and stabilization of nucleolar components in autoantigenic conformations. For now there is no direct connection between viruses and the "X chromosome-nucleolus nexus" hypothesis to the increased risk of cancers among autoimmune disease patients but we can consider the induction by viruses of increased polyamine levels and the possible reactivation of X-linked polyamine genes as means by which competition for the cellular methyl donor, SAM, could reduce DNA methylation and open oncogenes for overexpression in proliferation competent cells. A disrupted Barr body could generate an abundance of polyamines and Alu RNA from X-linked genes and elements that further stress and damage the nucleolus, making it very inefficient in its functions, even fragmenting it and possibly leading to cell death. cache = ./cache/cord-278081-tk7vn1v1.txt txt = ./txt/cord-278081-tk7vn1v1.txt === reduce.pl bib === id = cord-279267-iyobsuvz author = Hacker, David L. title = Polyethyleneimine-based transient gene expression processes for suspension-adapted HEK-293E and CHO-DG44 cells date = 2013-11-30 pages = extension = .txt mime = text/plain words = 7064 sentences = 364 flesch = 49 summary = Abstract Transient gene expression (TGE) from mammalian cells is an increasingly important tool for the rapid production of recombinant proteins for research applications in biochemistry, structural biology, and biomedicine. Here we review methods for the transfection of human embryo kidney (HEK-293) and Chinese hamster ovary (CHO) cells in suspension culture using the cationic polymer polyethylenimine (PEI) for gene delivery. Currently, the two major approaches to rapid protein production are non-viral transient gene expression (TGE) 1 using mammalian cells [7] [8] [9] [10] [11] and infection of insect cells with a baculovirus expression vector [12, 13] . These cells were used as the host for the TGE method described here because they are efficiently transfected, grow to a high density in suspension culture, and are widely used in the biopharmaceutical industry to generate stable cell lines for the production of therapeutic proteins [1] . cache = ./cache/cord-279267-iyobsuvz.txt txt = ./txt/cord-279267-iyobsuvz.txt === reduce.pl bib === id = cord-278397-u33x4jaw author = Abe, Takayuki title = Negative Regulation of Cytosolic Sensing of DNA date = 2018-10-29 pages = extension = .txt mime = text/plain words = 7194 sentences = 377 flesch = 41 summary = Recent efforts have focused on identifying relevant immune surveillance sensors and components of downstream signaling-Toll-like receptors (TLRs) and their cognate ligands, cytosolic sensing of RNA (primary mediated by the RIG-I/IPS-1 axis), cytosolic sensing of DNA (primary mediated by the cGAS/STING axis), and the inflammasome pathway (primary mediated by NOD-like receptors; NLRs) (Broz and Monack, 2013; Kieser and Kagan, 2017; Kumar et al., 2011a ). It has also been suggested that chronic cGAS/STING activation induced by self DNA may be responsible for induction of aberrant inflammatory diseases like systemic lupus erythematosus (SLE), Aicardi-Goutières syndrome (AGS), and polyarthritis (Barber, 2015; Crowl et al., 2017) . Use of DNA damage induced agents like 7,12-dimethylbenz-α-anthracene (DMBA) has helped shed light on the underlying events initiate the DNA damage-induced immune response via cytosolic DNA sensing pathway and implicates nucleosome leakage in eliciting cGAS/STING-dependent signal activation via recognition of self-DNA (Barber, 2015) . cache = ./cache/cord-278397-u33x4jaw.txt txt = ./txt/cord-278397-u33x4jaw.txt === reduce.pl bib === id = cord-279084-bbae1qyx author = Liu, Bin title = Free DNA, a reason for severe COVID-19 infection? date = 2020-05-05 pages = extension = .txt mime = text/plain words = 799 sentences = 61 flesch = 63 summary = I hypothesized that the damage induced by free DNA is a reason for severe COVID-19, which can explain many symptoms of this disease, such as cytokine storm, acute respiratory distress syndrome (ARDS) and muscus plug, acute injuries of heart, liver and kidney, and some special symptoms of COVID-19. I hypothesized that the damage induced by free DNA is a reason for severe 23 COVID-19, which can explain many symptoms of this disease, such as cytokine 24 storm, ARDS and muscus plug, acute injuries of heart, liver and kidney, and some 25 special symptoms of COVID-19. Level 60 of lymphocytes is thought as the early identification of risk factors for severe 61 COVID-19, [1] [2] [3] 8 while I hypothesized that it was related to free DNA-related cytokine 62 storm and blood vessel damage, which can explain many symptoms of this disease, 63 including some "special" symptoms in COVID-19, as shown in Figure 1 . cache = ./cache/cord-279084-bbae1qyx.txt txt = ./txt/cord-279084-bbae1qyx.txt === reduce.pl bib === id = cord-279229-2226jnfl author = Savan, R title = Loop‐mediated isothermal amplification: an emerging technology for detection of fish and shellfish pathogens date = 2005-11-22 pages = extension = .txt mime = text/plain words = 4188 sentences = 230 flesch = 45 summary = In this paper, we review a novel method of DNA amplification known as loop-mediated isothermal amplification (LAMP) of a target nucleic acid. Screening for KHV has become very important as trade of fancy carp is an easy route for geographical spread of the virus and a rapid and efficient system like LAMP is very Figure 2 Loop-mediated isothermal amplification reaction amplifying the haemolysin gene from Edwardsiella tarda isolates. Rapid detection of a fish iridovirus using loop-mediated isothermal amplification (LAMP) Rapid diagnosis of Tetracapsuloides bryosalmonae, the causative agent of proliferative kidney disease (PKD) in salmonid fish by a novel DNA amplification method, loop-mediated isothermal amplification (LAMP) Rapid diagnosis of herpes simplex virus infection by a loop-mediated isothermal amplification method A loop mediated isothermal amplification (LAMP) method for detection of infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss) Rapid diagnosis of human herpesvirus 6 infection by a novel DNA amplification method, loop-mediated isothermal amplification cache = ./cache/cord-279229-2226jnfl.txt txt = ./txt/cord-279229-2226jnfl.txt === reduce.pl bib === id = cord-278250-dwok857k author = Li, Heng title = The altered gut virome community in rhesus monkeys is correlated with the gut bacterial microbiome and associated metabolites date = 2019-08-19 pages = extension = .txt mime = text/plain words = 7452 sentences = 379 flesch = 44 summary = We performed metagenomic sequencing of fecal samples to detect the bacterial microbiome and virome composition of healthy one-year-old rhesus monkeys housed at the IMBCAMS (Fig. 1) . We comprehensively analyzed the interactions among the gut virome, bacterial microbiome and metabolomes based on the above results there were noticeable differences in bacterial β-diversity between control and experimental animals, as determined using principal component analysis (PCA), and the results showed good repeatability within a single group (Additional file 2: Figure S2F ). Briefly, the fecal virome composition was noticeably altered after depletion of the bacterial microbiome, and the abundances of many DNA viruses, bacteriophages and RNA viruses in the gut were clearly decreased. As expected, the whole gut bacterial microbiome, including gram-positive and gram-negative bacteria (Additional file 2: Figure S2E ), was depleted after treatment with the antibiotic cocktail, except for Escherichia-Shigella species belonging to Proteobacteria, which were resistant to the cocktail. cache = ./cache/cord-278250-dwok857k.txt txt = ./txt/cord-278250-dwok857k.txt === reduce.pl bib === id = cord-279827-921kvrrz author = Murata, Takayuki title = Growth behavior of bovine herpesvirus-1 in permissive and semi-permissive cells date = 1999-06-11 pages = extension = .txt mime = text/plain words = 7150 sentences = 368 flesch = 65 summary = MDBK or HmLu-1 cells in 35 mm dishes were incubated with 1.0× 10 5 , 1.0 ×10 4 or 1.0 × 10 3 plaque forming unit (pfu) of BHV-1 at a multiplicity of infection (moi) of 0.1, 0.01 or 0.001, respectively, at 4°C for 2 h to allow the virus to be adsorbed into the cells. MDBK or HmLu-1 cells in 60 mm dishes were infected with BHV-1/RSV/p32 at 4°C for 1 h, washed three times with ice-cold PBS and incubated at 37°C in the medium containing 400 mg/ml phosphonoacetic acid (PAA). Confluent monolayer cultures of MDBK cells or HmLu-1 cells were infected with BHV-1 at an moi of 5 and at 3, 6, 12, 24, and 48 h p.i., DNA was extracted as described in Section 2. The MDBK or HmLu-1 cells were infected with BHV-1/RSV/p32 at 4°C for 1 h, washed extensively with cold PBS and incubated with medium at 37°C for 0, 1, 2, and 5 h. cache = ./cache/cord-279827-921kvrrz.txt txt = ./txt/cord-279827-921kvrrz.txt === reduce.pl bib === id = cord-277293-eo3bei9x author = Fondong, Vincent N. title = Geminivirus protein structure and function date = 2013-04-25 pages = extension = .txt mime = text/plain words = 10141 sentences = 507 flesch = 47 summary = The replication-associated protein (Rep) encoded by the AC1 ORF (also called AL1) in bipartite geminiviruses and by C1 (also called L1) in monopartite geminiviruses (except mastreviruses) is conserved in sequence, position and function (Hanley-Bowdoin et al., 2004) and is expressed under the control of a bidirectional core promoter in the IR (Hanley-Bowdoin et al., 1999) . SINAC1 levels were shown to be higher in ToLCV-infected cells, suggesting that NAC1 is involved in viral DNA replication (Selth et al., 2005) , possibly through an interaction with REn. Recently, the Tomato leaf curl Kerala virus REn was shown to interact with Rep and enhance the Repmediated ATPase activity (Pasumarthy et al., 2010) , thus confirming a role for REn in viral DNA replication. cache = ./cache/cord-277293-eo3bei9x.txt txt = ./txt/cord-277293-eo3bei9x.txt === reduce.pl bib === id = cord-281883-l9yshyc7 author = Alekseeva, Ekaterina title = Enhancement of the expression of HCV core gene does not enhance core-specific immune response in DNA immunization: advantages of the heterologous DNA prime, protein boost immunization regimen date = 2009-06-08 pages = extension = .txt mime = text/plain words = 7595 sentences = 390 flesch = 45 summary = METHODS: Plasmids encoding core with no translation initiation signal (pCMVcore); with Kozak sequence (pCMVcoreKozak); and with HCV IRES (pCMVcoreIRES) were designed and expressed in a variety of eukaryotic cells. Single immunization with plasmids directing low levels of core expression induced similar levels of cytokines, strong T-cell proliferation (pCMVcoreIRES), and antibodies in titer 10(3)(pCMVcore). Boosting with pCMVcoreKozak induced low antibody response, core-specific T-cell proliferation and IFN- secretion that subsided after the 3rd plasmid injection. Boosting with pCMVcoreKozak induced low antibody response, core-specific T-cell proliferation and IFN- secretion that subsided after the 3rd plasmid injection. Significant responses in the form of core-specific IFN- and IL-2 secretion exceeding the background levels in empty-vector-immunized mice were detected five weeks after a single administration of HCV core gene (Fig.5) . Only the heterologous DNA-prime-protein boost regimen induced a significant core-specific antibody production and potent T-cell response of mainly Th1-profile. Enhancement of cellular and humoral immune responses to hepatitis C virus core protein using DNA-based vaccines augmented with cytokine-expressing plasmids cache = ./cache/cord-281883-l9yshyc7.txt txt = ./txt/cord-281883-l9yshyc7.txt === reduce.pl bib === id = cord-280429-4fota9rl author = Medvedev, Kirill E. title = Functional and evolutionary analysis of viral proteins containing a Rossmann‐like fold date = 2018-06-13 pages = extension = .txt mime = text/plain words = 7468 sentences = 465 flesch = 49 summary = 10 However, structural analyses of virion architecture and coat protein topology have revealed unexpected similarities, not visible in sequence comparisons, suggesting a common origin for viruses that infect hosts residing in different domains of life. In this current work, we provide functional and evolutionary analysis of viral proteins containing a Rossmann-like fold that can be found in the Evolutionary Classification of protein Domains (ECOD) database developed in our lab. The structures represented gene products from 21 viral taxonomical families with host ranges from all kingdoms of life (http://prodata.swmed.edu/rossmann_fold/viruses/). Our analysis detected 14 different bacterial virus structure topology types defined by ECOD T-groups that contain a Rossmann-like fold (Fig. 2, 12 topology groups shown). Like the bacterial and eukaryotic branches in the tree of life, the Archea are host to a multitude of Functional and Evolutionary Analysis of Viral Proteins viruses. 61 Among viral protein structures containing the minimal Rossmann fold, 14 protein families are known helicases (http://prodata.swmed.edu/ross-mann_fold/viruses/). cache = ./cache/cord-280429-4fota9rl.txt txt = ./txt/cord-280429-4fota9rl.txt === reduce.pl bib === id = cord-280549-bsnz24jx author = Fan, Ying title = Breaking Bad: How Viruses Subvert the Cell Cycle date = 2018-11-19 pages = extension = .txt mime = text/plain words = 18057 sentences = 867 flesch = 46 summary = A binding-deficient Tax variant failed to stimulate CDK4-cyclin D complex formation and lost its ability to antagonize the inhibitory effect of cyclin-dependent kinase inhibitor (CKI) p21 WAF1/CIP1 , underlying the importance of protein interaction in Tax-mediated cell cycle regulation (Haller et al., 2002) . The examples of Tax and Hobs illustrate how binding of viral protein to cyclin or CDK promotes cell cycle progression either by enhancing kinase activity and/or weakening the inhibitory effect of CKI. Thus, by targeting the E3 ligase of p21 WAF1/CIP1 and p27 KIP1 for degradation, Tax stabilizes these two CKIs. On the contrary, the association of chicken anemia virus protein Apoptin with APC1 inhibits the activity of theAPC/C ubiquitin ligase, leading to the stabilization of cyclin B1 and other APC/C substrates, with ensuing cell cycle G2/M arrest and apoptosis (Teodoro et al., 2004) . cache = ./cache/cord-280549-bsnz24jx.txt txt = ./txt/cord-280549-bsnz24jx.txt === reduce.pl bib === id = cord-280605-2i4gk7et author = Bachmann, María Consuelo title = The Challenge by Multiple Environmental and Biological Factors Induce Inflammation in Aging: Their Role in the Promotion of Chronic Disease date = 2020-10-14 pages = extension = .txt mime = text/plain words = 11128 sentences = 559 flesch = 32 summary = With increasing age, the dynamics and proportion of lymphocytes and myeloid cells differ depending on the sex due to the differential expression of 144 genes of the immune response in men and women (71) . Anti-inflammatory effect of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and their biologically active metabolites (D and E Resolvinsmediators derived from omega-3 fatty acids, primarily EPA and DHA that block the production of proinflammatory mediators and regulate leukocyte trafficking to inflammatory sites) can be mediated through one of the mechanisms capable of reducing inflammation of RAW-264.7 cells and of primary intraperitoneal macrophages (105) . Exposure to various alarm signals induce an acute inflammation that, when associated with deleterious environmental and biological factors, potentiates chronic inflammation, which can be further promoted by excess ROS production and oxidative stress that results from mitochondrial dysfunction or NOX2 activity, leading to inflammaging and eventually to age-related disease. cache = ./cache/cord-280605-2i4gk7et.txt txt = ./txt/cord-280605-2i4gk7et.txt === reduce.pl bib === id = cord-280249-kfon0l9h author = Granstrom, David E. title = Recent Advances in the Laboratory Diagnosis of Equine Parasitic Diseases date = 1995-12-31 pages = extension = .txt mime = text/plain words = 2073 sentences = 148 flesch = 53 summary = 5 • 12 • 15 Accurate antemortem diagnosis has been enhanced greatly by the recent development of the Western blot and polymerase chain reaction tests (Equine Biodiagnostics, Inc, Lexington, KY) to detect parasite-specific antibodies or parasite DNA in the blood or cerebrospinal fluid (CSF) of affected horses. neurona was developed to detect the parasite in blood or spinal fluid of affected horses.7 Amplification primers were designed from the nucleotide sequence of the 18S small ribosomal subunit gene of S. Generally, it has not been necessary to use the PCR test to confirm positive Western blot results for CSF samples. The presence of parasite DNA in an equine blood sample suggests that the horse recently ingested S. 4 , s, 9, 17 , 18 Although Cryptosporidium alone may cause foal diarrhea, it also has been associated with concurrent infection with other enteric pathogens (adenovirus, coronavirus, rotavirus, Giardia, Salmonella), 4 , 17 , 18, 19 It is im portant to consider testing for these agents as well. cache = ./cache/cord-280249-kfon0l9h.txt txt = ./txt/cord-280249-kfon0l9h.txt === reduce.pl bib === id = cord-281565-v8s2ski3 author = Belmonte-Reche, Efres title = Exploring G and C-quadruplex structures as potential targets against the severe acute respiratory syndrome coronavirus 2 date = 2020-08-20 pages = extension = .txt mime = text/plain words = 4545 sentences = 253 flesch = 53 summary = These PQS and PiMS have been assessed according to their potential to form, uniqueness, frequency of appearance, conservation rates between 3297 different 2019-nCoV clinical cases, confirmed quadruplex-forming sequence presence and localization within the genome. Then, these PQS and PiMS were evaluated by their frequency of appearance in the corresponding genome, the presence of known-to-form quadruplex structures sequences within and their probability of quadruplex-formation score (as the mean of G4Hunter (52) and the adaptation of the PQSfinder algorithm (53) ). A flexible configuration of quadruplex definitions will detect larger amounts of candidates at the expense of requiring more computing power and accepting sequences that are more ambiguous in forming quadruplex structures in vitro (as determined by their score; with longer loops, smaller runs, more bulges and more complementary G/C %, Figure 1 , B). Expanding the search for common candidates to the entire virus realm, we matched one PQS and PiMS from the 2019-nCoV with the potential quadruplexes found in four viruses from cache = ./cache/cord-281565-v8s2ski3.txt txt = ./txt/cord-281565-v8s2ski3.txt === reduce.pl bib === id = cord-281188-0cql96hu author = Baquero, Fernando title = Proximate and ultimate causes of the bactericidal action of antibiotics date = 2020-10-06 pages = extension = .txt mime = text/plain words = 8715 sentences = 411 flesch = 36 summary = (1) only free drug is active against the target bacteria, and protein binding of the drug decreases the rate of killing 19 ; (2) there are structures (such as porins) and mechanisms facilitating drug uptake, but also barriers that prevent the drug from entering the cells 20 ; (3) the drug can be pumped out, so the concentration needed for killing takes longer to achieve 21, 22 ; (4) the antibiotics with weak target-binding affinity will take longer to achieve the doses necessary for killing than those with greater affinity 23 ; (5) the targeted function might increase in the presence of the drug, thereby compensating for the inhibition by the drug 24 ; (6) the target function corresponds to the build-up of a cellular structure with slow turnover, which increases the amount of time for the antibiotic to kill 25,26 ; (7) the cells repair the damage produced by the antibiotics at rates that differ between drugs 27 ; (8) the damaged bacteria have inducible antibiotic-deactivating mechanisms 28 ; (9) the bacteria use alternative metabolic pathways that, to some extent, bypass those inhibited by the antibiotic 29, 30 ; (10) antibiotics differ in the extent to which they induce reactive oxygen species (ROS; deleterious) or SOS (potentially protective) responses and thereby the rate at which they kill the exposed bacteria [31] [32] [33] [34] ; (11) members of the antibiotic-exposed populations are either www.nature.com/nrmicro not replicating or are replicating slowly, and as such are killed at lower rates than the more active members of the population or their death is delayed; (12) the antibiotics produce a kind of 'stationary phase' by activating the general RpoS-mediated stringent response 35 . cache = ./cache/cord-281188-0cql96hu.txt txt = ./txt/cord-281188-0cql96hu.txt === reduce.pl bib === id = cord-280691-nzc8ir0n author = Guo, Sun-Wei title = China’s “Gene War of the Century” and Its Aftermath: The Contest Goes On date = 2013-08-30 pages = extension = .txt mime = text/plain words = 12487 sentences = 563 flesch = 52 summary = Around 1997, and amid the talks of Hong Kong's upcoming return to China and later the Asian financial crisis, a recurring topic in the Chinese media was the so-called ''gene war of the century'': the lopsided condemnation of foreign scientists coming purportedly to pilfer China's vast genetic resources for a profit. Despite his repeated proclamation as a staunch and unwavering patriot loyal to his beloved motherland and dedicated to the advancement of China's science and technology, he nonetheless later became embroiled in an avalanche of controversies surrounding the ''gene war.'' He effectively became a lightning rod for all the controversy on genetic resources, intellectual rights, informed consent, and the protection of human research subjects. (2) Chinese scientists should immediately grasp the opportunity to find disease genes and patent them; (3) We should educate the people, and raise the awareness and importance of protection of our genetic resources; (4) We welcome all international collaborations based on fairness and mutual benefits; (5) Through various avenues, the Chinese scientists should be vocal about certain views deemed to be harmful to China's genetic research (Xiao et al. cache = ./cache/cord-280691-nzc8ir0n.txt txt = ./txt/cord-280691-nzc8ir0n.txt === reduce.pl bib === id = cord-279346-7del8d2p author = Callendret, Benoît title = Heterologous viral RNA export elements improve expression of severe acute respiratory syndrome (SARS) coronavirus spike protein and protective efficacy of DNA vaccines against SARS date = 2007-07-05 pages = extension = .txt mime = text/plain words = 10731 sentences = 471 flesch = 49 summary = title: Heterologous viral RNA export elements improve expression of severe acute respiratory syndrome (SARS) coronavirus spike protein and protective efficacy of DNA vaccines against SARS Here, we demonstrated that efficient expression of S from the wild-type spike gene in cultured cells required the use of improved plasmid vectors containing donor and acceptor splice sites, as well as heterologous viral RNA export elements, such as the CTE of Mazon-Pfizer monkey virus or the PRE of Woodchuck hepatitis virus (WPRE). Upon immunization of mice with low doses (2 μg) of naked DNA, only intron and WPRE-containing vectors could induce neutralizing anti-S antibodies and provide protection against challenge with SARS-CoV. The influence of SS, MPMV-CTE or WPRE on expression of S protein in transfected cells and on induction of a protective SARS-CoV-specific immunity in mice after naked DNA immunization are compared. cache = ./cache/cord-279346-7del8d2p.txt txt = ./txt/cord-279346-7del8d2p.txt === reduce.pl bib === id = cord-281404-5a8au32c author = Gastaldello, Stefano title = Caspase-1 Promotes Epstein-Barr Virus Replication by Targeting the Large Tegument Protein Deneddylase to the Nucleus of Productively Infected Cells date = 2013-10-10 pages = extension = .txt mime = text/plain words = 7139 sentences = 337 flesch = 42 summary = The large tegument proteins of herpesviruses contain N-terminal cysteine proteases with potent ubiquitin and NEDD8-specific deconjugase activities, but the function of the enzymes during virus replication remains largely unknown. Here we report that induction of the productive virus cycle has no appreciable effects on the global levels of protein ubiquitination but is accompanied by a BPLF1-dependent decrease of cullin neddylation and stabilization of nuclear CRL substrates. The Akata-Bx1 cell line was used to study the contribution of the Ub-and NEDD8-specific deconjugase activities of the EBV large tegument protein BPLF1 to the productive virus cycle. In order to assess whether this regulatory interaction may operate during virus replication, the productive cycle was induced in Akata-Bx1 cells transiently transfected with plasmids expressing Myc-tagged CAND1 or the CAND1 Nterminus that compete for BPLF1 binding to cullins, or, as controls, the CAND1 C-terminus that binds to the opposite end of the cullin scaffold, and the empty vector ( Figure 5A ). cache = ./cache/cord-281404-5a8au32c.txt txt = ./txt/cord-281404-5a8au32c.txt === reduce.pl bib === id = cord-283807-4yo27web author = Ashtari, Parviz title = An efficient method for recovery of target ssDNA based on amino-modified silica-coated magnetic nanoparticles date = 2005-09-15 pages = extension = .txt mime = text/plain words = 2980 sentences = 185 flesch = 47 summary = title: An efficient method for recovery of target ssDNA based on amino-modified silica-coated magnetic nanoparticles Abstract In this paper, an improved recovery method for target ssDNA using amino-modified silica-coated magnetic nanoparticles (ASMNPs) is reported. In this paper, we reported an improved method for recovery of target ssDNA using amino-modified silica-coated magnetic nanoparticles (ASMNPs). Then, 1 ml of 4.1 × 10 −6 M biotin-labeled capture ssDNA(I) (5 -biotin-AAAAAAAAAAGTATCACGAGGCCCTATGCG-3 ) solution was added to the streptavidin derivatived amino-modified silica-coated magnetic nanoparticles and reacted at room temperature for 4 h. The method scheme for recovery of target ssDNA based on amino-modified silica-coated magnetic nanoparticles (ASMNPs). and hybridized with the capture ssDNA to form the DNA bio-conjugate, and it can be separated from the solution under the magnet field due to the magnetic characteristics of the amino-modified silica-coated magnetic nanoparticles. cache = ./cache/cord-283807-4yo27web.txt txt = ./txt/cord-283807-4yo27web.txt === reduce.pl bib === id = cord-283880-lrrkuist author = Kumar, Arvind title = Evolution of selective-sequencing approaches for virus discovery and virome analysis date = 2017-07-15 pages = extension = .txt mime = text/plain words = 5934 sentences = 286 flesch = 38 summary = Use of sequence dependent (i.e; generic PCR assays and microarray) and sequence independent (i.e; single primer amplification (SISPA) and random priming) approaches for nucleic acid amplification combined with Sanger sequencing or HTS allowed the rapid identification of new viruses after 1980 (Bishop-Lilly et al., 2010; Chang et al., 1994; Day et al., 2010; Grard et al., 2012; Kapoor et al., 2015; Ladner et al., 2016; Linnen et al., 1996; Matsui et al., 1991; Mokili et al., 2012; Muerhoff et al., 1997; Nichol et al., 1993; Qin et al., 2014; Quan et al., 2010; Simons et al., 1995b) (Fig. 1) . For the virome analysis of clinical samples with an abundance of host cells, like blood or tissues, pre-extraction based enrichment is not appropriate as the virus genome itself can be present in its non-capsidated or transcribed form. In positive selection methods, samples are enriched for viral nucleic acids directly using probes targeting the viruses like in PCR assays, microarray or virus capture (in solution based hybridization) approaches. cache = ./cache/cord-283880-lrrkuist.txt txt = ./txt/cord-283880-lrrkuist.txt === reduce.pl bib === id = cord-283249-pk5sc2ca author = Yoshida, Wataru title = Homogeneous DNA sensing using enzyme-inhibiting DNA aptamers date = 2006-09-15 pages = extension = .txt mime = text/plain words = 5356 sentences = 235 flesch = 56 summary = The structural change of the enzyme-inhibiting aptamer site induces a change in the inhibitory activity of the AES, which enables us to detect a target molecule by measuring the enzymatic activity of the whole aptameric complex in a homogeneous solution without bound/free separation. The stem-and-loop structure bearing the probe DNA sequence was inserted into the 3 0 -end T-T loop of the G-quartet structure of the 31-mer thrombin-inhibiting aptamer. We also inserted two additional T bases between the thrombin-inhibiting aptamer and the stem-and-loop structure in all AESs except AES 1, since the diameter of the DNA double helix is different from the distance between two Gs of the G-quartet structure (approximately 17 and 20 Å , respectively). For the measurement of the CD spectra of AES SARS 1, a stem-and-loop structure to be inserted into the 31-mer thrombin-inhibiting aptamer on AES SARS 1 was synthesized. cache = ./cache/cord-283249-pk5sc2ca.txt txt = ./txt/cord-283249-pk5sc2ca.txt === reduce.pl bib === id = cord-282618-tjvjlyn9 author = Luke, J M title = Improved antibiotic-free plasmid vector design by incorporation of transient expression enhancers date = 2010-11-25 pages = extension = .txt mime = text/plain words = 6241 sentences = 336 flesch = 43 summary = To maintain a low risk of insertional mutagenesis-mediated gene activation, expression-augmenting sequences would ideally function to improve transgene expression from transiently transfected intact plasmid, but not from spurious genomically integrated vectors. A neomycin resistance gene (NeoR) without an upstream Kozak sequence was cloned downstream of an enhanced green fluorescent protein (EGFP) transgene in different configurations similar to that used with PREs. Quantifiable neoR translation products were present in all tested configurations, as was biologically active neoR protein after plasmid transfection into both HEK293 and CHO cell lines (Supplementary Table S1 ). The assay was in the same format as in (a), except for the fact that Pol III inhibitor-treated cells were transfected with EGFP plasmids containing the CMV-HTLV-I R promoter with or without VA1; (c) Inhibition of PKR, not of adenosine deaminase acting on RNA (ADAR) or RNA interference (RNAI), was required for VA1 expression enhancement effect. cache = ./cache/cord-282618-tjvjlyn9.txt txt = ./txt/cord-282618-tjvjlyn9.txt === reduce.pl bib === id = cord-282251-r4on3lpr author = Veggiani, Gianluca title = Emerging drug development technologies targeting ubiquitination for cancer therapeutics date = 2019-03-07 pages = extension = .txt mime = text/plain words = 11388 sentences = 580 flesch = 41 summary = Within the span of 20 years, high-throughput technologies further advanced to include feats in protein engineering such as proteolysis-targeting chimeras (PROTACs) derived from the ubiquitination pathway (Zhou, Bogacki, McReynolds, & Howley, 2000) , streamlined phage display approaches that include Ub variants (UbV) to target protein-protein interactions in the UPS (Brown et al., 2016; Ernst et al., 2013; Ernst & Sidhu, 2013; Gabrielsen et al., 2017; Ordureau et al., 2018; Zhang et al., 2016; Zhang et al., 2017; Zhang et al., 2017; Zhang & Sidhu, 2018) and cell-based pharmacological HTS assays to enhance oncolytic virus cancer-cell-killing efficiency through viral sensitizer screens (Bourgeois-Daigneault et al., 2016; Diallo et al., 2010) (Fig. 2) . cache = ./cache/cord-282251-r4on3lpr.txt txt = ./txt/cord-282251-r4on3lpr.txt === reduce.pl bib === id = cord-277665-ac8txr3h author = Grichko, Varvara P. title = 15 Nanodiamond Designing the Bio-Platform date = 2006-12-31 pages = extension = .txt mime = text/plain words = 8852 sentences = 453 flesch = 38 summary = The chapter also summarizes different approaches to the surface functionalization of nanodiamonds (ND) particles—that is, the key in successful biomedical applications followed by a discussion of modification of diamond surfaces with nucleic acids and proteins. This chapter will be organized as follows: in the next section different approaches to the surface functionalization of ND particles, that is, the key in successful biomedical applications, will be summarized, followed by a discussion of modification of diamond surfaces with nucleic acids and proteins. Nanocrystalline diamond thin films covalently modified with DNA oligonucleotides following the photochemical modification of H-terminated surfaces with amine groups provide a very stable and highly selective platform for the surface hybridization reaction (Yang et al., 2002) . When made sufficiently electrically conducting by boron doping, thin-film and free-standing diamond electrodes exhibit remarkable chemical resistance to etching, a wide potential window, low background current responses, mechanical stability toward ultrasound-induced interfacial cavitation, a low stickiness in adsorption processes, and a high degree of tunability of the surface properties (reviewed by Compton et al., 2003) . cache = ./cache/cord-277665-ac8txr3h.txt txt = ./txt/cord-277665-ac8txr3h.txt === reduce.pl bib === id = cord-282106-7k088cqv author = Yang, Zhi-yong title = A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice date = 2004 pages = extension = .txt mime = text/plain words = 3739 sentences = 193 flesch = 48 summary = Here, we show that a DNA vaccine encoding the spike (S) glycoprotein of the SARS-CoV induces T cell and neutralizing antibody responses, as well as protective immunity, in a mouse model. Here, we show that a DNA vaccine encoding the spike (S) glycoprotein of the SARS-CoV induces T cell and neutralizing antibody responses, as well as protective immunity, in a mouse model. Viral replication was reduced by more than six orders of magnitude in the lungs of mice vaccinated with these S plasmid DNA expression vectors, and protection was mediated by a humoral but not a T-cell-dependent immune mechanism. Immunization and challenge were performed in mice as described previously 18 , and viral replication (mean log 10 TCID 50 per g tissue with standard error) in the lower (a) and upper (b) respiratory tract after challenge with SARS-CoV was measured for five immunized animals inoculated with SDCD, SDTM or empty plasmid vector control. cache = ./cache/cord-282106-7k088cqv.txt txt = ./txt/cord-282106-7k088cqv.txt === reduce.pl bib === id = cord-288390-p1q3v1ie author = Habjan, Matthias title = Cytoplasmic sensing of viral nucleic acids date = 2015-02-07 pages = extension = .txt mime = text/plain words = 4040 sentences = 252 flesch = 48 summary = These sensors induce expression of cytokines, affect cellular functions required for virus replication and directly target viral nucleic acids through degradation or sequestration. These sensors induce expression of cytokines, affect cellular functions required for virus replication and directly target viral nucleic acids through degradation or sequestration. In this review we concentrate on intracellular nucleic acid sensors and effector proteins that evolved to mediate specialised tasks including, firstly, expression of cytokines such as type I interferons (IFN-a/b); secondly, modulation of cellular machineries required for virus replication and thirdly, direct inhibition of virus growth ( Figure 1 ). Among the best characterised cytoplasmic proteins involved in virus sensing are RIG-I-like receptors (RLRs), a family of DExD/H-box helicases which specifically identify viral RNAs and have the ability to stimulate expression of IFN-a/b and other cytokines (Figure 3 ) [4, 17] . Virus infection activates a restricted set of sensor and effector proteins that modulate cellular pathways and directly target viral nucleic acid, thereby shaping the innate immune response. cache = ./cache/cord-288390-p1q3v1ie.txt txt = ./txt/cord-288390-p1q3v1ie.txt === reduce.pl bib === id = cord-282062-h9smg0w9 author = Takano, Tomomi title = Novel single-stranded, circular DNA virus identified in cats in Japan date = 2018-09-14 pages = extension = .txt mime = text/plain words = 1942 sentences = 124 flesch = 56 summary = We detected a novel feline stool-associated circular DNA virus (FeSCV) in fecal samples from cats with diarrhea using consensus primers matching those of circovirus and cyclovirus. Feline cyclovirus was identified by next-generation sequencing analysis in which the viral gene was detected in a pooled fecal sample collected from 4-5 healthy cats. In this study, we performed nested PCR using Circoviridae family consensus primers and detected novel CRESS DNA viruses in several cats with diarrhea symptoms. However, we concluded that FeSCV is a circular DNA virus based on the following: 1) No Giardia intestinalis was detected in the fecal test, and 2) the complete genome of FeSCV was amplified using the rolling-circle amplification and inverse PCR assays. We detected a novel CRESS DNA virus, FeSCV, in fecal samples from cats. Although it was detected using consensus primers of circovirus and cyclovirus, FeSCV was phylogenetically positioned in a clade different from that of these viruses. cache = ./cache/cord-282062-h9smg0w9.txt txt = ./txt/cord-282062-h9smg0w9.txt === reduce.pl bib === id = cord-285982-1a5u7uux author = Moss, Ronald B title = Prospects for control of emerging infectious diseases with plasmid DNA vaccines date = 2009-09-07 pages = extension = .txt mime = text/plain words = 4227 sentences = 202 flesch = 42 summary = The rapid manufacturing capabilities of DNA vaccines may be particularly important for emerging infectious diseases including the current novel H1N1 Influenza A pandemic, where pre-existing immunity is limited. Development in this area has greatly advanced over the years and human clinical trials of DNA vaccines have now been conducted against various infectious pathogens including the malaria parasite, dengue viruses, cytomegalovirus (CMV), Ebola virus, seasonal influenza viruses, avian or pandemic influenza viruses, West Nile virus (WMV), SARS coronavirus, hepatitis B virus, and HIV. Because the process of antigen production by host cells after DNA vaccination mimics the production of antigens during a natural infection, the resulting immune response is thought to be similar to the type induced by pathogens. Lastly, the first human clinical trial of a DNA vaccine formulated with Vaxfectin ® has been completed with plasmids that encode pandemic influenza virus antigens (H5N1). cache = ./cache/cord-285982-1a5u7uux.txt txt = ./txt/cord-285982-1a5u7uux.txt === reduce.pl bib === id = cord-286719-1xjmlwqr author = Draz, Mohamed Shehata title = Applications of gold nanoparticles in virus detection date = 2018-02-15 pages = extension = .txt mime = text/plain words = 18990 sentences = 901 flesch = 37 summary = The developed AuNP-based detection techniques are reported for various groups of clinically relevant viruses with a special focus on the applied types of bio-AuNP hybrid structures, virus detection targets, and assay modalities and formats. These techniques represent the majority of molecular techniques applied in virus detection and include various types of target amplification techniques (e.g., PCR, loop-mediated isothermal amplification (LAMP), transcription-mediated amplification, and nucleic acid sequence-based amplification), signal amplification techniques (e.g., branched DNA and hybrid capture), and probe amplification techniques (e.g., ligase chain reaction and strand-displacement amplification). [70] developed an impedimetric electrochemical assay for the detection of AIV M gene sequences based on measuring changes in the impedimetric behavior of the electrode when the target DNA hybridizes with the capture DNA probes immobilized onto its surface and is subsequently labeled by AuNPs via streptavidin/ biotin interaction (Fig. 12C) . cache = ./cache/cord-286719-1xjmlwqr.txt txt = ./txt/cord-286719-1xjmlwqr.txt === reduce.pl bib === id = cord-286684-2xmd3jfo author = Stefanetti, Valentina title = Retrospective Biomolecular Investigation of Coxiella burnetii and Leptospira spp. DNA in Cases of Abortion, Stillbirth and Neonatal Mortality in Dogs and Cats date = 2018-08-20 pages = extension = .txt mime = text/plain words = 3428 sentences = 183 flesch = 50 summary = Leptospira interrogans sensu lato is able to cause abortion or stillbirth in several animal species and its abortigenic role has occasionally been described in bitches and queens. DNA in a retrospective series of 103 cases of canine and feline abortion, stillbirth, and neonatal mortality submitted for the identification of possible infectious agents. DNA in a retrospective series of cases of canine and feline abortion, stillbirth, and neonatal mortality submitted to a diagnostic laboratory of infectious diseases. biflexa serovar patoc, type Patoc), and unrelated bacteria (Streptococcus spp.; Eschericia coli; Klebsiella pneumoniae; Pseudomonas aeruginosa; Staphylococcus intermedius; Proteus vulgaris; Enterococcus faecalis), as well as DNA from bovine and caprine faeces and clinical specimens from animals with previously diagnosed Leptospira infection, were used to test the specificity of the protocol. burnetii and Leptospira has been previously reported in the same geographical area and time frame in which this study was conducted, although in different animal species; leptospiral DNA was found in equine abortion and stillbirth, 25 whereas C. cache = ./cache/cord-286684-2xmd3jfo.txt txt = ./txt/cord-286684-2xmd3jfo.txt === reduce.pl bib === id = cord-288444-0vv4neq6 author = Cotrone, Serafina title = Microcantilevers and organic transistors: two promising classes of label-free biosensing devices which can be integrated in electronic circuits date = 2011-12-22 pages = extension = .txt mime = text/plain words = 6464 sentences = 302 flesch = 33 summary = This paper aims to review some recent results concerning the development of biosensing devices based on microcantilevers (MCLs) and organic transistors. Since biological systems are based on cell-cell interactions and the transduction of biosignals between cells, the possibility to interface cells to organic materials to be integrated in electronic devices will be here reviewed. Although these devices have been extensively studied as chemical [8, 25] and biological sensors [9, 26, 27] , the possibility of interfacing them with living cells requires that the organic electronic material establishes a stable interface with water and conducts not only electronic but also ionic carriers. In conclusion, both organic transistors and MCLs possess the requisites necessary for devices of interest in life science applications and possess such a high sensitivity as to even be able to detect single cells; very recently, an interesting combination between an OFET and a polymer cantilever platform was proposed. cache = ./cache/cord-288444-0vv4neq6.txt txt = ./txt/cord-288444-0vv4neq6.txt === reduce.pl bib === id = cord-285077-okwck5sv author = Sayahi, Tofigh title = Airborne Aerosolized Mouse Cytomegalovirus From Common Otolaryngology Procedures: Implications for COVID-19 Infection date = 2020-09-15 pages = extension = .txt mime = text/plain words = 4973 sentences = 300 flesch = 49 summary = CONCLUSION: Coblation and electrocautery procedures generate >100-fold increases in aerosol concentrations over background; only coblation and drilling produce aerosolized viral DNA. Coblation and electrocautery procedures generate .100-fold increases in aerosol concentrations over background; only coblation and drilling produce aerosolized viral DNA. 10, 11 We proposed to build on these studies by measuring particle size and concentration and by trying to detect aerosolized viral DNA and viable virus during common otolaryngology procedures, using a murine model for cytomegalovirus (CMV) infection. The results also indicated that drilling and microdebrider did not cause statistically significant increases in aerosol concentrations and total counts when compared with background (.870 \ Tukey-adjusted P value \ .930; Figures 2 and 3 , Table 3 ). The results from our study demonstrate that a number of these procedures can generate relatively large concentrations of aerosolized particles and that a significant percentage are small enough to pass unimpeded through conventional surgical and even N95 masks. cache = ./cache/cord-285077-okwck5sv.txt txt = ./txt/cord-285077-okwck5sv.txt === reduce.pl bib === === reduce.pl bib === id = cord-288131-dwhfrgje author = Zhao, Guodong title = Aberrant DNA Methylation of SEPT9 and SDC2 in Stool Specimens as an Integrated Biomarker for Colorectal Cancer Early Detection date = 2020-06-18 pages = extension = .txt mime = text/plain words = 4309 sentences = 234 flesch = 62 summary = A number of methylated DNA biomarkers have been found to associate with CRC and precancerous lesions in stool or plasma samples, including SEPT9 (Catherine et al., 2008; Lamb and Dhillon, 2017) , SDC2 (Barták et al., 2017; Han et al., 2019) , SFRP2 (Barták et al., 2017; Li et al., 2019) , and TFPI2 (Glöckner et al., 2009) , some of which have been developed into commercial kits for CRC early detection (Potter et al., 2014; Lamb and Dhillon, 2017; Li et al., 2019; Zhao et al., 2019) . We previously demonstrated a multiplex methylated DNA test in plasma, ColoDefense test, with high sensitivity and specificity for CRC early detection. Instead, we have demonstrated that the detection rates of plasma ColoDefense test for AA and early stage CRC were significantly improved by the combination of two biomarkers, mSEPT9 and mSDC2, with high specificity . cache = ./cache/cord-288131-dwhfrgje.txt txt = ./txt/cord-288131-dwhfrgje.txt === reduce.pl bib === === reduce.pl bib === id = cord-291749-revhbd0q author = Mongan, Arthur Elia title = Portable sequencer in the fight against infectious disease date = 2019-10-03 pages = extension = .txt mime = text/plain words = 3735 sentences = 222 flesch = 40 summary = Diagnosis can be upheld by observing the cause of disease under the microscope or detecting the presence of nucleic acid and proteins of the pathogens. Sequencing of PCR amplicons or whole pathogen genomic DNA can be applied to comprehensively screen for infecting agents and their drug resistance phenotype, if exists, at the same time. Sequencing ensures detection of DNA composition unique to an organism, the presence of antimicrobials-destroying genes, or mutation that can change the function or conformation of proteins related to drug resistance. Targeted sequencing with MinION is powerful and fast to detect pathogens in clinical samples. A novel diagnostic method for malaria using loopmediated isothermal amplification (LAMP) and MinION TM nanopore sequencer Rapid metagenomic identification of viral pathogens in clinical samples by real-time nanopore sequencing analysis MinION nanopore sequencing of multiple displacement amplified Mycobacteria DNA direct from sputum. cache = ./cache/cord-291749-revhbd0q.txt txt = ./txt/cord-291749-revhbd0q.txt === reduce.pl bib === === reduce.pl bib === id = cord-289535-srrfr1es author = Tregoning, J. S. title = Vaccines for COVID‐19 date = 2020-10-18 pages = extension = .txt mime = text/plain words = 14329 sentences = 793 flesch = 44 summary = One concern with vaccine development for SARS-CoV-2 is that the immune response can cause disease, often in the act of clearing the infection. Preclinical animal studies have demonstrated that DNA vaccines encoding the M, N, 3a or S proteins of the SARS-CoV-1 virus could elicit immune responses [180] [181] [182] . The S protein is the target of the only SARS-CoV-1 DNA vaccine to progress to Phase I clinical trial, delivered by bio-injector, and it was safe and induced neutralizing antibody responses [183] . T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial cache = ./cache/cord-289535-srrfr1es.txt txt = ./txt/cord-289535-srrfr1es.txt === reduce.pl bib === id = cord-291174-rym84kni author = Yang, Yazhi title = A label-free electrochemical assay for coronavirus IBV H120 strain quantification based on equivalent substitution effect and AuNPs-assisted signal amplification date = 2020-10-23 pages = extension = .txt mime = text/plain words = 3577 sentences = 234 flesch = 51 summary = title: A label-free electrochemical assay for coronavirus IBV H120 strain quantification based on equivalent substitution effect and AuNPs-assisted signal amplification According to the differences of S1 protein in various infectious bronchitis virus (IBV) strains, a target DNA sequence that can specifically recognize H120 RNA forming a DNA-RNA hybridized double-strand structure has been designed. Therefore, developing a rapid and sensitive method for identification and quantification of different IBV strains based on hypervariable region of S1 gene can effectively solve the problem, which plays important roles in IB early diagnosis and control, especially for vaccine production. Herein, a label-free electrochemical assay based on equivalent substitution effect and AuNPs-assisted signal amplification is developed for identification and quantification detection of IBV H120 strain. In this work, we designed the sequence of the target DNA based on the hypervariable region in the S1 gene between different IBV strains, then, constructed the standard plasmid containing characteristic sequence of S1 gene in H120 strain, Fig. 2 Real-time fluorescence quantitative PCR plot. cache = ./cache/cord-291174-rym84kni.txt txt = ./txt/cord-291174-rym84kni.txt === reduce.pl bib === id = cord-292794-okh6i4l1 author = Wang, Bin title = Protective efficacy of a broadly cross-reactive swine influenza DNA vaccine encoding M2e, cytotoxic T lymphocyte epitope and consensus H3 hemagglutinin date = 2012-06-27 pages = extension = .txt mime = text/plain words = 4776 sentences = 235 flesch = 44 summary = Results demonstrated that there was no detectable virus load in all the vaccine-immunized mice, while empty vector control group showed high lung viral titers ( Figure 4 ). Results indicated that all the mice that had been vaccinated with MHa had a detectable virus level, although showed a reduction in mean viral titers in both challenge groups compared with vector control, the reduction did not reach significance (p = 0.06 for rPan09 group and p = 0.67 for G11 group, Figure 4 ). The present study lays the foundation for universal swine influenza vaccine development, and call for further investigations in which the heterologous immune response should be further enhanced, such as the addition of molecular adjuvants [31, 32] and/or more copies of conserved viral protein encoding genes [33] , and the usage of DNA-prime protein/virus-boost immunization schedule [34, 35] . cache = ./cache/cord-292794-okh6i4l1.txt txt = ./txt/cord-292794-okh6i4l1.txt === reduce.pl bib === === reduce.pl bib === id = cord-284582-xwedgllw author = Korabecna, M. title = Cell-free DNA in plasma as an essential immune system regulator date = 2020-10-15 pages = extension = .txt mime = text/plain words = 5714 sentences = 306 flesch = 46 summary = These expression profiles provide evidence that the presence of cfDNA and its clearance in plasma of healthy individuals regulate fundamental mechanisms of the inflammation process and tissue homeostasis. We used native human plasma samples obtained from healthy volunteers with no animal serum addition to the cultivation medium in order to avoid the presence of uncharacterized animal cfDNA and DNases in the experiments. We used the validation phase results to perform a direct comparison of signaling pathways activated in cells as a consequence of their treatment with NP or TP samples (Table 1a , b) using the database Reactome. The changes in expression profiles of selected validated genes were detectable after the decrease of cfDNA levels to 69.10% of its original native concentration as the result of endogenous DNAse I activity ( Supplementary Fig. 1 ). However, the cells treated with identical plasma samples with degraded cfDNA directly activate IIR with elevated production of mRNA for interleukin 8 at the transcriptomic level. cache = ./cache/cord-284582-xwedgllw.txt txt = ./txt/cord-284582-xwedgllw.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-293072-giakcaki author = Xu, Wan-Xiang title = A simpler and more cost-effective peptide biosynthetic method using the truncated GST as carrier for epitope mapping date = 2017-10-12 pages = extension = .txt mime = text/plain words = 5303 sentences = 227 flesch = 52 summary = The protocol involves the following core steps: (i) design of plus and minus strands of DNA fragments encoding overlapping 8/18mer peptides; (ii) chemical synthesis of the designed DNA fragments; (iii) development of r-clones using pXXGST-3 vector expressing each 8/18mer peptide fused with truncated GST188 protein; (iv) screening r-clones by running the cell pellets from each induced clone on SDS-PAGE gel followed by sequencing of inserted DNA fragments for each verified r-clone; and (v) Western blotting with either monoclonal antibodies or polyclonal antibodies. cache = ./cache/cord-293072-giakcaki.txt txt = ./txt/cord-293072-giakcaki.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-292031-weiwksh6 author = Ramírez-Castillo, Flor Yazmín title = Waterborne Pathogens: Detection Methods and Challenges date = 2015-05-21 pages = extension = .txt mime = text/plain words = 7358 sentences = 378 flesch = 36 summary = Quantitative microbial risk assessment (QMRA) is a helpful tool to evaluate the scenarios for pathogen contamination that involve surveillance, detection methods, analysis and decision-making. Molecular techniques, such as nucleic acid amplification procedures, offer sensitive and analytical tools for detecting a variety of pathogens, including new emerging strains, present the possibility of automation, and real-time analysis to provide information for microbial risk assessment purposes [33] . Limitations of DNA based methods such as PCR include the inability to discriminate between viable from non-viable cells that both contain DNA, the low concentration of several pathogens in water such as Cryptosporidium, Giardia and viruses, and the lack of data to indicate the real infectious risk to a population. Oligonucleotide microarrays are a powerful genomic technology that is widely utilized to monitor gene expression under different cell growth conditions, detecting specific mutations in DNA sequences and characterizing microorganisms in environmental samples [76] . cache = ./cache/cord-292031-weiwksh6.txt txt = ./txt/cord-292031-weiwksh6.txt === reduce.pl bib === id = cord-291349-tq2n4mx3 author = Smith, Kevin R title = Gene transfer in higher animals: theoretical considerations and key concepts date = 2002-10-09 pages = extension = .txt mime = text/plain words = 12232 sentences = 661 flesch = 45 summary = The prospects for germline transgenesis via nuclear transfer (NT) are very significant: transgenes can be introduced to donor cells in vitro, permitting the production of genetically modified animals by NT . However, although retroviral-mediated gene therapy has been used successfully for (nonhuman) germline modifications, the most used */and to date the most useful */method for germline transgenesis is microinjection, reviewed in the following section. Because there are no special problems with microinjecting large transgene constructs, it is possible to incorporate structural gene-plus-promoter (plus other potentially useful sequences such as enhancers) combinations into the host genome. Therefore, the use of germline gene targeting as a means to avoiding transgene expression problems awaits progress in ES cell technology and NT technology. Following liposome-mediated gene transfer, amongst transgene molecules reaching the nucleus, only a minority integrate into the host cell chromosomes. cache = ./cache/cord-291349-tq2n4mx3.txt txt = ./txt/cord-291349-tq2n4mx3.txt === reduce.pl bib === id = cord-294712-kvvxmvqo author = Pelosse, Martin title = MultiBac: from protein complex structures to synthetic viral nanosystems date = 2017-10-30 pages = extension = .txt mime = text/plain words = 5379 sentences = 272 flesch = 38 summary = The MultiBac baculovirus/insect cell expression vector system was conceived as a user-friendly, modular tool-kit for producing multiprotein complexes for structural biology applications. We then turned our attention to eukaryotic methods, specifically an expression vector system relying on a recombinant baculovirus, to infect insect cell cultures for producing the complexes in which we had interest. This particular feature, and the-at least conceptually-relative ease of manipulating baculovirus in the laboratory by non-expert users, was exciting and led us on to the development of MultiBac: a baculovirus/insect cell system specifically engineered for expressing functional multiprotein complexes in the quality and quantity required for high-resolution structural and mechanistic studies [7] [8] [9] [10] [11] . The introduced genome alterations resulted in a virus that exhibited delayed lysis of the insect cells, allowing the production of recombinant protein complexes at very high levels while the cells seemingly remained intact [11] . The MultiBac baculovirus/insect cell expression vector system for producing complex protein biologics cache = ./cache/cord-294712-kvvxmvqo.txt txt = ./txt/cord-294712-kvvxmvqo.txt === reduce.pl bib === id = cord-286877-0h5vgi5c author = Dahiya, Shyam S. title = Immunogenicity of a DNA-launched replicon-based canine parvovirus DNA vaccine expressing VP2 antigen in dogs date = 2012-10-31 pages = extension = .txt mime = text/plain words = 5260 sentences = 261 flesch = 43 summary = When the pAlpha-CPV-VP2 was injected intradermal as DNA-launched replicon-based DNA vaccine in dogs, it induced CPV-specific humoral and cell mediated immune responses. To increase antigen production and immunogenicity with DNA vaccines, a new strategy has been developed to express the target heterologous antigen under the control of replicon from positive-strand RNA viruses with the promise of using the ability of these viruses to produce large amounts of viral proteins in infected cells. The replicon-based CPV DNA vaccine plasmid (pAlpha-CPV-VP2) encoding CPV-VP2 was constructed and evaluated to express CPV-VP2 protein in transfected cells in SDS-PAGE and Western blot (data not shown). To assess the protective efficacy of different CPV vaccines, sera collected from all immunized and control dogs were analyzed for presence of virus neutralizing (VN) antibody. CD8 + lymphocytes in dogs immunized with replicon-based CPV DNA vaccine compared to controls (Fig. 7) . There were over 24 thousand times more CPV-VP2 mRNA transcripts in pAlpha-CPV-VP2-transfected BHK-21 cells compared to respective non-replicating control indicating the self-replicating ability of replicon-based CPV-VP2 DNA vaccine. cache = ./cache/cord-286877-0h5vgi5c.txt txt = ./txt/cord-286877-0h5vgi5c.txt === reduce.pl bib === id = cord-296197-ohfhnpma author = Deborggraeve, Stijn title = A Simplified and Standardized Polymerase Chain Reaction Format for the Diagnosis of Leishmaniasis date = 2008-11-15 pages = extension = .txt mime = text/plain words = 4229 sentences = 207 flesch = 47 summary = A phase 1 evaluation of the text was conducted in clinical samples from 60 nonendemic and 45 endemic control subjects and from 44 patients with confirmed cutaneous leishmaniasis (CL), 12 with mucocutaneous leishmaniasis (MCL), and 43 with visceral leishmaniasis (VL) from Peru, Kenya, and Sudan. The Leishmania OligoC-TesT showed high specificity and sensitivity in clinical samples and was able to detect the parasite in samples obtained by less invasive means, such as blood, lymph, and lesion scrapings. Amplification of the parasite DNA by the polymerase chain reaction (PCR) has evolved into one of the most specific and sensitive methods for Leishmania detection [9, 10] . When evaluated in 56 clinical samples from patients with confirmed CL or MCL (definition based on microscopy and/or culture) collected in Peru, the Leishmania OligoC-TesT showed an overall diagnostic sensitivity of 92.9%, whereas all 8 dental biopsy specimens from healthy control subjects were negative. cache = ./cache/cord-296197-ohfhnpma.txt txt = ./txt/cord-296197-ohfhnpma.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-300040-rvrp5zvv author = Dutta, Noton Kumar title = Search for potential target site of nucleocapsid gene for the design of an epitope-based SARS DNA vaccine date = 2008-06-15 pages = extension = .txt mime = text/plain words = 4681 sentences = 255 flesch = 54 summary = We constructed eukaryotic expression plasmid encoding N [(N1 (nucleotide: 1-1269), N2 (nucleotide: 1-327), and N3 (nucleotide: 328-1296)) gene fragments of the SARS-CoV and compared their individual potential immune responses in BALB/c mice for use in the development of SARS vaccine candidates. In this report, we detected SARS-Cov N1 and N3 protein-specific immune response induced by pVAX-N1 and N3 DNA vaccination, respectively, and found significantly high titres of specific antibody and specific cell mediated immunity compared to control. These results indicate that N protein, which naturally exists in virus particles after binding of viral RNA, was able to induce strong humoral and cellular immune responses when induced by DNA vaccine, and it might be a prospective candidate gene for development of SARS-CoV vaccine. showed that expression of membrane protein augments the specific responses induced by SARS-CoV nucleocapsid DNA immunization. The expression of membrane protein augments the specific responses induced by SARS-CoV nucleocapsid DNA immunization cache = ./cache/cord-300040-rvrp5zvv.txt txt = ./txt/cord-300040-rvrp5zvv.txt === reduce.pl bib === === reduce.pl bib === id = cord-298697-v1qdizwx author = Chang, Jia Jin Marc title = Takeaways from Mobile DNA Barcoding with BentoLab and MinION date = 2020-09-24 pages = extension = .txt mime = text/plain words = 7206 sentences = 395 flesch = 56 summary = One of the most common applications of MinION is for nanopore-based DNA barcoding in situ for species identification and discovery, yet the existing sample capability is limited (n ≤ 10). We also tested the performance of the newly released R10.3 nanopore flow cell for DNA barcoding, and showed that the barcodes generated were ~99.9% accurate when compared to Illumina references. For the field sequencing phase, an additional 31 samples were collected and subjected to QE-based DNA extraction on the BentoLab. While we did not run the gel check in situ to save time, a postliminary amplification check on agarose back at the laboratory revealed 20 observable gel bands. For the field sequencing phase, an additional 31 samples were collected and subjected to QE-based DNA extraction on the BentoLab. While we did not run the gel check in situ to save time, a postliminary amplification check on agarose back at the laboratory revealed 20 observable gel bands. cache = ./cache/cord-298697-v1qdizwx.txt txt = ./txt/cord-298697-v1qdizwx.txt === reduce.pl bib === id = cord-298051-ej8qxkce author = Louten, Jennifer title = Detection and Diagnosis of Viral Infections date = 2016-05-06 pages = extension = .txt mime = text/plain words = 11204 sentences = 602 flesch = 57 summary = Cell lines can be infected with patient samples to allow viral replication within the cells; observable cytopathic effects can help to identify the identity of the virus. Infected cells can also be used for immunofluorescence assays, which use fluorescently labeled virus-specific antibodies to identify viruses in fixed cells or tissues. In the process of PCR, DNA (including any viral DNA present) is isolated from the clinical specimen, generally blood cells or tissue, and added to a tube containing primers, DNA polymerase, and nucleotides ( Fig. 7.14) . The diagnostic techniques described in this chapter identify the presence of a virus in a sample, or even the amount of viral nucleic acid, but these assays cannot determine the amount of virus present that is capable of productively infecting cells. Fluorescently labeled antibodies bind to viral antigens present in infected cells. cache = ./cache/cord-298051-ej8qxkce.txt txt = ./txt/cord-298051-ej8qxkce.txt === reduce.pl bib === id = cord-292757-d03byeee author = Zhou, Xianfeng title = Enhance immune response to DNA vaccine based on a novel multicomponent supramolecular assembly date = 2007-08-07 pages = extension = .txt mime = text/plain words = 4707 sentences = 237 flesch = 46 summary = Here, a novel multicomponent supramolecular system involving the preparation of mannose-bearing chitosan oligomers microspheres with entrapping complexes of DNA vaccine and polyethylenimine was developed to mimic many of the beneficial properties of the viruses. After delivery by intramuscular immunization in BALB/c mice, the microspheres induced an enhanced serum antibody responses two orders of magnitude greater than naked DNA vaccine. Here we have designed novel mannose-bearing chitosan oligomers (MBCO) microspheres with entrapping polyethylenimine (PEI)/DNA complexes to mimic the beneficial properties of viruses: Hence, the MBCO microspheres mimic the following five desirable characteristics of a virus: (i) DNA condensation; (ii) cell entry-targeting; (iii) endosome escape; (iv) compact viral size (200-300 nm) and (v) efficient decomplexation. These studies have demonstrated that MBCO microspheres were potent delivery systems for DNA vaccines and are capable of inducing the enhanced humoral and cellular responses (about 100-fold) after i.m. immunization with HBsAg plasmid. cache = ./cache/cord-292757-d03byeee.txt txt = ./txt/cord-292757-d03byeee.txt === reduce.pl bib === === reduce.pl bib === id = cord-296967-qiil3gqk author = Tatlow, Dean title = A novel concept for treatment and vaccination against Covid‐19 with an inhaled chitosan‐coated DNA vaccine encoding a secreted spike protein portion date = 2020-08-08 pages = extension = .txt mime = text/plain words = 2262 sentences = 143 flesch = 52 summary = A novel concept in DNA vaccine design is the creation of an inhaled DNA plasmid construct containing a portion of the coronavirus spike protein for treatment and vaccination. An inhaled plasmid DNA vaccine replicates the route of lung infection taken by coronavirus with transfected cells secreting spike protein portions to induce immunity. 3 These findings of the identified spike proteins in the SARS-CoV-2 receptor binding domain and ACE2 region may provide useful information for treatment or vaccine development. 5 In this paper a series of inhaled plasmid DNA vaccine construct containing various forms of the coronavirus spike protein sequence may provide potential treatment and vaccine options as revealed by Yu et al. 3 Once in the lower respiratory tract or alveolar region of the lung deposited plasmid DNA will be taken up and expression of coronavirus spike proteins by host cells such as pneumocytes will occur. cache = ./cache/cord-296967-qiil3gqk.txt txt = ./txt/cord-296967-qiil3gqk.txt === reduce.pl bib === id = cord-298514-l2hs1h9c author = Ghosh, Soma title = Central Role of Ubiquitination in Genome Maintenance: DNA Replication and Damage Repair date = 2012-02-08 pages = extension = .txt mime = text/plain words = 5360 sentences = 276 flesch = 39 summary = The ubiquitin system mediates the DNA damage response to all the above forms of replicative damage in the cell in order to prevent genomic instability and onset of cancer. The checkpoint apparatus targets the CDK regulators like cyclins, CDK inhibitors, or CDC25 family of dual-specificity phosphatases, depending upon the stage of the cell cycle in which the DNA damage has occurred. SCF ßTrCP also regulates checkpoint recovery: the ubiquitin-dependent degradation of CLASPIN (a DNA-binding protein required for the ATR mediated activation of Chk1 in response to DNA replication stress) in G2 allows efficient termination of DNA replication checkpoint which is necessary for progression of the cell into mitosis [36] [37] [38] [39] . Regulation of Claspin degradation by the ubiquitin-proteosome pathway during the cell cycle and in response to ATR-dependent checkpoint activation cache = ./cache/cord-298514-l2hs1h9c.txt txt = ./txt/cord-298514-l2hs1h9c.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-296356-qkvafy69 author = Garman, Elspeth title = SARS Proteomics Reveals Viral Secrets date = 2005-11-30 pages = extension = .txt mime = text/plain words = 1306 sentences = 74 flesch = 51 summary = The structure of the mutagenic base pair in the confines of a closed polymerase complex exposes some of those strategies. (2005) In a worldwide cooperative research effort involving a multidisciplinary approach, structural and functional characterization of the SARS virus and its host interactions has been swiftly pursued. By sequence alignment and structural comparison with all known H2A domains, as well as examination of functional data, the authors conjecture that proteins from this superfamily form an emerging group of nucleotide phosphatases, all with similar functionality. This has two pivotal consequences for understanding the biology of the virus: A systematic approach is essential, and, even more importantly, a deeper structural and functional knowledge of the many complexes that the SARS CoV proteins form with one another and with proteins of the host organisms will be required-research that is still in its infancy. cache = ./cache/cord-296356-qkvafy69.txt txt = ./txt/cord-296356-qkvafy69.txt === reduce.pl bib === === reduce.pl bib === id = cord-292569-h8fe0zio author = Lee, Si-Hyeong title = Preferential production of IgM-secreting hybridomas by immunization with DNA vaccines coding for Ebola virus glycoprotein: use of protein boosting for IgG-secreting hybridoma production date = 2017-07-26 pages = extension = .txt mime = text/plain words = 5460 sentences = 281 flesch = 58 summary = title: Preferential production of IgM-secreting hybridomas by immunization with DNA vaccines coding for Ebola virus glycoprotein: use of protein boosting for IgG-secreting hybridoma production These data suggest that immunization with GP DNA vaccines leads to preferential production of hybridomas secreting IgM Abs with little antigen specificity, and that boosting with GP can overcome this propensity. Taken together, these data suggest that boosting with GP could be useful for producing hybridomas that secrete antigen-specific IgG Abs. Six-week-old, female BALB/c mice were purchased from Daehan Biolink (Eumseong, Korea). These data suggest that 11 of the hybridoma clones may secrete IgM Abs with high avidity to mulIgG was purified from cell supernatants using the protein G-resin column (for A6-9). This finding, along with our previous findings, suggests that antigen-specific Ab responses, primed by DNA vaccination, may be boosted by protein immunization, leading to preferential production of IgG-secreting hybridomas. cache = ./cache/cord-292569-h8fe0zio.txt txt = ./txt/cord-292569-h8fe0zio.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-303265-v6ci69n0 author = Domingo, Esteban title = Introduction to virus origins and their role in biological evolution date = 2019-11-08 pages = extension = .txt mime = text/plain words = 15685 sentences = 764 flesch = 42 summary = Topics covered include molecular mechanisms of genetic variation, with emphasis on high mutation rates, Darwinian principles acting on viruses, quasispecies dynamics and its implications, consequences for virus-host interactions, fitness as a relevant parameter, experimental model systems in cell culture, ex-vivo and in vivo, long-term virus evolution, the current situation of antiviral strategies to confront quasispecies swarms, and conceptual extensions of quasispecies to nonviral systems. With regard to the concepts of genome stability versus variation addressed in this book, it is helpful to divide viruses into four groups, depending on whether it is DNA or RNA the type of genetic material, which acts as a replicative intermediate in the infected cell (bottom gray shaded boxes in Fig. 1.1 ). They were selected for replicability, stability, and evolvability with trade-offs 1.4 Origin of life: a brief historical account and current views (acquisition of benefits for one of the three traits at some cost for another trait) likely play a role at this stage (see Chapter 4 for trade-offs in virus evolution). cache = ./cache/cord-303265-v6ci69n0.txt txt = ./txt/cord-303265-v6ci69n0.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-301167-101lnq4f author = Liu, Quanjun title = Microarray-in-a-Tube for Detection of Multiple Viruses date = 2007-02-01 pages = extension = .txt mime = text/plain words = 3248 sentences = 177 flesch = 48 summary = Methods: We developed a novel PCR assay, the microarray-in-a-tube system, which integrates multiple PCR processes and DNA microarrays for multiple virus detection. A 5 × 5 oligonucleotide microarray for detecting 4 respiratory tract viruses (severe acute respiratory syndrome–associated coronavirus, influenza A virus, influenza B virus, and enterovirus) with inner controls was arranged on the inner surface of a specially designed Eppendorf cap with a flat, optically transparent window. We aimed to develop a microarray-in-a-tube that integrates RT-PCR and a DNA microarray for detecting and distinguishing 4 viruses causing human acute respiratory tract infection, SARS coronavirus, influenza A and B viruses, and enterovirus. The system (Fig. 1 ) has 3 parts, which include an optically transparent plastic cap with an oligonucleotide microarray on the inner surface, a black inner vessel that contains hybridization solution, and the body of the Eppendorf tube. cache = ./cache/cord-301167-101lnq4f.txt txt = ./txt/cord-301167-101lnq4f.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-305024-343l2ha7 author = Sonntag, Michael title = New Adenovirus in Bats, Germany date = 2009-12-17 pages = extension = .txt mime = text/plain words = 1686 sentences = 82 flesch = 44 summary = We performed an extensive search for unknown viruses in 55 German vespertilionid bats based on both generic PCR assays and virus isolation techniques, as part of a broader study investigating histopathologic changes in German bats in association with infectious pathogens. The obtained sequence of a fragment of the DNA polymerase gene (≈550 bp) indicated that the viruses were a novel virus type within the genus Mastadenovirus and was tentatively named bat adenovirus 2 (bat AdV-2) strain P. Although viruses were not detected by various generic PCR assays from homogenized frozen tissue samples, we isolated a novel virus from a hibernating insectivorous bat species. The acquired partial sequence of the bat AdV-2 DNA polymerase with the closest relation to canine adenovirus (only 74% at the nucleic acid level) and the isolation from a new animal host suggests that this virus is a new adenovirus species within the genus Mastadenovirus. cache = ./cache/cord-305024-343l2ha7.txt txt = ./txt/cord-305024-343l2ha7.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-031907-ilhr3iu5 author = nan title = ISEV2020 Abstract Book date = 2020-07-15 pages = extension = .txt mime = text/plain words = 200999 sentences = 11528 flesch = 44 summary = L.M., and the National Institutes of Health (R35GM119623) to T.R.G. The addition of a size exclusion chromatography step to various urinary extracellular vesicle concentrating methods reveals differences in the small RNA profile Introduction: Urinary extracellular vesicles (EVs) and their RNA cargo are a novel source of biomarkers for various diseases, however non-vesicular RNA (e.g. associated with proteins) is also present within urine. We then evaluated efficiency of heart targeting for eAAV9 or eAAV6 and standard AAV9 or AAV6 encoding for EGFP, mCherry or firefly luciferase in different human cell lines in vitro, in black mouse and in passive immunity nude mouse model in vivo using flow cytometry, confocal microscopy, Langendorff perfusion system and Methods: HLHS patients (n = 3) after Glenn procedure and swine (n = 3) after PAB were given RV injections of allogeneic/xenogeneic MSCs. Donor-specific, HLA-I+, exosomes were isolated from plasma. cache = ./cache/cord-031907-ilhr3iu5.txt txt = ./txt/cord-031907-ilhr3iu5.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-303978-z3888e3g author = Hong, Ka Lok title = Single-Stranded DNA Aptamers against Pathogens and Toxins: Identification and Biosensing Applications date = 2015-06-23 pages = extension = .txt mime = text/plain words = 15716 sentences = 988 flesch = 47 summary = Multiple virulent strains of the gram-negative bacteria, Escherichia coli, have been chosen as targets for the selection of specific ssDNA MREs due to their enterotoxigenic effects and the potential of contaminating food and water [39] . They also developed a sandwich detection system, in which biotinylated antibodies targeting the K88 strain were immobilized on magnetic beads as the capturing element and the 5 FITC labeled ssDNA library from round 13 selection served as the reporter in a fluorescent assay. In their later study, the affinities of selected candidate MREs were improved with reported values of in the nanomolar range and were specific for the target bacteria at different growth phases [57] . Acetamiprid Immobilization free 4.98 M -[27] Fluorescence plate based cross-binding assay showed the ssDNA MRE was approximately two to five times more selective on the alpha toxin than negative targets. cache = ./cache/cord-303978-z3888e3g.txt txt = ./txt/cord-303978-z3888e3g.txt === reduce.pl bib === id = cord-306754-qohrnpgq author = Lee, Justin S. title = Targeted Enrichment for Pathogen Detection and Characterization in Three Felid Species date = 2017-05-23 pages = extension = .txt mime = text/plain words = 7158 sentences = 335 flesch = 48 summary = Our report provides advances in investigating several important aspects of TGC assay design, including (i) the range of fold enrichment possible for targeted nucleic acids, (ii) comparison of TGC pathogen detection with traditional methods currently used by diagnostic laboratories, (iii) documentation that a single assay design can be applied to more than one host species, (iv) the applicability of TGC to characterize pathogens in the context of veterinary medicine, and (v) the ability of TGC-NGS to characterize intrahost genetic diversity of viral pathogens (4) (5) (6) . Mean enrichment values of 250,000-fold and 9,100,000-fold with the DNA and RNA probes, respectively, and 147,000-fold for FIV contained in tissues clearly demonstrate the ability of the targeted capture probes to dramatically alter the relative abundance of specific nucleic acids across a range of sample types and diverse pathogen taxa. cache = ./cache/cord-306754-qohrnpgq.txt txt = ./txt/cord-306754-qohrnpgq.txt === reduce.pl bib === id = cord-304869-l6a68tqn author = Bielińska-Wąż, Dorota title = Graphical and numerical representations of DNA sequences: statistical aspects of similarity date = 2011-08-28 pages = extension = .txt mime = text/plain words = 15408 sentences = 940 flesch = 60 summary = As a consequence, different aspects of similarity, as for example asymmetry of the gene structure, may be studied either using new similarity measures associated with four-component spectral representation of the DNA sequences or using alignment methods with corrections introduced in this paper. The corrections to the alignment methods and the statistical distribution moment-based descriptors derived from the four-component spectral representation of the DNA sequences are applied to similarity/dissimilarity studies of β-globin gene across species. How to restrict the graphs representing the sequences to two-dimensional plots and how to avoid degeneracies has been the subject of numerous studies which resulted in many graphical representations (see subsequent chapters). It is shown in the last chapter of this work that by using the four-component spectral representation one can recognize the difference in one base between a pair of sequences so it can be used for single nucleotide polymorfism (SNP) analyses which is subject of many investigation, as for example, in a recent work by Bhasi et al. cache = ./cache/cord-304869-l6a68tqn.txt txt = ./txt/cord-304869-l6a68tqn.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-304424-048xo7jn author = Greninger, Alexander L. title = A decade of RNA virus metagenomics is (not) enough date = 2018-01-15 pages = extension = .txt mime = text/plain words = 9606 sentences = 495 flesch = 43 summary = That same year 36,789 colony sequences from DNase-treated RNA extracted from viral concentrates of human feces revealed a preponderance of pepper mild mottle virus and other plant viruses, but no new human viruses (Zhang et al., 2005) . While finding a new virus in the environment is not necessarily a problem in either DNA or RNA, the low fidelity of RNA polymerases and the sequence space they are capable of sampling, along with the possibility of recombination, lend themselves to new species and genera that are the trophies of metagenomic viral discovery. While metagenomics delivered on the promise of finding novel human viruses, viral discovery in humans has increasingly become a tragic story of patients interacting with the wrong squirrel or tick on the wrong day and most samples sequenced are frankly negative (Hoffmann et al., 2015; McMullan et al., 2012) . The greatest paradigm shifter in recent viral metagenomics work has been the sheer number and diversity of novel RNA viruses present in arthropods and invertebrates. cache = ./cache/cord-304424-048xo7jn.txt txt = ./txt/cord-304424-048xo7jn.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-015394-uj7fe5y6 author = nan title = Scientific Abstracts date = 2008-12-23 pages = extension = .txt mime = text/plain words = 242330 sentences = 15267 flesch = 52 summary = Studies involving immunohistochemical analysis of normal ovaries have shown that granulosa cells express significantly higher levels of the activator protein-1 (AP-1) transcription factor, cFos compared to theca cells, where cFos expression is virtually absent. Following acute hypoxia (0.5% O2) for one to six hours, RhoA mRNA, total protein and activation (RhoA-GTP) levels were analysed, using semi-quantitative PCRs and western blot, and compared to normoxic non-pregnant human uterine smooth muscle control cells. Since there is an urgent need for non-invasive methods for determination of fetal (F) and placental (P) function, this study was designed to evaluate the genes differently and commonly expressed in P tissue and leukocytes in maternal (M) and F circulation.Material and Methods. The current study: 1) localized IL-6 mRNA levels in preeclamptic versus normal decidual sections; 2) evaluated mechanisms regulating IL-6 synthesis by targeting intracellular signaling pathways with specific inhibitors; 3) identified potential IL-6 targets by immunolocalizing the IL-6 receptor (IL-6R) to specific cell types in placental bed biopsies. cache = ./cache/cord-015394-uj7fe5y6.txt txt = ./txt/cord-015394-uj7fe5y6.txt === reduce.pl bib === id = cord-306798-f28264k3 author = Walsh, Geraldine M. title = Blood-Borne Pathogens: A Canadian Blood Services Centre for Innovation Symposium date = 2016-02-23 pages = extension = .txt mime = text/plain words = 15308 sentences = 723 flesch = 45 summary = Transfusion services can employ indirect measures such as surveillance, hemovigilance, and donor questioning (defense), protein-, or nucleic acid based direct testing (detection), or pathogen inactivation of blood products (destruction) as strategies to mitigate the risk of transmission-transmitted infection. Cost concerns make it likely that pathogen inactivation will be contemplated by blood operators through the lens of health economics and risk-based decision making, rather than in zero-risk paradigms previously embraced for transfusable products. Dr Margaret Fearon, CBS Medical Director, Medical Microbiology, and Assistant Professor, University of Toronto, discussed the current prevalence of classical transfusion-transmissible infections (TTIs) in CBS blood donors, new and emerging infectious diseases, how CBS prepares for and manages new risks, and also addressed new paradigms for risk management. Other transfusion-transmissible diseases are currently being monitored as potential emerging threats to the safety of the blood supply, including babesiosis, hepatitis E, CHIKV, and dengue virus. cache = ./cache/cord-306798-f28264k3.txt txt = ./txt/cord-306798-f28264k3.txt === reduce.pl bib === id = cord-306904-8iteddug author = Uversky, Vladimir N title = Unreported intrinsic disorder in proteins: Building connections to the literature on IDPs date = 2014-12-12 pages = extension = .txt mime = text/plain words = 18422 sentences = 1012 flesch = 48 summary = 86 Figure 8C represents the results of the computational disorder analysis in human APC (UniProt ID: P04070) and shows that mentioned loops enriched in basic residues are predicted to be disordered or very flexible, thereby providing an interesting mechanistic plane for the molecular basis of APC recognition and binding of FVIII. 96 Figure 8E shows that although human PECAM-1 (UniProt ID: P16284) is predicted to be mostly ordered, the residues, phosphorylation of which is crucial for its function (Y 663 and Y 686 ), are located within the highly disordered C-terminal tail. 210 Figure 14C represents the results of the disorder analysis of human AMSH (UniProt ID: O95630) and shows that this protein contains a long IDPR (residues 90-250) thereby illustrating that the N-terminal part of the analyzed catalytic domain is predicted to be disordered. [222] [223] [224] Figure 14D shows that human Purb protein (UniProt ID: O35295) is predicted to possess significant amount of functionally important intrinsic disorder. cache = ./cache/cord-306904-8iteddug.txt txt = ./txt/cord-306904-8iteddug.txt === reduce.pl bib === id = cord-306780-9xelf8oh author = Dale, Timothy D. title = Enhancement of wildlife disease surveillance using multiplex quantitative PCR: development of qPCR assays for major pathogens in UK squirrel populations date = 2016-07-28 pages = extension = .txt mime = text/plain words = 6931 sentences = 371 flesch = 54 summary = However, comparatively few wildlife epidemiological studies use quantitative PCR (qPCR) for pathogen detection, even fewer employ an internal control, to ensure confidence in negative results, and PCR's ability to multiplex and therefore detect several targets in a single reaction is underutilised. Tests on infected squirrel tissue demonstrate that simple swab samples (particularly from distal antebrachial skin) are sufficient to detect and identify the relative quantity of SQPV DNA in both squirrel species, while rectal swabs and blood cell pellets can be used to reliably indicate SADV infection. As grey squirrels appear asymptomatic, lower infection loads are recorded, and thus it is essential to use the more sensitive qPCR assays when screening for SQPV presence as part of a wildlife disease management programme for red squirrels. cache = ./cache/cord-306780-9xelf8oh.txt txt = ./txt/cord-306780-9xelf8oh.txt === reduce.pl bib === === reduce.pl bib === id = cord-311023-4ge4glq9 author = Hsieh, Yi-Fan title = A Lego(®)-like swappable fluidic module for bio-chem applications date = 2014-12-01 pages = extension = .txt mime = text/plain words = 3386 sentences = 172 flesch = 51 summary = In this study, we demonstrate an advanced Lego ® -like swappable fluidic module (SFM) concept using PDMS blocks with assorted channel geometries that effortlessly connect to form fully functional microfluidic devices. Gold nanoparticles were also synthesized by rapid mixing and reactive chloroauric acid (HAuCl 4 ) and sodium citrate (Na 3 Table 1 presents the modular fluidic components used to integrate Lego ® -like SFMs. The functional components consisted of finger-operated, electricity-free pumps, a one-way valve, vortextype mixer, reservoir, and heating block (with the associated block names P, OWV, VM, R, and HB), and the straight tube (ST), T-type tube (TT-F, TT-M with F, and M denoting a male to female type of sealing face), cross tube (CT-F, CT-M), corner tube (CT), and height tube (HT) were categorized as auxiliary components and the corresponding model numbers were listed below each schematic, which demonstrated the mass production feasibility of Lego ® -like SFMs in several sizes. cache = ./cache/cord-311023-4ge4glq9.txt txt = ./txt/cord-311023-4ge4glq9.txt === reduce.pl bib === === reduce.pl bib === id = cord-310268-8q4tk6fd author = Zhu, Qinchang title = DNA Aptamers in the Diagnosis and Treatment of Human Diseases date = 2015-11-25 pages = extension = .txt mime = text/plain words = 8649 sentences = 411 flesch = 47 summary = Nucleic acid aptamers are RNA and single-stranded (ss) DNA oligonucleotides with lengths typically ranging from 15 to 70 mers, which have the same level of target-binding affinity as monoclonal antibodies (the dissociation constant (K d ) usually ranges from 0.1 to 50 nM) [5, 6] . This SELEX is able to generate DNA aptamers that recognize the cell-surface or intracellular target protein in their native conformation, which shows great potential in cell-specific therapeutics and diagnostic applications [26] [27] [28] . Recently, modified cell-SELEX methods have been developed to select aptamers targeting specific cells like disease state cells and metastatic cells. In the era of personalized medicine, DNA aptamer-based therapeutics and diagnostics are believed to have great potential for extensive application because of their flexibility to specifically bind to any molecule targets. cache = ./cache/cord-310268-8q4tk6fd.txt txt = ./txt/cord-310268-8q4tk6fd.txt === reduce.pl bib === id = cord-310734-6v7oru2l author = Bolatti, Elisa M. title = A Preliminary Study of the Virome of the South American Free-Tailed Bats (Tadarida brasiliensis) and Identification of Two Novel Mammalian Viruses date = 2020-04-09 pages = extension = .txt mime = text/plain words = 8477 sentences = 405 flesch = 41 summary = By conventional nucleic acid detection techniques and/or bioinformatics approaches, the genomes of two novel viruses were completely covered clustering into the Papillomaviridae (Tadarida brasiliensis papillomavirus type 1, TbraPV1) and Genomoviridae (Tadarida brasiliensis gemykibivirus 1, TbGkyV1) families. Overall, a large number of phage-related sequences were detected (77.3% of viral read pairs and 39.9% of viral contigs), likely representing the most abundant entities infecting bacteria present in the bat digestive system, which exhibited similarity mostly to the families Inoviridae, Siphoviridae, and Myoviridae ( Table 1 ). Several mammalian viral families, supported by the contigs and sequencing reads, have been identified previously in New World [23, 24, 26] and Old World [17, 18, 89] bat species. Table S4 : Read pairs and contigs classified as similar to viruses and not taxonomical assigned to viral families identified in anal and oral swab samples of Tadarida brasiliensis obtained by metagenomics using Illumina technology. cache = ./cache/cord-310734-6v7oru2l.txt txt = ./txt/cord-310734-6v7oru2l.txt === reduce.pl bib === id = cord-307768-xx46w6dc author = Ding, Yun title = From single-molecule detection to next-generation sequencing: microfluidic droplets for high-throughput nucleic acid analysis date = 2017-03-10 pages = extension = .txt mime = text/plain words = 9490 sentences = 506 flesch = 44 summary = title: From single-molecule detection to next-generation sequencing: microfluidic droplets for high-throughput nucleic acid analysis Recent applications of such technologies to genetic analysis have suggested significant utility in low-cost, efficient and rapid workflows for DNA amplification, rare mutation detection, antibody screening and next-generation sequencing. 2003) , with the relative concentration of each reagent being defined by the Fig. 1 a Physical and chemical variables in droplet-based experiments: (1) Temperature can be controlled over wide ranges, enabling PCR in emulsions; (2) Hydrophobic substrates or ligands can be delivered through the oil phase into aqueous droplets; (3) Watersoluble components can be delivered through nanoscale droplets or swollen micelles, allowing the regulation of biochemical processes; (4) Internal pH can be altered, for example, by the delivery of acetic acid; (5) Photocaged substrates and ligands can be introduced into the droplets during emulsification and photoactivated at later times. Two recent studies describing single-cell RNA sequencing methods using droplet-based microfluidics [termed Drop-seq (Macosko et al. cache = ./cache/cord-307768-xx46w6dc.txt txt = ./txt/cord-307768-xx46w6dc.txt === reduce.pl bib === id = cord-307909-7vbxyns0 author = Ronda, Luca title = Rational Design of a User-Friendly Aptamer/Peptide-Based Device for the Detection of Staphylococcus aureus date = 2020-09-02 pages = extension = .txt mime = text/plain words = 9356 sentences = 417 flesch = 43 summary = We coupled the selectivity and affinity of aptamers, short nucleic acids sequences able to recognize specific epitopes on bacterial surface, immobilized at high density on a nanostructured zirconium dioxide surface, with the rational design of specifically interacting fluorescent peptides to assemble an easy-to-use detection device. λ-Cro is a 66 aa protein that plays a pivotal role in the switch from lysogenic to lytic phase in the growth cycle of phage λ and represented a suitable scaffold for several reasons: (i) the availability of threedimensional structures both in the presence and absence of its cognate DNA (PDB ID: 6cro [60] and 5cro [80] , respectively) allows detailed structural evaluations; (ii) the helix-turn-helix motif of the DNA binding domain is relatively small and all the interactions between the nucleobases of the consensus sequence and the peptidic backbone are well characterized; (iii) the minimum functional portion of the consensus sequence is quite short and made by contiguous nucleobases along the two strands of the DNA target; (iv) previous works reported successful examples of Cro reprogramming for binding consensus sequences that differ from the wild type [79] . cache = ./cache/cord-307909-7vbxyns0.txt txt = ./txt/cord-307909-7vbxyns0.txt === reduce.pl bib === === reduce.pl bib === id = cord-312757-58p5b2vw author = Pérez-Montoto, Lázaro G. title = Scoring function for DNA–drug docking of anticancer and antiparasitic compounds based on spectral moments of 2D lattice graphs for molecular dynamics trajectories date = 2009-11-30 pages = extension = .txt mime = text/plain words = 4825 sentences = 256 flesch = 53 summary = Abstract We introduce here a new class of invariants for MD trajectories based on the spectral moments πk (L) of the Markov matrix associated to lattice network-like (LN) graph representations of Molecular Dynamics (MD) trajectories. We propose this new model as a scoring function to guide DNA-docking studies in the drug design of new coumarins for anticancer or antiparasitic PUVA therapy. In addition, predicting drug activity we can use 3D drugtarget QSAR/QSBR models as scoring function to guide the search of optimal drug-target interaction geometries in drug-target docking studies [42] [43] [44] . The new model is also QSBR that has potential applications as scoring function for DNA-furocoumarin docking studies. The DNA-drug docking molecular dynamics trajectories or energetic profiles of all the starting intercalation complexes were obtained by means of the Monte Carlo [155] method, using the HyperChem package. We can obtain new types of 2D graph theoretical representation for Molecular Dynamics (MD) trajectories that resemble LNs used for DNA and protein sequences. cache = ./cache/cord-312757-58p5b2vw.txt txt = ./txt/cord-312757-58p5b2vw.txt === reduce.pl bib === id = cord-307914-lgprrwee author = Bartok, Eva title = Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids date = 2020-07-14 pages = extension = .txt mime = text/plain words = 17726 sentences = 1100 flesch = 51 summary = Indeed, the functionalization of CRISPR/Cas systems as a tool for genomic editing have revealed important differences in human and murine NA sensing, including distinct cell subset expression patterns of NA-sensing Toll-Like Receptors (TLRs) or species differences in the structural requirements for the detection of cyclic dinucleotide cGAMP by STING. As a long dsRNA with a 5 0 diphosphate terminus, polyI:C is known to activate the sensing receptors TLR3, MDA5, and RIG-I (Alexopoulou et al., 2001; Gitlin et al., 2006; Kato et al., 2008; Yoneyama et al., 2005) , accessory proteins such including LGP2 and members of the DDX and DHX families (reviewed in Oshiumi et al., 2016) as well as the restriction factors PKR and the OAS family (Farrell et al., 1978; Hovanessian et al., 1977; Zilberstein et al., 1978) . cache = ./cache/cord-307914-lgprrwee.txt txt = ./txt/cord-307914-lgprrwee.txt === reduce.pl bib === id = cord-309642-wwaa6ls0 author = Potgieter, Leon N.D. title = Pathogenesis of Viral Infections date = 1986-11-30 pages = extension = .txt mime = text/plain words = 10859 sentences = 770 flesch = 40 summary = 7 · 18 · 84 · 133 Such restrictions function at the cellular level either as the presence or absence of appropriate cell surface receptors (in some instances, they have been shown to be inherited as dominant alleles in a Mendelian manner) 9 · 18 · 26 · 46 · 68 · 97 ·u 9 · 120 or the intracellular hospitality of the cell (several genetic host restrictions on virus replication have been identified).18·32·59·80·82·108·109·120·126 Restricted growth of several DNA viruses in some cells results in transformation without production of progeny viruses. 112 The phenomenon appears to be mediated by virus-induced receptors on the surface membrane of cells and may be one mechanism of the often-encountered secondary bacterial infections associated with viral diseases. 51 · 52 · 104 Viral respiratory tract disease is a consequence of mechanical and biochemical injury to epithelial cells and alveolar macrophages, which can, in the most severe instances, result in secondary bacterial infection, pneumonia, and death. cache = ./cache/cord-309642-wwaa6ls0.txt txt = ./txt/cord-309642-wwaa6ls0.txt === reduce.pl bib === id = cord-309083-ew9cwiw0 author = Su, Hang title = Cyprinid viral diseases and vaccine development date = 2018-09-07 pages = extension = .txt mime = text/plain words = 11167 sentences = 585 flesch = 43 summary = In this review, authors summarized six major cyprinid viral diseases, including koi herpesvirus disease (KHVD), spring viraemia of carp (SVC), grass carp hemorrhagic disease (GCHD), koi sleepy disease (KSD), carp pox disease (CPD) and herpesviral haematopoietic necrosis (HPHN). Challenge experiment reveals that the oral recombinant subunit vaccine can protect 50%-60% grass carp from infection and generate immunity against GCRV [199] . Oral vaccination is an effective way to induce mucosal immunity [215] and this strategy has shown a successful induction of the antiviral responses against viral diseases in different fish species [165] . Gene expression analysis of common carp (Cyprinus carpio L.) lines during cyprinid herpesvirus 3 infection yields insights into differential immune responses Recombinant lactobacillus expressing G protein of spring viremia of carp virus (SVCV) combined with ORF81 protein of koi herpesvirus (KHV): a promising way to induce protective immunity against SVCV and KHV infection in cyprinid fish via oral vaccination cache = ./cache/cord-309083-ew9cwiw0.txt txt = ./txt/cord-309083-ew9cwiw0.txt === reduce.pl bib === id = cord-312517-b24zlaqt author = Kim, Denny title = The Brighton collaboration standardized template for collection of key information for benefit-risk assessment of nucleic acid (RNA and DNA) vaccines date = 2020-06-19 pages = extension = .txt mime = text/plain words = 1948 sentences = 98 flesch = 44 summary = title: The Brighton collaboration standardized template for collection of key information for benefit-risk assessment of nucleic acid (RNA and DNA) vaccines The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of nucleic acid vaccines. The Brighton Collaboration formed the Viral Vector Vaccines Safety Working Group (V3SWG) in October 2008 to improve the ability of key stakeholders to anticipate potential safety issues and meaningfully assess or interpret safety data, thereby facilitating greater public acceptance when viral vector vaccines are licensed [2] . When completing information on adverse effects in Section 8, please provide as many details as possible based on the Brighton Collaboration Guidelines for collection, analysis and presentation of vaccine safety data in pre-and post-licensure clinical studies [13] . cache = ./cache/cord-312517-b24zlaqt.txt txt = ./txt/cord-312517-b24zlaqt.txt === reduce.pl bib === id = cord-308687-wrzzb9cy author = Brunner, Jesse L. title = Pooled samples and eDNA-based detection can facilitate the “clean trade” of aquatic animals date = 2020-06-24 pages = extension = .txt mime = text/plain words = 6488 sentences = 322 flesch = 46 summary = swabs) and eDNA samples collected from finite populations and discuss key assumptions and considerations for their use with a focus on detecting Batrachochytrium salamandrivorans, an emerging pathogen that threatens global salamander diversity. www.nature.com/scientificreports www.nature.com/scientificreports/ context of screening U.S. service members for syphilis, pooling samples to reduce the number of tests required to detect rare infections is common in numerous contexts 22 , including surveys for disease freedom. In this paper I therefore develop formulae for imperfect tests of pooled samples in closed populations and eDNA, discuss the key assumptions and considerations in their application, and illustrate how eDNA may be especially useful for detecting infections in the live animal trade. Pooling and batch-processing samples collected from individual animals (e.g., swabs) can reduce several fold the number of diagnostic tests (e.g., DNA extractions and PCR reactions) required to detect rare infections. cache = ./cache/cord-308687-wrzzb9cy.txt txt = ./txt/cord-308687-wrzzb9cy.txt === reduce.pl bib === id = cord-312001-8p7scli8 author = Majzoub, Karim title = The Innate Antiviral Response in Animals: An Evolutionary Perspective from Flagellates to Humans date = 2019-08-16 pages = extension = .txt mime = text/plain words = 10056 sentences = 548 flesch = 46 summary = Consequently, animal cells have evolved devoted pathways which (1) sense and recognize pathogen-associated molecular patterns (PAMPs) and, more particularly, virus-associated molecular signatures; (2) initiate signaling cascades stemming from the site of detection, translocating the information to the nucleus; and (3) induce a transcriptional program that confers an antiviral state to the host ( Figure 1 ). While the cytosolic recognition of viral RNA is almost exclusively mediated by RLRs, several proteins have been proposed to play a role in DNA sensing and triggering innate immune responses, such as the DNA-dependent activator of IFN-regulatory factors (DAI), DDX41, RNA polymerase III, IFI16 and DNA-PK [62] [63] [64] [65] [66] [67] . Although the pathway leading to the transcriptional activation of Vago is still poorly understood in insects, these studies established that DExD/H-box helicase containing proteins, like Dicer and RLRs, may represent an evolutionarily conserved set of viral nucleic acid sensors that direct antiviral responses in animals [159] . cache = ./cache/cord-312001-8p7scli8.txt txt = ./txt/cord-312001-8p7scli8.txt === reduce.pl bib === id = cord-314503-u1y1bznk author = Jaluria, Pratik title = A perspective on microarrays: current applications, pitfalls, and potential uses date = 2007-01-25 pages = extension = .txt mime = text/plain words = 7764 sentences = 349 flesch = 38 summary = Therefore, this text aims to outline key features in microarray technology, paying particular attention to current applications as outlined in recent publications, experimental design, statistical methods, and potential uses. Several organizations such as the Microarray Gene Expression Data (MGED) Society and the European Bioinformatics Institute (EBI) have established guidelines to aid researchers in the design and implementation of microarray experiments [8, 9, 16] . As mentioned earlier, verification is critical in order to assign distinct expression patterns to specific genes with certainty (i.e. statistical significance) because of the inherent variability present in microarray data. To verify the results generated from microarray experiments, a combinatorial approach is usually needed; checking the statistical significance associated with the expression levels of specific genes, reviewing the literature, and conducting additional experiments such as RT-PCR or Northern blotting. A large number of microarray-related studies in the past have aimed to either characterize diseased cells in comparison to healthy cells or highlight the genes involved in a particular biological pathway [4, 8] . cache = ./cache/cord-314503-u1y1bznk.txt txt = ./txt/cord-314503-u1y1bznk.txt === reduce.pl bib === id = cord-314415-yr0uxok2 author = Guo, Zijing title = Identification and genomic characterization of a novel CRESS DNA virus from a calf with severe hemorrhagic enteritis in China date = 2018-08-15 pages = extension = .txt mime = text/plain words = 3767 sentences = 212 flesch = 55 summary = In this study, a novel circular replication-associated protein (Rep)-encoding single stranded (CRESS) DNA virus was discovered in diarrheic sample of a calf with severe hemorrhagic enteritis. The result showed that Bo-Circo-like virus CH is clustered into a independent branch with seven reported strains of proposed family Kirkoviridae and eight CRESS-DNA virus strains recently submitted to GenBank database; Bo-Circo-like virus CH is more closely related to Po-Circo-like virus and shows significant genetic differences with viruses in the families Circoviridae, Nanoviridae, Geminiviridae Genomoviridae, Bacilladnaviridae and Smacoviridae (Fig. 3) . The sequence alignments included strain Bo-Circo-like virus CH in this study, representative members of the Circoviridae, Geminiviridae, Nanoviridae, Genomoviridae, Bacilladnaviridae and Smacoviridae families, the proposed new genera of krikoviruses, and still unassigned novel CRESS-DNA viruses with the best BLASTp matchs in GenBank database. The sequence alignments included five Bo-Circo-like virus strains detected in this study and seven reported strains of the proposed family Kirkoviridae. cache = ./cache/cord-314415-yr0uxok2.txt txt = ./txt/cord-314415-yr0uxok2.txt === reduce.pl bib === id = cord-311839-61djk4bs author = Wei, Dan title = A novel hierarchical clustering algorithm for gene sequences date = 2012-07-23 pages = extension = .txt mime = text/plain words = 8033 sentences = 496 flesch = 61 summary = We propose a new alignment-free algorithm, mBKM, based on a new distance measure, DMk, for clustering gene sequences. DMk shows better performance than the k-tuple distance in our experiments, and mBKM outperforms SL, CL, AL, BKM and KM when tested on public gene sequence datasets. In this paper we propose a new alignment-free similarity measure, DMk, based on which we developed mBKM to cluster gene sequences. To evaluate the proposed similarity measure, we test DMk on gene sequence data sets and compare it with the k-tuple distance. Moreover, we use our method, mBKM with similarity measure DMk, in phylogenetic analysis to show how well the genes are grouped together and how well the resulting trees agree with existing phylogenies. In order to illustrate the efficiency of mBKM in gene sequence clustering, we ran mBKM with the k-tuple distance and DMk on real data sets listed in Table 1 . cache = ./cache/cord-311839-61djk4bs.txt txt = ./txt/cord-311839-61djk4bs.txt === reduce.pl bib === id = cord-316534-ep7ezoko author = Gamble, Lena J title = Current progress in the development of a prophylactic vaccine for HIV-1 date = 2010-12-22 pages = extension = .txt mime = text/plain words = 11945 sentences = 631 flesch = 40 summary = 67 The vaccine, a recombinant adenovirus serotype 5 (Ad5) virus incorporating the gag, pol, and nef genes from HIV-1, had been previously tested in an SHIV model in macaques and the results of that experiment were not suggestive of the results of the human trial. In hopes of creating a vaccine which elicits sterilizing immunity to HIV-1, researchers have focused their efforts on (1) the use of plasmid DNA vaccines, (2) live recombinant vectors for vaccine development (expressing or presenting HIV antigens), and (3) mucosal immunity. For instance, research performed by Harari and colleagues in 2008 demonstrated that vaccination by means of an HIV-1 clade C DNA prime in combination with a pox vector (NYVAC) boost induces a reliable polyfunctional and longlasting anti-HIV T-cell response in human participants. Repeated immunization with recombinant gp160 human immunodeficiency virus (HIV) envelope protein in early HIV-1 infection: evaluation of the T cell proliferative response cache = ./cache/cord-316534-ep7ezoko.txt txt = ./txt/cord-316534-ep7ezoko.txt === reduce.pl bib === id = cord-311349-145kwny3 author = Mariani, Stefano title = Surface plasmon resonance applications in clinical analysis date = 2014-02-25 pages = extension = .txt mime = text/plain words = 13425 sentences = 630 flesch = 39 summary = In the last 20 years, surface plasmon resonance (SPR) and its advancement with imaging (SPRi) emerged as a suitable and reliable platform in clinical analysis for label-free, sensitive, and real-time monitoring of biomolecular interactions. The advantages brought about by current SPR technology include real-time monitoring of the analyte/molecular markers, label free and parallel analysis (with SPRi), minimal sample pretreatment, quantitative response, and very good sensitivity and reproducibility, (reported detection limits are in atto-or femtomolar ranges and coefficient of variations below 10 %). Preventing nonspecific adsorption of biomolecules (e.g., protein) on the SPR sensing surface is another key-step for the development of specific biosensor, with real application to clinical diagnostics where complex matrices (such as serum, blood, and urine) are analyzed. cache = ./cache/cord-311349-145kwny3.txt txt = ./txt/cord-311349-145kwny3.txt === reduce.pl bib === id = cord-314642-oobbdgzh author = Campbell, Allan title = The future of bacteriophage biology date = 2003 pages = extension = .txt mime = text/plain words = 5945 sentences = 308 flesch = 53 summary = Several molecules of λ-integrase form an assemblage (the INTASOME) that binds to a specific segment of phage DNA, recruits the bacterial insertion sites into the complex, then makes concerted single-strand cuts in the two DNAs. The strand cutting proceeds through the covalent joining of a 3′ phosphate to a tyrosine of the integrase protein. Further efforts in this direction are desirable, not just for their intrinsic interest but also as models for viruses that infect eukaryotic hosts; for example, it is well documented that members of the coronavirus group, which has attracted attention recently through the emergence of a deadly new human pathogen that causes severe acute respiratory syndrome (SARS), undergo frequent recombination in nature 10, 11 . cache = ./cache/cord-314642-oobbdgzh.txt txt = ./txt/cord-314642-oobbdgzh.txt === reduce.pl bib === id = cord-315616-pvt0amth author = Poole, Anthony title = Methyl-RNA: an evolutionary bridge between RNA and DNA? date = 2004-06-17 pages = extension = .txt mime = text/plain words = 5623 sentences = 281 flesch = 54 summary = Ribonucleotide reductase itself, which synthesises deoxyribonucleotides from ribonucleotides, requires complex protein radical chemistry, and RNA world genomes may have reached their limits of coding capacity well before such complex enzymes had evolved. Even with this gap in the RNA world model, current knowledge suggests the RNA organism that evolved protein synthesis was likely to have been dangerously close to the Eigen limit for RNA, and probably emIn the ¢rst step, a radical is generated at some distance from the active site. By virtue of its non-speci¢c dsRNA methylating activity, this enzyme is hypothesised to have been recruited into methylation of genomic RNA, improving the stability of the genetic material prior to the origin of DNA. The predicted stabilising effect of 2P-O-methylation on genomic RNA argues that the coding capacity of the genome would have increased suf¢ciently for genuinely catalytic proteins such as RNA polymerase, and later ribonucleotide reductase, to arise, paving the way to the DNA world (Figure 4) . cache = ./cache/cord-315616-pvt0amth.txt txt = ./txt/cord-315616-pvt0amth.txt === reduce.pl bib === id = cord-316096-3fnwosst author = Jin, Huali title = Induction of Th1 type response by DNA vaccinations with N, M, and E genes against SARS-CoV in mice date = 2005-03-25 pages = extension = .txt mime = text/plain words = 4521 sentences = 222 flesch = 54 summary = After the intramuscular introduction into animals, we observed that the constructs of the E, M, and N genes could induce high levels of specific antibodies, T cell proliferations, IFN-γ, DTH responses, and in vivo cytotoxic T cells activities specifically against SARS-CoV antigens. All DNA vaccine constructs, encoding the E protein, the M glycoprotein, and the N protein of SARS-CoV, were obtained as follows: these genes were amplified from the cDNA by PCR amplifications using each set of specific primers, respectively. In the present study, it was consistent with their work that the N protein construct could induce the highest SARS-specific IgG, T cell proliferation, and in vivo CTL response (lysis rate of 50.6%) compared with M protein gene (lysis rate of 17%) and E protein gene (lysis rate of 5.6%) (Fig. 4) . In summary, the administrations with all three SARS-CoV DNA vaccines in our study were able to induce high levels of the antigen-specific IgG antibody, the T cell proliferation, IFN-c, DTH, and in vivo CTL responses. cache = ./cache/cord-316096-3fnwosst.txt txt = ./txt/cord-316096-3fnwosst.txt === reduce.pl bib === id = cord-313161-07iwwsfz author = Lundstrom, Kenneth title = Alphavirus-Based Vaccines date = 2014-06-16 pages = extension = .txt mime = text/plain words = 6844 sentences = 322 flesch = 30 summary = Furthermore, sequential immunization with SIN and VEE replicon particles expressing the type 1 HIV gp140 envelope (Env) and trimeric Env protein in MF59 adjuvant provided partial protection in macaques against intravenous challenges with high doses of simian-human immunodeficiency virus (SHIV) [61] . In another study, chimeric VEE/SIN replicon particles were applied for the expression of measles virus hemagglutinin (H) and fusion (F) proteins, which elicited high-titer neutralizing antibody and IFNɤ-producing T-cells in macaques after intradermal vaccination [48] . Furthermore, vaccination with recombinant particles expressing the P1A gene [105] and the human papilloma virus (HPV) E7 gene [89] from SFV and VEE vectors, respectively, provided protection against further tumor development in mice. When TRAMP mice were prophylactically immunized with a prostate stem cell antigen (PSCA) DNA plasmid followed by VEE-PSCA particle administration, a specific immune response and anti-tumor protection were observed in 90% of vaccinated animals [102] . cache = ./cache/cord-313161-07iwwsfz.txt txt = ./txt/cord-313161-07iwwsfz.txt === reduce.pl bib === id = cord-317591-qa6oxy4j author = Fukushima, Akiko title = Development of a Chimeric DNA-RNA Hammerhead Ribozyme Targeting SARS Virus date = 2009-05-07 pages = extension = .txt mime = text/plain words = 3605 sentences = 196 flesch = 53 summary = To develop an effective and specific medicine targeting the SARS-coronavirus (CoV), a chimeric DNA-RNA hammerhead ribozyme was designed and synthesized using a sequence homologous with the mouse hepatitis virus (MHV). The chimeric DNA-RNA hammerhead ribozyme targeting SARS-CoV significantly inhibited multiplication of MHV in DBT cells by about 60%. A chimeric DNA-RNA hammerhead ribozyme was designed and synthesized to target a common nucleotide sequence between SARS-CoV and mouse hepatitis virus (MHV), and its effectiveness on suppression of MHV and SARS-CoV RNA expression evaluated in vitro. Figure 4 shows effect of the chimeric DNA-RNA hammerhead ribozyme targeting SARS-CoV RNA on the multiplication of MHV in DBT cells. Therefore, the chimeric DNA-RNA hammerhead ribozyme was designed with complementarity to common regions of SARS-CoV and MHV that included the target GUC sequence. In the present study, inhibition on the multiplication of MVH was approximately 60%, with 60% transfection efficiency of the chimeric DNA-RNA ribozyme targeting SARS-CoV into DBT cells. cache = ./cache/cord-317591-qa6oxy4j.txt txt = ./txt/cord-317591-qa6oxy4j.txt === reduce.pl bib === id = cord-318276-so5jooj0 author = Bertholet, Christine title = Vaccinia virus produces late mRNAs by discontinuous synthesis date = 1987-07-17 pages = extension = .txt mime = text/plain words = 6225 sentences = 329 flesch = 60 summary = RNA was isolated from noninfected or infected cells and then hybridized to 32P-labeled probes isolated from the 5' end region, upstream of the 11K coding sequences of cDNA clones 3, 8, and 9 (see Figure 2 ). To confirm this, and to identify the regions from which they are transcribed, the cDNA-derived probes used in the previous experiment were hybridized to cloned DNA restriction fragments representing the entire vaccinia virus genome ( Figure 4 ). %P-labeled DNA probes (~3, ~9, p9, pllK) derived from the 5' region of the corresponding cDNA clones or from genomic DNA (see Figure 2 ) were hybridized lo RNA isolated from uninfected (HeLa) or infected (Early, Late) cells, or to tRNA immobilized on a nitrocellulose membrane. Total late RNA from infected cells protected fragments of 127 and 128 nucleotides of the genomic probe, consistent with the previous experiments, which demonstrated that the sequence complementarity between the genomic DNA and 11K mRNA ends just upstream of the 11K ATG codon. cache = ./cache/cord-318276-so5jooj0.txt txt = ./txt/cord-318276-so5jooj0.txt === reduce.pl bib === id = cord-315164-nidgnvvi author = Medkour, Hacène title = Adenovirus Infections in African Humans and Wild Non-Human Primates: Great Diversity and Cross-Species Transmission date = 2020-06-18 pages = extension = .txt mime = text/plain words = 6818 sentences = 359 flesch = 58 summary = Non-human primates (NHPs) are known hosts for adenoviruses (AdVs), so there is the possibility of the zoonotic or cross-species transmission of AdVs. As with humans, AdV infections in animals can cause diseases that range from asymptomatic to fatal. The aim of this study was to investigate the occurrence and diversity of AdVs in: (i) fecal samples of apes and monkeys from different African countries (Republic of Congo, Senegal, Djibouti and Algeria), (ii) stool of humans living near gorillas in the Republic of Congo, in order to explore the potential zoonotic risks. Samples were screened by real-time and standard PCRs, followed by the sequencing of the partial DNA polymerase gene in order to identify the AdV species. In the present study, we sought to investigate the presence and molecular diversity of AdVs in wild African NHPs, including great apes (gorillas and chimpanzees), macaques and other monkeys (baboons, green monkeys), living in close proximity to or outside human settlements. cache = ./cache/cord-315164-nidgnvvi.txt txt = ./txt/cord-315164-nidgnvvi.txt === reduce.pl bib === id = cord-316434-mz4y5am2 author = Yang, Benjamin title = Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination date = 2015-06-25 pages = extension = .txt mime = text/plain words = 5792 sentences = 269 flesch = 46 summary = In the current study, we aim to introduce an approach to elicit potent CD4(+) T cell help for the enhancement of antigen-specific CD8(+) T cell immune responses generated by CRT/E7 DNA vaccination by using co-administration of a DNA vector expressing papillomavirus major and minor capsid antigens, L1 and L2. Co-administration with vectors encoding papillomavirus L1 or L2 significantly enhances the antigen-specific CD8 + T cell immune responses generated by CRT/E7 or OVA DNA vaccination In order to characterize the antigen-specific CD8 + T cell immune responses generated by vaccination with CRT/ E7 or OVA DNA in combination with vectors containing codon-optimized BPV1 L1 or L2 DNA, C57BL/6 mice (five per group) were vaccinated intradermally via gene gun with CRT/E7 or OVA DNA with or without BPV1 L1 or L2 DNA twice at 1-week intervals. cache = ./cache/cord-316434-mz4y5am2.txt txt = ./txt/cord-316434-mz4y5am2.txt === reduce.pl bib === id = cord-312336-784izxqd author = Fouret, Julien title = Sequencing the Genome of Indian Flying Fox, Natural Reservoir of Nipah Virus, Using Hybrid Assembly and Conservative Secondary Scaffolding date = 2020-07-29 pages = extension = .txt mime = text/plain words = 7527 sentences = 389 flesch = 53 summary = medius genome, assembled by this method, has a length of 1,985 Mb and consists of 33,613 contigs and 16,113 scaffolds with an NG50 of 19 Mb. At least 22.5% of the assembled sequences is covered by interspersed repeats already described in other species and 19,823 coding genes are annotated. Then, we improve the assembly using secondary scaffolding methods, AGOUTI (gene-based) and Ragout (reference-assisted), using RNA seq data obtained with an Illumina 75 bp paired-end sequencing. medius with a length of 1,985 Mb, consisting of 33,613 contigs and 16,113 scaffolds with a NG50 of 19 Mb. Identified repeat elements covered 22.5% of the assembled sequences and 19,823 coding genes were annotated, thus providing the first genome sequence of this bat species and making it available for further studies and better understanding of the mechanisms of Nipah virus emergence. cache = ./cache/cord-312336-784izxqd.txt txt = ./txt/cord-312336-784izxqd.txt === reduce.pl bib === id = cord-023211-kt5gt26t author = nan title = Poster Session Abstracts date = 2007-08-29 pages = extension = .txt mime = text/plain words = 221224 sentences = 11772 flesch = 52 summary = Previous studies performed using fluorescence halide efflux measurements and short-circuit current voltage clamp have shown that treatment with PPARγ (peroxisome proliferator activated receptor gamma) agonists, such as pioglitazone and FLL (FMOC-L-leucine), resulted in an increased biosynthesis and trafficking of ∆F508-CFTR to the cell surface. Physiology, School of Medical Sciences, University of Bristol, Bristol, United Kingdom Recent progress in the development of small molecule correctors and potentiators capable of restoring CFTR function have increased the need for pre-clinical test models including cultured airway epithelial cells from human CF patients as well as CF mouse models. Clinical studies have linked increased sputum and peripheral blood neutrophil MPO activity with increased airflow obstruction in cystic fibrosis (CF) patients of the same age, gender, airway bacterial flora, and CFTR genotype. Because patients expressing low levels of normal CFTR mRNA (5-20%) have mild disease symptoms, these studies demonstrate that the incorporation of the ciliated cell-specific FOXJ1 promoter into gene therapy vectors may be useful for treatment of CF. cache = ./cache/cord-023211-kt5gt26t.txt txt = ./txt/cord-023211-kt5gt26t.txt === reduce.pl bib === id = cord-320501-xqgqq55q author = Theobald, Nigel title = Emerging vaccine delivery systems for COVID-19: Functionalised silica nanoparticles offer a potentially safe and effective alternative delivery system for DNA/RNA vaccines and may be useful in the hunt for a COVID-19 vaccine date = 2020-06-24 pages = extension = .txt mime = text/plain words = 1203 sentences = 58 flesch = 47 summary = title: Emerging vaccine delivery systems for COVID-19: Functionalised silica nanoparticles offer a potentially safe and effective alternative delivery system for DNA/RNA vaccines and may be useful in the hunt for a COVID-19 vaccine Liposomal encapsulation of drugs with bioavailability issues was a proven approach in small molecule pharma, and it was apparent to biopharma R&D scientists that LNPs could meet the basic requirements of an RNA/DNA delivery system too, namely to protect nucleic acid from in vivo digestion as it travels to the target. As scientists looked to alternative carriers that could be adapted to encapsulate and protect nucleic acids, mesoporous silica nanoparticles (MSNs)silica-based nanostructured materials with excellent biocompatibility and chemical stability This surface simply and effectively traps and protects nucleic acids (such as mRNA/pDNA) from nuclease enzymes as it travels to the cells. Once inside the cell, the DNA/RNA is released and will result in synthesis of the foreign/target protein which will activate the immune system, leading to both a cellular and humoral immune response. cache = ./cache/cord-320501-xqgqq55q.txt txt = ./txt/cord-320501-xqgqq55q.txt === reduce.pl bib === === reduce.pl bib === id = cord-319884-d8n0aokl author = Natesan, Mohan title = Protein Microarrays and Biomarkers of Infectious Disease date = 2010-12-16 pages = extension = .txt mime = text/plain words = 7088 sentences = 359 flesch = 36 summary = Fluorescencebased detection of protein interactions is similar to gene array methods, and data analysis often employs approaches previously developed for genome and transcription studies. A standard assay for measuring antibody interactions with proteins of the vaccinia proteome microarray was first developed with a pool of therapeutic human sera collected from vaccinia-immune individuals (VIg) and this data was compared to results obtained from individuals vaccinated against smallpox using Dryvax. Results from this study suggested that antibodies from vaccination recognized a small number of proteins shared with pathogenic viral strains, while recovery from infection also involved humoral immunity to antigens uniquely recognized within the monkeypox virus proteome (unpublished data). For example, a protein array produced from the outer membrane proteins of Pseudomonas aeruginosa was constructed [38] to study the immune response in patients, and several antibody-binding antigens were identified by this group as potential diagnostic markers. cache = ./cache/cord-319884-d8n0aokl.txt txt = ./txt/cord-319884-d8n0aokl.txt === reduce.pl bib === id = cord-312522-mymgnf8z author = Nelson, Megan M. title = Rapid molecular detection of macrolide resistance date = 2019-02-12 pages = extension = .txt mime = text/plain words = 5135 sentences = 277 flesch = 42 summary = METHODS: We use Recombinase Polymerase Assay (RPA) to detect the antimicrobial resistance gene mef(A) from raw lysates without nucleic acid purification. We show that detection of mef(A) accurately predicts real antimicrobial resistance assessed by traditional culture methods, and that the assay is robust to high levels of spiked-in non-specific nucleic acid contaminant. In this study, we developed and tested a novel RPA assay for the detection of the Macrolide Efflux A, or mef(A) gene, an efflux pump rendering host bacteria resistant to 14-and 15-membered macrolide antibiotics (including erythromycin A and azithromycin) [33, 34] . Our RPA assay uncovered an unexpected occurrence of the mef(A) gene within commensal Streptococcus salivarius strain, and subsequent laboratory testing confirmed that this strain has genuine antimicrobial resistance. To assess assay sensitivity we ran a serial dilution of DNA derived from mef(A)-positive Streptococcus pyogenes serotype M6 strain MGAS10394 [39] and found that confident detection was around 2000 genome copies (Fig. 1b) . cache = ./cache/cord-312522-mymgnf8z.txt txt = ./txt/cord-312522-mymgnf8z.txt === reduce.pl bib === id = cord-315570-khm1veuv author = González-Mora, Alejandro title = Bacteriophage-Based Vaccines: A Potent Approach for Antigen Delivery date = 2020-09-04 pages = extension = .txt mime = text/plain words = 9969 sentences = 455 flesch = 40 summary = This system relies on bacteriophages displaying proteins or peptides with high affinity to antigen-presenting cells or the antigen itself and at the same time they carry on their genome an eukaryotic expression cassette encoding a specific antigen with the final aim of increasing the immune response by combining both effects (Figure 1 ) [6] . developed a double-hybrid filamentous bacteriophage fd co-displaying peptides recognized by the Major Histocompatibility Complex (MHC) class I and MHC class II cell surface receptors and epitopes from the antigen MAGE aiming to enhance the anti-tumor immune activity based on CTL responses [62] . Thus, the adjuvant-like effect exhibited by phages in various vaccination studies along with their capacity to effectively present peptides or proteins to the immune system leading to the activation of cellular and humoral immune responses [40] demonstrates that engineered phage particles are a proper strategy to enhance the efficacy and safety of viral particle-based vaccines. cache = ./cache/cord-315570-khm1veuv.txt txt = ./txt/cord-315570-khm1veuv.txt === reduce.pl bib === id = cord-311328-k751tehv author = Rabti, Amal title = DNA markers and nano-biosensing approaches for tuberculosis diagnosis date = 2020-06-19 pages = extension = .txt mime = text/plain words = 7738 sentences = 340 flesch = 35 summary = The latter use carbonaceous nanomaterials (graphene and carbon nanotubes), noble metals (silver and gold), semi-conducting (metal oxides, magnetic beads, and quantum dots) in order to reveal and/or to amplify the signal after the recognition of target DNA biomarker. developed a sandwich-type of Mtb DNA biosensor based on the use of polyaniline-reduced graphene oxide, which was decorated with DNA label immobilized onto gold nanoparticles ( Fig. 13.1 ) [17] . In fact, hybridization of IS6110 amplified DNA target sequence, modified at 3′ end with AuNPs as mass enhancement, to the probe oligonucleotide immobilized onto gold electrode of the quartz crystal were studied through the changes in QCM frequency, which indicated that the developed biosensor could detect serial dilution of Mtb DNA limited to 5 pg of genomic DNA. An electrochemical DNA biosensor for the detection of Mycobacterium tuberculosis, based on signal amplification of graphene and a gold nanoparticle-polyaniline nanocomposite Reduced graphene oxide nanoribbon immobilized gold nanoparticles based electrochemical DNA biosensor for detection of Mycobacterium tuberculosis cache = ./cache/cord-311328-k751tehv.txt txt = ./txt/cord-311328-k751tehv.txt === reduce.pl bib === id = cord-315541-tirod4t6 author = Henriques, Ana Margarida title = Development and validation of a real-time PCR for the detection and quantification of porcine circovirus type 2 date = 2018-07-17 pages = extension = .txt mime = text/plain words = 3552 sentences = 167 flesch = 51 summary = This paper reports the development and validation of a real-time PCR targeted to ORF1 and based on a TaqMan probe for the detection of porcine circovirus type 2 DNA in swine samples. The real-time PCR method described in this paper was performed with DNA from this strain, and an amplification curve with Ct 19.9 was obtained, confirming that such mutation in the probe annealing sequence had no effect in the reaction. The test performed with a plasmid containing the fragment to be amplified in the qPCR, with known The DNA samples used for the determination of the intra-and inter-assay variabilities for medium Ct values was not the same due to the lack of available DNA Fig. 2 Amplification curves obtained in the real-time PCR reaction performed for the determination of the limit of detection. cache = ./cache/cord-315541-tirod4t6.txt txt = ./txt/cord-315541-tirod4t6.txt === reduce.pl bib === id = cord-318609-211m5b79 author = Yang, Chen title = Accurate, rapid and low-cost diagnosis of Mycoplasma pneumoniae via fast narrow-thermal-cycling denaturation bubble-mediated strand exchange amplification date = 2020-10-11 pages = extension = .txt mime = text/plain words = 4723 sentences = 192 flesch = 41 summary = Furthermore, ASEA exhibited excellent performance in clinical specimen analysis, with sensitivity and specificity of 96.2% and 100%, respectively, compared with the "gold standard" real-time PCR. pneumoniae nucleic acid testing of clinical specimens to verify the accuracy of this novel method by comparison with real-time PCR, the current "gold standard." The objective was to provide a rapid, low-cost and sensitive detection method with conventional instruments and easily available commercial polymerase for early diagnosis of M. The ASEA reaction was performed in 20 μL amplification mixture containing 2 μL of the relevant templates, 3.0 × 10 −6 M primers F and R, 2 μL ISO buffer, 0.5 μL EvaGreen, 0.2 μL Bst 2.0 WarmStart DNA polymerase and 1.6 μL dNTPs. The amplification mixture was subjected to rapid thermal cycles between a first temperature (T 1 ) and a second temperature (T 2 ) using the CFX Connect™ Real-Time PCR System (Bio-Rad, CA, USA). cache = ./cache/cord-318609-211m5b79.txt txt = ./txt/cord-318609-211m5b79.txt === reduce.pl bib === id = cord-316033-xg8eb2nm author = Easton, Alice title = Molecular evidence of hybridization between pig and human Ascaris indicates an interbred species complex infecting humans date = 2020-11-06 pages = extension = .txt mime = text/plain words = 10447 sentences = 522 flesch = 45 summary = suum transcripts (Jex et al., 2011; Wang et al., 2017) to the human Ascaris germline assembly to annotate the genome, identifying and classifying 17,902 protein-coding genes ( Table 1 , Supplementary file 1). As this reference-based assembly exhibits the best assembly attributes, including high continuity with a large N50, low gaps and unplaced sequences, and high-quality protein-coding genes (see Table 1 ), we suggest that this version should be used as a reference germline genome for a human Ascaris spp. We next took advantage of the abundant reads from the mitochondrial genome in our sequencing data (on average 7690X coverage, see Supplementary file 1) to perform de novo assembly of 68 complete human Ascaris spp. Furthermore, there were no significant associations between mitochondrial sequence variations and other factors (e.g. village, household, time of worm collection, host) based on PERMANOVA (see methods and Table 2 ) after translating the phylogenetic tree into a distance matrix, suggesting not only a lack of differentiation into distinct species but also a potentially large interbreeding population of worms being transmitted between individuals and across villages. cache = ./cache/cord-316033-xg8eb2nm.txt txt = ./txt/cord-316033-xg8eb2nm.txt === reduce.pl bib === id = cord-319799-h9kot3og author = Schäfer, Alexandra title = Epigenetic Landscape during Coronavirus Infection date = 2017-02-15 pages = extension = .txt mime = text/plain words = 10080 sentences = 465 flesch = 33 summary = By combining measures of epigenome reorganization with RNA and proteomic datasets, we articulate a spatial-temporal data integration approach to identify regulatory genomic clusters and regions that play a crucial role in the host's innate immune response, thereby defining a new viral antagonism mechanism following emerging coronavirus infection. By utilizing Calu3 cells, we have developed a robust human model platform to study innate immune regulatory control and epigenetics following emerging coronavirus and influenza virus infections as well as other highly pathogenic viruses ( Figure 6 ). Utilizing these model systems, we aim to study genome-wide histone modifications, DNA methylation patterns, and the chromatin landscape after virus infection across different cell types in the lung, revealing cell type-specific regulatory features that function to regulate infection outcomes. Utilizing these model systems, we aim to study genome-wide histone modifications, DNA methylation patterns, and the chromatin landscape after virus infection across different cell types in the lung, revealing cell type-specific regulatory features that function to regulate infection outcomes. cache = ./cache/cord-319799-h9kot3og.txt txt = ./txt/cord-319799-h9kot3og.txt === reduce.pl bib === id = cord-319116-2ts6zpdb author = Ruggiero, Emanuela title = G-quadruplexes and G-quadruplex ligands: targets and tools in antiviral therapy date = 2018-04-20 pages = extension = .txt mime = text/plain words = 9124 sentences = 410 flesch = 42 summary = Since the number of reports describing the presence of G4s in virus genomes has boomed in the past 2 years and treatment with several G4 ligands has shown potentially interesting therapeutic activity, we here aim at presenting, organizing and discussing an up-to-date close-up of the literature on G4s in viruses and the classes of molecules that have shown antiviral activity by viral G4 targeting. The research of G4s in the HIV-1 genome has been quite productive, concerning not only the two RNA viral genome copies, but also the integrated proviral genome, specifically For each virus the following information is shown: virion structure and dimension, genome size and organization; schematic representation of the G4 (red dots) location in the viral genomes or in the mRNA and G4 binding proteins; number of G4s assessed through bioinformatics analysis, according to the corresponding references; G4 ligands reported to date to display antiviral effect and corresponding references. cache = ./cache/cord-319116-2ts6zpdb.txt txt = ./txt/cord-319116-2ts6zpdb.txt === reduce.pl bib === === reduce.pl bib === id = cord-317021-o30zylrq author = Zhai, Yujia title = SmartBac, a new baculovirus system for large protein complex production date = 2019-02-10 pages = extension = .txt mime = text/plain words = 7669 sentences = 428 flesch = 56 summary = Here we report SmartBac, an easy and versatile system for constructing large-sized transfer plasmids used to generate recombinant baculoviruses that express large multiprotein complexes in insect cells. The second strategy used to express multiprotein complexes is to construct a transfer plasmid carrying multiple GECs. The commercial pFastbac-Dual vector features two promoters for expression of two proteins simultaneously. In Fig. 2a , a vector is designed to express a multiprotein complex composed of eight different subunits (subunits A, B, C, D, E, F, G and H) in insect cells. Obtaining large multiprotein complexes through recombinant expression has always been challenging for researchers who need a sufficient quantity of high-purity sample for structural and biochemical studies. The key to successful protein production using the baculovirus expression system is the construction of the final transfer plasmid containing genes of multiple protein subunits. cache = ./cache/cord-317021-o30zylrq.txt txt = ./txt/cord-317021-o30zylrq.txt === reduce.pl bib === id = cord-323973-wszo9s3d author = Zhu, Hanliang title = The vision of point-of-care PCR tests for the COVID-19 pandemic and beyond date = 2020-07-20 pages = extension = .txt mime = text/plain words = 9784 sentences = 493 flesch = 50 summary = [9] The analysis of larger volumes of biological fluids with a low viral load is likely to reduce the risk of false-negative results, but microfluidic point-of-care (POC) devices are typically unable to handle mL-scale volumes in a short time due to the requirement of slow flow rates. [15] The PCR test on samples prepared from blood and urine specimens is capable of detecting the virus in the early stages of the disease, resulting in early diagnosis and subsequent isolation of infected patients to block transmission. The total reaction time depends on a series of parameters, such as the chip size, the PCR master mix volume determining the value of C, the thermal conductivity of the substrate (G), and the temperature cycling rate. A number of fully integrated systems have so far been developed, starting with the non-portable GenExpert from Cepheid, which was first utilized for anthrax detection by the United States Postal Service, [64] and then with different primers to perform HIV and tuberculosis diagnostics in South Africa. cache = ./cache/cord-323973-wszo9s3d.txt txt = ./txt/cord-323973-wszo9s3d.txt === reduce.pl bib === id = cord-317213-vhprfb1o author = Tram, Dai Thien Nhan title = Advances in nanomaterials and their applications in point of care (POC) devices for the diagnosis of infectious diseases date = 2016-09-26 pages = extension = .txt mime = text/plain words = 11575 sentences = 794 flesch = 48 summary = This review presents an overview on how the POC-associated nanotechnology, currently applied for the identification of nucleic acids, proteins and antibodies, might be further exploited for the detection of infectious pathogens: although still premature, future integrations of nanoparticles with biological markers that target specific microorganisms will enable timely therapeutic intervention against life-threatening infectious diseases. • no tagging is required • about two orders of magnitude more sensitive than some common colorimetric techniques • selectivity down to the level of single-base mismatch • quantitative signal intensity varied with the length of target RNA sequence (Nam et al., 2004) Analyte: nucleotide sequence indicative of anthrax lethal factor Sample size: 30 μl Assay time: 3-4 h Detection range: 500 zM-5 fM Performance: cache = ./cache/cord-317213-vhprfb1o.txt txt = ./txt/cord-317213-vhprfb1o.txt === reduce.pl bib === id = cord-320015-lbr2q4qh author = Chinchar, V. Gregory title = The Molecular Biology of Frog Virus 3 and other Iridoviruses Infecting Cold-Blooded Vertebrates date = 2011-10-20 pages = extension = .txt mime = text/plain words = 9130 sentences = 433 flesch = 43 summary = Additional IE and DE proteins include proteins that may play roles in blocking host immune responses such as a virus-encoded, CARD (caspase activation and recruitment domain) motif-containing protein (vCARD), β-hydroxysteroid dehydrogenase (βHSD), and a RNAse III-like protein, catalytic proteins involved in nucleic acid synthesis (Proliferating Cell Nuclear Antigen [PCNA], DNA methyltransferase [DMTase], the large and small subunits of the viral homolog of cellular RNA polymerase II [vPOL-IIα and -IIβ], transcription factor IIS), catalytic proteins that may act to increase dTTP pool sizes and influence host range (deoxyuridine triphosphatase [dUTPase], deoxynucleotide kinase, the large and small subunits of ribonucleotide reductase), and proteins non-essential for replication in vitro, but needed for growth in vivo (the 18K protein) [22] . Lastly, Sample and co-workers observed that KD of the 18K IE protein had no observable effect on viral gene expression or replication in vitro suggesting that, at least in fathead minnow cells, 18K was not required for the production of infectious virions. cache = ./cache/cord-320015-lbr2q4qh.txt txt = ./txt/cord-320015-lbr2q4qh.txt === reduce.pl bib === id = cord-323029-7hqp8xuq author = Bognár, Zsófia title = Aptamers against Immunoglobulins: Design, Selection and Bioanalytical Applications date = 2020-08-11 pages = extension = .txt mime = text/plain words = 19331 sentences = 873 flesch = 45 summary = For aptamer selection against rIgG [6] and IgE [7] , homogenous processes were used and the separation of bound and unbound nucleic Several different SELEX methods have been used to generate immunoglobulin aptamers including homogeneous, heterogeneous, bead-based SELEX processes, CE-SELEX (capillary electrophoresis-SELEX), µFFE-SELEX (micro-free flow electrophoresis-SELEX) and fully integrated selection processes selection of aptamers with proper binding properties. Molecular Light Switch Complex 100-800 100 [128] Fluorescence enhancement using a DNA aptamer 92-37,000 57 [130] Amplification through allostery-triggered enzymatic recycling amplification NA 5 [131] Fluorescent oligonucleotide probe based on G-quadruplex scaffold for signal-on ultrasensitive protein assay 4.72-7560 0.095 [132] Fluorescence anisotropy 1000-60,000 350 [133] Fluorescence anisotropy assay NA 20 [134] Fluorescence protection assay 100-50,000 100 [136] Aptamer-barcode-based assay based on instantaneous derivatization chemiluminescence coupled to magnetic beads 4.88-20,000 4.6 [137] Competitive fluorescence quenching assay 350-35,000 170 [138] Rapid fluorescence detection of immunoglobulin E using an aptamer switch based on a binding-induced pyrene excimer NA 1600 [139] 6.1. cache = ./cache/cord-323029-7hqp8xuq.txt txt = ./txt/cord-323029-7hqp8xuq.txt === reduce.pl bib === id = cord-320628-uc97t0ea author = Huguenin, Antoine title = Broad respiratory virus detection in infants hospitalized for bronchiolitis by use of a multiplex RT‐PCR DNA microarray system date = 2012-04-12 pages = extension = .txt mime = text/plain words = 3572 sentences = 169 flesch = 41 summary = Multiplex RT-PCR DNA Microarray CLART 1 (CLinical ARray Technology) PneumoVir kit V16.3 (Genomica) is based on viral genome-specific fragments amplification located between 106-328 bp by multiplex PCR and its subsequent detection via hybridization with microorganism-specific binding probe on low-density microarrays, allowing simultaneous detection and identification of 17 types and subtypes of human respiratory viruses (influenza A including seasonal A/H1N1 and A/H3N2 strains, influenza B, influenza C, parainfluenza 1, 2, 3, 4A and 4B, hRSV A and B, human rhinoviruses, adenoviruses, EVs specie B, human bocavirus, coronavirus E-229 and the human metapneumovirus A and B) in clinical samples [Renois et al., 2010; Frobert et al., 2011] . In conclusion, the use of a multiplex RT-PCR DNA microarray system in clinical virology practice allows a rapid and an accurate identification of common and uncommon viral respiratory pathogens in infants hospitalized for bronchiolitis. cache = ./cache/cord-320628-uc97t0ea.txt txt = ./txt/cord-320628-uc97t0ea.txt === reduce.pl bib === id = cord-322240-z8zkl2xh author = Maeda, Ken title = Isolation of Novel Adenovirus from Fruit Bat (Pteropus dasymallus yayeyamae) date = 2008-02-17 pages = extension = .txt mime = text/plain words = 1686 sentences = 95 flesch = 51 summary = To date, only 1 case of disseminated infection has been reported in a solid-organ (kidney) transplant recipient; the diagnosis was made by molecular identifi cation in isolates from blood and marrow cultures. As a fi rst step in investigating unidentifi ed pathogens in bats and to help forecast the potential threat of emerging infectious diseases, we tried to isolate and characterize viruses that persistently infect bats. However, no viral nucleic acid sequence was detected from an RNA sample in the RV1-infected BKT1 cells. In addition, our success in DNA virus isolation might have resulted from usage of the adult animal latently and persistently infected with DNA viruses such as adenovirus and herpesvirus. Although its pathogenicity for humans is still unknown, knowledge of RV1 will be useful in epidemiologic studies of infectious diseases emerging from bats because persistently infecting viruses might be isolated together with primary pathogens. cache = ./cache/cord-322240-z8zkl2xh.txt txt = ./txt/cord-322240-z8zkl2xh.txt === reduce.pl bib === id = cord-324094-23kzr8rq author = Parida, M. M. title = Rapid and real-time detection technologies for emerging viruses of biomedical importance date = 2008-11-01 pages = extension = .txt mime = text/plain words = 5709 sentences = 243 flesch = 46 summary = We have developed two real-time assays ie., SYBR green I based real time reverse transcription polymerase chain reaction (RT-PCR) and RT-loop-mediated isothermal amplification (LAMP) assay for rapid detection as well as typing of some of the emerging viruses of biomedical importance viz. We have developed two real-time assays ie., SYBR green I based real time reverse transcription polymerase chain reaction (RT-PCR) and RT-loop-mediated isothermal amplifi cation (LAMP) assay for rapid detection as well as typing of some of the emerging viruses of biomedical importance viz. A one-step single tube real-time accelerated reverse transcription loop mediated isothermal amplifi cation (RT-LAMP) assays for rapid detection of some of the recently emerged human viral pathogens viz. Rapid detection and differentiation of dengue virus serotypes by a real-time reverse transcription-loop-mediated isothermal amplifi cation assay Development and evaluation of reverse transcription Loop mediated isothermal amplifi cation assay for rapid and Real-time detection of Japanese encephalitis virus cache = ./cache/cord-324094-23kzr8rq.txt txt = ./txt/cord-324094-23kzr8rq.txt === reduce.pl bib === id = cord-323691-5s5almd2 author = Mishin, Vasiliy P title = A ‘minimal’ approach in design of flavivirus infectious DNA date = 2001-12-04 pages = extension = .txt mime = text/plain words = 5060 sentences = 255 flesch = 49 summary = Abstract The 'infectious DNA' approach, which is based on in vivo transcription of (+)RNA virus genome cDNA cassettes from eukaryotic promoters in transfected cells, became a popular alternative to the classical scheme in the infectious clone methodology. Substantial difficulties, however, were encountered in design of flavivirus 'infectious DNA', requiring either modification of the viral genome cassette (Yamshchikov et al., 2001) to prevent unwanted expression of viral genome segments encoding toxic for Escherichia coli products, or deletion of the structural protein region (Varnavski et al., 2000) . For this reason we sought to investigate if the stability of constructs containing an unmodified virus genome cassette can be improved by preventing its deleterious expression at the transcriptional level, i.e. by minimizing spurious transcription from eukaryotic promoters in E. cache = ./cache/cord-323691-5s5almd2.txt txt = ./txt/cord-323691-5s5almd2.txt === reduce.pl bib === id = cord-321640-kx3t81yh author = Patrone, Paul N. title = Affine analysis for quantitative PCR measurements date = 2020-09-20 pages = extension = .txt mime = text/plain words = 7625 sentences = 458 flesch = 57 summary = Application to reverse-transcriptase qPCR measurements of a SARS-CoV-2 RNA construct points to the usefulness of this approach for improving confidence and reducing limits of detection in diagnostic testing of emerging diseases. Using this, we develop a data analysis approach employing constrained optimization to determine if an amplification curve exhibits characteristics that are representative of a true signal. We illustrate the validity of this approach on experimental data and demonstrate how it can improve interpretation of late-cycle amplification curves corresponding to low initial DNA concentrations [4] . Our data analysis leverages a universal property of qPCR, which states that under very general conditions, all amplification curves are the same up to an affine transformation, i.e. a multiplicative factor and horizontal shift. To demonstrate that optimization of the transformation parameters does not generate false positives, we performed the analysis described above on 17 non-template control (NTC) datasets that were baseline-corrected according to the same procedure used on the amplification curves. cache = ./cache/cord-321640-kx3t81yh.txt txt = ./txt/cord-321640-kx3t81yh.txt === reduce.pl bib === id = cord-321697-yua3apfi author = Crigna, Adriana Torres title = Cell-free nucleic acid patterns in disease prediction and monitoring—hype or hope? date = 2020-10-29 pages = extension = .txt mime = text/plain words = 10892 sentences = 608 flesch = 40 summary = This article highlights the involvement of circulating CFNAs in local and systemic processes dealing with the question, whether specific patterns of CFNAs in blood, their detection, quantity and quality (such as their methylation status) might be instrumental to predict a disease development/progression and could be further utilised for accompanying diagnostics, targeted prevention, creation of individualised therapy algorithms, therapy monitoring and prognosis. Especially severe, prolonged and/ or chronic stress of any origin such as exercise-induced oxidative stress [22] (see "Physical activity and exercise-induced oxidative stress" section), hormonal stress [23] , emotional stress and psychological burden [24] [25] [26] [27] as well as metabolic stress, e.g. in diabetes mellitus [28, 29] (see also below "Association between diabetes mellitus and carcinogenesis: diagnostic and therapeutic potential of cell-free nucleic acids" section) and hyperhomocysteinaemia [30, 31] amongst others, is associated with highly increased ROS production and insufficient repair capacity-both linked to oxidative damage of mitochondria and consequent mitochondrial dysfunction leading to the development of cardiovascular impairments [32] [33] [34] , neuro/degenerative pathologies [34] [35] [36] [37] , impaired healing [34] and malignant cell transformation [34, [38] [39] [40] [41] [42] . cache = ./cache/cord-321697-yua3apfi.txt txt = ./txt/cord-321697-yua3apfi.txt === reduce.pl bib === id = cord-324321-y96x8x3h author = Cai, Yingyun title = Down-regulation of transcription of the proapoptotic gene BNip3 in cultured astrocytes by murine coronavirus infection date = 2003-11-10 pages = extension = .txt mime = text/plain words = 8454 sentences = 416 flesch = 49 summary = Furthermore, treatment of cells with chloroquine, which blocks the acidification of endosomes, significantly inhibited the repression of the BNip3 promoter activity induced by the acidic pH-dependent MHV mutant OBLV60, which enters cells via endocytosis, indicating that the down-regulation of BNip3 expression is mediated by fusion between viral envelope and cell membranes during entry. To establish further the specificity of the down-regulation of BNip3 gene expression, we used vesicular stomatitis virus (VSV) in a parallel experiment, because VSV is also an enveloped RNA virus whose infection has a broad host cell range and is mediated by the interaction between the envelope G protein and cell membranes (Riedel et al., 1984) . By extrapolating the data from the mutant virus, we can envision that fusion between viral envelope and plasma/endosomal membranes during wild-type MHV infection is involved in the down-regulation of BNip3 gene expression. cache = ./cache/cord-324321-y96x8x3h.txt txt = ./txt/cord-324321-y96x8x3h.txt === reduce.pl bib === id = cord-321386-u1imic5l author = Li, Chun title = Protein Sequence Comparison and DNA-binding Protein Identification with Generalized PseAAC and Graphical Representation date = 2018-02-17 pages = extension = .txt mime = text/plain words = 5503 sentences = 311 flesch = 59 summary = METHODS: Based on two physicochemical properties of amino acids, a protein primary sequence was converted into a three-letter sequence, and then a graph without loops and multiple edges and its geometric line adjacency matrix were obtained. A generalized PseAAC (pseudo amino acid composition) model was thus constructed to characterize a protein sequence numerically. In addition, a generalized PseAAC based SVM (support vector machine) model was developed to identify DNA-binding proteins. Also, we develop a SVM (support vector machine) model using the generalized PseAAC to identify DNA-binding and non-binding proteins on three datasets. By combining these elements with the conventional amino acid composition (AAC), a dimensional feature vector can be constructed to numerically characterize a protein sequence: , By combining these elements with the frequencies of occurrence of 20 standard amino acids and their three representative letters, a generalized PseAAC model of a protein sequence was constructed. Numerical characterization of protein sequences based on the generalized Chou's pseudo amino acid composition cache = ./cache/cord-321386-u1imic5l.txt txt = ./txt/cord-321386-u1imic5l.txt === reduce.pl bib === id = cord-325280-4whzcmqv author = Takizawa, Naoki title = Current landscape and future prospects of antiviral drugs derived from microbial products date = 2017-10-11 pages = extension = .txt mime = text/plain words = 6601 sentences = 365 flesch = 34 summary = In this review, we summarize antiviral microbial products discovered by Institute of Microbial Chemistry (IMC) and discuss antiviral compounds against influenza virus and HBV, because these two viruses threaten global human health now and antiviral drug against these two viruses have been developed. THE CONTRIBUTIONS OF IMC TO ANTIVIRAL RESEARCH Nucleos(t)ide analogs are a major class of approved antiviral drugs that exert therapeutic effects through incorporation into viral DNA and RNA to inhibit virus replication. Viral polymerase complex is a promising target for the development of anti-influenza drugs, because transcription and replication are critical steps for virus propagation. Potential applications of microbial products in anti-HBV drug development Approved nucleos(t)ide analogs competitively inhibit DNA elongation of viral polymerase after the conversion to triphosphate form by cellular enzymes. cache = ./cache/cord-325280-4whzcmqv.txt txt = ./txt/cord-325280-4whzcmqv.txt === reduce.pl bib === id = cord-324137-nau83mjv author = Saranathan, Nandhini title = G-Quadruplexes: More Than Just a Kink in Microbial Genomes date = 2018-09-14 pages = extension = .txt mime = text/plain words = 6722 sentences = 379 flesch = 42 summary = Several reports convincingly demonstrate antimicrobial activity of quadruplex-binding ligands against clinically challenging pathogens, including HIV-1, HCV, Ebola virus, Plasmodium falciparum, and Mycobacterium tuberculosis. An earlier study reports that, following concatemeric replication of HHV-1, the cleavage of unit length genomes and their encapsidation is achieved by the binding of virus proteins to a DNA secondary structure formed by a DNA packaging sequence (pac-1) [50] . G4s have been shown to inhibit the transcription or translation of structural and nonstructural proteins in viruses, deleteriously affecting the virus loads and their pathogenicity; the stabilization of these quadruplexes with ligands has been investigated as a potential mechanism for targeting viruses. Negative regulation of virus transcription, translation or replication by quadruplex motifs in virus genomes forms the basis of using G4-binding ligands as antiviral agents. G-quadruplex forming structural motifs in the genome of Deinococcus radiodurans and their regulatory roles in promoter functions cache = ./cache/cord-324137-nau83mjv.txt txt = ./txt/cord-324137-nau83mjv.txt === reduce.pl bib === id = cord-321762-7kiahjyy author = Nandy, Ashesh title = Chapter 5 The GRANCH Techniques for Analysis of DNA, RNA and Protein Sequences date = 2015-12-31 pages = extension = .txt mime = text/plain words = 9780 sentences = 392 flesch = 46 summary = We presented our scheme at the First Indo-US Workshop on Mathematical Chemistry in Shantiniketan, West Bengal, India in 1998 [10] where we reported, as stated in the abstract, that "Geometrisation of macromolecular sequences in the form of a graphical representation provides one … technique where the nucleotides in a gene sequence can be viewed as objects in a 4-dimensional space; the method can be extended, in principle, to include, say proteins, in a 20-dimensional space. This review is a brief introduction to the readers of this new and exciting field of research on graphical representation and numerical characterization (GRANCH) of bio-molecular sequences, based on the talk I presented at the Second Mathematical Chemistry Workshop of the Americas in Bogota, Colombia, in July 2010 [13] . cache = ./cache/cord-321762-7kiahjyy.txt txt = ./txt/cord-321762-7kiahjyy.txt === reduce.pl bib === id = cord-324944-ixh3ykrc author = Mitsakakis, Konstantinos title = Diagnostic tools for tackling febrile illness and enhancing patient management date = 2018-12-05 pages = extension = .txt mime = text/plain words = 20805 sentences = 961 flesch = 45 summary = This review gives an overview of diagnostic technologies featuring a platform based approach: (i) assay (nucleic acid amplification technologies are examined); (ii) cartridge (microfluidic technologies are presented); (iii) instrument (various detection technologies are discussed); and at the end proposes a way that such technologies can be interfaced with electronic clinical decision-making algorithms towards a broad and complete diagnostic ecosystem. In studies that have recorded the clinical presentation of patients (and not only their laboratory results), the causes of fever in outpatients could be classified into four main syndromes: 1) acute respiratory infections (ARI, of any type); 2) diarrhea (gastroenteritis); 3) fever with another clear focus (e.g. meningitis or skin infection); and 4) non-specific fevers [13] (each diagnostic platform described in Section 5 focuses on at least one of the aforementioned cases). cache = ./cache/cord-324944-ixh3ykrc.txt txt = ./txt/cord-324944-ixh3ykrc.txt === reduce.pl bib === id = cord-324829-0nz0qioh author = Carabineiro, Sónia Alexandra Correia title = Applications of Gold Nanoparticles in Nanomedicine: Recent Advances in Vaccines † date = 2017-05-22 pages = extension = .txt mime = text/plain words = 7639 sentences = 420 flesch = 38 summary = Gold nanoparticles, in general, have remarkably high surface-to-volume ratio, are biocompatible and inert, and can be easily functionalized with several molecules; thus, they can also play an important role in the vaccine field as adjuvants, reducing toxicity, enhancing immunogenic activity, and providing stability of vaccine in storage, and have great potential as carriers for the development of a great diversity of fully synthetic vaccines [8] [9] [10] [11] [12] 15, 20, 21, 26, [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] . Gold nanoparticles, in general, have remarkably high surface-to-volume ratio, are biocompatible and inert, and can be easily functionalized with several molecules; thus, they can also play an important role in the vaccine field as adjuvants, reducing toxicity, enhancing immunogenic activity, and providing stability of vaccine in storage, and have great potential as carriers for the development of a great diversity of fully synthetic vaccines [8] [9] [10] [11] [12] 15, 20, 21, 26, [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] . cache = ./cache/cord-324829-0nz0qioh.txt txt = ./txt/cord-324829-0nz0qioh.txt === reduce.pl bib === id = cord-326785-le2t1l8g author = nan title = Pathological Society of Great Britain and Ireland. 163rd meeting, 3–5 July 1991 date = 2005-06-15 pages = extension = .txt mime = text/plain words = 22752 sentences = 2108 flesch = 42 summary = The lesions (usually multlpleand each 5 mm orless m diameter) were identified in lung parenchymaat a distance from the tumour and consisted of thickened alveolar walls lined by prominent, distinctly atypical cells morphologically Slmllar to type I 1 pneumacytes and cytologically different to the associated turnour Reactive changes 8" lung involved by obstrmtive pneumonitis were not included !n thts Sews All of the associated tumwra were peripheral adenocarcinamas and all showed a pattern of alveolar wall spread at the tumour periphery Clinically 7 of the patients were female and all were smokers or ex-smokers The slgnlflcance of this lesion in the histogenesis of primary pulmonary ademcarcinoma IS. cache = ./cache/cord-326785-le2t1l8g.txt txt = ./txt/cord-326785-le2t1l8g.txt === reduce.pl bib === id = cord-328518-umvk59dc author = Lee, Dana N. title = Two novel adenoviruses found in Cave Myotis bats (Myotis velifer) in Oklahoma date = 2019-12-03 pages = extension = .txt mime = text/plain words = 2380 sentences = 160 flesch = 60 summary = In this study, 30 pooled-guano samples were collected from a cave roost of Myotis velifer in Oklahoma. Phylogenetic analysis of these fragments confirmed our isolates were from the genus Mastadenovirus and had genetic diversity ranging from 20 to 50% when compared to other bat adenoviruses. Adenoviruses (AdVs) are double stranded DNA viruses found in vertebrate hosts of many different species [8, 10] . DNA sequence from Guano sample 21, 22, 24, and 25 represent a separate Adenovirus species and are further referred to as Cave Myotis AdV2. Little work has been done to investigate AdVs in North American species of bats; however, these studies [19, 29] and ours highlight the importance of identifying viruses housed in bats to better understand viral evolution, how viruses are maintained in bat colonies and evaluate risks for host transmission to other species. cache = ./cache/cord-328518-umvk59dc.txt txt = ./txt/cord-328518-umvk59dc.txt === reduce.pl bib === id = cord-327170-rv0efgg2 author = Decaro, Nicola title = Tissue distribution of the antigenic variants of canine parvovirus type 2 in dogs date = 2007-03-31 pages = extension = .txt mime = text/plain words = 2675 sentences = 143 flesch = 54 summary = Twelve dogs dead as consequence of natural infection caused by canine parvovirus (CPV) type 2a (n = 4), type 2b (n = 4) or type 2c (n = 4) were investigated for determining the viral DNA loads in different tissue samples. By means of a real-time PCR assay, CPV DNA was detected in all tissues examined, with the highest titres observed in the lymphoid tissue and the lowest loads in the urinary tract. In this study, by using real-time PCR, we investigated the pattern of distribution of the CPV variants in different tissues of dogs infected naturally. The viral DNA titres found in the different tissues of the dogs infected naturally by types 2a, 2b and 2c are reported in Fig. 1 . A real-time PCR assay for rapid detection and quantitation of canine parvovirus type 2 DNA in the feces of dogs A minor groove binder probe real-time PCR assay for discrimination between type 2-based vaccines and field strains of canine parvovirus cache = ./cache/cord-327170-rv0efgg2.txt txt = ./txt/cord-327170-rv0efgg2.txt === reduce.pl bib === id = cord-330581-g5r2b043 author = Marini, Elena title = HIV‐1 matrix protein p17 binds to monocytes and selectively stimulates MCP‐1 secretion: role of transcriptional factor AP‐1 date = 2007-10-26 pages = extension = .txt mime = text/plain words = 8241 sentences = 419 flesch = 52 summary = C. AP-1 protein family profiling for DNA-binding activity of an ELISA-based transcription factor assay kit using nuclear extracts (4 mg per sample) from human monocytes cultured for 1 h in the presence or absence of p17-and AP-1-specific oligonucleotides immobilized to a 96-well plate. Due to the large number of primary monocytes required for the analysis of transcription factor DNA-binding activity in protein nuclear extracts, we further investigated the involvement of AP-1 transcription factor in p17-induced MCP-1 transcriptional events using the monocytic cell line THP-1, which constitutively expresses p17Rs on its surface (data not shown). Among these, the HIV-1 matrix protein p17 has been recently identified as a critical determinant in AIDS pathogenesis as it binds to a cellular receptor expressed on immune cells and enhances viral replication and infectivity (De Francesco et al., 1998) , through a combination of different effector functions (De Francesco et al., 2002; Vitale et al., 2003) . cache = ./cache/cord-330581-g5r2b043.txt txt = ./txt/cord-330581-g5r2b043.txt === reduce.pl bib === id = cord-324811-yjwavea5 author = Kidgell, Claire title = Elucidating genetic diversity with oligonucleotide arrays date = 2005 pages = extension = .txt mime = text/plain words = 5561 sentences = 268 flesch = 37 summary = Oligonucleotide microarrays, predominantly high-density oligonucleotide arrays, have emerged as the principal platforms for performing genome-wide diversity analysis. Since a number of complex issues still remain with high-throughput microarray-based SNP genotyping in humans, in the remainder of this review, we will discuss the application of high-density oligonucleotide arrays to elucidate genetic diversity, with particular focus on studies undertaken with Saccharomyces cerevisiae (Winzeler et al. falciparum (Clark 2002) , the genome-wide analysis facilitated by hybridization of genomic DNA to the A¡ymetrix microarray identi¢ed signi¢cant di¡erences in potential selection pressure across di¡erent gene families and locations within the chromosome (Volkman et al. Although SNPs and deletions can be readily identi¢ed using A¡ymetrix high-density arrays, more complex types of genetic diversity may also be determined using this platform. cache = ./cache/cord-324811-yjwavea5.txt txt = ./txt/cord-324811-yjwavea5.txt === reduce.pl bib === id = cord-328899-kog99kk5 author = Ferrari, Stefano title = Barriers to and new approaches for gene therapy and gene delivery in cystic fibrosis date = 2002-12-05 pages = extension = .txt mime = text/plain words = 10491 sentences = 536 flesch = 45 summary = Strategies to overcome these barriers will be addressed in this review and include the use of: (i) clinically relevant adjuncts to overcome the extraand intracellular barriers; (ii) less-conventional delivery routes, such as intravenous or in utero administration; (iii) more efficient non-viral vectors and 'stealth' viruses which can be re-administered; and (iv) new approaches to prolong transgene expression by means of alternative promoters or integrating vectors. Interesting-Using an ex vivo sheep trachea model, we demonly, despite non-viral vectors being arguably less strated that cationic lipid-mediated gene transfer, but efficient than viruses in animal models and labora-not adenoviral vectors or recombinant Sendai virus tory studies, clinical trials have shown that this might [22] , was inhibited by normal mucus, with removal Extracellular barriers include the presence of infected mucus and sputum, mucociliary clearance and tight junctions between the cells, which limit the access of viral vectors to receptors localised on the basolateral membrane. cache = ./cache/cord-328899-kog99kk5.txt txt = ./txt/cord-328899-kog99kk5.txt === reduce.pl bib === id = cord-328206-iylw1bvw author = Yu, Daojun title = Simultaneous Detection and Differentiation of Human Papillomavirus Genotypes 6, 11, 16 and 18 by AllGlo Quadruplex Quantitative PCR date = 2012-11-09 pages = extension = .txt mime = text/plain words = 4070 sentences = 209 flesch = 48 summary = In this study, applying novel AllGlo fluorescent probes, we established a quadruplex quantitative PCR method to simultaneously detect and differentiate HPV 6, 11, 16 and 18 in a single tube. So AllGlo quadruplex quantitative PCR has the advantages of relatively high throughput, good reproducibility, high sensitivity, high specificity, it is easy for designing the probes and primers of multiplex qPCR and can increase the detection throughput. Two aliquots were used for the detection of HPV6-11 and HPV16-18 mixed types by TaqMan uniplex probe fluorescence quantitative PCR (Guangzhou Da'an Diagnostic Co., Ltd., China). Single-tube AllGlo probe quadruplex fluorescence qPCR could simultaneously type HPV 6, 11, 16, and 18 and quantitatively detect the viral load of each HPV at the same time. Single-tube AllGlo probe quadruplex fluorescence qPCR could simultaneously type HPV 6, 11, 16, and 18 and quantitatively detect the viral load of each HPV at the same time. cache = ./cache/cord-328206-iylw1bvw.txt txt = ./txt/cord-328206-iylw1bvw.txt === reduce.pl bib === id = cord-327883-s9nbr5y8 author = nan title = Section Virology date = 1990-03-31 pages = extension = .txt mime = text/plain words = 10576 sentences = 571 flesch = 48 summary = By improving the enzyme-linked immunosorbent assay (ELISA) for HSV-2-antibodies and additional testing of sera by Western blot, we were able to specifically identify HSV-l-and HSV-2-antibodies in serum samples. To get some insight into the molecular basis of processes controlling the viral expression we studied the sequence-specific DNA-protein interactions within the genomic regulatory regions. for Med. Microbiology, Univ., D-5300 Bonn Semiquantitative detection of Hepatitis B Virus (HBV) DNA in sera of infected individuals has become an important means of modern serological hepatitis diagnostics. THOMSSEN 1 In the course of acute Epstein-Barr virus (EBV) infection IgM antibodies always occur against two cellular antigens that were characterized as proteins with a molecular weight of 26 kD (p26) and 29 kD (p29), respectively. The frequency and specificity of antibodies to P-gene encoded proteins of human hepatitis B virus was tested in sera of acute and chronically infected patients with and without hepatocellular carcinoma (HCC). cache = ./cache/cord-327883-s9nbr5y8.txt txt = ./txt/cord-327883-s9nbr5y8.txt === reduce.pl bib === id = cord-328460-thx9zh11 author = Zanoli, Laura Maria title = Isothermal Amplification Methods for the Detection of Nucleic Acids in Microfluidic Devices date = 2012-12-27 pages = extension = .txt mime = text/plain words = 8972 sentences = 407 flesch = 36 summary = Miniaturized isothermal amplification systems will be then illustrated including nucleic acid sequence-based amplification (NASBA), loop-mediated isothermal amplification (LAMP), helicase-dependent amplification (HDA), rolling circle amplification (RCA), multiple displacement amplification (MDA) and recombinase polymerase amplification (RPA). In addition, the use of droplet-based microfluidic systems for PCR enables the amplification and the analysis of individual target sequences to be performed in a significantly lower time as a consequence of a higher thermal cycling speed. These include nucleic acid sequence-based amplification (NASBA), loop-mediated amplification (LAMP), helicase-dependent amplification (HDA), rolling circle amplification (RCA), recombinase polymerase amplification (RPA) and multiple displacement amplification (MDA) [7] . Unlike other electrochemical techniques [56], based on the immobilization of an oligonucleotide probe onto an electrode, hybridization of a complementary target sequence, and transduction of the hybridization event [57], the microfluidic detection of LAMP amplicons [55] does not require probe immobilization and bacteria detection can be accomplished in a single chamber without DNA extraction and purification steps, since the used isothermal temperature (66 °C) provides enough thermal shock to lyse the E. cache = ./cache/cord-328460-thx9zh11.txt txt = ./txt/cord-328460-thx9zh11.txt === reduce.pl bib === id = cord-326228-9x1233q6 author = Holley, Caroline L title = The rOX‐stars of inflammation: links between the inflammasome and mitochondrial meltdown date = 2020-02-10 pages = extension = .txt mime = text/plain words = 6351 sentences = 434 flesch = 32 summary = Nod-like receptor protein 3 (NLRP3) is a cytosolic PRR activated by a wide range of PAMPs (bacterial toxins, fungal and viral components) and DAMPs (e.g. extracellular ATP, lysosomal-disrupting crystals), including those of mitochondrial origin. The mechanisms by which mitochondria influence PRR activity and drive inflammatory responses are important research foci for understanding protective innate immune functions during host defence against infection, as well as innate immune pathology in disease. 55 It is possible that LLO-driven MAM disruption and mitochondrial fission removes a key site of inflammasome assembly to dampen K + effluxdependent NLRP3 signalling and thereby allows the bacterium to partially evade immune recognition. NLRP3 activation in mouse macrophages can be associated with loss of mitochondrial membrane potential or defective mitophagy, leading to mitoROS production and mtDNA release from mitochondria to the cytosol. cGAS/STING signalling may also be a downstream consequence of NLRP3 activation; for example, IL-1R signalling in the human THP-1 myeloid cell line drives loss of mitochondrial membrane potential and recognition of mtDNA by cGAS. cache = ./cache/cord-326228-9x1233q6.txt txt = ./txt/cord-326228-9x1233q6.txt === reduce.pl bib === id = cord-328940-8vtcochx author = Lee, Jeong Yoon title = Bacterial RecA Protein Promotes Adenoviral Recombination during In Vitro Infection date = 2018-06-20 pages = extension = .txt mime = text/plain words = 7979 sentences = 407 flesch = 39 summary = By analysis of known recombination hot spots across 38 human adenovirus genomes in species D (HAdV-D), we identified nucleotide sequence motifs similar to bacterial Chi sequences, which facilitate homologous recombination in the presence of bacterial Rec enzymes. We speculate that free Rec proteins present in gastrointestinal secretions upon bacterial cell death facilitate the evolution of human adenoviruses through homologous recombination, an example of viral commensalism and the complexity of virus-host interactions, including regional microbiota. Our computational analysis of similar GC content transitions across whole HAdV-D genomes showed comparable patterns of GC/AT transition at predicted recombination hot spots around hypervariable gene segments in the three major capsid genes-the same segments that constitute the molecular identity of each virus (14, 19, (41) (42) (43) -including the region containing Chi AD immediately 5= to penton base HVL2 (see Fig. S1 and Table S1 in the supplemental material). cache = ./cache/cord-328940-8vtcochx.txt txt = ./txt/cord-328940-8vtcochx.txt === reduce.pl bib === id = cord-328633-c31xsyeo author = Moser, Michael J. title = Thermostable DNA Polymerase from a Viral Metagenome Is a Potent RT-PCR Enzyme date = 2012-06-04 pages = extension = .txt mime = text/plain words = 7868 sentences = 441 flesch = 54 summary = Most RT-PCR protocols rely on two DNA polymerase (Pol) enzymes; a retroviral reverse transcriptase (RT) to copy RNA into cDNA and a thermostable DNA Pol to amplify the target sequence. Despite their wide use and general reliability, existing twoenzyme RT-PCR systems have several documented performance problems attributed to deficiencies inherent in retroviral RTs: 1) poor reagent stability, 2) low fidelity, 3) frequent rearrangements during cDNA synthesis, 4) secondary enzymatic activities (i.e. RNase H and strand switching), 5) bias for specific primers and templates, and 6) inhibition of PCR Pol enzymes [3, 4, 5, 6, 7] . We describe the discovery and biochemical attributes of one of these, 3173 Pol, its inherent RT activity and its incorporation into a single-enzyme PyroScriptH 2X RT-PCR Master Mix. The sensitivity, specificity and overall performance of this mix were compared to available one-and two-enzyme systems using a control MS2 RNA bacteriophage template, the clinically-relevant influenza A RNA and commonly used reference mRNA transcripts. cache = ./cache/cord-328633-c31xsyeo.txt txt = ./txt/cord-328633-c31xsyeo.txt === reduce.pl bib === id = cord-331641-u27ohm5p author = Liu, Xiaonan title = A direct isothermal amplification system adapted for rapid SNP genotyping of multifarious sample types date = 2018-09-15 pages = extension = .txt mime = text/plain words = 3850 sentences = 186 flesch = 51 summary = In this study, we devised a Direct-LAMP procedure, amplifying nucleic acids with various samples (including whole blood, dried blood spot, buccal swab and saliva) without DNA purification, which is essential for conventional nucleic acid detection methods. To evaluate the performance of the Direct-LAMP, a serial dilution of the target concentrations of whole blood sample and saliva sample with two different genotypes (wild type and homozygous mutation which confirmed by sequencing) of MTHFR C677T and ALDH2 Glu504Lys, respectively, were used to determine the detection limit. Here, we have established a rapid, easy-to-use and accurate SNP detection platform using Direct-LAMP, which enables us to use whole blood, dried blood spot, buccal swab or saliva as samples for genotyping without DNA purification. In this study, we presented a Direct-LAMP for SNP detection by using whole blood, dried blood spot, buccal swab or saliva as samples without DNA purification. cache = ./cache/cord-331641-u27ohm5p.txt txt = ./txt/cord-331641-u27ohm5p.txt === reduce.pl bib === id = cord-330800-s91zfzfi author = Reta, Daniel Hussien title = Molecular and Immunological Diagnostic Techniques of Medical Viruses date = 2020-09-04 pages = extension = .txt mime = text/plain words = 10548 sentences = 574 flesch = 43 summary = e nucleic acid amplification tests are very popular in the diagnosis of viral infections caused by several viruses, including hepatitis C virus (HCV), human immunodeficiency virus (HIV), dengue virus, Epstein-Barr virus (EBV), influenza viruses, Zika virus (ZIKV), Ebola virus, and coronavirus [26] [27] [28] [29] [30] [31] [32] . Owing to high sensitivity and specificity, short turnaround time for results, and ease of performance [33, 61] , most laboratories across the globe employ real-time PCR for the detection and quantification of medical DNA and RNA viruses in clinical specimens. For example, Co-Diagnostics (Salt Lake City, USA) has developed real-time RT-PCR kit (Logix Smart COVID-19 test) for qualitative detection of nucleic acid from the SARS-CoV-2 in lower respiratory samples (e.g., bronchoalveolar lavage, sputum, and tracheal aspirate) and upper respiratory specimens (e.g., oropharyngeal swabs, nasal swabs, and nasopharyngeal swabs). LAMP is another isothermal nucleic acid amplification method that is extensively utilized for sensitive, specific, rapid, and cost-effective detection of both DNA and RNA viruses in human specimens. cache = ./cache/cord-330800-s91zfzfi.txt txt = ./txt/cord-330800-s91zfzfi.txt === reduce.pl bib === id = cord-325750-x7jpsnxg author = Mokili, John L title = Metagenomics and future perspectives in virus discovery date = 2012-01-20 pages = extension = .txt mime = text/plain words = 8742 sentences = 463 flesch = 40 summary = In this article, we review virus discovery techniques with a focus on metagenomic approaches that employ high-throughput sequencing technologies to characterize novel viruses. This method lacks sufficient sensitivity to detect viruses when the viral burden is low or when the DNA sequence of the suspected etiological agent is not clearly distinguishable from the control sample [31] . The following items should be included in any report on viral metagenomic studies: firstly, the sequencing platform and its version number; secondly, raw sequence data accession numbers in a public database; thirdly, details about the bioinformatic analysis, including the homology search tool and the database being used to assign the taxonomy, and their versions; fourthly, a list of known and previously unknown viruses found, clearly showing if the 'novel' viruses are new strains of a previously described species or completely different viruses; and fifthly, causality evidence if any. cache = ./cache/cord-325750-x7jpsnxg.txt txt = ./txt/cord-325750-x7jpsnxg.txt === reduce.pl bib === id = cord-325915-dw989txm author = Wolf, Michael W title = Downstream processing of cell culture-derived virus particles date = 2014-01-09 pages = extension = .txt mime = text/plain words = 11861 sentences = 655 flesch = 34 summary = The number of publications [24, [38] [39] [40] [41] [42] [43] [44] [45] [46] and patents [301] [302] [303] describing the purification or concentration of virus particles by centrifugation methods demonstrates that these procedures are extensively used at industrial-and small-scale levels for viral vectors and vaccine production processes. In summary, the main advantages of ultrafiltration compared with other methods are their high-throughput and (for the concentration of active virus particles) the gentle processing at optimal operating conditions [43, 47] that results in improved efficacies for purification of viral vectors for gene therapy. Considering a complete purification train for the production of vaccines or gene therapy vectors (Figure 1) , current improvements of the dynamic binding capacities in chromatography media might facilitate the removal of the initial concentration step within the downstream process. cache = ./cache/cord-325915-dw989txm.txt txt = ./txt/cord-325915-dw989txm.txt === reduce.pl bib === id = cord-022940-atbjwpo5 author = nan title = Poster Sessions date = 2016-09-07 pages = extension = .txt mime = text/plain words = 241182 sentences = 12746 flesch = 47 summary = We have studied the effect of inhibition of IRE1 (inositol requiring enzyme 1), which is a central mediator of endoplasmic reticulum stress and controls cell proliferation and tumor growth, on hypoxic regulation of the expression of different proliferation related genes in U87 glioma cells. Transient inhibition of Akt and mTOR protein kinase activation in tumor cells followed by reactivation of signaling pathway did not result in a time-dependent difference on EGFR, HER2 and HER3 expression levels. In our study we aimed to determine cytotoxic effect of RES in K562 human CML cell line and to evaluate the expressions of miRNAs that are associated with genetics of leukemia after treatment with RES; to investigate target genes of miRNAs which show significant expression alterations and molecular mechanisms of RES treatment. cache = ./cache/cord-022940-atbjwpo5.txt txt = ./txt/cord-022940-atbjwpo5.txt === reduce.pl bib === id = cord-332379-340wczmq author = Pennington, Matthew R. title = Disparate Entry of Adenoviruses Dictates Differential Innate Immune Responses on the Ocular Surface date = 2019-09-13 pages = extension = .txt mime = text/plain words = 11584 sentences = 604 flesch = 36 summary = These findings suggest that adenoviruses may stimulate specific pattern recognition receptors in an entry/trafficking-dependent manner, leading to distinct immune responses dependent on the virus/cell type combination. Additional work is needed to understand the specific connections between adenoviral entry and the stimulation of innate immune responses by the various cell types present on the ocular surface. Innate immune responses to adenoviruses rely on the detection of pathogen-associated molecular patterns (PAMPs): distinct ligands present on the external surfaces, and nucleic acids of pathogens (but absent in the host) that feature molecular signatures able to be recognized by pattern recognition receptors (PRR) on or in infected host cells [43] [44] [45] [46] . Innate immune responses to adenoviruses rely on the detection of pathogen-associated molecular patterns (PAMPs): distinct ligands present on the external surfaces, and nucleic acids of pathogens (but absent in the host) that feature molecular signatures able to be recognized by pattern recognition receptors (PRR) on or in infected host cells [43] [44] [45] [46] . cache = ./cache/cord-332379-340wczmq.txt txt = ./txt/cord-332379-340wczmq.txt === reduce.pl bib === id = cord-329155-ddpfox68 author = Mindikoglu, Ayse L. title = Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome date = 2020-10-27 pages = extension = .txt mime = text/plain words = 8186 sentences = 379 flesch = 43 summary = Our results showed that 30-day intermittent fasting from dawn to sunset, the human activity phase, was associated with an anticancer serum proteome response and upregulated several key regulatory proteins that play a key role in tumor suppression, DNA repair, insulin signaling, glucose, and lipid metabolism, circadian clock, cytoskeletal remodeling, immune system, and cognitive function 15 . In accord with the findings of these murine and human studies 13,25 , we found a significant fold increase in the levels of specific tumor suppressor/anticancer proteins at the end of 4th week during 4-week intermittent fasting from dawn to sunset and/or 1 week after 4-week intermittent fasting from dawn to sunset, including CALR, CALU, INTS6, KIT, CROCC, PIGR, IGFBP4, and SEMA4B that are downregulated in several cancers resulting in cancer metastasis and poor prognosis (Table 2, Fig. 2 ). cache = ./cache/cord-329155-ddpfox68.txt txt = ./txt/cord-329155-ddpfox68.txt === reduce.pl bib === id = cord-331916-n744pymd author = Liu, Jue title = Inhibition of porcine circovirus type 2 replication in mice by RNA interference date = 2006-04-10 pages = extension = .txt mime = text/plain words = 6657 sentences = 350 flesch = 52 summary = Specific inhibition of endogenous or pathogen mRNA by RNAi can be triggered by the introduction of 21 -23 nucleotide (nt) duplexes of RNA (siRNA) or by transcription of DNA precursor into short hairpin RNAs (shRNA) homologous to target sequences (Brummelkamp et al., 2002; Elbashir et al., 2001a; Paddison et al., 2002) , opening up possibilities for controlling replicative processes of pathogens. To further examine the ability of ORF1 shRNA to suppress viral gene expression in PCV2-infected PK15 cells, single nucleotide mutations were introduced into pSIR3 sequence as shown in Fig. 4A . As shown in Fig. 4B , a mutant with one nucleotide mutation in the 5V-end of the sense strand (pSIR3-m1) still had an effective reduction in the synthesis of ORF1 and ORF2 proteins, whereas with a nucleotide substitution at the center (pSIR3-m2) or 3V-end (pSIR3-m3) of the sense sequence, the resultant shRNAs failed to significantly suppress expression of PCV2 ORF1 and ORF2 in the transfected cells, further verifying the specificity of RNAi as demonstrated (Amarzguioui et al., 2003; Harborth et al., 2003) . cache = ./cache/cord-331916-n744pymd.txt txt = ./txt/cord-331916-n744pymd.txt === reduce.pl bib === id = cord-328947-3l9ydspz author = Webb, L. G. title = Chikungunya virus antagonizes cGAS-STING mediated type-I interferon responses by degrading cGAS date = 2020-10-15 pages = extension = .txt mime = text/plain words = 9857 sentences = 544 flesch = 51 summary = CHIKV is no exception, the type-I interferon (IFN) response has been demonstrated to be key in controlling CHIKV infection [21] [22] [23] [24] [25] [26] and primary sensing of the virus is via the pattern recognition receptor (PRR) retinoic acid-inducible gene I (RIG-I)-mitochondrial antiviral signaling protein (MAVS) axis [24, 26] . The lack of cGAS degradation seen in the exogenous expression system when compared to the infected cells shows that although there is a clear interaction of cGAS with nsP4, the degradation of cGAS observed is not mediated by the non-structural proteins of CHIKV, but must require other viral or host factors. Chikungunya virus inhibits DNA sensing by degrading cGAS both mock and infected cells by 4 hpi suggesting that the stress produced during the process of infection (mock or CHIKV) in HFF-1s stimulates increased translation at early timepoints ( Fig 4D, lanes 2 and 5) . cache = ./cache/cord-328947-3l9ydspz.txt txt = ./txt/cord-328947-3l9ydspz.txt === reduce.pl bib === id = cord-332654-nav15g8k author = Paniri, Alireza title = Molecular effects and retinopathy induced by hydroxychloroquine during SARS-CoV-2 therapy: Role of CYP450 isoforms and epigenetic modulations date = 2020-08-04 pages = extension = .txt mime = text/plain words = 5712 sentences = 341 flesch = 47 summary = The major focus of the present review is to discuss about the pharmacokinetic and pharmacodynamic properties of CQ and HCQ that may be influenced by epigenetic mechanisms, and consequently cause several side effects especially retinopathy during SARS-CoV-2 therapy. Furthermore, growing body of evidence demonstrated that several factors including CYP450 single nucleotide polymorphisms (SNPs), and epigenetic molecules such as non-coding RNAs (ncRNAs), DNA methylation and histone acetylation influenced the expression levels of CYP450, and consequently might influence HCQ metabolism. The major purpose of this review is to discuss the pharmacokinetic and pharmacodynamic characteristics of CQ and HCQ that may be influenced by epigenetic mechanisms including ncRNAs and CYP2D6 SNPs, and thereby cause several side effects such as cardiotoxicity, prolonged QT interval, gastrointestinal problems (like dyspepsia and abdominal cramps), central nervous system or skin disorders, and especially retinopathy. cache = ./cache/cord-332654-nav15g8k.txt txt = ./txt/cord-332654-nav15g8k.txt === reduce.pl bib === id = cord-331718-rjggiklf author = Kubota, Takeo title = Epigenetic Effect of Environmental Factors on Autism Spectrum Disorders date = 2016-05-14 pages = extension = .txt mime = text/plain words = 4770 sentences = 243 flesch = 33 summary = Epigenetics, an essential mechanism for gene regulation based on chemical modifications of DNA and histone proteins, is also involved in congenital ASDs. It was recently demonstrated that environmental factors, such as endocrine disrupting chemicals and mental stress in early life, can change epigenetic status and gene expression, and can cause ASDs. Moreover, environmentally induced epigenetic changes are not erased during gametogenesis and are transmitted to subsequent generations, leading to changes in behavior phenotypes. These results suggest that close interaction between neuronal molecules and epigenetic molecules is important for normal brain development and failure of this interaction is potentially associated with ASDs. In this review, we introduce congenital epigenetic disorders with ASD-like phenotypes and environmental factors that affect epigenetic regulation of neuronal genes, and discuss transgenerational epigenetic inheritance and therapeutic strategies for ASDs taking advantage of use of the epigenetic reversibility. Rett syndrome (RTT) is a representative ASD characterized by repetitive and stereotypic hand movements, seizures, gait ataxia and autism [35] and is caused by mutations in the gene that encode methyl-CpG-binding protein 2 (MeCP2), which is associated with chromatin remodeling [36] . cache = ./cache/cord-331718-rjggiklf.txt txt = ./txt/cord-331718-rjggiklf.txt === reduce.pl bib === id = cord-010092-uftc8inx author = nan title = Abstract of 29th Regional Congress of the ISBT date = 2019-06-07 pages = extension = .txt mime = text/plain words = 233304 sentences = 13171 flesch = 54 summary = Prospective testing of blood donations in endemic areas of the U.S. revealed 0.38% of donors were positive for Babesia DNA or antibodies (Moritz, NEJM, 2016) Aims: -To report results of ongoing Babesia clinical trial -To explain significance of Babesia as a TT infection Methods: In cobas â Babesia for use on the cobas â 6800/8800 Systems, is a qualitative polymerase chain reaction nucleic acid amplification test, developed to detect in whole blood (WB) donor samples the 4 Babesia species that cause human disease: B. In sensitivity analyses, there were two discrepant results for HIV testing, three for HCV, and five for anti-HBc. Summary/Conclusions: Elecsys â infectious disease parameters on the cobas e 801 analyser demonstrate high specificity/sensitivity for screening first-time blood donor samples, with similar clinical performance to other commercially available assays. cache = ./cache/cord-010092-uftc8inx.txt txt = ./txt/cord-010092-uftc8inx.txt === reduce.pl bib === id = cord-331557-8axi74nn author = Raoult, Didier title = What does the future hold for clinical microbiology? date = 2004 pages = extension = .txt mime = text/plain words = 6513 sentences = 328 flesch = 35 summary = When PCR is used to detect DNA in clinical specimens, microarrays can then be used to identify the amplified products by hybridization to an array that is composed of pathogen-specific probes. Kits are available for the detection and quantification of DNA and RNA in clinical samples, and the technique has been specifically developed to enable the follow-up of patients with HIV and hepatitis C infections (Amplitech AME Bioscience; Bayer Diagnostics; Roche Diagnostics). Mass-spectrometry analysis of base-specific fragmentation patterns of PCRamplified DNA has recently been studied as a technique for the rapid identification of bacterial isolates and for the detection of specific 16S rRNA gene fragments that are amplified from complex environmental samples 35 . These automated microarrays will be suitable both for mass screening of sera in epidemiology studies and in blood banks, and for diagnostics that are carried out on single serum samples in clinical microbiology laboratories. cache = ./cache/cord-331557-8axi74nn.txt txt = ./txt/cord-331557-8axi74nn.txt === reduce.pl bib === id = cord-332844-2se4d1yp author = Yun, Sang-Im title = Bacterial Artificial Chromosomes: A Functional Genomics Tool for the Study of Positive-strand RNA Viruses date = 2015-12-29 pages = extension = .txt mime = text/plain words = 4793 sentences = 233 flesch = 52 summary = Here, the present report describes the strategic considerations in creating and amplifying a genetically stable full-length infectious JEV cDNA as a bacterial artificial chromosome (BAC) using the following general experimental procedures: viral RNA isolation, cDNA synthesis, cDNA subcloning and modification, assembly of a full-length cDNA, cDNA linearization, in vitro RNA synthesis, and virus recovery. This protocol provides a general methodology applicable to cloning full-length cDNA for a range of positive-strand RNA viruses, particularly those with a genome of >10 kb in length, into a BAC vector, from which infectious RNAs can be transcribed in vitro with a bacteriophage RNA polymerase. Generation of an infectious cDNA clone is a key step in developing a reverse genetics system for RNA viruses, especially for positive-strand RNA viruses, because its genome acts as viral mRNA that is translated into proteins by host cell ribosomes. cache = ./cache/cord-332844-2se4d1yp.txt txt = ./txt/cord-332844-2se4d1yp.txt === reduce.pl bib === id = cord-331698-rwow1ydx author = Latorre-Pérez, Adriel title = A lab in the field: applications of real-time, in situ metagenomic sequencing date = 2020-08-20 pages = extension = .txt mime = text/plain words = 6732 sentences = 335 flesch = 36 summary = This review discusses the main applications of real-time, in situ metagenomic sequencing developed to date, highlighting the relevance of this technology in current challenges (such as the management of global pathogen outbreaks) and in the next future of industry and clinical diagnosis. Therefore, the ultra-portability, affordability, and speed in data production make the MinION technology suitable for real-time sequencing in a variety of environments, such as Ebola surveillance in West Africa during the last outbreak [25] , microbial communities inspection in the Arctic [26] , DNA sequencing on the International Space Station (ISS) [27] , and even the recently emerging pandemic coronavirus SARS-CoV-2 [28, 29] . In fact, there are some critical points to be addressed before this technique could become a standard in the industry: (i) sequencing cost should be reduced; (ii) rapid and reliable in situ DNA extraction and library preparation protocols should be designed and validated; (iii) minimal sequencing yields should be determined for each specific application; (iv) fast and real-time pipelines should be created and tested; and (v) level of expertise for managing the data and the samples should be notably reduced. cache = ./cache/cord-331698-rwow1ydx.txt txt = ./txt/cord-331698-rwow1ydx.txt === reduce.pl bib === id = cord-335607-gv96hlw6 author = Yang, Dayong title = Novel DNA materials and their applications date = 2010-08-20 pages = extension = .txt mime = text/plain words = 9048 sentences = 526 flesch = 47 summary = One-dimensional (1D) DNA materials, including nanotubes and nanowires, can be fabricated through the programed self-assembly of DNA tiles, which have the potential to template the growth of nanowires 19, 49, 50 and induce alignment of membrane proteins. These connectors allowed planar DNA tiles to assemble into 2D array structures by taking advantage of the geometry of the 2.5 helical turns between two DNA tiles ( Figure 2 strand of DNA, 53 which resembled the self-assembly of natural protein nanofilaments. Mao and coworkers developed a concept in which DNA sequence symmetry could be used to design DNA building blocks for larger self-assembled structures. 23, 74 In contrast to the conventional crossover strategy, which creates single building blocks that self-assemble into larger structures in a 'two-step' process, DNA origami provides a versatile and simple 'one-pot' method using numerous short single strands of DNA (staple strands) to direct the folding of a long, single strand of DNA into the desired shape ( Figure 3 (g)). cache = ./cache/cord-335607-gv96hlw6.txt txt = ./txt/cord-335607-gv96hlw6.txt === reduce.pl bib === id = cord-336636-xgfw21hk author = Spezia, Pietro Giorgio title = Redondovirus DNA in human respiratory samples date = 2020-08-15 pages = extension = .txt mime = text/plain words = 1889 sentences = 110 flesch = 48 summary = Abstract Background Redondovirus (ReDoV) is a recently discovered circular, Rep-encoding single-stranded DNA (CRESS-DNA) virus in humans. While attempting to study human virome in bronchoalveolar lavage (BAL) samples of lung transplant patients [1, 2] , Abbas and colleagues identified sequence reads that aligned with low-coverage to a poorly characterized circovirus, named porcine stool-associated circular virus-5 (PoSCV-5) [3] . These observations suggest that ReDoV is not part of the normal oral and/or respiratory microflora of humans, differently to other circular single-stranded DNA viruses [5, 15] and that its infection might be involved in clinically relevant disorders. Redondoviridae, a family of small, circular DNA viruses of the human oro-respiratory tract associated with periodontitis and critical illness Identification and genetic characterization of a novel circular single-stranded DNA virus in a human upper respiratory tract sample cache = ./cache/cord-336636-xgfw21hk.txt txt = ./txt/cord-336636-xgfw21hk.txt === reduce.pl bib === id = cord-333220-tcvs4beg author = Lee, Szu-Yuan title = Compact optical diagnostic device for isothermal nucleic acids amplification date = 2008-08-12 pages = extension = .txt mime = text/plain words = 4844 sentences = 243 flesch = 48 summary = It has two major components, a disposable polymethyl methacrylate (PMMA) micro-reactor and a temperature-regulated optical detection unit (base apparatus) for real-time monitoring of the turbidity changes due to the precipitation of DNA amplification by-product, magnesium pyrophosphate. It has two major components, a disposable PMMA micro-reactor and a temperature-regulated optical detection unit (base apparatus) for real-time monitoring of the turbidity changes due to precipitation of DNA amplification by-product, magnesium pyrophosphate. Our integrated isothermal device has two major components, a disposable polymethyl methacrylate (PMMA) micro-reactor and a temperature-regulated optical detection unit (base apparatus) for real-time monitoring of the turbidity changes due to the precipitation of DNA amplification by-product, magnesium pyrophosphate. To confirm the results of the LAMP reaction for HBV DNA template amplification and detection in the integrated isothermal device, seven clinical serum specimens were obtained from patients with chronic hepatitis B at National Taiwan University Hospital. cache = ./cache/cord-333220-tcvs4beg.txt txt = ./txt/cord-333220-tcvs4beg.txt === reduce.pl bib === id = cord-333524-a6p6ma8r author = Khan, Pavana title = Isothermal SARS-CoV-2 Diagnostics: Tools for Enabling Distributed Pandemic Testing as a Means of Supporting Safe Reopenings date = 2020-09-23 pages = extension = .txt mime = text/plain words = 8841 sentences = 603 flesch = 50 summary = 19 The current most common diagnostic method used to identify SARS-CoV-2 infection is a molecular technique for detecting viral RNA through nucleic acid amplification, RT-PCR. Nucleic acid amplification tests (NAATs) are the most common diagnostic tests used to detect pathogens, and many of the current SARS-CoV-2 detection techniques are primarily based on NAATs. 21 NAATs involve nucleic acid amplification, a process that initiates with a small quantity of starting nucleic acids and uses primers that target specific, short nucleic acid sequences in conjunction with enzymes to amplify or increase the quantity of starting nucleic acids. 34 This test incorporates a nested nucleic acid amplification technique showing higher sensitivity of detection than LAMP alone and conventional RT-PCR for minimally processed SARS-CoV-2 samples. 55 The technique first uses RT-LAMP for reverse transcription and isothermal amplification of viral RNA, and then employs the Cas12a enzyme to identify sequences of SARS-CoV-2, allowing cleavage of a reporter molecule ( Figure 5 ). cache = ./cache/cord-333524-a6p6ma8r.txt txt = ./txt/cord-333524-a6p6ma8r.txt === reduce.pl bib === id = cord-335490-p63qlcnx author = Schenk, Thomas title = Disseminated Bocavirus Infection after Stem Cell Transplant date = 2007-09-17 pages = extension = .txt mime = text/plain words = 1928 sentences = 103 flesch = 46 summary = To the Editor: Human bocavirus (HBoV) (1) is increasingly recognized as a cause of respiratory infections worldwide. Retrospectively, the same NPA sample was reanalyzed for HBoV DNA by real-time PCR (7) and showed a viral load of 4.6 × 10 7 copies/mL (online Appendix Figure) ; specifi city was confi rmed by sequencing. Diarrheic stool samples obtained on day 21 and, after resolution of respiratory symptoms, on day 75 showed substantial HBoV DNA (2.5 × 10 6 and 6.0 × 10 5 copies/mg, respectively; online Appendix Figure) . Drug-induced PRCA is a rare blood disorder in adults and has already been reported in isoniazid-treated patients (3) (4) (5) . This hypothesis is supported by previously reported cases in which PRCA relapses occurred when treatment with isoniazid was resumed (3, 5) . Detection of human bocavirus in Japanese children with lower respiratory tract infections Human bocavirus DNA detected by quantitative real-time PCR in two children hospitalized for lower respiratory tract infection cache = ./cache/cord-335490-p63qlcnx.txt txt = ./txt/cord-335490-p63qlcnx.txt === reduce.pl bib === id = cord-335864-392xmrq0 author = Sun, Yu-Meng title = Principles and innovative technologies for decrypting noncoding RNAs: from discovery and functional prediction to clinical application date = 2020-08-10 pages = extension = .txt mime = text/plain words = 13942 sentences = 786 flesch = 45 summary = With recent developments in sequencing methods and information analysis, an increasing number of novel ncRNAs have been identified, including long noncoding RNAs (lncRNAs) [5, 6] , circular RNAs (circRNAs) [7, 8] , and novel small ncRNAs [9] [10] [11] . Most circRNAs derived from mRNA back-splicing lose translational capacity because of the lack of effective ORFs or ribosome entry approaches, while a few circRNAs from coding or Sno-lncRNAs maintain their stability by their classical stem-loop structures of snoRNAs. c Alternative splicing within circRNAs. d A number of novel small ncRNAs derived from rRNAs (rRFs), tRNAs (tsRNAs), and snoRNAs (sdRNAs) have also been found to be enriched in RNA-induced silencing complexes (RISCs) and function in a miRNA-like pathway This approach can provide in-depth analysis of transcripts from target regions of genome. cache = ./cache/cord-335864-392xmrq0.txt txt = ./txt/cord-335864-392xmrq0.txt === reduce.pl bib === id = cord-333914-c150ki1n author = Koba, Ryota title = Identification and characterization of a novel bat polyomavirus in Japan date = 2020-08-20 pages = extension = .txt mime = text/plain words = 1685 sentences = 104 flesch = 54 summary = A novel polyomavirus (PyV) was identified in the intestinal contents of Japanese eastern bent-wing bats (Miniopterus fuliginosus) via metagenomic analysis. To determine the complete viral genome of these PyV-like sequences, PCR was performed using LA Taq DNA polymerase (Takara Bio, Otsu, Japan) in accordance with the manufacturer's instructions. A noncoding regulatory region (NCCR) was located between the start of the early region and that of the late region, in line with previous findings for bat PyVs (Fig. 1a and Supplementary Table 1) [9] [10] [11] [12] . MfPyV VP1 displayed less than 72% nucleotide sequence identity with other bat PyVs (Supplementary Table 2 ). MfPyV TAg sequences contained features known to be conserved in TAgs of other bat PyVs, including the highly conserved DnaJ domain (HPDKGG), a retinoblastoma (Rb)-binding motif (LYCNE), and several functional motifs (Supplementary Fig. 2 ). In conclusion, we detected a novel PyV genome sequence in Japanese bats. cache = ./cache/cord-333914-c150ki1n.txt txt = ./txt/cord-333914-c150ki1n.txt === reduce.pl bib === id = cord-336749-qbko22vf author = Kalisch, Thomas title = New readers and interpretations of poly(ADP-ribosyl)ation date = 2012-09-30 pages = extension = .txt mime = text/plain words = 6658 sentences = 304 flesch = 44 summary = MacroH2A1.1, which is involved in the DNA damage response and transcriptional regulation, is able to bind PAR, ADPR and the SirT1 metabolite O-acetyl-ADP-ribose (OAADPR), which is produced during the NAD + -dependent deacetylation of acetylated proteins [22] . RNF146 is rapidly recruited to laser-induced DNA-damaged sites; its PAR-dependent E3 ligase activity promotes DNA repair and prevents cell death induced by g-irradiation, alkylating agents or hydrogen peroxide, but only at doses known to trigger cell death superfamily C-terminal domain associated with DEXDc-, DEAD-and DEAH-box proteins (lavender box); FHA, forkhead associated (light pink box); HECT, homologous to E6-AP carboxyl terminus domain, displaying E3-ligase activity (light orange box); lactamase B, domain homologous to b-lactamase endowed with nuclease activity (gray box); macro, homologous to the nonhistone part of macroH2A, displaying PAR-binding activity (see text; blue box); PARP, catalytic domain, homologous to the poly(ADP-ribose) synthesis domain of PARP-1, endowed with mono-or poly(ADP-ribosyl)ation activity (green box); PBZ, PAR-binding zinc finger (see text; orange box); RING, really interesting new gene: zinc binding domain with ubiquitin E3 ligase activity (sienna box); SAM-L, sterile a motif-like (purple box); SNF2-N, SNF2 family N-terminal domain (light steel blue box); UBA, ubiquitin-binding domain (silver gray box); WWE, named after its three conserved residues Trp, Trp and Glu, displaying PAR-binding activity (see text; dark yellow box); Zf-CCCH, zinc finger motif (pink box). cache = ./cache/cord-336749-qbko22vf.txt txt = ./txt/cord-336749-qbko22vf.txt === reduce.pl bib === id = cord-338582-o976nab9 author = Dahlhausen, Bob title = Future Veterinary Diagnostics date = 2010-09-19 pages = extension = .txt mime = text/plain words = 9199 sentences = 511 flesch = 35 summary = Genome sequencing has allowed efficient, sensitive, and specific diagnostic assays to be developed based on the detection of nucleic acids. PCR uses the highly specific molecular recognition ability of Watson-Crick base pairing to provide the selectivity needed for a nucleic acid probe to bind to a targeted DNA sequence and allow for its exponential amplification. It has been used to develop rapid diagnostic tests for several pathogenic viruses with singlestranded RNA genomes, including influenza A, 13 footand-mouth disease virus, 14 and severe acute respiratory syndrome (SARS)-associated coronavirus. DNA microarrays also permit relatively rapid interrogation of a clinical sample against thousands of genetic targets, allowing for simultaneous detection and discrimination among hundreds of pathogenic agents of veterinary interest. Unlike PCR technology where the target agent must be known to use specific test primers, microarrays can allow for the rapid diagnosis of multiple pathogenic agents in disease outbreaks and epidemics of unknown etiology. cache = ./cache/cord-338582-o976nab9.txt txt = ./txt/cord-338582-o976nab9.txt === reduce.pl bib === id = cord-334082-fyxn0g3v author = O’Carroll, I.P. title = Viral Nucleic Acids date = 2015-08-20 pages = extension = .txt mime = text/plain words = 5495 sentences = 271 flesch = 54 summary = This scheme in turn places two requirements on the nucleic acid: it must be replicated in the virus-producing cell, to provide the genetic material encased in the progeny virus particles; and it must encode the proteins needed for the production of the progeny particles, including at a minimum the structural proteins from which the particles will be assembled. The DNAs of ssDNA viruses are replicated by a mechanism similar to 'rolling circle' replication, involving synthesis of dsDNA intermediates containing multiple tandem copies of the viral genome. These viruses are unique in that their genomic RNA is translated immediately upon infection; that is, the virus particle is simply a package that introduces an mRNA molecule into the cell. When the particle infects a new host cell, the RNA-dependent DNA polymerase or 'reverse transcriptase' in the virus copies this RNA into dsDNA. cache = ./cache/cord-334082-fyxn0g3v.txt txt = ./txt/cord-334082-fyxn0g3v.txt === reduce.pl bib === id = cord-337867-hqmf6r7t author = Shim, Byoung-Shik title = Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses date = 2010-12-31 pages = extension = .txt mime = text/plain words = 3762 sentences = 221 flesch = 54 summary = title: Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses RESULTS: In the present study, the immune responses of BALB/c mice immunized via intranasal (i.n.) route with SARS DNA vaccine (pci-S) in a PEI/pci-S complex form have been examined. The result showed that SARS S-specific IgA antibody response was significantly (P < 0.01) increased in lung wash from mice immunized with PEI/pci-S complexes ( Figure 2B ). B220 + cells from mice immunized with PEI/pci-S complexes were highly proliferated after in vitro re-stimulation with SARS-CoV S protein ( Figure 2C ). The surface expression of CD80 and CD86 co-stimulatory molecules were significantly (P < 0.05) higher on DCs from mice treated with PEI/pci-S complexes than those from SARS-CoV DNA S vaccine alone ( Figure 3 ). DNA vaccine encoding full-length S protein has shown to induce humoral, cellular and protective immune responses against SARS-CoV [6] . cache = ./cache/cord-337867-hqmf6r7t.txt txt = ./txt/cord-337867-hqmf6r7t.txt === reduce.pl bib === id = cord-339419-b6tr2zyx author = Lee, Thomas Ming-Hung title = DNA-based bioanalytical microsystems for handheld device applications date = 2006-01-18 pages = extension = .txt mime = text/plain words = 5425 sentences = 331 flesch = 49 summary = Recent progresses in the miniaturization of various biological processing steps for the sample preparation, DNA amplification (polymerase chain reaction), and product detection are delineated in detail. The organization of the following contents is based upon the three basic DNA processing modules of sample preparation, target amplification, and product detection. Thermal lysis can be easily adapted to microfabricated amplification systems as the initial high-temperature step (∼95 • C) employed to denature the double-stranded (ds) DNA template is powerful enough to open up the cell membranes [10, 12, 19] . The sensing protocol basically involves the immobilization of an oligonucleotide onto a transducer surface, and upon the hybridization of complementary target sequence, the binding event is detected by optical, microgravimetric (mass-sensitive), or electrochemical methods. To further increase the sensitivity of the gold nanoparticle-based assay, a signal amplification step Pictorial representation of the working principle of the molecular beacon-type capture probe labeled with ferrocene group for the reagentless sequence-specific DNA detection. cache = ./cache/cord-339419-b6tr2zyx.txt txt = ./txt/cord-339419-b6tr2zyx.txt === reduce.pl bib === id = cord-336659-qddjqiw9 author = Ramos, Jheneffer Sonara Aguiar title = Multi-biomarker responses to pesticides in an agricultural population from Central Brazil date = 2020-08-21 pages = extension = .txt mime = text/plain words = 3842 sentences = 201 flesch = 48 summary = Our findings demonstrate that pesticides can exert various deleterious effects on human health by damaging the DNA as well as by influencing the immune system in the case of both direct or indirect exposure and these issues are associated to age, gender, intoxication and the nonuse of PPE. In this context, agricultural workers and their families and individuals who reside close to fields where pesticides are applied are considered to be the group that will receive the most considerable exposure at the highest risk for adverse health outcomes (Gangemi et al., 2016; Docea et al. This is the first study from Central Brazil that demonstrated how genetic and immune biomarkers are associated to the exposure of a complex mixture of pesticides Also, families of farmworkers are often environmentally exposed to multiple pesticides, either by living near crops or by having contact with contaminated clothes and work tools without personal protection (Damalas and Eleftherohorinos, 2011; Parks, 2016; Doğanlar et al. cache = ./cache/cord-336659-qddjqiw9.txt txt = ./txt/cord-336659-qddjqiw9.txt === reduce.pl bib === id = cord-340781-z348xbn0 author = Namvar, Ali title = In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine date = 2019-10-23 pages = extension = .txt mime = text/plain words = 6646 sentences = 357 flesch = 50 summary = Moreover, in vivo studies indicated that the combination of L1 and L2 DNA constructs without any adjuvant or delivery system induced effective immune responses, and protected mice against C3 tumor cells (the percentage of tumor-free mice: ~66.67%). The framework begins with conservancy analysis of all 13 high-risk HPV strains following with (1) B-cell epitope mapping, (2) T-cell epitope mapping (CD4 + and CD8 + ), (3) allergenicity assessment, (4) tap transport and proteasomal cleavage, (5) population coverage, (6) global and template-based docking and (7) data collection, analysis, and design of the L1 and L2 DNA constructs. In this study, for the first time, comprehensively integrated methods (using sequence-based tools in combination with flexible peptide-protein docking) were used to design highly immunogenic and protective vaccine candidates which were able to boost both humoral and cellular Table 12 . cache = ./cache/cord-340781-z348xbn0.txt txt = ./txt/cord-340781-z348xbn0.txt === reduce.pl bib === id = cord-338633-pxxon1ni author = Zuo, Yu title = Neutrophil extracellular traps and thrombosis in COVID-19 date = 2020-11-05 pages = extension = .txt mime = text/plain words = 2782 sentences = 167 flesch = 41 summary = We found that remnants of NETs (cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3) and neutrophil-derived S100A8/A9 (calprotectin) in patient sera were associated with higher risk of morbid thrombotic events in spite of prophylactic anticoagulation. Neutrophil-derived extracellular traps (NETs) play a pathogenic role in many thrombo-inflammatory states including sepsis [4, 5] , thrombosis [6] [7] [8] , and respiratory failure [9, 10] . Here, we describe 11 cases of thrombosis in patients hospitalized with COVID-19 and demonstrate an association with neutrophil hyperactivity and NET release. As compared with the control group, patients with a thrombotic event demonstrated significantly higher levels of calprotectin, a marker of neutrophil activation (Fig. 1a) . Finally, we asked whether there was an association between blood markers of neutrophil activation (such as calprotectin and cell-free DNA) and D-dimer within this cohort of COVID-19 patients (n = 44). cache = ./cache/cord-338633-pxxon1ni.txt txt = ./txt/cord-338633-pxxon1ni.txt === reduce.pl bib === id = cord-339522-jm2xpn1w author = Sharma, Nidhi title = Recombinase‐Based Isothermal Amplification of Nucleic Acids with Self‐Avoiding Molecular Recognition Systems (SAMRS) date = 2014-09-10 pages = extension = .txt mime = text/plain words = 3873 sentences = 219 flesch = 55 summary = In contrast, with the primers containing SAMRS components, clean amplification products (amplicons) of the correct identity (as judged by length) were produced if the reaction mixture contained the target DNA (Figure 3 A, lane 2) . Real-time amplification with STD primers resulted in a nonspecific signal that does not depend on the amount of target template added to the reaction mixtures (Figure 4 B, left) . Once again, STD primers amplified unwanted products in the negative control (Figure 5 A) , giving a background signal that obscured the desired amplicons when lower concentrations of viral RNA template was used in the RT-RPA reaction. These experiments show that, at least for these three cases, adding SAMRS nucleotides to primers used in RPA isothermal amplification eliminates assay artifacts, allows for readout by using real-time fluorescence signal, and increases the robustness of the assay with respect to using different target sequences. cache = ./cache/cord-339522-jm2xpn1w.txt txt = ./txt/cord-339522-jm2xpn1w.txt === reduce.pl bib === id = cord-341062-k3vjqumq author = Pruitt, Hawley C. title = Roles of N‐Myc and STAT interactor in cancer: From initiation to dissemination date = 2016-03-11 pages = extension = .txt mime = text/plain words = 6635 sentences = 409 flesch = 47 summary = N‐myc & STAT Interactor, NMI, is a protein that has mostly been studied for its physical interactions with transcription factors that play critical roles in tumor growth, progression and metastasis. The physical interactions of NMI with its binding partners have been linked to many aspects of tumor biology including DNA damage response, cell death, epithelial‐to‐mesenchymal transition and stemness. 45 NMI expression reversed mesenchymal phenotypes of highly invasive breast cancer cells through enhancing STAT5-mediated transcription of SMAD7. Tri-complex formation leads to the stabilization of cytosolic b-catenin, a transcriptional co-factor that can enter the nucleus, bind to a member of the TCF/LEF protein family and subsequently activate transcription of Wnt target genes. Stably expressing NMI in MDA-MB-231 and MDA-MB-435 cancer cell lines led to increased levels of DKK1 and concomitantly reduced levels of b-catenin and c-Myc, known downstream targets of Wnt signaling. cache = ./cache/cord-341062-k3vjqumq.txt txt = ./txt/cord-341062-k3vjqumq.txt === reduce.pl bib === id = cord-339915-8j04y50s author = Deng, Wei title = DV-Curve Representation of Protein Sequences and Its Application date = 2014-05-08 pages = extension = .txt mime = text/plain words = 2946 sentences = 176 flesch = 49 summary = Based on the detailed hydrophobic-hydrophilic(HP) model of amino acids, we propose dual-vector curve (DV-curve) representation of protein sequences, which uses two vectors to represent one alphabet of protein sequences. The utility of this approach is illustrated by two examples: one is similarity/dissimilarity comparison among different ND6 protein sequences based on their DV-curve figures the other is the phylogenetic analysis among coronaviruses based on their spike proteins. In this paper, we introduce DV-curve graphical representation of protein sequences based on the detailed hydrophobic-hydrophilic (HP) model of amino acids. Analysis of similarity/dissimilarity of DNA sequences based on novel 2-D graphical representation New graphical representation of a DNA sequence based on the ordered dinucleotides and its application to sequence analysis Analysis of similarity/dissimilarity of DNA sequences based on a condensed curve representation Similarity/dissimilarity studies of protein sequences based on a new 2d graphical representation cache = ./cache/cord-339915-8j04y50s.txt txt = ./txt/cord-339915-8j04y50s.txt === reduce.pl bib === id = cord-339152-wfakzb6w author = Trovato, Maria title = Viral Emerging Diseases: Challenges in Developing Vaccination Strategies date = 2020-09-03 pages = extension = .txt mime = text/plain words = 12000 sentences = 540 flesch = 38 summary = Ebola and Marburg hemorrhagic fevers, Lassa fever, Dengue fever, Yellow fever, West Nile fever, Zika, and Chikungunya vector-borne diseases, Swine flu, Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the recent Coronavirus disease 2019 (COVID-19) are examples of zoonoses that have spread throughout the globe with such a significant impact on public health that the scientific community has been called for a rapid intervention in preventing and treating emerging infections. The occurrence of significant disease outbreaks-such as SARS (severe acute respiratory syndrome) originating in China in 2002 (8) , the 2009 H1N1 swine flu pandemic from Mexico (9) , MERS (Middle East respiratory syndrome) that occurred in Saudi Arabia in 2012 (10) , the West African outbreak of Ebola virus (EBOV) in late 2013 (11) , the Zika virus (ZIKV) outbreak originating in Brazil in 2015 (12) , the 2018 health emergence in Nigeria caused by Lassa virus (13) , and the ongoing Coronavirus disease 2019 (COVID19) pandemic (14) -has renewed interests in developing strategies to faster prevent, treat, and/or control emerging and re-emerging viruses with high epidemic potential. cache = ./cache/cord-339152-wfakzb6w.txt txt = ./txt/cord-339152-wfakzb6w.txt === reduce.pl bib === id = cord-335839-wgdqu1s1 author = Singh, Meharban title = Pediatrics in 21(st) Century and Beyond date = 2016-08-10 pages = extension = .txt mime = text/plain words = 4423 sentences = 218 flesch = 47 summary = Availability of totipotent stem cells and developments in transplant technology are likely to revolutionize the management of a variety of hematologic cancers and life-threatening genetic disorders. Availability of totipotent stem cells and developments in transplant technology are likely to revolutionize the management of a variety of hematologic cancers and life-threatening genetic disorders. The availability of newer vaccines by recombinant technology for emerging infective and for non-infective lifestyle diseases is likely to improve survival and quality of life. The availability of newer vaccines by recombinant technology for emerging infective and for non-infective lifestyle diseases is likely to improve survival and quality of life. There is going to be a greater focus on the Bpatient^having the disease rather than Bdisease^per se by practicing holistic pediatrics by effective utilization of alternative or complementary strategies for health care. The concept of functional foods is being increasingly exploited to prevent illness, promote health and improve quality of life. cache = ./cache/cord-335839-wgdqu1s1.txt txt = ./txt/cord-335839-wgdqu1s1.txt === reduce.pl bib === id = cord-338942-q4neat3x author = Zhang, Haoqing title = LAMP-on-a-chip: Revising microfluidic platforms for loop-mediated DNA amplification date = 2019-01-31 pages = extension = .txt mime = text/plain words = 5757 sentences = 314 flesch = 41 summary = Isothermal deoxyribonucleic acid amplification methods, such as loop-mediated isothermal amplification (LAMP), exhibit characteristics ideal for point-of-care (POC) applications, since their instrumentation is simpler in comparison with the standard method of polymerase chain reaction. Nucleic acids amplification methods are primarily required to be performed, as the original number of either DNA or ribonucleic acid (RNA) copies in the clinical sample is insufficient for their direct detection. A microfluidic disk-based LAMP chip, integrating sample preparation and detection, was developed [44] (Fig. 2B ). Loop-mediated isothermal amplification integrated on microfluidic chips for point-of-care quantitative detection of pathogens An integrated rotary microfluidic system with DNA extraction, loop-mediated isothermal amplification, and lateral flow strip based detection for point-ofcare pathogen diagnostics An integrated microfluidic loop-mediated-isothermal-amplification system for rapid sample pre-treatment and detection of viruses Development and application of a loop-mediated isothermal amplification method on rapid detection Escherichia coli O157 strains from food samples cache = ./cache/cord-338942-q4neat3x.txt txt = ./txt/cord-338942-q4neat3x.txt === reduce.pl bib === id = cord-342629-mzi0krja author = Wu, Q. title = An Activated GOPS‐poly‐L‐Lysine‐ Coated Glass Surface for the Immobilization of 60mer Oligonucleotides date = 2005-11-16 pages = extension = .txt mime = text/plain words = 2086 sentences = 118 flesch = 49 summary = To explore a method for enhancing the immobilization and hybridization efficiency of oligonucleotides on DNA microarrays, conventional protocols of poly‐L‐lysine coating were modified by means of surface chemistry, namely, the slides were prepared by the covalently coupling of poly‐L‐lysine to a glycidoxy‐modified glass surface. The modified slides were then used to print microarrays for the detection of the SARS coronavirus by means of 60mer oligonucleotide probes. With the development of the DNA microarray technology, many reports on the modification of glass surfaces and the immobilization of oligonucleotides onto solid supports by covalent linkage have appeared [8±12]. In this paper, the process of slide surface chemistry based on conventional protocols for poly-L-lysine coating was improved [6, 13] in order to immobilize 60mer oligonucleotides by deposition technology. Oligo microarrays printed on an activated GOPS-PLL slide could undergo hybridization stripping cycles for at least three cycles. Preparation of SARS 60mer oligonucleotide probes for microarray printing cache = ./cache/cord-342629-mzi0krja.txt txt = ./txt/cord-342629-mzi0krja.txt === reduce.pl bib === id = cord-341029-49360l2a author = Nasir, Arshan title = A phylogenomic data-driven exploration of viral origins and evolution date = 2015-09-25 pages = extension = .txt mime = text/plain words = 14410 sentences = 794 flesch = 49 summary = Viruses harboring different replicon types and infecting distantly related hosts shared many metabolic and informational protein structural domains of ancient origin that were also widespread in cellular proteomes. Here, we analyzed a total of 5080 completely sequenced proteomes from cells and viruses and assigned FSF domains to their proteins using structure-based hidden Markov models (HMMs) defined by the SUPER-FAMILY database (version 1.75) (20) . Viral supergroup behaves similarly to cellular superkingdoms in terms of FSF sharing patterns A total of 1995 significant FSF domains (E < 0.0001) were detected iñ 11 million proteins of 5080 proteomes sampled from cells and viruses. It also suggests that viruses are very ancient and most likely infected the last common ancestor of each superkingdom because viral FSFs were present in a diverse array of cellular organisms ranging from small microbes to large eukaryotes. cache = ./cache/cord-341029-49360l2a.txt txt = ./txt/cord-341029-49360l2a.txt === reduce.pl bib === id = cord-343029-85ga6r7d author = Haghpanah, Abdolreza title = Potential mechanisms of SARS‐CoV‐2 action on male gonadal function and fertility: Current status and future prospects date = 2020-10-27 pages = extension = .txt mime = text/plain words = 4375 sentences = 218 flesch = 43 summary = The aim of this review was to provide new insights into different possible mechanisms of involvement of male gonads with SARS‐CoV‐2 including investigating the ACE2 axis in testis, hormonal alterations in patients with COVID‐19, possible formation of anti‐sperm antibodies (ASA) and subsequently immunological infertility as a complication of SARS‐CoV‐2 infection. Considering the fact that the testis is highly enriched in ACE2 receptors and its vulnerability to SARS-CoV-2 invasion, detectable changes in semen analysis, alteration in sex hormones balance and, most importantly, anti-sperm antibodies (ASA) formation and sperm DNA fragmentation are considered to play a major role in male infertility. Search phrases used for different databases strategy included the following: "severe acute respiratory syndrome coronavirus 2", "2019 nCoV", "SARS-CoV-2", "coronavirus", "COVID-19", "reproductive system", "fertility", "infertility", "germ cells", "gamete", "spermatogonia", "spermatogenesis" "spermatozoa", "spermatozoan", "testis", "Sertoli cells", "Leydig cells", "Androgen", "steroidogenesis", "spermiogenesis", "spermiation", "development", "fertilization", "gonadal function", "sex hormones", "angiotensin-converting enzyme 2 receptor", "ACE2", "anti-sperm antibodies", "ASA", "sperm DNA fragmentation index", "DFI", and "semen analysis". cache = ./cache/cord-343029-85ga6r7d.txt txt = ./txt/cord-343029-85ga6r7d.txt === reduce.pl bib === id = cord-336219-xndxn1r3 author = Chuang, Chi-Mu title = Treatment with Imiquimod enhances antitumor immunity induced by therapeutic HPV DNA vaccination date = 2010-04-28 pages = extension = .txt mime = text/plain words = 4726 sentences = 246 flesch = 54 summary = METHODS: In the current study, we explored the combination of the DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 (HPV-16) E7 antigen (CRT/E7) with the TLR7 agonist imiquimod for their ability to generate E7-specific immune responses and antitumor effects in tumor-bearing mice. RESULTS: We observed that treatment with CRT/E7 DNA in combination with imiquimod leads to an enhancement in the E7-specific CD8+ T cell immune responses and a decrease in the number of myeloid-derived suppressor cells in the tumor microenvironment of tumor-bearing mice. In the current study, we hypothesize that the combination of the DNA vaccine encoding CRT linked to HPV-16 E7 (CRT/E7) with topical application of imiquimod at the site of the tumor will lead to increased infiltration of effectior immune cells at the site of the tumor, resulting in enhanced antitumor effects against E7-expressing tumors in a preclinical model. cache = ./cache/cord-336219-xndxn1r3.txt txt = ./txt/cord-336219-xndxn1r3.txt === reduce.pl bib === id = cord-338164-pyam9yn3 author = Livingston, Andrew D title = Biochip sensors for the rapid and sensitive detection of viral disease date = 2005-05-26 pages = extension = .txt mime = text/plain words = 3506 sentences = 175 flesch = 41 summary = Recent advances in DNA and protein microarray methodology and the emerging technology of cell-based sensors have massively increased the speed and sensitivity with which we can detect viral infections. Recent advances in DNA and protein microarray methodology and the emerging technology of cellbased sensors have massively increased the speed and sensitivity with which we can detect viral infections. We therefore need a rapid, sensitive approach that is capable of identifying multiple viruses in parallel; this need is being addressed by the development of DNA and protein microarrays specifically designed for virus detection and identification. The authors [4] described the use of viral DNA microarrays to produce hybridization signatures of viral sequences that effectively serve as 'viral barcodes' for the identification of known, related or novel viruses. Cellular systems, such as the light-emitting B cells engineered by the Rider group [19] , while individually not having the parallel capabilities of the array, provide an extremely rapid detection system. cache = ./cache/cord-338164-pyam9yn3.txt txt = ./txt/cord-338164-pyam9yn3.txt === reduce.pl bib === id = cord-343775-tcljwdlo author = Tiee, Madeline S. title = Ghosts of infections past: using archival samples to understand a century of monkeypox virus prevalence among host communities across space and time date = 2018-01-31 pages = extension = .txt mime = text/plain words = 5321 sentences = 249 flesch = 45 summary = Here, we screened over 1000 museum specimens collected over the past 120 years to examine the historical distribution and prevalence of monkeypox virus (MPXV) in five species of African rope squirrel (Funisciurus sp.) collected across Central Africa. Here, we screened over 1000 museum specimens collected over the past 120 years to examine the historical distribution and prevalence of monkeypox virus (MPXV) in five species of African rope squirrel (Funisciurus sp.) collected across Central Africa. As long as the assumptions inherent to these methods are acknowledged and when possible controlled for (such as sampling bias or the effects of specimen preparation and preservation methodology on DNA quality and amplification), museum sampling can be valuable for identifying potential host species and understanding broad geographical and temporal patterns of disease, especially in regions difficult to sample. cache = ./cache/cord-343775-tcljwdlo.txt txt = ./txt/cord-343775-tcljwdlo.txt === reduce.pl bib === id = cord-339369-9z30nksl author = Chiappetta, Catarina Marcon title = Molecular Detection of Circovirus and Adenovirus in Feces of Fur Seals (Arctocephalus spp.) date = 2016-11-01 pages = extension = .txt mime = text/plain words = 3818 sentences = 220 flesch = 57 summary = The present study aimed to detect viral RNA or DNA in 23 free-ranging fur seals on the northern coastline of Rio Grande do Sul State, Brazil. Polymerase chain reaction was used to detect nucleic acids of circoviruses, adenoviruses, morbilliviruses, vesiviruses, and coronaviruses in the feces from twenty-one South American fur seals (Arctocephalus australis) and two Subantarctic fur seals (A. Adenovirus DNA fragments were detected in two South American fur seals; nucleotide sequences of these fragments revealed a high degree of similarity to human adenovirus type C. The present study aimed to detect the presence of circovirus, adenovirus, morbillivirus, vesivirus, and coronavirus nucleic acid in feces from two species of fur seals (A. The deduced amino acid sequences of circoviruses detected in samples FSCV-20 and FSCV-46 were identical to each other and highly similar to other sequences of members in the Circovirus genus known to infect multiple animal species (Li et al. cache = ./cache/cord-339369-9z30nksl.txt txt = ./txt/cord-339369-9z30nksl.txt === reduce.pl bib === id = cord-343470-w215pzdc author = Tsai, Kevin title = Epigenetic and epitranscriptomic regulation of viral replication date = 2020-06-12 pages = extension = .txt mime = text/plain words = 9761 sentences = 452 flesch = 41 summary = Eukaryotic gene expression is regulated not only by genomic enhancers and promoters, but also by covalent modifications added to both chromatin and RNAs. Whereas cellular gene expression may be either enhanced or inhibited by specific epigenetic modifications deposited on histones (in particular, histone H3), these epigenetic modifications can also repress viral gene expression, potentially functioning as a potent antiviral innate immune response in DNA virus-infected cells. First, the viral protein VP16, which is packaged into the tegument layer of incoming virions, recruits host proteins, including host-cell factor 1 (HCF-1) and octamer-binding factor (Oct-1), in order to form a complex that recruits the histone demethylases lysine-specific demethylase 1 (LSD1) and Jumonji domain 2 (JMJD2) family members as a means to remove repressive H3K9 marks from viral immediate early promoters 42 Upon entry into the cell nucleus, the DNA of many viruses initiates the replication process adjacent to subnuclear structures called pro-myelocytic leukaemia nuclear bodies (PML-NBs). cache = ./cache/cord-343470-w215pzdc.txt txt = ./txt/cord-343470-w215pzdc.txt === reduce.pl bib === id = cord-342737-hhs3owvr author = Jula, Alma title = Primary and Secondary Human Bocavirus 1 Infections in a Family, Finland date = 2013-08-17 pages = extension = .txt mime = text/plain words = 1728 sentences = 117 flesch = 55 summary = Human bocavirus 1 (HBoV1) was detected in a young child hospitalized for pneumonia and subsequently in his twin brother and other family members. Human bocavirus 1 (HBoV1) was detected in a young child hospitalized for pneumonia and subsequently in his twin brother and other family members. The index patient had an HBoV1 infection proven by detection of HBoV1 DNA in high copy numbers in NPA and BAL samples, as well as in serum. Three months after this episode of HBoV1 infection, all 4 family members had symptomatic parainfluenza type 1 virus infections, and clinical samples for the twin brother were again positive for HBoV1 DNA. During the acute phase of HBoV1 infection in the index patient, HRV RNA was identified in the NPA of 3 family members, an observation similar to that of many studies (1) . cache = ./cache/cord-342737-hhs3owvr.txt txt = ./txt/cord-342737-hhs3owvr.txt === reduce.pl bib === id = cord-341287-i1hyk962 author = Smith, Trevor R. F. title = Immunogenicity of a DNA vaccine candidate for COVID-19 date = 2020-05-20 pages = extension = .txt mime = text/plain words = 7803 sentences = 446 flesch = 54 summary = Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. In subjects immunized with INO-4700 (MERS-CoV S protein DNA vaccine) durable neutralizing antibodies (nAbs) and T cell immune responses were measured, and a seroconversion rate of 96% was observed and immunity was followed for 60 weeks in most study volunteers 9 . We followed the induction of immunity by the selected immunogen in mice and guinea pigs, measuring SARS-CoV-2 S protein-specific antibody levels in serum and in the lung fluid, and antibody functionality through competitive inhibition of ACE2 binding, pseudovirus and live virus neutralization. In summary, humoral immunogenicity testing in both mice and guinea pigs revealed the COVID-19 vaccine candidate, INO-4800, was capable of eliciting functional blocking antibody responses to SARS-CoV-2 spike protein. cache = ./cache/cord-341287-i1hyk962.txt txt = ./txt/cord-341287-i1hyk962.txt === reduce.pl bib === id = cord-338812-q24jycgk author = Zakaryan, H. title = Nuclear remodelling during viral infections date = 2011-04-28 pages = extension = .txt mime = text/plain words = 4462 sentences = 226 flesch = 37 summary = At present, we know that the nucleus contains the chromatin territories that mainly consist of DNA-protein complexes, as well as several distinct interchromosomal compartments (bodies) that support molecular activities, including replication, transcription and processing of nucleic acids (Fig. 1) . For many years the classical view of these components focused on their crucial role for the biogenesis of ribosomal subunits, but proteomic analysis of human nucleoli showed the presence of about 4500 nucleolar proteins with different functions, thus revealing the multifunctional nature of the nucleolus (Ahmad et al., 2009) . The previous decade of extensive studies implicated PML NBs in stress response (Maul et al., 1995) , gene regulation (Zhong et al., 2000) , oncogenesis (Salomoni and Pandolfi, 2002) , cell senescence (Bischof et al., 2002) , DNA damage repair (Dellaire and Bazett-Jones, 2004) , apoptosis (Takahashi et al., 2004) as well as in antiviral defence mechanisms (Everett and Chelbi-Alix, 2007) . cache = ./cache/cord-338812-q24jycgk.txt txt = ./txt/cord-338812-q24jycgk.txt === reduce.pl bib === id = cord-344749-omzhhr0k author = Kaya, Sariye Irem title = Electrochemical virus detections with nanobiosensors date = 2020-02-14 pages = extension = .txt mime = text/plain words = 8402 sentences = 508 flesch = 37 summary = Cell culture-based virus isolation has been accepted as a "gold standard" in the detection and identification of viruses and is the technique by which all other test methods have been compared [35] . A novel method for dengue virus detection and antibody screening using a graphene-polymer based electrochemical biosensor Chitosan-carbon nanofiber modified single-use graphite electrodes developed for electrochemical detection of DNA hybridization related to hepatitis B virus A sensitive electrochemical biosensor for specific DNA sequence detection based on flower-like VS2, graphene and Au nanoparticles signal amplification Electrochemical DNA biosensor based on a tetrahedral nanostructure probe for the detection of avian influenza A (H7N9) virus Electrochemical DNA biosensor based on gold nanorods for detecting hepatitis B virus Electrochemical-DNA biosensor development based on a modified carbon electrode with gold nanoparticles for influenza a (H1N1) detection: effect of spacer Magnetic nanoparticle-based immunosensor for electrochemical detection of hepatitis B surface antigen cache = ./cache/cord-344749-omzhhr0k.txt txt = ./txt/cord-344749-omzhhr0k.txt === reduce.pl bib === id = cord-345494-8lcdx719 author = Chao, Chien-Chung title = Development of Recombinase Polymerase Amplification Assays for Detection of Orientia tsutsugamushi or Rickettsia typhi date = 2015-07-10 pages = extension = .txt mime = text/plain words = 7022 sentences = 331 flesch = 52 summary = title: Development of Recombinase Polymerase Amplification Assays for Detection of Orientia tsutsugamushi or Rickettsia typhi Recombinase polymerase amplification (RPA) assays using a lateral flow test (RPA-nfo) and real-time fluorescent detection (RPA-exo) were developed targeting the 47-kDa gene of O. Almost all antigen/pathogen detection assays for rickettsial diseases are based on polymerase chain reaction (PCR [7, 8] ), quantitative real-time PCR (qPCR) or nested PCR targeting different genes, including 56 kDa [9] , 47kDa [10] , groEL [11] of O. The DNA was used as template for the 17-RPA assay to evaluate its performance and qPCR was used to quantitate the copy number of the 17 kDa gene. honei and R japonica were also evaluated to show that they were not detectable by 17-RPA-nfo unless 10 4 or more copies of DNA were present, same results were obtained using 17-RPA-exo. cache = ./cache/cord-345494-8lcdx719.txt txt = ./txt/cord-345494-8lcdx719.txt === reduce.pl bib === id = cord-345144-zvu22n8f author = Compagnone, D. title = Chapter 29 Rapid detection of organophosphates, Ochratoxin A, and Fusarium sp. in durum wheat via screen printed based electrochemical sensors date = 2007-12-31 pages = extension = .txt mime = text/plain words = 7893 sentences = 411 flesch = 46 summary = Additionally, the developed device, which consists of the hand-held potentiostat, the multiplexer for eight-channel control and a dedicated software, can be used to detect organophosphates pesticides, such as dichlorvos and pirimiphos methyl at contamination level below the maximum residue limit settled by the European Union and also amplified DNA of F. We successfully applied an AChE inhibition assay to the detection of dichlorvos in durum wheat samples using a simplified extraction procedure. Both the determinations reported here rely on the inhibition activity of OPs pesticides toward AChE combined with the detection of the AChE enzyme product choline at the surface of a mediator-modified screen-printed choline oxidase electrochemical biosensor. Here we report experimental data obtained using the proposed electrochemical assay with screen-printed choline oxidase biosensor for the detection of dichlorvos in durum wheat samples. cache = ./cache/cord-345144-zvu22n8f.txt txt = ./txt/cord-345144-zvu22n8f.txt === reduce.pl bib === id = cord-342819-p8wp6yvo author = De Groot, Anne S title = Making vaccines “on demand”: A potential solution for emerging pathogens and biodefense? date = 2013-09-01 pages = extension = .txt mime = text/plain words = 5661 sentences = 259 flesch = 40 summary = The accelerated process, as proposed by our group, would begin with analysis of the genomic sequence of an emerging pathogen with immunoinformatics tools, followed by rapid design of an epitope-based vaccine containing the most immunogenic components, using an integrated in silico approach illustrated in Figure 2 . Available evidence from animal studies suggests that the number of vaccine components (epitopes) required for full protection against disease is a small and definable subset that can be discovered using state-of-the-art computer programs such as the ones described and validated by EpiVax. 30, 31 We have proposed that any FastVax vaccine would include a minimum of 100 broadly reactive T cell epitopes in several strings, designed to induce multi-functional immune responses that are essential for protective immunity. cache = ./cache/cord-342819-p8wp6yvo.txt txt = ./txt/cord-342819-p8wp6yvo.txt === reduce.pl bib === id = cord-341521-dntkdwkj author = Luo, Yi-Ran title = Porcine Epidemic Diarrhoea Virus Induces Cell-cycle Arrest through the DNA Damage-signalling Pathway date = 2020-03-24 pages = extension = .txt mime = text/plain words = 4077 sentences = 168 flesch = 52 summary = MATERIAL AND METHODS: We observed the effect of the PEDV SHpd/2012 strain on an infected Vero cell cycle through flow cytometry and Western blot, investigating the interrelationships of cell-cycle arrest, the DNA damage–signalling pathway caused by PEDV and the phosphorylation levels of the key molecules Chk.2 and H2A.X involved upstream and downstream in this pathway. We used inhibitors of ATM and Chk.2 to block the DNA damage-signalling pathway and to confirm whether PEDV infection can lead to cell-cycle arrest. We also treated cells with chemical inhibitors of ATM and Chk.2 to determine if cell-cycle arrest after PEDV infection was linked with activation of the DNA damage-signalling pathway. These results revealed that cell-cycle arrest after infection of Vero cells with PEDV was caused by activation of the DNA damage-signalling pathway. cache = ./cache/cord-341521-dntkdwkj.txt txt = ./txt/cord-341521-dntkdwkj.txt === reduce.pl bib === id = cord-347221-g98q9cga author = Piyush, Ravikant title = Nucleic acid-based therapy for coronavirus disease 2019 date = 2020-09-19 pages = extension = .txt mime = text/plain words = 4217 sentences = 246 flesch = 50 summary = This review mainly focuses on various nucleic acid-based biologically active molecules and their therapeutic potentials in developing vaccines for SARS-CoV-2. This review mainly focuses on various nucleic acid-based biologically active molecules and their therapeutic potentials in developing vaccines for SARS-CoV-2. This phenomenon of producing an effective immunity is particularly important in their use against the development of nucleic acid based therapeutic drugs for the treatment of SARS-CoV-2. Nucleic acid-based therapies, especially, RNA therapies including RNAi (RNA interference), siRNAs (small interfering RNA) and RNA aptamers, Ribozymes and ASOs (antisense oligonucleotides) target and neutralize the crucial components of the virus-like specific mRNA molecules, viral proteins like E (envelope), M (membrane), or N (nucleocapsid), or SARS helicase, etc. The nucleic acid-based vaccination technologies involve the use of RNA (mRNA) [34] or plasmid DNA, which encodes for antigen. cache = ./cache/cord-347221-g98q9cga.txt txt = ./txt/cord-347221-g98q9cga.txt === reduce.pl bib === id = cord-345712-gmzue6lj author = Palazzo, Luca title = ADP‐ribosylation: new facets of an ancient modification date = 2017-04-26 pages = extension = .txt mime = text/plain words = 6641 sentences = 389 flesch = 42 summary = Altogether, ADPribosylation is a widespread modification that controls a vast number of cellular processes, including DNA damage repair, transcription, cell-cycle progression, cell division, unfolded protein response, aging, nitrogen fixation, microbial pathogenicity, cell death and many others [7, 14, [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] . As a consequence, macrodomain-containing proteins are involved in a diverse set of cellular functions, such as chromatin remodelling and DNA-damage repair, oxidative stress response, metabolic processes and pathogenic mechanisms [3,5,10-13,30,37, 53, 54, [59] [60] [61] . Studies looking either at the genomic context of ADPribosylating systems or their evolution in bacteria suggest that ADP-ribosylation might be involved in the regulation of many crucial cellular processes including bacterial persistence, oxidative stress response and adaptation to the host environment in general [5, 9, 49, 154] . cache = ./cache/cord-345712-gmzue6lj.txt txt = ./txt/cord-345712-gmzue6lj.txt === reduce.pl bib === id = cord-341634-mpk8mmp8 author = Sadana, Ajit title = Detection of Analytes on Arrays/Microarrays/DNA Chips date = 2010-09-02 pages = extension = .txt mime = text/plain words = 11089 sentences = 563 flesch = 62 summary = In this chapter we use fractal analysis to analyze (a) the binding and dissociation (hybridization) of different targets (400 nM) in solution to a probe immobilized on a DNA chip surface (Fiche et al., 2007) , (b) binding (hybridization) of different concentrations (in nM) of free-DNA in solution to a 22-mer strand (bound DNA) immobilized via a phenylene-diisocyanate linker molecule on a glass substrate (Michel et al., 2007) , (c) binding (hybridization) of SA-HRP (streptavidin-horseradish peroxide) in solution to a capture probe on a QCM (quartz crystal microbalance) electrode along with a detection probe (Feng et al., 2007) , (d) binding (hybridization) of a complementary and a noncomplementary (three-base mismatch strand) DNA in solution to a 30-mer 3 0 -thiolated DNA strand immobilized on an electrochemical enzymatic genosensor (Abad-Valle et al., 2007a,b) , (e) binding (hybridization) of (i) a perfectly matched oligonucleotide (ODN-P) and (ii) a noncomplementary ODN (ODN-N) to an electrochemical sensor with a EST2-A34 reporter (Wang et al., 2007) , (f) binding and dissociation during PNA-DNA hybridization-binding of different concentrations (in mM) of target DNA complementary to CYP2C9*2 (target DNA2) to CYP2C9*2 as a probe PNA immobilized on a ionsensitive field-effect transistor (IS-FET)-based biosensor (Uno et al., 2007) , (g) binding and dissociation during PNA-DNA hybridization-binding of different concentrations (in mM) of target DNA complementary to CYP2C9*2 (target DNA2) to CYP2C9*2 as a probe PNA immobilized on an IS-FET-based biosensor (Uno et al., 2007) , (h) binding and dissociation of RNA synthesized on a (i) 42 nM template and a (ii) 420 nM template (Blair et al., 2007) , and (i) binding (hybridization) of different concentrations of ss DNA in solution preincubated with prehybridized 22-nt FQ duplex to a "broken beacon" immobilized on a sensor surface (Blair et al., 2007) . cache = ./cache/cord-341634-mpk8mmp8.txt txt = ./txt/cord-341634-mpk8mmp8.txt === reduce.pl bib === id = cord-342782-xty16m8w author = Marrugal-Lorenzo, José A. title = Repositioning salicylanilide anthelmintic drugs to treat adenovirus infections date = 2019-01-09 pages = extension = .txt mime = text/plain words = 5099 sentences = 267 flesch = 47 summary = Data suggests that the studied salicylanilide anthelmintic drugs could be suitable for further clinical evaluation for the development of new antiviral drugs to treat infections by adenovirus in immunosuppressed patients and in immunocompetent individuals with community-acquired pneumonia. The three salicylanilide anthelmintic drugs showed a dose-dependent anti-HAdV activity against both HAdV5 and HAdV16, with 100% inhibition of plaques formation at 1.25, 5 and 2.5 μM for NIC, OXY and RAF, respectively ( Fig. 2a,b) . The CC 50 values for these molecules were in all cases significantly higher than the IC 50 concentrations required for inhibition in our antiviral activity and mechanistic assays for both 293β5 cells (Table 1 ) and A549 cells (22.9 ± 9.8 µM, 76.1 ± 14.4 µM and 80.6 ± 34.7 µM for NIC, OXY and RAF, respectively). The aim of this study was to evaluate the anti-HAdV activity of NIC, a salicylanilide anthelmintic drug of human use to set the basis for its further experimental and clinical development as a potential new treatment for HAdV infections. cache = ./cache/cord-342782-xty16m8w.txt txt = ./txt/cord-342782-xty16m8w.txt === reduce.pl bib === id = cord-346043-8vcvalhp author = Lee, Jong B. title = Multifunctional nanoarchitectures from DNA-based ABC monomers date = 2009-05-03 pages = extension = .txt mime = text/plain words = 2995 sentences = 191 flesch = 53 summary = To build up a multifunctional polymer from ABC monomers, we designed different modules separately including DNA capture probes, fluorescent dyes, quantum dots and gold nanoparticles (AuNPs, not shown in this paper; for DNA sequences see Supplementary Tables S1, S2 ). To characterize the ABC monomer at the individual molecule level, we generated donor Y-DNAs tethered with two different colours of quantum dots to be linked onto X-DNA (see Supplementary Figs S5, S6a). To synthesize multifunctional nanoarchitectures from an ABC monomer we designed each ABC monomer to have two quantum dots with three different colour configurations (2G, 1G1R or 2R; see Supplementary Fig. S8 ), one photo-responsive PEGA moiety, and one single-stranded oligonucleotide probe that was complementary to a specific pathogen DNA such as SARS coronavirus, Ebola virus or Bacillus anthracis (this unique DNA is termed the 'capture probe'; see 1A and 1B in Fig. 3a and Supplementary Table S3 ). cache = ./cache/cord-346043-8vcvalhp.txt txt = ./txt/cord-346043-8vcvalhp.txt === reduce.pl bib === id = cord-340503-zwdewiu1 author = Mokhtarzadeh, Ahad title = Nanomaterial-based biosensors for detection of pathogenic virus date = 2017-10-13 pages = extension = .txt mime = text/plain words = 7710 sentences = 401 flesch = 42 summary = Electron microscopy Viral particle Hours Broad spectrum; rapid method Necessity for presence of around 10 6 virus particles/mL for detection; similarity of morphologies [11] Hemagglutination assay Viral protein Hours Easy; inexpensive Poor sensitivity; necessity for fresh reagents [12] ELISA Viral protein Hours Only one incubation step; no hook effect at high analyte concentrations Limited concentration range in which the analyte can be quantified without sample dilution; and that the antigen or antibody produce the same response and not distinguishable in a one step [13] PCR Viral nucleic acid Hours Extremely high sensitivity; Easy to set up Extremely liable to contamination; Not easy to quantitate results; High degree of operator skill required [14] As an example for HIV, a type of virus that gradually attacks the immune system and makes it harder to fight off infections and diseases in infected body, a QDs-based rapid capture and imaging system was developed by Kim et al. cache = ./cache/cord-340503-zwdewiu1.txt txt = ./txt/cord-340503-zwdewiu1.txt === reduce.pl bib === id = cord-347992-coby2m6e author = Marton, Soledad title = In Vitro and Ex Vivo Selection Procedures for Identifying Potentially Therapeutic DNA and RNA Molecules date = 2010-06-28 pages = extension = .txt mime = text/plain words = 10035 sentences = 535 flesch = 45 summary = Although ribozymes and DNAzymes have been extensively assayed as potential therapeutic agents, and different clinical trials have already tested their efficiency against various diseases [49] [50] [51] [52] , very few reports have described the direct application of in vitro selection strategies in the development of potentially therapeutic catalytic nucleic acids. Molecular studies have shown that this aptamer binds to the cell surface protein nucleolin and inhibits the activity of NF-KB, a ubiquitous transcription factor, through intracellular complex formation [108] . In a different approach, SELEX has been performed with the E2F1 protein to find in vitro selected RNA aptamers that bind to and inhibit E2F activity. Astier-Gi's group described the characterization of two DNA aptamers (27v and 127v) that specifically bind to hepatitis C virus (HCV) RNA polymerase (NS5B), inhibiting its activity in vitro [146] . In vitro selection procedures for identifying DNA and RNA aptamers targeted to nucleic acids and proteins cache = ./cache/cord-347992-coby2m6e.txt txt = ./txt/cord-347992-coby2m6e.txt === reduce.pl bib === id = cord-345903-ggkn1w5y author = Revathidevi, Sundaramoorthy title = APOBEC: A molecular driver in cervical cancer pathogenesis date = 2020-10-07 pages = extension = .txt mime = text/plain words = 7008 sentences = 366 flesch = 44 summary = In general, APOBEC3 enzymes play a pivotal role in the deamination of cytidines to uracil in DNA and RNA to control diverse biological processes such as regulation of protein expression, innate immunity, and embryonic development. Innate antiviral activity of the APOBEC3 family members restrict retroviruses, endogenous retro-element, and DNA viruses including the HPV that is the leading risk factor for cervical cancer. Most HPV infections are cleared within months by the immune system but a few high-risk subtypes like HPV16 and HPV18 persist and express viral oncogenes E6 and E7 which lead to increased genomic instability, accumulation of somatic mutations, and integration of HPV into the host genome resulting in cervical cancer [3] . In relevance to persistent HPV infection and cervical carcinogenesis, a family of APOBEC enzymes with DNA/RNA editing capability has been analyzed as they are involved in various immune functions including restriction of viral replication, antigen presentation, and maturation of host immune receptors and are highly polymorphic in nature [79] . cache = ./cache/cord-345903-ggkn1w5y.txt txt = ./txt/cord-345903-ggkn1w5y.txt === reduce.pl bib === id = cord-345552-h6fwi0qn author = Li, Q.-G. title = Hydropathic characteristics of adenovirus hexons date = 1997-07-01 pages = extension = .txt mime = text/plain words = 3522 sentences = 206 flesch = 53 summary = The strength of the surface charge accumulated on the hydrophilic and hydrophobic regions correlated to the tissue tropism of the different adenovirus types. The sequence of the predicted protein, consisting of 937 amino acids, was obtained with the LaserGene software program EditSeq. The hydropathy data of hexon proteins from human adenovirus types 2, 3, 4, 5, 7, 12, 16, 40, 41, and 48, bovine adenovirus type 3, murine adenovirus type 1, and avian adenovirus types 1 and 10 were derived using the prediction method of Kyte-Doolittle in the LaserGene computer program Protean. The nucleotide and amino acid sequence pair distances and the phylogenetic tree of 14 hexon proteins showed serotypes of subgenera B, D and E to be closely related (Table 3 and Fig. 2) . DNA sequence of the adenovirus type 41 hexon gene and predicted structure of the protein cache = ./cache/cord-345552-h6fwi0qn.txt txt = ./txt/cord-345552-h6fwi0qn.txt === reduce.pl bib === id = cord-342015-bz2vab6e author = Ouadfeul, Sid-Ali title = Multifractal Analysis of SARS-CoV-2 Coronavirus genomes using the wavelet transform date = 2020-08-16 pages = extension = .txt mime = text/plain words = 1386 sentences = 86 flesch = 58 summary = In this paper, the 1D Wavelet Transform Modulus Maxima lines (WTMM) method is used to investigate the Long-Range Correlation (LRC) and to estimate the so-called Hurst exponent of 21 isolate RNA sequence downloaded from the NCBI database of patients infected by SARS-CoV-2, Coronavirus, the Knucleotidic, Purine, Pyramidine, Ameno, Keto and GC DNA coding are used. Arneodo et al (1996) published a paper deals with the study of the Long-Range Correlation (LRC) character of DNA sequences using the 1D continuous wavelet transform method. Audit et al (2004) published a paper deals with wavelet Analysis of DNA bending profiles reveals structural constraints on the evolution of genomic sequences, Voss (1996) published a paper deals with the evolution of Long-Range fractal correlations and 1/f noise in DNA base sequences. In this paper the 1D Wavelet Transform Modulus Maxima Lines (WTMM) method is used to demonstrate the monofractal behavior of SARS-CoV-2 RNA sequences downloaded from the NCBI database and to estimate the so-called Hurst exponent, the goal is to investigate the LRC character in these sequences. cache = ./cache/cord-342015-bz2vab6e.txt txt = ./txt/cord-342015-bz2vab6e.txt === reduce.pl bib === id = cord-346853-0c1qdjb5 author = Holmes, E. C. title = The Evolutionary Genetics of Viral Emergence date = 2007 pages = extension = .txt mime = text/plain words = 6123 sentences = 261 flesch = 45 summary = Despite the wealth of data describing the ecological factors that underpin viral emergence, little is known about the evolutionary processes that allow viruses to jump species barriers and establish productive infections in new hosts. We also emphasize the current lack of convincing data as to whether viral emergence requires adaptation to the new host species during the early stages of infection, or whether it is largely a chance process involving the transmission of a viral strain with the necessary genetic characteristics. For example, one model of viral emergence posits that adaptation to a new host species during the early period of an epidemic is of fundamental importance, because this raises the basic reproductive rate of the virus, R 0 , to greater than 1, so that sustained transmission networks can be established (Anita et al. cache = ./cache/cord-346853-0c1qdjb5.txt txt = ./txt/cord-346853-0c1qdjb5.txt === reduce.pl bib === id = cord-346308-9h2fk9qt author = Kaur, Rajwinder title = Microbiology of hospital wastewater date = 2020-05-01 pages = extension = .txt mime = text/plain words = 14673 sentences = 648 flesch = 34 summary = The study of hospital wastewater (HWW) microbiology is important to understand the pollution load, growth of particular pathogenic microbes, shift and drift in microbial community, development and spread of antibiotic resistance in microbes, and subsequent change in treatment efficiencies. Within past years, pieces of evidence have shown mobilization of these resistance genes from the environment into pathogenic bacteria causing health risks to humans and animals and also, demonstrating a link between environmental and clinical resistance [123] . The HWW has been reported to have two overexpressed β-lactam-resistance genes (bla GES and bla OXA ) as compared with the water collected from other aquatic bodies, which could be correlated with antibiotic usage over the time in hospitals and discharge of the residues of antibiotics in the wastewater [176] . Urban wastewater treatment plants as hotspots for antibiotic resistant bacteria and genes spread into the environment: a review cache = ./cache/cord-346308-9h2fk9qt.txt txt = ./txt/cord-346308-9h2fk9qt.txt === reduce.pl bib === id = cord-346280-7sw30bsz author = Ramos Venancio, D. B. title = Biomathematical models for genetic diversity analyses in complete genomes of SARS-CoV-2 date = 2020-10-02 pages = extension = .txt mime = text/plain words = 4036 sentences = 254 flesch = 52 summary = In this work, we evaluated the levels of genetic diversity in 38 complete genomes of SARS-CoV-2, publicly available on the National Center for Biotechnology Information (NCBI) platform and from six countries in South America (Brazil, Chile, Peru, Colombia, Uruguay and Venezuela with 16, 11, 1, 1, 1, 7 haplotypes, respectively), all with an extension of 29,906 bp and Phred values [≥] 40. The specific methodologies for Paired FST estimators, Molecular Variance (AMOVA), Genetic Distance, mismatch, demographic and spatial expansion analyses, molecular diversity and evolutionary divergence time analyses, were obtained using 20,000 random permutation. This stage is the most used in the LaBECom protocols because it allows to know the genetic structure of populations measuring their variances, this methodology, first defined by Cockerham in 1969 and and, later adapted by other researchers, is essentially similar to other approaches based on analyses of gene frequency variance, but takes into account the number of mutations between haplotypes. cache = ./cache/cord-346280-7sw30bsz.txt txt = ./txt/cord-346280-7sw30bsz.txt === reduce.pl bib === id = cord-344321-fjer281d author = Ning, Yi title = Aptamers used for biosensors and targeted therapy date = 2020-10-20 pages = extension = .txt mime = text/plain words = 16947 sentences = 1045 flesch = 49 summary = Aptamers, first raised by two research groups independently in 1990 [1, 2] , are single-stranded DNA (ssDNA) or RNA sequences obtained through systematic evolution of ligands by exponential enrichment (SELEX) that can fold into secondary and three-dimensional shapes, enabling them to recognize various target molecules with high specificity and affinity, including proteins [3, 4] , small molecules [5, 6] , metal ions [7, 8] , bacterial cells [9, 10] , viruses [11, 12] , cancer cells [13, 14] , and even tissues [15] . developed a novel QD-Apt conjugate to be loaded with Dox for the targeted delivery of drugs to PC cells based on the mechanism of binary (Bi)-FRET (Fig. 15A) [215] . The Apt-Dox-Lip complex showed selective internalization and enhanced cytotoxicity to MCF-7 breast cancer cells and xenograft MCF-7 breast tumors in nude mice, suggesting that AS1411 aptamer-functionalized liposomes can specifically bind nucleolin overexpressed on the MCF-7 cell surface, and implement drug delivery with high selectivity. cache = ./cache/cord-344321-fjer281d.txt txt = ./txt/cord-344321-fjer281d.txt === reduce.pl bib === id = cord-347569-9fvbshz2 author = Balakrishnan, Krishnan Nair title = Multiple gene targeting siRNAs for down regulation of Immediate Early-2 (Ie2) and DNA polymerase genes mediated inhibition of novel rat Cytomegalovirus (strain All-03) date = 2020-10-27 pages = extension = .txt mime = text/plain words = 8627 sentences = 513 flesch = 53 summary = On the other hand, negative control siRNA and untreated groups showed higher viral titer than siRNA treated groups: 4 log 10 TCID50/ml at day 10 p.i and 8 log 10 TCID50/ml at day 18 p.i. Analysis of RCMV ALL-03 infected cells undergoing apoptosis/necrosis upon combination siRNAs treatment were studied using flow cytometry. Taking into consideration as positive treatment control group, commercial drug GCV exhibited better rate of CPE inhibition (Fig. 7) compared to other combination siR-NAs but lesser efficient than dpc + ie2b siRNAs. In order to understand more on the role of each combination siRNAs during RCMV ALL-03 infection, all the four combination siRNAs targeting different regions were analyzed individually with specific primers. During the search of effective treatment for CMV, idea of controlling the disease by means of inhibiting virus replication and gene expression by combinations of two and more siRNAs had been explored in this study. cache = ./cache/cord-347569-9fvbshz2.txt txt = ./txt/cord-347569-9fvbshz2.txt === reduce.pl bib === id = cord-346104-18x8u2oe author = Black, Wendy title = Identification of gammaherpesvirus infection in free-ranging black bears (Ursus americanus) date = 2019-01-02 pages = extension = .txt mime = text/plain words = 5163 sentences = 298 flesch = 56 summary = Herpesvirus infection in the bear tissues and tissue cultures were detected by PCR using degenerate primers specific to the DNA polymerase gene (DPOL) and glycoprotein B gene (gB). To determine whether the observed viral particles are herpesviruses, tissues collected from the two NV black bears B1 and B2 were examined by nested PCR using panherpesvirus primers (Pozo et al., 2016 ) and herpesvirus consensus primers (VanDevanter et al., 1996) . To determine how common this UrHV-1 like virus is in black bear population, various tissues from 15 bears collected from Nevada, California, and Oregon were analyzed by this hybrid nested PCR with panherpesvirus primers in primary reaction and UrHV-1specific primers in the secondary reactions. Positive amplification with UrHV-1 specific primers was observed in total DNA of white blood cells (WBC) from two black bears from Nevada and one from Oregon. cache = ./cache/cord-346104-18x8u2oe.txt txt = ./txt/cord-346104-18x8u2oe.txt === reduce.pl bib === id = cord-347472-n6811ens author = Rosebrock, Adam P. title = Patient DNA cross-reactivity of the CDC SARS-CoV-2 extraction control leads to an inherent potential for false negative results date = 2020-05-15 pages = extension = .txt mime = text/plain words = 6252 sentences = 344 flesch = 51 summary = The US Centers for Disease Control and Prevention (CDC) have specified and given emergency use authorization (EUA) for a SARS-CoV-2 molecular diagnostic used to detect viral RNA in clinical samples (2) . Genomic DNA is co-purified in quantities sufficient to generate strong positive signals for the CDC-specified extraction control during work-up of clinical RNA specimens. To test for the presence of control-affecting DNA, qPCR reactions lacking reverse transcriptase were performed on SARS-CoV-2-positive clinical samples using the CDC-specified RP primer and probe. All clinical samples tested generated unambiguous extraction control positive signals in the absence of reverse transcription, a reaction context that could not have detected virus an RNA virus ( Fig. 2A) Single-digit copies of genomic DNA are sufficient to generate a positive control signal using the CDC-designed assay. Due to the presence of co-purifying genomic DNA in clinical samples, loss of RNA integrity leads to false-negative results using the CDC-specified control. cache = ./cache/cord-347472-n6811ens.txt txt = ./txt/cord-347472-n6811ens.txt === reduce.pl bib === id = cord-346965-0oq2n0af author = Liu, Zhi-Ping title = Bridging protein local structures and protein functions date = 2008-04-18 pages = extension = .txt mime = text/plain words = 14491 sentences = 810 flesch = 44 summary = The characteristics between interface and noninterface portions of a protein surface, such as sequence conservation, proportions of amino acids, secondary structure, solvent accessibility and side-chain conformational entropy, are often used to distinguish the specificity of local structures relating to protein binding function. The method relies on a simplified representation of the chemical groups found in amino acid side-chains to identify functional sites from a single protein structure and a number of its sequence homologs. (2006) improved previous approaches by combining two known measures of 'functionality' in proteins, i.e. cleft volume and residue conservation, to develop a method for identifying the location of ligand-binding pockets in proteins. (2006) applied an SVM method to predict DNA-binding sites using the features including amino acid sequence, profile of evolutionary conservation of sequence positions, and low-resolution structural information. (2006) developed a method to predict both protein-protein binding site location and interface type (obligate or non-obligate) using a Bayesian network in combination with surface patch analysis. cache = ./cache/cord-346965-0oq2n0af.txt txt = ./txt/cord-346965-0oq2n0af.txt === reduce.pl bib === id = cord-346450-x1u567ss author = del Fresno, Carlos title = Myeloid cells in sensing of tissue damage date = 2020-10-07 pages = extension = .txt mime = text/plain words = 4209 sentences = 222 flesch = 34 summary = During tissue injury, mitochondrial DNA (mtDNA) is also released extracellularly as a pro-inflammatory DAMP [16] that is primarily recognized by the endosomal Toll-Like Receptor 9 (TLR9) upon phagocytosis by myeloid cells [17] . In a similar way, histones released upon cell death are recognized by 36 Innate immunity Inflammatory and regulatory functions of myeloid receptors and DAMPs compiled in this review. During most of the conditions described before, the recognition of DAMPs by myeloid cells triggers direct inflammatory responses by activating signaling pathways downstream certain PRRs. However, the sensing of tissue injury is not always inflammatory but can rather regulate inflammation (Figure 1, right oval) . Tissue injury conditions lead to massive release of different DAMPs. As discussed in here, the recognition of this tissue damage by myeloid cells can generate both pro-inflammatory and regulatory responses. cache = ./cache/cord-346450-x1u567ss.txt txt = ./txt/cord-346450-x1u567ss.txt === reduce.pl bib === id = cord-349672-2kt7xw8i author = Dasgupta, Tumpa title = Mechanism of Type IA Topoisomerases date = 2020-10-17 pages = extension = .txt mime = text/plain words = 8538 sentences = 463 flesch = 53 summary = Here, based on available structural and biochemical data, we discuss how a type IA topoisomerase may recognize and bind single-stranded DNA or RNA to initiate its required catalytic function. In type IA topoisomerases, the hydroxyl group in the side chain of the active site tyrosine residue is responsible for the first nucleophilic attack on the scissile phosphate of a single-stranded DNA resulting in the cleavage of the G-strand and the formation of the transient 5 -phospho-tyrosyl covalent linkage [66] . Though the type IA topoisomerase core domain that forms the characteristic torus structure contains all the highly conserved motifs responsible for G-strand binding and cleavage religation, the C-terminal domains of bacterial topoisomerase I have been shown to be required for removing negative supercoils from DNA rapidly in a processive mechanism [61, 72, [84] [85] [86] [87] . cache = ./cache/cord-349672-2kt7xw8i.txt txt = ./txt/cord-349672-2kt7xw8i.txt === reduce.pl bib === id = cord-346890-4vozhns4 author = Prajapati, Deepak G. title = Progress in the Development of Intrinsically Conducting Polymer Composites as Biosensors date = 2019-04-23 pages = extension = .txt mime = text/plain words = 14599 sentences = 806 flesch = 39 summary = Similarly, intrinsically conducting polymers (ICPs) and their composites have lured immense interest in bio‐sensing due to their various attributes like compatibility with biological molecules, efficient electron transfer upon biochemical reactions, loading of bio‐reagent, and immobilization of biomolecules. Amperometric biosensor relies on determining the current produced by electrochemical redox reaction of electro-active species, as a function of time, with a fixed applied potential on the electrode surface, most commonly an ICP. [255] Graphene in combination with ICP created a surface with superior electrical conductivity that resulted in a selective and sensitive biosensor and AuNP provided high affinity toward DNA for immobilization. The sensitive and selective biosensor exhibited excellent conductivity, high surface area, and many functional groups that aided in excellent immobilization of antibodies with low detection limit of 3.7 fg mL −1 . cache = ./cache/cord-346890-4vozhns4.txt txt = ./txt/cord-346890-4vozhns4.txt === reduce.pl bib === id = cord-350807-qdq96723 author = Reckziegel, Maria title = Viruses and atypical bacteria in the respiratory tract of immunocompromised and immunocompetent patients with airway infection date = 2020-05-27 pages = extension = .txt mime = text/plain words = 4655 sentences = 283 flesch = 44 summary = Samples were tested by PCR for the presence of herpesviruses (HSV-1/-2; VZV; CMV; HHV6; EBV), adenoviruses, bocaviruses, entero-/rhinoviruses (HRV), parechoviruses, coronaviruses, influenza viruses (IV), parainfluenza viruses as well as for pneumoviruses (HMPV and RSV), and atypical bacteria (Mycoplasma pneumoniae, M.p.; Chlamydia pneumoniae, C.p.). Furthermore, particularly transplant patients are at risk for reactivation of diverse herpesviruses (herpes simplex virus-1/-2, HSV-1/-2; varicella zoster virus, VZV; cytomegalovirus, CMV; human herpesvirus 6, HHV-6; Epstein-Barr virus, EBV) [12, 15, [17] [18] [19] [20] . In this monocentric study, genome equivalents of viruses and M.p. were frequently detected in immunocompromised (66.7%) and immunocompetent (69.2%) patients with respiratory symptoms (Table 1) . Same authors indicated a mean age of 1.8 years Table 2 Detection of multiple pathogens in the respiratory tract of the overall study population (a) as well as of immunocompromised (b) and immunocompetent (c) patients. cache = ./cache/cord-350807-qdq96723.txt txt = ./txt/cord-350807-qdq96723.txt === reduce.pl bib === id = cord-348104-7662q8dg author = Yang, Xiaoyun title = Molecular basis for the MacroD1-mediated hydrolysis of ADP-ribosylation date = 2020-06-22 pages = extension = .txt mime = text/plain words = 4314 sentences = 254 flesch = 53 summary = Taken together, our study provides structural and functional insights into the molecular mechanism of MacroD1-mediated ADPR hydrolysis and its role in DNA damage repair. Combining with our structural analysis and ADPR hydrolyzation assay, it suggests that distinct catalytic residues are responsible for the MacroD1-mediated ADPR hydrolysis, rather than the catalytic residues Asn 174 , Asp 184 and His 188 in the deacetylation of OAADPr. It is observed that Phe 272 adopts a significant conformational change in the catalytic pocket of MacroD1 upon ADPR binding, and that the corresponding phenyl group is evolutionarily conserved among macro domain hydrolases. In contrast, the structure of ADPR bound to the MacroH2A1.1 macro domain (inactive) reveals that the corresponding residue for MacroD1 Phe 272 is Asn 316 , and the disappearance of steric hindrance, which is generated by phenyl group, makes the distal ribose in a relatively extended conformation, in which its C1″ atom is far away from the catalytic water ( Fig. S3) (38) . cache = ./cache/cord-348104-7662q8dg.txt txt = ./txt/cord-348104-7662q8dg.txt === reduce.pl bib === id = cord-349042-u9svz7pf author = Li, Jifen title = The successes and future prospects of the linear antisense RNA amplification methodology date = 2018-03-29 pages = extension = .txt mime = text/plain words = 5015 sentences = 253 flesch = 42 summary = The technique was originally developed to assess RNA populations from small amounts of starting material, including single cells, but over time its use has evolved to include the detection of various cellular entities such as proteins, RNA-binding-protein-associated cargoes, and genomic DNA. The technique was originally developed to assess RNA populations from small amounts of starting material, including single cells, but over time its use has evolved to include the detection of various cellular entities such as proteins, RNA-binding-protein-associated cargoes, and genomic DNA. Examination of expression profiles of single live cells has shown that linear aRNA amplification neither results in occurs after synthesis of double-stranded cDNA, when T7 RNA polymerase is added and aRNA is transcribed from the cDNA template. 45 developed a method to facilitate aRNA detection of antibody-antigen interactions by covalently attaching a double-stranded cDNA that contains a T7 RNA polymerase promoter in front of a reporter sequence to a specific antibody. cache = ./cache/cord-349042-u9svz7pf.txt txt = ./txt/cord-349042-u9svz7pf.txt === reduce.pl bib === id = cord-350890-ajxvjkmq author = Hsieh, Yi-Fan title = A real-time convective PCR machine in a capillary tube instrumented with a CCD-based fluorometer date = 2013-07-05 pages = extension = .txt mime = text/plain words = 4214 sentences = 207 flesch = 47 summary = This research reports the design, analysis, integration, and test of a prototype of a real-time convective polymerase chain reaction (RT-cPCR) machine that uses a color charged coupled device (CCD) for detecting the emission of fluorescence intensity from an RT-cPCR mix in a microliter volume glass capillary. The measured results from the image-processing scheme indicate that the RT-cPCR prototype with a CCD-based fluorometer can achieve similar DNA quantification reproducibility compared to commercial machines, even when the initial DNA concentration in the test PCR mix is reduced to 10 copies/μL To assess the performance of the prototype, a single DNA template, HBV 122 base pairs, with known concentrations and a single labeling dye, SYBR Green I, was used in the PCR mixes undergoing the same thermal cycling in both the prototype and commercial RT-PCR machines for comparing their measured and predicted fluorescence intensities emitted from the glass capillaries. cache = ./cache/cord-350890-ajxvjkmq.txt txt = ./txt/cord-350890-ajxvjkmq.txt === reduce.pl bib === id = cord-351197-xv6ymc4l author = Cibulski, Samuel title = A plate of viruses: Viral metagenomics of supermarket chicken, pork and beef from Brazil date = 2020-09-28 pages = extension = .txt mime = text/plain words = 1711 sentences = 124 flesch = 54 summary = From chicken, six distinct gyroviruses (GyV) were detected, including GyV3 and GyV6, which for the first time were detected in samples from avian species, plus a novel smacovirus species and two highly divergent circular Rep-encoding ssDNA (CRESS-DNA) viruses. A detailed taxonomic 136 classification, including the numbers of reads for each Eukarya-related viral contig 137 recovered is this study, is provided in Supplementary gives them the ability to persist and spread in the environment. A detailed taxonomic classification, including the numbers of 245 J o u r n a l P r e -p r o o f sequenced reads of each Eukarya-related viral contig recovered in this study, is 246 provided in Supplementary Table 1 . including numbers of sequenced reads of each Eukarya-related viral contig recovered in 334 this study, is provided in Supplementary Table 1 . Cressdnaviricota: a virus phylum unifying 7 families of Rep-encoding 519 viruses with single-stranded, circular DNA genomes cache = ./cache/cord-351197-xv6ymc4l.txt txt = ./txt/cord-351197-xv6ymc4l.txt === reduce.pl bib === id = cord-350004-o151wwcf author = An, D. J. title = A DNA miniarray system for simultaneous visual detection of porcine circovirus type 1 (PCV1) and 2 (PCV2) in pigs date = 2008-07-24 pages = extension = .txt mime = text/plain words = 3260 sentences = 169 flesch = 53 summary = title: A DNA miniarray system for simultaneous visual detection of porcine circovirus type 1 (PCV1) and 2 (PCV2) in pigs PMWS postweaning multisystemic wasting syndrome PDNS porcine dermatitis and nephropathy syndrome PCVAD porcine circovirus associated disease Introduction PCV1 is widespread in the swine population of many countries based on serological surveys (Allan and Ellis 2000) , and is a persistent contaminant of the porcine kidney cell line PK-15 (Tischer et al. Detection is based on a colorimetric reaction following the hybridization of amplified viral DNA that contains a biotinylated nucleotide (biotin-16-dUTP) with oligonucleotide probes that are dotted on a nylon membrane (Quere et al. The objective of this study was to develop a DNA miniarray for the simultaneous detection of PCV1 and PCV2 in pigs with non-PMWS, PMWS and/or PDNS. In conclusion, we have developed a DNA miniarray for simultaneous detection of PCVs that provides similar level of sensitivity (100%) and specificity (98.9%) as in situ hybridization. cache = ./cache/cord-350004-o151wwcf.txt txt = ./txt/cord-350004-o151wwcf.txt === reduce.pl bib === id = cord-350212-448mv4lt author = Chiuppesi, Flavia title = Development of a Multi-Antigenic SARS-CoV-2 Vaccine Using a Synthetic Poxvirus Platform date = 2020-07-17 pages = extension = .txt mime = text/plain words = 7728 sentences = 446 flesch = 52 summary = We demonstrate that these sMVA vectors stimulate robust SARS-CoV-2 antigen-speci c humoral and cellular immunity in mice, including potent NAb. These results emphasize the value of a novel vaccine platform based on synthetic DNA to e ciently produce recombinant poxvirus vectors and warrant further pre-clinical and clinical testing of a multiantigenic sMVA vaccine candidate to control the ongoing SARS-CoV-2 pandemic and its devastating consequences. In response to the ongoing global SARS-CoV-2 pandemic, we used this novel vaccine platform to rapidly produce sMVA vectors co-expressing SARS-CoV-2 S and N antigens and show that these vectors can induce potent SARS-CoV-2 antigen-speci c humoral and cellular immune responses in mice, including potent NAb. These results highlight the feasibility to e ciently produce recombinant MVA vectors from chemically synthesized DNA and to rapidly develop a synthetic poxvirusbased vaccine candidate to prevent SARS-CoV-2 infection. cache = ./cache/cord-350212-448mv4lt.txt txt = ./txt/cord-350212-448mv4lt.txt === reduce.pl bib === id = cord-351295-4toxlskr author = Lanave, Gianvito title = Identification of hepadnavirus in the sera of cats date = 2019-07-23 pages = extension = .txt mime = text/plain words = 2665 sentences = 159 flesch = 48 summary = Also, in 7/10 animals with suspected hepatic disease, virus load was >10(4) genome copies per mL, i.e. above the threshold considered at risk of active hepatitis and liver damage for HBV. DCH DNA was detected in 31 (17.8%) out of 174 sera collected with a request for diagnosis of infectious diseases (collection A) and in 11 (5.1%) out of 216 sera submitted to the laboratory for pre-surgical evaluation or for suspected metabolic or neoplastic disease (collection B) that were used to generate a baseline. In this study we observed a marked and significantly higher prevalence (17.8%, 31/174) in the cohort of cats with suspected infectious diseases (collection A) with respect to a group of animals (collection B) used as baseline. Almost half of the sera positive for DCH (14/31, 45 .2%) of this cohort were collected from cats with retroviral infection (FIV and/or feline leukemia virus, FeLV). cache = ./cache/cord-351295-4toxlskr.txt txt = ./txt/cord-351295-4toxlskr.txt === reduce.pl bib === id = cord-350019-4nlbu54e author = Robinson, Elektra K. title = The how and why of lncRNA function: An innate immune perspective() date = 2019-09-02 pages = extension = .txt mime = text/plain words = 13173 sentences = 715 flesch = 44 summary = Using this extensively studied biological system, we identified the first example of a TLR-stimulated lncRNA, lincRNA-Cox2, which was capable of positively and negatively regulating distinct types of innate immune genes [42] [43] [44] [45] [46] . The majority of lncRNAs studied in immunity were initially identified following RNA-sequencing to examine their expression profiles in specific cell lines or tissues during inflammatory activation. Hence future studies may opt to target TF binding sites, secondary structure and/or polyadenylation sites as a way to more finely dissect the functional portions of lncRNAs. The ease in which Cas9 can be targeted to specific genomic regions sparked the development of a modified (catalytically inactivated) version of the protein fused to the KRAB (Krüppel associated box) chromatin-silencing domain termed CRISPRi [174, 175] (Fig. 3C) . Genome-wide screening for functional long noncoding RNAs in human cells by Cas9 targeting of splice sites cache = ./cache/cord-350019-4nlbu54e.txt txt = ./txt/cord-350019-4nlbu54e.txt === reduce.pl bib === id = cord-353389-5dtwje1b author = Han, Guojun title = Absolute and Relative Quantification of Multiplex DNA Assays Based on an Elemental Labeling Strategy date = 2013-01-28 pages = extension = .txt mime = text/plain words = 3309 sentences = 174 flesch = 53 summary = [9] Compared with other methods, it contains two inherent advantages: 1) Owing to the benefits of a large number of elements or isotopes (up to 100) potentially used as elemental tags, as well as excellent mass resolution and multi-element detectors of ICP-MS, high-level multiplexed analysis can be successfully obtained without the limitation of spectral overlap; [10] 2) ICP-MS has allowed isotope ratio measurement with good accuracy and precision, thus in combination with isotope dilution analysis (IDA), absolute-quantitative measurement can be carried out as the complementary use of molecular mass spectrometry. As shown in Scheme 1 a, the procedure of labeling sequence-specific oligonucleotides with elemental tags involves two steps: 1) oligonucleotides, 3' end-functionalized with thiol ( À SH) groups, were specifically derivatized with malemide groups of 1,4,7,10-tetraazacyclododecane-1,4,7tris-aceticacid-10-maleimidoethylacetamide (MMA-DOTA), a compound commonly employed for chemical labeling of proteins or peptides; [17] 2) rare-earth elements (REEs) were chelated with high kinetic and thermodynamic stability (for reaction conditions (pH, mole ratio of MMA-DOTA to DNA, time, and temperature), see the Supporting Information). cache = ./cache/cord-353389-5dtwje1b.txt txt = ./txt/cord-353389-5dtwje1b.txt === reduce.pl bib === id = cord-348860-zaimorg0 author = Ratra, Ruchi title = Functional genomics as a tool in virus research date = 2008-06-01 pages = extension = .txt mime = text/plain words = 3379 sentences = 171 flesch = 39 summary = The genomics era has revolutionized the biological sciences and has heralded the emergence of new 'omics' methodologies such as transcriptomics (study of the gene expression and expression levels of mRNAs at a given time and condition), proteomics (study of the entire protein content of a cell/tissue under various conditions, their structure and functions), metabolomics (study of the metabolite profi le of different cellular processes), phosphoproteomics (a branch of proteomics that characterizes proteins that are phosphorylated), interactomics/system biology (a science that unifi es transcriptomics, proteomics and metabolomics to look at the organism as a whole) and so on. DNA microarrays, proteomics and bioinformatic analysis are routinely used to analyze changes in host and viral gene and protein expression that occur in a virus infected cell [25] . cache = ./cache/cord-348860-zaimorg0.txt txt = ./txt/cord-348860-zaimorg0.txt === reduce.pl bib === id = cord-352619-s2x53grh author = Payne, Natalie title = Novel Circoviruses Detected in Feces of Sonoran Felids date = 2020-09-15 pages = extension = .txt mime = text/plain words = 3263 sentences = 177 flesch = 45 summary = Genomes from several families of circular Rep-encoding single-stranded DNA viruses (CRESS-DNA viruses) are part of the phylum Cressdnaviricota [22] and have been identified in fecal samples of other mammals, including domestic cats [23, 24] , bobcats, African lions [25] , capybaras [26] , and Tasmanian devils [27] . Here we used a metagenomic approach to identify novel circoviruses in the feces of two species of Sonoran felids, the puma and bobcat; although not endangered, knowledge of viral threats facing these species could help prevent future population decline, as well as indicate potential threats to the endangered ocelot and jaguar. Based on the species-demarcation threshold for circoviruses which is 80% genome-wide identity [28] , both of these belong to a new species which we refer to as Sonfela (derived from Sonoran felid associated) circovirus 1. As the viral genomes were derived from scat samples, the circoviruses could have infected the bobcat prey species or the felids themselves or be environmentally derived. cache = ./cache/cord-352619-s2x53grh.txt txt = ./txt/cord-352619-s2x53grh.txt === reduce.pl bib === id = cord-347710-ff64y6ef author = Wan, Qianya title = Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development date = 2020-07-13 pages = extension = .txt mime = text/plain words = 36567 sentences = 2487 flesch = 46 summary = hnRNPs involve in a large number of cellular processes, including chromatin remodelling, transcription regulation, RNP assembly and stabilization, RNA export, virus replication, histone-like nucleoid structuring, and even intracellular immunity. 6, 13 It is well known that Hsp90 not only interacts and contributes to RNA polymerase assembly and nuclear import of some (−) ssRNA viruses (e.g., PB2 of influenza virus), but plays crucial roles in the folding process of viral capsid proteins and virion assemblies as well. 17, 18 As a critical component of cellular protein surveillance, the ATP-dependent molecular chaperone protects cells from damage caused by stress and takes part in a number of folding processes, including folding of newly synthesized polypeptides, recognition and refolding of misfolded or aggregated proteins, solubilization or degradation of proteins, transporting proteins, assembly or disassembly of oligomeric protein complexes, and the regulation of certain natively folded proteins. cache = ./cache/cord-347710-ff64y6ef.txt txt = ./txt/cord-347710-ff64y6ef.txt === reduce.pl bib === id = cord-354000-jxqskt4k author = Warren, Cody J. title = The Antiviral Restriction Factors IFITM1, 2 and 3 Do Not Inhibit Infection of Human Papillomavirus, Cytomegalovirus and Adenovirus date = 2014-05-14 pages = extension = .txt mime = text/plain words = 4420 sentences = 265 flesch = 47 summary = Here, we demonstrate that IFN-α or -β treatment of keratinocytes substantially decreases human papillomavirus 16 (HPV16) infection while robustly inducing IFITM1, 2 and 3 expression. IFITM protein expression induced by type I IFN inhibits infection of many RNA viruses [22] [23] [24] [25] [26] [27] [28] [29] [30] . Therefore, we analyzed induction of IFITM1, 2 and 3 expression by IFN-b treatment in human keratinocytes, the natural host cells for HPV. To determine the effect of IFITMs on HPV16 entry, HeLa cells stably expressing c-Myc-tagged IFITM1, 2 or 3 or with vector alone ( Fig. 2A-B) were infected with HPV16-LucF. Using various epithelial cell lines and primary keratinocytes expressing IFITMs, we show that HPV infection is surprisingly enhanced by IFITM1 and IFITM3 overexpression (Fig. 2) . Taken together, our results suggest that HPV and other DNA viruses may have evolved to avoid IFITM1, 2 and 3 restriction during entry into host cells. cache = ./cache/cord-354000-jxqskt4k.txt txt = ./txt/cord-354000-jxqskt4k.txt === reduce.pl bib === id = cord-352172-g0jiaenw author = Stoevesandt, Oda title = Protein microarrays: high-throughput tools for proteomics date = 2014-01-09 pages = extension = .txt mime = text/plain words = 7464 sentences = 373 flesch = 32 summary = While conventionally made by the spotting of purified proteins, recent advances in technology have made it possible to produce protein microarrays through in situ cell-free synthesis directly from corresponding DNA arrays. Protein microarray technology has rapidly developed into one of the most active areas in biotechnology today, and is being increasingly applied for the high-throughput discovery of molecular interactions, profiling of protein expression and monitoring of protein modifications. While genome sequencing and annotations provide comprehensive information on protein-encoding genes, and DNA arrays analyze gene expression at the mRNA level, these technologies need to be complemented by functional proteomic studies in order to better understand protein activities, expression levels and interactions at the system level. A reverse-phase micro array approach has been successfully applied to discover distinct pathway-activation differences among breast cancer cell lines, demonstrating the use of array-based ana lysis for multiple pharmacodynamic biomarkers responding to targeted kinase inhibitors [108] . cache = ./cache/cord-352172-g0jiaenw.txt txt = ./txt/cord-352172-g0jiaenw.txt === reduce.pl bib === id = cord-352891-ljmkqdzx author = Parang, Keykavous title = Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs against Human Coronavirus 229E (HCoV-229E) date = 2020-05-17 pages = extension = .txt mime = text/plain words = 3165 sentences = 182 flesch = 52 summary = title: Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs against Human Coronavirus 229E (HCoV-229E) Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5′-O-fatty acylated anti-HIV nucleoside conjugates. Therefore, HCoV-229E may be a good initial model for the evaluation of antiviral compounds that could have potential applications against other coronaviruses, such as SARS-COV-2, the coronavirus that causes COVID-19. We have previously shown that the conjugation of certain fatty acids to the anti-HIV NRTIs, such as FLT, 3TC and FTC, enhanced activity against X4, R5, cell-associated, and/or multi-drug resistant virus when compared with their parent nucleosides [24] [25] [26] [27] . A series of anti-HIV nucleosides and their fatty acyl derivatives were compared with remdesivir for antiviral activity against HCoV-229E in MRC-5 cells. cache = ./cache/cord-352891-ljmkqdzx.txt txt = ./txt/cord-352891-ljmkqdzx.txt === reduce.pl bib === id = cord-353297-jizitnfl author = Meyer, R.F. title = Viruses and Bioterrorism date = 2008-07-30 pages = extension = .txt mime = text/plain words = 3817 sentences = 184 flesch = 43 summary = The requirements for an ideal biological warfare agent include availability, ease of production, stability after production, a susceptible population, absence of specific treatment, ability to incapacitate or kill the host, appropriate particle size in aerosol so that the virus can be carried long distances by prevailing winds and inhaled deeply into the lungs of unsuspecting victims, ability to be disseminated via food or water, and the availability of a vaccine to protect certain groups. Instead, the ectromelia virus vector expressing IL-4 altered the host's immune response to this virus resulting in lethal infections in normally genetically Classification of viral agents that are considered to be of concern for bioterrorism and biowarfare and those that have been weaponized or studied for offensive or defensive purposes as part of former or current national biological weapons programs resistant mice (e.g., C57BL/6). cache = ./cache/cord-353297-jizitnfl.txt txt = ./txt/cord-353297-jizitnfl.txt === reduce.pl bib === id = cord-354990-2hx7f6ny author = ZAKIAN, VIRGINIA A. title = Telomere formation in yeast date = 1989 pages = extension = .txt mime = text/plain words = 698 sentences = 44 flesch = 51 summary = In two other families of viral GKS/Tcontaining proteins serine is encoded almost exclusively by UCN, with AGY occurring only once (see table) . An alternative mechanism involves the generation of a new serine codon next to the functionally important one (yielding a GKSS sequence with the two serines encoded by codons of different series) followed by deletion of the original codon. SIR-We recently demonstrated that dur-, ing formation of new telomeres in the yeast Saccharomyces cerevisiae, telomeric sequences are often transferred between DNA termini'. In a recent News and Views article', however, Szostak suggested that the telomere resolution reaction ' (the cleavage between two blocks of telomeric sequences that are oriented as a head-tohead inverted repeat'') can provide an alternative explanation for our data, a possibility that can be addressed definitively by DNA sequencing. Because the resolution reaction is excluded unequivocally by DNA sequence data , telomere-telomere recombination remains the only reasonable explanation for the transfer of telomeric sequences that we have observed. cache = ./cache/cord-354990-2hx7f6ny.txt txt = ./txt/cord-354990-2hx7f6ny.txt === reduce.pl bib === id = cord-355913-fhvt1ht1 author = Burrell, Christopher J. title = Virus Replication date = 2016-11-11 pages = extension = .txt mime = text/plain words = 9861 sentences = 405 flesch = 42 summary = Little is known about what determines whether a given picornavirus positive-sense RNA molecule will be directed (1) to a replication complex (a structure bound to smooth endoplasmic reticulum), where it serves as template for transcription by RNA-dependent RNA polymerase into negative-sense RNA, or (2) to a ribosome, where it serves as mRNA for translation into protein, or (3) to a procapsid, with which it associates to form a virion. In the case of positive-sense single-stranded RNA viruses, the incoming RNA genome can bind directly to ribosomes and be translated in full or in part without the need for any prior transcription; all other forms of incoming viral RNA must first be transcribed to produce mRNA, in order to begin the process of expression of the infecting viral genome. cache = ./cache/cord-355913-fhvt1ht1.txt txt = ./txt/cord-355913-fhvt1ht1.txt === reduce.pl bib === id = cord-356291-0x1jhya6 author = Tang, Liang title = Three-dimensional structure of the bacteriophage P22 tail machine date = 2005-06-02 pages = extension = .txt mime = text/plain words = 6191 sentences = 300 flesch = 60 summary = The three-dimensional structure of the P22 tail machine determined by electron cryo-microscopy and image reconstruction reveals how the five types of polypeptides present as 51 subunits are organized into this molecular machine through twelve-, sixand three-fold symmetry, and provides insights into molecular events during host cell attachment and phage DNA translocation. The electron cryo-microscopy (cryoEM) structure of Bacillus phage SPP1 portal in complex with head completion proteins gp15 and gp16, through which the tail is connected to the head, revealed local conformational change of the portal upon binding of gp15 and the function of gp16 as a valve (Orlova et al, 2003) . Here, we present the three-dimensional structures of the tail machine and a C-terminally truncated form of the portal protein of bacteriophage P22 determined by cryoEM and image reconstruction. cache = ./cache/cord-356291-0x1jhya6.txt txt = ./txt/cord-356291-0x1jhya6.txt === reduce.pl bib === id = cord-010119-t1x9gknd author = nan title = Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 date = 2017-09-04 pages = extension = .txt mime = text/plain words = 230193 sentences = 13234 flesch = 55 summary = Conclusion: The wide distribution in the concentration of bioactive lipids among 405 stored RBC units suggests that lipid degradation is highly donor-Background/Case Studies: To ensure availability of biological products to hospitals, blood banks have developed and validated multiple storage conditions for each of their products to maximize shelf life and quality. 1 The Department of Blood Transfusion, The PLA General Hospital, 2 The Department of Blood Transfusion, Air Force General Hospital, PLA Background/Case Studies: Recently, multi researches have reported that longer term-stored red blood cells(RBCs) units were associated with increased risks of clinically adverse events, especially in critically ill patients. Weak D types 1, 2 and 3 express all the major RhD epitopes and these patients can be managed as RhD-positive, which may lead to a reduction in unnecessary Rh immunoglobulin (RhIG) administration and conservation of RhD-negative RBCs. Study Design/Method: RHD genotyping was performed on all patient samples with weaker than expected or discrepant RhD typing results, utilizing a commercially available genotyping kit manufactured by Immucor (RHD BeadChip). cache = ./cache/cord-010119-t1x9gknd.txt txt = ./txt/cord-010119-t1x9gknd.txt ===== Reducing email addresses cord-000830-jiy4cp4n cord-004584-bcw90f5b cord-001835-0s7ok4uw cord-004534-jqm1hxps cord-010500-ajmj2hyj cord-012473-p66of6kq cord-014875-xhzxhwgo cord-014597-66vd2mdu cord-008777-i2reanan cord-017948-fqhl1qb4 cord-018526-rz7id5mt cord-023389-ilrp8vb7 cord-020010-q58x6xb0 cord-014794-yppi30a0 cord-102511-7zgd45fl cord-048359-lz37rh82 cord-252536-gfx4cq03 cord-257802-vgizgq2y cord-260422-z22t57ju cord-263570-6notzm6s cord-282106-7k088cqv cord-294712-kvvxmvqo cord-318609-211m5b79 cord-321386-u1imic5l cord-321640-kx3t81yh cord-348860-zaimorg0 Creating transaction Updating adr table ===== Reducing keywords cord-000049-rl7sdzd7 cord-000104-3b8b8p61 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cord-022940-atbjwpo5 cord-010119-t1x9gknd Creating transaction Updating pos table Building ./etc/reader.txt cord-022940-atbjwpo5 cord-022888-dnsdg04n cord-031907-ilhr3iu5 cord-022940-atbjwpo5 cord-004133-32w6g7qk cord-031907-ilhr3iu5 number of items: 647 sum of words: 8,357,975 average size in words: 15,477 average readability score: 46 nouns: cells; dna; cell; patients; protein; virus; results; blood; expression; gene; study; proteins; analysis; disease; detection; activity; infection; methods; time; data; treatment; samples; viruses; studies; system; levels; type; method; group; response; mice; cancer; genes; sequence; acid; cases; role; number; control; use; development; vaccine; effect; genome; assay; sequences; effects; surface; structure; function verbs: using; show; based; include; increased; induce; found; associated; compared; bind; identify; performed; detect; develop; determine; containing; followed; suggest; provided; reported; observed; require; expressed; causing; reduces; demonstrated; resulting; led; obtained; involving; produced; mediated; revealed; indicated; known; investigate; tested; treated; evaluated; described; study; allow; makes; related; present; target; occur; measured; give; derived adjectives: human; viral; different; high; specific; clinical; immune; positive; new; non; anti; molecular; significant; low; single; important; several; higher; first; many; cellular; negative; small; genetic; large; normal; similar; present; bacterial; dependent; novel; multiple; various; major; common; potential; possible; primary; free; severe; early; biological; nucleic; functional; available; active; inflammatory; lower; respiratory; acute adverbs: also; however; well; significantly; respectively; therefore; highly; recently; previously; even; often; still; furthermore; currently; moreover; directly; especially; now; usually; together; mainly; first; less; prior; approximately; particularly; specifically; finally; relatively; commonly; widely; generally; rather; far; fully; potentially; interestingly; clinically; successfully; frequently; yet; additionally; much; subsequently; later; thereby; alone; rapidly; strongly; already pronouns: we; it; their; its; our; they; i; them; he; his; us; her; she; itself; one; themselves; you; your; my; me; him; mrnas; himself; ourselves; s; rad5; mg; cyp2c9; 2h5-a14; pfh1p; ashcs; thy; p210bcr; mine; imagej; igg4; hmsh2; yÞ; ours; nsp10; igfbp2; iga1; i-; hipb; u; theirs; pcv2; p24ag; nr-818; myself proper nouns: RNA; PCR; DNA; C; T; Fig; B; University; HBV; SARS; mg; A; HIV; E.; II; S.; M; HCV; C.; S; HIV-1; IFN; RT; CF; mRNA; L; M.; D; USA; G; K; P.; RBC; CFTR; ELISA; Institute; MS; N; CD4; CD8; Table; pH; A.; Background; Department; ATP; van; AE; CMV; I keywords: dna; rna; cell; pcr; virus; protein; gene; study; patient; detection; sars; result; vaccine; university; sequence; method; hbv; ifn; expression; disease; hiv; human; hiv-1; hcv; infection; high; genome; sample; viral; response; hospital; cancer; activity; lamp; structure; institute; increase; blood; atp; vector; system; elisa; crispr; conclusion; amplification; sting; peptide; mhc; group; department one topic; one dimension: dna file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2656497/ titles(s): Detection of genetically modified organisms (GMOs) using isothermal amplification of target DNA sequences three topics; one dimension: dna; cells; patients file(s): https://www.sciencedirect.com/science/article/pii/S0065352707700040, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120058/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169338/ titles(s): A Guide to Viral Inclusions, Membrane Rearrangements, Factories, and Viroplasm Produced During Virus Replication | 1 Micro-organismen, de mens en het ontstaan van infectieziekten: algemene principes | EDUCATION DAY MONDAY: PLENARY SESSION 1 MONDAY: PARALLEL SESSIONS five topics; three dimensions: patients cells results; dna virus cells; blood dna detection; cells protein cell; dna pcr virus file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271214/, https://www.ncbi.nlm.nih.gov/pubmed/32661235/, https://doi.org/10.1371/journal.pone.0153359, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167823/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120058/ titles(s): Large Intestine (Colon) | Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development | Picoliter Well Array Chip-Based Digital Recombinase Polymerase Amplification for Absolute Quantification of Nucleic Acids | Poster Presentations | 1 Micro-organismen, de mens en het ontstaan van infectieziekten: algemene principes Type: cord title: keyword-dna-cord date: 2021-05-24 time: 23:33 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: keywords:dna ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-306104-hezi2tf9 author: Abad-Valle, Patricia title: Genosensor on gold films with enzymatic electrochemical detection of a SARS virus sequence() date: 2005-05-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A hybridisation-based genosensor was designed on a 100 nm sputtered gold film. This material worked as an immobilisation and transduction surface. A 30-mer sequence that encodes a short lysine-rich region, unique to SARS (severe acute respiratory syndrome) virus, was chosen as target. A complementary strand (probe), labelled with a thiol group at the 3′-end, was immobilised on the film. After blocking the surface, hybridisation with the biotin-conjugated SARS strand (at the 3′-end) took place. Interaction with alkaline phosphatase-labelled streptavidin permits amplified indirect electrochemical detection. The analytical signal is constituted by an electrochemical process of indigo carmine, the soluble product of the enzymatic hydrolysis of 3-indoxyl phosphate. The use of a sensitive electrochemical technique such as square wave voltammetry allowed a detection limit of 6 pM to be obtained for this DNA sequence, lower than any other found in the bibliography. The parameters affecting the methodology were studied, with special attention being placed on selectivity. Specificity was clearly enhanced when interaction time and stringency (in the form of formamide percentage) were increased. With 1 h of strand interaction and employing 50% of formamide in the hybridisation buffer, a 3-base mismatch strand was perfectly distinguished from the complementary. url: https://www.sciencedirect.com/science/article/pii/S0956566304005123 doi: 10.1016/j.bios.2004.10.019 id: cord-271635-tydlyc1q author: Abdel-Hamid, Nabil M. title: Herbal management of hepatocellular carcinoma through cutting the pathways of the common risk factors date: 2018-11-30 words: 10051.0 sentences: 543.0 pages: flesch: 36.0 cache: ./cache/cord-271635-tydlyc1q.txt txt: ./txt/cord-271635-tydlyc1q.txt summary: They can inhibit the liver cancer development and progression in several ways as protecting against liver carcinogens, enhancing effects of chemotherapeutic drugs, inhibiting tumor cell growth and metastasis, and suppression of oxidative stress and chronic inflammation. The co-treatment with LPP, orally, in NAFLD in rats, showed a significant improvement in the hepatic histology, reduction in the fibrosis, oxidative stress, inflammation, accumulation of fats and apoptosis, through modulating the transcriptional factors NF-κB and activator protein-1 (AP-1). The major polyphenol of green tea, epigallocatechin-3-gallate (EGCG), was used in CCl 4 -treated mice and showed a significant therapeutic potential in hepatic damage, inflammation and oxidative stress induced by CCl 4 in a dose-dependent manner at both biochemical and histological levels [34] . It was also reported that co-treatment of the whole green tea extract with alcohol administration showed an effective reduction of the hepatic oxidative stress and reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase systems in experimental alcohol-induced liver injury [35] . abstract: Abstract Hepatocellular carcinoma (HCC) is considered the most frequent tumor that associated with high mortality rate. Several risk factors contribute to the pathogenesis of HCC, such as chronic persistent infection with hepatitis C virus or hepatitis B virus, chronic untreated inflammation of liver with different etiology, oxidative stress and fatty liver disease. Several treatment protocols are used in the treatment of HCC but they also associated with diverse side effects. Many natural products are helpful in the co-treatment and prevention of HCC. Several mechanisms are involved in the action of these herbal products and their bioactive compounds in the prevention and co-treatment of HCC. They can inhibit the liver cancer development and progression in several ways as protecting against liver carcinogens, enhancing effects of chemotherapeutic drugs, inhibiting tumor cell growth and metastasis, and suppression of oxidative stress and chronic inflammation. In this review, we will discuss the utility of diverse natural products in the prevention and co-treatment of HCC, through its capturing of the common risk factors known to lead to HCC and shed the light on their possible mechanisms of action. Our theory assumes that shutting down the risk factor to cancer development pathways is a critical strategy in cancer prevention and management. We recommend the use of these plants side by side to recent chemical medications and after stopping these chemicals, as a maintenance therapy to avoid HCC progression and decrease its global incidence. url: https://api.elsevier.com/content/article/pii/S075333221834280X doi: 10.1016/j.biopha.2018.08.104 id: cord-278397-u33x4jaw author: Abe, Takayuki title: Negative Regulation of Cytosolic Sensing of DNA date: 2018-10-29 words: 7194.0 sentences: 377.0 pages: flesch: 41.0 cache: ./cache/cord-278397-u33x4jaw.txt txt: ./txt/cord-278397-u33x4jaw.txt summary: Recent efforts have focused on identifying relevant immune surveillance sensors and components of downstream signaling-Toll-like receptors (TLRs) and their cognate ligands, cytosolic sensing of RNA (primary mediated by the RIG-I/IPS-1 axis), cytosolic sensing of DNA (primary mediated by the cGAS/STING axis), and the inflammasome pathway (primary mediated by NOD-like receptors; NLRs) (Broz and Monack, 2013; Kieser and Kagan, 2017; Kumar et al., 2011a ). It has also been suggested that chronic cGAS/STING activation induced by self DNA may be responsible for induction of aberrant inflammatory diseases like systemic lupus erythematosus (SLE), Aicardi-Goutières syndrome (AGS), and polyarthritis (Barber, 2015; Crowl et al., 2017) . Use of DNA damage induced agents like 7,12-dimethylbenz-α-anthracene (DMBA) has helped shed light on the underlying events initiate the DNA damage-induced immune response via cytosolic DNA sensing pathway and implicates nucleosome leakage in eliciting cGAS/STING-dependent signal activation via recognition of self-DNA (Barber, 2015) . abstract: In mammals, cytosolic detection of nucleic acids is critical in initiating innate antiviral responses against invading pathogens (like bacteria, viruses, fungi and parasites). These programs are mediated by multiple cytosolic and endosomal sensors and adaptor molecules (c-GAS/STING axis and TLR9/MyD88 axis, respectively) and lead to the production of type I interferons (IFNs), pro-inflammatory cytokines, and chemokines. While the identity and role of multiple pattern recognition receptors (PRRs) have been elucidated, such immune surveillance systems must be tightly regulated to limit collateral damage and prevent aberrant responses to self- and non-self-nucleic acids. In this review, we discuss recent advances in our understanding of how cytosolic sensing of DNA is controlled during inflammatory immune responses. url: https://doi.org/10.1016/bs.ircmb.2018.09.002 doi: 10.1016/bs.ircmb.2018.09.002 id: cord-303319-v3iyur78 author: Abe, Takayuki title: Cytosolic DNA‐sensing immune response and viral infection date: 2019-02-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: How host cells recognize many kinds of RNA and DNA viruses and initiate innate antiviral responses against them has not yet been fully elucidated. Over the past decade, investigations into the mechanisms underlying these antiviral responses have focused extensively on immune surveillance sensors that recognize virus‐derived components (such as lipids, sugars and nucleic acids). The findings of these studies have suggested that antiviral responses are mediated by cytosolic or intracellular compartment sensors and their adaptor molecules (e.g., TLR, myeloid differentiation primary response 88, retinoic acid inducible gene‐I, IFN‐β promoter stimulator‐1, cyclic GMP‐AMP synthase and stimulator of IFN genes axis) for the primary sensing of virus‐derived nucleic acids, leading to production of type I IFNs, pro‐inflammatory cytokines and chemokines by the host cells. Thus, host cells have evolved an elaborate host defense machinery to recognize and eliminate virus infections. In turn, to achieve sustained viral infection and induce pathogenesis, viruses have also evolved several counteracting strategies for achieving immune escape by targeting immune sensors, adaptor molecules, intracellular kinases and transcription factors. In this review, we discuss recent discoveries concerning the role of the cytosolic nucleic acid‐sensing immune response in viral recognition and control of viral infection. In addition, we consider the regulatory machinery of the cytosolic nucleic acid‐sensing immune response because these immune surveillance systems must be tightly regulated to prevent aberrant immune responses to self and non‐self‐nucleic acids. url: https://doi.org/10.1111/1348-0421.12669 doi: 10.1111/1348-0421.12669 id: cord-000625-cpjlzutk author: Ablordey, Anthony title: Detection of Mycobacterium ulcerans by the Loop Mediated Isothermal Amplification Method date: 2012-04-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Buruli ulcer (BU) caused by Mycobacterium ulcerans (M. ulcerans) has emerged as an important public health problem in several rural communities in sub-Saharan Africa. Early diagnosis and prompt treatment are important in preventing disfiguring complications associated with late stages of the disease progression. Presently there is no simple and rapid test that is appropriate for early diagnosis and use in the low-resource settings where M. ulcerans is most prevalent. METHODOLOGY: We compared conventional and pocket warmer loop mediated isothermal amplification (LAMP) methods (using a heat block and a pocket warmer respectively as heat source for amplification reaction) for the detection of M. ulcerans in clinical specimens. The effect of purified and crude DNA preparations on the detection rate of the LAMP assays were also investigated and compared with that of IS2404 PCR, a reference assay for the detection of M. ulcerans. Thirty clinical specimens from suspected BU cases were examined by LAMP and IS2404 PCR. PRINCIPAL FINDINGS: The lower detection limit of both LAMP methods at 60°C was 300 copies of IS2404 and 30 copies of IS2404 for the conventional LAMP at 65°C. When purified DNA extracts were used, both the conventional LAMP and IS2404 PCR concordantly detected 21 positive cases, while the pocket warmer LAMP detected 19 cases. Nine of 30 samples were positive by both the LAMP assays as well as IS2404 PCR when crude extracts of clinical specimens were used. CONCLUSION/SIGNIFICANCE: The LAMP method can be used as a simple and rapid test for the detection of M. ulcerans in clinical specimens. However, obtaining purified DNA, as well as generating isothermal conditions, remains a major challenge for the use of the LAMP method under field conditions. With further improvement in DNA extraction and amplification conditions, the pwLAMP could be used as a point of care diagnostic test for BU url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317900/ doi: 10.1371/journal.pntd.0001590 id: cord-005400-50lmj4op author: Ada, Gordon title: Overview of vaccines and vaccination date: 2005 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Of the 80-plus known infectious agents pathogenic for humans, there are now more than 30 vaccines against 26 mainly viral and bacterial infections and these greatly minimize subsequent disease and prevent death after exposure to those agents. This article describes the nature of the vaccines, from live attenuated agents to subunits, their efficacy and safety, and the kind of the immune responses generated by those vaccines, which are so effective. To date, all licensed vaccines generate especially specific antibodies, which attach to the infectious agent and therefore can very largely prevent infection. These vaccines have been so effective in developed countries in preventing mortality after a subsequent infection that attempts are being made to develop vaccines against many of the remaining infectious agents. Many of the latter are difficult to manipulate; they can cause persisting infections or show great antigenic variation. A range of new approaches to improve selected immune responses, such as immunization with DNA or chimeric live vectors, viral or bacterial, are under intense scrutiny, as well as genomic analysis of the agent. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091467/ doi: 10.1385/mb:29:3:255 id: cord-297203-f3f31h4r author: Afrough, B. title: Emerging viruses and current strategies for vaccine intervention date: 2019-04-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: During the past decade several notable viruses have suddenly emerged from obscurity or anonymity to become serious global health threats, provoking concern regarding their sustained epidemic transmission in immunologically naive human populations. With each new threat comes the call for rapid vaccine development. Indeed, vaccines are considered a critical component of disease prevention for emerging viral infections because, in many cases, other medical options are limited or non‐existent, or that infections result in such a rapid clinical deterioration that the effectiveness of therapeutics is limited. While classic approaches to vaccine development are still amenable to emerging viruses, the application of molecular techniques in virology has profoundly influenced our understanding of virus biology, and vaccination methods based on replicating, attenuated and non‐replicating virus vector approaches have become useful vaccine platforms. Together with a growing understanding of viral disease emergence, a range of vaccine strategies and international commitment to underpin development, vaccine intervention for new and emerging viruses may become a possibility. url: https://www.ncbi.nlm.nih.gov/pubmed/30993690/ doi: 10.1111/cei.13295 id: cord-016808-gy8d8285 author: Agol, Vadim I. title: The Origin and Evolution of Viruses date: 2008 words: 3255.0 sentences: 172.0 pages: flesch: 44.0 cache: ./cache/cord-016808-gy8d8285.txt txt: ./txt/cord-016808-gy8d8285.txt summary: Modern hypotheses of viral origin are based on two major developments of the molecular biology: discovery of ribozymes (RNA-based enzymes) and formulation of the "RNA World" theory (RNA had been "invented" before proteins and DNA), on the one hand, and achievements of genomics (determination of the nucleotide sequences of a great number of cellular and viral genomes), on the other. Three distinct DNA viruses, which had infected RNA genome-containing cells, gave rise to the three distinct domains of life, bacteria, archea, and eukarya (Forterre, 2006) . To infect a human, an avian flu virus should change its receptor specificity, which depends on the interaction of viral hemagglutinin (HA) with a cellular membrane glycoprotein receptor. Such a change in the host range may be achieved by either mutations in the avian HA or acquisition by an avian virus of the HA gene from human influenza virus as a result of genetic exchange (reassortment) between these viruses during mixed infections. Three RNA cells for ribosomal lineages and three DNA viruses to replicate their genomes: A hypothesis for the origin of cellular domain abstract: The lecture covers three main topics: (i) Viruses: properties, place in the living world, and possible origin; (ii) Molecular basis of viral variability and evolution; and (iii) Evolution of viral pathogenicity and emerging viral infections. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121209/ doi: 10.1007/978-1-4020-8761-5_7 id: cord-001484-va0teako author: Ahmed, Sarah A. title: Rapid Identification of Black Grain Eumycetoma Causative Agents Using Rolling Circle Amplification date: 2014-12-04 words: 2922.0 sentences: 165.0 pages: flesch: 48.0 cache: ./cache/cord-001484-va0teako.txt txt: ./txt/cord-001484-va0teako.txt summary: A rapid, simple, and highly efficient molecular based method for identification of agents of black grain eumycetoma is introduced, aiming to improve diagnostic in endemic areas. Rolling circle amplification (RCA) is a powerful diagnostic method based on detection of specific nucleic-acid sequences and enzymatic amplification of circularized oligonucleotide probes under isothermal conditions [10] . The specificity of the 8 RCA probes was tested using strains of black-grain mycetoma causative species listed in table 1. Identification of mycetoma agent with phenotypic features is too limited, and physiological and biochemical techniques are laborious, time-consuming and nonspecific, whereas the currently available molecular methods based on DNA sequencing are specific but extremely expensive. We describe rolling circle amplification method for identification of black grain eumycetoma using species-specific padlock probes. In the present study we developed a simple, fast and highly specific molecular method for the identification of agents of black grain mycetoma. abstract: Accurate identification of mycetoma causative agent is a priority for treatment. However, current identification tools are far from being satisfactory for both reliable diagnosis and epidemiological investigations. A rapid, simple, and highly efficient molecular based method for identification of agents of black grain eumycetoma is introduced, aiming to improve diagnostic in endemic areas. Rolling Circle Amplification (RCA) uses species-specific padlock probes and isothermal DNA amplification. The tests were based on ITS sequences and developed for Falciformispora senegalensis, F. tompkinsii, Madurella fahalii, M. mycetomatis, M. pseudomycetomatis, M. tropicana, Medicopsis romeroi, and Trematosphaeria grisea. With the isothermal RCA assay, 62 isolates were successfully identified with 100% specificity and no cross reactivity or false results. The main advantage of this technique is the low-cost, high specificity, and simplicity. In addition, it is highly reproducible and can be performed within a single day. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4256478/ doi: 10.1371/journal.pntd.0003368 id: cord-048322-5eqdrd52 author: Aigner, Achim title: Delivery Systems for the Direct Application of siRNAs to Induce RNA Interference (RNAi) In Vivo date: 2006-05-18 words: 7333.0 sentences: 363.0 pages: flesch: 41.0 cache: ./cache/cord-048322-5eqdrd52.txt txt: ./txt/cord-048322-5eqdrd52.txt summary: The antitumorigenic effects of PEI/siRNA-mediated in vivo gene-targeting of tumor-relevant proteins like in mouse tumor xenograft models are described. The efficient protection against enzymatic or nonenzymatic degradation is particularly important for RNA molecules including siRNAs. In fact, while the therapeutic potential of siRNAs for the treatment of various diseases is in principle very promising, limitations of transfer vectors may turn out to be rate-limiting in the development of RNAi-based therapeutic strategies. Their ultimate success, however, will Figure 4 : Systemic treatment of mice with PEI-complexed HER-2-specific siRNAs leads to reduced growth of subcutaneous SKOV-3 tumor xenografts due to decreased HER-2 expression. RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo Atelocollagenmediated synthetic small interfering RNA delivery for effective gene silencing in vitro and in vivo abstract: RNA interference (RNAi) is a powerful method for specific gene silencing which may also lead to promising novel therapeutic strategies. It is mediated through small interfering RNAs (siRNAs) which sequence-specifically trigger the cleavage and subsequent degradation of their target mRNA. One critical factor is the ability to deliver intact siRNAs into target cells/organs in vivo. This review highlights the mechanism of RNAi and the guidelines for the design of optimal siRNAs. It gives an overview of studies based on the systemic or local application of naked siRNAs or the use of various nonviral siRNA delivery systems. One promising avenue is the the complexation of siRNAs with the polyethylenimine (PEI), which efficiently stabilizes siRNAs and, upon systemic administration, leads to the delivery of the intact siRNAs into different organs. The antitumorigenic effects of PEI/siRNA-mediated in vivo gene-targeting of tumor-relevant proteins like in mouse tumor xenograft models are described. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1559929/ doi: 10.1155/jbb/2006/71659 id: cord-267733-fuz8r3vj author: Al Ali, Sally title: Use of Reporter Genes in the Generation of Vaccinia Virus-Derived Vectors date: 2016-05-21 words: 7966.0 sentences: 392.0 pages: flesch: 41.0 cache: ./cache/cord-267733-fuz8r3vj.txt txt: ./txt/cord-267733-fuz8r3vj.txt summary: This broad host range allows infection of cell lines with recombinant viruses for large-scale expression of heterologous proteins, which reduces its cost This broad host range allows infection of cell lines with recombinant viruses for large-scale expression of heterologous proteins, which reduces its cost in comparison to other production systems [21, 24] . This reporter gene system has been widely used in transgenic plants, and it has also been successfully used in mammalian cells for VACV recombinant virus selection [54] . Reporter-gene assays have helped the pox virologists in basic research, for example for the study of the location, structure and function of many VACV proteins during the infection cycle and their interaction with proteins of the host cell [44, 70] . The main limitation of using VACV as a vector is the short-term gene expression, since it is a lytic virus killing the infected cells. Insertion sites for recombinant vaccinia virus construction: Effects on expression of a foreign protein abstract: Vaccinia virus (VACV) is one of the most extensively-studied viruses of the Poxviridae family. It is easy to genetically modify, so it has become a key tool for many applications. In this context, reporter genes facilitate the study of the role of foreign genes introduced into the genome of VACV. In this review, we describe the type of reporter genes that have been used to generate reporter-expressing VACV and the applications of the recombinant viruses obtained. Reporter-expressing VACV are currently employed in basic and immunology research, in the development of vaccines and cancer treatment. url: https://doi.org/10.3390/v8050134 doi: 10.3390/v8050134 id: cord-292172-aqsc9fbl author: Al Amin, Md. title: Screening of commercial meat products from supermarket chains for feline derivatives using SP-PCR-RLFP and lab-on-a-chip date: 2020-06-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Determination of feline meat in food products is an important issue for social, health, economic and religious concern. Hence this paper documented the application of species specific polymerase chain reaction-restriction fragment length polymorphism (SP-PCR-RFLP) assay targeting a short-fragments (69 bp) of mitochondrial cytochrome b (cytb) gene to screen feline meat in commercial meat products using lab-on-a-chip. The SP-PCR assay proved its specificity theoretically and experimentally while testing with different common animal, aquatic and plant species of DNA. The feline specific (69 bp, 43- and 26-bp) characteristic molecular DNA pattern was observed by SP-PCR and RFLP analysis. For assay performance, it was tested in three different types of commercial dummy meat products such as frankfurters, nuggets and meatballs and digested with AluI-restriction enzyme. The highest sensitivity of the assay using lab-on-a-chip was as low as 0.1 pg or 0.01% (w/w) in commercial dummy meat products. We have also applied this assay to screen three important commercial meat products of six different brand from six supermarket chains located at three different states of Malaysia. Thus total 378 samples were tested to validate the specificity, sensitivity, stability of the assay and utilization of it for commercial meat product screening. url: https://api.elsevier.com/content/article/pii/S0889157519302510 doi: 10.1016/j.jfca.2020.103565 id: cord-000988-79fp75u3 author: Al-Siyabi, Turkiya title: A cost effective real-time PCR for the detection of adenovirus from viral swabs date: 2013-06-07 words: 6247.0 sentences: 327.0 pages: flesch: 43.0 cache: ./cache/cord-000988-79fp75u3.txt txt: ./txt/cord-000988-79fp75u3.txt summary: Twentyseven virus culture-positive specimens and 169 virus culture-negative specimens were randomly selected and tested for the presence of HAdV using a well established in-house real-time PCR assay [18] following recovery of viral DNA was recovered by homogenization with heat treatment or automated nucleic acid extraction. This internally controlled quantitative real-time PCR assay targets the hexon gene of adenovirus, and is validated for detection Table 1 Nucleotide sequences of primers and probes used in this study The analytical sensitivity (or limit of detection, LoD) of the homogenization with heat treatment or nucleic acid extraction, in combination with the real-time PCR, was determined using 10-fold serial dilutions (in UTM) of a cultured HAdV-C type 6. Virus stock dilutions were quantified using commercial real-time PCR assay, and the LoD for homogenization or nucleic acid extraction-based protocols were shown to be approximately equivalent (Figure 2) . abstract: Compared to traditional testing strategies, nucleic acid amplification tests such as real-time PCR offer many advantages for the detection of human adenoviruses. However, commercial assays are expensive and cost prohibitive for many clinical laboratories. To overcome fiscal challenges, a cost effective strategy was developed using a combination of homogenization and heat treatment with an “in-house” real-time PCR. In 196 swabs submitted for adenovirus detection, this crude extraction method showed performance characteristics equivalent to viral DNA obtained from a commercial nucleic acid extraction. In addition, the in-house real-time PCR outperformed traditional testing strategies using virus culture, with sensitivities of 100% and 69.2%, respectively. Overall, the combination of homogenization and heat treatment with a sensitive in-house real-time PCR provides accurate results at a cost comparable to viral culture. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679997/ doi: 10.1186/1743-422x-10-184 id: cord-281883-l9yshyc7 author: Alekseeva, Ekaterina title: Enhancement of the expression of HCV core gene does not enhance core-specific immune response in DNA immunization: advantages of the heterologous DNA prime, protein boost immunization regimen date: 2009-06-08 words: 7595.0 sentences: 390.0 pages: flesch: 45.0 cache: ./cache/cord-281883-l9yshyc7.txt txt: ./txt/cord-281883-l9yshyc7.txt summary: METHODS: Plasmids encoding core with no translation initiation signal (pCMVcore); with Kozak sequence (pCMVcoreKozak); and with HCV IRES (pCMVcoreIRES) were designed and expressed in a variety of eukaryotic cells. Single immunization with plasmids directing low levels of core expression induced similar levels of cytokines, strong T-cell proliferation (pCMVcoreIRES), and antibodies in titer 10(3)(pCMVcore). Boosting with pCMVcoreKozak induced low antibody response, core-specific T-cell proliferation and IFN- secretion that subsided after the 3rd plasmid injection. Boosting with pCMVcoreKozak induced low antibody response, core-specific T-cell proliferation and IFN- secretion that subsided after the 3rd plasmid injection. Significant responses in the form of core-specific IFN- and IL-2 secretion exceeding the background levels in empty-vector-immunized mice were detected five weeks after a single administration of HCV core gene (Fig.5) . Only the heterologous DNA-prime-protein boost regimen induced a significant core-specific antibody production and potent T-cell response of mainly Th1-profile. Enhancement of cellular and humoral immune responses to hepatitis C virus core protein using DNA-based vaccines augmented with cytokine-expressing plasmids abstract: BACKGROUND: Hepatitis C core protein is an attractive target for HCV vaccine aimed to exterminate HCV infected cells. However, although highly immunogenic in natural infection, core appears to have low immunogenicity in experimental settings. We aimed to design an HCV vaccine prototype based on core, and devise immunization regimens that would lead to potent anti-core immune responses which circumvent the immunogenicity limitations earlier observed. METHODS: Plasmids encoding core with no translation initiation signal (pCMVcore); with Kozak sequence (pCMVcoreKozak); and with HCV IRES (pCMVcoreIRES) were designed and expressed in a variety of eukaryotic cells. Polyproteins corresponding to HCV 1b amino acids (aa) 1–98 and 1–173 were expressed in E. coli. C57BL/6 mice were immunized with four 25-μg doses of pCMVcoreKozak, or pCMV (I). BALB/c mice were immunized with 100 μg of either pCMVcore, or pCMVcoreKozak, or pCMVcoreIRES, or empty pCMV (II). Lastly, BALB/c mice were immunized with 20 μg of core aa 1–98 in prime and boost, or with 100 μg of pCMVcoreKozak in prime and 20 μg of core aa 1–98 in boost (III). Antibody response, [(3)H]-T-incorporation, and cytokine secretion by core/core peptide-stimulated splenocytes were assessed after each immunization. RESULTS: Plasmids differed in core-expression capacity: mouse fibroblasts transfected with pCMVcore, pCMVcoreIRES and pCMVcoreKozak expressed 0.22 ± 0.18, 0.83 ± 0.5, and 13 ± 5 ng core per cell, respectively. Single immunization with highly expressing pCMVcoreKozak induced specific IFN-γ and IL-2, and weak antibody response. Single immunization with plasmids directing low levels of core expression induced similar levels of cytokines, strong T-cell proliferation (pCMVcoreIRES), and antibodies in titer 10(3)(pCMVcore). Boosting with pCMVcoreKozak induced low antibody response, core-specific T-cell proliferation and IFN-γ secretion that subsided after the 3rd plasmid injection. The latter also led to a decrease in specific IL-2 secretion. The best was the heterologous pCMVcoreKozak prime/protein boost regimen that generated mixed Th1/Th2-cellular response with core-specific antibodies in titer ≥ 3 × 10(3). CONCLUSION: Thus, administration of highly expressed HCV core gene, as one large dose or repeated injections of smaller doses, may suppress core-specific immune response. Instead, the latter is induced by a heterologous DNA prime/protein boost regimen that circumvents the negative effects of intracellular core expression. url: https://www.ncbi.nlm.nih.gov/pubmed/19505299/ doi: 10.1186/1479-0556-7-7 id: cord-103735-nil1vv6h author: Alfano, Niccolo title: Non-invasive surveys of mammalian viruses using environmental DNA date: 2020-03-29 words: 5829.0 sentences: 373.0 pages: flesch: 53.0 cache: ./cache/cord-103735-nil1vv6h.txt txt: ./txt/cord-103735-nil1vv6h.txt summary: Using a curated set of RNA oligonucleotides based on the ViroChip microarray assay [7] as baits in a hybridization capture system, multiple mammalian RNA and DNA viruses were detected from both eDNA and iDNA samples. Highlights Environmental DNA (water and blood-sucking leeches) provided a non-invasive method of screening wildlife for viruses A comprehensive viral RNA oligonucleotide bait set was developed to capture known and unknown mammalian virus diversity Leech blood meal host determination and viruses identified were congruent Viruses determined from water correlated with known and observed species visiting the water sources In brief Alfano, Dayaram, et al. In filtered water and sediment samples collected from the same waterhole, only one virus per sample was generally identified and in one location (WM20 and SM20) contigs from different viral families were isolated based on sample type. We provide evidence that environmental and invertebrate-derived DNA samples including waterhole water, sediment and wild haematophagous terrestrial leeches can be used to survey known and unknown viruses. abstract: Environmental DNA (eDNA) and its subdiscipline, invertebrate-derived DNA (iDNA) have been used to survey biodiversity non-invasively [1,2]. Water is ubiquitous in most ecosystems, and, among invertebrates, terrestrial haematophagous leeches are abundant and can be easily collected in many tropical rainforests [3,4]. Such non-invasive nucleic acid sources can mitigate difficulties of obtaining wildlife samples, particularly in remote areas or for rare species. Recently, eDNA/iDNA sources have been applied to monitoring specific wildlife pathogens [5,6]. However, previous studies have focused on known pathogens, whereas most wildlife pathogens are uncharacterized and unknown. Non-invasive approaches to monitoring known and novel pathogens may be of particular benefit in ecosystems prone to viral emergence, many of which occur in areas where invasive sampling is challenging, such as tropical rainforests. Here, we show that both eDNA from natural waterholes, and iDNA from terrestrial haematophagous leeches, can be used to detect unknown viruses circulating in mammalian hosts (Figure 1). Using a curated set of RNA oligonucleotides based on the ViroChip microarray assay [7] as baits in a hybridization capture system, multiple mammalian RNA and DNA viruses were detected from both eDNA and iDNA samples. Congruence was found between host DNA assignment and viruses identified in leeches, and between animals observed visiting the waterholes and the viruses detected. Our results demonstrate that eDNA/iDNA samples may represent an effective non-invasive resource for studying wildlife viral diversity. Several of the detected viruses were novel, highlighting the potential of eDNA/iDNA for epidemiological analysis of emerging viruses prior to their emergence. Highlights Environmental DNA (water and blood-sucking leeches) provided a non-invasive method of screening wildlife for viruses A comprehensive viral RNA oligonucleotide bait set was developed to capture known and unknown mammalian virus diversity Leech blood meal host determination and viruses identified were congruent Viruses determined from water correlated with known and observed species visiting the water sources In brief Alfano, Dayaram, et al. demonstrate that environmental DNA from southeast Asian leech bloodmeals and waterholes from Africa and Mongolia can be used as to detect viruses circulating in wildlife. These nucleic acid sources may represent an effective non-invasive resource for studying wildlife viral diversity and emerging viruses pre-emergence. url: https://doi.org/10.1101/2020.03.26.009993 doi: 10.1101/2020.03.26.009993 id: cord-104321-fpoztmcl author: Almasi, Mohammad Amin title: Loop Mediated Isothermal Amplification (LAMP) for Embryo Sex Determination in Pregnant Women at Eight Weeks of Pregnancy date: 2017 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: In human, SRY (sex-determining region of the Y chromosome) is the major gene for the testis-determining factor which is found in normal XY males and in the rare XX males, and it is absent in normal XX females and many XY females. There are several methods which can indicate a male genotype by the presence of the amplified product of SRY gene. The aim of this study was to identify the SRY gene for embryo sex determination in human during pregnancy using loop mediated isothermal amplification (LAMP) method. METHODS: A total of 15 blood samples from pregnant women at eight weeks of pregnancy were collected, and Plasma DNA was extracted. LAMP assay was performed using DNA obtained for detection of SRY gene. Furthermore, colorimetric LAMP assay for rapid and easy detection of SRY gene was developed. RESULTS: LAMP results revealed that the positive reaction was highly specific only with samples containing XY chromosomes, while no amplification was found in samples containing XX chromosomes. A total of 15 blood samples from pregnant women were seven male embryos (46.6%) and eight female embryos (53.4%). All used visual components in the colorimetric assay could successfully make a clear distinction between positive and negative ones. CONCLUSION: The LAMP assay developed in this study is a valuable tool capable of monitoring the purity and detection of SRY gene for sex determination. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359858/ doi: nan id: cord-018133-2otxft31 author: Altman, Russ B. title: Bioinformatics date: 2006 words: 9592.0 sentences: 462.0 pages: flesch: 46.0 cache: ./cache/cord-018133-2otxft31.txt txt: ./txt/cord-018133-2otxft31.txt summary: Experimentation and bioinformatics have divided the research into several areas, and the largest are: (1) genome and protein sequence analysis, (2) macromolecular structure-function analysis, (3) gene expression analysis, and (4) proteomics. With the completion of the human genome and the abundance of sequence, structural, and gene expression data, a new field of systems biology that tries to understand how proteins and genes interact at a cellular level is emerging. The Entrez system from the National Center for Biological Information (NCBI) gives integrated access to the biomedical literature, protein, and nucleic acid sequences, macromolecular and small molecular structures, and genome project links (including both the Human Genome Project and sequencing projects that are attempting to determine the genome sequences for organisms that are either human pathogens or important experimental model organisms) in a manner that takes advantages of either explicit or computed links between these data resources. abstract: Why is sequence, structure, and biological pathway information relevant to medicine? Where on the Internet should you look for a DNA sequence, a protein sequence, or a protein structure? What are two problems encountered in analyzing biological sequence, structure, and function? How has the age of genomics changed the landscape of bioinformatics? What two changes should we anticipate in the medical record as a result of these new information sources? What are two computational challenges in bioinformatics for the future? url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122933/ doi: 10.1007/0-387-36278-9_22 id: cord-022037-4ik3jxjy author: Alvarez, Mar title: CANTILEVER BIOSENSORS date: 2008-07-05 words: 6805.0 sentences: 310.0 pages: flesch: 41.0 cache: ./cache/cord-022037-4ik3jxjy.txt txt: ./txt/cord-022037-4ik3jxjy.txt summary: Nanomechanical sensors are derived from the microfabricated cantilevers used in atomic force microscopy (AFM) and are based on the bending or resonance change induced in the cantilever when, for example, a biomolecular interaction takes place on one of its surfaces. The sensitivity of microcantilevers for measuring intermolecular forces, the commercial availability of cantilevers, and their fabrication using standard microelectronic technology resulted, around 1994, in a new type of sensor where the transducer system is based on a silicon microcantilever with a tipless free end (Figure 10 .6) (Gimzewski et al., 1994; Chen et al., 1995) . Biochemical applications for this type of sensor have been specifically developed for bending-based modes of measurement, with an optical read-out, due to the complexity required for working with the dynamic mode in liquids. Currently, there are many different and alternative ways to increase the sensitivity of cantilever-based biosensors, depending on the sensor working mode. abstract: This chapter describes the application of nano- and micro-electromechanical systems (NEMs and MEMs), and more specifically microcantilever structures, as transducers for highly sensitive biosensors. In these devices, named as ‘nanomechanical biosensors,’ a biomolecular interaction produces a change in the mechanical behavior of the transducer (a movement at nanometer scale), which can be measured and analyzed in real time. Microcantilevers translate the molecular recognition of biomolecules into a nanomechanical motion that is commonly coupled to an optical read-out system. This chapter discusses the main aspects regarding the physics of microcantilever as well the optical read-out techniques. It reviews the state-of-the-art, and discusses the prospective future directions of this new family of biosensors. Nanomechanical sensors are derived from the microfabricated cantilevers used in atomic force microscopy (AFM) and are based on the bending or resonance change induced in the cantilever when a biomolecular interaction takes place on one of its surfaces. The cantilever response depends on its mechanical properties, which are determined mainly by their spring constant and resonance frequency. Both parameters depend on the cantilever material and its geometry. The increasing number of applications of microcantilevers as biosensors has established these systems as a versatile platform for real-time and in situmeasurements of physical, chemical, and biochemical interactions. Further research is banked upon to provide information for increasing the biosensor sensitivity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152376/ doi: 10.1016/b978-044453125-4.50012-7 id: cord-019050-a9datsoo author: Ambrogi, Federico title: Bioinformatics and Nanotechnologies: Nanomedicine date: 2014 words: 8851.0 sentences: 367.0 pages: flesch: 31.0 cache: ./cache/cord-019050-a9datsoo.txt txt: ./txt/cord-019050-a9datsoo.txt summary: In this chapter we focus on the bioinformatics strategies for translating genome-wide expression analyses into clinically useful cancer markers with a specific focus on breast cancer with a perspective on new diagnostic device tools coming from the field of nanobiotechnology and the challenges related to high-throughput data integration, analysis, and assessment from multiple sources. In this chapter we focus on the bioinformatics strategies for translating genome-wide expression analyses into clinically useful cancer markers with a specific focus on breast cancer with a perspective on new diagnostic device tools coming from the field of nanobiotechnology and the challenges related to high-throughput data integration, analysis, and assessment from multiple sources. In particular, DNA microarray-based technology, with the simultaneous evaluation of thousands of genes, has provided researchers with an opportunity to perform comprehensive molecular and genetic profiling of breast cancer able to classify it into some clinically relevant subtypes and in the attempt to predict the prognosis or the response to treatment [32.5-8]. abstract: In this chapter we focus on the bioinformatics strategies for translating genome-wide expression analyses into clinically useful cancer markers with a specific focus on breast cancer with a perspective on new diagnostic device tools coming from the field of nanobiotechnology and the challenges related to high-throughput data integration, analysis, and assessment from multiple sources. Great progress in the development of molecular biology techniques has been seen since the discovery of the structure of deoxyribonucleic acid (DNA) and the implementation of a polymerase chain reaction (PCR) method. This started a new era of research on the structure of nucleic acids molecules, the development of new analytical tools, and DNA-based analyses that allowed the sequencing of the human genome, the completion of which has led to intensified efforts toward comprehensive analysis of mammalian cell struc ture and metabolism in order to better understand the mechanisms that regulate normal cell behavior and identify the gene alterations responsible for a broad spectrum of human diseases, such as cancer, diabetes, cardiovascular diseases, neurodegenerative disorders, and others. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124100/ doi: 10.1007/978-3-642-30574-0_32 id: cord-000436-k1hwh640 author: Amidi, Maryam title: Antigen-expressing immunostimulatory liposomes as a genetically programmable synthetic vaccine date: 2010-10-26 words: 5886.0 sentences: 313.0 pages: flesch: 47.0 cache: ./cache/cord-000436-k1hwh640.txt txt: ./txt/cord-000436-k1hwh640.txt summary: To show proof-of-concept for this artificial cell-based platform, a bacterial in vitro transcription and translation system together with a gene construct encoding the model antigen β-galactosidase were entrapped inside multilamellar liposomes. Vaccination studies in mice showed that such antigen-expressing immunostimulatory liposomes (AnExILs) elicited higher specific humoral immune responses against the produced antigen (β-galactosidase) than control vaccines (i.e. AnExILs without genetic input, liposomal β-galactosidase or pDNA encoding β-galactosidase). Here, we show that AnExILs expressing b-galactosidase are well tolerated after i.m. injection and were capable of inducing strong systemic immune responses, which were superior to that of liposomal DNA or protein vaccines encoding the same antigen. Characterization of AnExILs and liposomes loaded with b-galactosidase and/or pDNA Cell-free protein synthesis was used to transcribe and translate the lacZ gene encoding for E. AnExILs combine antigen-production, delivery and adjuvanticity in one system, making them more potent in inducing antibody responses compared to liposomal DNA vaccines as shown here. abstract: Liposomes are versatile (sub)micron-sized membrane vesicles that can be used for a variety of applications, including drug delivery and in vivo imaging but they also represent excellent models for artificial membranes or cells. Several studies have demonstrated that in vitro transcription and translation can take place inside liposomes to obtain compartmentalized production of functional proteins within the liposomes (Kita et al. in Chembiochem 9(15):2403–2410, 2008; Moritani et al.in FEBS J, 2010; Kuruma et al. in Methods Mol Biol 607:161–171, 2010; Murtas et al. in Biochem Biophys Res Commun 363(1):12–17, 2007; Sunami et al. in Anal Biochem 357(1):128–136, 2006; Ishikawa et al. in FEBS Lett 576(3):387–390, 2004; Oberholzer et al. in Biochem Biophys Res Commun 261(2):238–241, 1999). Such a minimal artificial cell-based model is ideal for synthetic biology based applications. In this study, we propose the use of liposomes as artificial microbes for vaccination. These artificial microbes can be genetically programmed to produce specific antigens at will. To show proof-of-concept for this artificial cell-based platform, a bacterial in vitro transcription and translation system together with a gene construct encoding the model antigen β-galactosidase were entrapped inside multilamellar liposomes. Vaccination studies in mice showed that such antigen-expressing immunostimulatory liposomes (AnExILs) elicited higher specific humoral immune responses against the produced antigen (β-galactosidase) than control vaccines (i.e. AnExILs without genetic input, liposomal β-galactosidase or pDNA encoding β-galactosidase). In conclusion, AnExILs present a new platform for DNA-based vaccines which combines antigen production, adjuvanticity and delivery in one system and which offer several advantages over existing vaccine formulations. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159695/ doi: 10.1007/s11693-010-9066-z id: cord-350004-o151wwcf author: An, D. J. title: A DNA miniarray system for simultaneous visual detection of porcine circovirus type 1 (PCV1) and 2 (PCV2) in pigs date: 2008-07-24 words: 3260.0 sentences: 169.0 pages: flesch: 53.0 cache: ./cache/cord-350004-o151wwcf.txt txt: ./txt/cord-350004-o151wwcf.txt summary: title: A DNA miniarray system for simultaneous visual detection of porcine circovirus type 1 (PCV1) and 2 (PCV2) in pigs PMWS postweaning multisystemic wasting syndrome PDNS porcine dermatitis and nephropathy syndrome PCVAD porcine circovirus associated disease Introduction PCV1 is widespread in the swine population of many countries based on serological surveys (Allan and Ellis 2000) , and is a persistent contaminant of the porcine kidney cell line PK-15 (Tischer et al. Detection is based on a colorimetric reaction following the hybridization of amplified viral DNA that contains a biotinylated nucleotide (biotin-16-dUTP) with oligonucleotide probes that are dotted on a nylon membrane (Quere et al. The objective of this study was to develop a DNA miniarray for the simultaneous detection of PCV1 and PCV2 in pigs with non-PMWS, PMWS and/or PDNS. In conclusion, we have developed a DNA miniarray for simultaneous detection of PCVs that provides similar level of sensitivity (100%) and specificity (98.9%) as in situ hybridization. abstract: A miniarray system was developed for the simultaneous detection of porcine circovirus type 1 (PCV1) and type 2 (PCV2) in pigs. The system consists of a polymerase chain reaction (PCR) step to amplify target viral DNA, followed by detection of the amplified DNA using a membrane-anchored probe array and an avidin-alkaline phosphatase (Av-AP) indicator system. The lower limit of detection of PCV using the miniarray was 10(1.9) tissue culture infectious dose 50 (TCID(50))/ml and 10(2.08)TCID(50)/ml for PCV1 and PCV2, respectively, and 100 viral copies/μl for both PCV1 and PCV2. We validated the miniarray system using 141 lymph node specimens from pigs with suspected postweaning multisystemic wasting syndrome or porcine dermatitis and nephropathy syndrome. Of the 141 samples evaluated, 55 were identified as positive for PCV by the miniarray. Relative to in situ hybridization, the sensitivity and specificity of the miniarray was 100% and 98.9%, respectively. In contrast to other microarray systems, the miniarray does not require a DNA chip reader, since the results can be determined by visual inspection of colorized spots on a nylon membrane. This system represents an effective alternative method for the differential detection of PCV1 and PCV2 in pigs, as well as the maintenance of PCV-free cell lines and pre-screening of commercial vaccines for possible contamination. url: https://www.ncbi.nlm.nih.gov/pubmed/18651234/ doi: 10.1007/s11259-008-9080-8 id: cord-013415-110b95cg author: Aquino-Martinez, Ruben title: Periodontal Disease and Senescent Cells: New Players for an Old Oral Health Problem? date: 2020-10-09 words: 10333.0 sentences: 522.0 pages: flesch: 27.0 cache: ./cache/cord-013415-110b95cg.txt txt: ./txt/cord-013415-110b95cg.txt summary: Although the host immune response rapidly protects against bacterial invasion, oxidative stress generated during inflammation can indirectly deteriorate periodontal tissues through the damage to vital cell macromolecules, including DNA. In contrast to transient DNA damage, persistent genomic lesions promote constitutive DNA damage signaling and cellular senescence, which is correlated with increased secretion of inflammatory signals [26, 30] In agreement with this observation, several studies have reported that premature senescence can also be induced by exposing human cells to subtoxic H 2 O 2 concentrations [31, 32] . As a consequence of chronological aging, the burden of senescent cells increases in different tissues in humans, mice, and other species, where they contribute to the development of chronic pathologies including arthritis, osteoporosis, Alzheimer''s disease, atherosclerosis, cancer, and diabetes [58, 59] Similar to other agerelated pathologies, the etiology of diabetes may be the result of the impact of different aging mechanism, including stem cell exhaustion, chronic low-grade inflammation, macromolecular damage, and cellular senescence. abstract: The recent identification of senescent cells in periodontal tissues has the potential to provide new insights into the underlying mechanisms of periodontal disease etiology. DNA damage-driven senescence is perhaps one of the most underappreciated delayed consequences of persistent Gram-negative bacterial infection and inflammation. Although the host immune response rapidly protects against bacterial invasion, oxidative stress generated during inflammation can indirectly deteriorate periodontal tissues through the damage to vital cell macromolecules, including DNA. What happens to those healthy cells that reside in this harmful environment? Emerging evidence indicates that cells that survive irreparable genomic damage undergo cellular senescence, a crucial intermediate mechanism connecting DNA damage and the immune response. In this review, we hypothesize that sustained Gram-negative bacterial challenge, chronic inflammation itself, and the constant renewal of damaged tissues create a permissive environment for the abnormal accumulation of senescent cells. Based on emerging data we propose a model in which the dysfunctional presence of senescent cells may aggravate the initial immune reaction against pathogens. Further understanding of the role of senescent cells in periodontal disease pathogenesis may have clinical implications by providing more sophisticated therapeutic strategies to combat tissue destruction. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587987/ doi: 10.3390/ijms21207441 id: cord-255536-x1z2o9gs author: Artusi, Sara title: The Herpes Simplex Virus-1 genome contains multiple clusters of repeated G-quadruplex: Implications for the antiviral activity of a G-quadruplex ligand date: 2015-04-03 words: 4823.0 sentences: 261.0 pages: flesch: 55.0 cache: ./cache/cord-255536-x1z2o9gs.txt txt: ./txt/cord-255536-x1z2o9gs.txt summary: The remarkably high guanine content of the Herpes Simplex Virus-1 (HSV-1) genome prompted us to investigate both the presence of G-quadruplex forming sequences in the viral genome and the possibility to target them with G-quadruplex ligands to obtain anti-HSV-1 effects with a novel mechanism of action. BRACO-19 was able to inhibit Taq polymerase processing at G-quadruplex forming sequences in the HSV-1 genome, and decreased intracellular viral DNA in infected cells. In the Epstein-Barr herpes virus (EBV), G-quadruplexes modulate EBV nuclear antigen 1 (EBNA1) activity and translation (Murat et al., 2014) ; in particular, BRACO-19 inhibited EBNA1-dependent stimulation of viral DNA replication http://dx.doi.org/10.1016/j.antiviral.2015.03.016 0166-3542/Ó 2015 Elsevier B.V. All rights reserved. We demonstrate that treatment with the G-quadruplex ligand BRACO-19 greatly stabilizes these sequences resulting in decrease of infectious viral particles, reduction of late viral transcripts, inhibition of Taq polymerase processing at the HSV-1 genome, specifically affecting viral DNA replication at G-quadruplex regions. abstract: Guanine-rich nucleic acids can fold into G-quadruplexes, secondary structures implicated in important regulatory functions at the genomic level in humans, prokaryotes and viruses. The remarkably high guanine content of the Herpes Simplex Virus-1 (HSV-1) genome prompted us to investigate both the presence of G-quadruplex forming sequences in the viral genome and the possibility to target them with G-quadruplex ligands to obtain anti-HSV-1 effects with a novel mechanism of action. Using biophysical, molecular biology and antiviral assays, we showed that the HSV-1 genome displays multiple clusters of repeated sequences that form very stable G-quadruplexes. These sequences are mainly located in the inverted repeats of the HSV-1 genome. Treatment of HSV-1 infected cells with the G-quadruplex ligand BRACO-19 induced inhibition of virus production. BRACO-19 was able to inhibit Taq polymerase processing at G-quadruplex forming sequences in the HSV-1 genome, and decreased intracellular viral DNA in infected cells. The last step targeted by BRACO-19 was viral DNA replication, while no effect on virus entry in the cells was observed. This work, presents the first evidence of extended G-quadruplex sites in key regions of the HSV-1 genome, indicates the possibility to block viral DNA replication by G-quadruplex-ligand and therefore provides a proof of concept for the use of G-quadruplex ligands as new anti-herpetic therapeutic options. url: https://www.sciencedirect.com/science/article/pii/S0166354215000807 doi: 10.1016/j.antiviral.2015.03.016 id: cord-283807-4yo27web author: Ashtari, Parviz title: An efficient method for recovery of target ssDNA based on amino-modified silica-coated magnetic nanoparticles date: 2005-09-15 words: 2980.0 sentences: 185.0 pages: flesch: 47.0 cache: ./cache/cord-283807-4yo27web.txt txt: ./txt/cord-283807-4yo27web.txt summary: title: An efficient method for recovery of target ssDNA based on amino-modified silica-coated magnetic nanoparticles Abstract In this paper, an improved recovery method for target ssDNA using amino-modified silica-coated magnetic nanoparticles (ASMNPs) is reported. In this paper, we reported an improved method for recovery of target ssDNA using amino-modified silica-coated magnetic nanoparticles (ASMNPs). Then, 1 ml of 4.1 × 10 −6 M biotin-labeled capture ssDNA(I) (5 -biotin-AAAAAAAAAAGTATCACGAGGCCCTATGCG-3 ) solution was added to the streptavidin derivatived amino-modified silica-coated magnetic nanoparticles and reacted at room temperature for 4 h. The method scheme for recovery of target ssDNA based on amino-modified silica-coated magnetic nanoparticles (ASMNPs). and hybridized with the capture ssDNA to form the DNA bio-conjugate, and it can be separated from the solution under the magnet field due to the magnetic characteristics of the amino-modified silica-coated magnetic nanoparticles. abstract: Abstract In this paper, an improved recovery method for target ssDNA using amino-modified silica-coated magnetic nanoparticles (ASMNPs) is reported. This method takes advantages of the amino-modified silica-coated magnetic nanoparticles prepared using water-in-oil microemulsion technique, which employs amino-modified silica as the shell and iron oxide as the core of the magnetic nanoparticles. The nanoparticles have a silica surface with amino groups and can be conjugated with any desired bio-molecules through many existing amino group chemistry. In this research, a linear DNA probe was immobilized onto nanoparticles through streptavidin conjugation using covalent bonds. A target ssDNA(I) (5′-TMR-CGCATAGGGCCTCGTGATAC-3′) has been successfully recovered from a crude sample under a magnet field through their special recognition and hybridization. A designed ssDNA fragment of severe acute respiratory syndrome (SARS) virus at a much lower concentration than the target ssDNA(I) was also recovered with high efficiency and good selectivity. url: https://api.elsevier.com/content/article/pii/S0039914005003917 doi: 10.1016/j.talanta.2005.06.043 id: cord-004561-cer5ifac author: Astua-Monge, G. title: Evidence for a prokaryotic insertion-sequence contamination in eukaryotic sequences registered in different databases date: 2002 words: 3807.0 sentences: 200.0 pages: flesch: 52.0 cache: ./cache/cord-004561-cer5ifac.txt txt: ./txt/cord-004561-cer5ifac.txt summary: An insertion-sequence of prokaryotic origin was detected in a genomic clone obtained from a Phaseolus vulgaris bacterial artificial chromosome (BAC) library. Southern hybridization of EcoRI-digested BnBAC25 and BnBAC55 clones vulgaris BAC clones resulting from the insertion of the prokaryotic transposable element IS10R. C A southern-blot of several BAC clones showing that only the mutant BnBAC55::IS10R has a 4.1-kb fragment that hybridizes to a probe derived from the IS10R sequence. The presence of the 2.3-kb EcoRV fragment in all clones after prolonged subculturing suggested that IS10R Fig. 2 Sample BAC filter-hybridization results with the IS10R sequence as a probe. BAC DNA prepared from the intensely hybridizing clones possesses a common restriction fragment that contains part of the IS10R sequence database sequence entries from diverse eukaryotic sources that include humans, Arabidopsis, yeast and Drosophila, among others. abstract: An insertion-sequence of prokaryotic origin was detected in a genomic clone obtained from a Phaseolus vulgaris bacterial artificial chromosome (BAC) library. This BAC clone, characterized as part of a contig constructed near a virus resistance gene, exhibited restriction fragment length polymorphism with an overlapping clone of the contig. Restriction analysis of DNA obtained from individual colonies of the stock culture indicated the presence of a mixed population of wild-type and insertional mutants. Sequence analysis of both members of the population revealed the presence of IS10R, an insertion-sequence from Escherichia coli. A BLAST search for IS10-like sequences detected unexpected homologies with a large number of eukaryotic sequences from Homo sapiens, Arabidopsis thaliana, Drosophila melanogaster and Caenorhabditis elegans. Southern analysis of a random sample of BAC clones failed to detect IS10 in the BAC DNA. However, prolonged sub-culturing of a set of 15 clones resulted in transposition into the BAC DNA. Eventually, all cultures acquired a 2.3-kb fragment that hybridized strongly with IS10. Sequence analysis revealed the presence of a preferred site for transposition in the BAC vector. These results indicate that a large number, if not all, of the BAC libraries from different organisms are contaminated with IS10R. The source of this element has been identified as the DH10B strain of E. coli used as the host for BAC libraries. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079927/ doi: 10.1007/s001220200005 id: cord-017208-7oew461e author: Aurigemma, Rosemarie title: Regulatory Aspects in the Development of Gene Therapies date: 2005 words: 18290.0 sentences: 816.0 pages: flesch: 37.0 cache: ./cache/cord-017208-7oew461e.txt txt: ./txt/cord-017208-7oew461e.txt summary: Table 1 Beyond a Good Idea: What the Successful Investigator Has Already Done With a Project Leading to Commercial Development Defined candidate biologic (or molecule) Made comparisons with similar products Characteristics of product are consistent with pharmaceutical requirements Production scale is adequate Product characterization is adequate Laboratory reference standard exists In vitro potency assay has been developed Stability studies develop confidence product is a "drug" Reproducible model systems have confirmed in vivo activity with clinical product Early animal work includes some toxicology Scale-up requirements practical for initial clinical trials In general, reflects experience and scientific maturity of investigator In addition to the US agencies that develop the regulations that govern drug development and licensing, the International Conference on Harmonization (ICH) was formed in April 1990 involving the United States, the European Union, and Japan to address the issue of globalizing such regulations. abstract: Preclinical therapeutics development research is directed toward fulfilling two overlapping sets of goals. A set of scientific goals includes defining the best molecule or biologic construct for the task at hand, and proving the case for its development. The second set of goals addresses regulatory requirements necessary to introduce the agent into human subjects. In the case of “small molecule” drugs, in most cases the identity of the molecule and appropriate safety studies are straightforward. In contrast, the development of biologic agents, including gene therapies discussed here, presents distinct challenges. The nature of the “drug” may be an organism subject to mutation or selection of variants through recombination. Its properties may vary depending on the scale and method of its preparation, purification, and storage. How to test adequately for its safety prior to first introduction in humans may not be straightforward owing to intrinsic differences in response to the agent expected in humans as compared to animals. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121712/ doi: 10.1007/978-1-59259-785-7_29 id: cord-258665-8q3tsggm author: Aydın, Hakan Berk title: Pixelated colorimetric nucleic acid assay date: 2020-03-01 words: 4056.0 sentences: 225.0 pages: flesch: 45.0 cache: ./cache/cord-258665-8q3tsggm.txt txt: ./txt/cord-258665-8q3tsggm.txt summary: Herein, we report a pixelated analysis approach for correlating colorimetric responses of CPE with nucleic acid concentrations down to 1 nM, in plasma samples, utilizing a smart phone with an algorithm that can perform analytical testing and data processing. A smart phone application is developed to capture and digitize the colorimetric response of the individual pixels of the digital images of CPE on the PVDF membrane, followed by an analysis using the algorithm. The proposed pixelated approach enables precise quantification of nucleic acid assay concentrations, thereby eliminating the margin of error involved in conventional methodologies adopted for interpretation of colorimetric responses, for instance, RGB analysis. Herein, we propose a smart phone application algorithm that evaluates the colorimetric responses based on a pixel level analysis approach, enabling quantification of nucleic acids with high precision at clinically relevant concentration ranges. A cartridge-based point of care assay for colorimetric detection of nucleic acids has been developed using a smart phone algorithm. abstract: Abstract Conjugated polyelectrolytes (CPEs) have been widely used as reporters in colorimetric assays targeting nucleic acids. CPEs provide naked eye detection possibility by their superior optical properties however, as concentration of target analytes decrease, trace amounts of nucleic acid typically yield colorimetric responses that are not readily perceivable by naked eye. Herein, we report a pixelated analysis approach for correlating colorimetric responses of CPE with nucleic acid concentrations down to 1 nM, in plasma samples, utilizing a smart phone with an algorithm that can perform analytical testing and data processing. The detection strategy employed relies on conformational transitions between single stranded nucleic acid-cationic CPE duplexes and double stranded nucleic acid-CPE triplexes that yield distinct colorimetric responses for enabling naked eye detection of nucleic acids. Cationic poly[N,N,N-triethyl-3-((4-methylthiophen-3-yl)oxy)propan-1-aminium bromide] is utilized as the CPE reporter deposited on a polyvinylidene fluoride (PVDF) membrane for nucleic acid assay. A smart phone application is developed to capture and digitize the colorimetric response of the individual pixels of the digital images of CPE on the PVDF membrane, followed by an analysis using the algorithm. The proposed pixelated approach enables precise quantification of nucleic acid assay concentrations, thereby eliminating the margin of error involved in conventional methodologies adopted for interpretation of colorimetric responses, for instance, RGB analysis. The obtained results illustrate that a ubiquitous smart phone could be utilized for point of care colorimetric nucleic acids assays in complex matrices without requiring sophisticated software or instrumentation. url: https://www.ncbi.nlm.nih.gov/pubmed/31892020/ doi: 10.1016/j.talanta.2019.120581 id: cord-102270-rfhtlodc author: Azhar, Mohd. title: Rapid, field-deployable nucleobase detection and identification using FnCas9 date: 2020-04-21 words: 3971.0 sentences: 217.0 pages: flesch: 50.0 cache: ./cache/cord-102270-rfhtlodc.txt txt: ./txt/cord-102270-rfhtlodc.txt summary: We then fixed the position of this mutation with respect to PAM and changed every other base in the sgRNA sequence to identify which combination led to complete loss of cleavage of a wild type substrate in an in vitro cleavage (IVC) assay with FnCas9 ( Figure 1B, Supplementary Figure 1A ). Taken together, these experiments suggest that FELUDA design can be universally used for detection of SNVs and and would not require extensive optimization or validation steps for new SNVs. To aid users for quick design and implementation of FELUDA for a target SNV, we have developed a webtool JATAYU (Junction for Analysis and Target Design for Your FELUDA assay) that incorporates the above features and generates primer sequences for amplicon and sgRNA synthesis (https:// jatayu.igib.res.in, Supplementary Figure 2 ). abstract: Detection of pathogenic sequences or variants in DNA and RNA through a point-of-care diagnostic approach is valuable for rapid clinical prognosis. In recent times, CRISPR based detection of nucleic acids has provided an economical and quicker alternative to sequencing-based platforms which are often difficult to implement in the field. Here, we present FnCas9 Editor Linked Uniform Detection Assay (FELUDA) that employs a highly accurate enzymatic readout for detecting nucleotide sequences, identifying nucleobase identity and inferring zygosity with precision. We demonstrate that FELUDA output can be adapted to multiple signal detection platforms and can be quickly designed and deployed for versatile applications including rapid diagnosis during infectious disease outbreaks like COVID-19. url: https://doi.org/10.1101/2020.04.07.028167 doi: 10.1101/2020.04.07.028167 id: cord-280605-2i4gk7et author: Bachmann, María Consuelo title: The Challenge by Multiple Environmental and Biological Factors Induce Inflammation in Aging: Their Role in the Promotion of Chronic Disease date: 2020-10-14 words: 11128.0 sentences: 559.0 pages: flesch: 32.0 cache: ./cache/cord-280605-2i4gk7et.txt txt: ./txt/cord-280605-2i4gk7et.txt summary: With increasing age, the dynamics and proportion of lymphocytes and myeloid cells differ depending on the sex due to the differential expression of 144 genes of the immune response in men and women (71) . Anti-inflammatory effect of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and their biologically active metabolites (D and E Resolvinsmediators derived from omega-3 fatty acids, primarily EPA and DHA that block the production of proinflammatory mediators and regulate leukocyte trafficking to inflammatory sites) can be mediated through one of the mechanisms capable of reducing inflammation of RAW-264.7 cells and of primary intraperitoneal macrophages (105) . Exposure to various alarm signals induce an acute inflammation that, when associated with deleterious environmental and biological factors, potentiates chronic inflammation, which can be further promoted by excess ROS production and oxidative stress that results from mitochondrial dysfunction or NOX2 activity, leading to inflammaging and eventually to age-related disease. abstract: The aging process is driven by multiple mechanisms that lead to changes in energy production, oxidative stress, homeostatic dysregulation and eventually to loss of functionality and increased disease susceptibility. Most aged individuals develop chronic low-grade inflammation, which is an important risk factor for morbidity, physical and cognitive impairment, frailty, and death. At any age, chronic inflammatory diseases are major causes of morbimortality, affecting up to 5–8% of the population of industrialized countries. Several environmental factors can play an important role for modifying the inflammatory state. Genetics accounts for only a small fraction of chronic-inflammatory diseases, whereas environmental factors appear to participate, either with a causative or a promotional role in 50% to 75% of patients. Several of those changes depend on epigenetic changes that will further modify the individual response to additional stimuli. The interaction between inflammation and the environment offers important insights on aging and health. These conditions, often depending on the individual’s sex, appear to lead to decreased longevity and physical and cognitive decline. In addition to biological factors, the environment is also involved in the generation of psychological and social context leading to stress. Poor psychological environments and other sources of stress also result in increased inflammation. However, the mechanisms underlying the role of environmental and psychosocial factors and nutrition on the regulation of inflammation, and how the response elicited for those factors interact among them, are poorly understood. Whereas certain deleterious environmental factors result in the generation of oxidative stress driven by an increased production of reactive oxygen and nitrogen species, endoplasmic reticulum stress, and inflammation, other factors, including nutrition (polyunsaturated fatty acids) and behavioral factors (exercise) confer protection against inflammation, oxidative and endoplasmic reticulum stress, and thus ameliorate their deleterious effect. Here, we discuss processes and mechanisms of inflammation associated with environmental factors and behavior, their links to sex and gender, and their overall impact on aging. url: https://www.ncbi.nlm.nih.gov/pubmed/33162985/ doi: 10.3389/fimmu.2020.570083 id: cord-016628-ljzsg9up author: Bajpai, Bhakti title: High Capacity Vectors date: 2013-10-22 words: 4070.0 sentences: 215.0 pages: flesch: 52.0 cache: ./cache/cord-016628-ljzsg9up.txt txt: ./txt/cord-016628-ljzsg9up.txt summary: An ideal cloning vehicle would have the following four properties: • Low-molecular weight • Ability to confer readily selectable phenotypic traits on host cells • Single sites for a large number of restriction endonucleases, preferably in genes with a scorable phenotype • Ability to replicate within the host cell, so that numerous copies of the recombinant DNA molecule can be produced and passed to daughter cells. The examples of naturally occurring or artificially constructed vectors include vectors based on Escherichia coli plasmids, bacteriophages (e.g., k, M13, P1), viruses (e.g., animal viruses-retrovirus, adenovirus, adeno-associated virus, Herpes Simplex virus, Vaccinia virus, etc.; insect viruses-baculo virus; plant viruses-cauliflower mosaic virus, potato virus X, Gemini virus, etc.), Agrobacterium tumefaciens based vectors, chimeric plasmids (e.g., cosmid, phagemid, phasmid, and fosmid), artificial chromosomes [e.g., YAC, BAC, PAC, MAC and HAC], and non-E. abstract: Since the construction of the first generation of general cloning vectors in the early 1970s, a large number of cloning vectors have been developed. Despite the bewildering choice of commercial and other available vectors, the selection of cloning vector to be used can be decided by applying a small number of criteria: insert size, copy number, incompatibility, selectable marker cloning sites, and specialized vector functions. Several of these criteria are dependent on each other. Most general cloning plasmids can carry a DNA insert up to around 15 kb in size. Several types of vectors are available for cloning large fragments of DNA too. This chapter presents a consolidated account of some new generation of high-capacity vectors such as cosmid, yeast artificial chromosome (YAC) , bacterial artificial chromosome (BAC), P1 phage artificial chromosome (PAC), and human artificial chromosome (HAC). url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120981/ doi: 10.1007/978-81-322-1554-7_1 id: cord-347569-9fvbshz2 author: Balakrishnan, Krishnan Nair title: Multiple gene targeting siRNAs for down regulation of Immediate Early-2 (Ie2) and DNA polymerase genes mediated inhibition of novel rat Cytomegalovirus (strain All-03) date: 2020-10-27 words: 8627.0 sentences: 513.0 pages: flesch: 53.0 cache: ./cache/cord-347569-9fvbshz2.txt txt: ./txt/cord-347569-9fvbshz2.txt summary: On the other hand, negative control siRNA and untreated groups showed higher viral titer than siRNA treated groups: 4 log 10 TCID50/ml at day 10 p.i and 8 log 10 TCID50/ml at day 18 p.i. Analysis of RCMV ALL-03 infected cells undergoing apoptosis/necrosis upon combination siRNAs treatment were studied using flow cytometry. Taking into consideration as positive treatment control group, commercial drug GCV exhibited better rate of CPE inhibition (Fig. 7) compared to other combination siR-NAs but lesser efficient than dpc + ie2b siRNAs. In order to understand more on the role of each combination siRNAs during RCMV ALL-03 infection, all the four combination siRNAs targeting different regions were analyzed individually with specific primers. During the search of effective treatment for CMV, idea of controlling the disease by means of inhibiting virus replication and gene expression by combinations of two and more siRNAs had been explored in this study. abstract: BACKGROUND: Cytomegalovirus (CMV) is an opportunistic pathogen that causes severe complications in congenitally infected newborns and non-immunocompetent individuals. Developing an effective vaccine is a major public health priority and current drugs are fronting resistance and side effects on recipients. In the present study, with the aim of exploring new strategies to counteract CMV replication, several anti-CMV siRNAs targeting IE2 and DNA polymerase gene regions were characterized and used as in combinations for antiviral therapy. METHODS: The rat embryo fibroblast (REF) cells were transfected with multi siRNA before infecting with CMV strain ALL-03. Viral growth inhibition was measured by tissue culture infectious dose (TCID50), cytopathic effect (CPE) and droplet digital PCR (ddPCR) while IE2 and DNA polymerase gene knockdown was determined by real-time PCR. Ganciclovir was deployed as a control to benchmark the efficacy of antiviral activities of respective individual siRNAs. RESULTS: There was no significant cytotoxicity encountered for all the combinations of siRNAs on REF cells analyzed by MTT colorimetric assay (P > 0.05). Cytopathic effects (CPE) in cells infected by RCMV ALL-03 had developed significantly less and at much slower rate compared to control group. The expression of targeted genes was downregulated successfully resulted in significant reduction (P < 0.05) of viral mRNA and DNA copies (dpb + dpc: 79%, 68%; dpb + ie2b: 68%, 60%; dpb + dpc + ie2b: 48%, 42%). Flow cytometry analysis showed a greater percentage of viable and early apoptosis of combined siRNAs-treated cells compared to control group. Notably, the siRNAs targeting gene regions were sequenced and mutations were not encountered, thereby avoiding the formation of mutant with potential resistant viruses. CONCLUSIONS: In conclusion. The study demonstrated a tremendous promise of innovative approach with the deployment of combined siRNAs targeting at several genes simultaneously with the aim to control CMV replication in host cells. url: https://www.ncbi.nlm.nih.gov/pubmed/33109247/ doi: 10.1186/s12985-020-01436-5 id: cord-292033-zkwiag7a author: Balboni, Andrea title: Molecular analysis of carnivore Protoparvovirus detected in white blood cells of naturally infected cats date: 2018-02-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Cats are susceptible to feline panleukopenia virus (FPV) and canine parvovirus (CPV) variants 2a, 2b and 2c. Detection of FPV and CPV variants in apparently healthy cats and their persistence in white blood cells (WBC) and other tissues when neutralising antibodies are simultaneously present, suggest that parvovirus may persist long-term in the tissues of cats post-infection without causing clinical signs. The aim of this study was to screen a population of 54 cats from Sardinia (Italy) for the presence of both FPV and CPV DNA within buffy coat samples using polymerase chain reaction (PCR). The DNA viral load, genetic diversity, phylogeny and antibody titres against parvoviruses were investigated in the positive cats. RESULTS: Carnivore protoparvovirus 1 DNA was detected in nine cats (16.7%). Viral DNA was reassembled to FPV in four cats and to CPV (CPV-2b and 2c) in four cats; one subject showed an unusually high genetic complexity with mixed infection involving FPV and CPV-2c. Antibodies against parvovirus were detected in all subjects which tested positive to DNA parvoviruses. CONCLUSIONS: The identification of FPV and CPV DNA in the WBC of asymptomatic cats, despite the presence of specific antibodies against parvoviruses, and the high genetic heterogeneity detected in one sample, confirmed the relevant epidemiological role of cats in parvovirus infection. url: https://doi.org/10.1186/s12917-018-1356-9 doi: 10.1186/s12917-018-1356-9 id: cord-032220-u5oo7mj2 author: Bao, Mengdi title: Magnetic Bead-Quantum Dot (MB-Qdot) Clustered Regularly Interspaced Short Palindromic Repeat Assay for Simple Viral DNA Detection date: 2020-09-04 words: 4825.0 sentences: 300.0 pages: flesch: 52.0 cache: ./cache/cord-032220-u5oo7mj2.txt txt: ./txt/cord-032220-u5oo7mj2.txt summary: [Image: see text] We have developed a novel detection system that couples clustered regularly interspaced short palindromic repeat-Cas recognition of target sequences, Cas-mediated nucleic acid probe cleavage, and quantum dots as highly sensitive reporter molecules for simple detection of viral nucleic acid targets. 18, 19 However, most of the CRISPR-Cas detection systems utilize reporter probes with organic dyes and quenchers that require external instruments and possess a high fluorescence background, which limits overall sensitivity. 20 In this study, we develop a novel probe system for CRISPR-Cas nucleic acid assays that use quantum dots (Qdots) as a reporter. After magnetic isolation, a high fluorescence intensity (∼14 counts) was detected, indicating that the MB-Qdot conjugate is mainly achieved by DNA complementary hybridization rather than non-specific absorption (control, blue). To avoid bulky and complicated sensing instruments, in this work, we developed a simple visual detection system coupled with quantum dots as an ultra-brightness indicator and CRISPR-Cas12a assay for isothermal viral DNA target sensing. abstract: [Image: see text] We have developed a novel detection system that couples clustered regularly interspaced short palindromic repeat-Cas recognition of target sequences, Cas-mediated nucleic acid probe cleavage, and quantum dots as highly sensitive reporter molecules for simple detection of viral nucleic acid targets. After target recognition and Cas-mediated cleavage of biotinylated ssDNA probe molecules, the probe molecules are bound to magnetic beads. A complementary ssDNA oligonucleotide quantum dot conjugate is then added, which only hybridizes to uncleaved probes on the magnetic beads. After separating hybridized quantum dots, the collected supernatant is illuminated by a portable ultraviolet flashlight, and it provides a simple “Yes-or-No” nucleic acid detection answer. By using a DNA target matching part of the African swine fever virus, detection limits of ∼0.5 and ∼1.25 nM are achieved in buffer and porcine plasma, respectively. The positive samples are readily confirmed by visual inspection, completely avoiding the need for complicated devices and instruments. This work establishes the feasibility of a simple assay for nucleic acid screening in both hospitals and point-of-care settings. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500431/ doi: 10.1021/acsami.0c12482 id: cord-281188-0cql96hu author: Baquero, Fernando title: Proximate and ultimate causes of the bactericidal action of antibiotics date: 2020-10-06 words: 8715.0 sentences: 411.0 pages: flesch: 36.0 cache: ./cache/cord-281188-0cql96hu.txt txt: ./txt/cord-281188-0cql96hu.txt summary: (1) only free drug is active against the target bacteria, and protein binding of the drug decreases the rate of killing 19 ; (2) there are structures (such as porins) and mechanisms facilitating drug uptake, but also barriers that prevent the drug from entering the cells 20 ; (3) the drug can be pumped out, so the concentration needed for killing takes longer to achieve 21, 22 ; (4) the antibiotics with weak target-binding affinity will take longer to achieve the doses necessary for killing than those with greater affinity 23 ; (5) the targeted function might increase in the presence of the drug, thereby compensating for the inhibition by the drug 24 ; (6) the target function corresponds to the build-up of a cellular structure with slow turnover, which increases the amount of time for the antibiotic to kill 25,26 ; (7) the cells repair the damage produced by the antibiotics at rates that differ between drugs 27 ; (8) the damaged bacteria have inducible antibiotic-deactivating mechanisms 28 ; (9) the bacteria use alternative metabolic pathways that, to some extent, bypass those inhibited by the antibiotic 29, 30 ; (10) antibiotics differ in the extent to which they induce reactive oxygen species (ROS; deleterious) or SOS (potentially protective) responses and thereby the rate at which they kill the exposed bacteria [31] [32] [33] [34] ; (11) members of the antibiotic-exposed populations are either www.nature.com/nrmicro not replicating or are replicating slowly, and as such are killed at lower rates than the more active members of the population or their death is delayed; (12) the antibiotics produce a kind of ''stationary phase'' by activating the general RpoS-mediated stringent response 35 . abstract: During the past 85 years of antibiotic use, we have learned a great deal about how these ‘miracle’ drugs work. We know the molecular structures and interactions of these drugs and their targets and the effects on the structure, physiology and replication of bacteria. Collectively, we know a great deal about these proximate mechanisms of action for virtually all antibiotics in current use. What we do not know is the ultimate mechanism of action; that is, how these drugs irreversibly terminate the ‘individuality’ of bacterial cells by removing barriers to the external world (cell envelopes) or by destroying their genetic identity (DNA). Antibiotics have many different ‘mechanisms of action’ that converge to irreversible lethal effects. In this Perspective, we consider what our knowledge of the proximate mechanisms of action of antibiotics and the pharmacodynamics of their interaction with bacteria tell us about the ultimate mechanisms by which these antibiotics kill bacteria. url: https://doi.org/10.1038/s41579-020-00443-1 doi: 10.1038/s41579-020-00443-1 id: cord-001859-d62iuk72 author: Baquero-Pérez, Belinda title: Hsp70 Isoforms Are Essential for the Formation of Kaposi’s Sarcoma-Associated Herpesvirus Replication and Transcription Compartments date: 2015-11-20 words: 15958.0 sentences: 876.0 pages: flesch: 50.0 cache: ./cache/cord-001859-d62iuk72.txt txt: ./txt/cord-001859-d62iuk72.txt summary: Similar Hsc70 localization was seen during early lytic replication (12 h reactivation), when RTA protein was diffuse in the nucleus, Successful enrichment of the nuclear envelope region and associated KSHV RTCs in HEK-293T rKSHV.219 cells. These results clearly demonstrate that KSHV specifically redistributes the molecular chaperones, Hsc70 and iHsp70, from the cytoplasm to the nucleus, in contrast to Grp78, which coincides with the initial formation of KSHV RTCs. Treatment with the small molecule inhibitor VER-155008 abrogated viral protein synthesis at non-cytotoxic concentrations Members of the HSP70 chaperone family possess an N-terminal nucleotide binding domain with ATPase activity which is essential for their function. Therefore to ascertain whether Hsp70 isoforms could stabilise the essential KSHV lytic proteins RTA and ORF57, TREx BCBL1-RTA cells were reactivated for 24 h to allow sufficient viral protein expression followed by addition of DMSO control or VER-155008 in conjunction with cycloheximide (CHX) at 50 μg/ml to block de novo protein synthesis. abstract: Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus associated with various AIDS-related malignancies. Like other herpesviruses, multiple processes required for KSHV lytic replication, including viral transcription, viral DNA synthesis and capsid assembly occur in virus-induced intranuclear structures, termed replication and transcription compartments (RTCs). Here we utilised a novel methodology, combining subcellular fractionation and quantitative proteomics, to identify cellular proteins which are recruited to KSHV-induced RTCs and thus play a key role in KSHV lytic replication. We show that several isoforms of the HSP70 chaperone family, Hsc70 and iHsp70, are redistributed from the cytoplasm into the nucleus coinciding with the initial formation of KSHV-induced RTCs. We demonstrate that nuclear chaperone foci are dynamic, initially forming adjacent to newly formed KSHV RTCs, however during later time points the chaperones move within KSHV RTCs and completely co-localise with actively replicating viral DNA. The functional significance of Hsp70 isoforms recruitment into KSHV RTCs was also examined using the specific Hsp70 isoform small molecule inhibitor, VER-155008. Intriguingly, results highlight an essential role of Hsp70 isoforms in the KSHV replication cycle independent of protein stability and maturation. Notably, inhibition of Hsp70 isoforms precluded KSHV RTC formation and RNA polymerase II (RNAPII) relocalisation to the viral genome leading to the abolishment of global KSHV transcription and subsequent viral protein synthesis and DNA replication. These new findings have revealed novel mechanisms that regulate KSHV lytic replication and highlight the potential of HSP70 inhibitors as novel antiviral agents. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654589/ doi: 10.1371/journal.ppat.1005274 id: cord-016313-n4ewq0pt author: Baranyi, Lajos title: Advances in Lentiviral Vector-based Cell Therapy with Mesenchymal Stem Cells date: 2012-09-27 words: 20575.0 sentences: 824.0 pages: flesch: 39.0 cache: ./cache/cord-016313-n4ewq0pt.txt txt: ./txt/cord-016313-n4ewq0pt.txt summary: The field of possible application of mesenchymal stem cells in medicine and research expanded tremendously with the advent of improved Lentiviral-vectors capable of inserting stable copies of genes of interest and expressing proteins or biologically active RNA species ad libitum, performing delicate gene editing or active gene silencing or serving as advanced drug delivery systems utilized in ex vivo cell therapy. Implantation of Lentiviral vector-transduced human bone marrow mesenchymal cells using collagen scaffolds into immunode fi cient mice resulted in ef fi cient engraftment of gene-engineered cells and provided sites for transgene-expression in vivo. Moreover, it did not alter the differentiation potential of either HSCs or MSCs. In addition, the therapeutic potential of CD133+ and MSC progenitor cells transduced ex vivo with Lentiviral vector encoding the mature form of vascular endothelial growth factor D (VEGF-D ) or the enhanced green fl uorescent protein (eGFP) marker gene achieved permanent gene expression. abstract: The field of possible application of mesenchymal stem cells in medicine and research expanded tremendously with the advent of improved Lentiviral-vectors capable of inserting stable copies of genes of interest and expressing proteins or biologically active RNA species ad libitum, performing delicate gene editing or active gene silencing or serving as advanced drug delivery systems utilized in ex vivo cell therapy. The combination of these two fields has created a number of new areas of research in the landscape of modern medicine which are now extensively studied and discussed here. These areas include tissue engineering, tissue repair, wound healing and tissue implants, anticancer therapies, angiogenesis, myocardial infarction and repair as well as understanding and treating acute lung damage and injury. In addition, genetically modified, tagged MSCs are being intensively deployed in research and therapeutic attempts of the various ailments of the central nervous system including Parkinson’s disease, Alzheimer’s disease, various phases of acute ischemia and trauma. The emergence of new and important data for type II diabetes research is being followed with treatment suggestions and studies of senescence to find novel applications for genetically engineered MSCs. We find in ­general that genetically modified MSCs are at the cusp of breaking through from basic research into the next phase of clinical trials. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120558/ doi: 10.1007/978-1-62703-200-1_14 id: cord-307914-lgprrwee author: Bartok, Eva title: Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids date: 2020-07-14 words: 17726.0 sentences: 1100.0 pages: flesch: 51.0 cache: ./cache/cord-307914-lgprrwee.txt txt: ./txt/cord-307914-lgprrwee.txt summary: Indeed, the functionalization of CRISPR/Cas systems as a tool for genomic editing have revealed important differences in human and murine NA sensing, including distinct cell subset expression patterns of NA-sensing Toll-Like Receptors (TLRs) or species differences in the structural requirements for the detection of cyclic dinucleotide cGAMP by STING. As a long dsRNA with a 5 0 diphosphate terminus, polyI:C is known to activate the sensing receptors TLR3, MDA5, and RIG-I (Alexopoulou et al., 2001; Gitlin et al., 2006; Kato et al., 2008; Yoneyama et al., 2005) , accessory proteins such including LGP2 and members of the DDX and DHX families (reviewed in Oshiumi et al., 2016) as well as the restriction factors PKR and the OAS family (Farrell et al., 1978; Hovanessian et al., 1977; Zilberstein et al., 1978) . abstract: All lifeforms have developed highly sophisticated systems equipped to detect altered self and non-self nucleic acids (NA). In vertebrates, NA-sensing receptors safeguard the integrity of the organism by detecting pathogens, dyshomeostasis and damage, and inducing appropriate responses to eliminate pathogens and reconstitute homeostasis. Effector mechanisms include i) immune signaling, ii) restriction of NA functions such as inhibition of mRNA translation, and iii) cell death pathways. An appropriate effector response is necessary for host defense, but dysregulated NA-sensing can lead to devastating autoimmune and autoinflammatory disease. Their inherent biochemical similarity renders the reliable distinction between self NA under homeostatic conditions and altered or exogenous NA particularly challenging. In this review, we provide an overview of recent progress in our understanding of the closely coordinated and regulated network of innate immune receptors, restriction factors, and nucleases to effectively respond to pathogens and maintain host integrity. url: https://doi.org/10.1016/j.immuni.2020.06.014 doi: 10.1016/j.immuni.2020.06.014 id: cord-018265-twp33bb6 author: Becker, Pablo D. title: Community-acquired pneumonia: paving the way towards new vaccination concepts date: 2007 words: 14121.0 sentences: 697.0 pages: flesch: 36.0 cache: ./cache/cord-018265-twp33bb6.txt txt: ./txt/cord-018265-twp33bb6.txt summary: A live vaccine based on a master virus strain developed at the Institute of Applied Microbiology (Austria) by growing wild influenza virus in Vero cells at 25°C was also demonstrated to be safe, well-tolerated and immunogenic after intranasal immunization in young adults [18]. Candidate vaccines should be able to replicate and induce a protective immune response in young infants, even in the presence of maternally acquired antibodies. This demonstrates that antibodies play a major role in protection against this disease, whereas T-cell immunity targeted to internal viral proteins appears to contribute to clearance. The second generation of PS-based conjugate vaccines stimulates stronger antibody responses, even in infants, young children and immune deficient individuals, as well as immunological memory. The resulting proteins are then used to perform immunological and/or functional studies to select the most promising candidates (e.g., able to induce the production of microbicidal or neutralizing antibodies, capacity to confer protective immunity). abstract: Despite the availability of antimicrobial agents and vaccines, community-acquired pneumonia remains a serious problem. Severe forms tend to occur in very young children and among the elderly, since their immune competence is eroded by immaturity and immune senescence, respectively. The main etiologic agents differ according to patient age and geographic area. Streptococcus pneumoniae, Haemophilus influenzae, respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV-3) are the most important pathogens in children, whereas influenza viruses are the leading cause of fatal pneumonia in the elderly. Effective vaccines are available against some of these organisms. However, there are still many agents against which vaccines are not available or the existent ones are suboptimal. To tackle this problem, empiric approaches are now being systematically replaced by rational vaccine design. This is facilitated by the growing knowledge in the fields of immunology, microbial pathogenesis and host response to infection, as well as by the availability of sophisticated strategies for antigen selection, potent immune modulators and efficient antigen delivery systems. Thus, a new generation of vaccines with improved safety and efficacy profiles compared to old and new agents is emerging. In this chapter, an overview is provided about currently available and new vaccination concepts. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123104/ doi: 10.1007/978-3-7643-7563-8_10 id: cord-281565-v8s2ski3 author: Belmonte-Reche, Efres title: Exploring G and C-quadruplex structures as potential targets against the severe acute respiratory syndrome coronavirus 2 date: 2020-08-20 words: 4545.0 sentences: 253.0 pages: flesch: 53.0 cache: ./cache/cord-281565-v8s2ski3.txt txt: ./txt/cord-281565-v8s2ski3.txt summary: These PQS and PiMS have been assessed according to their potential to form, uniqueness, frequency of appearance, conservation rates between 3297 different 2019-nCoV clinical cases, confirmed quadruplex-forming sequence presence and localization within the genome. Then, these PQS and PiMS were evaluated by their frequency of appearance in the corresponding genome, the presence of known-to-form quadruplex structures sequences within and their probability of quadruplex-formation score (as the mean of G4Hunter (52) and the adaptation of the PQSfinder algorithm (53) ). A flexible configuration of quadruplex definitions will detect larger amounts of candidates at the expense of requiring more computing power and accepting sequences that are more ambiguous in forming quadruplex structures in vitro (as determined by their score; with longer loops, smaller runs, more bulges and more complementary G/C %, Figure 1 , B). Expanding the search for common candidates to the entire virus realm, we matched one PQS and PiMS from the 2019-nCoV with the potential quadruplexes found in four viruses from abstract: In this paper we report the analysis of the 2019-nCoV genome and related viruses using an upgraded version of the open-source algorithm G4-iM Grinder. This version improves the functionality of the software, including an easy way to determine the potential biological features affected by the candidates found. The quadruplex definitions of the algorithm were optimized for 2019-nCoV. Using a lax quadruplex definition ruleset, which accepts amongst other parameters two residue G- and C-tracks, hundreds of potential quadruplex candidates were discovered. These sequences were evaluated by their in vitro formation probability, their position in the viral RNA, their uniqueness and their conservation rates (calculated in over three thousand different COVID-19 clinical cases and sequenced at different times and locations during the ongoing pandemic). These results were compared sequentially to other Coronaviridae members, other Group IV (+)ssRNA viruses and the entire realm. Sequences found in common with other species were further analyzed and characterized. Sequences with high scores unique to the 2019-nCoV were studied to investigate the variations amongst similar species. Quadruplex formation of the best candidates was then confirmed experimentally. Using NMR and CD spectroscopy, we found several highly stable RNA quadruplexes that may be suitable theranostic targets against the 2019-nCoV. GRAPHICAL ABSTRACT url: https://doi.org/10.1101/2020.08.19.257493 doi: 10.1101/2020.08.19.257493 id: cord-000248-zueoyesj author: Berretta, Regina title: Cancer Biomarker Discovery: The Entropic Hallmark date: 2010-08-18 words: 33594.0 sentences: 1678.0 pages: flesch: 43.0 cache: ./cache/cord-000248-zueoyesj.txt txt: ./txt/cord-000248-zueoyesj.txt summary: These authors cite, for example, ''''mitochondrial dysfunction'''' [5, 6] (including, but not limited to ''''glucose avidity'''' [7] and ''''a shift in glucosemetabolism from oxidative phosphorylation to glycolysis'''' [6, 8] , ''''altered glycolysis'''' [9] , ''''altered bioenergetic function of mitochondria'''' [10] ), ''''dysregulation of cell cycle and defective genome-integrity checkpoints'''' [11] , ''''aberrant DNA methylation'''' [12] (''''promoter hypermethylation of hallmark cancer genes'''' [13] and ''''CpG island hypermethylation and global genomic hypomethylation'''' [14] ), ''''shift in cellular metabolism'''' [15, 16, 17] , ''''regional hypoxia'''' [18] , ''''microenviroment acidosis'''' [19] , ''''abnormal microRNA regulation'''' [20, 21] , ''''aneuploidy'''' and ''''chromosome aberrations'''' [22, 23, 24, 25, 26] , ''''disruption of cellular junctions'''' [27] , ''''avoidance of the immune response'''' [28] , ''''pre-existing chronic inflammatory conditions'''' [29, 30] , ''''cancerrelated inflammation'''' [29] , ''''disabled autophagy'''' [28] , ''''impaired cellular senescence'''' [31] , ''''altered NF-kappaB signalling'''' [32] , ''''altered growth patterns, not altered growth per se'''' [33] , ''''disregulated DNA methylation and histone modifications'''' [34] , ''''tissue dedifferentiation'''' [35, 36] , and ''''somatically heritable molecular alterations'''' [37] . abstract: BACKGROUND: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. METHODOLOGY/PRINCIPAL FINDINGS: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. CONCLUSIONS/SIGNIFICANCE: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-througput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923618/ doi: 10.1371/journal.pone.0012262 id: cord-283461-xcyvisqu author: Berthelot, Jean-Marie title: Kawasaki-like diseases and thrombotic coagulopathy in COVID-19: delayed over-activation of the STING pathway? date: 2020-07-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We previously made the hypothesis that STING contributes to COVID-19. The present review detail new arguments for over-activation of STING pathways in COVID-19, following the description of hyper-coagulability and Kawasaki-like diseases in children. Indeed, Kawasaki disease is induced by overreaction of innate cells following exposition to various viruses, including herpes viruses which trigger STING. It predisposes to diffuse vasculitis and aneurysms, whereas STING is over-expressed in arterial aneurisms. The redness at the inoculation site of bacillus Calmette-Guérin, a specific feature of Kawasaki disease, is reproduced by activation of the STING pathway, which is inhibited upstream by aspirin, intravenous immunoglobulins, and Vitamin-D. SARS-CoV2 binding to ACE2 can lead to excessive angiotensin II signaling, which activates the STING pathway in mice. Over-activation of the STING-pathway promotes hyper-coagulability through release of interferon-β and tissue factor by monocytes-macrophages. Aspirin and dipyridamole, besides their anti-platelet activity, also reduce tissue factor procoagulant activity, and aspirin inhibits the STING pathway upstream of STING. Aspirin and dipyridamole may be used, in combination with drugs blocking downstream the activation of the STING pathway, like inhibitors of IL-6R and JAK/STAT pathways. The risk of bleeding should be low as bleeding has not been reported in severe COVID-19 patients. url: https://doi.org/10.1080/22221751.2020.1785336 doi: 10.1080/22221751.2020.1785336 id: cord-318276-so5jooj0 author: Bertholet, Christine title: Vaccinia virus produces late mRNAs by discontinuous synthesis date: 1987-07-17 words: 6225.0 sentences: 329.0 pages: flesch: 60.0 cache: ./cache/cord-318276-so5jooj0.txt txt: ./txt/cord-318276-so5jooj0.txt summary: RNA was isolated from noninfected or infected cells and then hybridized to 32P-labeled probes isolated from the 5'' end region, upstream of the 11K coding sequences of cDNA clones 3, 8, and 9 (see Figure 2 ). To confirm this, and to identify the regions from which they are transcribed, the cDNA-derived probes used in the previous experiment were hybridized to cloned DNA restriction fragments representing the entire vaccinia virus genome ( Figure 4 ). %P-labeled DNA probes (~3, ~9, p9, pllK) derived from the 5'' region of the corresponding cDNA clones or from genomic DNA (see Figure 2 ) were hybridized lo RNA isolated from uninfected (HeLa) or infected (Early, Late) cells, or to tRNA immobilized on a nitrocellulose membrane. Total late RNA from infected cells protected fragments of 127 and 128 nucleotides of the genomic probe, consistent with the previous experiments, which demonstrated that the sequence complementarity between the genomic DNA and 11K mRNA ends just upstream of the 11K ATG codon. abstract: Abstract We describe the unusual structure of a vaccinia virus late mRNA. In these molecules, the protein-coding sequences of a major late structural polypeptide are preceded by long leader RNAs, which in some cases are thousands of nucleotides long. These sequences map to different regions of the viral genome and in one instance are separated from the late gene by more than 100 kb of DNA. Moreover, the leader sequences map either upstream or downstream of the late gene, are transcribed from either DNA strand, and are fused to the late gene coding sequence via a poly(A) stretch. This demonstrates that vaccinia virus produces late mRNAs by tagging the protein-coding sequences onto the 3′ end of other RNAs. url: https://www.sciencedirect.com/science/article/pii/009286748790211X doi: 10.1016/0092-8674(87)90211-x id: cord-102866-40s64455 author: Bhadra, Sanchita title: One enzyme reverse transcription qPCR using Taq DNA polymerase date: 2020-05-30 words: 2863.0 sentences: 161.0 pages: flesch: 58.0 cache: ./cache/cord-102866-40s64455.txt txt: ./txt/cord-102866-40s64455.txt summary: To verify this activity and to determine whether Taq polymerasemediated reverse transcription might be leveraged for single enzyme RNA detection, we carried out the CDC-approved SARS-CoV-2-specific N1 TaqMan RT-qPCR assay using only Taq DNA polymerase and its accompanying commercial reaction buffer, ThermoPol, (New England Biolabs) seeded with different copies of N gene armored RNA (Asuragen), a commercial template preparation that is devoid of DNA. Even though the only polymerase present in these reactions was Taq DNA polymerase (NEB), and no dedicated reverse transcriptase was added, amplification curves were generated in response to 3 x 10 5 , 3 x 10 4 , and 3 x 10 3 copies of the SARS-CoV-2 N gene armored RNA templates (Figure 1 ). Similar to our results with armored N gene RNA, the NEB Taq DNA polymerase was able to perform TaqMan RT-qPCR analysis of SARS-CoV-2 viral genomic RNA with all three CDC assays (Figure 2 ). abstract: Taq DNA polymerase, one of the first thermostable DNA polymerases to be discovered, has been typecast as a DNA-dependent DNA polymerase commonly employed for PCR. However, Taq polymerase belongs to the same DNA polymerase superfamily as the Molony murine leukemia virus reverse transcriptase and has in the past been shown to possess reverse transcriptase activity. We report optimized buffer and salt compositions that promote the reverse transcriptase activity of Taq DNA polymerase, and thereby allow it to be used as the sole enzyme in TaqMan RT-qPCR reactions. We demonstrate the utility of Taq-alone RT-qPCR reactions by executing CDC SARS-CoV-2 N1, N2, and N3 TaqMan RT-qPCR assays that could detect as few as 2 copies/µL of input viral genomic RNA. url: https://doi.org/10.1101/2020.05.27.120238 doi: 10.1101/2020.05.27.120238 id: cord-304869-l6a68tqn author: Bielińska-Wąż, Dorota title: Graphical and numerical representations of DNA sequences: statistical aspects of similarity date: 2011-08-28 words: 15408.0 sentences: 940.0 pages: flesch: 60.0 cache: ./cache/cord-304869-l6a68tqn.txt txt: ./txt/cord-304869-l6a68tqn.txt summary: As a consequence, different aspects of similarity, as for example asymmetry of the gene structure, may be studied either using new similarity measures associated with four-component spectral representation of the DNA sequences or using alignment methods with corrections introduced in this paper. The corrections to the alignment methods and the statistical distribution moment-based descriptors derived from the four-component spectral representation of the DNA sequences are applied to similarity/dissimilarity studies of β-globin gene across species. How to restrict the graphs representing the sequences to two-dimensional plots and how to avoid degeneracies has been the subject of numerous studies which resulted in many graphical representations (see subsequent chapters). It is shown in the last chapter of this work that by using the four-component spectral representation one can recognize the difference in one base between a pair of sequences so it can be used for single nucleotide polymorfism (SNP) analyses which is subject of many investigation, as for example, in a recent work by Bhasi et al. abstract: New approaches aiming at a detailed similarity/dissimilarity analysis of DNA sequences are formulated. Several corrections that enrich the information which may be derived from the alignment methods are proposed. The corrections take into account the distributions along the sequences of the aligned bases (neglected in the standard alignment methods). As a consequence, different aspects of similarity, as for example asymmetry of the gene structure, may be studied either using new similarity measures associated with four-component spectral representation of the DNA sequences or using alignment methods with corrections introduced in this paper. The corrections to the alignment methods and the statistical distribution moment-based descriptors derived from the four-component spectral representation of the DNA sequences are applied to similarity/dissimilarity studies of β-globin gene across species. The studies are supplemented by detailed similarity studies for histones H1 and H4 coding sequences. The data are described according to the latest version of the EMBL database. The work is supplemented by a concise review of the state-of-art graphical representations of DNA sequences. url: https://www.ncbi.nlm.nih.gov/pubmed/32214591/ doi: 10.1007/s10910-011-9890-8 id: cord-252536-gfx4cq03 author: Bieniossek, Christoph title: MultiBac: expanding the research toolbox for multiprotein complexes date: 2011-12-07 words: 7120.0 sentences: 354.0 pages: flesch: 39.0 cache: ./cache/cord-252536-gfx4cq03.txt txt: ./txt/cord-252536-gfx4cq03.txt summary: It consists of an array of small synthetic DNA plasmids, an engineered baculovirus genome derived from the Autographa californica nuclear polyhedrosis virus (AcNPV; see Glossary) that is used to infect cells of the caterpillar Spodoptera frugiperda, and a set of protocols detailing every step from gene insertion into the plasmids to production of protein complexes in cultured insect cells [19, 20] . Donors and acceptors contain a resistance marker, a short imperfect inverted repeat (LoxP), an expression cassette consisting of a baculoviral promoter (p10 or polh), a DNA segment for inserting heterologous genes, and an efficient signal for eukaryotic polyadenylation (Figure 1a ). Two outstanding examples of the utility of MultiBac are the elegant production of the entire anaphase promoting complex, APC/Ca large (1.1 MDa) 13-subunit multiprotein assembly that regulates defined cell cycle transitions [34] and the recent crystal structure elucidation of the Mediator head modulea transcription factor complex that is essential for the expression of class II genes in eukaryotes [35] . abstract: Protein complexes composed of many subunits carry out most essential processes in cells and, therefore, have become the focus of intense research. However, deciphering the structure and function of these multiprotein assemblies imposes the challenging task of producing them in sufficient quality and quantity. To overcome this bottleneck, powerful recombinant expression technologies are being developed. In this review, we describe the use of one of these technologies, MultiBac, a baculovirus expression vector system that is particularly tailored for the production of eukaryotic multiprotein complexes. Among other applications, MultiBac has been used to produce many important proteins and their complexes for their structural characterization, revealing fundamental cellular mechanisms. url: https://www.ncbi.nlm.nih.gov/pubmed/22154230/ doi: 10.1016/j.tibs.2011.10.005 id: cord-000012-p56v8wi1 author: Bigot, Yves title: Molecular evidence for the evolution of ichnoviruses from ascoviruses by symbiogenesis date: 2008-09-18 words: 6419.0 sentences: 293.0 pages: flesch: 44.0 cache: ./cache/cord-000012-p56v8wi1.txt txt: ./txt/cord-000012-p56v8wi1.txt summary: CONCLUSION: Our results provide molecular evidence supporting the origin of ichnoviruses from ascoviruses by lateral transfer of ascoviral genes into ichneumonid wasp genomes, perhaps the first example of symbiogenesis between large DNA viruses and eukaryotic organisms. With respect to both species number and mechanisms that lead to successful parasitism, endoparasitic wasps are known to inject secretions at oviposition, but only a few lineages use viruses or virus-like particles (VLPs) to evade or to suppress host defences. Extending our investigations to proteins encoded by open reading frames of certain ascoviruses and bracoviruses, hosts and bacteria, in the light of recent analyses about the involvement of the replication machinery of virus groups related to ascoviruses in lateral gene transfer [29] , we discuss the robustness and the limits of the molecular evidence supporting an ascovirus origin for ichnovirus lineages. abstract: BACKGROUND: Female endoparasitic ichneumonid wasps inject virus-like particles into their caterpillar hosts to suppress immunity. These particles are classified as ichnovirus virions and resemble ascovirus virions, which are also transmitted by parasitic wasps and attack caterpillars. Ascoviruses replicate DNA and produce virions. Polydnavirus DNA consists of wasp DNA replicated by the wasp from its genome, which also directs particle synthesis. Structural similarities between ascovirus and ichnovirus particles and the biology of their transmission suggest that ichnoviruses evolved from ascoviruses, although molecular evidence for this hypothesis is lacking. RESULTS: Here we show that a family of unique pox-D5 NTPase proteins in the Glypta fumiferanae ichnovirus are related to three Diadromus pulchellus ascovirus proteins encoded by ORFs 90, 91 and 93. A new alignment technique also shows that two proteins from a related ichnovirus are orthologs of other ascovirus virion proteins. CONCLUSION: Our results provide molecular evidence supporting the origin of ichnoviruses from ascoviruses by lateral transfer of ascoviral genes into ichneumonid wasp genomes, perhaps the first example of symbiogenesis between large DNA viruses and eukaryotic organisms. We also discuss the limits of this evidence through complementary studies, which revealed that passive lateral transfer of viral genes among polydnaviral, bacterial, and wasp genomes may have occurred repeatedly through an intimate coupling of both recombination and replication of viral genomes during evolution. The impact of passive lateral transfers on evolutionary relationships between polydnaviruses and viruses with large double-stranded genomes is considered in the context of the theory of symbiogenesis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567993/ doi: 10.1186/1471-2148-8-253 id: cord-269839-jxqs51o5 author: Bitome-Essono, Paul-Yannick title: Tracking zoonotic pathogens using blood-sucking flies as ''flying syringes'' date: 2017-03-28 words: 5875.0 sentences: 319.0 pages: flesch: 57.0 cache: ./cache/cord-269839-jxqs51o5.txt txt: ./txt/cord-269839-jxqs51o5.txt summary: This study demonstrates that using hematophagous flies as ''flying syringes'' constitutes an interesting approach to investigate blood-borne pathogen diversity in wild vertebrates and could be used as an early detection tool of zoonotic pathogens. The omnipresence of hematophagous flies in certain habitats and their opportunistic blood-feeding behaviour (Muturi et al., 2011; Muzari et al., 2010; Späth, 2000) make of them compelling candidates to obtain blood meals from different vertebrate hosts for pathogen detection. In the present study, we investigated the possibility of using hematophagous flies as ''flying syringes'' to explore the diversity of extant malaria parasites (Haemosporida) infecting wild vertebrates living in the forests of Gabon (Central Africa). Overall, the blood meal origin was successfully identified in 428 fly samples (35%) using a PCR system amplifying long fragments of Cytb (450 bp) or COI genes (330 bp or 660 bp). In this study, we tested whether hematophagous flies could be used as ''flying syringes'' to identify blood-borne pathogens circulating in the wild vertebrate fauna of Gabon. abstract: About 60% of emerging infectious diseases in humans are of zoonotic origin. Their increasing number requires the development of new methods for early detection and monitoring of infectious agents in wildlife. Here, we investigated whether blood meals from hematophagous flies could be used to identify the infectious agents circulating in wild vertebrates. To this aim, 1230 blood-engorged flies were caught in the forests of Gabon. Identified blood meals (30%) were from 20 vertebrate species including mammals, birds and reptiles. Among them, 9% were infected by different extant malaria parasites among which some belonged to known parasite species, others to new parasite species or to parasite lineages for which only the vector was known. This study demonstrates that using hematophagous flies as ‘flying syringes’ constitutes an interesting approach to investigate blood-borne pathogen diversity in wild vertebrates and could be used as an early detection tool of zoonotic pathogens. DOI: http://dx.doi.org/10.7554/eLife.22069.001 url: https://www.ncbi.nlm.nih.gov/pubmed/28347401/ doi: 10.7554/elife.22069 id: cord-346104-18x8u2oe author: Black, Wendy title: Identification of gammaherpesvirus infection in free-ranging black bears (Ursus americanus) date: 2019-01-02 words: 5163.0 sentences: 298.0 pages: flesch: 56.0 cache: ./cache/cord-346104-18x8u2oe.txt txt: ./txt/cord-346104-18x8u2oe.txt summary: Herpesvirus infection in the bear tissues and tissue cultures were detected by PCR using degenerate primers specific to the DNA polymerase gene (DPOL) and glycoprotein B gene (gB). To determine whether the observed viral particles are herpesviruses, tissues collected from the two NV black bears B1 and B2 were examined by nested PCR using panherpesvirus primers (Pozo et al., 2016 ) and herpesvirus consensus primers (VanDevanter et al., 1996) . To determine how common this UrHV-1 like virus is in black bear population, various tissues from 15 bears collected from Nevada, California, and Oregon were analyzed by this hybrid nested PCR with panherpesvirus primers in primary reaction and UrHV-1specific primers in the secondary reactions. Positive amplification with UrHV-1 specific primers was observed in total DNA of white blood cells (WBC) from two black bears from Nevada and one from Oregon. abstract: Herpesvirus infection was investigated in black bears (Ursus americanus) with neurological signs and brain lesions of nonsuppurative encephalitis of unknown cause. Visible cytopathic effects (CPE) could only be observed on days 3–5 post-infection in HrT-18G cell line inoculated with bear tissue extracts. The observed CPE in HrT-18G cells included syncytia, intranuclear inclusions, and cell detachments seen in herpesvirus infection in vitro. Herpesvirus-like particles were observed in viral culture supernatant under the electron microscope, however, capsids ranging from 60 nm to 100 nm in size were often observed in viral cultures within the first two passages of propagation. Herpesvirus infection in the bear tissues and tissue cultures were detected by PCR using degenerate primers specific to the DNA polymerase gene (DPOL) and glycoprotein B gene (gB). DNA sequencing of the amplicon revealed that the detected herpesvirus has 94–95% identity to Ursid gammaherpesvirus 1 (UrHV-1) DNA sequences of DPOL. Phylogenetic analysis of DPOL sequences indicates that black bear herpesviruses and UrHV-1 are closely related and have small distances to members of Rhadinovirus. Interestingly, black bear herpesvirus infections were also found in bears without neurological signs. The DPOL DNA sequence of black bear herpesviruses detected in neurological bears were similar to the those detected in the non-neurological bears. However, the gB DNA sequence detected from the neurological bear is different from non-neurological bear and has only 64.5%–70% identity to each other. It is possible that at least two different types of gammaherpesviruses are present in the U. americanus population or several gammaherpesviruses exist in ursine species. url: https://www.sciencedirect.com/science/article/pii/S0168170218303678 doi: 10.1016/j.virusres.2018.10.016 id: cord-005281-wy0zk9p8 author: Blinov, V. M. title: Viral component of the human genome date: 2017-05-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Relationships between viruses and their human host are traditionally described from the point of view taking into consideration hosts as victims of viral aggression, which results in infectious diseases. However, these relations are in fact two-sided and involve modifications of both the virus and host genomes. Mutations that accumulate in the populations of viruses and hosts may provide them advantages such as the ability to overcome defense barriers of host cells or to create more efficient barriers to deal with the attack of the viral agent. One of the most common ways of reinforcing anti-viral barriers is the horizontal transfer of viral genes into the host genome. Within the host genome, these genes may be modified and extensively expressed to compete with viral copies and inhibit the synthesis of their products or modulate their functions in other ways. This review summarizes the available data on the horizontal gene transfer between viral and human genomes and discusses related problems. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089383/ doi: 10.1134/s0026893317020066 id: cord-278249-vvhq9vgp author: Blot, Mathieu title: CXCL10 could drive longer duration of mechanical ventilation during COVID-19 ARDS date: 2020-11-02 words: 6238.0 sentences: 346.0 pages: flesch: 45.0 cache: ./cache/cord-278249-vvhq9vgp.txt txt: ./txt/cord-278249-vvhq9vgp.txt summary: In addition, since most patients need to undergo mechanical ventilation in this context, ventilator-induced lung injury (VILI) could exacerbate tissue damage as well as local and systemic inflammation, thus acting as a "second hit." Our team has previously shown that mitochondrial alarmins (i.e., mitochondrial DNA) are released by human epithelial cells submitted to cyclic stretch, and these alarmins are also recovered from bronchoalveolar lavage (BAL) fluid obtained from either ventilated rabbits or ARDS patients. This comprehensive evaluation of systemic and pulmonary immune response showed that the higher CXCL10 concentrations in both the systemic and alveolar compartments of patients with COVID-19 ARDS were associated with a longer duration of mechanical ventilation. Finally, in both COVID-19 and non-COVID-19 patients, higher mitochondrial DNA concentrations in the plasma and ELF compartment were highly correlated with alveolar inflammation, as assessed by BALF cell count and ELF IL-8 and IL-1β concentrations. abstract: BACKGROUND: COVID-19-related ARDS has unique features when compared with ARDS from other origins, suggesting a distinctive inflammatory pathogenesis. Data regarding the host response within the lung are sparse. The objective is to compare alveolar and systemic inflammation response patterns, mitochondrial alarmin release, and outcomes according to ARDS etiology (i.e., COVID-19 vs. non-COVID-19). METHODS: Bronchoalveolar lavage fluid and plasma were obtained from 7 control, 7 non-COVID-19 ARDS, and 14 COVID-19 ARDS patients. Clinical data, plasma, and epithelial lining fluid (ELF) concentrations of 45 inflammatory mediators and cell-free mitochondrial DNA were measured and compared. RESULTS: COVID-19 ARDS patients required mechanical ventilation (MV) for significantly longer, even after adjustment for potential confounders. There was a trend toward higher concentrations of plasma CCL5, CXCL2, CXCL10, CD40 ligand, IL-10, and GM-CSF, and ELF concentrations of CXCL1, CXCL10, granzyme B, TRAIL, and EGF in the COVID-19 ARDS group compared with the non-COVID-19 ARDS group. Plasma and ELF CXCL10 concentrations were independently associated with the number of ventilator-free days, without correlation between ELF CXCL-10 and viral load. Mitochondrial DNA plasma and ELF concentrations were elevated in all ARDS patients, with no differences between the two groups. ELF concentrations of mitochondrial DNA were correlated with alveolar cell counts, as well as IL-8 and IL-1β concentrations. CONCLUSION: CXCL10 could be one key mediator involved in the dysregulated immune response. It should be evaluated as a candidate biomarker that may predict the duration of MV in COVID-19 ARDS patients. Targeting the CXCL10-CXCR3 axis could also be considered as a new therapeutic approach. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03955887 url: https://www.ncbi.nlm.nih.gov/pubmed/33138839/ doi: 10.1186/s13054-020-03328-0 id: cord-323029-7hqp8xuq author: Bognár, Zsófia title: Aptamers against Immunoglobulins: Design, Selection and Bioanalytical Applications date: 2020-08-11 words: 19331.0 sentences: 873.0 pages: flesch: 45.0 cache: ./cache/cord-323029-7hqp8xuq.txt txt: ./txt/cord-323029-7hqp8xuq.txt summary: For aptamer selection against rIgG [6] and IgE [7] , homogenous processes were used and the separation of bound and unbound nucleic Several different SELEX methods have been used to generate immunoglobulin aptamers including homogeneous, heterogeneous, bead-based SELEX processes, CE-SELEX (capillary electrophoresis-SELEX), µFFE-SELEX (micro-free flow electrophoresis-SELEX) and fully integrated selection processes selection of aptamers with proper binding properties. Molecular Light Switch Complex 100-800 100 [128] Fluorescence enhancement using a DNA aptamer 92-37,000 57 [130] Amplification through allostery-triggered enzymatic recycling amplification NA 5 [131] Fluorescent oligonucleotide probe based on G-quadruplex scaffold for signal-on ultrasensitive protein assay 4.72-7560 0.095 [132] Fluorescence anisotropy 1000-60,000 350 [133] Fluorescence anisotropy assay NA 20 [134] Fluorescence protection assay 100-50,000 100 [136] Aptamer-barcode-based assay based on instantaneous derivatization chemiluminescence coupled to magnetic beads 4.88-20,000 4.6 [137] Competitive fluorescence quenching assay 350-35,000 170 [138] Rapid fluorescence detection of immunoglobulin E using an aptamer switch based on a binding-induced pyrene excimer NA 1600 [139] 6.1. abstract: Nucleic acid aptamers show clear promise as diagnostic reagents, as highly specific strands were reported against a large variety of biomarkers. They have appealing benefits in terms of reproducible generation by chemical synthesis, controlled modification with labels and functionalities providing versatile means for detection and oriented immobilization, as along with high biochemical and temperature resistance. Aptamers against immunoglobulin targets—IgA, IgM, IgG and IgE—have a clear niche for diagnostic applications, therefore numerous aptamers have been selected and used in combination with a variety of detection techniques. The aim of this review is to overview and evaluate aptamers selected for the recognition of antibodies, in terms of their design, analytical properties and diagnostic applications. Aptamer candidates showed convincing performance among others to identify stress and upper respiratory tract infection through SIgA detection, for cancer cell recognition using membrane bound IgM, to detect and treat hemolytic transfusion reactions, autoimmune diseases with IgG and detection of IgE for allergy diseases. However, in general, their use still lags significantly behind what their claimed benefits and the plethora of application opportunities would forecast. url: https://www.ncbi.nlm.nih.gov/pubmed/32796581/ doi: 10.3390/ijms21165748 id: cord-310734-6v7oru2l author: Bolatti, Elisa M. title: A Preliminary Study of the Virome of the South American Free-Tailed Bats (Tadarida brasiliensis) and Identification of Two Novel Mammalian Viruses date: 2020-04-09 words: 8477.0 sentences: 405.0 pages: flesch: 41.0 cache: ./cache/cord-310734-6v7oru2l.txt txt: ./txt/cord-310734-6v7oru2l.txt summary: By conventional nucleic acid detection techniques and/or bioinformatics approaches, the genomes of two novel viruses were completely covered clustering into the Papillomaviridae (Tadarida brasiliensis papillomavirus type 1, TbraPV1) and Genomoviridae (Tadarida brasiliensis gemykibivirus 1, TbGkyV1) families. Overall, a large number of phage-related sequences were detected (77.3% of viral read pairs and 39.9% of viral contigs), likely representing the most abundant entities infecting bacteria present in the bat digestive system, which exhibited similarity mostly to the families Inoviridae, Siphoviridae, and Myoviridae ( Table 1 ). Several mammalian viral families, supported by the contigs and sequencing reads, have been identified previously in New World [23, 24, 26] and Old World [17, 18, 89] bat species. Table S4 : Read pairs and contigs classified as similar to viruses and not taxonomical assigned to viral families identified in anal and oral swab samples of Tadarida brasiliensis obtained by metagenomics using Illumina technology. abstract: Bats provide important ecosystem services as pollinators, seed dispersers, and/or insect controllers, but they have also been found harboring different viruses with zoonotic potential. Virome studies in bats distributed in Asia, Africa, Europe, and North America have increased dramatically over the past decade, whereas information on viruses infecting South American species is scarce. We explored the virome of Tadarida brasiliensis, an insectivorous New World bat species inhabiting a maternity colony in Rosario (Argentina), by a metagenomic approach. The analysis of five pooled oral/anal swab samples indicated the presence of 43 different taxonomic viral families infecting a wide range of hosts. By conventional nucleic acid detection techniques and/or bioinformatics approaches, the genomes of two novel viruses were completely covered clustering into the Papillomaviridae (Tadarida brasiliensis papillomavirus type 1, TbraPV1) and Genomoviridae (Tadarida brasiliensis gemykibivirus 1, TbGkyV1) families. TbraPV1 is the first papillomavirus type identified in this host and the prototype of a novel genus. TbGkyV1 is the first genomovirus reported in New World bats and constitutes a new species within the genus Gemykibivirus. Our findings extend the knowledge about oral/anal viromes of a South American bat species and contribute to understand the evolution and genetic diversity of the novel characterized viruses. url: https://doi.org/10.3390/v12040422 doi: 10.3390/v12040422 id: cord-018526-rz7id5mt author: Braun, Serge title: Non-viral Vector for Muscle-Mediated Gene Therapy date: 2018-12-14 words: 5181.0 sentences: 228.0 pages: flesch: 37.0 cache: ./cache/cord-018526-rz7id5mt.txt txt: ./txt/cord-018526-rz7id5mt.txt summary: Nevertheless, the local production of therapeutic proteins that may act distantly from the injected site and/or the hydrodynamic perfusion of safe plasmids remains a viable basis for the non-viral gene therapy of muscle disorders, cachexia, as well as peripheral neuropathies. In humans, intramuscular injections of naked plasmid encoding angiogenic factors (such as VEGF165 or HGF) were used in small numbers of patients with critical limb ischemia and did demonstrate promising clinical efficacy for the treatment of peripheral arterial disease. A meta-analysis of 12 clinical trials (1494 patients total) of local administration of pro-angiogenic growth factors (VEGF, FGF, HGF, Del-1, HIF-1alpha) using plasmid or viral gene transfer by intra-arterial or intramuscular injections showed that, despite promising results in single studies, no clear benefit could be identified in peripheral artery disease patients, irrespective of disease severity [51] . abstract: Non-viral gene delivery to skeletal muscle was one of the first applications of gene therapy that went into the clinic, mainly because skeletal muscle is an easily accessible tissue for local gene transfer and non-viral vectors have a relatively safe and low immunogenic track record. However, plasmid DNA, naked or complexed to the various chemistries, turn out to be moderately efficient in humans when injected locally and very inefficient (and very toxic in some cases) when injected systemically. A number of clinical applications have been initiated however, based on transgenes that were adapted to good local impact and/or to a wide physiological outcome (i.e., strong humoral and cellular immune responses following the introduction of DNA vaccines). Neuromuscular diseases seem more challenging for non-viral vectors. Nevertheless, the local production of therapeutic proteins that may act distantly from the injected site and/or the hydrodynamic perfusion of safe plasmids remains a viable basis for the non-viral gene therapy of muscle disorders, cachexia, as well as peripheral neuropathies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123420/ doi: 10.1007/978-3-030-03095-7_9 id: cord-010045-eqzs01au author: Britton, P. title: Sequence of the nucleoprotein gene from a virulent British field isolate of transmissible gastroenteritis virus and its expression in Saccharomyces cerevisiae date: 2006-10-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Subgenomic mRNA from a virulent isolate of porcine transmissible gastroenteritis virus (TGEV) was used to produce cDNA which was sequenced. Two non‐overlapping open reading frames (ORFs) were identified. The largest, encoding a polypeptide of 382 amino acids (relative molecular mass (M(r)) 43 483), was shown to be the viral nucleoprotein gene. The second ORF, found 3’to the larger ORF, encodes a polypeptide of 78 amino acids (M(r) 9068) which has yet to be assigned to a viral product. The nucleoprotein gene was expressed in yeast cells under the control of two types of yeast promoters: the constitutive PGK promoter, and the inducible GAL1 promoter. Yeast cells containing recombinant plasmids, with the nucleoprotein gene in the correct orientation, produced a polypeptide of M, 47000, identical to the viral product, that reacted with a specific monoclonal antibody. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168467/ doi: 10.1111/j.1365-2958.1988.tb00010.x id: cord-278081-tk7vn1v1 author: Brooks, Wesley H. title: Viral Impact in Autoimmune Diseases: Expanding the “X Chromosome–Nucleolus Nexus” Hypothesis date: 2017-11-28 words: 9823.0 sentences: 457.0 pages: flesch: 42.0 cache: ./cache/cord-278081-tk7vn1v1.txt txt: ./txt/cord-278081-tk7vn1v1.txt summary: Here is presented new details to the hypothesis, explaining how the disrupted chromatin can lead to subsequent disruption of the nucleolus, even nucleolar fragmentation, which results in ineffective nucleolar functioning, misfolded RNAs, misassembled or incompletely assembled ribonucleoprotein (RNP) complexes, and stabilization of nucleolar components in autoantigenic conformations. For now there is no direct connection between viruses and the "X chromosome-nucleolus nexus" hypothesis to the increased risk of cancers among autoimmune disease patients but we can consider the induction by viruses of increased polyamine levels and the possible reactivation of X-linked polyamine genes as means by which competition for the cellular methyl donor, SAM, could reduce DNA methylation and open oncogenes for overexpression in proliferation competent cells. A disrupted Barr body could generate an abundance of polyamines and Alu RNA from X-linked genes and elements that further stress and damage the nucleolus, making it very inefficient in its functions, even fragmenting it and possibly leading to cell death. abstract: Viruses are suspected of significant roles in autoimmune diseases but the mechanisms are unclear. We get some insight by considering demands a virus places on host cells. Viruses not only require production of their own proteins, RNA and/or DNA, but also production of additional cellular machinery, such as ribosomes, to handle the increased demands. Since the nucleolus is a major site of RNA processing and ribonucleoprotein assembly, nucleoli are targeted by viruses, directly when viral RNA and proteins enter the nucleolus and indirectly when viruses induce increased expression of cellular polyamine genes. Polyamines are at high levels in nucleoli to assist in RNA folding. The size and activity of nucleoli increase directly with increases in polyamines. Nucleolar expansion due to abnormal increases in polyamines could disrupt nearby chromatin, such as the inactive X chromosome, leading to expression of previously sequestered DNA. Sudden expression of a large concentration of Alu elements from the disrupted inactive X can compete with RNA transcripts containing intronic Alu sequences that normally maintain nucleolar structural integrity. Such disruption of nucleolar activity can lead to misfolded RNAs, misassembled ribonucleoprotein complexes, and fragmentation of the nucleolus. Many autoantigens in lupus are, at least transiently, components of the nucleolus. Considering these effects of viruses, the “X chromosome–nucleolus nexus” hypothesis, which proposed disruption of the inactive X by the nucleolus during stress, is now expanded here to propose subsequent disruption of the nucleolus by previously sequestered Alu elements, which can fragment the nucleolus, leading to generation of autoantigens. url: https://doi.org/10.3389/fimmu.2017.01657 doi: 10.3389/fimmu.2017.01657 id: cord-308687-wrzzb9cy author: Brunner, Jesse L. title: Pooled samples and eDNA-based detection can facilitate the “clean trade” of aquatic animals date: 2020-06-24 words: 6488.0 sentences: 322.0 pages: flesch: 46.0 cache: ./cache/cord-308687-wrzzb9cy.txt txt: ./txt/cord-308687-wrzzb9cy.txt summary: swabs) and eDNA samples collected from finite populations and discuss key assumptions and considerations for their use with a focus on detecting Batrachochytrium salamandrivorans, an emerging pathogen that threatens global salamander diversity. www.nature.com/scientificreports www.nature.com/scientificreports/ context of screening U.S. service members for syphilis, pooling samples to reduce the number of tests required to detect rare infections is common in numerous contexts 22 , including surveys for disease freedom. In this paper I therefore develop formulae for imperfect tests of pooled samples in closed populations and eDNA, discuss the key assumptions and considerations in their application, and illustrate how eDNA may be especially useful for detecting infections in the live animal trade. Pooling and batch-processing samples collected from individual animals (e.g., swabs) can reduce several fold the number of diagnostic tests (e.g., DNA extractions and PCR reactions) required to detect rare infections. abstract: The regional and international trade of live animals facilitates the movement, spillover, and emergence of zoonotic and epizootic pathogens around the world. Detecting pathogens in trade is critical for preventing their continued movement and introduction, but screening a sufficient fraction to ensure rare infections are detected is simply infeasible for many taxa and settings because of the vast numbers of animals involved—hundreds of millions of live animals are imported into the U.S.A. alone every year. Batch processing pools of individual samples or using environmental DNA (eDNA)—the genetic material shed into an organism’s environment—collected from whole consignments of animals may substantially reduce the time and cost associated with pathogen surveillance. Both approaches, however, lack a framework with which to determine sampling requirements and interpret results. Here I present formulae for pooled individual samples (e.g,. swabs) and eDNA samples collected from finite populations and discuss key assumptions and considerations for their use with a focus on detecting Batrachochytrium salamandrivorans, an emerging pathogen that threatens global salamander diversity. While empirical validation is key, these formulae illustrate the potential for eDNA-based detection in particular to reduce sample sizes and help bring clean trade into reach for a greater number of taxa, places, and contexts. url: https://www.ncbi.nlm.nih.gov/pubmed/32581260/ doi: 10.1038/s41598-020-66280-7 id: cord-255499-31xmue1g author: Bujarski, J.J. title: Recombination date: 2008-07-30 words: 4852.0 sentences: 253.0 pages: flesch: 41.0 cache: ./cache/cord-255499-31xmue1g.txt txt: ./txt/cord-255499-31xmue1g.txt summary: In general, homologous recombination events occur much more often and they are most commonly known as genetic crossing-over that happens in every DNA-based organism during meiosis. The mechanism may involve either homologous crossing-over events or copy-choice processes that rely on template switching by DNA replicase. Aberrant homologous recombination involves crossovers between related RNAs, but the crosses occur at not-corresponding sites leading to sequences insertions or deletions. A double-stranded RNA Pseudomonas phage Phi6 was hypothesized to recombine its RNA based on a copy-choice template switching mechanism, where the crossovers would have occurred inside the virus capsid structures at regions with almost no sequence similarity. In some cases, the base pairing between a partial nascent strand and the acceptor template can lead to the appearance of the rearranged regions in DI RNAs. In addition to rearranged DI RNAs, some RNA viruses accumulate defective RNAs due to a single internal deletion in the genomic RNA of the helper virus. abstract: Genetic recombination of viruses is a commonly found phenomenon in both DNA and RNA viruses. By exchanging of fragments of genetic material viruses gain important means leading to both variability and also to the repair of their genome. Biochemically, the processes of DNA and RNA recombination are different reflecting the specifics of DNA versus RNA replication as well as their use inside the cell. A variety of recombination mechanisms are discussed and illustrated by examples taken from specific viral species. url: https://api.elsevier.com/content/article/pii/B9780123744104005458 doi: 10.1016/b978-012374410-4.00545-8 id: cord-016309-6mw8okmt author: Bule, Mohammed title: Antivirals: Past, Present and Future date: 2019-06-06 words: 8200.0 sentences: 405.0 pages: flesch: 36.0 cache: ./cache/cord-016309-6mw8okmt.txt txt: ./txt/cord-016309-6mw8okmt.txt summary: Those included usage restricted to a single virus and specific animal species, problems with high spectrum activity and low cytotoxicity, high costs of development of new chemical compounds and absence of rapid diagnostic techniques allowing prompt use of a specific antiviral agent in the course of an acute infection (Rollinson 1992a, b) . Nevertheless, several licensed human antiviral agents are being used with cascade principle for treatment of animal diseases (e.g. acyclovir, idoxuridine and trifluridine against feline herpesvirus-1 ocular infection in cats) (Thiry et al. The discovery of PAA (Fig. 22.4) as an antiviral drug gave rise to intense research on its biological activities, which demonstrated PAA and its derivatives'' ability to inhibit the replication of a number of viruses such as immunodeficiency, hepatitis and herpes viruses. To conclude with, equine herpesvirus type 1 (EHV-1) infection causes outbreak of respiratory and various neurological diseases in horses, against which acyclovir and valacyclovir are the most common drugs, but also IFN targeting IFNGR complex as a key mediator of virus-specific cellular immunity (Poelaert et al. abstract: The uses of antiviral agents are increasing in the new era along with the development of vaccines for the effective control of viral diseases. The main aims of antiviral agents are to minimize harm to the host system and eradicate deadly viral diseases. However, the replications of viruses in host system represent a massive therapeutic challenge than bacteria and fungi. Antiviral drugs not just penetrate to disrupt the virus’ cellular divisions but also have a negative impact on normal physiological pathways in the host. Due to these issues, antiviral agents have a narrow therapeutic index than antibacterial drugs. Nephrotoxicity is the main adverse reaction of antiviral drugs in human and animals. In this chapter, we summarize the antiviral agents’ past, present and future perspectives with the main focus on the brief history of antiviral in animals, miscellaneous drugs, natural products, herbal and repurposing drugs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120554/ doi: 10.1007/978-981-13-9073-9_22 id: cord-355913-fhvt1ht1 author: Burrell, Christopher J. title: Virus Replication date: 2016-11-11 words: 9861.0 sentences: 405.0 pages: flesch: 42.0 cache: ./cache/cord-355913-fhvt1ht1.txt txt: ./txt/cord-355913-fhvt1ht1.txt summary: Little is known about what determines whether a given picornavirus positive-sense RNA molecule will be directed (1) to a replication complex (a structure bound to smooth endoplasmic reticulum), where it serves as template for transcription by RNA-dependent RNA polymerase into negative-sense RNA, or (2) to a ribosome, where it serves as mRNA for translation into protein, or (3) to a procapsid, with which it associates to form a virion. In the case of positive-sense single-stranded RNA viruses, the incoming RNA genome can bind directly to ribosomes and be translated in full or in part without the need for any prior transcription; all other forms of incoming viral RNA must first be transcribed to produce mRNA, in order to begin the process of expression of the infecting viral genome. abstract: Understanding the molecular events accompanying virus replication is essential for the proper understanding and control of all virus diseases. The virus replication cycle generates new viral genomes and proteins in sufficient quantities to ensure propagation of the viral genome; this requires that the extracellular viral genome is protected from enzymatic degradation and can be introduced into further target cells for further rounds of replication. The initial recognition between virus and host is more complex than originally supposed and may involve more than one cellular receptor. A critical first intracellular step is the generation of viral mRNA by one of a limited number of strategies first described by David Baltimore. Lacking ribosomes, viruses have no means of producing protein and are reliant on the host cell for protein synthesis. Viral proteins are often modified by host cell glycosylation during or after virus assembly. Temporal regulation of intracellular events is critical in all but the very simplest of viruses, and some form of suppression of the host innate immune response is common to nearly all human viruses. Infected cells often produce non-infectious particles with incomplete genomes, and these defective interfering particles may play a role in pathogenesis. Understanding these processes will open up a range of targets for the development of novel therapies. url: https://api.elsevier.com/content/article/pii/B9780123751560000047 doi: 10.1016/b978-0-12-375156-0.00004-7 id: cord-255043-uxdsjr39 author: Bustin, Stephen A. title: RT-qPCR Testing of SARS-CoV-2: A Primer date: 2020-04-24 words: 4552.0 sentences: 201.0 pages: flesch: 46.0 cache: ./cache/cord-255043-uxdsjr39.txt txt: ./txt/cord-255043-uxdsjr39.txt summary: The only reliable test in current use for testing acute infection targets the genome of SARS-CoV-2, and the most widely used method is quantitative fluorescence-based reverse transcription polymerase chain reaction (RT-qPCR). Given that on 9th January 2020 SARS-CoV-2 was definitively identified by the Chinese CDC as the causative agent for COVID-19 pneumonia and that its genomic sequence (GenBank accession number MN908947) was made available on 10th January, it is extraordinary that by the time the earliest documented transmission within the UK appeared on 28th February, no definitive action plan, stockpile of assays and required consumables, RNA extraction robots or high throughput qPCR instruments had been assembled to allow immediate and widespread RT-qPCR testing. This involves designing assays that generate PCR products of 60-80 bp, using fast RNA-and DNA-dependent DNA polymerases such as Superscript IV and KAPA Taq polymerase, respectively, and selecting instruments capable of rapid cycling, for example Eco from PCRMax. This allows the RT step to be limited to 2 min or less, with the denaturation and annealing/polymerisation steps limited to 1 s each ( Figure 3) . abstract: Testing for the presence of coronavirus is an essential diagnostic tool for monitoring and managing the current COVID-19 pandemic. The only reliable test in current use for testing acute infection targets the genome of SARS-CoV-2, and the most widely used method is quantitative fluorescence-based reverse transcription polymerase chain reaction (RT-qPCR). Despite its ubiquity, there is a significant amount of uncertainty about how this test works, potential throughput and reliability. This has resulted in widespread misrepresentation of the problems faced using this test during the current COVID-19 epidemic. This primer provides simple, straightforward and impartial information about RT-qPCR. url: https://www.ncbi.nlm.nih.gov/pubmed/32344568/ doi: 10.3390/ijms21083004 id: cord-264456-wjpc6zgq author: Bütepage, Mareike title: Intracellular Mono-ADP-Ribosylation in Signaling and Disease date: 2015-09-25 words: 10307.0 sentences: 575.0 pages: flesch: 46.0 cache: ./cache/cord-264456-wjpc6zgq.txt txt: ./txt/cord-264456-wjpc6zgq.txt summary: inactive mRNA regulation and miRNA silencing [36] Component of stress granules [17] Viral defense [36] ARTD14 (PARP7, TiPARP) MAR AHR signaling [37] [38] [39] [40] Translation [31] TCCD-induced hepatotoxicity [40] Inhibition of viral replication [31, 41] ARTD15 (PARP16) MAR Unfolded protein response [42] Not reported ARTD16 (PARP8) MAR Unclear Not reported ARTD17 (PARP6) MAR Regulates cell cycle progression [43] Inhibits cell proliferation, survival benefit in colorectal cancer [43] SIRT4 MAR Glutamine metabolism [44, 45] Tumor-suppressive [45, 46] SIRT6 MAR DNA repair [47] [48] [49] Retrotransposon silencing [50] Tumor suppressive [50] [51] [52] [53] [54] [55] [56] [57] and oncogenic functions [58, 59] MACROD1 (LRP16) Hydrolase ERα signaling [60, 61] AR signaling [62] Promotes cell proliferation [60, 62] Metastasis, invasion and survival in gastric and colorectal cancer [63, 64] . abstract: A key process in the regulation of protein activities and thus cellular signaling pathways is the modification of proteins by post-translational mechanisms. Knowledge about the enzymes (writers and erasers) that attach and remove post-translational modifications, the targets that are modified and the functional consequences elicited by specific modifications, is crucial for understanding cell biological processes. Moreover detailed knowledge about these mechanisms and pathways helps to elucidate the molecular causes of various diseases and in defining potential targets for therapeutic approaches. Intracellular adenosine diphosphate (ADP)-ribosylation refers to the nicotinamide adenine dinucleotide (NAD(+))-dependent modification of proteins with ADP-ribose and is catalyzed by enzymes of the ARTD (ADP-ribosyltransferase diphtheria toxin like, also known as PARP) family as well as some members of the Sirtuin family. Poly-ADP-ribosylation is relatively well understood with inhibitors being used as anti-cancer agents. However, the majority of ARTD enzymes and the ADP-ribosylating Sirtuins are restricted to catalyzing mono-ADP-ribosylation. Although writers, readers and erasers of intracellular mono-ADP-ribosylation have been identified only recently, it is becoming more and more evident that this reversible post-translational modification is capable of modulating key intracellular processes and signaling pathways. These include signal transduction mechanisms, stress pathways associated with the endoplasmic reticulum and stress granules, and chromatin-associated processes such as transcription and DNA repair. We hypothesize that mono-ADP-ribosylation controls, through these different pathways, the development of cancer and infectious diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/26426055/ doi: 10.3390/cells4040569 id: cord-004518-jd1wxobz author: Běláková, Jana title: DNA vaccines: are they still just a powerful tool for the future? date: 2007-12-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Vaccination is historically one of the most successful strategies for the prevention of infectious diseases. For safety reasons, modern vaccinology tends toward the usage of inactivated or attenuated microorganisms and uses predominantly subunit vaccines. The antigens need to be clearly defined, pure, stable, appropriately composed, and properly presented to the immune system of the host. Differing ratios of various proportions between specific CD4(+) and CD8(+) T cell responses are essential for conferring the required protection in the case of individual vaccines. To stimulate both CD4(+) and CD8(+) T cells, the antigens must be processed and presented to both antigen-presentation pathways, MHC I and MHC II. Protein antigens delivered by vaccination are processed as extracellular antigens. However, extracellularly delivered antigen can be directed towards intracellular presentation pathways in conjugation with molecules involved in antigen cross-presentation, e.g. heat shock proteins, or by genomic-DNA vaccination. In this overview, current knowledge of the host immune response to DNA vaccines is summarized in the introduction. The subsequent sections discuss techniques for enhancing DNA vaccine efficacy, such as DNA delivery to specific tissues, delivery of DNA to the cell cytoplasm or nucleus, and enhancement of the immune response using molecular adjuvants. Finally, the prospects of DNA vaccination and ongoing clinical trials with various DNA vaccines are discussed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079751/ doi: 10.1007/s00005-007-0044-4 id: cord-305872-66vij492 author: Caasi, Donna Ria J. title: A multi-target, non-infectious and clonable artificial positive control for routine PCR-based assays date: 2013-09-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Positive controls are essential for PCR reliability and are challenging to obtain for rare, exotic and/or emerging pathogens and pose biosafety risks if manufactured using infectious pathogens. Custom synthetic DNA inserts can be designed de novo in tandems of forward and reverse complement priming sequences to be inserted in circular plasmid vectors. To test this concept, artificial positive controls (APCs) for use in PCR were synthesized to contain primer sequences targeting four viruses (Barley yellow dwarf virus, Soilborne wheat mosaic virus, Triticum mosaic virus and Wheat streak mosaic virus) pathogenic to wheat and, as internal control, the plant mitochondrial nad5 gene. Thermodynamics and folding parameters of twenty-four APC inserts were assessed in silico. Two thermodynamically different APCs, designated optimal and sub-optimal, were cloned and tested using end point PCR. The optimal APC had a 100% amplification rate, while only 92% of virus-infected plant tissues, commonly used as reference positive controls, amplified. An array of APC priming sequences from different organisms and/or previously tested primers can be accommodated in a large and flexible number of positive control targets. APCs will streamline and standardize routine PCR, improve reliability and biosafety, and create opportunities for development and commercialization of new synthetic positive control sequences. url: https://www.sciencedirect.com/science/article/pii/S0167701213002832 doi: 10.1016/j.mimet.2013.08.017 id: cord-324321-y96x8x3h author: Cai, Yingyun title: Down-regulation of transcription of the proapoptotic gene BNip3 in cultured astrocytes by murine coronavirus infection date: 2003-11-10 words: 8454.0 sentences: 416.0 pages: flesch: 49.0 cache: ./cache/cord-324321-y96x8x3h.txt txt: ./txt/cord-324321-y96x8x3h.txt summary: Furthermore, treatment of cells with chloroquine, which blocks the acidification of endosomes, significantly inhibited the repression of the BNip3 promoter activity induced by the acidic pH-dependent MHV mutant OBLV60, which enters cells via endocytosis, indicating that the down-regulation of BNip3 expression is mediated by fusion between viral envelope and cell membranes during entry. To establish further the specificity of the down-regulation of BNip3 gene expression, we used vesicular stomatitis virus (VSV) in a parallel experiment, because VSV is also an enveloped RNA virus whose infection has a broad host cell range and is mediated by the interaction between the envelope G protein and cell membranes (Riedel et al., 1984) . By extrapolating the data from the mutant virus, we can envision that fusion between viral envelope and plasma/endosomal membranes during wild-type MHV infection is involved in the down-regulation of BNip3 gene expression. abstract: Murine coronavirus mouse hepatitis virus (MHV) causes encephalitis and demyelination in the central nervous system of susceptible rodents. Astrocytes are the major target for MHV persistence. However, the mechanisms by which astrocytes survive MHV infection and permit viral persistence are not known. Here we performed DNA microarray analysis on differential gene expression in astrocyte DBT cells by MHV infection and found that the mRNA of the proapoptotic gene BNip3 was significantly decreased following MHV infection. This finding was further confirmed by quantitative reverse transcription–polymerase chain reaction, Western blot analysis, and BNip3-promoter-luciferase reporter system. Interestingly, infection with live and ultraviolet light-inactivated viruses equally repressed BNip3 expression, indicating that the down-regulation of BNip3 expression does not require virus replication and is mediated during cell entry. Furthermore, treatment of cells with chloroquine, which blocks the acidification of endosomes, significantly inhibited the repression of the BNip3 promoter activity induced by the acidic pH-dependent MHV mutant OBLV60, which enters cells via endocytosis, indicating that the down-regulation of BNip3 expression is mediated by fusion between viral envelope and cell membranes during entry. Deletion analysis showed that the sequence between nucleotides 262 and 550 of the 588-base-pair BNip3 promoter is necessary and sufficient for driving the BNip3 expression and that it contains signals that are responsible for MHV-induced down-regulation of BNip3 expression in DBT cells. These results may provide insights into the mechanisms by which MHV evades host antiviral defense and promotes cell survival, thereby allowing its persistence in the host astrocytes. url: https://www.ncbi.nlm.nih.gov/pubmed/14599795/ doi: 10.1016/j.virol.2003.07.007 id: cord-279346-7del8d2p author: Callendret, Benoît title: Heterologous viral RNA export elements improve expression of severe acute respiratory syndrome (SARS) coronavirus spike protein and protective efficacy of DNA vaccines against SARS date: 2007-07-05 words: 10731.0 sentences: 471.0 pages: flesch: 49.0 cache: ./cache/cord-279346-7del8d2p.txt txt: ./txt/cord-279346-7del8d2p.txt summary: title: Heterologous viral RNA export elements improve expression of severe acute respiratory syndrome (SARS) coronavirus spike protein and protective efficacy of DNA vaccines against SARS Here, we demonstrated that efficient expression of S from the wild-type spike gene in cultured cells required the use of improved plasmid vectors containing donor and acceptor splice sites, as well as heterologous viral RNA export elements, such as the CTE of Mazon-Pfizer monkey virus or the PRE of Woodchuck hepatitis virus (WPRE). Upon immunization of mice with low doses (2 μg) of naked DNA, only intron and WPRE-containing vectors could induce neutralizing anti-S antibodies and provide protection against challenge with SARS-CoV. The influence of SS, MPMV-CTE or WPRE on expression of S protein in transfected cells and on induction of a protective SARS-CoV-specific immunity in mice after naked DNA immunization are compared. abstract: The SARS-CoV spike glycoprotein (S) is the main target of the protective immune response in humans and animal models of SARS. Here, we demonstrated that efficient expression of S from the wild-type spike gene in cultured cells required the use of improved plasmid vectors containing donor and acceptor splice sites, as well as heterologous viral RNA export elements, such as the CTE of Mazon-Pfizer monkey virus or the PRE of Woodchuck hepatitis virus (WPRE). The presence of both splice sites and WPRE markedly improved the immunogenicity of S-based DNA vaccines against SARS. Upon immunization of mice with low doses (2 μg) of naked DNA, only intron and WPRE-containing vectors could induce neutralizing anti-S antibodies and provide protection against challenge with SARS-CoV. Our observations are likely to be useful for the construction of plasmid and viral vectors designed for optimal expression of intronless genes derived from cytoplasmic RNA viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/17331558/ doi: 10.1016/j.virol.2007.01.012 id: cord-314642-oobbdgzh author: Campbell, Allan title: The future of bacteriophage biology date: 2003 words: 5945.0 sentences: 308.0 pages: flesch: 53.0 cache: ./cache/cord-314642-oobbdgzh.txt txt: ./txt/cord-314642-oobbdgzh.txt summary: Several molecules of λ-integrase form an assemblage (the INTASOME) that binds to a specific segment of phage DNA, recruits the bacterial insertion sites into the complex, then makes concerted single-strand cuts in the two DNAs. The strand cutting proceeds through the covalent joining of a 3′ phosphate to a tyrosine of the integrase protein. Further efforts in this direction are desirable, not just for their intrinsic interest but also as models for viruses that infect eukaryotic hosts; for example, it is well documented that members of the coronavirus group, which has attracted attention recently through the emergence of a deadly new human pathogen that causes severe acute respiratory syndrome (SARS), undergo frequent recombination in nature 10, 11 . abstract: After an illustrious history as one of the primary tools that established the foundations of molecular biology, bacteriophage research is now undergoing a renaissance in which the primary focus is on the phages themselves rather than the molecular mechanisms that they explain. Studies of the evolution of phages and their role in natural ecosystems are flourishing. Practical questions, such as how to use phages to combat human diseases that are caused by bacteria, how to eradicate phage pests in the food industry and what role they have in the causation of human diseases, are receiving increased attention. Phages are also useful in the deeper exploration of basic molecular and biophysical questions. url: https://www.ncbi.nlm.nih.gov/pubmed/12776216/ doi: 10.1038/nrg1089 id: cord-272357-fxe49zen author: Campolongo, Michael J. title: DNA nanomedicine: Engineering DNA as a polymer for therapeutic and diagnostic applications() date: 2010-04-30 words: 7365.0 sentences: 419.0 pages: flesch: 43.0 cache: ./cache/cord-272357-fxe49zen.txt txt: ./txt/cord-272357-fxe49zen.txt summary: Nanomedicine, the application of nanotechnology to medicine, encompasses a broad spectrum of fields including molecular detection, diagnostics, drug delivery, gene regulation and protein production. There are a variety of systems that take advantage of the hybridisation of linear DNA for nanomedicine applications, including oligonucleotide sensing, multiplexed pathogen detection, aptameric drug delivery and diagnostics, as well as stimuli-responsive hydrogels. Notably, a nanoparticle-based biobarcode assay was developed for the ultrasensitive detection of biomolecules, such as proteins [44] [45] [46] [47] [48] , messenger RNA (mRNA) [49] and the human immunodeficiency virus (HIV)-1 antigen [50] , as well as for the multiplexed detection with high selectivity but without the need for enzymatic target amplification and labelling [28, 47] (Fig. 2B) . Over the past 17 years, aptamers have been generated against a wide array of molecular targets, including many known proteins, carbohydrates, lipids, nucleotides and other small molecules, as well as highly complex structures such as viruses [64] [65] [66] . abstract: Nanomedicine, the application of nanotechnology to medicine, encompasses a broad spectrum of fields including molecular detection, diagnostics, drug delivery, gene regulation and protein production. In recent decades, DNA has received considerable attention for its functionality and versatility, allowing it to help bridge the gap between materials science and biological systems. The use of DNA as a structural nanoscale material has opened a new avenue towards the rational design of DNA nanostructures with different polymeric topologies. These topologies, in turn, possess unique characteristics that translate to specific therapeutic and diagnostic strategies within nanomedicine. url: https://doi.org/10.1016/j.addr.2010.03.004 doi: 10.1016/j.addr.2010.03.004 id: cord-023724-5at0rhqk author: Cann, Alan J. title: Infection date: 2015-07-24 words: 14979.0 sentences: 755.0 pages: flesch: 48.0 cache: ./cache/cord-023724-5at0rhqk.txt txt: ./txt/cord-023724-5at0rhqk.txt summary: The problems plant viruses face in initiating infections of host cells have already been described (Chapter 4), as has the fact that no known plant virus employs a specific cellular receptor of the types that animal and bacterial viruses use to attach to cells. There are probably many different mechanisms involved in systemic resistance, but in general terms there is a tendency of these processes to increase local necrosis when substances such as proteases and peroxidases are produced by the plant to destroy the virus and to prevent its spread and subsequent systemic infection. Virus-resistant plants have been created by the production of transgenic plants expressing recombinant virus proteins or nucleic acids which interfere with virus replication without producing the pathogenic consequences of infection, for example: I Virus coat proteins, which have a variety of complex effects, including inhibition of virus uncoating and interference of expression of the virus at the level of RNA ("gene silencing" by "untranslatable" RNAs), I Intact or partial virus replicases which interfere with genome replication, I Antisense RNAs, I Defective virus genomes, I Satellite sequences (see Chapter 8), I Catalytic RNA sequences (ribozymes), I Modified movement proteins. abstract: Virus infection of higher organisms is the cumulative result of all the processes of replication and gene expression described in the previous chapters. Together, these determine the overall course of each infection. Infections range in complexity and duration from a very brief, superficial interaction between the virus and its host to infections that may span the entire life of the host organism, from before birth to its eventual death. A common misconception is that virus infection inevitably results in disease. In reality, the reverse is true—only a small minority of virus infections gives rise to any disease symptoms. This chapter provides an overview of the numerous patterns of virus infection and forms an introduction to the discussion of virus pathogenesis in Chapter 7. Unlike previous and subsequent chapters, this chapter deals primarily with the interaction of viruses with intact organisms rather than with the molecular biologist’s usual concern about the interaction between a virus and the cell. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173531/ doi: 10.1016/b978-0-12-801946-7.00006-7 id: cord-324829-0nz0qioh author: Carabineiro, Sónia Alexandra Correia title: Applications of Gold Nanoparticles in Nanomedicine: Recent Advances in Vaccines † date: 2017-05-22 words: 7639.0 sentences: 420.0 pages: flesch: 38.0 cache: ./cache/cord-324829-0nz0qioh.txt txt: ./txt/cord-324829-0nz0qioh.txt summary: Gold nanoparticles, in general, have remarkably high surface-to-volume ratio, are biocompatible and inert, and can be easily functionalized with several molecules; thus, they can also play an important role in the vaccine field as adjuvants, reducing toxicity, enhancing immunogenic activity, and providing stability of vaccine in storage, and have great potential as carriers for the development of a great diversity of fully synthetic vaccines [8] [9] [10] [11] [12] 15, 20, 21, 26, [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] . Gold nanoparticles, in general, have remarkably high surface-to-volume ratio, are biocompatible and inert, and can be easily functionalized with several molecules; thus, they can also play an important role in the vaccine field as adjuvants, reducing toxicity, enhancing immunogenic activity, and providing stability of vaccine in storage, and have great potential as carriers for the development of a great diversity of fully synthetic vaccines [8] [9] [10] [11] [12] 15, 20, 21, 26, [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] . abstract: Nowadays, gold is used in (nano-)medicine, usually in the form of nanoparticles, due to the solid proofs given of its therapeutic effects on several diseases. Gold also plays an important role in the vaccine field as an adjuvant and a carrier, reducing toxicity, enhancing immunogenic activity, and providing stability in storage. An even brighter golden future is expected for gold applications in this area. url: https://www.ncbi.nlm.nih.gov/pubmed/28531163/ doi: 10.3390/molecules22050857 id: cord-012473-p66of6kq author: Celniker, Susan E. title: Unlocking the secrets of the genome date: 2009-06-17 words: 2556.0 sentences: 119.0 pages: flesch: 37.0 cache: ./cache/cord-012473-p66of6kq.txt txt: ./txt/cord-012473-p66of6kq.txt summary: T he primary objective of the Human Genome Project was to produce highquality sequences not just for the human genome but also for those of the chief model organisms: Escherichia coli, yeast (Saccharomyces cerevisiae), worm (Caenorhabditis elegans), fly (Drosophila melanogaster) and mouse (Mus musculus). Free access to the resultant data has prompted much biological research, including development of a map of common human genetic variants (the International HapMap Project) 1 , expression profiling of healthy and diseased cells 2 and in-depth studies of many individual genes. On the basis of this experience, the NHGRI launched two complementary programmes in 2007: an expansion of the human ENCODE project to the whole genome (www.genome.gov/ENCODE) and the model organism ENCODE (modENCODE) project to generate a comprehensive annotation of the functional elements in the C. The research communities that study these two organisms will rapidly make use of the modENCODE results, deploying powerful experimental approaches that are often not possible or practical in mammals, including genetic, genomic, transgenic, biochemical and RNAi assays. abstract: Despite the successes of genomics, little is known about how genetic information produces complex organisms. A look at the crucial functional elements of fly and worm genomes could change that. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/459927a) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843545/ doi: 10.1038/459927a id: cord-013837-x95r6bz8 author: Chai, Qiyao title: New insights into the evasion of host innate immunity by Mycobacterium tuberculosis date: 2020-07-29 words: 11189.0 sentences: 603.0 pages: flesch: 31.0 cache: ./cache/cord-013837-x95r6bz8.txt txt: ./txt/cord-013837-x95r6bz8.txt summary: In this review, we describe the emerging role of cytosolic nucleic acid-sensing pathways at the host–Mtb interface and summarize recently revealed mechanisms by which Mtb circumvents host cellular innate immune strategies such as membrane trafficking and integrity, cell death and autophagy. [19] [20] [21] The involvement of the cGAS-mediated DNA-sensing pathway in host anti-Mtb immunity is indicated by the findings that cGAS expression is upregulated and that cGAS is colocalized with mycobacteria in human TB lesions, and its deficiency impairs the induction of type I IFN responses and autophagy in Mtb-infected macrophages. 23 Therefore, specifically targeting mycobacterial ESX-1 products or host regulatory factors might enable the selective regulation of inflammasome and cGAS/STING pathway activation and, hence, contribute to the recovery of the equilibrium between Th1-type cytokine and type I IFN responses in TB patients to improve their anti-Mtb immunity. abstract: Mycobacterium tuberculosis (Mtb) is an extremely successful intracellular pathogen that causes tuberculosis (TB), which remains the leading infectious cause of human death. The early interactions between Mtb and the host innate immune system largely determine the establishment of TB infection and disease development. Upon infection, host cells detect Mtb through a set of innate immune receptors and launch a range of cellular innate immune events. However, these innate defense mechanisms are extensively modulated by Mtb to avoid host immune clearance. In this review, we describe the emerging role of cytosolic nucleic acid-sensing pathways at the host–Mtb interface and summarize recently revealed mechanisms by which Mtb circumvents host cellular innate immune strategies such as membrane trafficking and integrity, cell death and autophagy. In addition, we discuss the newly elucidated strategies by which Mtb manipulates the host molecular regulatory machinery of innate immunity, including the intranuclear regulatory machinery, the ubiquitin system, and cellular intrinsic immune components. A better understanding of innate immune evasion mechanisms adopted by Mtb will provide new insights into TB pathogenesis and contribute to the development of more effective TB vaccines and therapies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608469/ doi: 10.1038/s41423-020-0502-z id: cord-275886-502es8qm author: Chailapakul, Orawon title: Paper-based sensors for the application of biological compound detection date: 2020-06-05 words: 7032.0 sentences: 365.0 pages: flesch: 40.0 cache: ./cache/cord-275886-502es8qm.txt txt: ./txt/cord-275886-502es8qm.txt summary: Other venerable methods such as complex formation [12] and Griess test [13] were reported in the early development of PADs. The surface of nanoparticles can be modified with specific probe using precious metal and sulphur formation [14] which increases the selectivity of the materials towards target analytes. In 2009, our group reported for the first time an enzymatic electrochemical method based on paper based analytical device (PADs) for the simultaneous determination of uric acid, glucose and lactate in biological fluids. In order to improve the DNA based sensor to be an alternative sensor designed for point-of-care (POC) application, it has been quickly integrated into paper-based analytical devices (PADs) providing a low cost, simple and rapid diagnostic platform especially for developing countries and resourcelimited areas. [39] developed a paper-based electrochemical DNA biosensor using the acpcPNA probe labelled with anthroquinone (AQ) for detecting highrisk human papillomavirus (HPV) type 16 (Fig. 12) . abstract: Abstract This chapter describes the importance of PADs for biomarker detection. The screening of disease markers and other biomolecules that related to health conditions have play important roles for an indication of the risk from infections and other diseases. Paper-based analytical devices (PADs) is an excellent option for applications of biomarker detection because it contains all advantages which arise from the paper material. Moreover, the uncomplicated techniques including electrochemistry and colorimetry can be easily applied on PADs for the analytical detection. The detection method can be categorized into three main topics: enzymatic methods, immunoassays, and DNA sensors. Following the main context, other interesting applications also present in this chapter. url: https://www.sciencedirect.com/science/article/pii/S0166526X20300234 doi: 10.1016/bs.coac.2020.03.002 id: cord-298697-v1qdizwx author: Chang, Jia Jin Marc title: Takeaways from Mobile DNA Barcoding with BentoLab and MinION date: 2020-09-24 words: 7206.0 sentences: 395.0 pages: flesch: 56.0 cache: ./cache/cord-298697-v1qdizwx.txt txt: ./txt/cord-298697-v1qdizwx.txt summary: One of the most common applications of MinION is for nanopore-based DNA barcoding in situ for species identification and discovery, yet the existing sample capability is limited (n ≤ 10). We also tested the performance of the newly released R10.3 nanopore flow cell for DNA barcoding, and showed that the barcodes generated were ~99.9% accurate when compared to Illumina references. For the field sequencing phase, an additional 31 samples were collected and subjected to QE-based DNA extraction on the BentoLab. While we did not run the gel check in situ to save time, a postliminary amplification check on agarose back at the laboratory revealed 20 observable gel bands. For the field sequencing phase, an additional 31 samples were collected and subjected to QE-based DNA extraction on the BentoLab. While we did not run the gel check in situ to save time, a postliminary amplification check on agarose back at the laboratory revealed 20 observable gel bands. abstract: Since the release of the MinION sequencer in 2014, it has been applied to great effect in the remotest and harshest of environments, and even in space. One of the most common applications of MinION is for nanopore-based DNA barcoding in situ for species identification and discovery, yet the existing sample capability is limited (n ≤ 10). Here, we assembled a portable sequencing setup comprising the BentoLab and MinION and developed a workflow capable of processing 32 samples simultaneously. We demonstrated this enhanced capability out at sea, where we collected samples and barcoded them onboard a dive vessel moored off Sisters’ Islands Marine Park, Singapore. In under 9 h, we generated 105 MinION barcodes, of which 19 belonged to fresh metazoans processed immediately after collection. Our setup is thus viable and would greatly fortify existing portable DNA barcoding capabilities. We also tested the performance of the newly released R10.3 nanopore flow cell for DNA barcoding, and showed that the barcodes generated were ~99.9% accurate when compared to Illumina references. A total of 80% of the R10.3 nanopore barcodes also had zero base ambiguities, compared to 50–60% for R9.4.1, suggesting an improved homopolymer resolution and making the use of R10.3 highly recommended. url: https://www.ncbi.nlm.nih.gov/pubmed/32987804/ doi: 10.3390/genes11101121 id: cord-000765-r7y1cqou author: Chang, Yu-Ming title: Functional Studies of ssDNA Binding Ability of MarR Family Protein TcaR from Staphylococcus epidermidis date: 2012-09-21 words: 5770.0 sentences: 317.0 pages: flesch: 54.0 cache: ./cache/cord-000765-r7y1cqou.txt txt: ./txt/cord-000765-r7y1cqou.txt summary: title: Functional Studies of ssDNA Binding Ability of MarR Family Protein TcaR from Staphylococcus epidermidis However, the detailed mechanism of multiple antibiotic resistance regulator (MarR) family proteins such as TcaR is unclear and only restricted on the binding ability of double-strand DNA (dsDNA). Here we show by electrophoretic mobility shift assay (EMSA), electron microscopy (EM), circular dichroism (CD), and Biacore analysis that TcaR can interact strongly with single-stranded DNA (ssDNA), thereby identifying a new role in MarR family proteins. IcaR DNA1 probe duplex of 1 mM was pre-incubated with 2 mM TcaR (dimer) at room temperature for 15 min before mixing with increasing concentration of GC33 ssDNA, followed by the same procedure as described in the legend to Figure 1B . In the EMSA analysis, 1 mM IcaR DNA1 probe duplex was pre-incubated with 1 mM GC33 ssDNA fragment for 15 min at room temperature before mixing with TcaR protein of increasing concentration. abstract: The negative transcription regulator of the ica locus, TcaR, regulates proteins involved in the biosynthesis of poly-N-acetylglucosamine (PNAG). Absence of TcaR increases PNAG production and promotes biofilm formation in Staphylococci. Previously, the 3D structure of TcaR in its apo form and its complex structure with several antibiotics have been analyzed. However, the detailed mechanism of multiple antibiotic resistance regulator (MarR) family proteins such as TcaR is unclear and only restricted on the binding ability of double-strand DNA (dsDNA). Here we show by electrophoretic mobility shift assay (EMSA), electron microscopy (EM), circular dichroism (CD), and Biacore analysis that TcaR can interact strongly with single-stranded DNA (ssDNA), thereby identifying a new role in MarR family proteins. Moreover, we show that TcaR preferentially binds 33-mer ssDNA over double-stranded DNA and inhibits viral ssDNA replication. In contrast, such ssDNA binding properties were not observed for other MarR family protein and TetR family protein, suggesting that the results from our studies are not an artifact due to simple charge interactions between TcaR and ssDNA. Overall, these results suggest a novel role for TcaR in regulation of DNA replication. We anticipate that the results of this work will extend our understanding of MarR family protein and broaden the development of new therapeutic strategies for Staphylococci. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448645/ doi: 10.1371/journal.pone.0045665 id: cord-345494-8lcdx719 author: Chao, Chien-Chung title: Development of Recombinase Polymerase Amplification Assays for Detection of Orientia tsutsugamushi or Rickettsia typhi date: 2015-07-10 words: 7022.0 sentences: 331.0 pages: flesch: 52.0 cache: ./cache/cord-345494-8lcdx719.txt txt: ./txt/cord-345494-8lcdx719.txt summary: title: Development of Recombinase Polymerase Amplification Assays for Detection of Orientia tsutsugamushi or Rickettsia typhi Recombinase polymerase amplification (RPA) assays using a lateral flow test (RPA-nfo) and real-time fluorescent detection (RPA-exo) were developed targeting the 47-kDa gene of O. Almost all antigen/pathogen detection assays for rickettsial diseases are based on polymerase chain reaction (PCR [7, 8] ), quantitative real-time PCR (qPCR) or nested PCR targeting different genes, including 56 kDa [9] , 47kDa [10] , groEL [11] of O. The DNA was used as template for the 17-RPA assay to evaluate its performance and qPCR was used to quantitate the copy number of the 17 kDa gene. honei and R japonica were also evaluated to show that they were not detectable by 17-RPA-nfo unless 10 4 or more copies of DNA were present, same results were obtained using 17-RPA-exo. abstract: Sensitive, specific and rapid diagnostic tests for the detection of Orientia tsutsugamushi (O. tsutsugamushi) and Rickettsia typhi (R. typhi), the causative agents of scrub typhus and murine typhus, respectively, are necessary to accurately and promptly diagnose patients and ensure that they receive proper treatment. Recombinase polymerase amplification (RPA) assays using a lateral flow test (RPA-nfo) and real-time fluorescent detection (RPA-exo) were developed targeting the 47-kDa gene of O. tsutsugamushi or 17 kDa gene of R. typhi. The RPA assay was capable of detecting O. tsutsugamushi or R. typhi at levels comparable to that of the quantitative PCR method. Both the RPA-nfo and RPA-exo methods performed similarly with regards to sensitivity when detecting the 17 kDa gene of R. typhi. On the contrary, RPA-exo performed better than RPA-nfo in detecting the 47 kDa gene of O. tsutsugamushi. The clinical performance of the O. tsutsugamushi RPA assay was evaluated using either human patient samples or infected mouse samples. Eight out of ten PCR confirmed positives were determined positive by RPA, and all PCR confirmed negative samples were negative by RPA. Similar results were obtained for R. typhi spiked patient sera. The assays were able to differentiate O. tsutsugamushi and R. typhi from other phylogenetically related bacteria as well as mouse and human DNA. Furthermore, the RPA-nfo reaction was completed in 20 minutes at 37(o)C followed by a 10 minute incubation at room temperature for development of an immunochromatographic strip. The RPA-exo reaction was completed in 20 minutes at 39(o)C. The implementation of a cross contamination proof cassette to detect the RPA-nfo fluorescent amplicons provided an alternative to regular lateral flow detection strips, which are more prone to cross contamination. The RPA assays provide a highly time-efficient, sensitive and specific alternative to other methods for diagnosing scrub typhus or murine typhus. url: https://doi.org/10.1371/journal.pntd.0003884 doi: 10.1371/journal.pntd.0003884 id: cord-008588-4eu9v5d3 author: Chastain, Michael title: Structural Elements in RNA date: 2008-02-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: This chapter describes the RNA structural characteristics that have emerged so far. Folded RNA molecules are stabilized by a variety of interactions, the most prevalent of which are stacking and hydrogen bonding between bases. Many interactions among backbone atoms also occur in the structure of tRNA, although they are often ignored when considering RNA structure because they are not as well-characterized as interactions among bases. Backbone interactions include hydrogen bonding and the stacking of sugar or phosphate groups with bases or with other sugar and phosphate groups. The interactions found in a three-dimensional RNA structure can be divided into two categories: secondary interactions and tertiary interactions. This division is useful for several reasons. Secondary structures are routinely determined by a combination of techniques discussed in chapter, whereas tertiary interactions are more difficult to determine. Computer algorithms that generate RNA structures can search completely through possible secondary structures, but the inclusion of tertiary interactions makes a complete search of possible structures impractical for RNA molecules even as small as tRNA. The division of RNA structure into building blocks consisting of secondary or tertiary interactions makes it easier to describe RNA structures. In those cases in which RNA studies are incomplete, the studies of DNA are described with the rationalization that RNA structures may be analogous to DNA structures, or that the techniques used to study DNA could be applied to the analogous RNA structures. The chapter focuses on the aspects of RNA structure that affect the three-dimensional shape of RNA and that affect its ability to interact with other molecules. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133162/ doi: 10.1016/s0079-6603(08)60008-2 id: cord-189561-jhvwozsn author: Chechetkin, Vladimr R. title: Combining Detection and Reconstruction of Periodic Motifs in Genomic Sequences with Transitional Genome Mapping date: 2020-10-14 words: 4184.0 sentences: 268.0 pages: flesch: 54.0 cache: ./cache/cord-189561-jhvwozsn.txt txt: ./txt/cord-189561-jhvwozsn.txt summary: A method of transitional automorphic mapping of the genome on itself (TAMGI) is aimed at combining detection and reconstruction of periodic motifs in the genomic RNA/DNA sequences. Generally, TAMGI provides a convenient tool for the study of numerous molecular mechanisms with participation of both quasi-periodic motifs and complete repeats, the genome organization, contextual analysis of cis/trans regulatory elements, data mining, and correlations in the genomic sequences. f The distribution of k-mer lengths after TAMGI for the steps within interval 1-500 for the genome of SARS-CoV-2 (shown by crosses) and its comparison with the counterpart distribution for a random reshuffled sequence (shown by circles). The correspondence should be searched between the (generally multiple) elements of icosahedral symmetry and the character of large-scale quasi-periodic segmentation induced by weakly specific cooperative interactions between genomic RNA/DNA and capsid proteins. To sum up, TAMGI method developed in this article is quite general and can be applied to the combined detection/reconstruction of quasi-periodic motifs in the genomic RNA/DNA sequences. abstract: A method of transitional automorphic mapping of the genome on itself (TAMGI) is aimed at combining detection and reconstruction of periodic motifs in the genomic RNA/DNA sequences. The periodic motifs (whether tandem or sparse) are assumed to be randomly modified by point mutations and indels during molecular evolution and present in the genomes in a hidden form. TAMGI is robust with respect to patched phasing of periodic motifs induced by indels. We developed and tested the relevant theory and statistical criteria for TAMGI applications. The applications of TAMGI are illustrated by the study of hidden periodic motifs in the genomes of the severe acute respiratory syndrome coronaviruses SARS-CoV and SARS-CoV-2 (the latter coronavirus SARS-CoV-2 being responsible for the COVID-19 pandemia) packaged within filament-like helical capsid. Such ribonucleocapsid is transported into spherical membrane envelope with incorporated spike glycoproteins. Two other examples concern the genomes of viruses with icosahedral capsids, satellite tobacco mosaic virus (STMV) and bacteriophage PHIX174. A part of the quasi-periodic motifs in these viral genomes was evolved due to weakly specific cooperative interaction between genomic ssRNA/ssDNA and nucleocapsid proteins. The symmetry of the capsids leads to the natural selection of specific quasi-periodic motifs in the related genomic sequences. Generally, TAMGI provides a convenient tool for the study of numerous molecular mechanisms with participation of both quasi-periodic motifs and complete repeats, the genome organization, contextual analysis of cis/trans regulatory elements, data mining, and correlations in the genomic sequences. url: https://arxiv.org/pdf/2010.07006v1.pdf doi: nan id: cord-011113-n1yf0o2o author: Chen, Weiye title: A seven-gene-deleted African swine fever virus is safe and effective as a live attenuated vaccine in pigs date: 2020-03-01 words: 5944.0 sentences: 283.0 pages: flesch: 60.0 cache: ./cache/cord-011113-n1yf0o2o.txt txt: ./txt/cord-011113-n1yf0o2o.txt summary: As shown in Figure 4A , the pigs that were inoculated with one dose of 10 5 TCID 50 vaccine and challenged i.m. with 200 PLD 50 of HLJ/18 on day 28 post-vaccination all survived the 3-week observation period, but viral DNA was detected in the blood, tonsil, and two lymph nodes of one of the five pigs that were euthanized at the end of the observation period ( Figure 4A ), indicating that HLJ/18-7GD provides similar protection in both farmed and SPF pigs. abstract: African swine fever (ASF) is a devastating infectious disease in swine that is severely threatening the global pig industry. An efficacious vaccine is urgently required. Here, we used the Chinese ASFV HLJ/18 as a backbone and generated a series of gene-deleted viruses. The virulence, immunogenicity, safety, and protective efficacy evaluation in specific-pathogen-free pigs, commercial pigs, and pregnant sows indicated that one virus, namely HLJ/18-7GD, which has seven genes deleted, is fully attenuated in pigs, cannot convert to the virulent strain, and provides complete protection of pigs against lethal ASFV challenge. Our study shows that HLJ/-18-7GD is a safe and effective vaccine against ASFV, and as such is expected to play an important role in controlling the spread of ASFV. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1657-9 and is accessible for authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223596/ doi: 10.1007/s11427-020-1657-9 id: cord-274644-gr1eaj6k author: Chen, Zhao-Chi title: Thermally stable and uniform DNA amplification with picosecond laser ablated graphene rapid thermal cycling device date: 2019-12-15 words: 5152.0 sentences: 265.0 pages: flesch: 59.0 cache: ./cache/cord-274644-gr1eaj6k.txt txt: ./txt/cord-274644-gr1eaj6k.txt summary: This study reports a straightforward fabrication technique for patterning an on-chip graphene-based device with hole arrays, in which the mechanism of surface structures can achieve stable and uniform thermal control for the amplification of DNA fragments. Our results demonstrated that the proposed integration of a graphene-based device and a laser-pulse ablation process to form a thin-film PCR device has cost benefits in a small-volume reagent and holds great promise for practical medical use of DNA amplification. DNA amplification is performed using thermal cycling, with a high degree of control of stable and uniform temperature distribution being attributed to array structures (Bigham et al., 2017; Seo et al., 2018) , microchannel heat exchangers (Riera et al., 2013) , membrane-based microfluidics (Chen and Shen, 2017) , and doped hybrid materials (Seo et al., 2016) . abstract: Rapid thermal cycling (RTC) in an on-chip device can perform DNA amplification in vitro through precise thermal control at each step of the polymerase chain reaction (PCR). This study reports a straightforward fabrication technique for patterning an on-chip graphene-based device with hole arrays, in which the mechanism of surface structures can achieve stable and uniform thermal control for the amplification of DNA fragments. A thin-film based PCR device was fabricated using picosecond laser (PS-laser) ablation of the multilayer graphene (MLG). Under the optimal fluence of 4.72 J/cm(2) with a pulse overlap of 66%, the MLG can be patterned with arrays of 250 μm(2) hole surface structures. A 354-bp DNA fragment of VP1, an effective marker for diagnosing the BK virus, was amplified on an on-chip device in less than 60 min. A thin-film electrode with the aforementioned MLG as the heater was demonstrated to significantly enhance temperature stability for each stage of the thermal cycle. The temperature control of the heater was performed by means of a developed programmable PCR apparatus. Our results demonstrated that the proposed integration of a graphene-based device and a laser-pulse ablation process to form a thin-film PCR device has cost benefits in a small-volume reagent and holds great promise for practical medical use of DNA amplification. url: https://api.elsevier.com/content/article/pii/S0956566319306608 doi: 10.1016/j.bios.2019.111581 id: cord-339369-9z30nksl author: Chiappetta, Catarina Marcon title: Molecular Detection of Circovirus and Adenovirus in Feces of Fur Seals (Arctocephalus spp.) date: 2016-11-01 words: 3818.0 sentences: 220.0 pages: flesch: 57.0 cache: ./cache/cord-339369-9z30nksl.txt txt: ./txt/cord-339369-9z30nksl.txt summary: The present study aimed to detect viral RNA or DNA in 23 free-ranging fur seals on the northern coastline of Rio Grande do Sul State, Brazil. Polymerase chain reaction was used to detect nucleic acids of circoviruses, adenoviruses, morbilliviruses, vesiviruses, and coronaviruses in the feces from twenty-one South American fur seals (Arctocephalus australis) and two Subantarctic fur seals (A. Adenovirus DNA fragments were detected in two South American fur seals; nucleotide sequences of these fragments revealed a high degree of similarity to human adenovirus type C. The present study aimed to detect the presence of circovirus, adenovirus, morbillivirus, vesivirus, and coronavirus nucleic acid in feces from two species of fur seals (A. The deduced amino acid sequences of circoviruses detected in samples FSCV-20 and FSCV-46 were identical to each other and highly similar to other sequences of members in the Circovirus genus known to infect multiple animal species (Li et al. abstract: In some regions, little is known about exposure to viruses in coastal marine mammals. The present study aimed to detect viral RNA or DNA in 23 free-ranging fur seals on the northern coastline of Rio Grande do Sul State, Brazil. Polymerase chain reaction was used to detect nucleic acids of circoviruses, adenoviruses, morbilliviruses, vesiviruses, and coronaviruses in the feces from twenty-one South American fur seals (Arctocephalus australis) and two Subantarctic fur seals (A. tropicalis). Adenovirus DNA fragments were detected in two South American fur seals; nucleotide sequences of these fragments revealed a high degree of similarity to human adenovirus type C. Circovirus DNA fragments were detected in six animals of the same species. Two were phylogenetically similar to the Circovirus genus, whereas the other four nucleotide fragments showed no similarity to any of the known genera within the family Circoviridae. RNA fragments indicating the presence of coronavirus, vesivirus, and morbillivirus were not detected. These findings suggest that adenoviruses and circoviruses are circulating in fur seal populations found along the coast of Rio Grande do Sul State, Brazil. url: https://www.ncbi.nlm.nih.gov/pubmed/27803979/ doi: 10.1007/s10393-016-1195-8 id: cord-260653-5qwtvm9x author: Chikhlikar, Priya title: DNA Encoding an HIV-1 Gag/Human Lysosome-Associated Membrane Protein-1 Chimera Elicits a Broad Cellular and Humoral Immune Response in Rhesus Macaques date: 2006-12-27 words: 6117.0 sentences: 278.0 pages: flesch: 49.0 cache: ./cache/cord-260653-5qwtvm9x.txt txt: ./txt/cord-260653-5qwtvm9x.txt summary: Thomas; Marques, Ernesto T.A. title: DNA Encoding an HIV-1 Gag/Human Lysosome-Associated Membrane Protein-1 Chimera Elicits a Broad Cellular and Humoral Immune Response in Rhesus Macaques Previous studies of HIV-1 p55Gag immunization of mice have demonstrated the usefulness of targeting antigens to the cellular compartment containing the major histocompatibility complex type II (MHC II) complex molecules by use of a DNA antigen formulation encoding Gag as a chimera with the mouse lysosome-associated membrane protein (mLAMP/gag). In the present study, we have analyzed the magnitude and breadth of Gag-specific T-lymphocyte and antibody responses elicited in Rhesus macaques after immunization with DNA encoding a human LAMP/gag (hLAMP/gag) chimera. This study demonstrates that Rhesus macaques immunized with a DNA plasmid vaccine-encoding gag as an hLAMP/gag chimera develops strong antigen-specific humoral responses as well as CD4 + and CD8 + T-cell responses. abstract: Previous studies of HIV-1 p55Gag immunization of mice have demonstrated the usefulness of targeting antigens to the cellular compartment containing the major histocompatibility complex type II (MHC II) complex molecules by use of a DNA antigen formulation encoding Gag as a chimera with the mouse lysosome-associated membrane protein (mLAMP/gag). In the present study, we have analyzed the magnitude and breadth of Gag-specific T-lymphocyte and antibody responses elicited in Rhesus macaques after immunization with DNA encoding a human LAMP/gag (hLAMP/gag) chimera. ELISPOT analyses indicated that the average Gag-specific IFN-γ response elicited by the hLAMP/gag chimera was detectable after only two or three naked DNA immunizations in all five immunized macaques and reached an average of 1000 spot-forming cells (SFC)/10(6) PBMCs. High IFN-γ ELISPOT responses were detected in CD8(+)-depleted cells, indicating that CD4(+) T-cells play a major role in these responses. The T-cell responses of four of the macaques were also tested by use of ELISPOT to 12 overlapping 15-amino acids (aa) peptide pools containing ten peptides each, encompassing the complete Gag protein sequence. The two Mamu 08 immunized macaques responded to eight and twelve of the pools, the Mamu B01 to six, and the other macaque to five pools indicating that the hLAMP/gag DNA antigen formulation elicits a broad T-cell response against Gag. Additionally, there was a strong HIV-1-specific IgG response. The IgG antibody titers increased after each DNA injection, indicating a strong amnestic B-cell response, and were highly elevated in all the macaques after three immunizations. Moreover, the serum of each macaque recognized 13 of the 49 peptides of a 20-aa peptide library covering the complete Gag amino acid sequence. In addition, HIV-1-specific IgA antibodies were present in the plasma and external secretions, including nasal washes. These data support the findings of increased immunogenicity of genetic vaccines encoded as LAMP chimeras, including the response to DNA vaccines by non-human primates. url: https://www.ncbi.nlm.nih.gov/pubmed/17205139/ doi: 10.1371/journal.pone.0000135 id: cord-320015-lbr2q4qh author: Chinchar, V. Gregory title: The Molecular Biology of Frog Virus 3 and other Iridoviruses Infecting Cold-Blooded Vertebrates date: 2011-10-20 words: 9130.0 sentences: 433.0 pages: flesch: 43.0 cache: ./cache/cord-320015-lbr2q4qh.txt txt: ./txt/cord-320015-lbr2q4qh.txt summary: Additional IE and DE proteins include proteins that may play roles in blocking host immune responses such as a virus-encoded, CARD (caspase activation and recruitment domain) motif-containing protein (vCARD), β-hydroxysteroid dehydrogenase (βHSD), and a RNAse III-like protein, catalytic proteins involved in nucleic acid synthesis (Proliferating Cell Nuclear Antigen [PCNA], DNA methyltransferase [DMTase], the large and small subunits of the viral homolog of cellular RNA polymerase II [vPOL-IIα and -IIβ], transcription factor IIS), catalytic proteins that may act to increase dTTP pool sizes and influence host range (deoxyuridine triphosphatase [dUTPase], deoxynucleotide kinase, the large and small subunits of ribonucleotide reductase), and proteins non-essential for replication in vitro, but needed for growth in vivo (the 18K protein) [22] . Lastly, Sample and co-workers observed that KD of the 18K IE protein had no observable effect on viral gene expression or replication in vitro suggesting that, at least in fathead minnow cells, 18K was not required for the production of infectious virions. abstract: Frog virus 3 (FV3) is the best characterized member of the family Iridoviridae. FV3 study has provided insights into the replication of other family members, and has served as a model of viral transcription, genome replication, and virus-mediated host-shutoff. Although the broad outlines of FV3 replication have been elucidated, the precise roles of most viral proteins remain unknown. Current studies using knock down (KD) mediated by antisense morpholino oligonucleotides (asMO) and small, interfering RNAs (siRNA), knock out (KO) following replacement of the targeted gene with a selectable marker by homologous recombination, ectopic viral gene expression, and recombinant viral proteins have enabled researchers to systematically ascertain replicative- and virulence-related gene functions. In addition, the application of molecular tools to ecological studies is providing novel ways for field biologists to identify potential pathogens, quantify infections, and trace the evolution of ecologically important viral species. In this review, we summarize current studies using not only FV3, but also other iridoviruses infecting ectotherms. As described below, general principles ascertained using FV3 served as a model for the family, and studies utilizing other ranaviruses and megalocytiviruses have confirmed and extended our understanding of iridovirus replication. Collectively, these and future efforts will elucidate molecular events in viral replication, intrinsic and extrinsic factors that contribute to disease outbreaks, and the role of the host immune system in protection from disease. url: https://doi.org/10.3390/v3101959 doi: 10.3390/v3101959 id: cord-350212-448mv4lt author: Chiuppesi, Flavia title: Development of a Multi-Antigenic SARS-CoV-2 Vaccine Using a Synthetic Poxvirus Platform date: 2020-07-17 words: 7728.0 sentences: 446.0 pages: flesch: 52.0 cache: ./cache/cord-350212-448mv4lt.txt txt: ./txt/cord-350212-448mv4lt.txt summary: We demonstrate that these sMVA vectors stimulate robust SARS-CoV-2 antigen-speci c humoral and cellular immunity in mice, including potent NAb. These results emphasize the value of a novel vaccine platform based on synthetic DNA to e ciently produce recombinant poxvirus vectors and warrant further pre-clinical and clinical testing of a multiantigenic sMVA vaccine candidate to control the ongoing SARS-CoV-2 pandemic and its devastating consequences. In response to the ongoing global SARS-CoV-2 pandemic, we used this novel vaccine platform to rapidly produce sMVA vectors co-expressing SARS-CoV-2 S and N antigens and show that these vectors can induce potent SARS-CoV-2 antigen-speci c humoral and cellular immune responses in mice, including potent NAb. These results highlight the feasibility to e ciently produce recombinant MVA vectors from chemically synthesized DNA and to rapidly develop a synthetic poxvirusbased vaccine candidate to prevent SARS-CoV-2 infection. abstract: Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate. url: https://www.ncbi.nlm.nih.gov/pubmed/32702732/ doi: 10.21203/rs.3.rs-40198/v1 id: cord-258014-lzzi4rnz author: Chorna, Nataliya title: A Protocol for the Multi-Omic Integration of Cervical Microbiota and Urine Metabolomics to Understand Human Papillomavirus (HPV)-Driven Dysbiosis date: 2020-04-08 words: 6060.0 sentences: 394.0 pages: flesch: 47.0 cache: ./cache/cord-258014-lzzi4rnz.txt txt: ./txt/cord-258014-lzzi4rnz.txt summary: This methods article suggests detailed sample collection and laboratory processes of metabolomics, DNA extraction for microbiota, HPV typing, and the bioinformatic analyses of the data, both to characterize the metabolome, the microbiota, and joint multi-omic analyses, useful for the development of new point-of-care diagnostic tests based on these approaches. Recent studies have indicated that changes of the cervicovaginal microbiome [5] [6] [7] , such as bacterial vaginosis [8, 9] , cervical inflammation [10, 11] and vaginal pH [12, 13] , play a role in the susceptibility to cervical Human Papillomavirus (HPV) infection and the development of cervical intraepithelial neoplasia due to the profound shifts in the relative abundances of protective bacteria [10] . Derivatization solution without the sample only, and empty vials, must also be included as quality controls in the analysis to ensure that identified metabolites 11. abstract: The multi-omic integration of microbiota data with metabolomics has gained popularity. This protocol is based on a human multi-omics study, integrating cervicovaginal microbiota, HPV status and neoplasia, with urinary metabolites. Indeed, to understand the biology of the infections and to develop adequate interventions for cervical cancer prevention, studies are needed to characterize in detail the cervical microbiota and understand the systemic metabolome. This article is a detailed protocol for the multi-omic integration of cervical microbiota and urine metabolome to shed light on the systemic effects of cervical dysbioses associated with Human Papillomavirus (HPV) infections. This methods article suggests detailed sample collection and laboratory processes of metabolomics, DNA extraction for microbiota, HPV typing, and the bioinformatic analyses of the data, both to characterize the metabolome, the microbiota, and joint multi-omic analyses, useful for the development of new point-of-care diagnostic tests based on these approaches. url: https://doi.org/10.3390/biomedicines8040081 doi: 10.3390/biomedicines8040081 id: cord-013223-f43hks44 author: Chronopoulos, Antonios title: Emerging role of bacterial extracellular vesicles in cancer date: 2020-10-15 words: 5793.0 sentences: 264.0 pages: flesch: 29.0 cache: ./cache/cord-013223-f43hks44.txt txt: ./txt/cord-013223-f43hks44.txt summary: The increasing appreciation that microbiota-derived EV can enter the systemic circulation and be detected in human body fluids is likely to stimulate completely new areas of investigation in microbiome research, biomarkers and liquid biopsies, BEV-based therapeutics, onco-immunology, as well as fundamental microbial EV biology. In addition to potentially modulating the innate immune response via or more cytosolic DNA sensors, the possibility that pathogenic BEV-derived DNA can be transferred and detected in the nucleus of non-phagocytic cells (e.g. epithelial cells) [30] , raises the intriguing possibility that bacterial genetic material could be transferred to human somatic cells and integrated into the host genome. BEVs released by bacteria in the gut lumen can cross the epithelial barrier to gain access into the underlying submucosa enabling them to interact with various resident immune cell populations (dendritic cells, neutrophils and macrophages) as well as potentially disseminate more widely around the body via the systemic or lymphatic circulation to reach distant tissues and organs or even the brain (Fig. 2) . abstract: Shedding of microbial extracellular vesicles constitutes a universal mechanism for inter-kingdom and intra-kingdom communication that is conserved among prokaryotic and eukaryotic microbes. In this review we delineate fundamental aspects of bacterial extracellular vesicles (BEVs) including their biogenesis, cargo composition, and interactions with host cells. We critically examine the evidence that BEVs from the host gut microbiome can enter the circulatory system to disseminate to distant organs and tissues. The potential involvement of BEVs in carcinogenesis is evaluated and future research ideas explored. We further discuss the potential of BEVs in microbiome-based liquid biopsies for cancer diagnostics and bioengineering strategies for cancer therapy. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557313/ doi: 10.1038/s41388-020-01509-3 id: cord-336219-xndxn1r3 author: Chuang, Chi-Mu title: Treatment with Imiquimod enhances antitumor immunity induced by therapeutic HPV DNA vaccination date: 2010-04-28 words: 4726.0 sentences: 246.0 pages: flesch: 54.0 cache: ./cache/cord-336219-xndxn1r3.txt txt: ./txt/cord-336219-xndxn1r3.txt summary: METHODS: In the current study, we explored the combination of the DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 (HPV-16) E7 antigen (CRT/E7) with the TLR7 agonist imiquimod for their ability to generate E7-specific immune responses and antitumor effects in tumor-bearing mice. RESULTS: We observed that treatment with CRT/E7 DNA in combination with imiquimod leads to an enhancement in the E7-specific CD8+ T cell immune responses and a decrease in the number of myeloid-derived suppressor cells in the tumor microenvironment of tumor-bearing mice. In the current study, we hypothesize that the combination of the DNA vaccine encoding CRT linked to HPV-16 E7 (CRT/E7) with topical application of imiquimod at the site of the tumor will lead to increased infiltration of effectior immune cells at the site of the tumor, resulting in enhanced antitumor effects against E7-expressing tumors in a preclinical model. abstract: BACKGROUND: There is an urgent need to develop new innovative therapies for the control of advanced cancer. The combination of antigen-specific immunotherapy with the employment of immunomodulatory agents has emerged as a potentially plausible approach for the control of advanced cancer. METHODS: In the current study, we explored the combination of the DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 (HPV-16) E7 antigen (CRT/E7) with the TLR7 agonist imiquimod for their ability to generate E7-specific immune responses and antitumor effects in tumor-bearing mice. RESULTS: We observed that treatment with CRT/E7 DNA in combination with imiquimod leads to an enhancement in the E7-specific CD8+ T cell immune responses and a decrease in the number of myeloid-derived suppressor cells in the tumor microenvironment of tumor-bearing mice. Furthermore, treatment with CRT/E7 DNA in combination with imiquimod leads to significantly improved antitumor effects and prolonged survival in treated mice. In addition, treatment with imiquimod led to increased number of NK1.1+ cells and F4/80+ cells in the tumor microenvironment. Macrophages and NK1.1+ cells were found to play an important role in the antitumor effects mediated by treatment with CRT/E7 DNA in combination with imiquimod. CONCLUSIONS: Thus, our data suggests that the combination of therapeutic HPV DNA vaccination with topical treatment with the TLR7 agonist imiquimod enhances the antitumor immunity induced by DNA vaccination. The current study has significant implications for future clinical translation. url: https://www.ncbi.nlm.nih.gov/pubmed/20426849/ doi: 10.1186/1423-0127-17-32 id: cord-351197-xv6ymc4l author: Cibulski, Samuel title: A plate of viruses: Viral metagenomics of supermarket chicken, pork and beef from Brazil date: 2020-09-28 words: 1711.0 sentences: 124.0 pages: flesch: 54.0 cache: ./cache/cord-351197-xv6ymc4l.txt txt: ./txt/cord-351197-xv6ymc4l.txt summary: From chicken, six distinct gyroviruses (GyV) were detected, including GyV3 and GyV6, which for the first time were detected in samples from avian species, plus a novel smacovirus species and two highly divergent circular Rep-encoding ssDNA (CRESS-DNA) viruses. A detailed taxonomic 136 classification, including the numbers of reads for each Eukarya-related viral contig 137 recovered is this study, is provided in Supplementary gives them the ability to persist and spread in the environment. A detailed taxonomic classification, including the numbers of 245 J o u r n a l P r e -p r o o f sequenced reads of each Eukarya-related viral contig recovered in this study, is 246 provided in Supplementary Table 1 . including numbers of sequenced reads of each Eukarya-related viral contig recovered in 334 this study, is provided in Supplementary Table 1 . Cressdnaviricota: a virus phylum unifying 7 families of Rep-encoding 519 viruses with single-stranded, circular DNA genomes abstract: A viral metagenomics study was conducted in beef, pork, and chicken sold in supermarkets from Southern Brazil. From chicken, six distinct gyroviruses (GyV) were detected, including GyV3 and GyV6, which for the first time were detected in samples from avian species, plus a novel smacovirus species and two highly divergent circular Rep-encoding ssDNA (CRESS-DNA) viruses. From pork, genomes of numerous anelloviruses, porcine parvovirus 5 (PPV5) and 6 (PPV6), two new genomoviruses and two new CRESS-DNA viruses were found. Finally, two new CRESS-DNA genomes were recovered from beef. Although none of these viruses have history of transmission to humans, the findings reported here reveal that such agents are inevitably consumed in diets that include these types of meat. url: https://www.ncbi.nlm.nih.gov/pubmed/33032031/ doi: 10.1016/j.virol.2020.09.005 id: cord-000830-jiy4cp4n author: Cobo, Fernando title: Application of Molecular Diagnostic Techniques for Viral Testing date: 2012-11-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Nucleic acid amplification techniques are commonly used currently to diagnose viral diseases and manage patients with this kind of illnesses. These techniques have had a rapid but unconventional route of development during the last 30 years, with the discovery and introduction of several assays in clinical diagnosis. The increase in the number of commercially available methods has facilitated the use of this technology in the majority of laboratories worldwide. This technology has reduced the use of some other techniques such as viral culture based methods and serological assays in the clinical virology laboratory. Moreover, nucleic acid amplification techniques are now the methods of reference and also the most useful assays for the diagnosis in several diseases. The introduction of these techniques and their automation provides new opportunities for the clinical laboratory to affect patient care. The main objectives in performing nucleic acid tests in this field are to provide timely results useful for high-quality patient care at a reasonable cost, because rapid results are associated with improvements in patients care. The use of amplification techniques such as polymerase chain reaction, real-time polymerase chain reaction or nucleic acid sequence-based amplification for virus detection, genotyping and quantification have some advantages like high sensitivity and reproducibility, as well as a broad dynamic range. This review is an up-to-date of the main nucleic acid techniques and their clinical applications, and special challenges and opportunities that these techniques currently provide for the clinical virology laboratory. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3522074/ doi: 10.2174/1874357901206010104 id: cord-302486-z36hcvrx author: Cobo, Fernando title: Diagnostic approaches for viruses and prions in stem cell banks date: 2006-03-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Some stem cell lines may contain an endogenous virus or can be contaminated with exogenous viruses (even of animal origin) and may secrete viral particles or express viral antigens on their surface. Moreover, certain biotechnological products (e.g. bovine fetal serum, murine feeder cells) may contain prion particles. Viral and prion contamination of cell cultures and “feeder” cells, which is a common risk in all biotechnological products derived from the cell lines, is the most challenging and potentially serious outcome to address, due to the difficulty involved in virus and prion detection and the potential to cause serious disease in recipients of these cell products. Stem cell banks should introduce adequate quality assurance programs like the microbiological control program and can provide researchers with valuable support in the standardization and safety of procedures and protocols used for the viral and prion testing and in validation programs to assure the quality and safety of the cells. url: https://api.elsevier.com/content/article/pii/S0042682205007725 doi: 10.1016/j.virol.2005.11.026 id: cord-263282-a7emso89 author: Coghlan, Megan L. title: Egg forensics: An appraisal of DNA sequencing to assist in species identification of illegally smuggled eggs date: 2011-07-07 words: 4869.0 sentences: 245.0 pages: flesch: 51.0 cache: ./cache/cord-263282-a7emso89.txt txt: ./txt/cord-263282-a7emso89.txt summary: Clearly the lack of validated DNA reference sequences is hindering our ability to accurately assign a species identity, and accordingly, we advocate that more attention needs to be paid to establishing validated, multi locus mtDNA reference databases for exotic birds that can both assist in genetic identifications and withstand legal scrutiny. Clearly the lack of validated DNA reference sequences is hindering our ability to accurately assign a species identity, and accordingly, we advocate that more attention needs to be paid to establishing validated, multi locus mtDNA reference databases for exotic birds that can both assist in genetic identifications and withstand legal scrutiny. In wildlife forensics, DNA species identification is commonly carried out by amplifying and sequencing fragments of the mitochondrial DNA (mtDNA) genes cytochrome oxidase I (COI), cytochrome b (Cytb), or 12S ribosomal RNA (12S) [15, 17, 20, 21] . abstract: Psittaciformes (parrots and cockatoos) are charismatic birds, their plumage and capacity for learning make them highly sought after pets. The illegal trade in parrots and cockatoos poses a serious threat to the viability of native populations; in addition, species transported to non-endemic areas may potentially vector disease and genetically ‘pollute’ local native avifauna. To reduce the logistical difficulties associated with trafficking live birds, smugglers often transport eggs. This creates a problem for authorities in elucidating accurate species identification without the laborious task of incubation and hand rearing until a morphological identification can be made. Here, we use 99 avian eggs seized from carriers coming into and within Australia, as a result of suspected illegal trade. We investigate and evaluate the use of mitochondrial DNA (mtDNA) to accurately identify eggs to family, genus or species level. However, Identification of a species based on percentage mtDNA similarities is difficult without good representations of the inter- and intra-levels of species variation. Based on the available reference database, we were able to identify 52% of the eggs to species level. Of those, 10 species from eight genera were detected, all of which belong to the parrot (Psittacidae) and cockatoo (Cacatuidae) families. Of the remaining 48%, a further 36% of eggs were identified to genus level, and 12% identified to family level using our assignment criteria. Clearly the lack of validated DNA reference sequences is hindering our ability to accurately assign a species identity, and accordingly, we advocate that more attention needs to be paid to establishing validated, multi locus mtDNA reference databases for exotic birds that can both assist in genetic identifications and withstand legal scrutiny. url: https://www.sciencedirect.com/science/article/pii/S1872497311001323 doi: 10.1016/j.fsigen.2011.06.006 id: cord-004501-guiy89x8 author: Cojocaru, Florina-Daniela title: Nanomaterials Designed for Antiviral Drug Delivery Transport across Biological Barriers date: 2020-02-18 words: 13993.0 sentences: 673.0 pages: flesch: 37.0 cache: ./cache/cord-004501-guiy89x8.txt txt: ./txt/cord-004501-guiy89x8.txt summary: According to the literature data results, namomaterials designed with different shapes and morphologies display numerous advantages for use in antiviral therapy, namely: nanometric size that permits drug delivery through impermeable barriers [88] , large surface area to volume ratios for large drug payloads incorporation [117] and improved efficacy, surface modification and/or backbone functionalization versatility that facilitates cellular membranes passage [118] or enhancing stability and bioavailability [119] , virucidal activity against a series of viruses (HIV, HSV, HBV, etc.) due to biomimetic properties [120] , increased specificity, improved antiviral delivery and controlled drug release to the target [121] through engineered moieties, decrease the emergence of drug resistance, personalized therapy possibility, protection of the drugs and low adverse drug side effects mainly due to the composition. abstract: Viral infections are a major global health problem, representing a significant cause of mortality with an unfavorable continuously amplified socio-economic impact. The increased drug resistance and constant viral replication have been the trigger for important studies regarding the use of nanotechnology in antiviral therapies. Nanomaterials offer unique physico-chemical properties that have linked benefits for drug delivery as ideal tools for viral treatment. Currently, different types of nanomaterials namely nanoparticles, liposomes, nanospheres, nanogels, nanosuspensions and nanoemulsions were studied either in vitro or in vivo for drug delivery of antiviral agents with prospects to be translated in clinical practice. This review highlights the drug delivery nanosystems incorporating the major antiviral classes and their transport across specific barriers at cellular and intracellular level. Important reflections on nanomedicines currently approved or undergoing investigations for the treatment of viral infections are also discussed. Finally, the authors present an overview on the requirements for the design of antiviral nanotherapeutics. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076512/ doi: 10.3390/pharmaceutics12020171 id: cord-017867-8cn4c6cu author: Collántes-Fernández, Esther title: Trichomonas date: 2017-11-08 words: 24060.0 sentences: 1231.0 pages: flesch: 48.0 cache: ./cache/cord-017867-8cn4c6cu.txt txt: ./txt/cord-017867-8cn4c6cu.txt summary: In addition, the OIE Terrestrial Manual also provides recommendations for PCR analyses, which can be applied in combination either with or after culture as an ancillary test or-more often-direct as the primary test to examine bovine samples-i.e., preputial material, uterine or vaginal secretions, or abomasal content of aborted fetuses. In bovine tritrichomonosis cultivation became an important diagnostic tool, because parasite numbers in bovine samples-e.g., preputial smegma or cervico-vaginal mucus-are usually too low to be detected by direct microscopy and a multiplication of parasites after a few days of cultivation increases the chance to find infected bulls. Sensitivity and specificity of culture and PCR of smegma samples of bulls experimentally infected with Tritrichomonas foetus Evaluation of a PCR test for the diagnosis of Tritrichomonas foetus infection in bulls: effects of sample collection method, storage and transport medium on the test Comparison of sampling and culture methods for the diagnosis of Tritrichomonas foetus infection in bulls abstract: The most widely known trichomonad in veterinary medicine is Tritrichomonas foetus. It is the etiologic agent of bovine tritrichomonosis, a sexually transmitted disease in extensively managed herds throughout many geographic regions worldwide. The same trichomonad species is also regarded as the causative agent of chronic diarrhea in the domestic cat, although more recent studies observed molecular differences between bovine- and feline-derived T. foetus. Trichomonosis in cats has a worldwide distribution and is mainly present among cats from high-density housing environments. Other trichomonads are found as inhabitants of the gastrointestinal tract in birds, such as Trichomonas gallinae. Particularly, Columbiformes, Falconiformes, Strigiformes, and wild Passeriformes can be severely affected by avian trichomonads. Diagnosis of trichomonosis is often complicated by the fragility of the parasite. To ensure valid test results, it is essential to collect and handle specimens in the right way prior to analysis. Cultivation tests, the specific amplification of parasites, or a combination of both test methods is the most efficient and most commonly used way to diagnose trichomonosis in animals. Bovine tritrichomonosis is mainly controlled by the identification and withdrawal of infected animals from bovine herds. The control of feline and avian trichomonosis relies mainly on preventive measures. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122547/ doi: 10.1007/978-3-319-70132-5_14 id: cord-345144-zvu22n8f author: Compagnone, D. title: Chapter 29 Rapid detection of organophosphates, Ochratoxin A, and Fusarium sp. in durum wheat via screen printed based electrochemical sensors date: 2007-12-31 words: 7893.0 sentences: 411.0 pages: flesch: 46.0 cache: ./cache/cord-345144-zvu22n8f.txt txt: ./txt/cord-345144-zvu22n8f.txt summary: Additionally, the developed device, which consists of the hand-held potentiostat, the multiplexer for eight-channel control and a dedicated software, can be used to detect organophosphates pesticides, such as dichlorvos and pirimiphos methyl at contamination level below the maximum residue limit settled by the European Union and also amplified DNA of F. We successfully applied an AChE inhibition assay to the detection of dichlorvos in durum wheat samples using a simplified extraction procedure. Both the determinations reported here rely on the inhibition activity of OPs pesticides toward AChE combined with the detection of the AChE enzyme product choline at the surface of a mediator-modified screen-printed choline oxidase electrochemical biosensor. Here we report experimental data obtained using the proposed electrochemical assay with screen-printed choline oxidase biosensor for the detection of dichlorvos in durum wheat samples. abstract: Publisher Summary Most of the inhibition bioassays or biosensors for organophosphate and carbamate pesticides are based on the amperometric detection of the enzymatic product of the reaction. Applications of amperometric biosensing strategies for pesticide detection in real or spiked food samples have been recently reported. Most of the applications have been developed for vegetable matrices. Different formats of biosensors have been used: disposable screenprinted choline oxidase biosensors using acetylcholinesterase (AChE) in solution were utilized to detect pesticides. Screen-printed sensor developed using photolithographic conducting copper track, graphite–epoxy composite, and either AChE or butirrylcholinesterase was also used in the analysis of spiked (paraoxon and carbofuran) samples of tap water and fruit juices at sub-nanomolar concentration. Additionally, the developed device, which consists of the hand-held potentiostat, the multiplexer for eight-channel control and a dedicated software, can be used to detect organophosphates pesticides, such as dichlorvos and pirimiphos methyl at contamination level below the maximum residue limit settled by the European Union and also amplified DNA of F. culmorum. url: https://www.sciencedirect.com/science/article/pii/S0166526X06490292 doi: 10.1016/s0166-526x(06)49029-2 id: cord-288444-0vv4neq6 author: Cotrone, Serafina title: Microcantilevers and organic transistors: two promising classes of label-free biosensing devices which can be integrated in electronic circuits date: 2011-12-22 words: 6464.0 sentences: 302.0 pages: flesch: 33.0 cache: ./cache/cord-288444-0vv4neq6.txt txt: ./txt/cord-288444-0vv4neq6.txt summary: This paper aims to review some recent results concerning the development of biosensing devices based on microcantilevers (MCLs) and organic transistors. Since biological systems are based on cell-cell interactions and the transduction of biosignals between cells, the possibility to interface cells to organic materials to be integrated in electronic devices will be here reviewed. Although these devices have been extensively studied as chemical [8, 25] and biological sensors [9, 26, 27] , the possibility of interfacing them with living cells requires that the organic electronic material establishes a stable interface with water and conducts not only electronic but also ionic carriers. In conclusion, both organic transistors and MCLs possess the requisites necessary for devices of interest in life science applications and possess such a high sensitivity as to even be able to detect single cells; very recently, an interesting combination between an OFET and a polymer cantilever platform was proposed. abstract: Most of the success of electronic devices fabricated to actively interact with a biological environment relies on the proper choice of materials and efficient engineering of surfaces and interfaces. Organic materials have proved to be among the best candidates for this aim owing to many properties, such as the synthesis tunability, processing, softness and self-assembling ability, which allow them to form surfaces that are compatible with biological tissues. This review reports some research results obtained in the development of devices which exploit organic materials’ properties in order to detect biologically significant molecules as well as to trigger/capture signals from the biological environment. Among the many investigated sensing devices, organic field-effect transistors (OFETs), organic electrochemical transistors (OECTs) and microcantilevers (MCLs) have been chosen. The main factors motivating this choice are their label-free detection approach, which is particularly important when addressing complex biological processes, as well as the possibility to integrate them in an electronic circuit. Particular attention is paid to the design and realization of biocompatible surfaces which can be employed in the recognition of pertinent molecules as well as to the research of new materials, both natural and inspired by nature, as a first approach to environmentally friendly electronics. [Figure: see text] url: https://www.ncbi.nlm.nih.gov/pubmed/22189629/ doi: 10.1007/s00216-011-5610-2 id: cord-321697-yua3apfi author: Crigna, Adriana Torres title: Cell-free nucleic acid patterns in disease prediction and monitoring—hype or hope? date: 2020-10-29 words: 10892.0 sentences: 608.0 pages: flesch: 40.0 cache: ./cache/cord-321697-yua3apfi.txt txt: ./txt/cord-321697-yua3apfi.txt summary: This article highlights the involvement of circulating CFNAs in local and systemic processes dealing with the question, whether specific patterns of CFNAs in blood, their detection, quantity and quality (such as their methylation status) might be instrumental to predict a disease development/progression and could be further utilised for accompanying diagnostics, targeted prevention, creation of individualised therapy algorithms, therapy monitoring and prognosis. Especially severe, prolonged and/ or chronic stress of any origin such as exercise-induced oxidative stress [22] (see "Physical activity and exercise-induced oxidative stress" section), hormonal stress [23] , emotional stress and psychological burden [24] [25] [26] [27] as well as metabolic stress, e.g. in diabetes mellitus [28, 29] (see also below "Association between diabetes mellitus and carcinogenesis: diagnostic and therapeutic potential of cell-free nucleic acids" section) and hyperhomocysteinaemia [30, 31] amongst others, is associated with highly increased ROS production and insufficient repair capacity-both linked to oxidative damage of mitochondria and consequent mitochondrial dysfunction leading to the development of cardiovascular impairments [32] [33] [34] , neuro/degenerative pathologies [34] [35] [36] [37] , impaired healing [34] and malignant cell transformation [34, [38] [39] [40] [41] [42] . abstract: Interest in the use of cell-free nucleic acids (CFNAs) as clinical non-invasive biomarker panels for prediction and prevention of multiple diseases has greatly increased over the last decade. Indeed, circulating CFNAs are attributable to many physiological and pathological processes such as imbalanced stress conditions, physical activities, extensive apoptosis of different origin, systemic hypoxic-ischemic events and tumour progression, amongst others. This article highlights the involvement of circulating CFNAs in local and systemic processes dealing with the question, whether specific patterns of CFNAs in blood, their detection, quantity and quality (such as their methylation status) might be instrumental to predict a disease development/progression and could be further utilised for accompanying diagnostics, targeted prevention, creation of individualised therapy algorithms, therapy monitoring and prognosis. Presented considerations conform with principles of 3P medicine and serve for improving individual outcomes and cost efficacy of medical services provided to the population. url: https://doi.org/10.1007/s13167-020-00226-x doi: 10.1007/s13167-020-00226-x id: cord-030295-jlhht2l9 author: Cruz-Flores, Roberto title: Genome reconstruction of white spot syndrome virus (WSSV) from archival Davidson’s-fixed paraffin embedded shrimp (Penaeus vannamei) tissue date: 2020-08-10 words: 4004.0 sentences: 209.0 pages: flesch: 49.0 cache: ./cache/cord-030295-jlhht2l9.txt txt: ./txt/cord-030295-jlhht2l9.txt summary: title: Genome reconstruction of white spot syndrome virus (WSSV) from archival Davidson''s-fixed paraffin embedded shrimp (Penaeus vannamei) tissue In this study, the complete genome of white spot syndrome virus (WSSV) was reconstructed from ~ 2-year-old archived Davidson''s-fixed paraffin-embedded (DFPE) shrimp tissue using Next Generation Sequencing (NGS). Archived Davidson''s-fixed paraffin-embedded (DFPE) tissues in the Aquaculture Pathology Laboratory of The University of Arizona are an untapped invaluable resource for pathogen discovery, metagenomic and evolutionary studies to understand the origin, evolution and spread of shrimp pathogens worldwide. Our results confirm that NGS from DNA extracted from DFPE tissue is also a viable approach to detect know viral sequences. The ability to reconstruct DNA viral genomes as large as 300 kbp size from DFPE tissues shows the feasibility to generate baseline genetic data from archived tissue and determine how pathogens have evolved over time. abstract: Formalin-fixed paraffin-embedded (FFPE) tissues are a priceless resource for diagnostic laboratories worldwide. However, DNA extracted from these tissues is often not optimal for most downstream molecular analysis due to fragmentation and chemical modification. In this study, the complete genome of white spot syndrome virus (WSSV) was reconstructed from ~ 2-year-old archived Davidson’s-fixed paraffin-embedded (DFPE) shrimp tissue using Next Generation Sequencing (NGS). A histological analysis was performed on archived DFPE shrimp tissue and a sample showing a high level of WSSV infection was selected for molecular analysis. The viral infection was further confirmed by molecular methods. DNA isolated from DFPE and fresh frozen (FF) tissues were sequenced by NGS. The complete genome reconstruction of WSSV (~ 305 kbp) was achieved from both DFPE and FF tissue. Single nucleotide polymorphisms, insertion and deletions were compared between the genomes. Thirty-eight mutations were identified in the WSSV genomes from the DFPE and FF that differed from the reference genome. This is the first study that has successfully sequenced the complete genome of a virus of over 300 kbp from archival DFPE tissue. These findings demonstrate that DFPE shrimp tissue represents an invaluable resource for prospective and retrospective studies, evolutionary studies and opens avenues for pathogen discovery. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417530/ doi: 10.1038/s41598-020-70435-x id: cord-286877-0h5vgi5c author: Dahiya, Shyam S. title: Immunogenicity of a DNA-launched replicon-based canine parvovirus DNA vaccine expressing VP2 antigen in dogs date: 2012-10-31 words: 5260.0 sentences: 261.0 pages: flesch: 43.0 cache: ./cache/cord-286877-0h5vgi5c.txt txt: ./txt/cord-286877-0h5vgi5c.txt summary: When the pAlpha-CPV-VP2 was injected intradermal as DNA-launched replicon-based DNA vaccine in dogs, it induced CPV-specific humoral and cell mediated immune responses. To increase antigen production and immunogenicity with DNA vaccines, a new strategy has been developed to express the target heterologous antigen under the control of replicon from positive-strand RNA viruses with the promise of using the ability of these viruses to produce large amounts of viral proteins in infected cells. The replicon-based CPV DNA vaccine plasmid (pAlpha-CPV-VP2) encoding CPV-VP2 was constructed and evaluated to express CPV-VP2 protein in transfected cells in SDS-PAGE and Western blot (data not shown). To assess the protective efficacy of different CPV vaccines, sera collected from all immunized and control dogs were analyzed for presence of virus neutralizing (VN) antibody. CD8 + lymphocytes in dogs immunized with replicon-based CPV DNA vaccine compared to controls (Fig. 7) . There were over 24 thousand times more CPV-VP2 mRNA transcripts in pAlpha-CPV-VP2-transfected BHK-21 cells compared to respective non-replicating control indicating the self-replicating ability of replicon-based CPV-VP2 DNA vaccine. abstract: Abstract A replicon-based DNA vaccine encoding VP2 gene of canine parvovirus (CPV) was developed by cloning CPV-VP2 gene into a replicon-based DNA vaccine vector (pAlpha). The characteristics of a replicon-based DNA vaccine like, self-amplification of transcripts and induction of apoptosis were analyzed in transfected mammalian cells. When the pAlpha-CPV-VP2 was injected intradermal as DNA-launched replicon-based DNA vaccine in dogs, it induced CPV-specific humoral and cell mediated immune responses. The virus neutralization antibody and lymphocyte proliferative responses were higher than conventional CPV DNA vaccine and commercial CPV vaccine. These results indicated that DNA-launched replicon-based CPV DNA vaccine was effective in inducing both CPV-specific humoral and cellular immune responses and can be considered as effective alternative to conventional CPV DNA vaccine and commercial CPV vaccine. url: https://api.elsevier.com/content/article/pii/S0034528812000616 doi: 10.1016/j.rvsc.2012.01.017 id: cord-338582-o976nab9 author: Dahlhausen, Bob title: Future Veterinary Diagnostics date: 2010-09-19 words: 9199.0 sentences: 511.0 pages: flesch: 35.0 cache: ./cache/cord-338582-o976nab9.txt txt: ./txt/cord-338582-o976nab9.txt summary: Genome sequencing has allowed efficient, sensitive, and specific diagnostic assays to be developed based on the detection of nucleic acids. PCR uses the highly specific molecular recognition ability of Watson-Crick base pairing to provide the selectivity needed for a nucleic acid probe to bind to a targeted DNA sequence and allow for its exponential amplification. It has been used to develop rapid diagnostic tests for several pathogenic viruses with singlestranded RNA genomes, including influenza A, 13 footand-mouth disease virus, 14 and severe acute respiratory syndrome (SARS)-associated coronavirus. DNA microarrays also permit relatively rapid interrogation of a clinical sample against thousands of genetic targets, allowing for simultaneous detection and discrimination among hundreds of pathogenic agents of veterinary interest. Unlike PCR technology where the target agent must be known to use specific test primers, microarrays can allow for the rapid diagnosis of multiple pathogenic agents in disease outbreaks and epidemics of unknown etiology. abstract: The development of rapid, accurate, and sensitive diagnostic methods for detecting pathogens is the basis for treating, controlling, and eradicating infectious diseases of veterinary importance. Scientific and technological advancements have revolutionized the field of veterinary diagnostics. Genome sequencing has allowed efficient, sensitive, and specific diagnostic assays to be developed based on the detection of nucleic acids. The integration of advances in biochemistry, proteomics, engineering, and medicine offers enormous potential for the rapid and accurate diagnosis of viral, microbial, genetic, and metabolic disease. In the future, polymerase chain reaction assays, microarray testing, genomic analysis, and metabolic profiling will be accomplished in a rapid, portable, sensitive, and cost-efficient manner. url: https://doi.org/10.1053/j.jepm.2010.05.006 doi: 10.1053/j.jepm.2010.05.006 id: cord-268549-2lg8i9r1 author: Dai, Qi title: Sequence comparison via polar coordinates representation and curve tree date: 2012-01-07 words: 4360.0 sentences: 272.0 pages: flesch: 59.0 cache: ./cache/cord-268549-2lg8i9r1.txt txt: ./txt/cord-268549-2lg8i9r1.txt summary: It considers whole distribution of dual bases and employs polar coordinates method to map a biological sequence into a closed curve. First, many graphical representations were designed by assigning the single bases or dual nucleotides to corresponding direction/points/cells in Cartesian coordinates, so little attention has been paid to the whole distribution of the single nucleotide or dual nucleotides in biological sequences. Based on the whole distribution of the dual bases, we proposed a polar coordinates representation that maps a biological sequence into a closed curve. Here, we propose a novel graphical representation of DNA sequence in polar coordinates based on the distribution of the dual nucleotides. In contrast to the existing graphical representations, we used the whole distribution of the dual bases to map a biological sequence into a closed curve in polar coordinates. Analysis of similarity/dissimilarity of DNA sequences based on novel 2-D graphical representation abstract: Abstract Sequence comparison has become one of the essential bioinformatics tools in bioinformatics research, which could serve as evidence of structural and functional conservation, as well as of evolutionary relations among the sequences. Existing graphical representation methods have achieved promising results in sequence comparison, but there are some design challenges with the graphical representations and feature-based measures. We reported here a new method for sequence comparison. It considers whole distribution of dual bases and employs polar coordinates method to map a biological sequence into a closed curve. The curve tree was then constructed to numerically characterize the closed curve of biological sequences, and further compared biological sequences by evaluating the distance of the curve tree of the query sequence matching against a corresponding curve tree of the template sequence. The proposed method was tested by phylogenetic analysis, and its performance was further compared with alignment-based methods. The results demonstrate that using polar coordinates representation and curve tree to compare sequences is more efficient. url: https://doi.org/10.1016/j.jtbi.2011.09.030 doi: 10.1016/j.jtbi.2011.09.030 id: cord-306780-9xelf8oh author: Dale, Timothy D. title: Enhancement of wildlife disease surveillance using multiplex quantitative PCR: development of qPCR assays for major pathogens in UK squirrel populations date: 2016-07-28 words: 6931.0 sentences: 371.0 pages: flesch: 54.0 cache: ./cache/cord-306780-9xelf8oh.txt txt: ./txt/cord-306780-9xelf8oh.txt summary: However, comparatively few wildlife epidemiological studies use quantitative PCR (qPCR) for pathogen detection, even fewer employ an internal control, to ensure confidence in negative results, and PCR''s ability to multiplex and therefore detect several targets in a single reaction is underutilised. Tests on infected squirrel tissue demonstrate that simple swab samples (particularly from distal antebrachial skin) are sufficient to detect and identify the relative quantity of SQPV DNA in both squirrel species, while rectal swabs and blood cell pellets can be used to reliably indicate SADV infection. As grey squirrels appear asymptomatic, lower infection loads are recorded, and thus it is essential to use the more sensitive qPCR assays when screening for SQPV presence as part of a wildlife disease management programme for red squirrels. abstract: Rapid development in polymerase chain reaction (PCR) technology has revolutionised the speed and accuracy of many diagnostic assays. However, comparatively few wildlife epidemiological studies use quantitative PCR (qPCR) for pathogen detection, even fewer employ an internal control, to ensure confidence in negative results, and PCR’s ability to multiplex and therefore detect several targets in a single reaction is underutilised. Here, we describe the development of two multiplex qPCR assays for the red and grey squirrel that detect the pathogens squirrelpox virus (SQPV) and adenovirus in squirrels (SADV), both of which cause mortality in the red squirrel. Both assays use a section of the squirrel phosphoglycerate kinase gene as an endogenous internal control that identifies and compensates for both, inadequate sampling or PCR inhibition. Tests on infected squirrel tissue demonstrate that simple swab samples (particularly from distal antebrachial skin) are sufficient to detect and identify the relative quantity of SQPV DNA in both squirrel species, while rectal swabs and blood cell pellets can be used to reliably indicate SADV infection. These assays are sensitive and specific with an endogenous internal control providing confidence in negative results and allowing comparison across laboratories. Using such assays should prove advantageous in wildlife studies with limited resources while allowing the maximum data yield. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10344-016-1031-z) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1007/s10344-016-1031-z doi: 10.1007/s10344-016-1031-z id: cord-272943-q09i8fqu author: Dalhoff, A. title: Antiviral, antifungal, and antiparasitic activities of fluoroquinolones optimized for treatment of bacterial infections: a puzzling paradox or a logical consequence of their mode of action? date: 2014-12-17 words: 4715.0 sentences: 256.0 pages: flesch: 36.0 cache: ./cache/cord-272943-q09i8fqu.txt txt: ./txt/cord-272943-q09i8fqu.txt summary: Surprisingly, the use of fluoroquinolones in indications other than bacterial infections has never been exploited, although not only nalidixic acid and its congener chloroquine exerts pleiotropic actions but, e.g., β-lactams and aminoglycosides are characterized by a broad range of biological activities too [47, 48] , so that a multitude of antimicrobial effects would not have been unusual. Fluoroquinolones inhibit not only enzymic activity of viral topoisomerases/helicases, but inhibit in vitro human immunodeficiency virus (HIV) reverse transcriptase as well; complete inhibition was observed at concentrations of ciprofloxacin and ofloxacin of 3 μM and norfloxacin of 1 μM, respectively [71] [72] [73] . Fluoroquinolones like ciprofloxacin, amifloxacin, enoxacin, norfloxacin, ofloxacin, pefloxacin, grepafloxacin, trovafloxacin, and 16 additional commercially available quinolones exhibit marked in vitro activity and in vivo efficacy against Plasmodium spp. abstract: This review summarizes evidence that commercially available fluoroquinolones used for the treatment of bacterial infections are active against other non-bacterial infectious agents as well. Any of these fluoroquinolones exerts, in parallel to its antibacterial action, antiviral, antifungal, and antiparasitic actions at clinically achievable concentrations. This broad range of anti-infective activities is due to one common mode of action, i.e., the inhibition of type II topoisomerases or inhibition of viral helicases, thus maintaining the selective toxicity of fluoroquinolones inhibiting microbial topoisomerases at low concentrations but mammalian topoisomerases at much higher concentrations. Evidence suggests that standard doses of the fluoroquinolones studied are clinically effective against viral and parasitic infections, whereas higher doses administered topically were active against Candida spp. causing ophthalmological infections. Well-designed clinical studies should be performed to substantiate these findings. url: https://doi.org/10.1007/s10096-014-2296-3 doi: 10.1007/s10096-014-2296-3 id: cord-262733-icnkx1rx author: Daneluz, Larissa O. title: Efficiency and cell viability implications using tip type electroporation in zebrafish sperm cells date: 2020-07-13 words: 4961.0 sentences: 254.0 pages: flesch: 46.0 cache: ./cache/cord-262733-icnkx1rx.txt txt: ./txt/cord-262733-icnkx1rx.txt summary: Sperm kinetics parameters were assessed using Computer Assisted Semen Analysis (CASA) and cell integrity, reactive oxygen species (ROS), mitochondrial functionality and transfection rate were evaluated by flow cytometry. increased DNA uptake by sperm cells, some problems are associated with the conventional cuvette type electroporation, such as low transfection rate, mosaic gene expression, and negative effects on cell viability [9] . The objective of this study was to demonstrate the feasibility of tip type electroporation in Danio rerio sperm, allowing its further use in SMGT, showing a protocol that provide high transfection efficiency, with minimal sideeffects on sperm cells. Cell integrity, membrane fluidity, mitochondrial functionality, concentration of reactive oxygen species (ROS) and total of sperm-bound exogenous DNA were evaluated by flow cytometry (Attune® Acoustic Focusing Cytometer, Applied Biosystems, USA) as previously described [30] . Here, transfection rate of fish spermatozoa was positively affected for tip type electroporation, increasing the number of cells containing exogenous DNA. abstract: Sperm-mediated gene transfer (SMGT) has a potential use for zebrafish transgenesis. However, transfection into fish sperm cells still needs to be improved. The objective was to demonstrate the feasibility of tip type electroporation in zebrafish sperm, showing a protocol that provide high transfection efficiency, with minimal side-effects. Sperm was transfected with a Cy3-labelled DNA using tip type electroporation with voltages ranging from 500 to 1500 V. Sperm kinetics parameters were assessed using Computer Assisted Semen Analysis (CASA) and cell integrity, reactive oxygen species (ROS), mitochondrial functionality and transfection rate were evaluated by flow cytometry. The transfection rates were positively affected by tip type electroporation, reaching 64.9% ± 3.6 in the lowest voltage used (500 V) and 86.6% ± 1.9 in the highest (1500 V). The percentage of overall motile sperm in the electrotransfected samples was found to decrease with increasing field strength (P < 0.05). Increase in the sperm damaged plasma membrane was observed with increasing field strength (P < 0.05). ROS and sperm mitochondrial functionality did not present a negative response after the electroporation (P > 0.05). Overall results indicate that tip type electroporation enhances the internalization of exogenous DNA into zebrafish sperm cells with minimal harmful effects to sperm cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11033-020-05658-2) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1007/s11033-020-05658-2 doi: 10.1007/s11033-020-05658-2 id: cord-349672-2kt7xw8i author: Dasgupta, Tumpa title: Mechanism of Type IA Topoisomerases date: 2020-10-17 words: 8538.0 sentences: 463.0 pages: flesch: 53.0 cache: ./cache/cord-349672-2kt7xw8i.txt txt: ./txt/cord-349672-2kt7xw8i.txt summary: Here, based on available structural and biochemical data, we discuss how a type IA topoisomerase may recognize and bind single-stranded DNA or RNA to initiate its required catalytic function. In type IA topoisomerases, the hydroxyl group in the side chain of the active site tyrosine residue is responsible for the first nucleophilic attack on the scissile phosphate of a single-stranded DNA resulting in the cleavage of the G-strand and the formation of the transient 5 -phospho-tyrosyl covalent linkage [66] . Though the type IA topoisomerase core domain that forms the characteristic torus structure contains all the highly conserved motifs responsible for G-strand binding and cleavage religation, the C-terminal domains of bacterial topoisomerase I have been shown to be required for removing negative supercoils from DNA rapidly in a processive mechanism [61, 72, [84] [85] [86] [87] . abstract: Topoisomerases in the type IA subfamily can catalyze change in topology for both DNA and RNA substrates. A type IA topoisomerase may have been present in a last universal common ancestor (LUCA) with an RNA genome. Type IA topoisomerases have since evolved to catalyze the resolution of topological barriers encountered by genomes that require the passing of nucleic acid strand(s) through a break on a single DNA or RNA strand. Here, based on available structural and biochemical data, we discuss how a type IA topoisomerase may recognize and bind single-stranded DNA or RNA to initiate its required catalytic function. Active site residues assist in the nucleophilic attack of a phosphodiester bond between two nucleotides to form a covalent intermediate with a 5′-phosphotyrosine linkage to the cleaved nucleic acid. A divalent ion interaction helps to position the 3′-hydroxyl group at the precise location required for the cleaved phosphodiester bond to be rejoined following the passage of another nucleic acid strand through the break. In addition to type IA topoisomerase structures observed by X-ray crystallography, we now have evidence from biophysical studies for the dynamic conformations that are required for type IA topoisomerases to catalyze the change in the topology of the nucleic acid substrates. url: https://doi.org/10.3390/molecules25204769 doi: 10.3390/molecules25204769 id: cord-022142-d4yxgv83 author: David, Ayelet title: Polymer-Based DNA Delivery Systems for Cancer Immunotherapy date: 2016-05-28 words: 7778.0 sentences: 367.0 pages: flesch: 43.0 cache: ./cache/cord-022142-d4yxgv83.txt txt: ./txt/cord-022142-d4yxgv83.txt summary: A number of polymer-based nanomedicines have been developed to deliver genes into DCs, primarily by incorporating tumor-specific, antigen-encoding plasmid DNA with polycationic molecules to facilitate DNA loading and intracellular trafficking. Direct in vivo targeting of plasmid DNA to DC surface receptors can induce high transfection efficiency and long-term gene expression, essential for antigen loading onto major histocompatibility complex molecules and stimulation of T-cell responses. This chapter highlights the repertoire of non-viral, nanosized polymeric DNA delivery systems (polyplexes) available to achieve effi cient gene transfer into DCs for immunotherapeutic applications in cancer therapy. With respect to clinical translation, effi cacious non-viral gene delivery into DCs will depend on the combination of intelligent material design, the appropriate tumor specifi c antigen-encoding DNA and immuno-stimulatory molecules to promote DC maturation and activation. abstract: The use of gene delivery systems for the expression of antigenic proteins is an established means for activating a patient’s own immune system against the cancer they carry. Since tumor cells are poor antigen-presenting cells, cross-presentation of tumor antigens by dendritic cells (DCs) is essential for the generation of tumor-specific cytotoxic T-lymphocyte responses. A number of polymer-based nanomedicines have been developed to deliver genes into DCs, primarily by incorporating tumor-specific, antigen-encoding plasmid DNA with polycationic molecules to facilitate DNA loading and intracellular trafficking. Direct in vivo targeting of plasmid DNA to DC surface receptors can induce high transfection efficiency and long-term gene expression, essential for antigen loading onto major histocompatibility complex molecules and stimulation of T-cell responses. This chapter summarizes the physicochemical properties and biological information on polymer-based non-viral vectors used for targeting DCs, and discusses the main challenges for successful in vivo gene transfer into DCs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153417/ doi: 10.1007/978-1-4939-3634-2_10 id: cord-342819-p8wp6yvo author: De Groot, Anne S title: Making vaccines “on demand”: A potential solution for emerging pathogens and biodefense? date: 2013-09-01 words: 5661.0 sentences: 259.0 pages: flesch: 40.0 cache: ./cache/cord-342819-p8wp6yvo.txt txt: ./txt/cord-342819-p8wp6yvo.txt summary: The accelerated process, as proposed by our group, would begin with analysis of the genomic sequence of an emerging pathogen with immunoinformatics tools, followed by rapid design of an epitope-based vaccine containing the most immunogenic components, using an integrated in silico approach illustrated in Figure 2 . Available evidence from animal studies suggests that the number of vaccine components (epitopes) required for full protection against disease is a small and definable subset that can be discovered using state-of-the-art computer programs such as the ones described and validated by EpiVax. 30, 31 We have proposed that any FastVax vaccine would include a minimum of 100 broadly reactive T cell epitopes in several strings, designed to induce multi-functional immune responses that are essential for protective immunity. abstract: The integrated US Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) has made great strides in strategic preparedness and response capabilities. There have been numerous advances in planning, biothreat countermeasure development, licensure, manufacturing, stockpiling and deployment. Increased biodefense surveillance capability has dramatically improved, while new tools and increased awareness have fostered rapid identification of new potential public health pathogens. Unfortunately, structural delays in vaccine design, development, manufacture, clinical testing and licensure processes remain significant obstacles to an effective national biodefense rapid response capability. This is particularly true for the very real threat of “novel pathogens” such as the avian-origin influenzas H7N9 and H5N1, and new coronaviruses such as hCoV-EMC. Conventional approaches to vaccine development, production, clinical testing and licensure are incompatible with the prompt deployment needed for an effective public health response. An alternative approach, proposed here, is to apply computational vaccine design tools and rapid production technologies that now make it possible to engineer vaccines for novel emerging pathogen and WMD biowarfare agent countermeasures in record time. These new tools have the potential to significantly reduce the time needed to design string-of-epitope vaccines for previously unknown pathogens. The design process—from genome to gene sequence, ready to insert in a DNA plasmid—can now be accomplished in less than 24 h. While these vaccines are by no means “standard,” the need for innovation in the vaccine design and production process is great. Should such vaccines be developed, their 60-d start-to-finish timeline would represent a 2-fold faster response than the current standard. url: https://doi.org/10.4161/hv.25611 doi: 10.4161/hv.25611 id: cord-102336-ex3zlq38 author: De Wijngaert, Brent title: Cryo-EM structures reveal transcription initiation steps by yeast mitochondrial RNA polymerase date: 2020-04-14 words: 2266.0 sentences: 127.0 pages: flesch: 60.0 cache: ./cache/cord-102336-ex3zlq38.txt txt: ./txt/cord-102336-ex3zlq38.txt summary: Cryo-EM structures of transcription pre-initiation complex (PIC) and initiation complex (IC) of yeast mitochondrial RNA polymerase show fully resolved transcription bubbles and explain promoter melting, template alignment, DNA scrunching, transition into elongation, and abortive synthesis. Hence, the structural basis for promoter melting, DNA scrunching, and transcription initiation remains largely unknown for the mtRNAPs. RPO41 (∆N100) and MTF1 were assembled on a pre-melted promoter (-21 to +12, 15S yeast mtDNA promoter; Fig. 1A ) to generate the yeast mitochondrial transcription preinitiation complex (y-mtPIC) (Fig. S1 ). The 3.7 Å density map of IC locates many previously uncharacterized structural elements, including the C-tail of MTF1 and the scrunched DNA ( Fig. 2B-C) , and reveals the mechanism of template alignment and RNA synthesis during initiation. During the transition, the upstream DNA from position -1 onward is locked in the MTF1 NT-groove while the template strand undergoes a large conformational switching to align with the 2-mer RNA and the incoming UTPaS at the active site ( Fig. 2C; Movie S2). abstract: Cryo-EM structures of transcription pre-initiation complex (PIC) and initiation complex (IC) of yeast mitochondrial RNA polymerase show fully resolved transcription bubbles and explain promoter melting, template alignment, DNA scrunching, transition into elongation, and abortive synthesis. Promoter melting initiates in PIC with MTF1 trapping the −4 to −2 non-template (NT) bases in its NT-groove. Transition to IC is marked by a large-scale movement that aligns the template with RNA at the active site. RNA synthesis scrunches the NT strand into an NT-loop, which interacts with centrally positioned MTF1 C-tail. Steric clashes of the C-tail with RNA:DNA and NT-loop, and dynamic scrunching-unscrunching of DNA explain abortive synthesis and transition into elongation. Capturing the catalytically active IC-state with UTPαS poised for incorporation enables modeling toxicity of antiviral nucleosides/nucleotides. url: https://doi.org/10.1101/2020.04.13.038620 doi: 10.1101/2020.04.13.038620 id: cord-258035-2tk7maqk author: DeFilippis, Victor title: Functional genomics in virology and antiviral drug discovery date: 2003-10-31 words: 4769.0 sentences: 255.0 pages: flesch: 39.0 cache: ./cache/cord-258035-2tk7maqk.txt txt: ./txt/cord-258035-2tk7maqk.txt summary: Given that virus replication involves use and manipulation of multiple host proteins and molecular processes, cellular pathways related to transcription and translation, signal transduction, metabolism, host defense and cell cycle control are Review commonly altered in response to, or as a result of, infection with diverse virus types. A special case of virus modulation of host cell gene expression in which functional genomics will reveal novel targets and treatments is viral oncogenesis. The most recent method for analyzing gene inhibition studies has been RNAi or siRNA, where small 21 -23-nucleotide (nt) RNA duplexes interfere with the transcription program by directing degradation of homologous mRNA [34] [35] [36] [37] . Both new-generation antisense oligomers and siRNA can be used to knockdown expression of genes that were found by DNA microarrays to be upregulated in virally infected cells or organisms. RNA interference directed against viral and cellular targets inhibits human immunodeficiency virus type 1 replication abstract: Abstract Virology research and antiviral drug discovery are poised to benefit from the post-genomic revolution for three main reasons. First, viruses need the host to replicate and are therefore vulnerable to inhibition of cellular pathways. Knowledge of complete genomic sequences of both virus and host now permits the study of this interplay on a global scale. Combining transcriptomics and proteomics with large-scale gene knockdown experiments will enable the identification of novel antiviral targets. Second, massive parallel assay systems, such as DNA microarrays, which define the post-genomic era, will facilitate viral diagnostics. Third, the combination of genetics with genomics will enable the analysis of viral mutants and strains on an unprecedented scale. The dramatic effects of viral infection on host cell transcriptional patterns have been well-documented and will be briefly highlighted. In addition, we discuss recent trends that apply functional genomics methods to the discovery of new targets and therapies for viral disease. url: https://www.ncbi.nlm.nih.gov/pubmed/14512232/ doi: 10.1016/s0167-7799(03)00207-5 id: cord-276271-3nz3169p author: Deborggraeve, Stijn title: T. cruzi OligoC-TesT: A Simplified and Standardized Polymerase Chain Reaction Format for Diagnosis of Chagas Disease date: 2009-06-02 words: 4732.0 sentences: 261.0 pages: flesch: 52.0 cache: ./cache/cord-276271-3nz3169p.txt txt: ./txt/cord-276271-3nz3169p.txt summary: cruzi OligoC-TesT: A Simplified and Standardized Polymerase Chain Reaction Format for Diagnosis of Chagas Disease The specificity and sensitivity of the assay were evaluated on blood samples from 60 Chagas non-endemic and 48 endemic control persons and on biological samples from 33 patients, 7 reservoir animals, and 14 vectors collected in Chile. We assessed the diagnostic accuracy of the assay on a broad spectrum of biological samples from Chagas non-endemic and endemic control persons, infected children, adults, reservoir animals and vectors. DNA from 25 different Trypanosoma rangeli isolates (Table 1) and from Leishmania donovani, Trypanosoma brucei gambiense, Mycobacterium tuberculosis, Schistosoma mansoni and Plasmodium falciparum was obtained from other research groups. cruzi OligoC-TesT, a simple and standardized dipstick format for detection of PCR amplified T. cruzi OligoC-TesT, a simple and standardized dipstick format for detection of PCR amplified T. abstract: BACKGROUND: PCR has evolved into one of the most promising tools for T. cruzi detection in the diagnosis and control of Chagas disease. However, general use of the technique is hampered by its complexity and the lack of standardization. METHODOLOGY: We here present the development and phase I evaluation of the T. cruzi OligoC-TesT, a simple and standardized dipstick format for detection of PCR amplified T. cruzi DNA. The specificity and sensitivity of the assay were evaluated on blood samples from 60 Chagas non-endemic and 48 endemic control persons and on biological samples from 33 patients, 7 reservoir animals, and 14 vectors collected in Chile. PRINCIPAL FINDINGS: The lower detection limits of the T. cruzi OligoC-TesT were 1 pg and 1 to 10 fg of DNA from T. cruzi lineage I and II, respectively. The test showed a specificity of 100% (95% confidence interval [CI]: 96.6%–100%) on the control samples and a sensitivity of 93.9% (95% CI: 80.4%–98.3%), 100% (95% CI: 64.6%–100%), and 100% (95% CI: 78.5%–100%) on the human, rodent, and vector samples, respectively. CONCLUSIONS: The T. cruzi OligoC-TesT showed high sensitivity and specificity on a diverse panel of biological samples. The new tool is an important step towards simplified and standardized molecular diagnosis of Chagas disease. url: https://doi.org/10.1371/journal.pntd.0000450 doi: 10.1371/journal.pntd.0000450 id: cord-296197-ohfhnpma author: Deborggraeve, Stijn title: A Simplified and Standardized Polymerase Chain Reaction Format for the Diagnosis of Leishmaniasis date: 2008-11-15 words: 4229.0 sentences: 207.0 pages: flesch: 47.0 cache: ./cache/cord-296197-ohfhnpma.txt txt: ./txt/cord-296197-ohfhnpma.txt summary: A phase 1 evaluation of the text was conducted in clinical samples from 60 nonendemic and 45 endemic control subjects and from 44 patients with confirmed cutaneous leishmaniasis (CL), 12 with mucocutaneous leishmaniasis (MCL), and 43 with visceral leishmaniasis (VL) from Peru, Kenya, and Sudan. The Leishmania OligoC-TesT showed high specificity and sensitivity in clinical samples and was able to detect the parasite in samples obtained by less invasive means, such as blood, lymph, and lesion scrapings. Amplification of the parasite DNA by the polymerase chain reaction (PCR) has evolved into one of the most specific and sensitive methods for Leishmania detection [9, 10] . When evaluated in 56 clinical samples from patients with confirmed CL or MCL (definition based on microscopy and/or culture) collected in Peru, the Leishmania OligoC-TesT showed an overall diagnostic sensitivity of 92.9%, whereas all 8 dental biopsy specimens from healthy control subjects were negative. abstract: Background. Definite diagnosis of Leishmania infections is based on demonstration of the parasite by microscopic analysis of tissue biopsy specimens or aspirate samples. However, microscopy generally shows low sensitivity and requires invasive sampling. Methods. We describe here the development of a simple and rapid test for the detection of polymerase chain reaction-amplified Leishmania DNA. A phase 1 evaluation of the text was conducted in clinical samples from 60 nonendemic and 45 endemic control subjects and from 44 patients with confirmed cutaneous leishmaniasis (CL), 12 with mucocutaneous leishmaniasis (MCL), and 43 with visceral leishmaniasis (VL) from Peru, Kenya, and Sudan. Results. The lower detection limits of the assay are 10 fg of Leishmania DNA and 1 parasite in 180 µL of blood. The specificity was 98.3% (95% confidence interval [CI], 91.1%–99.7%) and 95.6% (95% CI, 85.2%–98.8%) for nonendemic and endemic control samples, respectively, and the sensitivity was 93.2% (95% CI, 81.8%–97.7%), 91.7% (95% CI, 64.6%–98.5%), and 86% (95% CI, 72.7%–93.4%) for lesions from patients with CL or MCL and blood from patients with VL, respectively. Conclusions. The Leishmania OligoC-TesT showed high specificity and sensitivity in clinical samples and was able to detect the parasite in samples obtained by less invasive means, such as blood, lymph, and lesion scrapings. The assay is a promising new tool for simplified and standardized molecular detection of Leishmania parasites. url: https://www.ncbi.nlm.nih.gov/pubmed/18816188/ doi: 10.1086/592509 id: cord-257284-dash9udv author: Decaro, Nicola title: Development and validation of a real-time PCR assay for specific and sensitive detection of canid herpesvirus 1 date: 2010-07-30 words: 3138.0 sentences: 149.0 pages: flesch: 52.0 cache: ./cache/cord-257284-dash9udv.txt txt: ./txt/cord-257284-dash9udv.txt summary: The detection limit was 10(1) and 1.20 × 10(1) DNA copies per 10 μl(−1) of template for standard DNA and a CHV-1-positive kidney sample, respectively: about 1-log higher than a gel-based PCR assay targeting the thymidine kinase gene. Unlike other CHV-1-specific diagnostic methods, this quantitative assay permits simultaneous detection and quantitation of CHV-1 DNA in a wide range of canine tissues and body fluids, thus providing a useful tool for confirmation of a clinical diagnosis, for the study of viral pathogenesis and for evaluation of the efficacy of vaccines and antiviral drugs. To evaluate the detection limits of the real-time PCR assay, 10fold dilutions of the plasmid DNA, ranging from 10 9 to 10 0 copies, were made in a CHV-1-negative kidney homogenate and tested subsequently. The development and validation of a real-time PCR assay for detection and absolute quantitation of CHV-1 DNA in tissue samples and body fluids of dogs are described. abstract: A TaqMan-based real-time PCR assay targeting the glycoprotein B-encoding gene was developed for diagnosis of canid herpesvirus 1 (CHV-1) infection. The established assay was highly specific, since no cross-reactions were observed with other canine DNA viruses, including canine parvovirus type 2, canine minute virus, or canine adenovirus types 1 and 2. The detection limit was 10(1) and 1.20 × 10(1) DNA copies per 10 μl(−1) of template for standard DNA and a CHV-1-positive kidney sample, respectively: about 1-log higher than a gel-based PCR assay targeting the thymidine kinase gene. The assay was also reproducible, as shown by satisfactory low intra-assay and inter-assay coefficients of variation. CHV-1 isolates of different geographical origins were recognised by the TaqMan assay. Tissues and clinical samples collected from three pups which died of CHV-1 neonatal infection were also tested, displaying a wide distribution of CHV-l DNA in their organs. Unlike other CHV-1-specific diagnostic methods, this quantitative assay permits simultaneous detection and quantitation of CHV-1 DNA in a wide range of canine tissues and body fluids, thus providing a useful tool for confirmation of a clinical diagnosis, for the study of viral pathogenesis and for evaluation of the efficacy of vaccines and antiviral drugs. url: https://api.elsevier.com/content/article/pii/S0166093410002636 doi: 10.1016/j.jviromet.2010.07.021 id: cord-327170-rv0efgg2 author: Decaro, Nicola title: Tissue distribution of the antigenic variants of canine parvovirus type 2 in dogs date: 2007-03-31 words: 2675.0 sentences: 143.0 pages: flesch: 54.0 cache: ./cache/cord-327170-rv0efgg2.txt txt: ./txt/cord-327170-rv0efgg2.txt summary: Twelve dogs dead as consequence of natural infection caused by canine parvovirus (CPV) type 2a (n = 4), type 2b (n = 4) or type 2c (n = 4) were investigated for determining the viral DNA loads in different tissue samples. By means of a real-time PCR assay, CPV DNA was detected in all tissues examined, with the highest titres observed in the lymphoid tissue and the lowest loads in the urinary tract. In this study, by using real-time PCR, we investigated the pattern of distribution of the CPV variants in different tissues of dogs infected naturally. The viral DNA titres found in the different tissues of the dogs infected naturally by types 2a, 2b and 2c are reported in Fig. 1 . A real-time PCR assay for rapid detection and quantitation of canine parvovirus type 2 DNA in the feces of dogs A minor groove binder probe real-time PCR assay for discrimination between type 2-based vaccines and field strains of canine parvovirus abstract: Twelve dogs dead as consequence of natural infection caused by canine parvovirus (CPV) type 2a (n = 4), type 2b (n = 4) or type 2c (n = 4) were investigated for determining the viral DNA loads in different tissue samples. By means of a real-time PCR assay, CPV DNA was detected in all tissues examined, with the highest titres observed in the lymphoid tissue and the lowest loads in the urinary tract. Surprisingly, the nervous tissue was found to contain considerable amounts of CPV nucleic acid. Similar patterns of tissue distribution were observed in all the examined dogs irrespective of the antigenic variant causing the disease. url: https://api.elsevier.com/content/article/pii/S0378113506004603 doi: 10.1016/j.vetmic.2006.11.005 id: cord-339915-8j04y50s author: Deng, Wei title: DV-Curve Representation of Protein Sequences and Its Application date: 2014-05-08 words: 2946.0 sentences: 176.0 pages: flesch: 49.0 cache: ./cache/cord-339915-8j04y50s.txt txt: ./txt/cord-339915-8j04y50s.txt summary: Based on the detailed hydrophobic-hydrophilic(HP) model of amino acids, we propose dual-vector curve (DV-curve) representation of protein sequences, which uses two vectors to represent one alphabet of protein sequences. The utility of this approach is illustrated by two examples: one is similarity/dissimilarity comparison among different ND6 protein sequences based on their DV-curve figures the other is the phylogenetic analysis among coronaviruses based on their spike proteins. In this paper, we introduce DV-curve graphical representation of protein sequences based on the detailed hydrophobic-hydrophilic (HP) model of amino acids. Analysis of similarity/dissimilarity of DNA sequences based on novel 2-D graphical representation New graphical representation of a DNA sequence based on the ordered dinucleotides and its application to sequence analysis Analysis of similarity/dissimilarity of DNA sequences based on a condensed curve representation Similarity/dissimilarity studies of protein sequences based on a new 2d graphical representation abstract: Based on the detailed hydrophobic-hydrophilic(HP) model of amino acids, we propose dual-vector curve (DV-curve) representation of protein sequences, which uses two vectors to represent one alphabet of protein sequences. This graphical representation not only avoids degeneracy, but also has good visualization no matter how long these sequences are, and can reflect the length of protein sequence. Then we transform the 2D-graphical representation into a numerical characterization that can facilitate quantitative comparison of protein sequences. The utility of this approach is illustrated by two examples: one is similarity/dissimilarity comparison among different ND6 protein sequences based on their DV-curve figures the other is the phylogenetic analysis among coronaviruses based on their spike proteins. url: https://doi.org/10.1155/2014/203871 doi: 10.1155/2014/203871 id: cord-302895-471zei5o author: Deng, Zengqin title: Structural basis for the regulatory function of a complex zinc-binding domain in a replicative arterivirus helicase resembling a nonsense-mediated mRNA decay helicase date: 2013-12-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: All positive-stranded RNA viruses with genomes >∼7 kb encode helicases, which generally are poorly characterized. The core of the nidovirus superfamily 1 helicase (HEL1) is associated with a unique N-terminal zinc-binding domain (ZBD) that was previously implicated in helicase regulation, genome replication and subgenomic mRNA synthesis. The high-resolution structure of the arterivirus helicase (nsp10), alone and in complex with a polynucleotide substrate, now provides first insights into the structural basis for nidovirus helicase function. A previously uncharacterized domain 1B connects HEL1 domains 1A and 2A to a long linker of ZBD, which further consists of a novel RING-like module and treble-clef zinc finger, together coordinating three Zn atoms. On substrate binding, major conformational changes were evident outside the HEL1 domains, notably in domain 1B. Structural characterization, mutagenesis and biochemistry revealed that helicase activity depends on the extensive relay of interactions between the ZBD and HEL1 domains. The arterivirus helicase structurally resembles the cellular Upf1 helicase, suggesting that nidoviruses may also use their helicases for post-transcriptional quality control of their large RNA genomes. url: https://www.ncbi.nlm.nih.gov/pubmed/24369429/ doi: 10.1093/nar/gkt1310 id: cord-269352-0o3mryu1 author: Dhama, K. title: DNA vaccines and their applications in veterinary practice: current perspectives date: 2008-04-19 words: 6856.0 sentences: 339.0 pages: flesch: 41.0 cache: ./cache/cord-269352-0o3mryu1.txt txt: ./txt/cord-269352-0o3mryu1.txt summary: Inoculation of plasmid DNA, encoding an immunogenic protein gene of an infectious agent, stands out as a novel approach for developing new generation vaccines for prevention of infectious diseases of animals. As an effective vaccine, plasmid DNA have a gene encoding a protective antigen of a pathogen, which when injected into host, is transcribed and translated, to induce a specific immune response. Regarding veterinary practice, the last few years have seen numerous trials of DNA vaccines against various animal diseases like foot and mouth disease (FMD) and herpes virus infection in cattle, Aujeszky''s disease and classical swine fever in swine, rabies and canine distemper in canines, and avian influenza, infectious bronchitis, infectious bursal disease and coccidiosis in birds (Oshop et al. Besides, DNA vaccines have been developed against major viral infections of poultry like avian influenza, utilizing the HA gene of the virus (Kodihalli et al. abstract: Inoculation of plasmid DNA, encoding an immunogenic protein gene of an infectious agent, stands out as a novel approach for developing new generation vaccines for prevention of infectious diseases of animals. The potential of DNA vaccines to act in presence of maternal antibodies, its stability and cost effectiveness and the non-requirement of cold chain have heightened the prospects. Even though great strides have been made in nucleic acid vaccination, still there are many areas that need further research for its wholesome practical implementation. Major areas of concern are vaccine delivery, designing of suitable vectors and cytotoxic T cell responses. Also, the induction of immune responses by DNA vaccines is inconclusive due to the lack of knowledge regarding the concentration of the protein expressed in vivo. Alternative delivery systems having higher transfection efficiency and the use of cytokines, as immunomodulators, needs to be further explored. Recently, efforts are being made to modulate and prolong the active life of dendritic cells, in order to make antigen presentation a more efficacious one. For combating diseases like acquired immunodeficiency syndrome (AIDS), influenza, malaria and tuberculosis in humans; and foot and mouth disease, Aujesky’s disease, swine fever, rabies, canine distemper and brucellosis in animals, DNA vaccine clinical trials are underway. This review highlights the salient features of DNA vaccines, and measures to enhance their efficacy so as to devise an effective and novel vaccination strategy against animal diseases. url: https://doi.org/10.1007/s11259-008-9040-3 doi: 10.1007/s11259-008-9040-3 id: cord-307768-xx46w6dc author: Ding, Yun title: From single-molecule detection to next-generation sequencing: microfluidic droplets for high-throughput nucleic acid analysis date: 2017-03-10 words: 9490.0 sentences: 506.0 pages: flesch: 44.0 cache: ./cache/cord-307768-xx46w6dc.txt txt: ./txt/cord-307768-xx46w6dc.txt summary: title: From single-molecule detection to next-generation sequencing: microfluidic droplets for high-throughput nucleic acid analysis Recent applications of such technologies to genetic analysis have suggested significant utility in low-cost, efficient and rapid workflows for DNA amplification, rare mutation detection, antibody screening and next-generation sequencing. 2003) , with the relative concentration of each reagent being defined by the Fig. 1 a Physical and chemical variables in droplet-based experiments: (1) Temperature can be controlled over wide ranges, enabling PCR in emulsions; (2) Hydrophobic substrates or ligands can be delivered through the oil phase into aqueous droplets; (3) Watersoluble components can be delivered through nanoscale droplets or swollen micelles, allowing the regulation of biochemical processes; (4) Internal pH can be altered, for example, by the delivery of acetic acid; (5) Photocaged substrates and ligands can be introduced into the droplets during emulsification and photoactivated at later times. Two recent studies describing single-cell RNA sequencing methods using droplet-based microfluidics [termed Drop-seq (Macosko et al. abstract: Droplet-based microfluidic technologies have proved themselves to be of significant utility in the performance of high-throughput chemical and biological experiments. By encapsulating and isolating reagents within femtoliter–nanoliter droplet, millions of (bio) chemical reactions can be processed in a parallel fashion and on ultra-short timescales. Recent applications of such technologies to genetic analysis have suggested significant utility in low-cost, efficient and rapid workflows for DNA amplification, rare mutation detection, antibody screening and next-generation sequencing. To this end, we describe and highlight some of the most interesting recent developments and applications of droplet-based microfluidics in the broad area of nucleic acid analysis. In addition, we also present a cursory description of some of the most essential functional components, which allow the creation of integrated and complex workflows based on flowing streams of droplets. url: https://www.ncbi.nlm.nih.gov/pubmed/32214953/ doi: 10.1007/s10404-017-1889-4 id: cord-270082-byxd4o4m author: Doheny, Kimberly Floy title: Identification of essential components of the S. cerevisiae kinetochore date: 1993-05-21 words: 9918.0 sentences: 556.0 pages: flesch: 54.0 cache: ./cache/cord-270082-byxd4o4m.txt txt: ./txt/cord-270082-byxd4o4m.txt summary: Readthrough Assay and Secondary Screen of the ctf Collection When transcription from a strong promoter is initiated toward a CEN DNA sequence, the mitotic segregational function of the centromere is destroyed (Hill and Bloom, 1987) without disruption of its 180-220 bp nuclease protected region (Bloom et al., 1984; Hill and Bloom, 1987) , indicating that at least some of the kinetochore complex remains intact. To test the hypothesis that a CfN DNA-protein complex was responsible for the transcriptional block, we replaced the wild-type CENG sequence with a CEN6 sequence containing a single-nucleotide point mutation (CDEIII-15C) in the central element of the palindrome of CDEIII (CCG). Of 34 cff mutants screened (see Experimental Procedures for list), 7 were identified as putative kinetochore mutants because they produced an intermediate level of blue colony color between the levels of the CTF+ strains carrying the wild-type and mutant CEN reporters. abstract: Abstract We have designed and utilized two in vivo assays of kinetochore integrity in S. cerevisiae. One assay detects relaxation of a transcription block formed at centromeres; the other detects an increase in the mitotic stability of a dicentric test chromosome. ctf13-30 and ctf14-42 were identified as putative kinetochore mutants by both assays. CTF14 is identical to NDC10 CBF2 , a recently identified essential gene that encodes a 110 kd kinetochore component. CTF13 is an essential gene that encodes a predicted 478 amino acid protein with no homology to known proteins. ctf13 mutants missegregate chromosomes at permissive temperature and transiently arrest at nonpermissive temperature as large-budded cells with a G2 DNA content and a short spindle. Antibodies recognizing epitope-tagged CTF13 protein decrease the electrophoretic mobility of a CEN DNA-protein complex formed in vitro. Together, the genetic and biochemical data indicate that CTF13 is an essential kinetochore protein. url: https://www.ncbi.nlm.nih.gov/pubmed/8500169/ doi: 10.1016/0092-8674(93)90255-o id: cord-103417-2uinislh author: Doi, Hideyuki title: On-site eDNA detection of species using ultra-rapid mobile PCR date: 2020-10-01 words: 1507.0 sentences: 91.0 pages: flesch: 50.0 cache: ./cache/cord-103417-2uinislh.txt txt: ./txt/cord-103417-2uinislh.txt summary: Our method reduced the measurement time to 30 min and provided high detectability of aquatic organisms compared to the national observation surveys using multiple fishing nets and laboratory extraction/detection using a benchtop qPCR platform. Ultra-rapid methods from DNA collection to detection are still not well developed (1), especially for environmental DNA (eDNA) analysis, which uses water or soil samples to track the presence of target species (2, 3) . Here, we developed a new innovative method for the field processing of eDNA samples and measurements using an ultra-rapid mobile PCR platform (hereafter, mobile PCR) to reduce the measurement time to 30 min and maintain high detectability of aquatic organisms. We compared the on-site eDNA measurement to the laboratory extraction and detection using a benchtop qPCR platform and the national survey to confirm the performance. Our ultra-rapid on-site eDNA extraction and measurement method using mobile PCR successfully detected the eDNA of H. abstract: Molecular methods, including environmental DNA (eDNA) methods, provide essential information for biological and conservation sciences. Molecular measurements are often performed in the laboratory, which limits their scope, especially for rapid on-site analysis. eDNA methods for species detection provide essential information for the management and conservation of species and communities in various environments. We developed an innovative novel method for on-site eDNA measurements using an ultra-rapid mobile PCR platform. We tested the ability of our method to detect the distribution of silver carp, Hypophthalmichthys molitrix, an invasive fish in Japanese rivers and lakes. Our method reduced the measurement time to 30 min and provided high detectability of aquatic organisms compared to the national observation surveys using multiple fishing nets and laboratory extraction/detection using a benchtop qPCR platform. Our on-site eDNA method can be immediately applied to various taxa and environments. url: https://doi.org/10.1101/2020.09.28.314625 doi: 10.1101/2020.09.28.314625 id: cord-022128-r8el8nqm author: Domingo, Esteban title: Molecular basis of genetic variation of viruses: error-prone replication date: 2019-11-08 words: 17663.0 sentences: 798.0 pages: flesch: 39.0 cache: ./cache/cord-022128-r8el8nqm.txt txt: ./txt/cord-022128-r8el8nqm.txt summary: In the case of viral genomes, mutations can result from different mechanisms: (i) template miscopying (direct incorporation of an incorrect nucleotide); (ii) primer-template misalignments that include miscoding followed by realignment, and misalignment of the template relative to the growing chain (polymerase "slippage" or "stuttering"); (iii) activity of cellular enzymes (i.e., deaminases), or (iv) chemical damage to the viral nucleic acids (deamination, depurination, depyrimidination, reactions with oxygen radicals, direct and indirect effects of ionizing radiation, photochemical reactions, etc.) (Naegeli, 1997; Bloomfield et al., 2000; Friedberg et al., 2006) . In addition to the general environmental and sequence context consequences for templatecopying fidelity that may affect any genome type, mutation rates for DNA viruses will also be influenced by: (i) whether the DNA polymerase that catalyzes viral DNA synthesis includes or lacks a functional proofreading-repair activity. abstract: Genetic variation is a necessity of all biological systems. Viruses use all known mechanisms of variation; mutation, several forms of recombination, and segment reassortment in the case of viruses with a segmented genome. These processes are intimately connected with the replicative machineries of viruses, as well as with fundamental physical-chemical properties of nucleotides when acting as template or substrate residues. Recombination has been viewed as a means to rescue viable genomes from unfit parents or to produce large modifications for the exploration of phenotypic novelty. All types of genetic variation can act conjointly as blind processes to provide the raw materials for adaptation to the changing environments in which viruses must replicate. A distinction is made between mechanistically unavoidable and evolutionarily relevant mutation and recombination. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153327/ doi: 10.1016/b978-0-12-816331-3.00002-7 id: cord-303265-v6ci69n0 author: Domingo, Esteban title: Introduction to virus origins and their role in biological evolution date: 2019-11-08 words: 15685.0 sentences: 764.0 pages: flesch: 42.0 cache: ./cache/cord-303265-v6ci69n0.txt txt: ./txt/cord-303265-v6ci69n0.txt summary: Topics covered include molecular mechanisms of genetic variation, with emphasis on high mutation rates, Darwinian principles acting on viruses, quasispecies dynamics and its implications, consequences for virus-host interactions, fitness as a relevant parameter, experimental model systems in cell culture, ex-vivo and in vivo, long-term virus evolution, the current situation of antiviral strategies to confront quasispecies swarms, and conceptual extensions of quasispecies to nonviral systems. With regard to the concepts of genome stability versus variation addressed in this book, it is helpful to divide viruses into four groups, depending on whether it is DNA or RNA the type of genetic material, which acts as a replicative intermediate in the infected cell (bottom gray shaded boxes in Fig. 1.1 ). They were selected for replicability, stability, and evolvability with trade-offs 1.4 Origin of life: a brief historical account and current views (acquisition of benefits for one of the three traits at some cost for another trait) likely play a role at this stage (see Chapter 4 for trade-offs in virus evolution). abstract: Viruses are diverse parasites of cells and extremely abundant. They might have arisen during an early phase of the evolution of life on Earth dominated by ribonucleic acid or RNA-like macromolecules, or when a cellular world was already well established. The theories of the origin of life on Earth shed light on the possible origin of primitive viruses or virus-like genetic elements in our biosphere. Some features of present-day viruses, notably error-prone replication, might be a consequence of the selective forces that mediated their ancestral origin. Two views on the role of viruses in our biosphere predominate; viruses considered as opportunistic, selfish elements, and viruses considered as active participants in the construction of the cellular world via the lateral transfer of genes. These two models have a bearing on viruses being considered predominantly as disease agents or predominantly as cooperators in the shaping of differentiated cellular organisms. url: https://www.sciencedirect.com/science/article/pii/B9780128163313000015 doi: 10.1016/b978-0-12-816331-3.00001-5 id: cord-252147-bvtchcbt author: Domingo-Espín, Joan title: Engineered Biological Entities for Drug Delivery and Gene Therapy: Protein Nanoparticles date: 2011-11-15 words: 17193.0 sentences: 888.0 pages: flesch: 39.0 cache: ./cache/cord-252147-bvtchcbt.txt txt: ./txt/cord-252147-bvtchcbt.txt summary: Modular protein engineering, virus-like particles (VLPs), and other self-assembling entities are envisioned as modulatable novel protein nanoparticles able to include many desirable properties in the correct delivery of drugs and nucleic acids. 120 Modular fusion proteins that combine distinct functions required for cell type-specific uptake and intracellular delivery of DNA or drugs present an attractive approach for the development of self-assembling vectors for targeted gene or drug delivery. 215, 216 Although VLP-based vaccines have been primarily developed for their use against the corresponding virus, in the last decades genetic engineering or chemical modifications have been applied in order to generate chimeric VLPs. Thus, on the one hand, commonly short heterologous peptide epitopes or full proteins that are unable to form VLPs or that are unsafe for vaccination have been presented on surface-exposed loops or fused to N-or C-exposed termini of structural viral capsid proteins on VLPs. 154, 161, 210 Different HPV, 217-219 HBV, 220,221 parvovirus, 222, 223 and chimeric polyoma VLPs have been engineered 170, 175 and tested for different applications including vaccination against viral or bacterial diseases, against virus-induced tumors, and more recently, for immunotherapy of nonviral cancer. abstract: The development of genetic engineering techniques has speeded up the growth of the biotechnological industry, resulting in a significant increase in the number of recombinant protein products on the market. The deep knowledge of protein function, structure, biological interactions, and the possibility to design new polypeptides with desired biological activities have been the main factors involved in the increase of intensive research and preclinical and clinical approaches. Consequently, new biological entities with added value for innovative medicines such as increased stability, improved targeting, and reduced toxicity, among others have been obtained. Proteins are complex nanoparticles with sizes ranging from a few nanometers to a few hundred nanometers when complex supramolecular interactions occur, as for example, in viral capsids. However, even though protein production is a delicate process that imposes the use of sophisticated analytical methods and negative secondary effects have been detected in some cases as immune and inflammatory reactions, the great potential of biodegradable and tunable protein nanoparticles indicates that protein-based biotechnological products are expected to increase in the years to come. url: https://doi.org/10.1016/b978-0-12-416020-0.00006-1 doi: 10.1016/b978-0-12-416020-0.00006-1 id: cord-286719-1xjmlwqr author: Draz, Mohamed Shehata title: Applications of gold nanoparticles in virus detection date: 2018-02-15 words: 18990.0 sentences: 901.0 pages: flesch: 37.0 cache: ./cache/cord-286719-1xjmlwqr.txt txt: ./txt/cord-286719-1xjmlwqr.txt summary: The developed AuNP-based detection techniques are reported for various groups of clinically relevant viruses with a special focus on the applied types of bio-AuNP hybrid structures, virus detection targets, and assay modalities and formats. These techniques represent the majority of molecular techniques applied in virus detection and include various types of target amplification techniques (e.g., PCR, loop-mediated isothermal amplification (LAMP), transcription-mediated amplification, and nucleic acid sequence-based amplification), signal amplification techniques (e.g., branched DNA and hybrid capture), and probe amplification techniques (e.g., ligase chain reaction and strand-displacement amplification). [70] developed an impedimetric electrochemical assay for the detection of AIV M gene sequences based on measuring changes in the impedimetric behavior of the electrode when the target DNA hybridizes with the capture DNA probes immobilized onto its surface and is subsequently labeled by AuNPs via streptavidin/ biotin interaction (Fig. 12C) . abstract: Viruses are the smallest known microbes, yet they cause the most significant losses in human health. Most of the time, the best-known cure for viruses is the innate immunological defense system of the host; otherwise, the initial prevention of viral infection is the only alternative. Therefore, diagnosis is the primary strategy toward the overarching goal of virus control and elimination. The introduction of a new class of nanoscale materials with multiple unique properties and functions has sparked a series of breakthrough applications. Gold nanoparticles (AuNPs) are widely reported to guide an impressive resurgence in biomedical and diagnostic applications. Here, we review the applications of AuNPs in virus testing and detection. The developed AuNP-based detection techniques are reported for various groups of clinically relevant viruses with a special focus on the applied types of bio-AuNP hybrid structures, virus detection targets, and assay modalities and formats. We pay particular attention to highlighting the functional role and activity of each core Au nanostructure and the resultant detection improvements in terms of sensitivity, detection range, and time. In addition, we provide a general summary of the contributions of AuNPs to the mainstream methods of virus detection, technical measures, and recommendations required in guidance toward commercial in-field applications. url: https://doi.org/10.7150/thno.23856 doi: 10.7150/thno.23856 id: cord-014661-mrh2pbi6 author: Dumitrascu, Georgiana R. title: Critical physiological and pathological functions of Forkhead Box O tumor suppressors date: 2013-12-31 words: 9235.0 sentences: 419.0 pages: flesch: 38.0 cache: ./cache/cord-014661-mrh2pbi6.txt txt: ./txt/cord-014661-mrh2pbi6.txt summary: FOXO proteins are considered unique cellular targets, regulating a wide variety of critical cellular processes, such as: apoptosis, oxidative stress, DNA damage repair, cell cycle, stem cell proliferation and maintenance, metabolism, angiogenesis, vascular tone, cardiovascular development, fertility, immune response and neuronal survival 4, 20 . Hence, the FOXO transcription factors control the expression of a wide spectrum of genes that regulate essential physiological cellular processes, such as cell death/cell survival, cell cycle, cell proliferation, cell differentiation/development, angiogenesis, cell metabolism, stress response and stem cell maintenance 33,34,35,36,37,38 (Figure 2) . Moreover, the consensus FOXO recognition element (FRE) -(G/C)(T/A)AA(C/T)AA -which differs from that of other forkhead proteins, seems to have a very important role in both apoptotic pathways, since matching functional FRE sites have been identified in the promoters of FOXO target genes encoding Fas ligand (FasL), insulin like growth factorbinding protein 1 (IGFBP1), the apoptotic regulator Bcl-2 interacting mediator of cell death (Bim) and others 30 . abstract: The Forkhead box, subclass O (FOXO) proteins are critical transcription factors, ubiquitously expressed in the human body. These proteins are characterized by a remarkable functional diversity, being involved in cell cycle arrest, apoptosis, oxidative detoxification, DNA damage repair, stem cell maintenance, cell differentiation, cell metabolism, angiogenesis, cardiac development, aging and others. In addition, FOXO have critical implications in both normal and cancer stem cell biology. New strategies to modulate FOXO expression and activity may now be developed since the discovery of novel FOXO regulators and non-coding RNAs (such as microRNAs) targeting FOXO transcription factors. This review focuses on physiological and pathological functions of FOXO proteins and on their action as fine regulators of cell fate and context-dependent cell decisions. A better understanding of the structure and critical functions of FOXO transcription factors and tumor suppressors may contribute to the development of novel therapies for cancer and other diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941590/ doi: 10.15190/d.2013.5 id: cord-252302-qi9dtaow author: Dutse, Sabo Wada title: Microfluidics-Based Lab-on-Chip Systems in DNA-Based Biosensing: An Overview date: 2011-05-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Microfluidics-based lab-on-chip (LOC) systems are an active research area that is revolutionising high-throughput sequencing for the fast, sensitive and accurate detection of a variety of pathogens. LOCs also serve as portable diagnostic tools. The devices provide optimum control of nanolitre volumes of fluids and integrate various bioassay operations that allow the devices to rapidly sense pathogenic threat agents for environmental monitoring. LOC systems, such as microfluidic biochips, offer advantages compared to conventional identification procedures that are tedious, expensive and time consuming. This paper aims to provide a broad overview of the need for devices that are easy to operate, sensitive, fast, portable and sufficiently reliable to be used as complementary tools for the control of pathogenic agents that damage the environment. url: https://www.ncbi.nlm.nih.gov/pubmed/22163925/ doi: 10.3390/s110605754 id: cord-300040-rvrp5zvv author: Dutta, Noton Kumar title: Search for potential target site of nucleocapsid gene for the design of an epitope-based SARS DNA vaccine date: 2008-06-15 words: 4681.0 sentences: 255.0 pages: flesch: 54.0 cache: ./cache/cord-300040-rvrp5zvv.txt txt: ./txt/cord-300040-rvrp5zvv.txt summary: We constructed eukaryotic expression plasmid encoding N [(N1 (nucleotide: 1-1269), N2 (nucleotide: 1-327), and N3 (nucleotide: 328-1296)) gene fragments of the SARS-CoV and compared their individual potential immune responses in BALB/c mice for use in the development of SARS vaccine candidates. In this report, we detected SARS-Cov N1 and N3 protein-specific immune response induced by pVAX-N1 and N3 DNA vaccination, respectively, and found significantly high titres of specific antibody and specific cell mediated immunity compared to control. These results indicate that N protein, which naturally exists in virus particles after binding of viral RNA, was able to induce strong humoral and cellular immune responses when induced by DNA vaccine, and it might be a prospective candidate gene for development of SARS-CoV vaccine. showed that expression of membrane protein augments the specific responses induced by SARS-CoV nucleocapsid DNA immunization. The expression of membrane protein augments the specific responses induced by SARS-CoV nucleocapsid DNA immunization abstract: It is believed today that nucleocapsid protein (N) of severe acute respiratory syndrome (SARS)-CoV is one of the most promising antigen candidates for vaccine design. In this study, three fragments [N1 (residues: 1–422); N2 (residues: 1–109); N3 (residues: 110–422)] of N protein of SARS-CoV were expressed in Escherichia coli and analyzed by pooled sera of convalescence phase of SARS patients. Three gene fragments [N1 (1–1269 nt), N2 (1–327 nt) and N3 (328–1269 nt)—expressing the same proteins of N1, N2 and N3, respectively] of SARS-N were cloned into pVAX-1 and used to immunize BALB/c mice by electroporation. Humoral (by enzyme-linked immunosorbent assay, ELISA) and cellular (by cell proliferation and CD4(+):CD8(+) assay) immunity was detected by using recombinant N1 and N3 specific antigen. Results showed that N1 and N3 fragments of N protein expressed by E. coli were able to react with sera of SARS patients but N2 could not. Specific humoral and cellular immunity in mice could be induced significantly by inoculating SARS-CoV N1 and N3 DNA vaccine. In addition, the immune response levels in N3 were significantly higher for antibody responses (IgG and IgG1 but not IgG2a) and cell proliferation but not in CD4(+):CD8(+) assay compared to N1 vaccine. The identification of antigenic N protein fragments has implications to provide basic information for the design of DNA vaccine against SARS-CoV. The present results not only suggest that DNA immunization with pVax-N3 could be used as potential DNA vaccination approaches to induce antibody in BALB/c mice, but also illustrates that gene immunization with these SARS DNA vaccines can generate different immune responses. url: https://www.ncbi.nlm.nih.gov/pubmed/18440652/ doi: 10.1016/j.imlet.2008.03.003 id: cord-262870-r3w44mg0 author: Duval, R.-E. title: Interest of designed cyclodextrin-tools in gene delivery date: 2012-11-30 words: 3768.0 sentences: 189.0 pages: flesch: 42.0 cache: ./cache/cord-262870-r3w44mg0.txt txt: ./txt/cord-262870-r3w44mg0.txt summary: Among them, Capillary electrophoresis (CE) was used to perfectly characterize our CyD-siRNA and CyD-DNA complexes and shown to be a very attractive method with advantages of low sample consumption, rapid analysis speed, and high efficiency that make this technology a major tool for association constant measurement. Finally, we present the different biological methods that can be used, in vitro, to study gene delivery, and more precisely ones we have performed to evaluate the capability of our original model bis-guanidinium-tetrakis-β-cyclodextrin dendrimeric tetrapod, to deliver efficiently DNA or siRNA in eukaryotic cells. In this part, we present the different biological methods that can be used, in vitro, to study gene delivery, and more precisely ones we have performed to evaluate the capability of our original model, i.e. bis-guanidiniumtetrakis-␤-cyclodextrin dendrimeric tetrapod, to deliver efficiently DNA or siRNA [18, 20] . abstract: Summary Cyclodextrins (CyDs) currently displays even today the image of a natural macrocyclic compound largely dominant in the formation of inclusion complexes with small hydrophobic molecules. During the past 10years, advances in this field allowed to achieve more and more sophisticated CyDs derivatives opening a simple access in scale-up quantities to original and better CyD-based gene delivery systems. In addition, possibility to combine covalent and supramolecular approaches offers new venues for the design of tailor-made CyD-based nanovehicles to improve their transfection ability and gene transfer in cells. In this account, we describe our recent progress in the construction of a novel CyD-based G0 (generation number) core dendrimer, scalable to CyD oligomers by a strategy using protonable guanidine tethers and whose concept can be generalized for the assembly of CyD pre-coated dendrimers. The synthetic strategy based on an original Staudinger-Aza-Wittig tandem coupling reaction. We present an outline of the different analytical strategies to characterize CyD-ODN (cyclodextrin-oligodeoxynucleotide) complexes. Among them, Capillary electrophoresis (CE) was used to perfectly characterize our CyD-siRNA and CyD-DNA complexes and shown to be a very attractive method with advantages of low sample consumption, rapid analysis speed, and high efficiency that make this technology a major tool for association constant measurement. Finally, we present the different biological methods that can be used, in vitro, to study gene delivery, and more precisely ones we have performed to evaluate the capability of our original model bis-guanidinium-tetrakis-β-cyclodextrin dendrimeric tetrapod, to deliver efficiently DNA or siRNA in eukaryotic cells. url: https://www.sciencedirect.com/science/article/pii/S0003450912001447 doi: 10.1016/j.pharma.2012.09.005 id: cord-010500-ajmj2hyj author: ELLEGREN, H. title: Limited polymorphism at major histocompatibility complex (MHC) loci in the Swedish moose A. alces date: 2008-06-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The Swedish moose was analysed for genetic variability at major histocompatibility complex (MHC) class I and class II DQA, DQB and DRB loci using restriction fragment length polymorphism (RFLP) and single strand conformation polymorphism (SSCP) techniques. Both methods revealed limited amounts of polymorphism. Since the SSCP analysis concerned an expressed DRB gene it can be concluded that the level of functional MHC class II polymorphism, at least at the DRB locus, is low in Swedish moose. DNA fingerprinting was used to determine if the unusual pattern of low MHC variability could be explained by a low degree of genome‐wide genetic diversity. Hybridizations with two minisatellite probes gave similarity indices somewhat higher than the average for other natural population, but the data suggest that the low MHC variability cannot be explained by a recent population bottleneck. However, since minisatellite sequences evolve more rapidly than MHC sequences, the low levels of MHC diversity may be attributed to a bottleneck of more ancient origin. The selection pressure for MHC variability in moose may also be reduced and we discuss the possibility that its solitary life style may reduce lateral transmission of pathogens in the population. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192233/ doi: 10.1111/j.1365-294x.1996.tb00286.x id: cord-316033-xg8eb2nm author: Easton, Alice title: Molecular evidence of hybridization between pig and human Ascaris indicates an interbred species complex infecting humans date: 2020-11-06 words: 10447.0 sentences: 522.0 pages: flesch: 45.0 cache: ./cache/cord-316033-xg8eb2nm.txt txt: ./txt/cord-316033-xg8eb2nm.txt summary: suum transcripts (Jex et al., 2011; Wang et al., 2017) to the human Ascaris germline assembly to annotate the genome, identifying and classifying 17,902 protein-coding genes ( Table 1 , Supplementary file 1). As this reference-based assembly exhibits the best assembly attributes, including high continuity with a large N50, low gaps and unplaced sequences, and high-quality protein-coding genes (see Table 1 ), we suggest that this version should be used as a reference germline genome for a human Ascaris spp. We next took advantage of the abundant reads from the mitochondrial genome in our sequencing data (on average 7690X coverage, see Supplementary file 1) to perform de novo assembly of 68 complete human Ascaris spp. Furthermore, there were no significant associations between mitochondrial sequence variations and other factors (e.g. village, household, time of worm collection, host) based on PERMANOVA (see methods and Table 2 ) after translating the phylogenetic tree into a distance matrix, suggesting not only a lack of differentiation into distinct species but also a potentially large interbreeding population of worms being transmitted between individuals and across villages. abstract: Human ascariasis is a major neglected tropical disease caused by the nematode Ascaris lumbricoides. We report a 296 megabase (Mb) reference-quality genome comprised of 17,902 protein-coding genes derived from a single, representative Ascaris worm. An additional 68 worms were collected from 60 human hosts in Kenyan villages where pig husbandry is rare. Notably, the majority of these worms (63/68) possessed mitochondrial genomes that clustered closer to the pig parasite Ascaris suum than to A. lumbricoides. Comparative phylogenomic analyses identified over 11 million nuclear-encoded SNPs but just two distinct genetic types that had recombined across the genomes analyzed. The nuclear genomes had extensive heterozygosity, and all samples existed as genetic mosaics with either A. suum-like or A. lumbricoides-like inheritance patterns supporting a highly interbred Ascaris species genetic complex. As no barriers appear to exist for anthroponotic transmission of these ‘hybrid’ worms, a one-health approach to control the spread of human ascariasis will be necessary. url: https://www.ncbi.nlm.nih.gov/pubmed/33155980/ doi: 10.7554/elife.61562 id: cord-263570-6notzm6s author: Elia, Gabriella title: Detection of infectious canine parvovirus type 2 by mRNA real-time RT-PCR date: 2007-08-10 words: 3990.0 sentences: 224.0 pages: flesch: 58.0 cache: ./cache/cord-263570-6notzm6s.txt txt: ./txt/cord-263570-6notzm6s.txt summary: The load and distribution of CPV-2 mRNA in samples from infected dogs were estimated in comparison with the load of virus DNA, as evaluated by real-time PCR. The analytic specificity of spliced CPV-2 mRNA detection by real-time RT-PCR was assessed by testing RNA and DNA preparations of other canine pathogens, including canine coronavirus types I and II (CCoVI, CCoVII) (Decaro et al., 2005d) , canine distemper virus (CDV) (Elia et al., 2006) , canine adenovirus (CAdV) (Decaro et al., 2006a) , reoviruses (Decaro et al., 2005b) and rotaviruses . To compare the amount of viral DNA in the tissue samples and in the infected cell cultures, a real-time PCR assay was used as described previously (Decaro et al., 2005c) . The newly developed real-time RT-PCR assay was applied to determine the viral mRNA loads in different tissues of CPV-2 naturally infected dogs. A real-time PCR assay for rapid detection and quantitation of canine parvovirus type 2 DNA in the feces of dogs abstract: A TaqMan real-time RT-PCR assay was developed for detection of RNA transcripts produced by replicating CPV-2. A pair of primers and a TaqMan probe targeting the spliced NS2 mRNA were designed. A synthetic DNA fragment was constructed to mimic the spliced NS2 mRNA by PCR-based gene assembly and was used for generation of standard RNAs. The detection limit of the assay was 1 × 10(2) RNA copies and standard curve displayed a linear range from 1 × 10(2) to 1 × 10(9) copies and a good reproducibility. The assay was then applied to determine the mRNA loads in the tissues of dogs naturally infected by CPV-2. mRNA was detected in a variety of tissues, including the central nervous system. url: https://www.ncbi.nlm.nih.gov/pubmed/17692932/ doi: 10.1016/j.jviromet.2007.06.017 id: cord-272579-aenuyht0 author: Emmett, Stevan R. title: The Cell Cycle and Virus Infection date: 2005 words: 6456.0 sentences: 388.0 pages: flesch: 60.0 cache: ./cache/cord-272579-aenuyht0.txt txt: ./txt/cord-272579-aenuyht0.txt summary: A number of different viruses interact with the cell cycle in order to subvert host-cell function and increase the efficiency of virus replication; examples can be found from DNA, retro, and RNA viruses. The majority of studies have been conducted on DNA and retroviruses whose primary site of replication is the nucleus, but increasingly a number of researchers are demonstrating that RNA viruses, whose primary site of replication is normally the cytoplasm, also interfere with the cell cycle. Viral interference with the cell cycle can have a myriad of different effects to improve virus infection, for example to promote replication of viral DNA genomes, or to delay the cell cycle to allow sufficient time for RNA virus assembly. Increasingly we have found that proteomic approaches allow the rapid analysis of a whole plethora of cell cycle proteins that may be affected by virus infection. abstract: A number of different viruses interact with the cell cycle in order to subvert host-cell function and increase the efficiency of virus replication; examples can be found from DNA, retro, and RNA viruses. The majority of studies have been conducted on DNA and retroviruses whose primary site of replication is the nucleus, but increasingly a number of researchers are demonstrating that RNA viruses, whose primary site of replication is normally the cytoplasm, also interfere with the cell cycle. Viral interference with the cell cycle can have a myriad of different effects to improve virus infection, for example to promote replication of viral DNA genomes, or to delay the cell cycle to allow sufficient time for RNA virus assembly. Although cell cycle control is fairly well characterized in terms of checkpoints and control molecules (e.g., cyclins), in recent years several researchers have demonstrated that the nucleolus is also involved in cell cycle control. The nucleolus and associated subnuclear structures can sequester cell cycle regulatory complexes, and nucleolar proteins also have a direct and indirect effect on the cycling cell. Viruses also interact with the nucleolus. In order to study the interactions between a virus and the cell cycle and vice versa we have developed and adapted a number of different approaches and strategies. These include determinations of virus yield and measurements of virus replication to flow cytometry and confocal analysis of the host cell. Increasingly we have found that proteomic approaches allow the rapid analysis of a whole plethora of cell cycle proteins that may be affected by virus infection. url: https://www.ncbi.nlm.nih.gov/pubmed/15576934/ doi: 10.1385/1-59259-857-9:197 id: cord-293215-6flf5ig0 author: Eriksson, Klara Kristin title: Generation of Recombinant Coronaviruses Using Vaccinia Virus as the Cloning Vector and Stable Cell Lines Containing Coronaviral Replicon RNAs date: 2007-11-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Coronavirus reverse genetic systems have become valuable tools for studying the molecular biology of coronavirus infections. They have been applied to the generation of recombinant coronaviruses, selectable replicon RNAs, and coronavirus-based vectors for heterologous gene expression. Here we provide a collection of protocols for the generation, cloning, and modification of full-length coronavirus cDNA using vaccinia virus as a cloning vector. Based on cloned coronaviral cDNA, we describe the generation of recombinant coronaviruses and stable cell lines containing coronaviral replicon RNAs. Initially, the vaccinia virus-based reverse genetic system was established for the generation of recombinant human coronavirus 229E. However, it is also applicable to the generation of other coronaviruses, such as the avian infectious bronchitis virus, mouse hepatitis virus, and SARS coronavirus. url: https://www.ncbi.nlm.nih.gov/pubmed/19057873/ doi: 10.1007/978-1-59745-181-9_18 id: cord-022196-1tionxun author: FENNER, FRANK title: The Nature and Classification of Animal Viruses date: 2013-11-17 words: 9588.0 sentences: 406.0 pages: flesch: 46.0 cache: ./cache/cord-022196-1tionxun.txt txt: ./txt/cord-022196-1tionxun.txt summary: With most isometric particles and in all complex virions, the capsid encloses another protein structure containing the viral genome, called the core. All animal viruses with tubular nucleocapsids are enveloped, and in these the lipid layer from which glycoprotein peplomers project is probably applied to a protein shell (the membrane protein; see Fig. 1 -1), which may be relatively rigid, as in Rhabdovirus, or readily distorted (as in the myxoviruses) so that in negatively stained electron micrographs the virions appear to be pleomorphic. The RNA viruses that have the largest (single-stranded) genomes, those of the Leukovirus genus, also have a highly complex structure with an envelope enclosing an icosahedral capsid that, in turn, surrounds a tubular nucleocapsid. The conventional physicochemical criteria [(a) nucleic acid: type, strandedness, fragmentation, and molecular weight; (b) virion: shape, size, and symmetry] are suitable for classification at this level of family/genus, perhaps assisted by the serological cross-reactivity of "group" antigens where these have been recognized. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155428/ doi: 10.1016/b978-0-12-253040-1.50006-3 id: cord-023705-3q9yr6np author: FENNER, FRANK title: Viral Replication date: 2014-06-27 words: 8331.0 sentences: 424.0 pages: flesch: 51.0 cache: ./cache/cord-023705-3q9yr6np.txt txt: ./txt/cord-023705-3q9yr6np.txt summary: Many important biochemical phenomena such as the splicing and other types of posttranscriptional processing of RNA, the posttranslational cleavage and glycosylation of proteins, the replication of RNA, reverse transcription, integration, and the transposition of viral genes and cellular oncogenes were first elucidated by virologists and have general application in cell biology. Many important biochemical phenomena, such as splicing and other types of posttranscriptional processing of RNA, posttranslational cleavage and glycosylation of proteins, replica tion of RNA, reverse transcription, integration, and transposition of viral genes and cellular oncogenes, were first elucidated by virologists and have general application in cell biology. The proteins translated from the early transcripts of DNA viruses include enzymes and other proteins required for the replication of viral nucleic acid, as well as proteins that suppress host cell RNA and protein synthesis. abstract: Viral replication is the central focus of much experimental virology and is a significant part of molecular biology. Studies with bacteriophages in their prokaryotic host cells in the 1940s and 1950s provided the first insights into the complexities of viral replication. With the development of mammalian cell culture procedures, the techniques used for the study of bacteriophages were adapted to animal viruses. Progress has been such that the basic mechanisms of transcription, translation, and nucleic acid replication have been characterized for all the major families of animal viruses and the strategy of gene expression and its regulation clarified. Many important biochemical phenomena such as the splicing and other types of posttranscriptional processing of RNA, the posttranslational cleavage and glycosylation of proteins, the replication of RNA, reverse transcription, integration, and the transposition of viral genes and cellular oncogenes were first elucidated by virologists and have general application in cell biology. The chapter provides a general overview on viral replication for understanding pathogenesis, immunity, chemotherapy, and the role of viruses in cancer. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173495/ doi: 10.1016/b978-0-12-253055-5.50008-6 id: cord-017838-fbotc479 author: Fagone, Paolo title: Electroporation-Mediated DNA Vaccination date: 2010-12-15 words: 5279.0 sentences: 221.0 pages: flesch: 31.0 cache: ./cache/cord-017838-fbotc479.txt txt: ./txt/cord-017838-fbotc479.txt summary: Thus, electroporation-mediated DNA vaccination represents a promising new strategy for the elicitation of strong immune responses directed against the expressed antigen(s) and not the vector, and ongoing studies are currently underway to optimize the working parameters of this technique. [26] demonstrated in mice that upon electroporative treatment, the delivery of a weakly immunogenic hepatitis B virus (HBV) surface antigen (Hbs Ag) DNA vaccine resulted in an increased humoral immune response, characterized by rapid onset and higher titers of anti-Hbs Ag antibodies. In addition, the authors observed in the same study that the potency of an HIV gag pDNA vaccine was increased as shown by the lower dosage of DNA required to induce higher antigen-specific antibody levels and increased CD8 + T cell responses. [31] have demonstrated that gene electrotransfer efficiently increased the cellular immune response both in mice and rhesus macaques vaccinated with a plasmid encoding a nonstructural region of hepatitis C virus (HCV). abstract: There are many positive attributes to DNA vaccination that make it a conceptually desirable platform. In clinical studies, however, standard DNA injection alone generally induces low levels of transgene-specific immunity when compared to other vaccine approaches. In order to boost the immunogenicity of this platform, next-generation DNA vaccines require additional techniques such as the administration of electroporation. This new method involves the generation of a brief electric field in tissue around a local injection site that results in the transient poration, or permeabilization, of the cellular membranes. As a result, antigen-specific immune responses are greatly enhanced and are likely due to increased DNA uptake and antigen expression. Thus, electroporation-mediated DNA vaccination represents a promising new strategy for the elicitation of strong immune responses directed against the expressed antigen(s) and not the vector, and ongoing studies are currently underway to optimize the working parameters of this technique. Here, we review the uses of this technology in conjunction with vaccination and suggest future directions for its further exploration. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122510/ doi: 10.1007/978-1-4419-8363-3_18 id: cord-280549-bsnz24jx author: Fan, Ying title: Breaking Bad: How Viruses Subvert the Cell Cycle date: 2018-11-19 words: 18057.0 sentences: 867.0 pages: flesch: 46.0 cache: ./cache/cord-280549-bsnz24jx.txt txt: ./txt/cord-280549-bsnz24jx.txt summary: A binding-deficient Tax variant failed to stimulate CDK4-cyclin D complex formation and lost its ability to antagonize the inhibitory effect of cyclin-dependent kinase inhibitor (CKI) p21 WAF1/CIP1 , underlying the importance of protein interaction in Tax-mediated cell cycle regulation (Haller et al., 2002) . The examples of Tax and Hobs illustrate how binding of viral protein to cyclin or CDK promotes cell cycle progression either by enhancing kinase activity and/or weakening the inhibitory effect of CKI. Thus, by targeting the E3 ligase of p21 WAF1/CIP1 and p27 KIP1 for degradation, Tax stabilizes these two CKIs. On the contrary, the association of chicken anemia virus protein Apoptin with APC1 inhibits the activity of theAPC/C ubiquitin ligase, leading to the stabilization of cyclin B1 and other APC/C substrates, with ensuing cell cycle G2/M arrest and apoptosis (Teodoro et al., 2004) . abstract: Interactions between the host and viruses during the course of their co-evolution have not only shaped cellular function and the immune system, but also the counter measures employed by viruses. Relatively small genomes and high replication rates allow viruses to accumulate mutations and continuously present the host with new challenges. It is therefore, no surprise that they either escape detection or modulate host physiology, often by redirecting normal cellular pathways to their own advantage. Viruses utilize a diverse array of strategies and molecular targets to subvert host cellular processes, while evading detection. These include cell-cycle regulation, major histocompatibility complex-restricted antigen presentation, intracellular protein transport, apoptosis, cytokine-mediated signaling, and humoral immune responses. Moreover, viruses routinely manipulate the host cell cycle to create a favorable environment for replication, largely by deregulating cell cycle checkpoints. This review focuses on our current understanding of the molecular aspects of cell cycle regulation that are often targeted by viruses. Further study of their interactions should provide fundamental insights into cell cycle regulation and improve our ability to exploit these viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/30510918/ doi: 10.3389/fcimb.2018.00396 id: cord-009562-b3qxlphe author: Feldkamp, Udo title: Dendritic DNA Building Blocks for Amplified Detection Assays and Biomaterials date: 2009-06-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: DNA branches out: Recent advances in the assembly of dendritic DNA structures enable applications in biosensing of pathogens and the generation of novel pads of DNA hydrogel biomaterials (see scheme, left). These pads are immersed in a cell extract containing RNA polymerase (red), ribosomes (yellow), and other components for in vitro protein biosynthesis, where they can be used as templates for cell‐free protein production.[Image: see text] url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159622/ doi: 10.1002/anie.200902285 id: cord-256278-jvfjf7aw author: Feng, Jie title: New method for comparing DNA primary sequences based on a discrimination measure date: 2010-10-21 words: 2864.0 sentences: 186.0 pages: flesch: 53.0 cache: ./cache/cord-256278-jvfjf7aw.txt txt: ./txt/cord-256278-jvfjf7aw.txt summary: title: New method for comparing DNA primary sequences based on a discrimination measure Three years after, Blaisdell (1989) proved that the dissimilarity values observed by using distance measures based on word frequencies are directly related to the ones requiring sequence alignment. In Table 2 , we present the similarity/dissimilarity matrix for the full DNA sequences of bÀglobin gene from 10 species listed in Table 1 by our new method. In Fig. 2, we show the phylogenetic tree of 10 bÀglobin gene sequences based on the distance matrix DM, using NJ method. In this paper, we propose a new method for the similarity analysis of DNA sequences. Our algorithm is not necessarily an improvement as compared to some existing methods, but an alternative for the similarity analysis of DNA sequences. Analysis of similarity/ dissimilarity of DNA sequences based on novel 2-D graphical representation A measure of DNA sequence dissimilarity based on Mahalanobis distance between frequencies of words abstract: Abstract We introduce a new approach to compare DNA primary sequences. The core of our method is a new measure of pairwise distances among sequences. Using the primitive discrimination substrings of sequence S and Q, a discrimination measure DM(S, Q) is defined for the similarity analysis of them. The proposed method does not require multiple alignments and is fully automatic. To illustrate its utility, we construct phylogenetic trees on two independent data sets. The results indicate that the method is efficient and powerful. url: https://www.sciencedirect.com/science/article/pii/S0022519310003978 doi: 10.1016/j.jtbi.2010.07.040 id: cord-328899-kog99kk5 author: Ferrari, Stefano title: Barriers to and new approaches for gene therapy and gene delivery in cystic fibrosis date: 2002-12-05 words: 10491.0 sentences: 536.0 pages: flesch: 45.0 cache: ./cache/cord-328899-kog99kk5.txt txt: ./txt/cord-328899-kog99kk5.txt summary: Strategies to overcome these barriers will be addressed in this review and include the use of: (i) clinically relevant adjuncts to overcome the extraand intracellular barriers; (ii) less-conventional delivery routes, such as intravenous or in utero administration; (iii) more efficient non-viral vectors and ''stealth'' viruses which can be re-administered; and (iv) new approaches to prolong transgene expression by means of alternative promoters or integrating vectors. Interesting-Using an ex vivo sheep trachea model, we demonly, despite non-viral vectors being arguably less strated that cationic lipid-mediated gene transfer, but efficient than viruses in animal models and labora-not adenoviral vectors or recombinant Sendai virus tory studies, clinical trials have shown that this might [22] , was inhibited by normal mucus, with removal Extracellular barriers include the presence of infected mucus and sputum, mucociliary clearance and tight junctions between the cells, which limit the access of viral vectors to receptors localised on the basolateral membrane. abstract: Clinical trials of gene therapy for cystic fibrosis suggest that current levels of gene transfer efficiency are probably too low to result in clinical benefit, largely as a result of the barriers faced by gene transfer vectors within the airways. The respiratory epithelium has evolved a complex series of extracellular barriers (mucus, lack of receptors, immune surveillance, etc.) aimed at preventing penetration of lumenally delivered materials, including gene therapy vectors. In addition, once in the cell, further hurdles have to be overcome, including DNA degradation, nuclear import and the ability to maintain long-term transgene expression. Strategies to overcome these barriers will be addressed in this review and include the use of: (i) clinically relevant adjuncts to overcome the extra- and intracellular barriers; (ii) less-conventional delivery routes, such as intravenous or in utero administration; (iii) more efficient non-viral vectors and ‘stealth’ viruses which can be re-administered; and (iv) new approaches to prolong transgene expression by means of alternative promoters or integrating vectors. These advances have the potential to improve the efficiency of gene delivery to the airway epithelium, thus making gene therapy a more realistic option for cystic fibrosis. url: https://www.ncbi.nlm.nih.gov/pubmed/12458150/ doi: 10.1016/s0169-409x(02)00145-x id: cord-264814-v4wnmg03 author: Flanagan, Katie L. title: Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines date: 2020-10-02 words: 15130.0 sentences: 700.0 pages: flesch: 44.0 cache: ./cache/cord-264814-v4wnmg03.txt txt: ./txt/cord-264814-v4wnmg03.txt summary: Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. Comprehensive safety studies are particularly critical because some candidate vaccines use platform technologies that have not been examined extensively in human subjects to date, including some of the viral vectors, mRNA and nanoparticle constructs, and because of the potential for enhanced disease and adverse events related to aberrant immune responses to be seen upon infection pre-and post-licensure. abstract: There are currently around 200 SARS-CoV-2 candidate vaccines in preclinical and clinical trials throughout the world. The various candidates employ a range of vaccine strategies including some novel approaches. Currently, the goal is to prove that they are safe and immunogenic in humans (phase 1/2 studies) with several now advancing into phase 2 and 3 trials to demonstrate efficacy and gather comprehensive data on safety. It is highly likely that many vaccines will be shown to stimulate antibody and T cell responses in healthy individuals and have an acceptable safety profile, but the key will be to confirm that they protect against COVID-19. There is much hope that SARS-CoV-2 vaccines will be rolled out to the entire world to contain the pandemic and avert its most damaging impacts. However, in all likelihood this will initially require a targeted approach toward key vulnerable groups. Collaborative efforts are underway to ensure manufacturing can occur at the unprecedented scale and speed required to immunize billions of people. Ensuring deployment also occurs equitably across the globe will be critical. Careful evaluation and ongoing surveillance for safety will be required to address theoretical concerns regarding immune enhancement seen in previous contexts. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. We provide details of some of the frontrunner vaccines and discuss potential issues including adverse effects, scale-up and delivery. url: https://doi.org/10.3389/fimmu.2020.579250 doi: 10.3389/fimmu.2020.579250 id: cord-277293-eo3bei9x author: Fondong, Vincent N. title: Geminivirus protein structure and function date: 2013-04-25 words: 10141.0 sentences: 507.0 pages: flesch: 47.0 cache: ./cache/cord-277293-eo3bei9x.txt txt: ./txt/cord-277293-eo3bei9x.txt summary: The replication-associated protein (Rep) encoded by the AC1 ORF (also called AL1) in bipartite geminiviruses and by C1 (also called L1) in monopartite geminiviruses (except mastreviruses) is conserved in sequence, position and function (Hanley-Bowdoin et al., 2004) and is expressed under the control of a bidirectional core promoter in the IR (Hanley-Bowdoin et al., 1999) . SINAC1 levels were shown to be higher in ToLCV-infected cells, suggesting that NAC1 is involved in viral DNA replication (Selth et al., 2005) , possibly through an interaction with REn. Recently, the Tomato leaf curl Kerala virus REn was shown to interact with Rep and enhance the Repmediated ATPase activity (Pasumarthy et al., 2010) , thus confirming a role for REn in viral DNA replication. abstract: Geminiviruses are a family of plant viruses that cause economically important plant diseases worldwide. These viruses have circular single‐stranded DNA genomes and four to eight genes that are expressed from both strands of the double‐stranded DNA replicative intermediate. The transcription of these genes occurs under the control of two bidirectional promoters and one monodirectional promoter. The viral proteins function to facilitate virus replication, virus movement, the assembly of virus‐specific nucleoprotein particles, vector transmission and to counteract plant host defence responses. Recent research findings have provided new insights into the structure and function of these proteins and have identified numerous host interacting partners. Most of the viral proteins have been shown to be multifunctional, participating in multiple events during the infection cycle and have, indeed, evolved coordinated interactions with host proteins to ensure a successful infection. Here, an up‐to‐date review of viral protein structure and function is presented, and some areas requiring further research are identified. url: https://www.ncbi.nlm.nih.gov/pubmed/23615043/ doi: 10.1111/mpp.12032 id: cord-017156-ximzvqbm author: Forsdyke, Donald R. title: Chargaff’s GC rule date: 2010-05-18 words: 9179.0 sentences: 467.0 pages: flesch: 55.0 cache: ./cache/cord-017156-ximzvqbm.txt txt: ./txt/cord-017156-ximzvqbm.txt summary: The model predicts that, for preventing recombination (i.e. creating reproductive isolation), a non-complementarity between the sequences of potentially pairing strands, in itself, might be less important than a noncomplementarity associated with sequence differences that change the pattern of stem-loops. By continuous backcrossing to sylvestris the chromosomes deriv ed from sylvestris can be tested because they form tetrads with the sylvestrisThe surv ival of a duplicate copy of a gene depends on a var iety of factors , including (i) natural selection favouring organisms where a function encoded by the gene is either increased or changed (i.e . Each isochore would have arisen as a random fluctuation in the base composition of a genomic region such that a copy of a duplicated gene that had transposed to that region was able to survive without recombination with the original gene for a sufficient number of generations to allow differentiation between the copy and its original to occur. abstract: Evolutionary selective pressures sometimes act to preserve nucleic acid features at the expense of encoded proteins. That this might occur in the case of nucleic acid secondary structure was noted in Chapter 5. That this might also apply to the species-dependent component of the base composition, (G+C)%, was shown by Sueoka in 1961 [2]. The amino acid composition of the proteins of bacteria is influenced, not only by the demands of the environment on the proteins, but also by the (G+C)% of the genome encoding those proteins. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121649/ doi: 10.1007/978-0-387-33419-6_8 id: cord-312336-784izxqd author: Fouret, Julien title: Sequencing the Genome of Indian Flying Fox, Natural Reservoir of Nipah Virus, Using Hybrid Assembly and Conservative Secondary Scaffolding date: 2020-07-29 words: 7527.0 sentences: 389.0 pages: flesch: 53.0 cache: ./cache/cord-312336-784izxqd.txt txt: ./txt/cord-312336-784izxqd.txt summary: medius genome, assembled by this method, has a length of 1,985 Mb and consists of 33,613 contigs and 16,113 scaffolds with an NG50 of 19 Mb. At least 22.5% of the assembled sequences is covered by interspersed repeats already described in other species and 19,823 coding genes are annotated. Then, we improve the assembly using secondary scaffolding methods, AGOUTI (gene-based) and Ragout (reference-assisted), using RNA seq data obtained with an Illumina 75 bp paired-end sequencing. medius with a length of 1,985 Mb, consisting of 33,613 contigs and 16,113 scaffolds with a NG50 of 19 Mb. Identified repeat elements covered 22.5% of the assembled sequences and 19,823 coding genes were annotated, thus providing the first genome sequence of this bat species and making it available for further studies and better understanding of the mechanisms of Nipah virus emergence. abstract: Indian fruit bats, flying fox Pteropus medius was identified as an asymptomatic natural host of recently emerged Nipah virus, which is known to induce a severe infectious disease in humans. The absence of P. medius genome sequence presents an important obstacle for further studies of virus–host interactions and better understanding of mechanisms of zoonotic viral emergence. Generation of the high-quality genome sequence is often linked to a considerable effort associated to elevated costs. Although secondary scaffolding methods have reduced sequencing expenses, they imply the development of new tools for the integration of different data sources to achieve more reliable sequencing results. We initially sequenced the P. medius genome using the combination of Illumina paired-end and Nanopore sequencing, with a depth of 57.4x and 6.1x, respectively. Then, we introduced the novel scaff2link software to integrate multiple sources of information for secondary scaffolding, allowing to remove the association with discordant information among two sources. Different quality metrics were next produced to validate the benefits from secondary scaffolding. The P. medius genome, assembled by this method, has a length of 1,985 Mb and consists of 33,613 contigs and 16,113 scaffolds with an NG50 of 19 Mb. At least 22.5% of the assembled sequences is covered by interspersed repeats already described in other species and 19,823 coding genes are annotated. Phylogenetic analysis demonstrated the clustering of P. medius genome with two other Pteropus bat species, P. alecto and P. vampyrus, for which genome sequences are currently available. SARS-CoV entry receptor ACE2 sequence of P. medius was 82.7% identical with ACE2 of Rhinolophus sinicus bats, thought to be the natural host of SARS-CoV. Altogether, our results confirm that a lower depth of sequencing is enough to obtain a valuable genome sequence, using secondary scaffolding approaches and demonstrate the benefits of the scaff2link application. The genome sequence is now available to the scientific community to (i) proceed with further genomic analysis of P. medius, (ii) to characterize the underlying mechanism allowing Nipah virus maintenance and perpetuation in its bat host, and (iii) to monitor their evolutionary pathways toward a better understanding of bats’ ability to control viral infections. url: https://doi.org/10.3389/fmicb.2020.01807 doi: 10.3389/fmicb.2020.01807 id: cord-298183-cisrvghj author: Fredricks, David N title: The infectious aetiology of disease: the search for new agents date: 2005-03-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract There are many diseases for which a microbial aetiology is suspected. The hypothesis that a disease has an infectious cause is supported by: clinical features (similar to those of known infectious diseases, e.g. fever, leucocytosis), epidemiology (case clustering in time or location), histology (inflammation of affected tissues, e.g. granulomata) or characteristic microbial structures, treatment (clinical response to antimicrobial treatment), and prevention of disease by vaccines targeting microbial antigens. Proof that a microbe causes a disease requires more rigorous evidence. Future attempts to identify novel microbes associated with human disease may use sequence-based approaches. High-throughput sequencing may allow identification of unique microbial nucleic acid sequences in a background of host DNA. The complete sequencing of the human genome and multiple microbial genomes make this approach more feasible. DNA microarrays are also likely to be used in the search for novel pathogens. url: https://doi.org/10.1383/medc.33.3.37.61122 doi: 10.1383/medc.33.3.37.61122 id: cord-317591-qa6oxy4j author: Fukushima, Akiko title: Development of a Chimeric DNA-RNA Hammerhead Ribozyme Targeting SARS Virus date: 2009-05-07 words: 3605.0 sentences: 196.0 pages: flesch: 53.0 cache: ./cache/cord-317591-qa6oxy4j.txt txt: ./txt/cord-317591-qa6oxy4j.txt summary: To develop an effective and specific medicine targeting the SARS-coronavirus (CoV), a chimeric DNA-RNA hammerhead ribozyme was designed and synthesized using a sequence homologous with the mouse hepatitis virus (MHV). The chimeric DNA-RNA hammerhead ribozyme targeting SARS-CoV significantly inhibited multiplication of MHV in DBT cells by about 60%. A chimeric DNA-RNA hammerhead ribozyme was designed and synthesized to target a common nucleotide sequence between SARS-CoV and mouse hepatitis virus (MHV), and its effectiveness on suppression of MHV and SARS-CoV RNA expression evaluated in vitro. Figure 4 shows effect of the chimeric DNA-RNA hammerhead ribozyme targeting SARS-CoV RNA on the multiplication of MHV in DBT cells. Therefore, the chimeric DNA-RNA hammerhead ribozyme was designed with complementarity to common regions of SARS-CoV and MHV that included the target GUC sequence. In the present study, inhibition on the multiplication of MVH was approximately 60%, with 60% transfection efficiency of the chimeric DNA-RNA ribozyme targeting SARS-CoV into DBT cells. abstract: OBJECTIVE: Severe acute respiratory syndrome (SARS) is a severe pulmonary infectious disease caused by a novel coronavirus. To develop an effective and specific medicine targeting the SARS-coronavirus (CoV), a chimeric DNA-RNA hammerhead ribozyme was designed and synthesized using a sequence homologous with the mouse hepatitis virus (MHV). METHOD: Chimeric DNA-RNA hammerhead ribozyme targeting MHV and SARS-CoV were designed and synthesized. To confirm its activity, in vitro cleavage reactions were performed with the synthesized ribozyme. Effects of the chimeric ribozyme were evaluated on multiplication of MHV. Effects of the chimeric ribozyme on expression of SARS-CoV were evaluated in cultured 3T3 cells. RESULT: The synthetic ribozyme cleaved the synthetic target MHV and SARS-CoV RNA into fragments of predicted length. The chimeric DNA-RNA hammerhead ribozyme targeting SARS-CoV significantly inhibited multiplication of MHV in DBT cells by about 60%. The chimeric DNA-RNA hammerhead ribozyme targeting SARS-CoV significantly inhibited the expression of SARS-CoV RNA in 3T3 cells transfected with the recombinant plasmid. The chimeric DNA-RNA ribozyme targeting SARS-CoV significantly inhibited MHV viral activity and expression of recombinant SARS RNA in vitro. CONCLUSION: These findings indicate that the synthetic chimeric DNA-RNA ribozyme could provide a feasible treatment for SARS. url: https://www.ncbi.nlm.nih.gov/pubmed/19420961/ doi: 10.1159/000215946 id: cord-017881-5jjlx7ot author: Fulekar, M. H. title: Nanotechnology — In Relation to Bioinformatics date: 2009 words: 2668.0 sentences: 150.0 pages: flesch: 49.0 cache: ./cache/cord-017881-5jjlx7ot.txt txt: ./txt/cord-017881-5jjlx7ot.txt summary: Eric Drexler, in 1986, published book "Engines of Creation" in which he described his ideas of molecular nanotechnology used to build miniature machines and devices from the bottom up using self-assembly. National Science and Technology Council (US) (2000) has defined Nanotechnology as: "Research and Technology development at the atomic, molecular, or macromolecular levels in the length of approximately 1-100 nm range, to provide fundamental understanding of phenomena and materials at the nanoscale, and to create and use structures, devices and systems that have novel properties and functions because of their small size. Nanotechnology research and development includes integration of nanoscale structure into larger material components, systems, and architectures. Nanotechnology will complement genomic and proteomic research and accelerate the ability of scientist to prevent, detect and treat cancer. The development of tools in genomics, proteomics, molecular imaging, bioinformatics, nanotechnology and other advanced technologies is a critical step. abstract: The first use of word “Nanotechnology” has been attributed to Norio Taniguchi in a paper published in 1974. Eric Drexler, in 1986, published book “Engines of Creation” in which he described his ideas of molecular nanotechnology used to build miniature machines and devices from the bottom up using self-assembly. Many scientists from mainstream disciplines—biology, chemistry or physics—will argue of course that they are and have been ‘doing’ nanotechnology for years and that it is nothing new. Indeed chemists play with atoms and molecules which are sub-nano and molecular biology deals with the understanding and application of biological nano-scale components. Nature has used nanotechnology and, in fact, it has taken millions of years to develop this by a process of evolution and natural selection. Nanotechnology is an emerging research field which promises to have a wide range of interesting applications. Nanotechnology, encompasses all technology that aims to create nanometre-scaled structures or is able to address or manipulate matter at the nanometre level. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122563/ doi: 10.1007/978-1-4020-8880-3_11 id: cord-253295-82ydczid author: Funkhouser, William K. title: Pathology: the clinical description of human disease date: 2020-07-24 words: 8864.0 sentences: 396.0 pages: flesch: 34.0 cache: ./cache/cord-253295-82ydczid.txt txt: ./txt/cord-253295-82ydczid.txt summary: Patient workup uses present illness history with reference to past medical history, review of other organ systems for other abnormalities, review of family history, physical examination, radiographic studies, clinical laboratory studies (for example, peripheral blood or CSF specimens), and anatomic pathology laboratory studies (for example, tissue biopsy or pleural fluid cytology specimens). Obviously, arrival at the correct diagnosis is a function of the examining physician and pathologist (fund of knowledge, experience, alertness), the prevalence of the disease in question in the particular patient (age, race, sex, site), and the sensitivity/ specificity of the screening tests used (physical exam, vital signs, blood solutes, tissue stains, genetic assays). However, understanding the molecular and cellular pathogenesis of a disease allows development of screening methods to determine risk for clinically unaffected individuals, as well as mechanistic approaches to specific therapy. abstract: Pathology is that field of science and medicine concerned with the study of diseases, specifically their initial causes (etiologies), their step-wise progressions (pathogenesis), and their effects on normal structure and function. This chapter will consider the history of relevant discoveries and technologies that have led to our current understanding of diseases, as well as the Pathologist’s current role in the diagnosis, prognosis, and prediction of response of human diseases. url: https://api.elsevier.com/content/article/pii/B9780128132579000115 doi: 10.1016/b978-0-12-813257-9.00011-5 id: cord-316534-ep7ezoko author: Gamble, Lena J title: Current progress in the development of a prophylactic vaccine for HIV-1 date: 2010-12-22 words: 11945.0 sentences: 631.0 pages: flesch: 40.0 cache: ./cache/cord-316534-ep7ezoko.txt txt: ./txt/cord-316534-ep7ezoko.txt summary: 67 The vaccine, a recombinant adenovirus serotype 5 (Ad5) virus incorporating the gag, pol, and nef genes from HIV-1, had been previously tested in an SHIV model in macaques and the results of that experiment were not suggestive of the results of the human trial. In hopes of creating a vaccine which elicits sterilizing immunity to HIV-1, researchers have focused their efforts on (1) the use of plasmid DNA vaccines, (2) live recombinant vectors for vaccine development (expressing or presenting HIV antigens), and (3) mucosal immunity. For instance, research performed by Harari and colleagues in 2008 demonstrated that vaccination by means of an HIV-1 clade C DNA prime in combination with a pox vector (NYVAC) boost induces a reliable polyfunctional and longlasting anti-HIV T-cell response in human participants. Repeated immunization with recombinant gp160 human immunodeficiency virus (HIV) envelope protein in early HIV-1 infection: evaluation of the T cell proliferative response abstract: Since its discovery and characterization in the early 1980s as a virus that attacks the immune system, there has been some success for the treatment of human immunodeficiency virus-1 (HIV-1) infection. However, due to the overwhelming public health impact of this virus, a vaccine is needed urgently. Despite the tireless efforts of scientist and clinicians, there is still no safe and effective vaccine that provides sterilizing immunity. A vaccine that provides sterilizing immunity against HIV infection remains elusive in part due to the following reasons: 1) degree of diversity of the virus, 2) ability of the virus to evade the hosts’ immunity, and 3) lack of appropriate animal models in which to test vaccine candidates. There have been several attempts to stimulate the immune system to provide protection against HIV-infection. Here, we will discuss attempts that have been made to induce sterilizing immunity, including traditional vaccination attempts, induction of broadly neutralizing antibody production, DNA vaccines, and use of viral vectors. Some of these attempts show promise pending continued research efforts. url: https://www.ncbi.nlm.nih.gov/pubmed/21267356/ doi: 10.2147/dddt.s6959 id: cord-294864-x7mam4y3 author: García-González, Raquel title: Methylene blue covalently attached to single stranded DNA as electroactive label for potential bioassays date: 2014-02-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Methylene blue is an electroactive molecule that has been employed for the detection of the DNA hybridization event in electrochemical sensors. However, its use as a covalent label is very scarce and in most of the cases, non-covalent interactions (hydrophobic, electrostatic) are employed. Although it has advantages as simplicity and fewer number of procedure steps, the covalent attachment is less exploited in the development of these sensors. In this article, the electrochemical behavior of methylene blue attached to different DNA-strands is studied. Several lengths (15- and 30-mer) and different degree of DNA modification (MB-DNA, MB-DNA-MB and MB-DNA-SH) have been studied. The highest signals were obtained for longer strands with two MB molecules. In all the cases the signal is enhanced by CNT-nanostructuration of the electrode. Adsorption on these modified screen-printed electrodes allowed the amplification by employing an accumulation time. In this way, a sensitivity of −0.2864μAμM−1 and a limit of detection of 800nM for a 120s accumulation time were obtained. url: https://api.elsevier.com/content/article/pii/S0925400513012239 doi: 10.1016/j.snb.2013.10.037 id: cord-296356-qkvafy69 author: Garman, Elspeth title: SARS Proteomics Reveals Viral Secrets date: 2005-11-30 words: 1306.0 sentences: 74.0 pages: flesch: 51.0 cache: ./cache/cord-296356-qkvafy69.txt txt: ./txt/cord-296356-qkvafy69.txt summary: The structure of the mutagenic base pair in the confines of a closed polymerase complex exposes some of those strategies. (2005) In a worldwide cooperative research effort involving a multidisciplinary approach, structural and functional characterization of the SARS virus and its host interactions has been swiftly pursued. By sequence alignment and structural comparison with all known H2A domains, as well as examination of functional data, the authors conjecture that proteins from this superfamily form an emerging group of nucleotide phosphatases, all with similar functionality. This has two pivotal consequences for understanding the biology of the virus: A systematic approach is essential, and, even more importantly, a deeper structural and functional knowledge of the many complexes that the SARS CoV proteins form with one another and with proteins of the host organisms will be required-research that is still in its infancy. abstract: Worldwide cooperative efforts to understand the biology of the SARS coronavirus have already born significant fruit. In a further advance, the X-ray structure of a domain of nonstructural protein 3 is reported by Saikatendu et al. (2005) in this issue of Structure. url: https://api.elsevier.com/content/article/pii/S0969212605003540 doi: 10.1016/j.str.2005.10.004 id: cord-281404-5a8au32c author: Gastaldello, Stefano title: Caspase-1 Promotes Epstein-Barr Virus Replication by Targeting the Large Tegument Protein Deneddylase to the Nucleus of Productively Infected Cells date: 2013-10-10 words: 7139.0 sentences: 337.0 pages: flesch: 42.0 cache: ./cache/cord-281404-5a8au32c.txt txt: ./txt/cord-281404-5a8au32c.txt summary: The large tegument proteins of herpesviruses contain N-terminal cysteine proteases with potent ubiquitin and NEDD8-specific deconjugase activities, but the function of the enzymes during virus replication remains largely unknown. Here we report that induction of the productive virus cycle has no appreciable effects on the global levels of protein ubiquitination but is accompanied by a BPLF1-dependent decrease of cullin neddylation and stabilization of nuclear CRL substrates. The Akata-Bx1 cell line was used to study the contribution of the Ub-and NEDD8-specific deconjugase activities of the EBV large tegument protein BPLF1 to the productive virus cycle. In order to assess whether this regulatory interaction may operate during virus replication, the productive cycle was induced in Akata-Bx1 cells transiently transfected with plasmids expressing Myc-tagged CAND1 or the CAND1 Nterminus that compete for BPLF1 binding to cullins, or, as controls, the CAND1 C-terminus that binds to the opposite end of the cullin scaffold, and the empty vector ( Figure 5A ). abstract: The large tegument proteins of herpesviruses contain N-terminal cysteine proteases with potent ubiquitin and NEDD8-specific deconjugase activities, but the function of the enzymes during virus replication remains largely unknown. Using as model BPLF1, the homologue encoded by Epstein-Barr virus (EBV), we found that induction of the productive virus cycle does not affect the total level of ubiquitin-conjugation but is accompanied by a BPLF1-dependent decrease of NEDD8-adducts and accumulation of free NEDD8. Expression of BPLF1 promotes cullin degradation and the stabilization of cullin-RING ligases (CRLs) substrates in the nucleus, while cytoplasmic CRLs and their substrates are not affected. The inactivation of nuclear CRLs is reversed by the N-terminus of CAND1, which inhibits the binding of BPLF1 to cullins and prevents efficient viral DNA replication. Targeting of the deneddylase activity to the nucleus is dependent on processing of the catalytic N-terminus by caspase-1. Inhibition of caspase-1 severely impairs viral DNA synthesis and the release of infectious virus, pointing a previously unrecognized role of the cellular response to danger signals triggered by EBV reactivation in promoting virus replication. url: https://doi.org/10.1371/journal.ppat.1003664 doi: 10.1371/journal.ppat.1003664 id: cord-014397-7b88ycv8 author: Gavora, JS title: Resistance of livestock to viruses: mechanisms and strategies for genetic engineering date: 1996-12-15 words: 11583.0 sentences: 528.0 pages: flesch: 41.0 cache: ./cache/cord-014397-7b88ycv8.txt txt: ./txt/cord-014397-7b88ycv8.txt summary: Thus introduction of new mechanisms of disease resistance in livestock by gene transfer may be viewed as a logical continuation of the creative influence of humans on the evolution of farm animals and birds that could benefit mankind by improvements in food safety and production efficiency. As background for the discussion of the subject, the article deals briefly with coevolution of hosts and parasites and principal elements of virus-host interactions, and reviews past improvement of disease resistance in plants and livestock by conventional breeding and genetic engineering, as well as the potential ''biological cost'' of genetic manipulation. Basic understanding of the parallel evolution of viruses and their hosts provides a useful starting point for the consideration of strategies for genetic engineering of new mechanisms of resistance. Genetic engineering strategies that prevent entry of viruses into host cells would be effective against all three types of viral infection. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2708302/ doi: 10.1186/1297-9686-28-5-385 id: cord-011073-uiabpbxd author: Gebrekidan, Hagos title: An appraisal of oriental theileriosis and the Theileria orientalis complex, with an emphasis on diagnosis and genetic characterisation date: 2019-12-06 words: 7011.0 sentences: 406.0 pages: flesch: 46.0 cache: ./cache/cord-011073-uiabpbxd.txt txt: ./txt/cord-011073-uiabpbxd.txt summary: Oriental theileriosis, a tick-borne disease of bovids caused by members of the Theileria orientalis complex, has a worldwide distribution. orientalis complex, including conventional polymerase chain reaction (PCR), nested-PCR, reverse line blot hybridisation assay (RLB), loop-mediated isothermal amplification (LAMP), real-time/quantitative PCR (qPCR) using hydrolysis probes and multiplexed tandem PCR (MT-PCR) assays (Table 2) . nPCR Members of the Theileria orientalis complex have been detected in cattle blood samples in Brazil, Iran, South Africa, Uganda and the USA using semi-nested or nested PCR (nPCR) assay employing the SSU or ITS loci (Chae et al. orientalis allow for a rapid and accurate diagnosis (mainly for the two pathogenic genotypes chitose and ikeda), some assays can be expensive for routine use due to individual testing of blood samples, particularly when outbreaks of oriental theileriosis occur in cattle herds. Development and evaluation of a real-time PCR assay for the quantitative detection of Theileria annulata in cattle abstract: Oriental theileriosis, a tick-borne disease of bovids caused by members of the Theileria orientalis complex, has a worldwide distribution. Globally, at least 11 distinct genotypes of T. orientalis complex, including type 1 (chitose), type 2 (ikeda), type 3 (buffeli), types 4 to 8, and N1–N3, have been described based on the sequence of the major piroplasm surface protein (MPSP) gene. Of these 11 genotypes, mainly ikeda and chitose are known to be pathogenic and cause considerable morbidity (including high fever, anaemia, jaundice and abortion), production losses and/or mortality in cattle. Mixed infections with two or more genotypes of T. orientalis is common, but do not always lead to a clinical disease, posing challenges in the diagnosis of asymptomatic or subclinical forms of oriental theileriosis. The diagnosis of oriental theileriosis is usually based on clinical signs, the detection of piroplasms of T. orientalis in blood smears, and/or the use of serological or molecular techniques. This paper reviews current methods used for the diagnosis of T. orientalis infections and the genetic characterisation of members of the T. orientalis complex, and proposes that advanced genomic tools should be established for investigations of these and related haemoparasites. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223495/ doi: 10.1007/s00436-019-06557-7 id: cord-292928-a4bn30ul author: Ghosh, Bipasha title: Review of bioaerosols in indoor environment with special reference to sampling, analysis and control mechanisms date: 2015-10-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Several tiny organisms of various size ranges present in air are called airborne particles or bioaerosol which mainly includes live or dead fungi and bacteria, their secondary metabolites, viruses, pollens, etc. which have been related to health issues of human beings and other life stocks. Bio-terror attacks in 2001 as well as pandemic outbreak of flue due to influenza A H1N1 virus in 2009 have alarmed us about the importance of bioaerosol research. Hence characterization i.e. identification and quantification of different airborne microorganisms in various indoor environments is necessary to identify the associated risks and to establish exposure threshold. Along with the bioaerosol sampling and their analytical techniques, various literatures revealing the concentration levels of bioaerosol have been mentioned in this review thereby contributing to the knowledge of identification and quantification of bioaerosols and their different constituents in various indoor environments (both occupational and non-occupational sections). Apart from recognition of bioaerosol, developments of their control mechanisms also play an important role. Hence several control methods have also been briefly reviewed. However, several individual levels of efforts such as periodic cleaning operations, maintenance activities and proper ventilation system also serve in their best way to improve indoor air quality. url: https://doi.org/10.1016/j.envint.2015.09.018 doi: 10.1016/j.envint.2015.09.018 id: cord-298514-l2hs1h9c author: Ghosh, Soma title: Central Role of Ubiquitination in Genome Maintenance: DNA Replication and Damage Repair date: 2012-02-08 words: 5360.0 sentences: 276.0 pages: flesch: 39.0 cache: ./cache/cord-298514-l2hs1h9c.txt txt: ./txt/cord-298514-l2hs1h9c.txt summary: The ubiquitin system mediates the DNA damage response to all the above forms of replicative damage in the cell in order to prevent genomic instability and onset of cancer. The checkpoint apparatus targets the CDK regulators like cyclins, CDK inhibitors, or CDC25 family of dual-specificity phosphatases, depending upon the stage of the cell cycle in which the DNA damage has occurred. SCF ßTrCP also regulates checkpoint recovery: the ubiquitin-dependent degradation of CLASPIN (a DNA-binding protein required for the ATR mediated activation of Chk1 in response to DNA replication stress) in G2 allows efficient termination of DNA replication checkpoint which is necessary for progression of the cell into mitosis [36] [37] [38] [39] . Regulation of Claspin degradation by the ubiquitin-proteosome pathway during the cell cycle and in response to ATR-dependent checkpoint activation abstract: Faithful transmission of genetic information through generations ensures genomic stability and integrity. However, genetic alterations occur every now and then during the course of genome duplication. In order to repair these genetic defects and lesions, nature has devised several repair pathways which function promptly to prevent the cell from accumulating permanent mutations. These repair mechanisms seem to be significantly impacted by posttranslational modifications of proteins like phosphorylation and ubiquitination. Protein ubiquitination is emerging as a critical regulatory mechanism of DNA damage response. Non-proteolytic, proteasome-independent functions of ubiquitin involving monoubiquitination and polyubiquitination of DNA repair proteins contribute significantly to the signaling of DNA repair pathways. In this paper, we will particularly highlight the work on ubiquitin-mediated signaling in the repair processes involving the Fanconi anemia pathway, translesional synthesis, nucleotide excision repair, and repair of double-strand breaks. We will also discuss the role of ubiquitin ligases in regulating checkpoint mechanisms, the role of deubiquitinating enzymes, and the growing possibilities of therapeutic intervention in this ubiquitin-conjugation system. url: https://doi.org/10.5402/2012/146748 doi: 10.5402/2012/146748 id: cord-018969-0zrnfaad author: Giese, Matthias title: Types of Recombinant Vaccines date: 2015-09-24 words: 14221.0 sentences: 811.0 pages: flesch: 48.0 cache: ./cache/cord-018969-0zrnfaad.txt txt: ./txt/cord-018969-0zrnfaad.txt summary: New vaccines and vaccination strategies are being developed including the use of attenuated live mycobacteria, recombinant microorganisms, and subunits, prime-boost strategies based on the successive administration of a certain mycobacterial antigen under two different vaccine vectors, and DNA vaccines [ 1 ] . However, several animal models have been developed to study the pathogenesis of Shigella , the resulting immune response against Shigella antigens, and the protection efficacy of candidate vaccines against shigellosis: [ 31 ] . The GAS M protein is the major protective antigen and an ideal target for vaccine development; however it contains heart tissue cross-reactive epitopes particularly in the conserved region [ 98 ] . Immunization of mice with a C-region peptide GAS vaccine candidate called J8 conjugated to the carrier protein diphtheria toxoid (dT) and co-delivery with an appropriate adjuvant led to protection against systemic and mucosal GAS infection [ 104 ] (Fig. 9.29 ). abstract: The original scientific strategy behind vaccinology has historically been to “isolate, inactivate, and inject,” first invoked by Louis Pasteur. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123991/ doi: 10.1007/978-3-319-25832-4_9 id: cord-260345-ugd8kkor author: Giles, Ian G. title: A compendium of reviews in biochemistry and molecular biology published in the first half of 1992 date: 1992-12-31 words: 5327.0 sentences: 701.0 pages: flesch: 45.0 cache: ./cache/cord-260345-ugd8kkor.txt txt: ./txt/cord-260345-ugd8kkor.txt summary: 203, sodium dodecyl-sulfate.; ted blood-cells; phosphoenolpyruvate carboxylase activity; nucleotide-linked dehydrogenases; alkaline-phosphatase isoenzymes; pathogenesis-related proteins; cr-L-fucosidase; polyactylamide-gel; produce phosphate; general-method. low-density~l&protein; high-performance liquid; chrcmatogmphy mass spectmmetry; chicken vitellogam gene; thin-layer chmmatography; apolipoprotein-VLDL-II; fatty-acid composition; laying turkey hens; egg-yolk; plasma-lipoproteins. human-skin fibroblests; IGF binding-protein; messenger ribonucleic-acid; cooh-teminal truncation; monoclonal-antibody; endothelial-cells; factor receptoc amniotic-fluid; DNA-synthesis; rat-heart. factor-binding-protein; erythroid colony formation; cultured human-tibroblasts; factor messenger-RNA, N-terminal sequence; fetal bovine serum; IGF-I; somatomedin C, clinical-applicstians; stimulating factors. shon-hved protein; dependent pmteolytic system; ubiquitin-conjugating enzyme; repair gene ra&, Escherichia coli; transfer RNA; Sacclurroqces cercvisiue; endoplasmic-reticulum; cell-cycle; amino-acid. polymense chain-reaction; fragment length polymorphisms; dependent diabetes-mellitus; sickle-cell anemia; factor-M gene; enzymatic AMPlificatiat; genomic DNA; mutations; sequence; diagnosis; predisposition; genetics. T-cell receptor; messenger-RNA degradation; gamma-delta; stress proteins; antigen-receptor, lymphocytes-T; ~ycobactcrium fuberc&arir. Wiskott-Aldrich syndrome; heat-shock proteins; receptor-delta; ataxia telangiectasia; transgenic mice; lymphocytes T; bearing cells; recognition; expression; incmase. human granulocyte-macmphage; protein kinase-c; recombinant human interleukin-3; cell growth-factor, murine bone-marrow; express functional receptors; acute lymphocytic-leukemia; GTPase-activating pm&n; factor-independent growth. abstract: Abstract 1. 1. A compendium of reviews and mini-reviews in Biochemistry and Molecular Biology published in the first half of 1992 is presented. In all 499 titles are listed from 95 different publications. 2. 2. This compendium presents the references by Journal Name. Keywords have been included with each reference to increase the value of the collection. Keyword and author cross-reference indexes are not included but are available in the electronic database from which this version was constructed. Should anyone wish to have this information in electronic form it can be distributed on MS-DOS formatted flopppy disks in either Reference Manager or Medline format. The author should be contacted for details of the number of preformatted floppy disks required. url: https://www.sciencedirect.com/science/article/pii/0020711X92902837 doi: 10.1016/0020-711x(92)90283-7 id: cord-260422-z22t57ju author: Godet, Julien title: Comparative nucleic acid chaperone properties of the nucleocapsid protein NCp7 and Tat protein of HIV-1 date: 2012-06-26 words: 9180.0 sentences: 486.0 pages: flesch: 49.0 cache: ./cache/cord-260422-z22t57ju.txt txt: ./txt/cord-260422-z22t57ju.txt summary: Today''s view is that RNA chaperones are nucleic acid binding proteins present in all living organisms, including viruses, where they Abbreviations: HIV-1, human immunodeficiency virus-type I; NCp7, nucleocapsid protein of HIV-1; ZF, zinc finger; NA, nucleic acid; TAR, transactivation response element; PBS, primer binding site; AA, amino acids. The substantial nucleic acid chaperone properties exhibited by Tat may account for its ability to promote the annealing of the primer tRNA to the viral RNA (Kameoka et al., 2002) and intervene in the first strand transfer (Boudier et al., 2010) and by this way, to stimulate RTion as does NCp7 (Harrich et al., 1997; Ulich et al., 1999; Apolloni et al., 2007) . Human immunodeficiency virus Type 1 nucleocapsid protein (NCp7) directs specific initiation of minusstrand DNA synthesis primed by human tRNA(Lys3) in vitro: studies of viral RNA molecules mutated in regions that flank the primer binding site abstract: RNA chaperones are proteins able to rearrange nucleic acid structures towards their most stable conformations. In retroviruses, the reverse transcription of the viral RNA requires multiple and complex nucleic acid rearrangements that need to be chaperoned. HIV-1 has evolved different viral-encoded proteins with chaperone activity, notably Tat and the well described nucleocapsid protein NCp7. We propose here an overview of the recent reports that examine and compare the nucleic acid chaperone properties of Tat and NCp7 during reverse transcription to illustrate the variety of mechanisms of action of the nucleic acid chaperone proteins. url: https://www.sciencedirect.com/science/article/pii/S0168170212002183 doi: 10.1016/j.virusres.2012.06.021 id: cord-315570-khm1veuv author: González-Mora, Alejandro title: Bacteriophage-Based Vaccines: A Potent Approach for Antigen Delivery date: 2020-09-04 words: 9969.0 sentences: 455.0 pages: flesch: 40.0 cache: ./cache/cord-315570-khm1veuv.txt txt: ./txt/cord-315570-khm1veuv.txt summary: This system relies on bacteriophages displaying proteins or peptides with high affinity to antigen-presenting cells or the antigen itself and at the same time they carry on their genome an eukaryotic expression cassette encoding a specific antigen with the final aim of increasing the immune response by combining both effects (Figure 1 ) [6] . developed a double-hybrid filamentous bacteriophage fd co-displaying peptides recognized by the Major Histocompatibility Complex (MHC) class I and MHC class II cell surface receptors and epitopes from the antigen MAGE aiming to enhance the anti-tumor immune activity based on CTL responses [62] . Thus, the adjuvant-like effect exhibited by phages in various vaccination studies along with their capacity to effectively present peptides or proteins to the immune system leading to the activation of cellular and humoral immune responses [40] demonstrates that engineered phage particles are a proper strategy to enhance the efficacy and safety of viral particle-based vaccines. abstract: Vaccines are considered one of the most important bioproducts in medicine. Since the development of the smallpox vaccine in 1796, several types of vaccines for many diseases have been created. However, some vaccines have shown limitations as high cost and low immune responses. In that regard, bacteriophages have been proposed as an attractive alternative for the development of more cost-effective vaccines. Phage-displayed vaccines consists in the expression of antigens on the phage surface. This approach takes advantage of inherent properties of these particles such as their adjuvant capacity, economic production and high stability, among others. To date, three types of phage-based vaccines have been developed: phage-displayed, phage DNA and hybrid phage-DNA vaccines. Typically, phage display technology has been used for the identification of new and protective epitopes, mimotopes and antigens. In this context, phage particles represent a versatile, effective and promising alternative for the development of more effective vaccine delivery systems which should be highly exploited in the future. This review describes current advances in the development of bacteriophage-based vaccines, with special attention to vaccine delivery strategies. Moreover, the immunological aspects of phage-based vaccines, as well as the applications of phage display for vaccine development, are explored. Finally, important challenges and the future of phage-bases vaccines are discussed. url: https://doi.org/10.3390/vaccines8030504 doi: 10.3390/vaccines8030504 id: cord-003609-p0ydzjre author: Goodman, Danielle E. title: Enhanced Replication of Mouse Adenovirus Type 1 following Virus-Induced Degradation of Protein Kinase R (PKR) date: 2019-04-23 words: 8894.0 sentences: 487.0 pages: flesch: 55.0 cache: ./cache/cord-003609-p0ydzjre.txt txt: ./txt/cord-003609-p0ydzjre.txt summary: RNA was purified from fractions containing monosomes MAV-1 Degrades PKR during Infection ® and polysomes and then used to generate cDNA, which we assayed for PKR mRNA by qPCR (Fig. 4C) . Thus, the 18-hpi time point is considered an early time point during MAV-1 infection of CMT93 cells, prior to DNA replication, suggesting the involvement of an early viral protein in PKR depletion. We examined PKR protein levels during MAV-1 infection and found that PKR was depleted from the cells as early as 12 hpi (Fig. 7) . While the PKR mRNAs in C57BL/6 MEFs were depleted 33% at 48 hpi and 40% at 72 hpi compared to mock-infected lysates, this was not sufficient to explain the 84% and 94% reductions, respectively, in PKR protein levels at those time points (Fig. 2B ). abstract: Protein kinase R (PKR) plays a major role in activating host immunity during infection by sensing double-stranded RNA (dsRNA) produced by viruses. Once activated by dsRNA, PKR phosphorylates the translation factor eukaryotic initiation factor 2α (eIF2α), halting cellular translation. Many viruses have methods of inhibiting PKR activation or its downstream effects, circumventing protein synthesis shutdown. These include sequestering dsRNA or producing proteins that bind to and inhibit PKR activation. Here we describe our finding that in multiple cell types, PKR was depleted during mouse adenovirus type 1 (MAV-1) infection. MAV-1 did not appear to be targeting PKR at the transcriptional or translational level, because total PKR mRNA levels and levels of PKR mRNA bound to polysomes were unchanged or increased during MAV-1 infection. However, inhibiting the proteasome reduced the PKR depletion seen in MAV-1-infected cells, whereas inhibiting the lysosome had no effect. This suggests that proteasomal degradation alone is responsible for PKR degradation during MAV-1 infection. Time course experiments indicated that the degradation occurs early after infection. Infecting cells with UV-inactivated virus prevented PKR degradation, whereas inhibiting viral DNA replication did not. Together, these results suggest that an early viral gene is responsible. Degradation of PKR is a rare mechanism to oppose PKR activity, and it has been described in only six RNA viruses. To our knowledge, this is the first example of a DNA virus counteracting PKR by degrading it. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479006/ doi: 10.1128/mbio.00668-19 id: cord-016713-pw4f8asc author: Goyal, Amit K. title: Nanotechnological Approaches for Genetic Immunization date: 2013-05-24 words: 16034.0 sentences: 814.0 pages: flesch: 34.0 cache: ./cache/cord-016713-pw4f8asc.txt txt: ./txt/cord-016713-pw4f8asc.txt summary: The use of nonviral particulate carriers for DNA-based vaccination could provide better and safe delivery of encapsulated genetic material, circumvent the need for muscle involvement and facilitate instead the uptake of the Fig. 4 Schematic representation of immunological response greeted by novel DNA-loaded nanocarrier DNA by APCs. However, transfection of APCs with encapsulated DNA into particulate carrier systems will be dependent upon choice of carrier surface charge, size, and lipid/polymer composition, or presence of other biological [e.g., interleukin 2 and interferon-γ (IFN-γ)]. Modification of lipid/DNA complexes by the polymer poly(D,L-lactic acid) was found to be consistently and significantly more effective than either unmodified liposomal DNA or naked DNA in eliciting transgene-specific immune responses to plasmid-encoded antigen when administered by the s.c. route (Bramwell et al. abstract: Genetic immunization is one of the important findings that provide multifaceted immunological response against infectious diseases. With the advent of r-DNA technology, it is possible to construct vector with immunologically active genes against specific pathogens. Nevertheless, site-specific delivery of constructed genetic material is an important contributory factor for eliciting specific cellular and humoral immune response. Nanotechnology has demonstrated immense potential for the site-specific delivery of biomolecules. Several polymeric and lipidic nanocarriers have been utilized for the delivery of genetic materials. These systems seem to have better compatibility, low toxicity, economical and capable to delivering biomolecules to intracellular site for the better expression of desired antigens. Further, surface engineering of nanocarriers and targeting approaches have an ability to offer better presentation of antigenic material to immunological cells. This chapter gives an overview of existing and emerging nanotechnological approaches for the delivery of genetic materials. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121080/ doi: 10.1007/978-3-642-36853-0_4 id: cord-280249-kfon0l9h author: Granstrom, David E. title: Recent Advances in the Laboratory Diagnosis of Equine Parasitic Diseases date: 1995-12-31 words: 2073.0 sentences: 148.0 pages: flesch: 53.0 cache: ./cache/cord-280249-kfon0l9h.txt txt: ./txt/cord-280249-kfon0l9h.txt summary: 5 • 12 • 15 Accurate antemortem diagnosis has been enhanced greatly by the recent development of the Western blot and polymerase chain reaction tests (Equine Biodiagnostics, Inc, Lexington, KY) to detect parasite-specific antibodies or parasite DNA in the blood or cerebrospinal fluid (CSF) of affected horses. neurona was developed to detect the parasite in blood or spinal fluid of affected horses.7 Amplification primers were designed from the nucleotide sequence of the 18S small ribosomal subunit gene of S. Generally, it has not been necessary to use the PCR test to confirm positive Western blot results for CSF samples. The presence of parasite DNA in an equine blood sample suggests that the horse recently ingested S. 4 , s, 9, 17 , 18 Although Cryptosporidium alone may cause foal diarrhea, it also has been associated with concurrent infection with other enteric pathogens (adenovirus, coronavirus, rotavirus, Giardia, Salmonella), 4 , 17 , 18, 19 It is im portant to consider testing for these agents as well. abstract: This article reviews recent advances in laboratory diagnosis of equine parasitic diseases. Laboratory diagnosis of most equine parasitic diseases continues to rely on standard methods. Only laboratory diagnostic testing for EPM, cryptosporidiosis, and giardiasis are included, and the criteria for testing and interpretation of results for each new diagnostic method are explained. url: https://www.ncbi.nlm.nih.gov/pubmed/8925419/ doi: 10.1016/s0749-0739(17)30309-7 id: cord-287286-4l963z2q author: Green, Victoria A. title: Molecular mechanisms of viral infection and propagation: An overview of the second Advanced Summer School in Africa date: 2010-07-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/20681023/ doi: 10.1002/iub.364 id: cord-304424-048xo7jn author: Greninger, Alexander L. title: A decade of RNA virus metagenomics is (not) enough date: 2018-01-15 words: 9606.0 sentences: 495.0 pages: flesch: 43.0 cache: ./cache/cord-304424-048xo7jn.txt txt: ./txt/cord-304424-048xo7jn.txt summary: That same year 36,789 colony sequences from DNase-treated RNA extracted from viral concentrates of human feces revealed a preponderance of pepper mild mottle virus and other plant viruses, but no new human viruses (Zhang et al., 2005) . While finding a new virus in the environment is not necessarily a problem in either DNA or RNA, the low fidelity of RNA polymerases and the sequence space they are capable of sampling, along with the possibility of recombination, lend themselves to new species and genera that are the trophies of metagenomic viral discovery. While metagenomics delivered on the promise of finding novel human viruses, viral discovery in humans has increasingly become a tragic story of patients interacting with the wrong squirrel or tick on the wrong day and most samples sequenced are frankly negative (Hoffmann et al., 2015; McMullan et al., 2012) . The greatest paradigm shifter in recent viral metagenomics work has been the sheer number and diversity of novel RNA viruses present in arthropods and invertebrates. abstract: It is hard to overemphasize the role that metagenomics has had on our recent understanding of RNA virus diversity. Metagenomics in the 21st century has brought with it an explosion in the number of RNA virus species, genera, and families far exceeding that following the discovery of the microscope in the 18th century for eukaryotic life or culture media in the 19th century for bacteriology or the 20th century for virology. When the definition of success in organism discovery is measured by sequence diversity and evolutionary distance, RNA viruses win. This review explores the history of RNA virus metagenomics, reasons for the successes so far in RNA virus metagenomics, and methodological concerns. In addition, the review briefly covers clinical metagenomics and environmental metagenomics and highlights some of the critical accomplishments that have defined the fast pace of RNA virus discoveries in recent years. Slightly more than a decade in, the field is exhausted from its discoveries but knows that there is yet even more out there to be found. url: https://www.ncbi.nlm.nih.gov/pubmed/29055712/ doi: 10.1016/j.virusres.2017.10.014 id: cord-277665-ac8txr3h author: Grichko, Varvara P. title: 15 Nanodiamond Designing the Bio-Platform date: 2006-12-31 words: 8852.0 sentences: 453.0 pages: flesch: 38.0 cache: ./cache/cord-277665-ac8txr3h.txt txt: ./txt/cord-277665-ac8txr3h.txt summary: The chapter also summarizes different approaches to the surface functionalization of nanodiamonds (ND) particles—that is, the key in successful biomedical applications followed by a discussion of modification of diamond surfaces with nucleic acids and proteins. This chapter will be organized as follows: in the next section different approaches to the surface functionalization of ND particles, that is, the key in successful biomedical applications, will be summarized, followed by a discussion of modification of diamond surfaces with nucleic acids and proteins. Nanocrystalline diamond thin films covalently modified with DNA oligonucleotides following the photochemical modification of H-terminated surfaces with amine groups provide a very stable and highly selective platform for the surface hybridization reaction (Yang et al., 2002) . When made sufficiently electrically conducting by boron doping, thin-film and free-standing diamond electrodes exhibit remarkable chemical resistance to etching, a wide potential window, low background current responses, mechanical stability toward ultrasound-induced interfacial cavitation, a low stickiness in adsorption processes, and a high degree of tunability of the surface properties (reviewed by Compton et al., 2003) . abstract: Publisher Summary This chapter discusses various methods of surface modification for the development of functionalized diamond nanoparticles for biomedical applications. To be used in biomedical applications, nanoparticles must be biocompatible, non-toxic, non-detective by immune systems, and should not induce side effects. Size control of particles is a prerequisite for biomedical applications. Carbon nanostructures span the same length scale as bio-compounds, ranging from subnanometer-size nucleotides to tens and hundreds of nanometer-sized organelles and viruses, and up to micron-sized cell sizes. The chapter also summarizes different approaches to the surface functionalization of nanodiamonds (ND) particles—that is, the key in successful biomedical applications followed by a discussion of modification of diamond surfaces with nucleic acids and proteins. Both current and potential applications of diamond films and particles in the area of biosensing are addressed. url: https://api.elsevier.com/content/article/pii/B9780815515241500172 doi: 10.1016/b978-081551524-1.50017-2 id: cord-013290-j3assowx author: Guibinga, Ghiabe H. title: Protection against Borreliella burgdorferi infection mediated by a synthetically engineered DNA vaccine date: 2020-08-12 words: 5081.0 sentences: 281.0 pages: flesch: 50.0 cache: ./cache/cord-013290-j3assowx.txt txt: ./txt/cord-013290-j3assowx.txt summary: We describe the development of a novel synthetically engineered DNA vaccine, pLD1 targeting the outer-surface protein A (OspA) of Borreliella burgdorferi. Immunization of C3 H/HeN mice with pLD1 elicits robust humoral and cellular immune responses that confer complete protection against a live Borreliella burgdorferi bacterial challenge. The data show that pDL1 DNA vaccine elicits robust humoral and cellular immune responses in mice against the OspA antigen that confers protection against Borreliella burgdorferi spirochete tissue colonization following a live bacterial challenge. We show that a synthetically engineered vaccine pLD1 elicits robust and durable anti-OspA IgG levels, and confers protection against Borreliella burgdorferi infection in a C3 H/HeN mouse needle challenge model. These data indicate the immune response elicited by pLD1 can generate antibodies which can bind to the same OspA epitopes as mAbs which have been shown to prevent transmission of Lyme disease spirochetes. abstract: Lyme disease is the most common vector-borne disease in North America. The etiological agent is the spirochete Borreliella burgdorferi, transmitted to mammalian hosts by the Ixodes tick. In recent years there has been an increase in the number of cases of Lyme disease. Currently, there is no vaccine on the market for human use. We describe the development of a novel synthetically engineered DNA vaccine, pLD1 targeting the outer-surface protein A (OspA) of Borreliella burgdorferi. Immunization of C3 H/HeN mice with pLD1 elicits robust humoral and cellular immune responses that confer complete protection against a live Borreliella burgdorferi bacterial challenge. We also assessed intradermal (ID) delivery of pLD1 in Hartley guinea pigs, demonstrating the induction of robust and durable humoral immunity that lasts at least 1 year. We provide evidence of the potency of pLD1 by showing that antibodies targeting the OspA epitopes which have been associated with protection are prominently raised in the immunized guinea pigs. The described study provides the basis for the advancement of pDL1 as a potential vaccine for Lyme disease control. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553707/ doi: 10.1080/21645515.2020.1789408 id: cord-002706-m3y35ozx author: Guo, Fang title: HBV core protein allosteric modulators differentially alter cccDNA biosynthesis from de novo infection and intracellular amplification pathways date: 2017-09-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Hepatitis B virus (HBV) core protein assembles viral pre-genomic (pg) RNA and DNA polymerase into nucleocapsids for reverse transcriptional DNA replication to take place. Several chemotypes of small molecules, including heteroaryldihydropyrimidines (HAPs) and sulfamoylbenzamides (SBAs), have been discovered to allosterically modulate core protein structure and consequentially alter the kinetics and pathway of core protein assembly, resulting in formation of irregularly-shaped core protein aggregates or “empty” capsids devoid of pre-genomic RNA and viral DNA polymerase. Interestingly, in addition to inhibiting nucleocapsid assembly and subsequent viral genome replication, we have now demonstrated that HAPs and SBAs differentially modulate the biosynthesis of covalently closed circular (ccc) DNA from de novo infection and intracellular amplification pathways by inducing disassembly of nucleocapsids derived from virions as well as double-stranded DNA-containing progeny nucleocapsids in the cytoplasm. Specifically, the mistimed cuing of nucleocapsid uncoating prevents cccDNA formation during de novo infection of hepatocytes, while transiently accelerating cccDNA synthesis from cytoplasmic progeny nucleocapsids. Our studies indicate that elongation of positive-stranded DNA induces structural changes of nucleocapsids, which confers ability of mature nucleocapsids to bind CpAMs and triggers its disassembly. Understanding the molecular mechanism underlying the dual effects of the core protein allosteric modulators on nucleocapsid assembly and disassembly will facilitate the discovery of novel core protein-targeting antiviral agents that can more efficiently suppress cccDNA synthesis and cure chronic hepatitis B. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629035/ doi: 10.1371/journal.ppat.1006658 id: cord-280691-nzc8ir0n author: Guo, Sun-Wei title: China’s “Gene War of the Century” and Its Aftermath: The Contest Goes On date: 2013-08-30 words: 12487.0 sentences: 563.0 pages: flesch: 52.0 cache: ./cache/cord-280691-nzc8ir0n.txt txt: ./txt/cord-280691-nzc8ir0n.txt summary: Around 1997, and amid the talks of Hong Kong''s upcoming return to China and later the Asian financial crisis, a recurring topic in the Chinese media was the so-called ''''gene war of the century'''': the lopsided condemnation of foreign scientists coming purportedly to pilfer China''s vast genetic resources for a profit. Despite his repeated proclamation as a staunch and unwavering patriot loyal to his beloved motherland and dedicated to the advancement of China''s science and technology, he nonetheless later became embroiled in an avalanche of controversies surrounding the ''''gene war.'''' He effectively became a lightning rod for all the controversy on genetic resources, intellectual rights, informed consent, and the protection of human research subjects. (2) Chinese scientists should immediately grasp the opportunity to find disease genes and patent them; (3) We should educate the people, and raise the awareness and importance of protection of our genetic resources; (4) We welcome all international collaborations based on fairness and mutual benefits; (5) Through various avenues, the Chinese scientists should be vocal about certain views deemed to be harmful to China''s genetic research (Xiao et al. abstract: Following the successful cloning of genes for mostly rare genetic diseases in the early 1990s, there was a nearly universal enthusiasm that similar approaches could be employed to hunt down genes predisposing people to complex diseases. Around 1996, several well-funded international gene-hunting teams, enticed by the low cost of collecting biological samples and China’s enormous population, and ushered in by some well-connected Chinese intermediaries, came to China to hunt down disease susceptibility genes. This alarmed and, in some cases, enraged many poorly funded Chinese scientists, who perceived them as formidable competitors. Some depicted foreign gene-hunters as greedy pilferers of the vast Chinese genetic gold mine, comparing it to the plundering of national treasures from China by invaders in the past, and called upon the government and their fellow countrymen to rise up and protect China’s genetic gold mine. Media uproar ensued, proclaiming the imminent “gene war of the century.” This article chronicles the key events surrounding this “war” and its aftermath, exposes some inherent complexities in identifying susceptibility genes for complex diseases, highlights some issues obscured or completely overlooked in the passionate and patriotic rhetoric, and debunks some misconceptions embedded in this conflict. In addition, it argues that during the entire course of this “war,” the public’s interest went conspicuously unmentioned. Finally, it articulates several lessons that can be learned from this conflict, and outlines challenges facing human genetics researchers. url: https://www.ncbi.nlm.nih.gov/pubmed/32214463/ doi: 10.1007/s11024-013-9237-7 id: cord-314415-yr0uxok2 author: Guo, Zijing title: Identification and genomic characterization of a novel CRESS DNA virus from a calf with severe hemorrhagic enteritis in China date: 2018-08-15 words: 3767.0 sentences: 212.0 pages: flesch: 55.0 cache: ./cache/cord-314415-yr0uxok2.txt txt: ./txt/cord-314415-yr0uxok2.txt summary: In this study, a novel circular replication-associated protein (Rep)-encoding single stranded (CRESS) DNA virus was discovered in diarrheic sample of a calf with severe hemorrhagic enteritis. The result showed that Bo-Circo-like virus CH is clustered into a independent branch with seven reported strains of proposed family Kirkoviridae and eight CRESS-DNA virus strains recently submitted to GenBank database; Bo-Circo-like virus CH is more closely related to Po-Circo-like virus and shows significant genetic differences with viruses in the families Circoviridae, Nanoviridae, Geminiviridae Genomoviridae, Bacilladnaviridae and Smacoviridae (Fig. 3) . The sequence alignments included strain Bo-Circo-like virus CH in this study, representative members of the Circoviridae, Geminiviridae, Nanoviridae, Genomoviridae, Bacilladnaviridae and Smacoviridae families, the proposed new genera of krikoviruses, and still unassigned novel CRESS-DNA viruses with the best BLASTp matchs in GenBank database. The sequence alignments included five Bo-Circo-like virus strains detected in this study and seven reported strains of the proposed family Kirkoviridae. abstract: In this study, a novel circular replication-associated protein (Rep)-encoding single stranded (CRESS) DNA virus was discovered in diarrheic sample of a calf with severe hemorrhagic enteritis. The virus, named Bo-Circo-like virus CH, has a circular genome with 3909 nucleotides (nt). Six putative open reading frames (ORFs) were identified, including Rep, capsid (Cap) and four proteins of unknown function. Both the genome size and the number as well as the organization of encoded ORFs, Bo-Circo-like virus CH is most closely related to Po-Circo-like virus 21 detected in pig faeces. A preliminary survey using specific primers for the Rep region showed that 5.3% (4/75) of diarrheic samples were positive for Bo-Circo-like virus, and all 42 healthy samples were negative. In conclusion, our results indicate that Bo-Circo-like virus CH may represent a new virus in bovine. Further investigation is needed to determine the relationship between the virus infection and diarrhea. url: https://doi.org/10.1016/j.virusres.2018.07.015 doi: 10.1016/j.virusres.2018.07.015 id: cord-024149-qnclsjym author: Gupta, Ankit title: Microbes and Environment date: 2016-10-15 words: 11674.0 sentences: 625.0 pages: flesch: 39.0 cache: ./cache/cord-024149-qnclsjym.txt txt: ./txt/cord-024149-qnclsjym.txt summary: Genome sequencing of a free-living heterotroph bacteria found in aerobic soil, e.g., Chthoniobacter flavus, suggests that it is able to metabolize plant polysaccharides but not amino acids except pyruvate. Sphingobacteria are known to be involved in aerobic degradation of plant materials present in soil and complex organic molecules, e.g., starch, proteins, cellulose, and chitin. Other microbes such as green and purple sulfur bacteria participate in carbon cycle by degrading hydrogen sulfide (H 2 S) into compounds having carbon during energy production (see in reaction). In rhizosphere different microbes colonize around growing roots, which may either result in symbiotic, neutralistic, or parasitic interactions depending upon nutritional status of soil, soil environment, plant defense mechanism, and the type of microbial proliferation in the rhizosphere zone. Numerous fungi, bacteria, viruses, and nematodes are pathogenic in nature and caused many plant and animal diseases (Tables 3.4 and 3.5). abstract: Microbes are omnipresent in the biosphere, and their presence invariably affects the environment in which they grow. The effects of microbes on their environment can be beneficial or harmful or inapparent with regard to human measure or observation. The most significant effect of the microbes on earth is their ability to recycle the primary elements that make up all living systems, especially carbon, oxygen, and nitrogen (N). Primary production involves photosynthetic organisms which take up CO(2) from the atmosphere and convert it to organic (cellular) material. The process is also called CO(2) fixation, and it accounts for a very large portion of organic carbon available for synthesis of cell material. Decomposition or biodegradation results in the breakdown of complex organic materials to other forms of carbon that can be used by other organisms. There is no naturally occurring organic compound that cannot be degraded by some microbe, although some synthetic compounds such as Teflon, plastics, insecticides, and pesticides are broken down very slowly or not at all. Through the microbial metabolic processes of fermentation and respiration, organic molecules are eventually broken down to CO(2) which is returned to the atmosphere for continuous process of primary production. Biological nitrogen fixation is a process found only in some bacteria which remove N(2) from the atmosphere and converts it to ammonia (NH(3)), for use by the plants and animals. Nitrogen fixation also results in replenishment of soil nitrogen removed by agricultural processes. Thus along with all these benefits, microbes greatly contribute in maintaining sustainability of environment. This chapter mainly focuses on beneficial and harmful impacts of microbes on environment and their role to maintain quality, health, and sustainability of environment. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189961/ doi: 10.1007/978-981-10-1866-4_3 id: cord-301293-jqy7lcbk author: Gupta, Vandana title: SARS coronavirus nucleocapsid immunodominant T-cell epitope cluster is common to both exogenous recombinant and endogenous DNA-encoded immunogens date: 2006-03-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Correspondence between the T-cell epitope responses of vaccine immunogens and those of pathogen antigens is critical to vaccine efficacy. In the present study, we analyzed the spectrum of immune responses of mice to three different forms of the SARS coronavirus nucleocapsid (N): (1) exogenous recombinant protein (N-GST) with Freund's adjuvant; (2) DNA encoding unmodified N as an endogenous cytoplasmic protein (pN); and (3) DNA encoding N as a LAMP-1 chimera targeted to the lysosomal MHC II compartment (p-LAMP-N). Lysosomal trafficking of the LAMP/N chimera in transfected cells was documented by both confocal and immunoelectron microscopy. The responses of the immunized mice differed markedly. The strongest T-cell IFN-γ and CTL responses were to the LAMP-N chimera followed by the pN immunogen. In contrast, N-GST elicited strong T cell IL-4 but minimal IFN-γ responses and a much greater antibody response. Despite these differences, however, the immunodominant T-cell ELISpot responses to each of the three immunogens were elicited by the same N peptides, with the greatest responses being generated by a cluster of five overlapping peptides, N(76–114), each of which contained nonameric H2(d) binding domains with high binding scores for both class I and, except for N(76–93), class II alleles. These results demonstrate that processing and presentation of N, whether exogenously or endogenously derived, resulted in common immunodominant epitopes, supporting the usefulness of modified antigen delivery and trafficking forms and, in particular, LAMP chimeras as vaccine candidates. Nevertheless, the profiles of T-cell responses were distinctly different. The pronounced Th-2 and humoral response to N protein plus adjuvant are in contrast to the balanced IFN-γ and IL-4 responses and strong memory CTL responses to the LAMP-N chimera. url: https://www.sciencedirect.com/science/article/pii/S004268220500783X doi: 10.1016/j.virol.2005.11.042 id: cord-015683-a9a82of4 author: Gupta, Varsha title: Molecular Diagnostics date: 2016-10-23 words: 4774.0 sentences: 294.0 pages: flesch: 52.0 cache: ./cache/cord-015683-a9a82of4.txt txt: ./txt/cord-015683-a9a82of4.txt summary: Molecular diagnostics such as Western blot , ELISA , PCR , DNA, and protein microarrays are 7 revolutionizing the clinical practice of infectious diseases. Molecular diagnostics such as Western blot , ELISA , PCR , DNA, and protein microarrays are 7 revolutionizing the clinical practice of infectious diseases. Binding of another antigen-specifi c antibody linked with enzyme results in color formation upon addition of the substrate 9.2 Diagnosis of Bacterial, Viral, and Parasitic Diseases peptide may react in some assays but not in others as some regions of a peptide may be more immunogenic than others. Because of the specifi city, homogeneity, and unlimited availability of the MAbs, vast amount of work has been carried out on the production/development The immuno-diagnoses of protozoan and parasitic diseases have signifi cantly been improved by MAb technology because the tests involving MAb as diagnostic reagents overcome the limitations of polyclonal antibodies. The sensitivity and specifi city of a PCR assay is dependent on target genes, primer sequences, PCR techniques, DNA extraction procedures, and PCR product detection methods. abstract: Effective and early management of diseases requires record of the history, behavioral parameters, and travel information. These are helpful for the diagnosis, prevention, and control of the disease. There have been several advancements in the methods for diagnosing infectious diseases. The wide spectrum of tests such as biochemical evaluation, microbiological tools, immunological and molecular biology techniques, etc., is available. Each type of diagnostic technique is strong and reliable in its own sense but poses certain limitations. These limitations may be complemented by using a combination of tests. Older techniques such as microscopy and culturing of organisms from clinical specimens are error-free but are very labor intensive and extremely time consuming. There is a need to develop rapid and sensitive tests that can be used in both high- and low-resource settings. Molecular diagnostics such as Western blot, ELISA, PCR, DNA, and protein microarrays are revolutionizing the clinical practice of infectious diseases. Their effects are significant in acute-care settings where timely and accurate diagnostic tools are critical for patient treatment decisions and outcomes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115026/ doi: 10.1007/978-981-10-0875-7_9 id: cord-288390-p1q3v1ie author: Habjan, Matthias title: Cytoplasmic sensing of viral nucleic acids date: 2015-02-07 words: 4040.0 sentences: 252.0 pages: flesch: 48.0 cache: ./cache/cord-288390-p1q3v1ie.txt txt: ./txt/cord-288390-p1q3v1ie.txt summary: These sensors induce expression of cytokines, affect cellular functions required for virus replication and directly target viral nucleic acids through degradation or sequestration. These sensors induce expression of cytokines, affect cellular functions required for virus replication and directly target viral nucleic acids through degradation or sequestration. In this review we concentrate on intracellular nucleic acid sensors and effector proteins that evolved to mediate specialised tasks including, firstly, expression of cytokines such as type I interferons (IFN-a/b); secondly, modulation of cellular machineries required for virus replication and thirdly, direct inhibition of virus growth ( Figure 1 ). Among the best characterised cytoplasmic proteins involved in virus sensing are RIG-I-like receptors (RLRs), a family of DExD/H-box helicases which specifically identify viral RNAs and have the ability to stimulate expression of IFN-a/b and other cytokines (Figure 3 ) [4, 17] . Virus infection activates a restricted set of sensor and effector proteins that modulate cellular pathways and directly target viral nucleic acid, thereby shaping the innate immune response. abstract: Viruses are the most abundant pathogens on earth. A fine-tuned framework of intervening pathways is in place in mammalian cells to orchestrate the cellular defence against these pathogens. Key for this system is sensor proteins that recognise specific features associated with nucleic acids of incoming viruses. Here we review the current knowledge on cytoplasmic sensors for viral nucleic acids. These sensors induce expression of cytokines, affect cellular functions required for virus replication and directly target viral nucleic acids through degradation or sequestration. Their ability to respond to a given nucleic acid is based on both the differential specificity of the individual proteins and the downstream signalling or adaptor proteins. The cooperation of these multiple proteins and pathways plays a key role in inducing successful immunity against virus infections. url: https://api.elsevier.com/content/article/pii/S1879625715000140 doi: 10.1016/j.coviro.2015.01.012 id: cord-279267-iyobsuvz author: Hacker, David L. title: Polyethyleneimine-based transient gene expression processes for suspension-adapted HEK-293E and CHO-DG44 cells date: 2013-11-30 words: 7064.0 sentences: 364.0 pages: flesch: 49.0 cache: ./cache/cord-279267-iyobsuvz.txt txt: ./txt/cord-279267-iyobsuvz.txt summary: Abstract Transient gene expression (TGE) from mammalian cells is an increasingly important tool for the rapid production of recombinant proteins for research applications in biochemistry, structural biology, and biomedicine. Here we review methods for the transfection of human embryo kidney (HEK-293) and Chinese hamster ovary (CHO) cells in suspension culture using the cationic polymer polyethylenimine (PEI) for gene delivery. Currently, the two major approaches to rapid protein production are non-viral transient gene expression (TGE) 1 using mammalian cells [7] [8] [9] [10] [11] and infection of insect cells with a baculovirus expression vector [12, 13] . These cells were used as the host for the TGE method described here because they are efficiently transfected, grow to a high density in suspension culture, and are widely used in the biopharmaceutical industry to generate stable cell lines for the production of therapeutic proteins [1] . abstract: Abstract Transient gene expression (TGE) from mammalian cells is an increasingly important tool for the rapid production of recombinant proteins for research applications in biochemistry, structural biology, and biomedicine. Here we review methods for the transfection of human embryo kidney (HEK-293) and Chinese hamster ovary (CHO) cells in suspension culture using the cationic polymer polyethylenimine (PEI) for gene delivery. url: https://api.elsevier.com/content/article/pii/S1046592813001721 doi: 10.1016/j.pep.2013.09.001 id: cord-343029-85ga6r7d author: Haghpanah, Abdolreza title: Potential mechanisms of SARS‐CoV‐2 action on male gonadal function and fertility: Current status and future prospects date: 2020-10-27 words: 4375.0 sentences: 218.0 pages: flesch: 43.0 cache: ./cache/cord-343029-85ga6r7d.txt txt: ./txt/cord-343029-85ga6r7d.txt summary: The aim of this review was to provide new insights into different possible mechanisms of involvement of male gonads with SARS‐CoV‐2 including investigating the ACE2 axis in testis, hormonal alterations in patients with COVID‐19, possible formation of anti‐sperm antibodies (ASA) and subsequently immunological infertility as a complication of SARS‐CoV‐2 infection. Considering the fact that the testis is highly enriched in ACE2 receptors and its vulnerability to SARS-CoV-2 invasion, detectable changes in semen analysis, alteration in sex hormones balance and, most importantly, anti-sperm antibodies (ASA) formation and sperm DNA fragmentation are considered to play a major role in male infertility. Search phrases used for different databases strategy included the following: "severe acute respiratory syndrome coronavirus 2", "2019 nCoV", "SARS-CoV-2", "coronavirus", "COVID-19", "reproductive system", "fertility", "infertility", "germ cells", "gamete", "spermatogonia", "spermatogenesis" "spermatozoa", "spermatozoan", "testis", "Sertoli cells", "Leydig cells", "Androgen", "steroidogenesis", "spermiogenesis", "spermiation", "development", "fertilization", "gonadal function", "sex hormones", "angiotensin-converting enzyme 2 receptor", "ACE2", "anti-sperm antibodies", "ASA", "sperm DNA fragmentation index", "DFI", and "semen analysis". abstract: The novel coronavirus was recognised in December 2019 and caught humanity off guard. The virus employs the angiotensin‐converting enzyme 2 (ACE2) receptor for entry into human cells. ACE2 is expressed on different organs, which is raising concern as to whether these organs can be infected by the virus or not. The testis appears to be an organ enriched with levels of ACE2, while the possible mechanisms of involvement of the male reproductive system by SARS‐CoV‐2 are not fully elucidated. The major focus of the present studies is on the short‐term complications of the coronavirus and gains importance on studying the long‐term effects, including the possible effects of the virus on the male reproductive system. The aim of this review was to provide new insights into different possible mechanisms of involvement of male gonads with SARS‐CoV‐2 including investigating the ACE2 axis in testis, hormonal alterations in patients with COVID‐19, possible formation of anti‐sperm antibodies (ASA) and subsequently immunological infertility as a complication of SARS‐CoV‐2 infection. Finally, we suggest measuring the sperm DNA fragmentation index (DFI) as a determiner of male fertility impairment in patients with COVID‐19 along with other options such as sex‐related hormones and semen analysis. Invasion of SARS‐CoV‐2 to the spermatogonia, Leydig cells and Sertoli cells can lead to sex hormonal alteration and impaired gonadal function. Once infected, changes in ACE2 signalling pathways followed by oxidative stress and inflammation could cause spermatogenesis failure, abnormal sperm motility, DNA fragmentation and male infertility. url: https://www.ncbi.nlm.nih.gov/pubmed/33108833/ doi: 10.1111/and.13883 id: cord-011030-o4jn5883 author: Hakki, Morgan title: Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy date: 2020-01-24 words: 7454.0 sentences: 384.0 pages: flesch: 39.0 cache: ./cache/cord-011030-o4jn5883.txt txt: ./txt/cord-011030-o4jn5883.txt summary: A subset of patients were categorized as CMV high-risk, including HLA-A, B, or DR mismatch related donor, HLA-A, B, C, and DRB1 mismatch unrelated Excludes overlapping toxicities with agents commonly used after HCT 3 Approved by the US FDA (year of approval) for prevention and/or treatment 4 ND, not determined donor, haploidentical donor, cord blood transplant, ex vivo T cell-depleted graft, or graft-versus-host disease (GVHD) of grade 2 or greater requiring ≥ 1 mg/kg/day prednisone (or equivalent). A subsequent phase 3 study evaluated maribavir at 100 mg twice daily compared with placebo for the prevention of CMV infection and disease in allogeneic HCT recipients [64] . Maribavir for refractory or resistant cytomegalovirus infections in hematopoietic-cell or solid-organ transplant recipients: a randomized, dose-ranging, double-blind, phase 2 study Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem-cell transplant recipients: a multicenter, randomized, double-blind, placebo-controlled, doseranging study abstract: PURPOSE OF REVIEW: CMV DNA polymerase inhibitors such as ganciclovir and foscarnet have dramatically reduced the burden of CMV infection in the HCT recipient. However, their use is often limited by toxicities and resistance. Agents with novel mechanisms and favorable toxicity profiles are critically needed. We review recent developments in CMV antivirals and immune-based approaches to mitigating CMV infection. RECENT FINDINGS: Letermovir, an inhibitor of the CMV terminase complex, was approved in 2017 for primary CMV prophylaxis in adult seropositive allogeneic HCT recipients. Maribavir, an inhibitor of the CMV UL97 kinase, is currently in two phase 3 treatment studies. Adoptive immunotherapy using third-party T cells has proven safe and effective in preliminary studies. Vaccine development continues, with several promising candidates currently under study. SUMMARY: No longer limited to DNA polymerase inhibitors, the prevention and treatment of CMV infections in the HCT recipient is a rapidly evolving field which should translate into improvements in CMV-related outcomes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223398/ doi: 10.1007/s11899-020-00557-6 id: cord-292643-n6xp5mlz author: Hall, Richard J. title: Evaluation of rapid and simple techniques for the enrichment of viruses prior to metagenomic virus discovery date: 2013-09-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The discovery of new or divergent viruses using metagenomics and high-throughput sequencing has become more commonplace. The preparation of a sample is known to have an effect on the representation of virus sequences within the metagenomic dataset yet comparatively little attention has been given to this. Physical enrichment techniques are often applied to samples to increase the number of viral sequences and therefore enhance the probability of detection. With the exception of virus ecology studies, there is a paucity of information available to researchers on the type of sample preparation required for a viral metagenomic study that seeks to identify an aetiological virus in an animal or human diagnostic sample. A review of published virus discovery studies revealed the most commonly used enrichment methods, that were usually quick and simple to implement, namely low-speed centrifugation, filtration, nuclease-treatment (or combinations of these) which have been routinely used but often without justification. These were applied to a simple and well-characterised artificial sample composed of bacterial and human cells, as well as DNA (adenovirus) and RNA viruses (influenza A and human enterovirus), being either non-enveloped capsid or enveloped viruses. The effect of the enrichment method was assessed by both quantitative real-time PCR and metagenomic analysis that incorporated an amplification step. Reductions in the absolute quantities of bacteria and human cells were observed for each method as determined by qPCR, but the relative abundance of viral sequences in the metagenomic dataset remained largely unchanged. A 3-step method of centrifugation, filtration and nuclease-treatment showed the greatest increase in the proportion of viral sequences. This study provides a starting point for the selection of a purification method in future virus discovery studies, and highlights the need for more data to validate the effect of enrichment methods on different sample types, amplification, bioinformatics approaches and sequencing platforms. This study also highlights the potential risks that may attend selection of a virus enrichment method without any consideration for the sample type being investigated. url: https://doi.org/10.1016/j.jviromet.2013.08.035 doi: 10.1016/j.jviromet.2013.08.035 id: cord-023698-wvk200j0 author: Hammerschlag, Margaret R. title: Chlamydia pneumoniae date: 2014-10-31 words: 10016.0 sentences: 533.0 pages: flesch: 38.0 cache: ./cache/cord-023698-wvk200j0.txt txt: ./txt/cord-023698-wvk200j0.txt summary: Because the organism has been difficult to grow and because of the lack of a commercially available other diagnostic assay, most original associations with respiratory diseases have been use of serology with the microimmunofluorescence (MIF) test. 38, 39 For an example of the complexity of this issue, consider that two multicenter pneumonia treatment studies in children showed that although 7% to 13% of the patients in the study had positive culture results and 7% to 18% met the serologic criteria with the MIF test for acute infection, they were not the same patients. pneumoniae infection is that the MIF method used to detect serum antibodies is not standardized; recent studies have shown substantial interlaboratory variation in the performance of these tests. Multicenter comparison trial of DNA extraction methods and PCR assays for detection of Chlamydia pneumoniae in endarterectomy specimens Multicenter comparison trial of DNA extraction methods and PCR assays for detection of Chlamydia pneumoniae in endarterectomy specimens abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173483/ doi: 10.1016/b978-1-4557-4801-3.00184-3 id: cord-276101-quis0c6e author: Hamula, Camille L.A. title: Selection and analytical applications of aptamers binding microbial pathogens date: 2011-09-09 words: 4741.0 sentences: 259.0 pages: flesch: 51.0 cache: ./cache/cord-276101-quis0c6e.txt txt: ./txt/cord-276101-quis0c6e.txt summary: This article describes recent advances in the development of aptamers targeting specific pathogens (e.g., live bacteria, whole viral particles, and virally-infected mammalian cells). Specific aptamers against pathogens have been used as affinity reagents to develop sandwich assays, to label and to image cells, to bind with cells for flow-cytometry analysis, and to act as probes for development of whole-cell biosensors. Aptamers can be chemically modified and incorporated into a variety of simple assays for pathogen detection, as well as more complex assay formats, including flow cytometry, cell imaging, and aptamerbased biosensors. Aptamers binding to the cell surface can be used to purify and to identify their respective target molecules post-SELEX. The aptamers were shown to bind different cell-surface targets via a competitive flow-cytometry experiment; using five aptamers combined, rather than individually, was superior at detecting bacteria in pyogenic fluid. abstract: DNA aptamers specifically recognizing microbial cells and viruses have a range of analytical and therapeutic applications. This article describes recent advances in the development of aptamers targeting specific pathogens (e.g., live bacteria, whole viral particles, and virally-infected mammalian cells). Specific aptamers against pathogens have been used as affinity reagents to develop sandwich assays, to label and to image cells, to bind with cells for flow-cytometry analysis, and to act as probes for development of whole-cell biosensors. Future applications of aptamers to pathogens will benefit from recent advances in improved selection and new aptamers containing modified nucleotides, particularly slow off-rate modified aptamers (SOMAmers). url: https://www.sciencedirect.com/science/article/pii/S0165993611002585 doi: 10.1016/j.trac.2011.08.006 id: cord-353389-5dtwje1b author: Han, Guojun title: Absolute and Relative Quantification of Multiplex DNA Assays Based on an Elemental Labeling Strategy date: 2013-01-28 words: 3309.0 sentences: 174.0 pages: flesch: 53.0 cache: ./cache/cord-353389-5dtwje1b.txt txt: ./txt/cord-353389-5dtwje1b.txt summary: [9] Compared with other methods, it contains two inherent advantages: 1) Owing to the benefits of a large number of elements or isotopes (up to 100) potentially used as elemental tags, as well as excellent mass resolution and multi-element detectors of ICP-MS, high-level multiplexed analysis can be successfully obtained without the limitation of spectral overlap; [10] 2) ICP-MS has allowed isotope ratio measurement with good accuracy and precision, thus in combination with isotope dilution analysis (IDA), absolute-quantitative measurement can be carried out as the complementary use of molecular mass spectrometry. As shown in Scheme 1 a, the procedure of labeling sequence-specific oligonucleotides with elemental tags involves two steps: 1) oligonucleotides, 3'' end-functionalized with thiol ( À SH) groups, were specifically derivatized with malemide groups of 1,4,7,10-tetraazacyclododecane-1,4,7tris-aceticacid-10-maleimidoethylacetamide (MMA-DOTA), a compound commonly employed for chemical labeling of proteins or peptides; [17] 2) rare-earth elements (REEs) were chelated with high kinetic and thermodynamic stability (for reaction conditions (pH, mole ratio of MMA-DOTA to DNA, time, and temperature), see the Supporting Information). abstract: Elements and quantification: A nucleic acid assay has been developed, based on an elemental labeling strategy using magnetic microparticles (MMPs), which provides quantification of multiple DNA targets. Rare‐earth elements, indium, and stable isotopes could be labeled with oligonucleotides serving as DNA probes. Quantitative analysis was then carried out using the designed systems (see picture) and elemental mass spectrometry.[Image: see text] url: https://doi.org/10.1002/anie.201206903 doi: 10.1002/anie.201206903 id: cord-001677-p6ikd8ns author: Hansra, Satyender title: Exploration of New Sites in Adenovirus Hexon for Foreign Peptides Insertion date: 2015-05-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Adenoviral vectors are now being explored as vaccine carriers to prevent infectious diseases in humans and animals. There are two strategies aimed at the expression of a vaccine antigen by adenoviral vectors. The first includes an insertion of the foreign gene expression cassette into the E1 region. The second strategy is antigen incorporation into the viral capsid proteins. To extend this methodology, we have searched for new sites at the human adenovirus serotype 5 major capsid protein hexon for a vaccine antigen insertion. To this end, we utilized sites in the hexon hypervariable region (HVR) 7, 8 and 9 to display a 15-mer peptide containing the main neutralizing epitope of porcine reproductive and respiratory syndrome virus. However, we could not rescue the viruses with the insertions of the peptide into HVR 8 and 9, consistent with the viruses being unable to tolerate insertions at these sites. In contrast, the virus with the insertion of the peptide in HVR 7 was viable - growing well in cell culture and the inserted peptide was exposed on the virion surface. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4460227/ doi: 10.2174/1874357901509010001 id: cord-007382-5kb16qb7 author: Hartmann, G. title: Nucleic Acid Immunity date: 2016-12-15 words: 16155.0 sentences: 915.0 pages: flesch: 47.0 cache: ./cache/cord-007382-5kb16qb7.txt txt: ./txt/cord-007382-5kb16qb7.txt summary: With the additions of RNAi and the CRISPR/Cas system, specific nucleases including the restriction-modification (R-M) systems, and antiviral effector proteins partially discovered only recently in the context of rare hereditary inflammatory diseases, the new concept of nucleic acid immunity evolves. While innate nucleic acid immune-sensing receptors elicit antiviral signaling pathways, a number of nucleic acid-detecting effector proteins (viral restriction factors, e.g., PKR, ADAR1, IFIT1) directly detect and restrict nucleic acid function and replication. Another member of the RIG-I-like helicase family of receptors is MDA5 which was found to be responsible for the long sought after type I IFN-inducing activity of cytosolic long double-stranded RNA including poly(I:C) . Extrinsic effects inside the same cell include degradation of the nucleic acid (e.g., RNase L activated by 2 0 -5 0 -OA generated by OAS1 upon binding of long double-stranded RNA). abstract: Organisms throughout biology need to maintain the integrity of their genome. From bacteria to vertebrates, life has established sophisticated mechanisms to detect and eliminate foreign genetic material or to restrict its function and replication. Tremendous progress has been made in the understanding of these mechanisms which keep foreign or unwanted nucleic acids from viruses or phages in check. Mechanisms reach from restriction-modification systems and CRISPR/Cas in bacteria and archaea to RNA interference and immune sensing of nucleic acids, altogether integral parts of a system which is now appreciated as nucleic acid immunity. With inherited receptors and acquired sequence information, nucleic acid immunity comprises innate and adaptive components. Effector functions include diverse nuclease systems, intrinsic activities to directly restrict the function of foreign nucleic acids (e.g., PKR, ADAR1, IFIT1), and extrinsic pathways to alert the immune system and to elicit cytotoxic immune responses. These effects act in concert to restrict viral replication and to eliminate virus-infected cells. The principles of nucleic acid immunity are highly relevant for human disease. Besides its essential contribution to antiviral defense and restriction of endogenous retroelements, dysregulation of nucleic acid immunity can also lead to erroneous detection and response to self nucleic acids then causing sterile inflammation and autoimmunity. Even mechanisms of nucleic acid immunity which are not established in vertebrates are relevant for human disease when they are present in pathogens such as bacteria, parasites, or helminths or in pathogen-transmitting organisms such as insects. This review aims to provide an overview of the diverse mechanisms of nucleic acid immunity which mostly have been looked at separately in the past and to integrate them under the framework nucleic acid immunity as a basic principle of life, the understanding of which has great potential to advance medicine. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112058/ doi: 10.1016/bs.ai.2016.11.001 id: cord-261417-4pf5nsw2 author: Harwig, Alex title: The Battle of RNA Synthesis: Virus versus Host date: 2017-10-21 words: 7864.0 sentences: 443.0 pages: flesch: 53.0 cache: ./cache/cord-261417-4pf5nsw2.txt txt: ./txt/cord-261417-4pf5nsw2.txt summary: Why the virus prefers to use these snRNAs as targets has yet to be experimentally established, but it has been proposed that the selective de-capping of U1 and U2 RNAs in combination with the binding of the viral NS1 protein to U6 snRNA may serve to inhibit host pre-mRNA splicing [66] . The folding of the TAR hairpin is key to the regulation of HIV-1 transcription [94] as it is used as a scaffold to recruit essential transcription factors, including the 86-101 amino acid (aa) viral trans-activator protein (Tat) [83] ( Figure 3C ). Interestingly, the human T-lymphotropic virus type 1 transcriptional activator Tax also utilizes P-TEFb for viral transcription and displaces P-TEFb from 7SK snRNP through binding CycT1 [101, 102] , suggesting that P-TEFb liberation from 7SK snRNP could be a common theme developed by different viruses to support their replication in host cells. abstract: Transcription control is the foundation of gene regulation. Whereas a cell is fully equipped for this task, viruses often depend on the host to supply tools for their transcription program. Over the course of evolution and adaptation, viruses have found diverse ways to optimally exploit cellular host processes such as transcription to their own benefit. Just as cells are increasingly understood to employ nascent RNAs in transcription regulation, recent discoveries are revealing how viruses use nascent RNAs to benefit their own gene expression. In this review, we first outline the two different transcription programs used by viruses, i.e., transcription (DNA-dependent) and RNA-dependent RNA synthesis. Subsequently, we use the distinct stages (initiation, elongation, termination) to describe the latest insights into nascent RNA-mediated regulation in the context of each relevant stage. url: https://www.ncbi.nlm.nih.gov/pubmed/29065472/ doi: 10.3390/v9100309 id: cord-102504-d840uu3e author: Hass, Kenneth N. title: Integrated Micropillar Polydimethylsiloxane Accurate CRISPR Detection (IMPACT) System for Rapid Viral DNA Sensing date: 2020-03-20 words: 4432.0 sentences: 285.0 pages: flesch: 57.0 cache: ./cache/cord-102504-d840uu3e.txt txt: ./txt/cord-102504-d840uu3e.txt summary: This miniaturized and fully packed IMPACT chip demonstrates rapid, sensitive, and simple nucleic acid detection and is an ideal candidate for the next generation molecular diagnostic platform for point-of-care (POC) applications, responding to emerging and deadly pathogen outbreaks. On the solid surface, reporter probes do not require a quencher since they are only measured in the liquid phase after degradation, thus no fluorescent signal will be detected without the target DNA present in the assay. Leveraging the high activity of CRISPR-Cas12a enzyme and the ability of micropillars to bind more reporter probes, we successfully detect double-stranded DNA target without background issues. As shown in Fig. 3 , for streptavidin coated surface, the number of DNA immobilized on the surface does not show significant change with an incubation time between 10 to 60 min as the integrated fluorescence intensity of the retrieved DNA ranges between 50,000 to 60,000 counts. The extended surface provided by high-aspect ratio micropillars significantly increases the reporter probe binding capacity. abstract: A fully Integrated Micropillar Polydimethylsiloxane Accurate CRISPR Detection (IMPACT) system is developed for viral DNA detection. This powerful system is patterned with high-aspect ratio micropillars to enhance reporter probe binding. After surface modification and probe immobilization, CRISPR Cas12a/crRNA complex is injected into the fully enclosed system. With the presence of double-stranded DNA target, the CRISPR enzyme is activated and non-specifically cleaves the ssDNA reporters initially immobilized on the micropillars. This collateral cleavage releases fluorescence dyes into the assay, and the intensity is linearly proportional to the target DNA concentration ranging from 0.1 to 10 nM. Importantly, this system does not rely on traditional dye-quencher labeled probe thus eliminating the fluorescence background presented in the assay. Furthermore, our one-step detection protocol is performed at isothermal conditions (37°C) without using complicated and time-consuming off-chip probe hybridization and denaturation. This miniaturized and fully packed IMPACT chip demonstrates rapid, sensitive, and simple nucleic acid detection and is an ideal candidate for the next generation molecular diagnostic platform for point-of-care (POC) applications, responding to emerging and deadly pathogen outbreaks. url: https://doi.org/10.1101/2020.03.17.994137 doi: 10.1101/2020.03.17.994137 id: cord-262660-t1ndfn2l author: Hass, Kenneth N. title: Integrated Micropillar Polydimethylsiloxane Accurate CRISPR Detection System for Viral DNA Sensing date: 2020-10-13 words: 5219.0 sentences: 317.0 pages: flesch: 54.0 cache: ./cache/cord-262660-t1ndfn2l.txt txt: ./txt/cord-262660-t1ndfn2l.txt summary: This miniaturized and fully packed IMPACT chip demonstrates sensitive and accurate DNA detection within 120 min and paves ways to the next-generation point-of-care diagnostics, responding to emerging and deadly pathogen outbreaks. On the solid surface, reporter probes do not require a quencher since they are only measured in the liquid phase after degradation; thus, the fluorescent signal will be largely reduced without the target DNA present in the assay. 19, 20 Here, we present a fully enclosed Integrated Micropillar Polydimethylsiloxane Accurate CRISPR deTection (IMPACT) system for nucleic acid target detection on the solid-surface of polydimethylsiloxane (PDMS) utilizing CRISPR-Cas12a. Leveraging the high activity of CRISPR-Cas12a enzyme and the ability of micropillars to bind more reporter probes, we successfully detected a double-stranded DNA target without background issues. The extended surface provided by high-aspect ratio micropillars significantly increases the reporter probe binding capacity. abstract: [Image: see text] A fully Integrated Micropillar Polydimethylsiloxane Accurate CRISPR deTection (IMPACT) system is developed for viral DNA detection. This powerful system is patterned with high-aspect-ratio micropillars to enhance reporter probe binding. After surface modification and probe immobilization, the CRISPR-Cas12a/crRNA complex is injected into the fully enclosed microchannel. With the presence of a double-stranded DNA target, the CRISPR enzyme is activated and denatures the single-stranded DNA reporters from the micropillars. This collateral cleavage releases fluorescence reporters into the assay, and the intensity is linearly proportional to the target DNA concentration ranging from 0.1 to 10 nM. Importantly, this system does not rely on the traditional dye-quencher-labeled probe, thus reducing the fluorescence background presented in the assay. Furthermore, our one-step detection protocol is performed on-chip at isothermal conditions (37 °C) without using complicated and time-consuming off-chip probe hybridization and denaturation. This miniaturized and fully packed IMPACT chip demonstrates sensitive and accurate DNA detection within 120 min and paves ways to the next-generation point-of-care diagnostics, responding to emerging and deadly pathogen outbreaks. url: https://doi.org/10.1021/acsomega.0c03917 doi: 10.1021/acsomega.0c03917 id: cord-016041-427mbaqc author: Hengge, Ulrich R. title: Gentherapie date: 2008 words: 7287.0 sentences: 824.0 pages: flesch: 46.0 cache: ./cache/cord-016041-427mbaqc.txt txt: ./txt/cord-016041-427mbaqc.txt summary: Die somatische Gentherapie befasst sich mit der Behandlung von somatischen (Körper-)Zellen (>Tab. 4.1.1), wobei das therapeutische Gen ein im Organismus benötigtes Protein kodiert. Die somatische Gentherapie befasst sich mit der Behandlung von somatischen (Körper-)Zellen (>Tab. 4.1.1), wobei das therapeutische Gen ein im Organismus benötigtes Protein kodiert. Neue Verfahren des Vektor-Targetings sowie interessante Techniken wie Elektroporation und hydrodynamische Injektion konnten die Transgenexpression in vivo verbessern, indem eine verbesserte Verteilung der Plasmid-DNA im Zielorgan erreicht wurde (Wolff u. Bei einer weiteren Zytokin-Gentherapie wurde Melanompatienten intratumoral ein Canarypox-Virus-Vektor injiziert, der das IL-12-Gen exprimierte, und zur T-Zell-Akkumulation in injizierten Melanomen führte (Triozzi et al. Es ist jedoch schwierig, einen Zusammenhang zwischen Tumorregression und der Existenz einer durch die Vakzinierung induzierten zytotoxischen T-Zell-Antwort unzweifelhaft festzustellen, da nicht alle Patienten mit zellulären Immunantworten auf den Tumor eine Regression desselben zeigen. Ein Paradebeispiel hierfür ist das p53-Protein, das erst nach einem aufgetretenen DNA-Schaden den Zellzyklus blockiert und die Zellen der Apoptose unterwirft (Roth 2006) . abstract: Die Gentherapie ist eine junge Wissenschaft, die Nukleinsäuren zur Therapie einsetzt (Hengge u. Bardenheuer 2004). Die somatische Gentherapie befasst sich mit der Behandlung von somatischen (Körper-)Zellen (⧁ Tab. 4.1.1), wobei das therapeutische Gen ein im Organismus benötigtes Protein kodiert. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120194/ doi: 10.1007/978-3-540-69414-4_16 id: cord-315541-tirod4t6 author: Henriques, Ana Margarida title: Development and validation of a real-time PCR for the detection and quantification of porcine circovirus type 2 date: 2018-07-17 words: 3552.0 sentences: 167.0 pages: flesch: 51.0 cache: ./cache/cord-315541-tirod4t6.txt txt: ./txt/cord-315541-tirod4t6.txt summary: This paper reports the development and validation of a real-time PCR targeted to ORF1 and based on a TaqMan probe for the detection of porcine circovirus type 2 DNA in swine samples. The real-time PCR method described in this paper was performed with DNA from this strain, and an amplification curve with Ct 19.9 was obtained, confirming that such mutation in the probe annealing sequence had no effect in the reaction. The test performed with a plasmid containing the fragment to be amplified in the qPCR, with known The DNA samples used for the determination of the intra-and inter-assay variabilities for medium Ct values was not the same due to the lack of available DNA Fig. 2 Amplification curves obtained in the real-time PCR reaction performed for the determination of the limit of detection. abstract: Porcine circovirus type 2 (PCV2) is a spherical and non-enveloped virus belonging to the genus Circovirus of the Circoviridae family with a single stranded circular DNA genome. This virus, already detected worldwide, has been associated to several diseases and was implicated as the etiological agent of a disease named postweaning multisystemic wasting syndrome. Several methods have been described for the detection of PCV2, being real-time PCR the most simple and reliable. As far as we know, all the real-time PCR systems described until now are based on ORF2 gene, that exhibit the highest variability. This paper reports the development and validation of a real-time PCR targeted to ORF1 and based on a TaqMan probe for the detection of porcine circovirus type 2 DNA in swine samples. Due to the lack of PCV1 samples, the ability of the test to discriminate between PCV1 and PCV2 positive samples was evaluated in silico. Estimations of 100% specificity and 100% sensitivity were obtained based on the qPCR results with panel of 81 swine samples (known PCV2-positive (n = 50); known PCV2-negative (n = 17); samples positive to other common swine viral pathogens (n = 13) and one sample from a BFDV-positive parrot (n = 1)). Intra- and inter-assay coefficients of variation obtained with three positive samples of different viral charges in five replicates or in five independent assays were below the acceptance threshold. The limit of detection determined with a recombinant plasmid containing the amplicon, led to conclude that this assay can detect at least three plasmid copies. url: https://www.ncbi.nlm.nih.gov/pubmed/30159371/ doi: 10.1007/s13337-018-0476-y id: cord-274128-kgtr77e7 author: Hochstetter, Axel title: Lab-on-a-Chip Technologies for the Single Cell Level: Separation, Analysis, and Diagnostics date: 2020-04-29 words: 14656.0 sentences: 748.0 pages: flesch: 49.0 cache: ./cache/cord-274128-kgtr77e7.txt txt: ./txt/cord-274128-kgtr77e7.txt summary: Given the vast adaptability of microfluidics to any kind of single or multi-cellular assay [63] , the ability to combine it with various light microscopy techniques [64] , image processing [65] , optical or acoustic traps [53] , generation of chemical gradients [66] , and even cell culture [4, [67] [68] [69] [70] [71] [72] [73] [74] [75] [76] [77] [78] [79] [80] [81] [82] [83] , any cellular or subcellular target seems to be possible for future on-chip diagnostics. If the sample is in the continuous phase, we can separate the target cells either using deterministic lateral displacement (DLD), ratchets, dean-flow, di-electrophoresis, surface acoustic waves (SAW), optical and acoustic tweezers or by using optical density/refractive index. abstract: In the last three decades, microfluidics and its applications have been on an exponential rise, including approaches to isolate rare cells and diagnose diseases on the single-cell level. The techniques mentioned herein have already had significant impacts in our lives, from in-the-field diagnosis of disease and parasitic infections, through home fertility tests, to uncovering the interactions between SARS-CoV-2 and their host cells. This review gives an overview of the field in general and the most notable developments of the last five years, in three parts: 1. What can we detect? 2. Which detection technologies are used in which setting? 3. How do these techniques work? Finally, this review discusses potentials, shortfalls, and an outlook on future developments, especially in respect to the funding landscape and the field-application of these chips. url: https://www.ncbi.nlm.nih.gov/pubmed/32365567/ doi: 10.3390/mi11050468 id: cord-007724-2nwrhk1d author: Hofmann, Martin A. title: Sequencing DNA Amplified Directly from a Bacterial Colony date: 1993 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A few hundred bacterial cells obtained by touching a bacterial colony with a sterile toothpick can be used directly in a polymerase chain reaction (PCR) amplification procedure to identify and orient a plasmid insert (1,2). By combining this procedure with one in which asymmetrically amplified DNA is used for sequencing (ref. 3 and Fig. 3), we have demonstrated that DNA amplified from a bacterial colony can be sequenced directly by the dideoxy chain-termination method to yield results as good as those obtained when purified template DNA is used for amplification (ref.4 and Fig. 2). By end-labeling the primer that is used in limiting amounts during the amplification step and using it for sequencing, an entire insert of 300 nucleotides or less can be sequenced in one step. Inserts of larger size can be sequenced by using labeled primers that bind within the amplified single-stranded DNA sequence. The procedure is rapid and enables one to obtain sequences from as many as 20 clones in a single day. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121285/ doi: 10.1385/0-89603-244-2:205 id: cord-017563-jkhvcjcb author: Holland, Tod D. title: Modeling Brain Tumors Using Avian Retroviral Gene Transfer date: 2008-12-12 words: 4703.0 sentences: 213.0 pages: flesch: 51.0 cache: ./cache/cord-017563-jkhvcjcb.txt txt: ./txt/cord-017563-jkhvcjcb.txt summary: Mice bearing RCAS/tv-a-induced brain tumors are currently being used for preclinical trials to understand the biology of therapeutic response in the various cell types that make up gliomas and medulloblastomas. These oncogenes appeared to be stolen from the host genome and then expressed either in the wrong cell type or in an unregulated manner by the virus leading to the formation of cancer (Kurth, 1983) . Gliomas probably form from stem cells or progenitors and are driven by the signaling pathways that drive normal development in the CNS such as PDGF and downstream effectors such as RAS and Akt. The most potent oncogene in the formation of gliomas is the PDGFB ligand . Then SHH gene transfer with RCAS vectors into nestin-expressing cells of the rhombic lip created medulloblastomas in a minority of mice (Rao et al., 2004) . abstract: RCAS/tv-a is a system for postnatal cell-type-specific gene transfer. It is used for the modeling of gliomas and medulloblastomas. This system provides a combination of lineage tracing from the cell origin with oncogenesis induced by mis-expression of specific genes. The genes that are most potent at inducing tumors are those that encode components of signal transduction and undifferentiated cells are most capable of serving as the cell of origin. The system effectively generates tumors with the histologic characteristics of human disease. Mice bearing RCAS/tv-a-induced brain tumors are currently being used for preclinical trials to understand the biology of therapeutic response in the various cell types that make up gliomas and medulloblastomas. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122153/ doi: 10.1007/978-1-60327-553-8_2 id: cord-326228-9x1233q6 author: Holley, Caroline L title: The rOX‐stars of inflammation: links between the inflammasome and mitochondrial meltdown date: 2020-02-10 words: 6351.0 sentences: 434.0 pages: flesch: 32.0 cache: ./cache/cord-326228-9x1233q6.txt txt: ./txt/cord-326228-9x1233q6.txt summary: Nod-like receptor protein 3 (NLRP3) is a cytosolic PRR activated by a wide range of PAMPs (bacterial toxins, fungal and viral components) and DAMPs (e.g. extracellular ATP, lysosomal-disrupting crystals), including those of mitochondrial origin. The mechanisms by which mitochondria influence PRR activity and drive inflammatory responses are important research foci for understanding protective innate immune functions during host defence against infection, as well as innate immune pathology in disease. 55 It is possible that LLO-driven MAM disruption and mitochondrial fission removes a key site of inflammasome assembly to dampen K + effluxdependent NLRP3 signalling and thereby allows the bacterium to partially evade immune recognition. NLRP3 activation in mouse macrophages can be associated with loss of mitochondrial membrane potential or defective mitophagy, leading to mitoROS production and mtDNA release from mitochondria to the cytosol. cGAS/STING signalling may also be a downstream consequence of NLRP3 activation; for example, IL-1R signalling in the human THP-1 myeloid cell line drives loss of mitochondrial membrane potential and recognition of mtDNA by cGAS. abstract: The nod‐like receptor protein 3 (NLRP3) inflammasome drives inflammation in response to mitochondrial dysfunction. As metabolic powerhouses with prokaryotic ancestry, mitochondria are a cache for danger‐associated molecular patterns and pathogen‐associated molecular pattern‐like molecules that elicit potent innate immune responses. Persistent mitochondrial damage caused by infection, or genetic or environmental factors, can lead to inappropriate or sustained inflammasome signalling. Here, we review the features of mitochondria that drive inflammatory signalling, with a particular focus on mitochondrial activation of the NLRP3 inflammasome. Given that mitochondrial network dynamics, metabolic activity and redox state are all intricately linked to each other and to NLRP3 inflammasome activity, we highlight the importance of a holistic approach to investigations of NLRP3 activation by dysfunctional mitochondria. url: https://doi.org/10.1002/cti2.1109 doi: 10.1002/cti2.1109 id: cord-269426-82g5eiyg author: Holman, David H. title: Viral Vectors date: 2009-01-30 words: 8734.0 sentences: 420.0 pages: flesch: 40.0 cache: ./cache/cord-269426-82g5eiyg.txt txt: ./txt/cord-269426-82g5eiyg.txt summary: Abstract Traditional vaccine development platforms such as live-attenuated virus, killed virus, or recombinant subunit-based vaccines are often effective in eliciting long-term immunity to a number of infectious human pathogens. Finally, it is suggested that vaccination by alternate routes of administration (such as oral or intranasal) rather than injection can overcome pre-existing vector immunity ( Appaiahgari et al., 2006 ; Xiang et al., 2003 ) , which is supported by data from a human clinical trial ( Van Kampen et al., 2005 Lusky et al., 1998 ; Moorhead et al., 1999 ) or the E4 region ( Dedieu et al., 1997 ; Gao et al., 1996 ) of the Ad genome, which reduced or eliminated the expression of E2 or E4 proteins. High-level primary CD8( ϩ ) T-cell response to human immunodeficiency virus type 1 gag and env generated by vaccination with recombinant vesicular stomatitis viruses abstract: Abstract Traditional vaccine development platforms such as live-attenuated virus, killed virus, or recombinant subunit-based vaccines are often effective in eliciting long-term immunity to a number of infectious human pathogens. However, for many human pathogens, vaccine platforms such as these are unsuitable for human use due to safety concerns, poor efficacy, or simple impracticality. As a result, much work has focused on the use of recombinant virus vectors as a means for vaccination against human pathogens. Viral vectors can express foreign proteins at high levels in host cells, resulting in strong, long-lasting immune responses against the target proteins. This chapter describes the use of virus vectors in the context of vaccination against human pathogens. Various vector platforms are discussed, compared, and contrasted. url: https://api.elsevier.com/content/article/pii/B978012369408900007X doi: 10.1016/b978-0-12-369408-9.00007-x id: cord-346853-0c1qdjb5 author: Holmes, E. C. title: The Evolutionary Genetics of Viral Emergence date: 2007 words: 6123.0 sentences: 261.0 pages: flesch: 45.0 cache: ./cache/cord-346853-0c1qdjb5.txt txt: ./txt/cord-346853-0c1qdjb5.txt summary: Despite the wealth of data describing the ecological factors that underpin viral emergence, little is known about the evolutionary processes that allow viruses to jump species barriers and establish productive infections in new hosts. We also emphasize the current lack of convincing data as to whether viral emergence requires adaptation to the new host species during the early stages of infection, or whether it is largely a chance process involving the transmission of a viral strain with the necessary genetic characteristics. For example, one model of viral emergence posits that adaptation to a new host species during the early period of an epidemic is of fundamental importance, because this raises the basic reproductive rate of the virus, R 0 , to greater than 1, so that sustained transmission networks can be established (Anita et al. abstract: Despite the wealth of data describing the ecological factors that underpin viral emergence, little is known about the evolutionary processes that allow viruses to jump species barriers and establish productive infections in new hosts. Understanding the evolutionary basis to virus emergence is therefore a key research goal and many of the debates in this area can be considered within the rigorous theoretical framework established by evolutionary genetics. In particular, the respective roles played by natural selection and genetic drift in shaping genetic diversity are also of fundamental importance for understanding the nature of viral emergence. Herein, we discuss whether there are evolutionary rules to viral emergence, and especially whether certain types of virus, or those that infect a particular type of host species, are more likely to emerge than others. We stress the complex interplay between rates of viral evolution and the ability to recognize cell receptors from phylogenetically divergent host species. We also emphasize the current lack of convincing data as to whether viral emergence requires adaptation to the new host species during the early stages of infection, or whether it is largely a chance process involving the transmission of a viral strain with the necessary genetic characteristics. url: https://www.ncbi.nlm.nih.gov/pubmed/17848060/ doi: 10.1007/978-3-540-70962-6_3 id: cord-303978-z3888e3g author: Hong, Ka Lok title: Single-Stranded DNA Aptamers against Pathogens and Toxins: Identification and Biosensing Applications date: 2015-06-23 words: 15716.0 sentences: 988.0 pages: flesch: 47.0 cache: ./cache/cord-303978-z3888e3g.txt txt: ./txt/cord-303978-z3888e3g.txt summary: Multiple virulent strains of the gram-negative bacteria, Escherichia coli, have been chosen as targets for the selection of specific ssDNA MREs due to their enterotoxigenic effects and the potential of contaminating food and water [39] . They also developed a sandwich detection system, in which biotinylated antibodies targeting the K88 strain were immobilized on magnetic beads as the capturing element and the 5 FITC labeled ssDNA library from round 13 selection served as the reporter in a fluorescent assay. In their later study, the affinities of selected candidate MREs were improved with reported values of in the nanomolar range and were specific for the target bacteria at different growth phases [57] . Acetamiprid Immobilization free 4.98 M -[27] Fluorescence plate based cross-binding assay showed the ssDNA MRE was approximately two to five times more selective on the alpha toxin than negative targets. abstract: Molecular recognition elements (MREs) can be short sequences of single-stranded DNA, RNA, small peptides, or antibody fragments. They can bind to user-defined targets with high affinity and specificity. There has been an increasing interest in the identification and application of nucleic acid molecular recognition elements, commonly known as aptamers, since they were first described in 1990 by the Gold and Szostak laboratories. A large number of target specific nucleic acids MREs and their applications are currently in the literature. This review first describes the general methodologies used in identifying single-stranded DNA (ssDNA) aptamers. It then summarizes advancements in the identification and biosensing application of ssDNA aptamers specific for bacteria, viruses, their associated molecules, and selected chemical toxins. Lastly, an overview of the basic principles of ssDNA aptamer-based biosensors is discussed. url: https://doi.org/10.1155/2015/419318 doi: 10.1155/2015/419318 id: cord-001072-pjv3wy80 author: Hong, Xiaoyun title: Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine date: 2013-09-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Microneedles were first conceptualized for drug delivery many decades ago, overcoming the shortages and preserving the advantages of hypodermic needle and conventional transdermal drug-delivery systems to some extent. Dissolving and biodegradable microneedle technologies have been used for transdermal sustained deliveries of different drugs and vaccines. This review describes microneedle geometry and the representative dissolving and biodegradable microneedle delivery methods via the skin, followed by the fabricating methods. Finally, this review puts forward some perspectives that require further investigation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771849/ doi: 10.2147/dddt.s44401 id: cord-311023-4ge4glq9 author: Hsieh, Yi-Fan title: A Lego(®)-like swappable fluidic module for bio-chem applications date: 2014-12-01 words: 3386.0 sentences: 172.0 pages: flesch: 51.0 cache: ./cache/cord-311023-4ge4glq9.txt txt: ./txt/cord-311023-4ge4glq9.txt summary: In this study, we demonstrate an advanced Lego ® -like swappable fluidic module (SFM) concept using PDMS blocks with assorted channel geometries that effortlessly connect to form fully functional microfluidic devices. Gold nanoparticles were also synthesized by rapid mixing and reactive chloroauric acid (HAuCl 4 ) and sodium citrate (Na 3 Table 1 presents the modular fluidic components used to integrate Lego ® -like SFMs. The functional components consisted of finger-operated, electricity-free pumps, a one-way valve, vortextype mixer, reservoir, and heating block (with the associated block names P, OWV, VM, R, and HB), and the straight tube (ST), T-type tube (TT-F, TT-M with F, and M denoting a male to female type of sealing face), cross tube (CT-F, CT-M), corner tube (CT), and height tube (HT) were categorized as auxiliary components and the corresponding model numbers were listed below each schematic, which demonstrated the mass production feasibility of Lego ® -like SFMs in several sizes. abstract: A Lego(®)-like swappable fluidic module (SFM) is proposed in this research. We designed and fabricated selected modular fluidic components, including functional and auxiliary types that can be effortlessly swapped and integrated into a variety of modular devices to rapidly assemble a fully-portable, disposable fluidic system. In practice, an integrated SFM uses finger-operated, electricity-free pumps to deliver fluids. Using a swirling mechanism, the vortex mixer can rapidly mix two liquids in a one-shot mixing event. We demonstrate the successful application of this SFM in several microfluidic applications, such as the synthesis of gold nanoparticles (AuNPs) from chloroauric acid (HAuCl(4)), and nucleic acid amplification from the Hepatitis B virus (HBV) with a capillary convective polymerase chain reaction (ccPCR). url: https://doi.org/10.1016/j.snb.2014.07.122 doi: 10.1016/j.snb.2014.07.122 id: cord-350890-ajxvjkmq author: Hsieh, Yi-Fan title: A real-time convective PCR machine in a capillary tube instrumented with a CCD-based fluorometer date: 2013-07-05 words: 4214.0 sentences: 207.0 pages: flesch: 47.0 cache: ./cache/cord-350890-ajxvjkmq.txt txt: ./txt/cord-350890-ajxvjkmq.txt summary: This research reports the design, analysis, integration, and test of a prototype of a real-time convective polymerase chain reaction (RT-cPCR) machine that uses a color charged coupled device (CCD) for detecting the emission of fluorescence intensity from an RT-cPCR mix in a microliter volume glass capillary. The measured results from the image-processing scheme indicate that the RT-cPCR prototype with a CCD-based fluorometer can achieve similar DNA quantification reproducibility compared to commercial machines, even when the initial DNA concentration in the test PCR mix is reduced to 10 copies/μL To assess the performance of the prototype, a single DNA template, HBV 122 base pairs, with known concentrations and a single labeling dye, SYBR Green I, was used in the PCR mixes undergoing the same thermal cycling in both the prototype and commercial RT-PCR machines for comparing their measured and predicted fluorescence intensities emitted from the glass capillaries. abstract: This research reports the design, analysis, integration, and test of a prototype of a real-time convective polymerase chain reaction (RT-cPCR) machine that uses a color charged coupled device (CCD) for detecting the emission of fluorescence intensity from an RT-cPCR mix in a microliter volume glass capillary. Because of its simple mechanism, DNA amplification involves employing the cPCR technique with no need for thermocycling control. The flow pattern and temperature distribution can greatly affect the cPCR process in the capillary tube, a computational fluid dynamics (CFD) simulation was conducted in this study for the first time to estimate the required period of an RT-cPCR cycle. This study also tested the PCR mix containing hepatitis B virus (HBV) plasmid samples by using SYBR Green I fluorescence labeling dye to assess the prototype performance. The measured results from the image-processing scheme indicate that the RT-cPCR prototype with a CCD-based fluorometer can achieve similar DNA quantification reproducibility compared to commercial machines, even when the initial DNA concentration in the test PCR mix is reduced to 10 copies/μL url: https://doi.org/10.1016/j.snb.2013.04.003 doi: 10.1016/j.snb.2013.04.003 id: cord-000865-rrscfo33 author: Hu, Tingsong title: Identification of a novel Getah virus by Virus-Discovery-cDNA random amplified polymorphic DNA (RAPD) date: 2012-12-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: The identification of new virus strains is important for the study of infectious disease, but current (or existing) molecular biology methods are limited since the target sequence must be known to design genome-specific PCR primers. Thus, we developed a new method for the discovery of unknown viruses based on the cDNA - random amplified polymorphic DNA (cDNA-RAPD) technique. Getah virus, belonging to the family Togaviridae in the genus Alphavirus, is a mosquito-borne enveloped RNA virus that was identified using the Virus-Discovery-cDNA RAPD (VIDISCR) method. RESULTS: A novel Getah virus was identified by VIDISCR from suckling mice exposed to mosquitoes (Aedes albopictus) collected in Yunnan Province, China. The non-structural protein gene, nsP3, the structural protein gene, the capsid protein gene, and the 3'-untranslated region (UTR) of the novel Getah virus isolate were cloned and sequenced. Nucleotide sequence identities of each gene were determined to be 97.1–99.3%, 94.9–99.4%, and 93.6–99.9%, respectively, when compared with the genomes of 10 other representative strains of Getah virus. CONCLUSIONS: The VIDISCR method was able to identify known virus isolates and a novel isolate of Getah virus from infected mice. Phylogenetic analysis indicated that the YN08 isolate was more closely related to the Hebei HB0234 strain than the YN0540 strain, and more genetically distinct from the MM2021 Malaysia primitive strain. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547691/ doi: 10.1186/1471-2180-12-305 id: cord-015941-4fz79wzf author: Hu, Yuan title: Molecular Techniques for Blood and Blood Product Screening date: 2018-11-10 words: 7210.0 sentences: 381.0 pages: flesch: 50.0 cache: ./cache/cord-015941-4fz79wzf.txt txt: ./txt/cord-015941-4fz79wzf.txt summary: Through the application of molecular biology, biological and biochemical analyses have been revolutionized, and nucleic acid, gene-based techniques have been developed to screen blood and plasma donations for evidence of very recent and earlier viral infections that might otherwise be missed by conventional serologic testing. Because NAT detects a virus''s genetic material instead of waiting for the body''s response, the formation of antibodies, as with many current tests, it offers the opportunity to reduce the window period during which an infecting agent is undetectable by traditional tests [21] , thus further improving blood safety. One reason for this is that currently available blood screening technologies detect core antibodies or surface antigens, which appear up to 8 weeks after infection. The anti-HBc test developed in 1987 detects an antibody to the hepatitis B virus that is produced during and after infection. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-amplification testing abstract: Blood product safety is a high priority for manufacturing industries, hospitals, and regulatory agencies. An important step in ensuring safety is the screening of donated blood for infectious diseases. Molecular technologies for screening infectious diseases have improved remarkably over the years. Molecular biological assay significantly reduced the risk of transfusion-transmitted infections. Unlike previous methods, molecular technologies for screening infectious diseases are specific, efficient, easy to use, and economical. A new era in molecular biology is coming to the field of blood safety. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120069/ doi: 10.1007/978-3-319-95111-9_2 id: cord-017948-fqhl1qb4 author: Hu, Yuan title: Molecular Techniques for Blood and Blood Product Screening date: 2012-04-05 words: 7304.0 sentences: 372.0 pages: flesch: 54.0 cache: ./cache/cord-017948-fqhl1qb4.txt txt: ./txt/cord-017948-fqhl1qb4.txt summary: Currently, nucleic acid testing techniques have been developed to screen blood and plasma products for evidence of very recent viral infections that could be missed by conventional serologic tests. Through the application of molecular biology, biological and biochemical analyses have been revolutionized, and nucleic acid, gene-based techniques have been developed to screen blood and plasma donations for evidence of very recent and earlier viral infections that might otherwise be missed by conventional serologic testing. Because NAT detects a virus''s genetic material instead of waiting for the body''s response, the formation of antibodies, as with many current tests, it offers the opportunity to reduce the window period during which an infecting agent is undetectable by traditional tests [ 19 ] , thus further improving blood safety. Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-ampli fi cation testing abstract: The Food and Drug Administration (FDA) is responsible for ensuring the safety of the more than 15 million units of blood and blood components donated each year in the United States. “Blood banking has become a manufacturing industry, an industry that must conform to high standards and quality control requirements comparable to those of pharmaceutical companies or other regulated industries,” said David A. Kessler, MD, former FDA commissioner [1]. Screening donated blood for infectious diseases that can be transmitted through blood transfusion is a very important step in ensuring safety. The United States has the safest blood supply in the world [1] and the FDA is striving to keep it safe by decreasing the risk of infectious disease transmission. The regulatory agency is continuously updating its requirements and standards for collecting and processing blood. As mentioned earlier, an important step in ensuring safety is the screening of donated blood for infectious diseases. In the United States, tests for infectious diseases are routinely conducted on each unit of donated blood, and these tests are designed to comply with regulatory requirements (Table 28.1). The field of clinical microbiology and virology are now focusing on molecular technology. Currently, nucleic acid testing techniques have been developed to screen blood and plasma products for evidence of very recent viral infections that could be missed by conventional serologic tests. It is time for all blood safety procedures to include molecular detection techniques. This approach can significantly aid in blood safety to reduce the risk of transmission of serious disease by transfusion. This chapter reviews the current antigen/antibody-based technology, molecular biological technology, and published regulatory policy data for blood safety. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122649/ doi: 10.1007/978-1-4614-3970-7_28 id: cord-003945-esnyjoq5 author: Hu, Zheng title: Customized one-step preparation of sgRNA transcription templates via overlapping PCR Using short primers and its application in vitro and in vivo gene editing date: 2019-10-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Overlap extension polymerase chain reaction (PCR) is a powerful technology for DNA assembly. Based on this technology, we synthesized DNA templates, which were transcribed into sgRNA in vitro, and further detected their efficiency of purified sgRNAs with Cas9 nuclease. The sgRNAs synthesized by this approach can effectively cleave the DNA fragments of interest in vitro and in vivo. Compared with the conventional method for generating sgRNA, it does not require construction of recombinant plasmids and design of primers to amplify sgRNA core fragment. Only several short primers with overlapped sequences are needed to assemble a DNA fragment as the template of sgRNA. This modified and simplified method is highly applicable and less time-consuming. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814055/ doi: 10.1186/s13578-019-0350-7 id: cord-021063-4y8m33ea author: Hug, Peter title: Chapter 18 The advantages of liposome-based gene therapy: A comparison of viral versus liposome-based gene delivery date: 2007-09-02 words: 6270.0 sentences: 341.0 pages: flesch: 51.0 cache: ./cache/cord-021063-4y8m33ea.txt txt: ./txt/cord-021063-4y8m33ea.txt summary: Potential problems associated with the use of viral vectors include: (i) the possibility of recombination events that could convert a replication-defective vector into an infectious agent, (ii) the possibility that superinfection with another retrovirus may allow unwanted transfer of the introduced gene between individuals, (iii) a 7-13 kb limit on the amount of DNA that can be packaged, (iv) potential problems in targeting the virus to specific cells, and (v) difficulty in maintaining high-level expression of the exogenous gene. While both cationic liposomes and retroviral gene delivery vectors lack the ability to target specific cells, the lack of length constraints makes tissue-specific expression easier to achieve using DNA-lipid complexes as compared to retroviruses. Second, limiting the number of cells that are transfected reduces the amount of DNA, lipid, and other proteins needed to perform the gene therapy. The central problem of any liposome-based gene therapy system is that DNA must be introduced into the cytoplasm of the target cell. abstract: Viruses have evolved in such a way they are able to efficiently introduce and express exogenous genes in eukaryotic cells. Most viruses need to maintain high-level expression of their proteins for only a short time and need not be concerned with the viability of the host cell after infection. Attempts to modify a virus into a gene therapy vector can be hampered by this conflict. Virus-based methods of gene therapy are likely to be most useful in applications that require a burst of high-level expression in many of the patient's cells, such as in cancer therapy. Liposomal methods of gene therapy are flexible in that all the components of the system are controlled by designers. As these systems have become more sophisticated, they have begun to take on several characteristics of the viruses that they are intended to replace. The use of basic substances to condense DNA has increased the efficiency of encapsulation. The addition of nucleophilic proteins raises the efficiency of transfection. By adding antibodies or other targeting molecules to the surface of liposomes, preferential binding of vesicles to a desired cell type has been increased. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148944/ doi: 10.1016/s1569-2582(97)80043-8 id: cord-320628-uc97t0ea author: Huguenin, Antoine title: Broad respiratory virus detection in infants hospitalized for bronchiolitis by use of a multiplex RT‐PCR DNA microarray system date: 2012-04-12 words: 3572.0 sentences: 169.0 pages: flesch: 41.0 cache: ./cache/cord-320628-uc97t0ea.txt txt: ./txt/cord-320628-uc97t0ea.txt summary: Multiplex RT-PCR DNA Microarray CLART 1 (CLinical ARray Technology) PneumoVir kit V16.3 (Genomica) is based on viral genome-specific fragments amplification located between 106-328 bp by multiplex PCR and its subsequent detection via hybridization with microorganism-specific binding probe on low-density microarrays, allowing simultaneous detection and identification of 17 types and subtypes of human respiratory viruses (influenza A including seasonal A/H1N1 and A/H3N2 strains, influenza B, influenza C, parainfluenza 1, 2, 3, 4A and 4B, hRSV A and B, human rhinoviruses, adenoviruses, EVs specie B, human bocavirus, coronavirus E-229 and the human metapneumovirus A and B) in clinical samples [Renois et al., 2010; Frobert et al., 2011] . In conclusion, the use of a multiplex RT-PCR DNA microarray system in clinical virology practice allows a rapid and an accurate identification of common and uncommon viral respiratory pathogens in infants hospitalized for bronchiolitis. abstract: Newly available molecular tools allow a sensitive detection of a broad panel of viruses in respiratory tract specimens. In the present study, the application of a multiplex RT‐PCR DNA microarray in diagnosis and epidemiological survey of viral infections in infants hospitalized for bronchiolitis was assessed. One hundred and thirty‐eight nasopharyngeal aspirates collected from October 2007 to September 2008 were tested by direct immunofluorescence and viral culture, a combination of referenced RT‐PCRs and the DNA microarray. One or more viruses were detected in 96, 126 and 126 of the specimens by direct immunofluorescence and viral culture, RT‐PCRs and DNA microarray, respectively (70 vs. 91 vs. 91%, P < 10(−3)). The RT‐PCRs and the DNA microarray yielded concordant results for 99% of specimens and identified mixed viral infections in 85 (62%). The most common associations were: human bocavirus and respiratory syncytial virus (32%), adenovirus and respiratory syncytial virus (30%), and parainfluenza virus type 3 and respiratory syncytial virus (23%). None of the bronchiolitis severity parameters including intensive care unit admission, O(2) supply, O(2) saturation percentage, O(2) length and length of stay at the hospital appeared to be significantly increased in multiple viral infections compared to single viral infections (P > 0.1). In conclusion, the use of this DNA microarray in clinical virology practice allows rapid and accurate identification of common and uncommon viral respiratory pathogens in infants hospitalized for bronchiolitis. It should improve the clinical management, the epidemiological survey, and the prevention of the nosocomial transmission of respiratory viruses in pediatric wards. J. Med. Virol. 84:979–985, 2012. © 2012 Wiley Periodicals, Inc. url: https://www.ncbi.nlm.nih.gov/pubmed/22499022/ doi: 10.1002/jmv.23272 id: cord-304283-nv4ret1f author: Hung, Chuan-Fu title: A novel siRNA validation system for functional screening and identification of effective RNAi probes in mammalian cells date: 2006-08-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Small interfering RNAs (siRNAs) have become the most powerful and widely used gene silencing reagents for reverse functional genomics and molecular therapeutics. The key challenge for achieving effective gene silencing in particular for the purpose of the therapeutics is primarily dependent on the effectiveness and specificity of the RNAi targeting sequence. However, only a limited number of siRNAs is capable of inducing highly effective and sequence-specific gene silencing by RNA interference (RNAi) mechanism. In addition, the efficacy of siRNA-induced gene silencing can only be experimentally measured based on inhibition of the target gene expression. Therefore, it is important to establish a fully robust and comparative validating system for determining the efficacy of designed siRNAs. In this study, we have developed a reliable and quantitative reporter-based siRNA validation system that consists of a short synthetic DNA fragment containing an RNAi targeting sequence of interest and two expression vectors for targeting reporter and triggering siRNA expression. The efficacy of the siRNAs is measured by their abilities to inhibit expression of the targeting reporter gene with easily quantified readouts including enhanced green fluorescence protein (EGFP) and firefly luciferase. Using fully analyzed siRNAs against human hepatitis B virus (HBV) surface antigen (HBsAg) and tumor suppressor protein p53, we have demonstrated that this system could effectively and faithfully report the efficacy of the corresponding siRNAs. In addition, we have further applied this system for screening and identification of the highly effective siRNAs that could specifically inhibit expression of mouse matrix metalloproteinase-7 (MMP-7), Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1), and human serine/threonine kinase AKT1. Since only a readily available short synthetic DNA fragment is needed for constructing this novel reporter-based siRNA validation system, this system not only provides a powerful strategy for screening highly effective siRNAs but also implicates in the use of RNAi for studying novel gene function in mammals. url: https://www.ncbi.nlm.nih.gov/pubmed/16793020/ doi: 10.1016/j.bbrc.2006.05.164 id: cord-004995-5jmjejbp author: Hunt, Hamish C. title: Optofluidic integration for microanalysis date: 2007-09-11 words: 17310.0 sentences: 797.0 pages: flesch: 42.0 cache: ./cache/cord-004995-5jmjejbp.txt txt: ./txt/cord-004995-5jmjejbp.txt summary: Integration of waveguides from which light emerges into a microfluidic channel is an attractive advance upon the use of external lenses or the hybrid integration of individual optical fibres to realise dual-beam traps, in terms of robustness, alignment and potential for mass production. Detection and analysis of chemical and biochemical species in microfluidic systems is challenging due to short optical path-lengths, small sample volumes, and the need to analyse individual particles or molecules. This section reviews optical detection schemes for chemical analysis in microfluidic systems, divided according to the principal optical phenomena employed: scattering, absorption, refractive index, fluorescence, Raman spectroscopy, and thermal lensing. Kamei and Wada (2006) built upon earlier work (Kamei et al 2005) demonstrating microfluidic separation of biomolecules, and realised a detection platform shown in Fig. 11 , which included a 2 mm diameter half-ball lens for fluorescence collection, a microstructured interference filter deposited directly on a pin photodiode, and an aperture through the centre of the detector and filter via which excitation light from a 488 nm frequency-doubled VCSEL was introduced. abstract: This review describes recent research in the application of optical techniques to microfluidic systems for chemical and biochemical analysis. The “lab-on-a-chip” presents great benefits in terms of reagent and sample consumption, speed, precision, and automation of analysis, and thus cost and ease of use, resulting in rapidly escalating adoption of microfluidic approaches. The use of light for detection of particles and chemical species within these systems is widespread because of the sensitivity and specificity which can be achieved, and optical trapping, manipulation and sorting of particles show significant benefits in terms of discrimination and reconfigurability. Nonetheless, the full integration of optical functions within microfluidic chips is in its infancy, and this review aims to highlight approaches, which may contribute to further miniaturisation and integration. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087941/ doi: 10.1007/s10404-007-0223-y id: cord-285262-690kpupt author: Imre, Gergely title: The involvement of regulated cell death forms in modulating the bacterial and viral pathogenesis date: 2020-01-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Apoptosis, necroptosis and pyroptosis represent three distinct types of regulated cell death forms, which play significant roles in response to viral and bacterial infections. Whereas apoptosis is characterized by cell shrinkage, nuclear condensation, bleb formation and retained membrane integrity, necroptosis and pyroptosis exhibit osmotic imbalance driven cytoplasmic swelling and early membrane damage. These three cell death forms exert distinct immune stimulatory potential. The caspase driven apoptotic cell demise is considered in many circumstances as anti-inflammatory, whereas the two lytic cell death modalities can efficiently trigger immune response by releasing damage associated molecular patterns to the extracellular space. The relevance of these cell death modalities in infections can be best demonstrated by the presence of viral proteins that directly interfere with cell death pathways. Conversely, some pathogens hijack the cell death signaling routes to initiate a targeted attack against the immune cells of the host, and extracellular bacteria can benefit from the destruction of intact extracellular barriers upon cell death induction. The complexity and the crosstalk between these cell death modalities reflect a continuous evolutionary race between pathogens and host. This chapter discusses the current advances in the research of cell death signaling with regard to viral and bacterial infections and describes the network of the cell death initiating molecular mechanisms that selectively recognize pathogen associated molecular patterns. url: https://api.elsevier.com/content/article/pii/S1937644819301273 doi: 10.1016/bs.ircmb.2019.12.008 id: cord-003207-ow3aez9v author: Ismail, Ashrafali M. title: Adenoviromics: Mining the Human Adenovirus Species D Genome date: 2018-09-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Human adenovirus (HAdV) infections cause disease world-wide. Whole genome sequencing has now distinguished 90 distinct genotypes in 7 species (A-G). Over half of these 90 HAdVs fall within species D, with essentially all of the HAdV-D whole genome sequences generated in the last decade. Herein, we describe recent new findings made possible by mining of this expanded genome database, and propose future directions to elucidate new functional elements and new functions for previously known viral components. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141750/ doi: 10.3389/fmicb.2018.02178 id: cord-267714-ji88tvsl author: JAKUPCIAK, JOHN P. title: Biological agent detection technologies date: 2009-04-21 words: 3526.0 sentences: 175.0 pages: flesch: 35.0 cache: ./cache/cord-267714-ji88tvsl.txt txt: ./txt/cord-267714-ji88tvsl.txt summary: PCR-based methods have critical limitations, since they depend on a priori knowledge of what sequence to detect in a sample further complicated by recent demonstrations of greater variability in genomic sequence than expected. A platform for genome identification of a specimen from any source must not only be sensitive and specific, but must also detect a variety of pathogens with high accuracy, including modified or previously uncharacterized agents, and this challenge is daunting when identification must be achieved using nucleic acids in a complex sample matrix. The build-out of genome identification DNA sequencing technology in the form of practical instrumentation will be achieved by incorporating the critical requirements for accurate long reads, without dependency for template amplification, capable of manipulating terabytes of data to provide reliable and useful identification of genetic sequences within any unknown sample, whether clinical, environmental, or other type of specimen. abstract: The challenge for first responders, physicians in the emergency room, public health personnel, as well as for food manufacturers, distributors and retailers is accurate and reliable identification of pathogenic agents and their corresponding diseases. This is the weakest point in biological agent detection capability today. There is intense research for new molecular detection technologies that could be used for very accurate detection of pathogens that would be a concern to first responders. These include the need for sensors for multiple applications as varied as understanding the ecology of pathogenic micro‐organisms, forensics, environmental sampling for detect‐to‐treat applications, biological sensors for ‘detect to warn’ in infrastructure protection, responses to reports of ‘suspicious powders’, and customs and borders enforcement, to cite a few examples. The benefits of accurate detection include saving millions of dollars annually by reducing disruption of the workforce and the national economy and improving delivery of correct countermeasures to those who are most in need of the information to provide protective and/or response measures. url: https://doi.org/10.1111/j.1755-0998.2009.02632.x doi: 10.1111/j.1755-0998.2009.02632.x id: cord-257318-jejgkcql author: Jain, K.K. title: Synthetic Biology and Personalized Medicine date: 2012-08-16 words: 6096.0 sentences: 285.0 pages: flesch: 33.0 cache: ./cache/cord-257318-jejgkcql.txt txt: ./txt/cord-257318-jejgkcql.txt summary: Methods based on synthetic biology enable the design of novel strategies for the treatment of cancer, immune diseases metabolic disorders and infectious diseases as well as the production of cheap drugs [2] . Whereas genetic engineering focuses on individual genes, synthetic biology strings together a series of molecular components, such as DNA, RNA, proteins and cells, into circuits and networks. Synthetic gene network design and prototype therapeutic circuits will have an impact on future gene-and cell-based therapies and usher a new era of drug discovery that may enable treatment of complex diseases in a personalized manner. Among new technologies, synthetic biology will contribute by the introduction of therapeutic systems based on a synthetic genome, using an expanded genetic code, and designed for specific personalized drug synthesis as well as delivery and activation by a pathological signal. abstract: Synthetic biology, application of synthetic chemistry to biology, is a broad term that covers the engineering of biological systems with structures and functions not found in nature to process information, manipulate chemicals, produce energy, maintain cell environment and enhance human health. Synthetic biology devices contribute not only to improve our understanding of disease mechanisms, but also provide novel diagnostic tools. Methods based on synthetic biology enable the design of novel strategies for the treatment of cancer, immune diseases metabolic disorders and infectious diseases as well as the production of cheap drugs. The potential of synthetic genome, using an expanded genetic code that is designed for specific drug synthesis as well as delivery and activation of the drug in vivo by a pathological signal, was already pointed out during a lecture delivered at Kuwait University in 2005. Of two approaches to synthetic biology, top-down and bottom-up, the latter is more relevant to the development of personalized medicines as it provides more flexibility in constructing a partially synthetic cell from basic building blocks for a desired task. url: https://doi.org/10.1159/000341794 doi: 10.1159/000341794 id: cord-314503-u1y1bznk author: Jaluria, Pratik title: A perspective on microarrays: current applications, pitfalls, and potential uses date: 2007-01-25 words: 7764.0 sentences: 349.0 pages: flesch: 38.0 cache: ./cache/cord-314503-u1y1bznk.txt txt: ./txt/cord-314503-u1y1bznk.txt summary: Therefore, this text aims to outline key features in microarray technology, paying particular attention to current applications as outlined in recent publications, experimental design, statistical methods, and potential uses. Several organizations such as the Microarray Gene Expression Data (MGED) Society and the European Bioinformatics Institute (EBI) have established guidelines to aid researchers in the design and implementation of microarray experiments [8, 9, 16] . As mentioned earlier, verification is critical in order to assign distinct expression patterns to specific genes with certainty (i.e. statistical significance) because of the inherent variability present in microarray data. To verify the results generated from microarray experiments, a combinatorial approach is usually needed; checking the statistical significance associated with the expression levels of specific genes, reviewing the literature, and conducting additional experiments such as RT-PCR or Northern blotting. A large number of microarray-related studies in the past have aimed to either characterize diseased cells in comparison to healthy cells or highlight the genes involved in a particular biological pathway [4, 8] . abstract: With advances in robotics, computational capabilities, and the fabrication of high quality glass slides coinciding with increased genomic information being available on public databases, microarray technology is increasingly being used in laboratories around the world. In fact, fields as varied as: toxicology, evolutionary biology, drug development and production, disease characterization, diagnostics development, cellular physiology and stress responses, and forensics have benefiting from its use. However, for many researchers not familiar with microarrays, current articles and reviews often address neither the fundamental principles behind the technology nor the proper designing of experiments. Although, microarray technology is relatively simple, conceptually, its practice does require careful planning and detailed understanding of the limitations inherently present. Without these considerations, it can be exceedingly difficult to ascertain valuable information from microarray data. Therefore, this text aims to outline key features in microarray technology, paying particular attention to current applications as outlined in recent publications, experimental design, statistical methods, and potential uses. Furthermore, this review is not meant to be comprehensive, but rather substantive; highlighting important concepts and detailing steps necessary to conduct and interpret microarray experiments. Collectively, the information included in this text will highlight the versatility of microarray technology and provide a glimpse of what the future may hold. url: https://www.ncbi.nlm.nih.gov/pubmed/17254338/ doi: 10.1186/1475-2859-6-4 id: cord-002441-w731ehtz author: Jeon, Young Joo title: Interferon-Stimulated Gene 15 in the Control of Cellular Responses to Genotoxic Stress date: 2017-02-28 words: 4141.0 sentences: 227.0 pages: flesch: 44.0 cache: ./cache/cord-002441-w731ehtz.txt txt: ./txt/cord-002441-w731ehtz.txt summary: The expression of interferon-stimulated gene 15 (ISG15), the first identified ubiquitin-like protein, has recently been shown to be induced under various DNA damage conditions, such as exposure to UV, camptothecin, and doxorubicin. Here we overview the recent findings on the role of ISG15 and its conjugation to target proteins (e.g., p53, ΔNp63α, and PCNA) in the control of cellular responses to genotoxic stress, such as the inhibition of cell growth and tumorigenesis. Accordingly, treatment with DNA-damaging agents, such as UV, camptothecin, and doxorubicin, markedly induces both the mRNA and protein further accelerates p53 ISGylation and subsequent processes for suppression of cell growth and tumor development by forming a positive feedback loop. Thus, it appears clear that ISG15 and its conjugation to target proteins play a crucial function in the control of cellular responses to genotoxic stresses and in turn in suppression of DNA damage-mediated tumorigenesis. abstract: Error-free replication and repair of DNA are pivotal to organisms for faithful transmission of their genetic information. Cells orchestrate complex signaling networks that sense and resolve DNA damage. Post-translational protein modifications by ubiquitin and ubiquitin-like proteins, including SUMO and NEDD8, are critically involved in DNA damage response (DDR) and DNA damage tolerance (DDT). The expression of interferon-stimulated gene 15 (ISG15), the first identified ubiquitin-like protein, has recently been shown to be induced under various DNA damage conditions, such as exposure to UV, camptothecin, and doxorubicin. Here we overview the recent findings on the role of ISG15 and its conjugation to target proteins (e.g., p53, ΔNp63α, and PCNA) in the control of cellular responses to genotoxic stress, such as the inhibition of cell growth and tumorigenesis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339507/ doi: 10.14348/molcells.2017.0027 id: cord-294196-3gox5art author: Jin, Hongwei title: Structural insights into the effect of isonucleosides on B-DNA duplexes using molecular-dynamics simulations date: 2006-02-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Some structural insights into the conformations of the isonucleosides containing duplexes have been provided. Unrestrained molecular-dynamics simulations on 18-mer duplexes with isonucleosides incorporated at the 3'-end or in the center of one strand have been carried out with explicit solvent under periodic boundary conditions using the AMBER force field and the particle mesh Ewald method. The Watson–Crick hydrogen-bonding patterns of the duplexes studied remained intact throughout the simulation. For the modified duplexes, the changes observed in the inter-base pair parameters and backbone torsional angles were primarily localized at the isonucleoside-inserted area. All five structures studied remained in the B-form family. The decreased stacking abilities indicated by the large changes in inter-base pair parameters and the large changes in backbones made the modified duplexes show a minor thermal destabilization in comparison with native DNA. The MM_PBSA method for estimating binding free energies on two complementary strands was used. The results showed that the binding free energies of isonucleoside-incorporated DNA duplexes were lower than the native DNA duplex, which is in good agreement with experimental observations. [Image: see text] url: https://www.ncbi.nlm.nih.gov/pubmed/16450112/ doi: 10.1007/s00894-005-0085-8 id: cord-316096-3fnwosst author: Jin, Huali title: Induction of Th1 type response by DNA vaccinations with N, M, and E genes against SARS-CoV in mice date: 2005-03-25 words: 4521.0 sentences: 222.0 pages: flesch: 54.0 cache: ./cache/cord-316096-3fnwosst.txt txt: ./txt/cord-316096-3fnwosst.txt summary: After the intramuscular introduction into animals, we observed that the constructs of the E, M, and N genes could induce high levels of specific antibodies, T cell proliferations, IFN-γ, DTH responses, and in vivo cytotoxic T cells activities specifically against SARS-CoV antigens. All DNA vaccine constructs, encoding the E protein, the M glycoprotein, and the N protein of SARS-CoV, were obtained as follows: these genes were amplified from the cDNA by PCR amplifications using each set of specific primers, respectively. In the present study, it was consistent with their work that the N protein construct could induce the highest SARS-specific IgG, T cell proliferation, and in vivo CTL response (lysis rate of 50.6%) compared with M protein gene (lysis rate of 17%) and E protein gene (lysis rate of 5.6%) (Fig. 4) . In summary, the administrations with all three SARS-CoV DNA vaccines in our study were able to induce high levels of the antigen-specific IgG antibody, the T cell proliferation, IFN-c, DTH, and in vivo CTL responses. abstract: Abstract Vaccination against the SARS-CoV infection is an attractive means to control the spread of viruses in public. In this study, we employed a DNA vaccine technology with the levamisole, our newly discovered chemical adjuvant, to generate Th1 type of response. To avoid the enhancement antibody issue, genes encoding the nucleocapsid, membrane, and envelope protein of SARS-CoV were cloned and their expressions in mammalian cells were determined. After the intramuscular introduction into animals, we observed that the constructs of the E, M, and N genes could induce high levels of specific antibodies, T cell proliferations, IFN-γ, DTH responses, and in vivo cytotoxic T cells activities specifically against SARS-CoV antigens. The highest immune responses were generated by the construct encoding the nucleocapsid protein. The results suggest that the N, M, and E genes could be used as the targets to prevent SARS-CoV infection in the DNA vaccine development. url: https://www.sciencedirect.com/science/article/pii/S0006291X05001026 doi: 10.1016/j.bbrc.2005.01.048 id: cord-301128-woe6knpv author: Joyeux, Marc title: Requirements for DNA-bridging proteins to act as topological barriers of the bacterial genome date: 2020-08-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Bacterial genomes have been shown to be partitioned into several kilobases long chromosomal domains that are topologically independent from each other, meaning that change of DNA superhelicity in one domain does not propagate to neighbors. Both in vivo and in vitro experiments have been performed to question the nature of the topological barriers at play, leading to several predictions on possible molecular actors. Here, we address the question of topological barriers using polymer models of supercoiled DNA chains that are constrained such as to mimic the action of predicted molecular actors. More specifically, we determine under which conditions DNA-bridging proteins may act as topological barriers. To this end, we developed a coarse-grained bead-and-spring model and investigated its properties through Brownian dynamics simulations. As a result, we find that DNA-bridging proteins must exert rather strong constraints on their binding sites: they must block the diffusion of the excess of twist through the two binding sites on the DNA molecule and, simultaneously, prevent the rotation of one DNA segment relative to the other one. Importantly, not all DNA-bridging proteins satisfy this second condition. For example, single bridges formed by proteins that bind DNA non-specifically, like H-NS dimers, are expected to fail with this respect. Our findings might also explain, in the case of specific DNA-bridging proteins like LacI, why multiple bridges are required to create stable independent topological domains. Strikingly, when the relative rotation of the DNA segments is not prevented, relaxation results in complex intrication of the two domains. Moreover, while the value of the torsional stress in each domain may vary, their differential is preserved. Our work also predicts that nucleoid associated proteins known to wrap DNA must form higher protein-DNA complexes to efficiently work as topological barriers. url: https://api.elsevier.com/content/article/pii/S0006349520306007 doi: 10.1016/j.bpj.2020.08.004 id: cord-342737-hhs3owvr author: Jula, Alma title: Primary and Secondary Human Bocavirus 1 Infections in a Family, Finland date: 2013-08-17 words: 1728.0 sentences: 117.0 pages: flesch: 55.0 cache: ./cache/cord-342737-hhs3owvr.txt txt: ./txt/cord-342737-hhs3owvr.txt summary: Human bocavirus 1 (HBoV1) was detected in a young child hospitalized for pneumonia and subsequently in his twin brother and other family members. Human bocavirus 1 (HBoV1) was detected in a young child hospitalized for pneumonia and subsequently in his twin brother and other family members. The index patient had an HBoV1 infection proven by detection of HBoV1 DNA in high copy numbers in NPA and BAL samples, as well as in serum. Three months after this episode of HBoV1 infection, all 4 family members had symptomatic parainfluenza type 1 virus infections, and clinical samples for the twin brother were again positive for HBoV1 DNA. During the acute phase of HBoV1 infection in the index patient, HRV RNA was identified in the NPA of 3 family members, an observation similar to that of many studies (1) . abstract: Human bocavirus 1 (HBoV1) was detected in a young child hospitalized for pneumonia and subsequently in his twin brother and other family members. The mother’s nasopharyngeal samples intermittently showed HBoV1 DNA; the grandmother had HBoV1 reinfection. Findings in this family lead to consideration of HBoV virulence, latency, and reactivation. url: https://doi.org/10.3201/eid.1908.130074 doi: 10.3201/eid.1908.130074 id: cord-254527-zddwajzg author: Junter, Guy-Alain title: Polysaccharide-based chromatographic adsorbents for virus purification and viral clearance date: 2020-01-13 words: 16940.0 sentences: 907.0 pages: flesch: 42.0 cache: ./cache/cord-254527-zddwajzg.txt txt: ./txt/cord-254527-zddwajzg.txt summary: Table 2 gathers a variety of packed-bed column chromatography procedures applied to viral particle purification in which the stationary phase consists of AG -essentially Sepharose® ("Separation-Pharmacia-AG"; GE Healthcare, Chicago, Ill.) (Seph) -or CELe.g., Cellufine™ (JNC Corporation, Tokyo, Japan) -gel beads, modified to fulfill varying separation modes, i.e., ion exchange, size exclusion and affinity (Table 3 [77] [78] [79] [80] [81] ). For instance, the purification process for Nuwiq®, a recombinant coagulation factor VIII (a blood-clotting protein whose deficiency is associated with hemophilia A) patented by Octapharma AG (Lachen, Switzerland) [195] , includes solvent/detergent (S/D) treatment, Planova NF, and five chromatography steps using PS-based stationary phases, i.e., MMC (Capto MMC), CEC (SP Seph FF), AFC (VIIISelect, a Capto matrix with factor VIIIselective ligand), AEC (Q Seph FF) and SEC (Superdex 200). abstract: Viruses still represent a significant threat to human and animal health worldwide. In the fight against viral infections, high-purity viral stocks are needed for manufacture of safer vaccines. It is also a priority to ensure the viral safety of biopharmaceuticals such as blood products. Chromatography techniques are widely implemented at both academic and industrial levels in the purification of viral particles, whole viruses and virus-like particles, and to remove viral contaminants from biopharmaceutical products. This paper focuses on polysaccharide adsorbents, particulate resins and membrane adsorbers, used in virus purification/removal chromatography processes. Different chromatographic modes are surveyed, with particular attention on ion exchange and affinity/pseudo-affinity adsorbents among which commercially available agarose-based resins (Sepharose®) and cellulose-based membrane adsorbers (Sartobind®) occupy a dominant position. Mainly built on the development of new ligands coupled to conventional agarose/cellulose matrices, the development perspectives of polysaccharide-based chromatography media in this antiviral area are stressed in a conclusive part. url: https://www.sciencedirect.com/science/article/pii/S209517791930838X?v=s5 doi: 10.1016/j.jpha.2020.01.002 id: cord-336749-qbko22vf author: Kalisch, Thomas title: New readers and interpretations of poly(ADP-ribosyl)ation date: 2012-09-30 words: 6658.0 sentences: 304.0 pages: flesch: 44.0 cache: ./cache/cord-336749-qbko22vf.txt txt: ./txt/cord-336749-qbko22vf.txt summary: MacroH2A1.1, which is involved in the DNA damage response and transcriptional regulation, is able to bind PAR, ADPR and the SirT1 metabolite O-acetyl-ADP-ribose (OAADPR), which is produced during the NAD + -dependent deacetylation of acetylated proteins [22] . RNF146 is rapidly recruited to laser-induced DNA-damaged sites; its PAR-dependent E3 ligase activity promotes DNA repair and prevents cell death induced by g-irradiation, alkylating agents or hydrogen peroxide, but only at doses known to trigger cell death superfamily C-terminal domain associated with DEXDc-, DEAD-and DEAH-box proteins (lavender box); FHA, forkhead associated (light pink box); HECT, homologous to E6-AP carboxyl terminus domain, displaying E3-ligase activity (light orange box); lactamase B, domain homologous to b-lactamase endowed with nuclease activity (gray box); macro, homologous to the nonhistone part of macroH2A, displaying PAR-binding activity (see text; blue box); PARP, catalytic domain, homologous to the poly(ADP-ribose) synthesis domain of PARP-1, endowed with mono-or poly(ADP-ribosyl)ation activity (green box); PBZ, PAR-binding zinc finger (see text; orange box); RING, really interesting new gene: zinc binding domain with ubiquitin E3 ligase activity (sienna box); SAM-L, sterile a motif-like (purple box); SNF2-N, SNF2 family N-terminal domain (light steel blue box); UBA, ubiquitin-binding domain (silver gray box); WWE, named after its three conserved residues Trp, Trp and Glu, displaying PAR-binding activity (see text; dark yellow box); Zf-CCCH, zinc finger motif (pink box). abstract: Poly(ADP-ribosyl)ation (PARylation), a protein post-translational modification that was originally connected to the DNA damage response, is now known to engage in a continuously increasing number of biological processes. Despite extensive research and ceaseless, important findings about its role and mode of action, poly(ADP-ribose) remains an enigma regarding its structural complexity and diversity. The recent identification and structural characterization of four different poly(ADP-ribose) binding motifs represents a quantum leap in the comprehension of how this molecule can be decoded. Moreover, the recent discovery of a direct connection between PARylation and poly-ubiquitylation in targeting proteins for degradation by the proteasome has paved the way for a new interpretation of this protein modification. These two novel aspects, poly(ADP-ribose) recognition and readout by the ubiquitylation/proteasome system are developed here. url: https://doi.org/10.1016/j.tibs.2012.06.001 doi: 10.1016/j.tibs.2012.06.001 id: cord-007383-5yb3dxse author: Kang, Jun-Gu title: Vaccination with single plasmid DNA encoding IL-12 and antigens of severe fever with thrombocytopenia syndrome virus elicits complete protection in IFNAR knockout mice date: 2020-03-20 words: 5369.0 sentences: 272.0 pages: flesch: 49.0 cache: ./cache/cord-007383-5yb3dxse.txt txt: ./txt/cord-007383-5yb3dxse.txt summary: title: Vaccination with single plasmid DNA encoding IL-12 and antigens of severe fever with thrombocytopenia syndrome virus elicits complete protection in IFNAR knockout mice Immunization of NS antigen with Freund''s adjuvant in C57BL/6 mice, which are naturally resistant to SFTSV but partially mimic human infections [12] , failed to enhance viral clearance, although it induced high titer of anti-NS antibodies and significantly elevated IFN-γ levels in sera upon viral challenge [9] . Vaccination of pSFTSV-IL12 provided complete protection of IFNAR KO mice upon lethal SFTSV challenge, whereas immunization with pSFTSV elicits only partial protection, indicating that antigen-specific cellular immune responses enhanced by co-expression of IL-12 could play a significant role in protection against lethal SFTSV infection. Since we observed significant elevation of T cell responses specific to the viral antigens in IFNAR KO mice immunized with pSFTSV-IL12 DNA vaccine, we tested whether it could provide protective immunity against lethal SFTSV infection. abstract: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by SFTS virus (SFTSV) infection. Despite a gradual increase of SFTS cases and high mortality in endemic regions, no specific viral therapy nor vaccine is available. Here, we developed a single recombinant plasmid DNA encoding SFTSV genes, Gn and Gc together with NP-NS fusion antigen, as a vaccine candidate. The viral antigens were fused with Fms-like tyrosine kinase-3 ligand (Flt3L) and IL-12 gene was incorporated into the plasmid to enhance cell-mediated immunity. Vaccination with the DNA provides complete protection of IFNAR KO mice upon lethal SFTSV challenge, whereas immunization with a plasmid without IL-12 gene resulted in partial protection. Since we failed to detect antibodies against surface glycoproteins, Gn and Gc, in the immunized mice, antigen-specific cellular immunity, as confirmed by enhanced antigen-specific T cell responses, might play major role in protection. Finally, we evaluated the degree of protective immunity provided by protein immunization of the individual glycoprotein, Gn or Gc. Although both protein antigens induced a significant level of neutralizing activity against SFTSV, Gn vaccination resulted in relatively higher neutralizing activity and better protection than Gc vaccination. However, both antigens failed to provide complete protection. Given that DNA vaccines have failed to induce sufficient immunogenicity in human trials when compared to protein vaccines, optimal combinations of DNA and protein elements, proper selection of target antigens, and incorporation of efficient adjuvant, need to be further investigated for SFTSV vaccine development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112229/ doi: 10.1371/journal.pntd.0007813 id: cord-267928-dflkggjt author: Kantola, Kalle title: Merkel cell polyomavirus DNA in tumor-free tonsillar tissues and upper respiratory tract samples: Implications for respiratory transmission and latency date: 2009-05-22 words: 2731.0 sentences: 162.0 pages: flesch: 58.0 cache: ./cache/cord-267928-dflkggjt.txt txt: ./txt/cord-267928-dflkggjt.txt summary: STUDY DESIGN: Altogether 1390 samples from immunocompetent or immunocompromised patients, including (i) tonsillar tissues and sera from tonsillectomy patients; (ii) nasopharyngeal aspirates (NPAs) and sera from wheezing children and (iii) nasal swabs, sera and stools from febrile leukemic children were studied for MCPyV. RESULTS: MCPyV DNA was detected in 14 samples altogether; 8 of 229 (3.5%) tonsillar tissues, 3 of 140 (2.1%) NPAs, 2 of 106 (1.9%) nasal swabs and 1 of 840 (0.1%) sera. In this study MCPyV DNA was detected in clinical samples of many different types: nasal swabs and nasopharyngeal aspirates, tumor-free tonsillar tissues and sera. Among immunocompetent children, the absence of MCPyV from the 496 serum samples tested is in accordance with our recent study (in submission) in which the two other polyomaviruses KIPyV and WUPyV were absent from all of these sera. abstract: BACKGROUND: Merkel cell polyomavirus (MCPyV) was discovered recently. It is considered a potential causative agent of Merkel cell carcinoma, a life-threatening skin cancer. OBJECTIVES: To study the prevalence of MCPyV in a large number of clinical samples of various types. Most of the samples were examined also for the other newly found polyomaviruses KI (KIPyV) and WU (WUPyV). STUDY DESIGN: Altogether 1390 samples from immunocompetent or immunocompromised patients, including (i) tonsillar tissues and sera from tonsillectomy patients; (ii) nasopharyngeal aspirates (NPAs) and sera from wheezing children and (iii) nasal swabs, sera and stools from febrile leukemic children were studied for MCPyV. The tonsils, nasal swabs and stools were also studied for KIPyV and WUPyV. RESULTS: MCPyV DNA was detected in 14 samples altogether; 8 of 229 (3.5%) tonsillar tissues, 3 of 140 (2.1%) NPAs, 2 of 106 (1.9%) nasal swabs and 1 of 840 (0.1%) sera. WUPyV and KIPyV were detected in 5 (2.2%) and 0 tonsils, 1 (0.9%) and 4 (3.8%) nasal swabs and 0 and 2 (2.7%) fecal samples, respectively. The patients carrying in tonsils MCPyV were of significantly higher age (median 42 years) than those carrying WUPyV (4 years, p < 0.001). CONCLUSIONS: MCPyV DNA occurs in tonsils more frequently in adults than in children. By contrast, WUPyV DNA is found preferentially in children. MCPyV occurs also in nasal swabs and NPAs, in a frequency similar to that of KIPyV and WUPyV. The tonsil may be an initial site of WUPyV infection and a site of MCPyV persistence. url: https://api.elsevier.com/content/article/pii/S138665320900167X doi: 10.1016/j.jcv.2009.04.008 id: cord-307603-uqr6r14u author: Kauppinen, S. title: Locked Nucleic Acid: High-Affinity Targeting of Complementary RNA for RNomics date: 2006 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Locked nucleic acid (LNA) is a nucleic acid analog containing one or more LNA nucleotide monomers with a bicyclic furanose unit locked in an RNA-mimicking sugar conformation. This conformational restriction is translated into unprecedented hybridization affinity towards complementary single-stranded RNA molecules. That makes fully modified LNAs, LNA/DNA mixmers, or LNA/RNA mixmers uniquely suited for mimicking RNA structures and for RNA targeting in vitro or in vivo. The focus of this chapter is on LNA antisense, LNA-modified DNAzymes (LNAzymes), LNA-modified small interfering (si)RNA (siLNA), LNA-enhanced expression profiling by real-time RT-PCR and detection and analysis of microRNAs by LNA-modified probes. url: https://www.ncbi.nlm.nih.gov/pubmed/16594628/ doi: 10.1007/3-540-27262-3_21 id: cord-277054-eq4obbte author: Kaur, Manpreet title: Rabies DNA vaccine: No impact of MHC Class I and Class II targeting sequences on immune response and protection against lethal challenge date: 2009-03-26 words: 6906.0 sentences: 378.0 pages: flesch: 45.0 cache: ./cache/cord-277054-eq4obbte.txt txt: ./txt/cord-277054-eq4obbte.txt summary: The potency of modified DNA vaccines assessed by total antibody response, antibody isotypes, cytokine profile, neutralizing antibody titer and protection conferred against in vivo challenge; was enhanced in comparison to native unmodified vaccine, but the response elicited did not pertain to the type of target sequence and the directed arm of immunity. The ability of these DNA vaccines to elicit protective responses in immunized mice was assessed by intracerebral challenge with 20 LD 50 of virulent rabies virus CVS strain. In an effort to develop an optimal DNA vaccine against rabies virus, this study was aimed at evaluating the immune enhancement potential of different antigen targeting strategies to selectively improve responses mediated by CD8 + and CD4 + T lymphocytes and by antibodies, induced after intramuscular immunization with DNA plasmids. also reported that DNA vaccine encoding rabies virus glycoprotein lacking transmembrane domain though enhances antibody response but does not confer protection [35] . abstract: Rabies is progressive fatal encephalitis. WHO estimates 55,000 rabies deaths and more than 10 million PEP every year world-wide. A variety of cell-culture derived vaccines are available for prophylaxis against rabies. However, their high cost restricts their usage in developing countries, where such cases are most often encountered. This is driving the quest for newer vaccine formulations; DNA vaccines being most promising amongst them. Here, we explored strategies of antigen trafficking to various cellular compartments aiming at improving both humoral and cellular immunity. These strategies include use of signal sequences namely Tissue Plasminogen Activator (TPA), Ubiquitin (UQ) and Lysosomal-Associated Membrane Protein-1 (LAMP-1). TPA, LAMP-1 and their combination were aimed at enhancing the CD4(+) T cell and antibody response. In contrast, the UQ tag was utilized for enhancing CD8(+) response. The potency of modified DNA vaccines assessed by total antibody response, antibody isotypes, cytokine profile, neutralizing antibody titer and protection conferred against in vivo challenge; was enhanced in comparison to native unmodified vaccine, but the response elicited did not pertain to the type of target sequence and the directed arm of immunity. Interestingly, the DNA vaccines that had been designed to generate different type of immune responses yielded in effect similar response. In conclusion, our data indicate that the directing target sequence is not the exclusive deciding factor for type and extent of immune response elicited and emphasizes on the antigen dependence of immune enhancement strategies. url: https://www.sciencedirect.com/science/article/pii/S0264410X0900200X doi: 10.1016/j.vaccine.2009.01.128 id: cord-346308-9h2fk9qt author: Kaur, Rajwinder title: Microbiology of hospital wastewater date: 2020-05-01 words: 14673.0 sentences: 648.0 pages: flesch: 34.0 cache: ./cache/cord-346308-9h2fk9qt.txt txt: ./txt/cord-346308-9h2fk9qt.txt summary: The study of hospital wastewater (HWW) microbiology is important to understand the pollution load, growth of particular pathogenic microbes, shift and drift in microbial community, development and spread of antibiotic resistance in microbes, and subsequent change in treatment efficiencies. Within past years, pieces of evidence have shown mobilization of these resistance genes from the environment into pathogenic bacteria causing health risks to humans and animals and also, demonstrating a link between environmental and clinical resistance [123] . The HWW has been reported to have two overexpressed β-lactam-resistance genes (bla GES and bla OXA ) as compared with the water collected from other aquatic bodies, which could be correlated with antibiotic usage over the time in hospitals and discharge of the residues of antibiotics in the wastewater [176] . Urban wastewater treatment plants as hotspots for antibiotic resistant bacteria and genes spread into the environment: a review abstract: The study of hospital wastewater (HWW) microbiology is important to understand the pollution load, growth of particular pathogenic microbes, shift and drift in microbial community, development and spread of antibiotic resistance in microbes, and subsequent change in treatment efficiencies. This chapter investigates the potential microbes such as bacteria, viruses, fungi, and parasites present in HWW along with the diseases associated and methods of treatment used. Due to the indiscriminate release of antibiotics from hospitals, HWW serves as a hotspot for emergence of antibiotic-resistance genes (ARGs) and antibiotic-resistance bacteria. This chapter discusses the ARGs occurrence in HWW, their prevalence in the environment, the molecular tools used for identification, and different mechanisms of horizontal gene transfer. Thus better understanding of the microbiology of HWW could further help in development of advanced treatment technologies for effective removal of microbes and their bioproducts (toxins and infectious nucleic acid) from HWW and contaminated water. url: https://www.sciencedirect.com/science/article/pii/B9780128197226000043 doi: 10.1016/b978-0-12-819722-6.00004-3 id: cord-344749-omzhhr0k author: Kaya, Sariye Irem title: Electrochemical virus detections with nanobiosensors date: 2020-02-14 words: 8402.0 sentences: 508.0 pages: flesch: 37.0 cache: ./cache/cord-344749-omzhhr0k.txt txt: ./txt/cord-344749-omzhhr0k.txt summary: Cell culture-based virus isolation has been accepted as a "gold standard" in the detection and identification of viruses and is the technique by which all other test methods have been compared [35] . A novel method for dengue virus detection and antibody screening using a graphene-polymer based electrochemical biosensor Chitosan-carbon nanofiber modified single-use graphite electrodes developed for electrochemical detection of DNA hybridization related to hepatitis B virus A sensitive electrochemical biosensor for specific DNA sequence detection based on flower-like VS2, graphene and Au nanoparticles signal amplification Electrochemical DNA biosensor based on a tetrahedral nanostructure probe for the detection of avian influenza A (H7N9) virus Electrochemical DNA biosensor based on gold nanorods for detecting hepatitis B virus Electrochemical-DNA biosensor development based on a modified carbon electrode with gold nanoparticles for influenza a (H1N1) detection: effect of spacer Magnetic nanoparticle-based immunosensor for electrochemical detection of hepatitis B surface antigen abstract: Infectious diseases are caused from pathogens, which need a reliable and fast diagnosis. Today, expert personnel and centralized laboratories are needed to afford much time in diagnosing diseases caused from pathogens. Recent progress in electrochemical studies shows that biosensors are very simple, accurate, precise, and cheap at virus detection, for which researchers find great interest in this field. The clinical levels of these pathogens can be easily analyzed with proposed biosensors. Their working principle is based on affinity between antibody and antigen in body fluids. The progress still continues on these biosensors for accurate, rapid, reliable sensors in future. url: https://www.sciencedirect.com/science/article/pii/B9780128198704000177 doi: 10.1016/b978-0-12-819870-4.00017-7 id: cord-006049-sw1hki4r author: Keefe, Anthony D. title: Aptamers as therapeutics date: 2010 words: 9789.0 sentences: 510.0 pages: flesch: 42.0 cache: ./cache/cord-006049-sw1hki4r.txt txt: ./txt/cord-006049-sw1hki4r.txt summary: Nucleic acid aptamers can be selected from pools of random-sequence oligonucleotides to bind a wide range of biomedically relevant proteins with affinities and specificities that are comparable to antibodies. Although this is true for biological nucleic acids [1] [2] [3] [4] , it was only recently that a series of technological advances allowed the development of in vitro evolutionary methods for the discovery of additional, non-biological oligonucleotides that can bind to protein targets. Since the invention of the SELEX process around 1990 (REfS 5, 6) , researchers have identified high-affinity aptamers that target a broad cross-section of protein families including cytokines, proteases, kinases, cell-surface receptors and cell-adhesion molecules (TABLE 1) . In particular, the site-specific placement of functional groups for conjugation means that the modification of aptamers after the solid-phase step (for example with high molecular mass PEG 46 ) leads to products with discrete stoichiometries and defined chemical structures. Selection of a RNA aptamer that binds to human activated protein C and inhibits its protease function abstract: Nucleic acid aptamers can be selected from pools of random-sequence oligonucleotides to bind a wide range of biomedically relevant proteins with affinities and specificities that are comparable to antibodies. Aptamers exhibit significant advantages relative to protein therapeutics in terms of size, synthetic accessibility and modification by medicinal chemistry. Despite these properties, aptamers have been slow to reach the marketplace, with only one aptamer-based drug receiving approval so far. A series of aptamers currently in development may change how nucleic acid therapeutics are perceived. It is likely that in the future, aptamers will increasingly find use in concert with other therapeutic molecules and modalities. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097324/ doi: 10.1038/nrd3141 id: cord-001406-huz0tpmi author: Kersting, Sebastian title: Multiplex isothermal solid-phase recombinase polymerase amplification for the specific and fast DNA-based detection of three bacterial pathogens date: 2014-02-18 words: 4671.0 sentences: 255.0 pages: flesch: 41.0 cache: ./cache/cord-001406-huz0tpmi.txt txt: ./txt/cord-001406-huz0tpmi.txt summary: title: Multiplex isothermal solid-phase recombinase polymerase amplification for the specific and fast DNA-based detection of three bacterial pathogens The isothermal RPA was applied to amplify specific target sequences from the pathogens Neisseria gonorrhoeae, Salmonella enterica and methicillin-resistant Staphylococcus aureus (MRSA) using genomic DNA. A possible alternative to the PCR are isothermal nucleic acid amplification techniques which are carried out at a single temperature throughout the entire reaction using different mechanisms e.g. the strand-displacement activity of certain polymerases or the addition of further proteins used in the natural replication processes [4] . To our knowledge this highly multiplex pathogen detection is the first combination of isothermal RPA and microarray technology and offers new possibilities for the development of point-of-care testing devices for nucleic acids. (i) The excess of reverse primer in the reaction and the subsequent polymerase elongation leads to a preferred amplification of a single strand antisense DNA strand which can hybridize to the target specific probe structure on the surface. abstract: We report on the development of an on-chip RPA (recombinase polymerase amplification) with simultaneous multiplex isothermal amplification and detection on a solid surface. The isothermal RPA was applied to amplify specific target sequences from the pathogens Neisseria gonorrhoeae, Salmonella enterica and methicillin-resistant Staphylococcus aureus (MRSA) using genomic DNA. Additionally, a positive plasmid control was established as an internal control. The four targets were amplified simultaneously in a quadruplex reaction. The amplicon is labeled during on-chip RPA by reverse oligonucleotide primers coupled to a fluorophore. Both amplification and spatially resolved signal generation take place on immobilized forward primers bount to expoxy-silanized glass surfaces in a pump-driven hybridization chamber. The combination of microarray technology and sensitive isothermal nucleic acid amplification at 38 °C allows for a multiparameter analysis on a rather small area. The on-chip RPA was characterized in terms of reaction time, sensitivity and inhibitory conditions. A successful enzymatic reaction is completed in <20 min and results in detection limits of 10 colony-forming units for methicillin-resistant Staphylococcus aureus and Salmonella enterica and 100 colony-forming units for Neisseria gonorrhoeae. The results show this method to be useful with respect to point-of-care testing and to enable simplified and miniaturized nucleic acid-based diagnostics. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00604-014-1198-5) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4167443/ doi: 10.1007/s00604-014-1198-5 id: cord-288187-84oj3xtp author: Khan, Ali S. title: Forensic public health: epidemiological and microbiological investigations for biosecurity date: 2019-12-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Deliberate dissemination of a biological agent via several different routes presents the latest challenge to global public health security. Novel pathogens and transmission methods can easily be exploited to cause disease outbreaks. Advancements in molecular biology that make it possible to genetically modify, edit, or disrupt the genome of pathogens increase the disease risk of an accidental or intentional release of pathogens with pandemic potential. The occurrence of a disease at more than an endemic level may stimulate an investigation to determine the source of the disease, who has the disease, when it occurred, and how it spreads. When intentional release of pathogens is suspected, investigators have the additional task of attributing the outbreak not only to a pathogen but also to a human source. The deliberate nature of such dissemination may be obvious. However, some forms of bioterrorism may be more covert, requiring molecular methods to uncover. The field of microbial forensics emerged following the anthrax attack in the United States in 2001 to extend epidemiologic principles to aid in the investigation of bioterrorism incidents. Microbial forensics combines epidemiology with genomic and microbiologic methods, to identify, characterize, and ascribe the cause of an incident resulting from the intentional or unintentional release of a harmful pathogen. Unlike routine epidemiologic investigations, microbial forensic investigations are undertaken when there is a potential crime due to the release of a pathogen with disease-causing potential. The investigation is conducted to attribute cause to a source based on indisputable evidence and is used to support criminal charges against the perpetrator(s). However, because bioterrorism may be unannounced, the initial investigation will start the same as to any public health incident of concern. This chapter discusses how epidemiology integrated with laboratory science can be used to identify the source of diseases caused by microorganisms or toxins—especially for attribution purposes. url: https://www.sciencedirect.com/science/article/pii/B9780128153796000088 doi: 10.1016/b978-0-12-815379-6.00008-8 id: cord-333524-a6p6ma8r author: Khan, Pavana title: Isothermal SARS-CoV-2 Diagnostics: Tools for Enabling Distributed Pandemic Testing as a Means of Supporting Safe Reopenings date: 2020-09-23 words: 8841.0 sentences: 603.0 pages: flesch: 50.0 cache: ./cache/cord-333524-a6p6ma8r.txt txt: ./txt/cord-333524-a6p6ma8r.txt summary: 19 The current most common diagnostic method used to identify SARS-CoV-2 infection is a molecular technique for detecting viral RNA through nucleic acid amplification, RT-PCR. Nucleic acid amplification tests (NAATs) are the most common diagnostic tests used to detect pathogens, and many of the current SARS-CoV-2 detection techniques are primarily based on NAATs. 21 NAATs involve nucleic acid amplification, a process that initiates with a small quantity of starting nucleic acids and uses primers that target specific, short nucleic acid sequences in conjunction with enzymes to amplify or increase the quantity of starting nucleic acids. 34 This test incorporates a nested nucleic acid amplification technique showing higher sensitivity of detection than LAMP alone and conventional RT-PCR for minimally processed SARS-CoV-2 samples. 55 The technique first uses RT-LAMP for reverse transcription and isothermal amplification of viral RNA, and then employs the Cas12a enzyme to identify sequences of SARS-CoV-2, allowing cleavage of a reporter molecule ( Figure 5 ). abstract: [Image: see text] The COVID-19 pandemic, caused by the SARS-CoV-2 virus, poses grave threats to both the global economy and health. The predominant diagnostic screens in use for SARS-CoV-2 detection are molecular techniques such as nucleic acid amplification tests. In this Review, we compare current and emerging isothermal diagnostic methods for COVID-19. We outline the molecular and serological techniques currently being used to detect SARS-CoV-2 infection, past or present, in patients. We also discuss ongoing research on isothermal techniques, CRISPR-mediated detection assays, and point-of-care diagnostics that have potential for use in SARS-CoV-2 detection. Large-scale viral testing during a global pandemic presents unique challenges, chief among them the simultaneous need for testing supplies, durable equipment, and personnel in many regions worldwide, with each of these regions possessing testing needs that vary as the pandemic progresses. The low-cost isothermal technologies described in this Review provide a promising means by which to address these needs and meet the global need for testing of symptomatic individuals as well as provide a possible means for routine testing of asymptomatic individuals, providing a potential means of safely enabling reopenings and early monitoring of outbreaks. url: https://www.ncbi.nlm.nih.gov/pubmed/32966744/ doi: 10.1021/acssynbio.0c00359 id: cord-260042-cs0wp99n author: Khan, Samiullah title: Genes involved in mitochondrial biogenesis and function may not show synchronised responses to mitochondria in shell gland of laying chickens under infectious bronchitis virus challenge date: 2019-04-01 words: 6931.0 sentences: 362.0 pages: flesch: 47.0 cache: ./cache/cord-260042-cs0wp99n.txt txt: ./txt/cord-260042-cs0wp99n.txt summary: The present study aimed to: a) determine mitochondrial counts in the cells of oviduct segments in laying hens at different time-points of egg formation in relation to the requirement of energy for egg production during IBV challenge; b) to determine the expression of nuclear DNA encoded genes in the shell gland to gain insights into their responses to IBV infection and time-points of egg-shell formation. Based on the lack of significant differences in mitochondrial count in the cells between the challenged and control groups for the magnum and isthmus, we focused further on shell gland tissue and studied the expression level of genes involved in mitochondrial density, biogenesis and fission. The lack of any significant difference in the relative expression levels of all of the genes except SDHA, between the control and IBV T challenged groups, may indicate that mitochondrial function may have been enhanced and thus overall egg quality may not have been affected by fewer mitochondria in the shell gland cells of IBV T infected hens. abstract: BACKGROUND: Egg formation takes place in the oviduct of laying hens over a 24 h period. Infectious bronchitis virus (IBV) causes pathological lesions in the chicken oviduct. In the current study, mitochondrial counts were determined in three different segments of the oviduct during egg formation in laying chickens challenged with IBV T strain. Nuclear DNA encoded genes that are involved in mitochondrial biogenesis, fission and function were studied in the shell gland of the oviduct undergoing virus multiplication. RESULTS: In the shell gland, the mitochondrial count was significantly lower (P < 0.05) in the challenged group, compared with the control group. However, it did not vary in response to IBV challenge in the isthmus and magnum regions of the oviduct. The gene succinate dehydrogenase complex, subunit A, flavoprotein variant (SDHA) was down-regulated in the shell gland by IBV challenge (P < 0.05), while other genes being studied did not show responses to the challenge (P > 0.05). Differential expression of the genes was observed at different time-points of egg-shell formation. The expression levels of citrate synthase (CS), cytochrome C, somatic (CYC, S) and sodium-potassium adenosine triphosphatase (Na(+)-K(+)ATPase) genes were significantly higher, while those of SDHA and dynamin related protein 1 (Drp1) genes were significantly lower, at 15 h compared with 5 h following oviposition of the previous egg. The expression level of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) did not show significant change at different time-points. CONCLUSIONS: It was concluded that IBV T strain infection in laying hens reduced mitochondrial counts only in the shell gland region of the oviduct. The genes involved in mitochondrial biogenesis or function may not show synchronised responses to that of mitochondria in the shell gland of chickens under T strain of IBV challenge. url: https://doi.org/10.1186/s12860-019-0190-7 doi: 10.1186/s12860-019-0190-7 id: cord-102511-7zgd45fl author: Khodakov, Dmitriy title: Donut PCR: a rapid, portable, multiplexed, and quantitative DNA detection platform with single-nucleotide specificity date: 2020-05-05 words: 4279.0 sentences: 214.0 pages: flesch: 44.0 cache: ./cache/cord-102511-7zgd45fl.txt txt: ./txt/cord-102511-7zgd45fl.txt summary: Here, we present the Donut PCR platform that features high multiplexing, rapid turnaround times, single nucleotide discrimination, and precise quantitation of DNA targets in a portable, affordable, and battery-powered instrument using closed consumables that minimize contamination. Here, we present the Donut PCR platform for DNA detection that combines scalable and massive multiplexing, rapid turnaround times, single nucleotide discrimination, and precise quantitation in a portable, affordable, and batterypowered instrument using closed consumables that minimize contamination risks ( Table 1 ). By engineering a donut-shaped reaction chamber in the PCR chip, we remove most of the dead volume, and are able to achieve similar PCR specificity on human genomic DNA as the commercial Bio-Rad CFX96 instrument (Fig. 2a) . The Donut PCR platform presented here achieves rapid, sensitive, and quantitative detection of many DNA targets from a single sample using a closed, portable, and affordable instrument. abstract: Current platforms for molecular analysis of DNA markers are either limited in multiplexing (qPCR, isothermal amplification), turnaround time (microarrays, NGS), quantitation accuracy (isothermal amplification, microarray, nanopore sequencing), or specificity against single-nucleotide differences (microarrays, nanopore sequencing). Here, we present the Donut PCR platform that features high multiplexing, rapid turnaround times, single nucleotide discrimination, and precise quantitation of DNA targets in a portable, affordable, and battery-powered instrument using closed consumables that minimize contamination. We built a bread-board instrument prototype and three assays/chips to demonstrate the capabilities of Donut PCR: (1) a 9-plex mammal identification panel, (2) a 15-plex bacterial identification panel, and (3) a 30-plex human SNP genotyping assay. The limit of detection of the platform is under 10 genomic copies in under 30 minutes, and the quantitative dynamic range is at least 4 logs. We envision that this platform would be useful for a variety of applications where rapid and highly multiplexed nucleic acid detection is needed at the point of care. url: https://doi.org/10.1101/2020.04.24.058453 doi: 10.1101/2020.04.24.058453 id: cord-273716-vv3pyft4 author: Khosravi-Darani, Kianoush title: The role of high-resolution imaging in the evaluation of nanosystems for bioactive encapsulation and targeted nanotherapy date: 2007-07-03 words: 10230.0 sentences: 514.0 pages: flesch: 34.0 cache: ./cache/cord-273716-vv3pyft4.txt txt: ./txt/cord-273716-vv3pyft4.txt summary: This review will focus on nanoscale bioactive delivery and targeting mechanisms and the role of high-resolution imaging techniques in the evaluation and development of nanocarriers. Applications of nanotechnology in medicine are particularly promising and areas such as molecular imaging, disease diagnosis, bioactive encapsulation and targeted delivery at specific sites in the body are being intensively investigated and some products undergoing clinical trials (Moghimi et al., 2005; Shaffer, 2005; Wilkinson, 2003) . Usefulness of high-resolution scanning probe imaging in the study of lipidic gene transfer vectors and the interaction between liposomes and DNA molecules have recently been reviewed by Mozafari et al. Modern nanocarrier systems such as nanoliposomes, niosomes, solid lipid nanoparticles (Saupe and Rades, 2006) , as well as silicon-, carbon-and polymer-based nanocarriers play an important role in controlled delivery of the bioactive agents to the desired site of action, limiting the side effects at nontarget sites (Ruozi et al., 2007) . abstract: Nanotechnology has already started to significantly impact many industries and scientific fields including biotechnology, pharmaceutics, food technology and semiconductors. Nanotechnology-based tools and devices, including high-resolution imaging techniques, enable characterization and manipulation of materials at the nanolevel and further elucidate nanoscale phenomena and equip us with the ability to fabricate novel materials and structures. One of the most promising impacts of nanotechnology is in the area of nanotherapy. Employing nanosystems such as dendrimers, nanoliposomes, niosomes, nanotubes, emulsions and quantum dots, nanotherapy leads toward the concept of personalized medicine and the potential for early diagnoses coupled with efficient targeted therapy. The development of smart targeted nanocarriers that can deliver bioactives at a controlled rate directly to the designated cells and tissues will provide better efficacy and reduced side effects. Nanocarriers improve the solubility of bioactives and allow for the delivery of not only small-molecule drugs but also the delivery of nucleic acids and proteins. This review will focus on nanoscale bioactive delivery and targeting mechanisms and the role of high-resolution imaging techniques in the evaluation and development of nanocarriers. url: https://api.elsevier.com/content/article/pii/S0968432807001023 doi: 10.1016/j.micron.2007.06.009 id: cord-324811-yjwavea5 author: Kidgell, Claire title: Elucidating genetic diversity with oligonucleotide arrays date: 2005 words: 5561.0 sentences: 268.0 pages: flesch: 37.0 cache: ./cache/cord-324811-yjwavea5.txt txt: ./txt/cord-324811-yjwavea5.txt summary: Oligonucleotide microarrays, predominantly high-density oligonucleotide arrays, have emerged as the principal platforms for performing genome-wide diversity analysis. Since a number of complex issues still remain with high-throughput microarray-based SNP genotyping in humans, in the remainder of this review, we will discuss the application of high-density oligonucleotide arrays to elucidate genetic diversity, with particular focus on studies undertaken with Saccharomyces cerevisiae (Winzeler et al. falciparum (Clark 2002) , the genome-wide analysis facilitated by hybridization of genomic DNA to the A¡ymetrix microarray identi¢ed signi¢cant di¡erences in potential selection pressure across di¡erent gene families and locations within the chromosome (Volkman et al. Although SNPs and deletions can be readily identi¢ed using A¡ymetrix high-density arrays, more complex types of genetic diversity may also be determined using this platform. abstract: DNA microarrays, initially designed to measure gene expression levels, also provide an ideal platform for determining genetic diversity. Oligonucleotide microarrays, predominantly high-density oligonucleotide arrays, have emerged as the principal platforms for performing genome-wide diversity analysis. They have wide-ranging potential applications including comparative genomics, polymorphism discovery and genotyping. The identification of inheritable genetic markers also permits the analysis of quantitative traits, population studies and linkage analysis. In this review, we will discuss the application of oligonucleotide arrays, in particular high-density oligonucleotide arrays for elucidating genetic diversity and highlight some of the directions that the field may take. url: https://www.ncbi.nlm.nih.gov/pubmed/15868417/ doi: 10.1007/s10577-005-1503-6 id: cord-312517-b24zlaqt author: Kim, Denny title: The Brighton collaboration standardized template for collection of key information for benefit-risk assessment of nucleic acid (RNA and DNA) vaccines date: 2020-06-19 words: 1948.0 sentences: 98.0 pages: flesch: 44.0 cache: ./cache/cord-312517-b24zlaqt.txt txt: ./txt/cord-312517-b24zlaqt.txt summary: title: The Brighton collaboration standardized template for collection of key information for benefit-risk assessment of nucleic acid (RNA and DNA) vaccines The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of nucleic acid vaccines. The Brighton Collaboration formed the Viral Vector Vaccines Safety Working Group (V3SWG) in October 2008 to improve the ability of key stakeholders to anticipate potential safety issues and meaningfully assess or interpret safety data, thereby facilitating greater public acceptance when viral vector vaccines are licensed [2] . When completing information on adverse effects in Section 8, please provide as many details as possible based on the Brighton Collaboration Guidelines for collection, analysis and presentation of vaccine safety data in pre-and post-licensure clinical studies [13] . abstract: Nucleic acid (DNA and RNA) vaccines are among the most advanced vaccines for COVID-19 under development. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of nucleic acid vaccines. This will facilitate the assessment by key stakeholders of potential safety issues and understanding of overall benefit-risk. The structured assessment provided by the template can also help improve communication and public acceptance of licensed nucleic acid vaccines. url: https://api.elsevier.com/content/article/pii/S0264410X20307891 doi: 10.1016/j.vaccine.2020.06.017 id: cord-023369-xwclh6ih author: Kim, Faith title: Human Herpesvirus-6 Meningitis in a Premature Infant with Fevers: A Case and Literature Review date: 2020-04-18 words: 4890.0 sentences: 219.0 pages: flesch: 43.0 cache: ./cache/cord-023369-xwclh6ih.txt txt: ./txt/cord-023369-xwclh6ih.txt summary: They both had IgM antibodies in the acute phase and PCR detection of HHV-6 DNA in the serum at high copy numbers suggestive of a primary infection despite presence of preexisting maternal antibodies, which the authors isolated from both mothers. 18 Infants with congenital infection due to ciHHV6 had evidence of high viral loads in the cord blood and detection of HHV-6 DNA in hair follicles in both the infants and at least one parent. In summary, we present a case of a premature infant with multiple anomalies who acquired acute HHV-6 viral meningitis in the setting of intermittent high fevers, elevated inflammatory markers, and diagnostic testing from her CSF that confirmed the diagnosis. Transplacental human herpesvirus 6 (HHV-6) congenital infection caused by maternal chromosomally integrated virus abstract: Human herpesvirus-6 (HHV-6) is a common virus that can cause nearly universal infection in infancy and early childhood. It typically manifests as an acute febrile illness. We describe a case of a premature infant with congenital hydrocephalus secondary to aqueductal stenosis with a ventriculoperitoneal shunt in place who developed intermittent fevers while she was admitted to the neonatal intensive care unit. She was ultimately diagnosed with acute HHV-6 meningitis. In addition to this report, we present a literature review regarding this virus’s potential modes of transmission and forms of clinical presentation in the neonatal period. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169356/ doi: 10.1177/1179547620912952 id: cord-279503-w4tn03w0 author: Kim, Hanbi title: Development of Label-Free Colorimetric Assay for MERS-CoV Using Gold Nanoparticles date: 2019-05-07 words: 3541.0 sentences: 185.0 pages: flesch: 49.0 cache: ./cache/cord-279503-w4tn03w0.txt txt: ./txt/cord-279503-w4tn03w0.txt summary: In this study, we propose a colorimetric assay based on an extended form of double-stranded DNA (dsDNA) self-assembly shielded gold nanoparticles (AuNPs) under positive electrolyte (e.g., 0.1 M MgCl(2)) for detection of Middle East respiratory syndrome coronavirus (MERS-CoV). This assay could be highly reliable for MERS-CoV diagnosis as we have followed WHO updated recommendations for infectious disease laboratory testing, which targets the two regions on MERS-CoV considered for potential preclinical screening and high sensitivity 20 The developed assay platform was able to detect the target DNA through optical properties of the gold nanoparticles such as color changes with the naked eye and spectral shifts on UV− vis wavelength. We proposed a colorimetric assay using disulfide bonds formed by hybridizing with thiolated probes and a target; this method inhibited the aggregation of AuNPs by salt and limits the color change for diagnosis of MERS. abstract: [Image: see text] Worldwide outbreaks of infectious diseases necessitate the development of rapid and accurate diagnostic methods. Colorimetric assays are a representative tool to simply identify the target molecules in specimens through color changes of an indicator (e.g., nanosized metallic particle, and dye molecules). The detection method is used to confirm the presence of biomarkers visually and measure absorbance of the colored compounds at a specific wavelength. In this study, we propose a colorimetric assay based on an extended form of double-stranded DNA (dsDNA) self-assembly shielded gold nanoparticles (AuNPs) under positive electrolyte (e.g., 0.1 M MgCl(2)) for detection of Middle East respiratory syndrome coronavirus (MERS-CoV). This platform is able to verify the existence of viral molecules through a localized surface plasmon resonance (LSPR) shift and color changes of AuNPs in the UV–vis wavelength range. We designed a pair of thiol-modified probes at either the 5′ end or 3′ end to organize complementary base pairs with upstream of the E protein gene (upE) and open reading frames (ORF) 1a on MERS-CoV. The dsDNA of the target and probes forms a disulfide-induced long self-assembled complex, which protects AuNPs from salt-induced aggregation and transition of optical properties. This colorimetric assay could discriminate down to 1 pmol/μL of 30 bp MERS-CoV and further be adapted for convenient on-site detection of other infectious diseases, especially in resource-limited settings. url: https://www.ncbi.nlm.nih.gov/pubmed/31062580/ doi: 10.1021/acssensors.9b00175 id: cord-253826-63dgq551 author: Kim, Jisung title: State of diagnosing infectious pathogens using colloidal nanomaterials date: 2017-08-17 words: 10488.0 sentences: 535.0 pages: flesch: 39.0 cache: ./cache/cord-253826-63dgq551.txt txt: ./txt/cord-253826-63dgq551.txt summary: This review article discusses current advances of diagnostic systems using colloidal nanomaterials (e.g., gold nanoparticles, quantum dots, magnetic nanoparticles) for identifying and differentiating infectious pathogens. Similarly, Raman dye labeled oligonucleotide probes have been conjugated to GNPs in a scanometric assay to generate spectroscopic codes for individual target DNA and demonstrate a multiplexed detection (Fig. 6C ). While this technology is still early in development, these results show that thermal contrast may enhance the analytical sensitivity to enable detection of infectious pathogens, which are normally done with more complex molecular diagnostics. For detection of nucleic acids, none of the nanodiagnostic approaches were as sensitive as PCR (zM), except for the Mirkin''s bio-barcode assay that utilized magnetic separation, and two levels of signal amplification. As we discussed in this review article, nanoparticles have been exploited to improve the analytical sensitivity of diagnostic assays, provide various readout signals, simultaneously detect multiple targets, and simplify diagnostic procedures. abstract: Infectious diseases are a major global threat that accounts for one of the leading causes of global mortality and morbidity. Prompt diagnosis is a crucial first step in the management of infectious threats, which aims to quarantine infected patients to avoid contacts with healthy individuals and deliver effective treatments prior to further spread of diseases. This review article discusses current advances of diagnostic systems using colloidal nanomaterials (e.g., gold nanoparticles, quantum dots, magnetic nanoparticles) for identifying and differentiating infectious pathogens. The challenges involved in the clinical translation of these emerging nanotechnology based diagnostic devices will also be discussed. url: https://www.ncbi.nlm.nih.gov/pubmed/28898761/ doi: 10.1016/j.biomaterials.2017.08.013 id: cord-000452-1gd006zy author: Kim, Y. C. title: Delivery Systems for Intradermal Vaccination date: 2011-04-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Intradermal (ID) vaccination can offer improved immunity and simpler logistics of delivery, but its use in medicine is limited by the need for simple, reliable methods of ID delivery. ID injection by the Mantoux technique requires special training and may not reliably target skin, but is nonetheless used currently for BCG and rabies vaccination. Scarification using a bifurcated needle was extensively used for smallpox eradication, but provides variable and inefficient delivery into the skin. Recently, ID vaccination has been simplified by introduction of a simple-to-use hollow microneedle that has been approved for ID injection of influenza vaccine in Europe. Various designs of hollow microneedles have been studied preclinically and in humans. Vaccines can also be injected into skin using needle-free devices, such as jet injection, which is receiving renewed clinical attention for ID vaccination. Projectile delivery using powder and gold particles (i.e., gene gun) have also been used clinically for ID vaccination. Building off the scarification approach, a number of preclinical studies have examined solid microneedle patches for use with vaccine coated onto metal microneedles, encapsulated within dissolving microneedles or added topically to skin after microneedle pretreatment, as well as adapting tattoo guns for ID vaccination. Finally, technologies designed to increase skin permeability in combination with a vaccine patch have been studied through the use of skin abrasion, ultrasound, electroporation, chemical enhancers, and thermal ablation. The prospects for bringing ID vaccination into more widespread clinical practice are encouraging, given the large number of technologies for ID delivery under development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173582/ doi: 10.1007/82_2011_123 id: cord-102359-k1xxz4hc author: Klotsa, Daphne title: Electronic Transport in DNA date: 2005-04-04 words: 6669.0 sentences: 412.0 pages: flesch: 62.0 cache: ./cache/cord-102359-k1xxz4hc.txt txt: ./txt/cord-102359-k1xxz4hc.txt summary: In most models of electronic transport [13, 60] it has been assumed that the transmission channels are along the long axis of the DNA molecule [61] and that the conduction path is due to π-orbital overlap between consecutive bases [52] ; density-functional calculations [37] have shown that the bases, especially Guanine, are rich in π-orbitals. The main advantage of both methods is that they work reliably (i) for short DNA strands ranging from 13 (DFT studies [37] ) base pairs up to 30 base pairs length which are being used in the nanoscopic transport measurements [15] as well as (ii) for somewhat longer DNA sequences as modelled in the electron transfer results and (iii) even for complete DNA sequences which contain, e.g. for human chromosomes up to 245 million base pairs [2] . The fishbone and ladder models studied in the present paper give qualitatively similar results, i.e. a gap in the DOS on the order of the hopping energies to the backbone, extended states for periodic DNA sequences and localised states for any non-zero disorder strength. abstract: We study the electronic properties of DNA by way of a tight-binding model applied to four particular DNA sequences. The charge transfer properties are presented in terms of localisation lengths, crudely speaking the length over which electrons travel. Various types of disorder, including random potentials, are employed to account for different real environments. We have performed calculations on poly(dG)-poly(dC), telomeric-DNA, random-ATGC DNA and lambda-DNA. We find that random and lambda-DNA have localisation lengths allowing for electron motion among a few dozen base pairs only. A novel enhancement of localisation lengths is observed at particular energies for an increasing binary backbone disorder. We comment on the possible biological relevance of sequence dependent charge transfer in DNA. url: https://arxiv.org/pdf/q-bio/0504004v1.pdf doi: 10.1529/biophysj.105.064014 id: cord-333914-c150ki1n author: Koba, Ryota title: Identification and characterization of a novel bat polyomavirus in Japan date: 2020-08-20 words: 1685.0 sentences: 104.0 pages: flesch: 54.0 cache: ./cache/cord-333914-c150ki1n.txt txt: ./txt/cord-333914-c150ki1n.txt summary: A novel polyomavirus (PyV) was identified in the intestinal contents of Japanese eastern bent-wing bats (Miniopterus fuliginosus) via metagenomic analysis. To determine the complete viral genome of these PyV-like sequences, PCR was performed using LA Taq DNA polymerase (Takara Bio, Otsu, Japan) in accordance with the manufacturer''s instructions. A noncoding regulatory region (NCCR) was located between the start of the early region and that of the late region, in line with previous findings for bat PyVs (Fig. 1a and Supplementary Table 1) [9] [10] [11] [12] . MfPyV VP1 displayed less than 72% nucleotide sequence identity with other bat PyVs (Supplementary Table 2 ). MfPyV TAg sequences contained features known to be conserved in TAgs of other bat PyVs, including the highly conserved DnaJ domain (HPDKGG), a retinoblastoma (Rb)-binding motif (LYCNE), and several functional motifs (Supplementary Fig. 2 ). In conclusion, we detected a novel PyV genome sequence in Japanese bats. abstract: A novel polyomavirus (PyV) was identified in the intestinal contents of Japanese eastern bent-wing bats (Miniopterus fuliginosus) via metagenomic analysis. We subsequently sequenced the full genome of the virus, which has been tentatively named Miniopterus fuliginosus polyomavirus (MfPyV). The nucleotide sequence identity of the genome with those of other bat PyVs was less than 80%. Phylogenetic analysis revealed that MfPyV belonged to the same cluster as PyVs detected in Miniopterus schreibersii. This study has identified the presence of a novel PyV in Japanese bats and provided genetic information about the virus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11262-020-01789-7) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/32816186/ doi: 10.1007/s11262-020-01789-7 id: cord-007755-o2r8ktie author: Kokoszka, Malgorzata E. title: Mapping Protein–Protein Interactions with Phage-Displayed Combinatorial Peptide Libraries and Alanine Scanning date: 2014-10-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: One avenue for inferring the function of a protein is to learn what proteins it may bind to in the cell. Among the various methodologies, one way for doing so is to affinity select peptide ligands from a phage-displayed combinatorial peptide library and then to examine if the proteins that carry such peptide sequences interact with the target protein in the cell. With the protocols described in this chapter, a laboratory with skills in microbiology, molecular biology, and protein biochemistry can readily identify peptides in the library that bind selectively, and with micromolar affinity, to a given target protein on the time scale of 2 months. To illustrate this approach, we use a library of bacteriophage M13 particles, which display 12-mer combinatorial peptides, to affinity select different peptide ligands for two different targets, the SH3 domain of the human Lyn protein tyrosine kinase and a segment of the yeast serine/threonine protein kinase Cbk1. The binding properties of the selected peptide ligands are then dissected by sequence alignment, Kunkel mutagenesis, and alanine scanning. Finally, the peptide ligands can be used to predict cellular interacting proteins and serve as the starting point for drug discovery. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122165/ doi: 10.1007/978-1-4939-2020-4_12 id: cord-258363-gmgbus9i author: Kolla, Venkatadri title: Synthesis of a bacteriophage MB78 late protein by novel ribosomal frameshifting() date: 2000-08-22 words: 4578.0 sentences: 279.0 pages: flesch: 63.0 cache: ./cache/cord-258363-gmgbus9i.txt txt: ./txt/cord-258363-gmgbus9i.txt summary: In vitro transcription-translation yields a major protein that migrates as 28 kDa, whereas in vivo expression using pET expression vectors yields two equally expressed proteins of molecular sizes 28 and 26 kDa. A putative slippery sequence TTTAAAG and a pseudoknot structure, two essential cis elements required for the classical ribosomal frameshifting, are identified in the reading frame. The chelating agent EDTA is an effective It is now known that two proteins can be expressed inhibitor of its DNA synthesis, whereas EGTA and from a single open reading frame through ''ribosomal orthophenanthroline have practically no effect on the frameshifting''. During the process of ''ribosomal frameshifting'', two or more proteins can result, starting from a single initiation codon Abbreviations: bp, base pairs; IPTG, isopropyl b-thiogalactosidase; ( Farabaugh and Vimaladithan, 1998 direction (+1 frame shift) has been described in the k The nucleotide sequence reported in this paper has been deposited yeast retrotransposon TY (Belcourt and Farabaugh, in the EMBL/GenBank database under Accession No. X87092. abstract: MB78 is a virulent phage of Salmonella typhimurium that possesses a number of interesting features, making it a suitable organism to study the regulation of gene expression. A detailed physical map of this phage genome has been constructed and is being extensively studied at the molecular level. Here, we demonstrate the expression of two late proteins of bacteriophage MB78 derived from the same gene as a result of possible ribosomal frameshifting. In vitro transcription-translation yields a major protein that migrates as 28 kDa, whereas in vivo expression using pET expression vectors yields two equally expressed proteins of molecular sizes 28 and 26 kDa. A putative slippery sequence TTTAAAG and a pseudoknot structure, two essential cis elements required for the classical ribosomal frameshifting, are identified in the reading frame. Mutations created at the slippery sequence resulted in a single 28 kDa protein and completely abolished the expression of 26 kDa protein. Thus, we have produced the first evidence that ribosomal frameshifting occurs in bacteriophage MB78 of Salmonella typhimurium. url: https://www.sciencedirect.com/science/article/pii/S037811190000264X doi: 10.1016/s0378-1119(00)00264-x id: cord-284582-xwedgllw author: Korabecna, M. title: Cell-free DNA in plasma as an essential immune system regulator date: 2020-10-15 words: 5714.0 sentences: 306.0 pages: flesch: 46.0 cache: ./cache/cord-284582-xwedgllw.txt txt: ./txt/cord-284582-xwedgllw.txt summary: These expression profiles provide evidence that the presence of cfDNA and its clearance in plasma of healthy individuals regulate fundamental mechanisms of the inflammation process and tissue homeostasis. We used native human plasma samples obtained from healthy volunteers with no animal serum addition to the cultivation medium in order to avoid the presence of uncharacterized animal cfDNA and DNases in the experiments. We used the validation phase results to perform a direct comparison of signaling pathways activated in cells as a consequence of their treatment with NP or TP samples (Table 1a , b) using the database Reactome. The changes in expression profiles of selected validated genes were detectable after the decrease of cfDNA levels to 69.10% of its original native concentration as the result of endogenous DNAse I activity ( Supplementary Fig. 1 ). However, the cells treated with identical plasma samples with degraded cfDNA directly activate IIR with elevated production of mRNA for interleukin 8 at the transcriptomic level. abstract: The cell-free DNA (cfDNA) is always present in plasma, and it is biomarker of growing interest in prenatal diagnostics as well as in oncology and transplantology for therapy efficiency monitoring. But does this cfDNA have a physiological role? Here we show that cfDNA presence and clearance in plasma of healthy individuals plays an indispensable role in immune system regulation. We exposed THP1 cells to healthy individuals’ plasma with (NP) and without (TP) cfDNA. In cells treated with NP, we found elevated expression of genes whose products maintain immune system homeostasis. Exposure of cells to TP triggered an innate immune response (IIR), documented particularly by elevated expression of pro-inflammatory interleukin 8. The results of mass spectrometry showed a higher abundance of proteins associated with IIR activation due to the regulation of complement cascade in cells cultivated with TP. These expression profiles provide evidence that the presence of cfDNA and its clearance in plasma of healthy individuals regulate fundamental mechanisms of the inflammation process and tissue homeostasis. The detailed understanding how neutrophil extracellular traps and their naturally occurring degradation products affect the performance of immune system is of crucial interest for future medical applications. url: https://doi.org/10.1038/s41598-020-74288-2 doi: 10.1038/s41598-020-74288-2 id: cord-331718-rjggiklf author: Kubota, Takeo title: Epigenetic Effect of Environmental Factors on Autism Spectrum Disorders date: 2016-05-14 words: 4770.0 sentences: 243.0 pages: flesch: 33.0 cache: ./cache/cord-331718-rjggiklf.txt txt: ./txt/cord-331718-rjggiklf.txt summary: Epigenetics, an essential mechanism for gene regulation based on chemical modifications of DNA and histone proteins, is also involved in congenital ASDs. It was recently demonstrated that environmental factors, such as endocrine disrupting chemicals and mental stress in early life, can change epigenetic status and gene expression, and can cause ASDs. Moreover, environmentally induced epigenetic changes are not erased during gametogenesis and are transmitted to subsequent generations, leading to changes in behavior phenotypes. These results suggest that close interaction between neuronal molecules and epigenetic molecules is important for normal brain development and failure of this interaction is potentially associated with ASDs. In this review, we introduce congenital epigenetic disorders with ASD-like phenotypes and environmental factors that affect epigenetic regulation of neuronal genes, and discuss transgenerational epigenetic inheritance and therapeutic strategies for ASDs taking advantage of use of the epigenetic reversibility. Rett syndrome (RTT) is a representative ASD characterized by repetitive and stereotypic hand movements, seizures, gait ataxia and autism [35] and is caused by mutations in the gene that encode methyl-CpG-binding protein 2 (MeCP2), which is associated with chromatin remodeling [36] . abstract: Both environmental factors and genetic factors are involved in the pathogenesis of autism spectrum disorders (ASDs). Epigenetics, an essential mechanism for gene regulation based on chemical modifications of DNA and histone proteins, is also involved in congenital ASDs. It was recently demonstrated that environmental factors, such as endocrine disrupting chemicals and mental stress in early life, can change epigenetic status and gene expression, and can cause ASDs. Moreover, environmentally induced epigenetic changes are not erased during gametogenesis and are transmitted to subsequent generations, leading to changes in behavior phenotypes. However, epigenetics has a reversible nature since it is based on the addition or removal of chemical residues, and thus the original epigenetic status may be restored. Indeed, several antidepressants and anticonvulsants used for mental disorders including ASDs restore the epigenetic state and gene expression. Therefore, further epigenetic understanding of ASDs is important for the development of new drugs that take advantages of epigenetic reversibility. url: https://www.ncbi.nlm.nih.gov/pubmed/27187441/ doi: 10.3390/ijerph13050504 id: cord-283880-lrrkuist author: Kumar, Arvind title: Evolution of selective-sequencing approaches for virus discovery and virome analysis date: 2017-07-15 words: 5934.0 sentences: 286.0 pages: flesch: 38.0 cache: ./cache/cord-283880-lrrkuist.txt txt: ./txt/cord-283880-lrrkuist.txt summary: Use of sequence dependent (i.e; generic PCR assays and microarray) and sequence independent (i.e; single primer amplification (SISPA) and random priming) approaches for nucleic acid amplification combined with Sanger sequencing or HTS allowed the rapid identification of new viruses after 1980 (Bishop-Lilly et al., 2010; Chang et al., 1994; Day et al., 2010; Grard et al., 2012; Kapoor et al., 2015; Ladner et al., 2016; Linnen et al., 1996; Matsui et al., 1991; Mokili et al., 2012; Muerhoff et al., 1997; Nichol et al., 1993; Qin et al., 2014; Quan et al., 2010; Simons et al., 1995b) (Fig. 1) . For the virome analysis of clinical samples with an abundance of host cells, like blood or tissues, pre-extraction based enrichment is not appropriate as the virus genome itself can be present in its non-capsidated or transcribed form. In positive selection methods, samples are enriched for viral nucleic acids directly using probes targeting the viruses like in PCR assays, microarray or virus capture (in solution based hybridization) approaches. abstract: Abstract Recent advances in sequencing technologies have transformed the field of virus discovery and virome analysis. Once mostly confined to the traditional Sanger sequencing based individual virus discovery, is now entirely replaced by high throughput sequencing (HTS) based virus metagenomics that can be used to characterize the nature and composition of entire viromes. To better harness the potential of HTS for the study of viromes, sample preparation methodologies use different approaches to exclude amplification of non-viral components that can overshadow low-titer viruses. These virus-sequence enrichment approaches mostly focus on the sample preparation methods, like enzymatic digestion of non-viral nucleic acids and size exclusion of non-viral constituents by column filtration, ultrafiltration or density gradient centrifugation. However, recently a new approach of virus-sequence enrichment called virome-capture sequencing, focused on the amplification or HTS library preparation stage, was developed to increase the ability of virome characterization. This new approach has the potential to further transform the field of virus discovery and virome analysis, but its technical complexity and sequence-dependence warrants further improvements. In this review we discuss the different methods, their applications and evolution, for selective sequencing based virome analysis and also propose refinements needed to harness the full potential of HTS for virome analysis. url: https://www.sciencedirect.com/science/article/pii/S0168170216305986 doi: 10.1016/j.virusres.2017.06.005 id: cord-018046-jzoykn0y author: Kumar, Sanjay title: Fabrication of Nanostructures with Bottom-up Approach and Their Utility in Diagnostics, Therapeutics, and Others date: 2017-11-18 words: 7643.0 sentences: 456.0 pages: flesch: 42.0 cache: ./cache/cord-018046-jzoykn0y.txt txt: ./txt/cord-018046-jzoykn0y.txt summary: Nanofabrication has been a critical area of research in the last two decades and has found wide-ranging application in improvising material properties, sensitive clinical diagnostics, and detection, improving the efficiency of electron transport processes within materials, generating high energy densities leading to pulse power, novel therapeutic mechanisms, environmental remediation and control. It also covers the recent advancements in fabrication of ZnO-based nanostructures, DNA-based nanostructures, polymer-based nanostructures, and metal-based nanostructures and their widespread applications in the field of diagnostics, therapeutics, and others. Some of the methods used in bottom-up approach include plasma arcing, chemical vapor deposition process, metal organic decomposition, laser pyrolysis, molecular beam epitaxy, solgel method, wet synthesis, and self-assembly processes. Several fabrication techniques have been described in the literature for fabrication of ZnO nanostructures, such as sputtering, laser ablation, molecular beam epitaxy, physical vapor deposition, thermal evaporation, electrochemical deposition, template-based synthesis, and solgel methods (Yao et al. abstract: Nanofabrication has been a critical area of research in the last two decades and has found wide-ranging application in improvising material properties, sensitive clinical diagnostics, and detection, improving the efficiency of electron transport processes within materials, generating high energy densities leading to pulse power, novel therapeutic mechanisms, environmental remediation and control. The continued improvements in the various fabrication technologies have led to realization of highly sensitive nanostructure-based devices. The fabrication of nanostructures is in principle carried out primarily using top-down or bottom-up approaches. This chapter summarizes the important bottom-up nanofabrication processes for realizing nanostructures and also highlights the recent research conducted in the domain of therapeutics and diagnostics. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122830/ doi: 10.1007/978-981-10-7751-7_8 id: cord-018737-1h84yi2i author: Kumar, Sudeep title: Live-Attenuated Bacterial Vectors for Delivery of Mucosal Vaccines, DNA Vaccines, and Cancer Immunotherapy date: 2019-01-10 words: 10719.0 sentences: 586.0 pages: flesch: 34.0 cache: ./cache/cord-018737-1h84yi2i.txt txt: ./txt/cord-018737-1h84yi2i.txt summary: Activation of antigen-presenting cells by live-attenuated bacterial vectors leads to adaptive immune response: Various pathogen-associated molecular patterns present in the liveattenuated bacterial vectors interact with Toll-like receptors expressed on the surface or in endosomal membranes. Live-attenuated microbes exhibit superior ability to deliver vaccine antigens to the mucosal immune system, as many of them are derived from natural mucosal pathogens, including Salmonella spp., Lm, E. Adaptation of the endogenous Salmonella enterica serovar Typhi clyA-encoded hemolysin for antigen export enhances the immunogenicity of anthrax protective antigen domain 4 expressed by the attenuated live-vector vaccine strain CVD 908-htrA Immune responses to recombinant pneumococcal PspA antigen delivered by live attenuated Salmonella enterica serovar typhimurium vaccine Regulated delayed expression of rfc enhances the immunogenicity and protective efficacy of a heterologous antigen delivered by live attenuated Salmonella enterica vaccines Attenuated deltaguaBA Salmonella typhi vaccine strain CVD 915 as a live vector utilizing prokaryotic or eukaryotic expression systems to deliver foreign antigens and elicit immune responses abstract: Vaccines save millions of lives each year from various life-threatening infectious diseases, and there are more than 20 vaccines currently licensed for human use worldwide. Moreover, in recent decades immunotherapy has become the mainstream therapy, which highlights the tremendous potential of immune response mediators, including vaccines for prevention and treatment of various forms of cancer. However, despite the tremendous advances in microbiology and immunology, there are several vaccine preventable diseases which still lack effective vaccines. Classically, weakened forms (attenuated) of pathogenic microbes were used as vaccines. Although the attenuated microbes induce effective immune response, a significant risk of reversion to pathogenic forms remains. While in the twenty-first century, with the advent of genetic engineering, microbes can be tailored with desired properties. In this review, I have focused on the use of genetically modified bacteria for the delivery of vaccine antigens. More specifically, the live-attenuated bacteria, derived from pathogenic bacteria, possess many features that make them highly suitable vectors for the delivery of vaccine antigens. Bacteria can theoretically express any heterologous gene or can deliver mammalian expression vectors harboring vaccine antigens (DNA vaccines). These properties of live-attenuated microbes are being harnessed to make vaccines against several infectious and noninfectious diseases. In this regard, I have described the desired features of live-attenuated bacterial vectors and the mechanisms of immune responses manifested by live-attenuated bacterial vectors. Interestingly anaerobic bacteria are naturally attracted to tumors, which make them suitable vehicles to deliver tumor-associated antigens thus I have discussed important studies investigating the role of bacterial vectors in immunotherapy. Finally, I have provided important discussion on novel approaches for improvement and tailoring of live-attenuated bacterial vectors for the generation of desired immune responses. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123696/ doi: 10.1007/978-3-030-01881-8_2 id: cord-002966-9z350ucm author: Kwasna, Dominika title: Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability date: 2018-04-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Deubiquitinating enzymes (DUBs) are important regulators of ubiquitin signaling. Here, we report the discovery of deubiquitinating activity in ZUFSP/C6orf113. High-resolution crystal structures of ZUFSP in complex with ubiquitin reveal several distinctive features of ubiquitin recognition and catalysis. Our analyses reveal that ZUFSP is a novel DUB with no homology to any known DUBs, leading us to classify ZUFSP as the seventh DUB family. Intriguingly, the minimal catalytic domain does not cleave polyubiquitin. We identify two ubiquitin binding domains in ZUFSP: a ZHA (ZUFSP helical arm) that binds to the distal ubiquitin and an atypical UBZ domain in ZUFSP that binds to polyubiquitin. Importantly, both domains are essential for ZUFSP to selectively cleave K63-linked polyubiquitin. We show that ZUFSP localizes to DNA lesions, where it plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5896202/ doi: 10.1016/j.molcel.2018.02.023 id: cord-257046-er5orx8s author: Ladekjær-Mikkelsen, A.-S title: Reproduction of postweaning multisystemic wasting syndrome (PMWS) in immunostimulated and non-immunostimulated 3-week-old piglets experimentally infected with porcine circovirus type 2 (PCV2) date: 2002-10-22 words: 6752.0 sentences: 360.0 pages: flesch: 49.0 cache: ./cache/cord-257046-er5orx8s.txt txt: ./txt/cord-257046-er5orx8s.txt summary: title: Reproduction of postweaning multisystemic wasting syndrome (PMWS) in immunostimulated and non-immunostimulated 3-week-old piglets experimentally infected with porcine circovirus type 2 (PCV2) Reproduction of postweaning multisystemic wasting syndrome (PMWS) in immunostimulated and non-immunostimulated 3-week-old piglets experimentally infected with porcine circovirus type 2 (PCV2) PCV1 is considered to be a non-pathogenic virus (Tischer et al., 1986; Allan et al., 1995) , whereas infection of swine with PCV2 is causally associated with development of postweaning multisystemic wasting syndrome (PMWS) in weaned 5-to 12-week-old piglets (Allan et al., 1998; Ellis et al., 1998) . In contrast, dual infection with PCV2 and porcine parvovirus (PPV) or porcine reproductive and respiratory syndrome virus (PRRSV) potentiates the replication and distribution of PCV2 and induces clinical disease in addition to more severe histopathological lesions Kennedy et al., 2000; Krakowka et al., 2000; Harms et al., 2001) . abstract: Postweaning multisystemic wasting syndrome (PMWS) in swine is causally associated with the newly recognised pathogen, porcine circovirus type 2 (PCV2). In this study, 3-week-old SPF PCV2-seronegative piglets were inoculated intranasally with PCV2. The effect of immunostimulation on the induction of PMWS was investigated by immunisation with keyhole limpet hemocyanin (KLH) emulsified in incomplete Freunds adjuvant. The study was terminated 5 weeks after inoculation. While disease was not observed in the age-matched controls, two out of five non-immunised PCV2-infected piglets died on postinoculation day (PID) 21, and one was euthanized on PID 25 in moribund condition. These animals had appeared lethargic with persistent fever from PID 12 onwards. The euthanized pig appeared smaller than littermates and suffered from jaundice. At postmortem examination, gastric ulceration, icterus, and liver and thymus atrophy were observed. Furthermore, histological lesions of degenerating hepatocytes and hepatitis in combination with lymphoid depletion and syncytial cells in lymph nodes were consistent with the diagnosis of PMWS. One out of five immunostimulated PCV2-infected piglets was euthanized on PID 22 with convulsions after a period with wasting. This pig was lethargic from PID 14 onwards with persistent fever from PID 8 and transient dyspnoea. No differences in clinical signs, gross pathologic or histological findings were observed for the remaining non-immunostimulated and immunostimulated PCV2-infected piglets. All 10 PCV2-inoculated piglets seroconverted to PCV2 within 14 days after inoculation. By virus isolation, quantitative polymerase chain reaction (Q-PCR), and immunostaining of cryostat sections, it was demonstrated that lymphoid tissue contained abundant PCV2 antigen. Viral DNA load in serum samples was assessed by Q-PCR. All four PMWS-affected piglets had high levels of PCV2 DNA in serum, suggesting that there was a correlation between high levels of viral DNA in serum and the development of PMWS. In conclusion, infection with PCV2 caused PMWS in SPF piglets, however, the immunostimulation did not seem to play a critical role. url: https://www.ncbi.nlm.nih.gov/pubmed/12243888/ doi: 10.1016/s0378-1135(02)00174-8 id: cord-351295-4toxlskr author: Lanave, Gianvito title: Identification of hepadnavirus in the sera of cats date: 2019-07-23 words: 2665.0 sentences: 159.0 pages: flesch: 48.0 cache: ./cache/cord-351295-4toxlskr.txt txt: ./txt/cord-351295-4toxlskr.txt summary: Also, in 7/10 animals with suspected hepatic disease, virus load was >10(4) genome copies per mL, i.e. above the threshold considered at risk of active hepatitis and liver damage for HBV. DCH DNA was detected in 31 (17.8%) out of 174 sera collected with a request for diagnosis of infectious diseases (collection A) and in 11 (5.1%) out of 216 sera submitted to the laboratory for pre-surgical evaluation or for suspected metabolic or neoplastic disease (collection B) that were used to generate a baseline. In this study we observed a marked and significantly higher prevalence (17.8%, 31/174) in the cohort of cats with suspected infectious diseases (collection A) with respect to a group of animals (collection B) used as baseline. Almost half of the sera positive for DCH (14/31, 45 .2%) of this cohort were collected from cats with retroviral infection (FIV and/or feline leukemia virus, FeLV). abstract: Hepadnaviruses infect several animal species. The prototype species, human hepatitis B virus (HBV), increases the risk of liver diseases and may cause cirrhosis and hepatocellular carcinoma. Recently a novel hepadnavirus, similar to HBV, has been identified through transcriptomics studies in a domestic cat with large cell lymphoma in Australia. Herewith, a collection of 390 feline serum samples was screened for hepadnavirus. Overall, the virus was identified in 10.8% of the sera with a significantly higher prevalence (17.8%) in the sera of animals with a clinical suspect of infectious disease. Upon genome sequencing, the virus was closely related (97.0% nt identity) to the prototype Australian feline virus Sydney 2016. The mean and median values of hepadnavirus in the feline sera were 1.3 × 10(6) and 2.1 × 10(4) genome copies per mL (range 3.3 × 10(0)–2.5 × 10(7) genome copies per mL). For a subset of hepadnavirus-positive samples, information on the hemato-chemical parameters was available and in 10/20 animals a profile suggestive of liver damage was present. Also, in 7/10 animals with suspected hepatic disease, virus load was >10(4) genome copies per mL, i.e. above the threshold considered at risk of active hepatitis and liver damage for HBV. url: https://www.ncbi.nlm.nih.gov/pubmed/31337847/ doi: 10.1038/s41598-019-47175-8 id: cord-017817-ztp7w9yh author: Land, Walter Gottlieb title: Cell-Autonomous (Cell-Intrinsic) Stress Responses date: 2018-03-28 words: 17727.0 sentences: 855.0 pages: flesch: 40.0 cache: ./cache/cord-017817-ztp7w9yh.txt txt: ./txt/cord-017817-ztp7w9yh.txt summary: Autophagy is an evolutionarily highly conserved self-digestive process in response to environmental stress to eukaryotic cells, by which cytoplasmic components such as defective/damaged or redundant organelles or protein aggregates are delivered to the lysosome for recycling and degradation. More recent studies then revealed that these transcription factors, notably Nrf2, are activated by Keap1 as the primary negative regulator of Nrf2, that is, a molecule that simultaneously operates as a sensor protein able to perceive dyshomeostatic Subclass IIC-4 DAMPs, for example, in terms of redox changes reflecting electrophilic stress. Strikingly, a complex relationship reportedly exists between autophagy and DAMPs in cellular adaption to stress and injury and cell death characterized by a crosstalk between autophagy induction and secretion or release of DAMPs. In fact, growing evidence indicates that autophagic mechanisms are involved in regulating release and degradation of DAMPs including CALR, HMGB1, ATP, and DNA in several cell types [37, 148, 175] . abstract: In this chapter, the role of cell-intrinsic stress responses is examined which include autophagic processes, the oxidative stress response, the heat shock response, the unfolded proteins response, and the DNA damage response. Autophagy (macroautophagy, microautophagy, and chaperone-mediated autophagy) is a self-digestive process in response to environmental stress to eukaryotic cells, by which cytoplasmic components are delivered to the lysosome for recycling and degradation. The oxidative stress response is directed against any oxidative stress and is mediated by antioxidative defense systems including antioxidant enzymes such as superoxide dismutase, detoxifying enzymes such as glutathione peroxidase, and energy-dependent efflux pumps. The heat shock response is induced upon exposure of cells to any stress condition and characterized by emission of heat shock proteins which operate as DAMPs to maintain and restore homeostasis. The unfolded protein response is induced by any stress of the endoplasmic reticulum that is perceived by three sensor molecules. Under remediable endoplasmic reticulum stress conditions, the sensors trigger signalling pathways to resolve this stress. However, in severe irremediable endoplasmic reticulum stress, the unfolded protein response may lead to pro-inflammatory and pro-apoptotic responses resulting in regulated cell death. Finally, the DNA damage response is induced by any DNA damage that occurs in a variety of exogenous and endogenous conditions. When successful, this stress response leads to DNA repair and is associated with the emission of various DAMPs which contribute to restoration of homeostasis. When unsuccessful, the DNA damage response, like the unsuccessful unfolded protein response, can result in regulated cell death, either in form of apoptosis or necrosis. Together, the ultimate goal of all the stress responses is to maintain cellular homeostasis and ensure cell integrity. When they fail, the incidence of regulated cell death is frequently observed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122488/ doi: 10.1007/978-3-319-78655-1_18 id: cord-015677-67md3xox author: Lang, Hans Peter title: Nanomechanical Cantilever Array Sensors date: 2010 words: 10409.0 sentences: 597.0 pages: flesch: 42.0 cache: ./cache/cord-015677-67md3xox.txt txt: ./txt/cord-015677-67md3xox.txt summary: In addition to application of such sensors for gas and chemical-vapor sensing, for example as an artificial nose, they have also been employed to measure physical properties of tiny amounts of materials in miniaturized versions of conventional standard techniques such as calorimetry, thermogravimetry, weighing, photothermal spectroscopy, as well as for monitoring chemical reactions such as catalysis on small surfaces. In addition to application of such sensors for gas and chemicalvapor sensing, for example as an artificial nose, they have also been employed to measure physical properties of tiny amounts of materials in miniaturized versions of conventional standard techniques such as calorimetry, thermogravimetry, weighing, photothermal spectroscopy, as well as for monitoring chemical reactions such as catalysis on small surfaces. Besides chemical and biochemical sensing, microcantilevers can also detect changes in physical properties of surrounding media, such as gas or liquid, or of layers deposited on the cantilever itself. abstract: Microfabricated cantilever sensors have attracted much interest in recent years as devices for the fast and reliable detection of small concentrations of molecules in air and solution. In addition to application of such sensors for gas and chemical-vapor sensing, for example as an artificial nose, they have also been employed to measure physical properties of tiny amounts of materials in miniaturized versions of conventional standard techniques such as calorimetry, thermogravimetry, weighing, photothermal spectroscopy, as well as for monitoring chemical reactions such as catalysis on small surfaces. In the past few years, the cantilever-sensor concept has been extended to biochemical applications and as an analytical device for measurements of biomaterials. Because of the label-free detection principle of cantilever sensors, their small size and scalability, this kind of device is advantageous for diagnostic applications and disease monitoring, as well as for genomics or proteomics purposes. The use of microcantilever arrays enables detection of several analytes simultaneously and solves the inherent problem of thermal drift often present when using single microcantilever sensors, as some of the cantilevers can be used as sensor cantilevers for detection, and other cantilevers serve as passivated reference cantilevers that do not exhibit affinity to the molecules to be detected. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115015/ doi: 10.1007/978-3-642-02525-9_15 id: cord-331698-rwow1ydx author: Latorre-Pérez, Adriel title: A lab in the field: applications of real-time, in situ metagenomic sequencing date: 2020-08-20 words: 6732.0 sentences: 335.0 pages: flesch: 36.0 cache: ./cache/cord-331698-rwow1ydx.txt txt: ./txt/cord-331698-rwow1ydx.txt summary: This review discusses the main applications of real-time, in situ metagenomic sequencing developed to date, highlighting the relevance of this technology in current challenges (such as the management of global pathogen outbreaks) and in the next future of industry and clinical diagnosis. Therefore, the ultra-portability, affordability, and speed in data production make the MinION technology suitable for real-time sequencing in a variety of environments, such as Ebola surveillance in West Africa during the last outbreak [25] , microbial communities inspection in the Arctic [26] , DNA sequencing on the International Space Station (ISS) [27] , and even the recently emerging pandemic coronavirus SARS-CoV-2 [28, 29] . In fact, there are some critical points to be addressed before this technique could become a standard in the industry: (i) sequencing cost should be reduced; (ii) rapid and reliable in situ DNA extraction and library preparation protocols should be designed and validated; (iii) minimal sequencing yields should be determined for each specific application; (iv) fast and real-time pipelines should be created and tested; and (v) level of expertise for managing the data and the samples should be notably reduced. abstract: High-throughput metagenomic sequencing is considered one of the main technologies fostering the development of microbial ecology. Widely used second-generation sequencers have enabled the analysis of extremely diverse microbial communities, the discovery of novel gene functions, and the comprehension of the metabolic interconnections established among microbial consortia. However, the high cost of the sequencers and the complexity of library preparation and sequencing protocols still hamper the application of metagenomic sequencing in a vast range of real-life applications. In this context, the emergence of portable, third-generation sequencers is becoming a popular alternative for the rapid analysis of microbial communities in particular scenarios, due to their low cost, simplicity of operation, and rapid yield of results. This review discusses the main applications of real-time, in situ metagenomic sequencing developed to date, highlighting the relevance of this technology in current challenges (such as the management of global pathogen outbreaks) and in the next future of industry and clinical diagnosis. url: https://doi.org/10.1093/biomethods/bpaa016 doi: 10.1093/biomethods/bpaa016 id: cord-274707-mxh38hwd author: Laureano, Ana Flávia Santarine title: The different tests for the diagnosis of COVID-19 - A review in Brazil so far date: 2020 words: 3736.0 sentences: 204.0 pages: flesch: 50.0 cache: ./cache/cord-274707-mxh38hwd.txt txt: ./txt/cord-274707-mxh38hwd.txt summary: The virus is now widespread and causing the current pandemic of COVID-19, a highly pathogenic viral pneumonia, commonly presented with fever and cough, which frequently lead to lower respiratory tract disease with poor clinical outcomes associated with older age and underlying health conditions. Most rapid tests use colloidal gold particles in a technique known as immunochromatography, also called lateral flow immunoassay, a type of sandwich assay that relies on a pair of antibodies used to recognize two independent epitopes of a protein, and therefore it can achieve high specificity (Zhou et al., 2012) . One of the first rapid tests (lateral flow immunoassay) for SARS-CoV-2 IgG and IgM immune responses was developed by professor''s Feng Ye group at the National Clinical Research Centre for Respiratory Disease in Guangzhou, China. Development and Clinical Application of A Rapid IgM-IgG Combined Antibody Test for SARS-CoV-2 Infection Diagnosis abstract: SARS-CoV-2 is a novel virus from the coronavirus family that emerged in the end of December 2019 in Wuhan, China. The virus is now widespread and causing the current pandemic of COVID-19, a highly pathogenic viral pneumonia, commonly presented with fever and cough, which frequently lead to lower respiratory tract disease with poor clinical outcomes associated with older age and underlying health conditions. Supportive care for patients is typically the standard protocol because no specific effective antiviral therapies have been identified so far. The current outbreak is challenging governments and health authorities all over the world. In here we present a comparison among the current diagnostic tools and kits being used to test Brazilian population. url: https://www.ncbi.nlm.nih.gov/pubmed/32491306/ doi: 10.5935/1518-0557.20200046 id: cord-000937-8vk89i4h author: Law, John title: Identification of Hepatotropic Viruses from Plasma Using Deep Sequencing: A Next Generation Diagnostic Tool date: 2013-04-17 words: 6644.0 sentences: 332.0 pages: flesch: 50.0 cache: ./cache/cord-000937-8vk89i4h.txt txt: ./txt/cord-000937-8vk89i4h.txt summary: RNA and DNA libraries were sequenced from plasma filtrates enriched in viral particles to catalog virus populations. Seven RNA libraries (aihP01, hbvP02, hcvP02, hcvP03, hcvP05, nshP01, norP01) and seven DNA libraries (aihP01D, hbvP02D, hcvP02D, hcvP03D, hcvP05D, nshP01D, norP01D) were constructed from patients with autoimmune hepatitis (AIH), hepatitis B virus (HBV) chronic infection, hepatitis C virus (HCV) chronic infection, non-alcoholic steatohepatitis (NASH), and healthy subjects (NOR). Plasma samples were obtained from patients with autoimmune hepatitis (AIH), chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, non-alcoholic steatohepatitis (NASH), and healthy subjects (NOR); each RNA library was named by diagnosis (e.g. aihP01) and a suffix ''D'' was added for each DNA library (e.g. aihP01D). To a lesser extent (about one read per million), we also detected sequences resembling RNA viruses in our DNA libraries (Supplemental Tables S15-S28 ). Assembly of viral sequences was also possible for all viruses shown in Figure 2 as the most abundant virus in each library (data not shown). abstract: We conducted an unbiased metagenomics survey using plasma from patients with chronic hepatitis B, chronic hepatitis C, autoimmune hepatitis (AIH), non-alcoholic steatohepatitis (NASH), and patients without liver disease (control). RNA and DNA libraries were sequenced from plasma filtrates enriched in viral particles to catalog virus populations. Hepatitis viruses were readily detected at high coverage in patients with chronic viral hepatitis B and C, but only a limited number of sequences resembling other viruses were found. The exception was a library from a patient diagnosed with hepatitis C virus (HCV) infection that contained multiple sequences matching GB virus C (GBV-C). Abundant GBV-C reads were also found in plasma from patients with AIH, whereas Torque teno virus (TTV) was found at high frequency in samples from patients with AIH and NASH. After taxonomic classification of sequences by BLASTn, a substantial fraction in each library, ranging from 35% to 76%, remained unclassified. These unknown sequences were assembled into scaffolds along with virus, phage and endogenous retrovirus sequences and then analyzed by BLASTx against the non-redundant protein database. Nearly the full genome of a heretofore-unknown circovirus was assembled and many scaffolds that encoded proteins with similarity to plant, insect and mammalian viruses. The presence of this novel circovirus was confirmed by PCR. BLASTx also identified many polypeptides resembling nucleo-cytoplasmic large DNA viruses (NCLDV) proteins. We re-evaluated these alignments with a profile hidden Markov method, HHblits, and observed inconsistencies in the target proteins reported by the different algorithms. This suggests that sequence alignments are insufficient to identify NCLDV proteins, especially when these alignments are only to small portions of the target protein. Nevertheless, we have now established a reliable protocol for the identification of viruses in plasma that can also be adapted to other patient samples such as urine, bile, saliva and other body fluids. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629200/ doi: 10.1371/journal.pone.0060595 id: cord-013412-gj443yei author: Lebedeva, Natalya Sh. title: The Application of Porphyrins and Their Analogues for Inactivation of Viruses date: 2020-09-23 words: 13428.0 sentences: 626.0 pages: flesch: 46.0 cache: ./cache/cord-013412-gj443yei.txt txt: ./txt/cord-013412-gj443yei.txt summary: The purpose of this review paper is to summarize the main approaches developed to date in the chemical and photodynamic inactivation of human and animal viruses using porphyrins and their analogues and to analyze and discuss the information on viral targets and antiviral activity of porphyrins, chlorins, of their conjugates with organic/inorganic compounds obtained in the last 10–15 years in order to identify the most promising areas. A cationic substituent is necessary to increase the solubility of porphyrins and their analogues in aqueous media, and three nitro groups provide linking of the gp120 protein with the glycoprotein ( Figure 3 ) and thereby inhibit fusion between the virus and the cell membrane. A cationic substituent is necessary to increase the solubility of porphyrins and their analogues in aqueous media, and three nitro groups provide linking of the gp120 protein with the glycoprotein ( Figure 3 ) and thereby inhibit fusion between the virus and the cell membrane. abstract: The problem of treating viral infections is extremely relevant due to both the emergence of new viral diseases and to the low effectiveness of existing approaches to the treatment of known viral infections. This review focuses on the application of porphyrin, chlorin, and phthalocyanine series for combating viral infections by chemical and photochemical inactivation methods. The purpose of this review paper is to summarize the main approaches developed to date in the chemical and photodynamic inactivation of human and animal viruses using porphyrins and their analogues and to analyze and discuss the information on viral targets and antiviral activity of porphyrins, chlorins, of their conjugates with organic/inorganic compounds obtained in the last 10–15 years in order to identify the most promising areas. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583985/ doi: 10.3390/molecules25194368 id: cord-328518-umvk59dc author: Lee, Dana N. title: Two novel adenoviruses found in Cave Myotis bats (Myotis velifer) in Oklahoma date: 2019-12-03 words: 2380.0 sentences: 160.0 pages: flesch: 60.0 cache: ./cache/cord-328518-umvk59dc.txt txt: ./txt/cord-328518-umvk59dc.txt summary: In this study, 30 pooled-guano samples were collected from a cave roost of Myotis velifer in Oklahoma. Phylogenetic analysis of these fragments confirmed our isolates were from the genus Mastadenovirus and had genetic diversity ranging from 20 to 50% when compared to other bat adenoviruses. Adenoviruses (AdVs) are double stranded DNA viruses found in vertebrate hosts of many different species [8, 10] . DNA sequence from Guano sample 21, 22, 24, and 25 represent a separate Adenovirus species and are further referred to as Cave Myotis AdV2. Little work has been done to investigate AdVs in North American species of bats; however, these studies [19, 29] and ours highlight the importance of identifying viruses housed in bats to better understand viral evolution, how viruses are maintained in bat colonies and evaluate risks for host transmission to other species. abstract: Bats are carriers of potentially zoonotic viruses, therefore it is crucial to identify viruses currently found in bats to better understand how they are maintained in bat populations and evaluate risks for transmission to other species. Adenoviruses have been previously detected in bats throughout the world, but sampling is still limited. In this study, 30 pooled-guano samples were collected from a cave roost of Myotis velifer in Oklahoma. A portion of the DNA polymerase gene from Adenoviridae was amplified successfully in 18 M. velifer samples; however, DNA sequence was obtained from only 6 of these M. velifer samples. One was collected in October 2016, one in March 2017, and 4 in July 2017. The October and March samples contained viral DNA that was 3.1% different from each other but 33% different than the novel viral sequence found in the July 2017 samples. Phylogenetic analysis of these fragments confirmed our isolates were from the genus Mastadenovirus and had genetic diversity ranging from 20 to 50% when compared to other bat adenoviruses. url: https://www.ncbi.nlm.nih.gov/pubmed/31797220/ doi: 10.1007/s11262-019-01719-2 id: cord-000049-rl7sdzd7 author: Lee, David title: Detection of genetically modified organisms (GMOs) using isothermal amplification of target DNA sequences date: 2009-02-02 words: 2899.0 sentences: 141.0 pages: flesch: 55.0 cache: ./cache/cord-000049-rl7sdzd7.txt txt: ./txt/cord-000049-rl7sdzd7.txt summary: Here we have applied the loop-mediated isothermal amplification (LAMP) method to amplify GMO-related DNA sequences, ''internal'' commonly-used motifs for controlling transgene expression and event-specific (plant-transgene) junctions. Moreover, the sensitivity and ability to amplify targets, even with a high background of DNA, here demonstrated, highlights the advantages of this isothermal amplification when applied for GMO detection. Here we assess the LAMP protocol for the detection of GMOs using primers that target event-specific sequences for transgenic MS8 and RF3 oilseed rape (Brassica napus L.) and generic GMO sequences such as the cauliflower mosaic virus 35S promoter (P-35S) and the promoter and terminator for the nopaline synthase gene (P-nos and T-nos, respectively) from Agrobacterium spp. LAMP sensitivity was assessed by the detection of ten RoundUp Ready™ GMO targets in a background of 100 ng of genomic oilseed rape DNA (Figure 3 ). abstract: BACKGROUND: The most common method of GMO detection is based upon the amplification of GMO-specific DNA amplicons using the polymerase chain reaction (PCR). Here we have applied the loop-mediated isothermal amplification (LAMP) method to amplify GMO-related DNA sequences, 'internal' commonly-used motifs for controlling transgene expression and event-specific (plant-transgene) junctions. RESULTS: We have tested the specificity and sensitivity of the technique for use in GMO studies. Results show that detection of 0.01% GMO in equivalent background DNA was possible and dilutions of template suggest that detection from single copies of the template may be possible using LAMP. CONCLUSION: This work shows that GMO detection can be carried out using LAMP for routine screening as well as for specific events detection. Moreover, the sensitivity and ability to amplify targets, even with a high background of DNA, here demonstrated, highlights the advantages of this isothermal amplification when applied for GMO detection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2656497/ doi: 10.1186/1472-6750-9-7 id: cord-004003-rlgzgyzn author: Lee, Jeewon title: Applying a Linear Amplification Strategy to Recombinase Polymerase Amplification for Uniform DNA Library Amplification date: 2019-11-12 words: 3386.0 sentences: 200.0 pages: flesch: 51.0 cache: ./cache/cord-004003-rlgzgyzn.txt txt: ./txt/cord-004003-rlgzgyzn.txt summary: Thus, to amplify the size-variable DNA library uniformly, we introduced a linear amplification strategy with RPA and successfully improved the uniformity. Also, the average percentages of bases in the uniform range (uniformity value between 0.5 and 1.5) about the triplet experiment was improved from 56.3 and 49.2% by two-primer RPA to 73.6 and 75.7% by linear RPA for the small and large DNA libraries, respectively (Figures 2b and S5) . Taken together, the data show that RPA uniformly amplifies DNA libraries of the same size and has different amplification preferences than PCR. However, during the experiment, an accelerated small-sized DNA amplification by two-primer RPA reaction caused lower uniformity compared to PCR. It was noted that during the analysis, different amplification preferences were found between the PCR and RPA amplified oligo library sequencing data. Taken together, we show that single-primer linear RPA can be one of the alternative methods to PCR for DNA library amplification. abstract: [Image: see text] Recombinase polymerase amplification (RPA) is an isothermal DNA amplification method with broad applications as a point-of-care test and in molecular biology techniques. Currently, most of the applications are focused on target-specific amplification. Because RPA has the advantage of amplifying DNA under isothermal conditions, we utilized RPA as a DNA library amplification tool. In this study, we used a sheared genomic DNA library and an oligonucleotide (oligo) library for the comparison of polymerase chain reaction and RPA. For the sheared DNA library, we observed biased amplification after RPA was conducted. Thus, to amplify the size-variable DNA library uniformly, we introduced a linear amplification strategy with RPA and successfully improved the uniformity. On the other hand, using the same-sized oligo library, we confirmed that RPA amplified this library uniformly without modification of the protocol. These results demonstrate that RPA can be applied not only to amplify a specific target as previously demonstrated but also to amplify a complex DNA library composed of a large number of different DNA molecules. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882106/ doi: 10.1021/acsomega.9b02886 id: cord-328940-8vtcochx author: Lee, Jeong Yoon title: Bacterial RecA Protein Promotes Adenoviral Recombination during In Vitro Infection date: 2018-06-20 words: 7979.0 sentences: 407.0 pages: flesch: 39.0 cache: ./cache/cord-328940-8vtcochx.txt txt: ./txt/cord-328940-8vtcochx.txt summary: By analysis of known recombination hot spots across 38 human adenovirus genomes in species D (HAdV-D), we identified nucleotide sequence motifs similar to bacterial Chi sequences, which facilitate homologous recombination in the presence of bacterial Rec enzymes. We speculate that free Rec proteins present in gastrointestinal secretions upon bacterial cell death facilitate the evolution of human adenoviruses through homologous recombination, an example of viral commensalism and the complexity of virus-host interactions, including regional microbiota. Our computational analysis of similar GC content transitions across whole HAdV-D genomes showed comparable patterns of GC/AT transition at predicted recombination hot spots around hypervariable gene segments in the three major capsid genes-the same segments that constitute the molecular identity of each virus (14, 19, (41) (42) (43) -including the region containing Chi AD immediately 5= to penton base HVL2 (see Fig. S1 and Table S1 in the supplemental material). abstract: Adenovirus infections in humans are common and sometimes lethal. Adenovirus-derived vectors are also commonly chosen for gene therapy in human clinical trials. We have shown in previous work that homologous recombination between adenoviral genomes of human adenovirus species D (HAdV-D), the largest and fastest growing HAdV species, is responsible for the rapid evolution of this species. Because adenovirus infection initiates in mucosal epithelia, particularly at the gastrointestinal, respiratory, genitourinary, and ocular surfaces, we sought to determine a possible role for mucosal microbiota in adenovirus genome diversity. By analysis of known recombination hot spots across 38 human adenovirus genomes in species D (HAdV-D), we identified nucleotide sequence motifs similar to bacterial Chi sequences, which facilitate homologous recombination in the presence of bacterial Rec enzymes. These motifs, referred to here as Chi(AD), were identified immediately 5′ to the sequence encoding penton base hypervariable loop 2, which expresses the arginine-glycine-aspartate moiety critical to adenoviral cellular entry. Coinfection with two HAdV-Ds in the presence of an Escherichia coli lysate increased recombination; this was blocked in a RecA mutant strain, E. coli DH5α, or upon RecA depletion. Recombination increased in the presence of E. coli lysate despite a general reduction in viral replication. RecA colocalized with viral DNA in HAdV-D-infected cell nuclei and was shown to bind specifically to Chi(AD) sequences. These results indicate that adenoviruses may repurpose bacterial recombination machinery, a sharing of evolutionary mechanisms across a diverse microbiota, and unique example of viral commensalism. IMPORTANCE Adenoviruses are common human mucosal pathogens of the gastrointestinal, respiratory, and genitourinary tracts and ocular surface. Here, we report finding Chi-like sequences in adenovirus recombination hot spots. Adenovirus coinfection in the presence of bacterial RecA protein facilitated homologous recombination between viruses. Genetic recombination led to evolution of an important external feature on the adenoviral capsid, namely, the penton base protein hypervariable loop 2, which contains the arginine-glycine-aspartic acid motif critical to viral internalization. We speculate that free Rec proteins present in gastrointestinal secretions upon bacterial cell death facilitate the evolution of human adenoviruses through homologous recombination, an example of viral commensalism and the complexity of virus-host interactions, including regional microbiota. url: https://www.ncbi.nlm.nih.gov/pubmed/29925671/ doi: 10.1128/msphere.00105-18 id: cord-288445-6i5fbdcu author: Lee, Jieon title: Biosensors based on graphene oxide and its biomedical application() date: 2016-10-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Graphene oxide (GO) is one of the most attributed materials for opening new possibilities in the development of next generation biosensors. Due to the coexistence of hydrophobic domain from pristine graphite structure and hydrophilic oxygen containing functional groups, GO exhibits good water dispersibility, biocompatibility, and high affinity for specific biomolecules as well as properties of graphene itself partly depending on preparation methods. These properties of GO provided a lot of opportunities for the development of novel biological sensing platforms, including biosensors based on fluorescence resonance energy transfer (FRET), laser desorption/ionization mass spectrometry (LDI-MS), surface-enhanced Raman spectroscopy (SERS), and electrochemical detection. In this review, we classify GO-based biological sensors developed so far by their signal generation strategy and provide the comprehensive overview of them. In addition, we offer insights into how the GO attributed in each sensor system and how they improved the sensing performance. url: https://doi.org/10.1016/j.addr.2016.06.001 doi: 10.1016/j.addr.2016.06.001 id: cord-346043-8vcvalhp author: Lee, Jong B. title: Multifunctional nanoarchitectures from DNA-based ABC monomers date: 2009-05-03 words: 2995.0 sentences: 191.0 pages: flesch: 53.0 cache: ./cache/cord-346043-8vcvalhp.txt txt: ./txt/cord-346043-8vcvalhp.txt summary: To build up a multifunctional polymer from ABC monomers, we designed different modules separately including DNA capture probes, fluorescent dyes, quantum dots and gold nanoparticles (AuNPs, not shown in this paper; for DNA sequences see Supplementary Tables S1, S2 ). To characterize the ABC monomer at the individual molecule level, we generated donor Y-DNAs tethered with two different colours of quantum dots to be linked onto X-DNA (see Supplementary Figs S5, S6a). To synthesize multifunctional nanoarchitectures from an ABC monomer we designed each ABC monomer to have two quantum dots with three different colour configurations (2G, 1G1R or 2R; see Supplementary Fig. S8 ), one photo-responsive PEGA moiety, and one single-stranded oligonucleotide probe that was complementary to a specific pathogen DNA such as SARS coronavirus, Ebola virus or Bacillus anthracis (this unique DNA is termed the ''capture probe''; see 1A and 1B in Fig. 3a and Supplementary Table S3 ). abstract: The ability to attach different functional moieties to a molecular building block(1,2) could lead to applications in nanoelectronics(3), nanophotonics(4), intelligent sensing(5) and drug delivery(6,7). The building unit needs to be both multivalent and anisotropic, and although many anisotropic building blocks have been created(1,8,9,10,11,12), these have not been universally applicable. Recently, DNA has been used to generate various nanostructures(13,14,15,16,17) or hybrid systems(18,19,20,21,22,23,24,25), and as a generic building block for various applications(26,27,28,29,30). Here, we report the creation of anisotropic, branched and crosslinkable building blocks (ABC monomers) from which multifunctional nanoarchitectures have been assembled. In particular, we demonstrate a target-driven polymerization process in which polymers are generated only in the presence of a specific DNA molecule, leading to highly sensitive pathogen detection. Using this monomer system, we have also designed a biocompatible nanovector that delivers both drugs and tracers simultaneously. Our approach provides a general yet versatile route towards the creation of a range of multifunctional nanoarchitectures. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nnano.2009.93) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1038/nnano.2009.93 doi: 10.1038/nnano.2009.93 id: cord-306754-qohrnpgq author: Lee, Justin S. title: Targeted Enrichment for Pathogen Detection and Characterization in Three Felid Species date: 2017-05-23 words: 7158.0 sentences: 335.0 pages: flesch: 48.0 cache: ./cache/cord-306754-qohrnpgq.txt txt: ./txt/cord-306754-qohrnpgq.txt summary: Our report provides advances in investigating several important aspects of TGC assay design, including (i) the range of fold enrichment possible for targeted nucleic acids, (ii) comparison of TGC pathogen detection with traditional methods currently used by diagnostic laboratories, (iii) documentation that a single assay design can be applied to more than one host species, (iv) the applicability of TGC to characterize pathogens in the context of veterinary medicine, and (v) the ability of TGC-NGS to characterize intrahost genetic diversity of viral pathogens (4) (5) (6) . Mean enrichment values of 250,000-fold and 9,100,000-fold with the DNA and RNA probes, respectively, and 147,000-fold for FIV contained in tissues clearly demonstrate the ability of the targeted capture probes to dramatically alter the relative abundance of specific nucleic acids across a range of sample types and diverse pathogen taxa. abstract: Traditional diagnostic assays often lack sensitivity and can be difficult to multiplex across many pathogens. Next-generation sequencing (NGS) can overcome some of these problems but has limited application in the detection of low-copy-number pathogens in complex samples. Targeted genome capture (TGC) utilizes oligonucleotide probes to enrich specific nucleic acids in heterogeneous extracts and can therefore increase the proportion of NGS reads for low-abundance targets. While earlier studies have demonstrated the utility of this technology for detection of novel pathogens in human clinical samples, the capacity and practicality of TGC-NGS in a veterinary diagnostic setting have not yet been evaluated. Here we report the use of TGC-NGS assays for the detection and characterization of diverse feline pathogen taxa. We detected 31 pathogens comprising nine pathogen taxa in 28 felid samples analyzed. This included 20 pathogens detected via traditional PCR and 11 additional pathogens that had not been previously detected in the same samples. Most of the pathogens detected were sequenced at sufficient breadth and depth to confidently classify them at the species or subspecies level. Target nucleic acids were enriched from a low of 58-fold to 56 million-fold relative to host nucleic acids. Despite the promising performance of these assays, a number of pathogens detected by conventional PCR or serology were not isolated by TGC-NGS, suggesting that further validation is required before this technology can be used in lieu of quality-controlled standard assays. We conclude that TGC-NGS offers great potential as a broad multiplex pathogen characterization assay in veterinary diagnostic and research settings. url: https://www.ncbi.nlm.nih.gov/pubmed/28330894/ doi: 10.1128/jcm.01463-16 id: cord-292569-h8fe0zio author: Lee, Si-Hyeong title: Preferential production of IgM-secreting hybridomas by immunization with DNA vaccines coding for Ebola virus glycoprotein: use of protein boosting for IgG-secreting hybridoma production date: 2017-07-26 words: 5460.0 sentences: 281.0 pages: flesch: 58.0 cache: ./cache/cord-292569-h8fe0zio.txt txt: ./txt/cord-292569-h8fe0zio.txt summary: title: Preferential production of IgM-secreting hybridomas by immunization with DNA vaccines coding for Ebola virus glycoprotein: use of protein boosting for IgG-secreting hybridoma production These data suggest that immunization with GP DNA vaccines leads to preferential production of hybridomas secreting IgM Abs with little antigen specificity, and that boosting with GP can overcome this propensity. Taken together, these data suggest that boosting with GP could be useful for producing hybridomas that secrete antigen-specific IgG Abs. Six-week-old, female BALB/c mice were purchased from Daehan Biolink (Eumseong, Korea). These data suggest that 11 of the hybridoma clones may secrete IgM Abs with high avidity to mulIgG was purified from cell supernatants using the protein G-resin column (for A6-9). This finding, along with our previous findings, suggests that antigen-specific Ab responses, primed by DNA vaccination, may be boosted by protein immunization, leading to preferential production of IgG-secreting hybridomas. abstract: PURPOSE: The goal of this study was to investigate the utility of DNA vaccines encoding Ebola virus glycoprotein (GP) as a vaccine type for the production of GP-specific hybridomas and antibodies. MATERIALS AND METHODS: DNA vaccines were constructed to express Ebola virus GP. Mice were injected with GP DNA vaccines and their splenocytes were used for hybridoma production. Enzyme-linked immunosorbent assays (ELISAs), limiting dilution subcloning, antibody purification methods, and Western blot assays were used to select GP-specific hybridomas and purify monoclonal antibodies (MAbs) from the hybridoma cells. RESULTS: Twelve hybridomas, the cell supernatants of which displayed GP-binding activity, were selected by ELISA. When purified MAbs from 12 hybridomas were tested for their reactivity to GP, 11 MAbs, except for 1 MAb (from the A6-9 hybridoma) displaying an IgG2a type, were identified as IgM isotypes. Those 11 MAbs failed to recognize GP. However, the MAb from A6-9 recognized the mucin-like region of GP and remained reactive to the antigen at the lowest tested concentration (1.95 ng/mL). This result suggests that IgM-secreting hybridomas are predominantly generated by DNA vaccination. However, boosting with GP resulted in greater production of IgG-secreting hybridomas than GP DNA vaccination alone. CONCLUSION: DNA vaccination may preferentially generate IgM-secreting hybridomas, but boosting with the protein antigen can reverse this propensity. Thus, this protein boosting approach may have implications for the production of IgG-specific hybridomas in the context of the DNA vaccination platform. In addition, the purified monoclonal IgG antibodies may be useful as therapeutic antibodies for controlling Ebola virus infection. url: https://www.ncbi.nlm.nih.gov/pubmed/28775978/ doi: 10.7774/cevr.2017.6.2.135 id: cord-333220-tcvs4beg author: Lee, Szu-Yuan title: Compact optical diagnostic device for isothermal nucleic acids amplification date: 2008-08-12 words: 4844.0 sentences: 243.0 pages: flesch: 48.0 cache: ./cache/cord-333220-tcvs4beg.txt txt: ./txt/cord-333220-tcvs4beg.txt summary: It has two major components, a disposable polymethyl methacrylate (PMMA) micro-reactor and a temperature-regulated optical detection unit (base apparatus) for real-time monitoring of the turbidity changes due to the precipitation of DNA amplification by-product, magnesium pyrophosphate. It has two major components, a disposable PMMA micro-reactor and a temperature-regulated optical detection unit (base apparatus) for real-time monitoring of the turbidity changes due to precipitation of DNA amplification by-product, magnesium pyrophosphate. Our integrated isothermal device has two major components, a disposable polymethyl methacrylate (PMMA) micro-reactor and a temperature-regulated optical detection unit (base apparatus) for real-time monitoring of the turbidity changes due to the precipitation of DNA amplification by-product, magnesium pyrophosphate. To confirm the results of the LAMP reaction for HBV DNA template amplification and detection in the integrated isothermal device, seven clinical serum specimens were obtained from patients with chronic hepatitis B at National Taiwan University Hospital. abstract: We recently reported the successful use of the loop-mediated isothermal amplification (LAMP) reaction for hepatitis B virus (HBV) DNA amplification and its optimal primer design method. In this study, we report the development of an integrated isothermal device for both amplification and detection of targeted HBV DNA. It has two major components, a disposable polymethyl methacrylate (PMMA) micro-reactor and a temperature-regulated optical detection unit (base apparatus) for real-time monitoring of the turbidity changes due to the precipitation of DNA amplification by-product, magnesium pyrophosphate. We have established a correlation curve (R(2) = 0.99) between the concentration of pyrophosphate ions and the level of turbidity by using a simulated chemical reaction to evaluate the characteristics of our device. For the applications of rapid pathogens detection, we also have established a standard curve (R(2) = 0.96) by using LAMP reaction with a standard template in our device. Moreover, we also have successfully used the device on seven clinical serum specimens where HBV DNA levels have been confirmed by real-time PCR. The result indicates that different amounts of HBV DNA can be successfully detected by using this device within 1 h. url: https://api.elsevier.com/content/article/pii/S0925400508001998 doi: 10.1016/j.snb.2008.03.008 id: cord-339419-b6tr2zyx author: Lee, Thomas Ming-Hung title: DNA-based bioanalytical microsystems for handheld device applications date: 2006-01-18 words: 5425.0 sentences: 331.0 pages: flesch: 49.0 cache: ./cache/cord-339419-b6tr2zyx.txt txt: ./txt/cord-339419-b6tr2zyx.txt summary: Recent progresses in the miniaturization of various biological processing steps for the sample preparation, DNA amplification (polymerase chain reaction), and product detection are delineated in detail. The organization of the following contents is based upon the three basic DNA processing modules of sample preparation, target amplification, and product detection. Thermal lysis can be easily adapted to microfabricated amplification systems as the initial high-temperature step (∼95 • C) employed to denature the double-stranded (ds) DNA template is powerful enough to open up the cell membranes [10, 12, 19] . The sensing protocol basically involves the immobilization of an oligonucleotide onto a transducer surface, and upon the hybridization of complementary target sequence, the binding event is detected by optical, microgravimetric (mass-sensitive), or electrochemical methods. To further increase the sensitivity of the gold nanoparticle-based assay, a signal amplification step Pictorial representation of the working principle of the molecular beacon-type capture probe labeled with ferrocene group for the reagentless sequence-specific DNA detection. abstract: Abstract This article reviews and highlights the current development of DNA-based bioanalytical microsystems for point-of-care diagnostics and on-site monitoring of food and water. Recent progresses in the miniaturization of various biological processing steps for the sample preparation, DNA amplification (polymerase chain reaction), and product detection are delineated in detail. Product detection approaches utilizing “portable” detection signals and electrochemistry-based methods are emphasized in this work. The strategies and challenges for the integration of individual processing module on the same chip are discussed. url: https://www.sciencedirect.com/science/article/pii/S0003267005009438 doi: 10.1016/j.aca.2005.05.075 id: cord-004378-g1rxygef author: Leinisch, Fabian title: UV oxidation of cyclic AMP receptor protein, a global bacterial gene regulator, decreases DNA binding and cleaves DNA at specific sites date: 2020-02-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: UV light is a widely-employed, and environmentally-sensitive bactericide but its mechanism of action is not fully defined. Proteins are major chromophores and targets for damage due to their abundance, but the role of proteins in inducing damage to bound DNA, and the effects on DNA-protein interactions is less well characterized. In E. coli (and other Gram-negative bacteria) the cyclic AMP receptor protein (CRP/CAP) regulates more than 500 genes. In this study we show that exposure of isolated dimeric CRP-cAMP to UV modifies specific Met, Trp, Tyr, and Pro side-chains, induces inter-protein Tyr63-Tyr41 cross-links, and decreases DNA binding via oxidation of Met114/Pro110 residues in close proximity at the CRP dimer interface. UV exposure also modifies DNA-bound cAMP-CRP, with this resulting in DNA cleavage at specific G/C residues within the sequence bound to CRP, but not at other G/C sites. Oxidation also increases CRP dissociation from DNA. The modifications at the CRP dimer interface, and the site-specific DNA strand cleavage are proposed to occur via oxidation of two species Met residues (Met114 and Met189, respectively) to reactive persulfoxides that damage neighbouring amino acids and DNA bases. These data suggest that modification to CRP, and bound DNA, contributes to UV sensitivity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033146/ doi: 10.1038/s41598-020-59855-x id: cord-016304-uusmg786 author: Lemuth, Karin title: Microarrays as Research Tools and Diagnostic Devices date: 2015-03-11 words: 8577.0 sentences: 457.0 pages: flesch: 41.0 cache: ./cache/cord-016304-uusmg786.txt txt: ./txt/cord-016304-uusmg786.txt summary: Starting from mono-parametric tests within the last years, technologies have evolved that allow for the detection of many parameters in parallel, e.g., by using multiplex nucleic acid amplification techniques, microarrays, or next-generation sequencing technologies. Further, closed lab-on-a-chip devices that use DNA microarrays as detection tools are discussed, and additionally, an outlook toward applications of next-generation sequencing tools in diagnostics will be given. First used for multiparametric transcriptional profiling, the technology rapidly developed toward a tool for the detection of all kinds of biological targets (DNA, RNA, proteins, cells, nucleic acids, carbohydrates, etc.) or their modifications (methylation, phosphorylation, etc.) within the last 20 years. This 70-gene signature has been validated in several clinical trials, in general using fresh biopsy tissue for preparation of the transcriptional profiles during the last years and is now commercially available via Agendia as MammaPrint ® (using Microarrays based on Agilent technology) for guided therapy of early-stage breast cancer (Exner et al. abstract: Molecular diagnostics comprises a main analytical division in clinical laboratory diagnostics. The analysis of RNA or DNA helps to diagnose infectious diseases and identify genetic determined disorders or even cancer. Starting from mono-parametric tests within the last years, technologies have evolved that allow for the detection of many parameters in parallel, e.g., by using multiplex nucleic acid amplification techniques, microarrays, or next-generation sequencing technologies. The introduction of closed-tube systems as well as lab-on-a-chip devices further resulted in a higher automation degree with a reduced contamination risk. These applications complement or even stepwise replace classical methods in clinical microbiology like virus cultures, resistance determination, microscopic and metabolic analyses, as well as biochemical or immunohistochemical assays. In addition, novel diagnostic markers appear, like noncoding RNAs and miRNAs providing additional room for novel biomarkers. This article provides an overview of microarrays as diagnostics devices and research tools. Introduced in 1995 for transcription analysis, microarrays are used today to detect several different biomolecules like DNA, RNA, miRNA, and proteins among others. Mainly used in research, some microarrays also found their way to clinical diagnostics. Further, closed lab-on-a-chip devices that use DNA microarrays as detection tools are discussed, and additionally, an outlook toward applications of next-generation sequencing tools in diagnostics will be given. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120549/ doi: 10.1007/978-3-319-17305-4_13 id: cord-321386-u1imic5l author: Li, Chun title: Protein Sequence Comparison and DNA-binding Protein Identification with Generalized PseAAC and Graphical Representation date: 2018-02-17 words: 5503.0 sentences: 311.0 pages: flesch: 59.0 cache: ./cache/cord-321386-u1imic5l.txt txt: ./txt/cord-321386-u1imic5l.txt summary: METHODS: Based on two physicochemical properties of amino acids, a protein primary sequence was converted into a three-letter sequence, and then a graph without loops and multiple edges and its geometric line adjacency matrix were obtained. A generalized PseAAC (pseudo amino acid composition) model was thus constructed to characterize a protein sequence numerically. In addition, a generalized PseAAC based SVM (support vector machine) model was developed to identify DNA-binding proteins. Also, we develop a SVM (support vector machine) model using the generalized PseAAC to identify DNA-binding and non-binding proteins on three datasets. By combining these elements with the conventional amino acid composition (AAC), a dimensional feature vector can be constructed to numerically characterize a protein sequence: , By combining these elements with the frequencies of occurrence of 20 standard amino acids and their three representative letters, a generalized PseAAC model of a protein sequence was constructed. Numerical characterization of protein sequences based on the generalized Chou''s pseudo amino acid composition abstract: AIM AND OBJECTIVE: The rapid increase in the amount of protein sequence data available leads to an urgent need for novel computational algorithms to analyze and compare these sequences. This study is undertaken to develop an efficient computational approach for timely encoding protein sequences and extracting the hidden information. METHODS: Based on two physicochemical properties of amino acids, a protein primary sequence was converted into a three-letter sequence, and then a graph without loops and multiple edges and its geometric line adjacency matrix were obtained. A generalized PseAAC (pseudo amino acid composition) model was thus constructed to characterize a protein sequence numerically. RESULTS: By using the proposed mathematical descriptor of a protein sequence, similarity comparisons among β-globin proteins of 17 species and 72 spike proteins of coronaviruses were made, respectively. The resulting clusters agreed well with the established taxonomic groups. In addition, a generalized PseAAC based SVM (support vector machine) model was developed to identify DNA-binding proteins. Experiment results showed that our method performed better than DNAbinder, DNA-Prot, iDNA-Prot and enDNA-Prot by 3.29-10.44% in terms of ACC, 0.056-0.206 in terms of MCC, and 1.45-15.76% in terms of F1M. When the benchmark dataset was expanded with negative samples, the presented approach outperformed the four previous methods with improvement in the range of 2.49-19.12% in terms of ACC, 0.05-0.32 in terms of MCC, and 3.82-33.85% in terms of F1M. CONCLUSION: These results suggested that the generalized PseAAC model was very efficient for comparison and analysis of protein sequences, and very competitive in identifying DNA-binding proteins. url: https://doi.org/10.2174/1386207321666180130100838 doi: 10.2174/1386207321666180130100838 id: cord-002687-ql6zo8ka author: Li, Dan title: A potent human neutralizing antibody Fc-dependently reduces established HBV infections date: 2017-09-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Hepatitis B virus (HBV) infection is a major global health problem. Currently-available therapies are ineffective in curing chronic HBV infection. HBV and its satellite hepatitis D virus (HDV) infect hepatocytes via binding of the preS1 domain of its large envelope protein to sodium taurocholate cotransporting polypeptide (NTCP). Here, we developed novel human monoclonal antibodies that block the engagement of preS1 with NTCP and neutralize HBV and HDV with high potency. One antibody, 2H5-A14, functions at picomolar level and exhibited neutralization-activity-mediated prophylactic effects. It also acts therapeutically by eliciting antibody-Fc-dependent immunological effector functions that impose durable suppression of viral infection in HBV-infected mice, resulting in reductions in the levels of the small envelope antigen and viral DNA, with no emergence of escape mutants. Our results illustrate a novel antibody-Fc-dependent approach for HBV treatment and suggest 2H5-A14 as a novel clinical candidate for HBV prevention and treatment of chronic HBV infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614562/ doi: 10.7554/elife.26738 id: cord-278250-dwok857k author: Li, Heng title: The altered gut virome community in rhesus monkeys is correlated with the gut bacterial microbiome and associated metabolites date: 2019-08-19 words: 7452.0 sentences: 379.0 pages: flesch: 44.0 cache: ./cache/cord-278250-dwok857k.txt txt: ./txt/cord-278250-dwok857k.txt summary: We performed metagenomic sequencing of fecal samples to detect the bacterial microbiome and virome composition of healthy one-year-old rhesus monkeys housed at the IMBCAMS (Fig. 1) . We comprehensively analyzed the interactions among the gut virome, bacterial microbiome and metabolomes based on the above results there were noticeable differences in bacterial β-diversity between control and experimental animals, as determined using principal component analysis (PCA), and the results showed good repeatability within a single group (Additional file 2: Figure S2F ). Briefly, the fecal virome composition was noticeably altered after depletion of the bacterial microbiome, and the abundances of many DNA viruses, bacteriophages and RNA viruses in the gut were clearly decreased. As expected, the whole gut bacterial microbiome, including gram-positive and gram-negative bacteria (Additional file 2: Figure S2E ), was depleted after treatment with the antibiotic cocktail, except for Escherichia-Shigella species belonging to Proteobacteria, which were resistant to the cocktail. abstract: BACKGROUND: The gut microbiome is closely associated with the health of the host; although the interaction between the bacterial microbiome and the whole virome has rarely been studied, it is likely of medical importance. Examination of the interactions between the gut bacterial microbiome and virome of rhesus monkey would significantly contribute to revealing the gut microbiome composition. METHODS: Here, we conducted a metagenomic analysis of the gut microbiome of rhesus monkeys in a longitudinal cohort treated with an antibiotic cocktail, and we documented the interactions between the bacterial microbiome and virome. The depletion of viral populations was confirmed at the species level by real-time PCR. We also detected changes in the gut metabolome by GC-MS and LC-MS. RESULTS: A majority of bacteria were depleted after treatment with antibiotics, and the Shannon diversity index decreased from 2.95 to 0.22. Furthermore, the abundance-based coverage estimator (ACE) decreased from 104.47 to 33.84, and the abundance of eukaryotic viruses also changed substantially. In the annotation, 6 families of DNA viruses and 1 bacteriophage family were present in the normal monkeys but absent after gut bacterial microbiome depletion. Intriguingly, we discovered that changes in the gut bacterial microbiome composition may promote changes in the gut virome composition, and tryptophan, arginine, and quinone may play roles in the interaction between the bacterial microbiome and virome. CONCLUSION: Our results indicated that the clearly altered composition of the virome was correlated with depletion in the bacterial community and that metabolites produced by bacteria possibly play important roles in the interaction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-019-1211-z) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1186/s12985-019-1211-z doi: 10.1186/s12985-019-1211-z id: cord-349042-u9svz7pf author: Li, Jifen title: The successes and future prospects of the linear antisense RNA amplification methodology date: 2018-03-29 words: 5015.0 sentences: 253.0 pages: flesch: 42.0 cache: ./cache/cord-349042-u9svz7pf.txt txt: ./txt/cord-349042-u9svz7pf.txt summary: The technique was originally developed to assess RNA populations from small amounts of starting material, including single cells, but over time its use has evolved to include the detection of various cellular entities such as proteins, RNA-binding-protein-associated cargoes, and genomic DNA. The technique was originally developed to assess RNA populations from small amounts of starting material, including single cells, but over time its use has evolved to include the detection of various cellular entities such as proteins, RNA-binding-protein-associated cargoes, and genomic DNA. Examination of expression profiles of single live cells has shown that linear aRNA amplification neither results in occurs after synthesis of double-stranded cDNA, when T7 RNA polymerase is added and aRNA is transcribed from the cDNA template. 45 developed a method to facilitate aRNA detection of antibody-antigen interactions by covalently attaching a double-stranded cDNA that contains a T7 RNA polymerase promoter in front of a reporter sequence to a specific antibody. abstract: It has been over a quarter of a century since the introduction of the linear RNA amplification methodology known as antisense RNA (aRNA) amplification. Whereas most molecular biology techniques are rapidly replaced owing to the fast-moving nature of development in the field, the aRNA procedure has become a base that can be built upon through varied uses of the technology. The technique was originally developed to assess RNA populations from small amounts of starting material, including single cells, but over time its use has evolved to include the detection of various cellular entities such as proteins, RNA-binding-protein-associated cargoes, and genomic DNA. In this Perspective we detail the linear aRNA amplification procedure and its use in assessing various components of a cell's chemical phenotype. This procedure is particularly useful in efforts to multiplex the simultaneous detection of various cellular processes. These efforts are necessary to identify the quantitative chemical phenotype of cells that underlies cellular function. url: https://doi.org/10.1038/nprot.2018.011 doi: 10.1038/nprot.2018.011 id: cord-048359-lz37rh82 author: Li, Jin title: s-RT-MELT for rapid mutation scanning using enzymatic selection and real time DNA-melting: new potential for multiplex genetic analysis date: 2007-06-01 words: 6258.0 sentences: 299.0 pages: flesch: 49.0 cache: ./cache/cord-048359-lz37rh82.txt txt: ./txt/cord-048359-lz37rh82.txt summary: Subsequently, melting curve analysis, on conventional or nano-technology real-time PCR platforms, detects the samples that contain mutations in a high-throughput and closed-tube manner. Following denaturation and re-annealing of PCR products that leads to formation of cross-hybridized sequences at the positions of mutations ( Figure 1A ) the sample is exposed to Surveyor TM endonuclease that recognizes base pair mismatches or small loops with high specificity (28) and generates a break on both DNA strands 3 0 to the mismatch. Finally, because the amplified mutated sequences contain defined primers at their ends, direct sequencing of enzymatically selected PCR products is readily possible following the real-time melting step, enabling sequencing of low-level mutations identified by Surveyor TM . Here we enabled Surveyor TM , an endonuclease that recognizes selectively mismatches formed by mutations and small deletions following ''cross-hybridized sequence'' formation, to generate mutation-specific DNA fragments that are amplified and screened via differential melting curve analysis. abstract: The rapidly growing understanding of human genetic pathways, including those that mediate cancer biology and drug response, leads to an increasing need for extensive and reliable mutation screening on a population or on a single patient basis. Here we describe s-RT-MELT, a novel technology that enables highly expanded enzymatic mutation scanning in human samples for germline or low-level somatic mutations, or for SNP discovery. GC-clamp-containing PCR products from interrogated and wild-type samples are hybridized to generate mismatches at the positions of mutations over one or multiple sequences in-parallel. Mismatches are converted to double-strand breaks using a DNA endonuclease (Surveyor™) and oligonucleotide tails are enzymatically attached at the position of mutations. A novel application of PCR enables selective amplification of mutation-containing DNA fragments. Subsequently, melting curve analysis, on conventional or nano-technology real-time PCR platforms, detects the samples that contain mutations in a high-throughput and closed-tube manner. We apply s-RT-MELT in the screening of p53 and EGFR mutations in cell lines and clinical samples and demonstrate its advantages for rapid, multiplexed mutation scanning in cancer and for genetic variation screening in biology and medicine. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1919510/ doi: 10.1093/nar/gkm403 id: cord-345552-h6fwi0qn author: Li, Q.-G. title: Hydropathic characteristics of adenovirus hexons date: 1997-07-01 words: 3522.0 sentences: 206.0 pages: flesch: 53.0 cache: ./cache/cord-345552-h6fwi0qn.txt txt: ./txt/cord-345552-h6fwi0qn.txt summary: The strength of the surface charge accumulated on the hydrophilic and hydrophobic regions correlated to the tissue tropism of the different adenovirus types. The sequence of the predicted protein, consisting of 937 amino acids, was obtained with the LaserGene software program EditSeq. The hydropathy data of hexon proteins from human adenovirus types 2, 3, 4, 5, 7, 12, 16, 40, 41, and 48, bovine adenovirus type 3, murine adenovirus type 1, and avian adenovirus types 1 and 10 were derived using the prediction method of Kyte-Doolittle in the LaserGene computer program Protean. The nucleotide and amino acid sequence pair distances and the phylogenetic tree of 14 hexon proteins showed serotypes of subgenera B, D and E to be closely related (Table 3 and Fig. 2) . DNA sequence of the adenovirus type 41 hexon gene and predicted structure of the protein abstract: The complete nucleotide sequence and the predicted amino acid sequence of the adenovirus type 7 hexon gene were determined. The hydro-pathy of the hexon proteins from human adenovirus types 2, 3, 4, 5, 7, 12, 16, 40, 41, and 48, bovine adenovirus type 3, murine adenovirus type 1, and avian adenovirus types 1 and 10 was analysed. The presence of purines and pyrimid-ines in the second position of the codons was correlated to hydrophilicity and hydrophobicity, respectively. Comparison of the hydrophilicity plots of eight hexons showed seven hypervariable regions to be distributed on the surface. A large portion of the hypervariable regions manifests hydrophilicity. The strength of the surface charge accumulated on the hydrophilic and hydrophobic regions correlated to the tissue tropism of the different adenovirus types. Analysis of codon usage for adenovirus hexons showed that among synony-mous codons those with cytidine in the third position were preferably used to a great extent. Analysis of the nucleotide and amino acid sequence pair distances and the phylogenetic tree of 14 hexon proteins showed members of subgenera B, D and E to be closely related, especially Ad4 and Ad16, and subgenus A to be closely related to subgenus F. url: https://www.ncbi.nlm.nih.gov/pubmed/9267445/ doi: 10.1007/s007050050162 id: cord-011630-lfm34fsw author: Li, Yan title: Epigenetic inheritance of circadian period in clonal cells date: 2020-05-27 words: 5694.0 sentences: 306.0 pages: flesch: 43.0 cache: ./cache/cord-011630-lfm34fsw.txt txt: ./txt/cord-011630-lfm34fsw.txt summary: By examining large-scale phenotype-associated gene expression profiles in hundreds of mouse clonal cell lines, we identified and validated multiple novel candidate genes involved in circadian period determination in the absence of significant genomic variants. Here, by examining phenotype-associated high-throughput multi-omics profiles in clonal cell populations, we identified and validated a pool of novel candidate genes regulating circadian period length and uncovered complex gene co-expression networks highly enriched in stress response and metabolic pathways. Using weighted gene co-expression network analysis (WGCNA), we generated 31 modules from the 10 clonal cell lines RNA-seq data ( Figure 4A , Figure 4 -source data 1). Dnmt1 and Dnmt3a knockdown in the ten clonal cell lines showed the same overall results, suggesting that DNA methylation affects circadian periodicity in the same way in all clones tested ( Figure 7C ). abstract: Circadian oscillations are generated via transcriptional-translational negative feedback loops. However, individual cells from fibroblast cell lines have heterogeneous rhythms, oscillating independently and with different period lengths. Here we showed that heterogeneity in circadian period is heritable and used a multi-omics approach to investigate underlying mechanisms. By examining large-scale phenotype-associated gene expression profiles in hundreds of mouse clonal cell lines, we identified and validated multiple novel candidate genes involved in circadian period determination in the absence of significant genomic variants. We also discovered differentially co-expressed gene networks that were functionally associated with period length. We further demonstrated that global differential DNA methylation bidirectionally regulated these same gene networks. Interestingly, we found that depletion of DNMT1 and DNMT3A had opposite effects on circadian period, suggesting non-redundant roles in circadian gene regulation. Together, our findings identify novel gene candidates involved in periodicity, and reveal DNA methylation as an important regulator of circadian periodicity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289596/ doi: 10.7554/elife.54186 id: cord-288960-v6l6o5va author: Li, Yang title: Regulating STING in health and disease date: 2017-06-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The presence of cytosolic double-stranded DNA molecules can trigger multiple innate immune signalling pathways which converge on the activation of an ER-resident innate immune adaptor named “STimulator of INterferon Genes (STING)”. STING has been found to mediate type I interferon response downstream of cyclic dinucleotides and a number of DNA and RNA inducing signalling pathway. In addition to its physiological function, a rapidly increasing body of literature highlights the role for STING in human disease where variants of the STING proteins, as well as dysregulated STING signalling, have been implicated in a number of inflammatory diseases. This review will summarise the recent structural and functional findings of STING, and discuss how STING research has promoted the development of novel therapeutic approaches and experimental tools to improve treatment of tumour and autoimmune diseases. url: https://doi.org/10.1186/s12950-017-0159-2 doi: 10.1186/s12950-017-0159-2 id: cord-264880-0tmd9knh author: Li, Zhao title: Picoliter Well Array Chip-Based Digital Recombinase Polymerase Amplification for Absolute Quantification of Nucleic Acids date: 2016-04-13 words: 5347.0 sentences: 260.0 pages: flesch: 46.0 cache: ./cache/cord-264880-0tmd9knh.txt txt: ./txt/cord-264880-0tmd9knh.txt summary: We developed a picoliter well array (PWA) chip with 27,000 consistently sized picoliter reactions (314 pL) for isothermal DNA quantification using digital RPA (dRPA) at 39°C. To avoid thermal cycling, different isothermal amplification methods have been developed that rapidly amplify nucleic acids to detectable levels at a single temperature [42, 43] , such as loop-mediated amplification (LAMP) [44] , rolling circle amplification (RCA) [45] , helicasedependent amplification (HDA) [46] , nucleic acid sequence-based amplification (NASBA) [47] , recombinase polymerase amplification (RPA) [48] , transcription-mediated amplification (TMA) [49] , multiple displacement amplification (MDA) [50] , and strand-displacement amplification (SDA) [51] . Finally, we sealed the PWA chip in a homemade copper chamber filled with oil and successfully performed real-time dRPA on an isothermal incubation setup for the absolute quantification of serial dilutions of a Listeria monocytogenes gDNA stock solution. abstract: Absolute, precise quantification methods expand the scope of nucleic acids research and have many practical applications. Digital polymerase chain reaction (dPCR) is a powerful method for nucleic acid detection and absolute quantification. However, it requires thermal cycling and accurate temperature control, which are difficult in resource-limited conditions. Accordingly, isothermal methods, such as recombinase polymerase amplification (RPA), are more attractive. We developed a picoliter well array (PWA) chip with 27,000 consistently sized picoliter reactions (314 pL) for isothermal DNA quantification using digital RPA (dRPA) at 39°C. Sample loading using a scraping liquid blade was simple, fast, and required small reagent volumes (i.e., <20 μL). Passivating the chip surface using a methoxy-PEG-silane agent effectively eliminated cross-contamination during dRPA. Our creative optical design enabled wide-field fluorescence imaging in situ and both end-point and real-time analyses of picoliter wells in a 6-cm(2) area. It was not necessary to use scan shooting and stitch serial small images together. Using this method, we quantified serial dilutions of a Listeria monocytogenes gDNA stock solution from 9 × 10(-1) to 4 × 10(-3) copies per well with an average error of less than 11% (N = 15). Overall dRPA-on-chip processing required less than 30 min, which was a 4-fold decrease compared to dPCR, requiring approximately 2 h. dRPA on the PWA chip provides a simple and highly sensitive method to quantify nucleic acids without thermal cycling or precise micropump/microvalve control. It has applications in fast field analysis and critical clinical diagnostics under resource-limited settings. url: https://doi.org/10.1371/journal.pone.0153359 doi: 10.1371/journal.pone.0153359 id: cord-256320-zocunore author: Liao, Bo title: Coronavirus phylogeny based on triplets of nucleic acids bases date: 2006-04-15 words: 1972.0 sentences: 171.0 pages: flesch: 72.0 cache: ./cache/cord-256320-zocunore.txt txt: ./txt/cord-256320-zocunore.txt summary: Abstract We considered the fully overlapping triplets of nucleotide bases and proposed a 2D graphical representation of protein sequences consisting of 20 amino acids and a stop code. Based on this 2D graphical representation, we outlined a new approach to analyze the phylogenetic relationships of coronaviruses by constructing a covariance matrix. Based on these graphical representation, several authors outlined some approaches to make comparison of DNA sequences [21] [22] [23] [24] [25] . In this Letter, we proposed a 2D graphical representation of the protein sequences consisting of 20 amino acids and a stop code. Using the translate tool, we can obtain three protein sequences consisting of 20 amino acids and a stop code. Using the translate tool, one can obtain three protein sequences consisting of 20 amino acids and a stop code corresponding three reading frame start at position 1, 2 and 3. The current two-dimensional graphical representation of DNA sequences provides different approach for constructing phylogenetic tree. abstract: Abstract We considered the fully overlapping triplets of nucleotide bases and proposed a 2D graphical representation of protein sequences consisting of 20 amino acids and a stop code. Based on this 2D graphical representation, we outlined a new approach to analyze the phylogenetic relationships of coronaviruses by constructing a covariance matrix. The evolutionary distances are obtained through measuring the differences among the two-dimensional curves. url: https://www.sciencedirect.com/science/article/pii/S0009261406000728 doi: 10.1016/j.cplett.2006.01.030 id: cord-306059-plsspth8 author: Liao, Bo title: Coronavirus phylogeny based on 2D graphical representation of DNA sequence date: 2006-06-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A novel coronavirus has been identified as the cause of the outbreak of severe acute respiratory syndrome (SARS). Previous phylogenetic analyses based on sequence alignments show that SARS‐CoVs form a new group distantly related to the other three groups of previously characterized coronaviruses. In this aritcle, a new approach based on the 2D graphical representation of the whole genome sequence is proposed to analyze the phylogenetic relationships of coronaviruses. The evolutionary distances are obtained through measuring the differences among the two‐dimensional curves. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1196–1202, 2006 url: https://www.ncbi.nlm.nih.gov/pubmed/16752365/ doi: 10.1002/jcc.20439 id: cord-001537-i34vmfpp author: Lima, Francisco Esmaile de Sales title: Genomic Characterization of Novel Circular ssDNA Viruses from Insectivorous Bats in Southern Brazil date: 2015-02-17 words: 3874.0 sentences: 195.0 pages: flesch: 53.0 cache: ./cache/cord-001537-i34vmfpp.txt txt: ./txt/cord-001537-i34vmfpp.txt summary: The predicted protein sequences encoded by ORF2 (cap) and ORF1 (rep) of BatCV I-VI genomes were used for phylogenetic analysis with representative and recently discovered circoviruses/cycloviruses; Pepper golden mosaic virus was used as outgroup, as they are somewhat related to other members in the Circoviridae family (Fig. 3A, 3B and 3C ). The phylogenetic analysis constructed based on the alignments of the complete REP and CAP protein confirms that BatCV POA/II and VI cluster into the genus Cyclovirus along with the Chinese cycloviruses sequences clade detected in bat feces [18] and sharing less than 65% of identity at the CAP/REP amino acid level. BatCV POA I and V had a low amino acid identity with CAP (<20%) and REP (<10%) sequences of two other sequences detected in bat feces in this study with known circoviruses/cycloviruses (Table 2) . abstract: Circoviruses are highly prevalent porcine and avian pathogens. In recent years, novel circular ssDNA genomes have recently been detected in a variety of fecal and environmental samples using deep sequencing approaches. In this study the identification of genomes of novel circoviruses and cycloviruses in feces of insectivorous bats is reported. Pan-reactive primers were used targeting the conserved rep region of circoviruses and cycloviruses to screen DNA bat fecal samples. Using this approach, partial rep sequences were detected which formed five phylogenetic groups distributed among the Circovirus and the recently proposed Cyclovirus genera of the Circoviridae. Further analysis using inverse PCR and Sanger sequencing led to the characterization of four new putative members of the family Circoviridae with genome size ranging from 1,608 to 1,790 nt, two inversely arranged ORFs, and canonical nonamer sequences atop a stem loop. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331541/ doi: 10.1371/journal.pone.0118070 id: cord-279084-bbae1qyx author: Liu, Bin title: Free DNA, a reason for severe COVID-19 infection? date: 2020-05-05 words: 799.0 sentences: 61.0 pages: flesch: 63.0 cache: ./cache/cord-279084-bbae1qyx.txt txt: ./txt/cord-279084-bbae1qyx.txt summary: I hypothesized that the damage induced by free DNA is a reason for severe COVID-19, which can explain many symptoms of this disease, such as cytokine storm, acute respiratory distress syndrome (ARDS) and muscus plug, acute injuries of heart, liver and kidney, and some special symptoms of COVID-19. I hypothesized that the damage induced by free DNA is a reason for severe 23 COVID-19, which can explain many symptoms of this disease, such as cytokine 24 storm, ARDS and muscus plug, acute injuries of heart, liver and kidney, and some 25 special symptoms of COVID-19. Level 60 of lymphocytes is thought as the early identification of risk factors for severe 61 COVID-19, [1] [2] [3] 8 while I hypothesized that it was related to free DNA-related cytokine 62 storm and blood vessel damage, which can explain many symptoms of this disease, 63 including some "special" symptoms in COVID-19, as shown in Figure 1 . abstract: The fast-growing outbreak of 2019 novel coronaviruses (SARS-CoV-2) reached all continents except the Antarctica in merely three months. Severe SARS-CoV-2 infection (COVID-19) has a bad clinical outcome, and some reports emphasized the role of cytokine storm and dysfunctions of multiple organs. However, the etiology of severe COVID-19 has been largely unknown. Similar as SARS-CoV and MERS-CoV, SARS-CoV-2 is also thought derived from bat coronaviruses. However, it is not pathogenic for bat at all, because free DNA in cytoplasm or blood cannot bring up violent immune response in bat; but it can produce severe inflammations in human. I hypothesized that the damage induced by free DNA is a reason for severe COVID-19, which can explain many symptoms of this disease, such as cytokine storm, acute respiratory distress syndrome (ARDS) and muscus plug, acute injuries of heart, liver and kidney, and some special symptoms of COVID-19. My hypothesis will be helpful for better understand the etiology of severe COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32416412/ doi: 10.1016/j.mehy.2020.109812 id: cord-001111-qqmj4v0u author: Liu, Chengyu title: Strategies for Designing Transgenic DNA Constructs date: 2013-03-08 words: 8122.0 sentences: 382.0 pages: flesch: 47.0 cache: ./cache/cord-001111-qqmj4v0u.txt txt: ./txt/cord-001111-qqmj4v0u.txt summary: Finally, the strategies for conducting each of the major types of transgenic research are discussed, including gene overexpression, promoter characterization, cell-lineage tracing, mutant complementation, expression of double or multiple transgenes, siRNA knockdown, and conditional and inducible systems. Generating a typical transgenic construct involves assembling three basic DNA elements: (1) a promoter and/or enhancer which confers the desired spatial and temporal pattern of transgene expression; (2) the gene to be transcribed, which may or may not encode a protein; and (3) a transcription termination or polyadenylation signal sequence to stop transcription and enable 3 ¢ end processing. BACs can be used for driving expression of Cre and FLP recombinase genes in desired tissues, but as will be discussed in Subheading 4.6 , the commonly used BAC vectors already contain loxP sites, which can be problematic when crossbred to fl oxed mouse lines. abstract: Generation and characterization of transgenic mice are important elements of biomedical research. In recent years, transgenic technology has become more versatile and sophisticated, mainly because of the incorporation of recombinase-mediated conditional expression and targeted insertion, site-specific endonuclease-mediated genome editing, siRNA-mediated gene knockdown, various inducible gene expression systems, and fluorescent protein marking and tracking techniques. Site-specific recombinases (such as PhiC31) and engineered endonucleases (such as ZFN and Talen) have significantly enhanced our ability to target transgenes into specific genomic loci, but currently a great majority of transgenic mouse lines are continuingly being created using the conventional random insertion method. A major challenge for using this conventional method is that the genomic environment at the integration site has a substantial influence on the expression of the transgene. Although our understanding of such chromosomal position effects and our means to combat them are still primitive, adhering to some general guidelines can significantly increase the odds of successful transgene expression. This chapter first discusses the major problems associated with transgene expression, and then describes some of the principles for using plasmid and bacterial artificial chromosomes (BACs) for generating transgenic constructs. Finally, the strategies for conducting each of the major types of transgenic research are discussed, including gene overexpression, promoter characterization, cell-lineage tracing, mutant complementation, expression of double or multiple transgenes, siRNA knockdown, and conditional and inducible systems. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815551/ doi: 10.1007/978-1-60327-369-5_8 id: cord-294877-bbs8a8jz author: Liu, ChuanPeng title: A glimpse of enzymology within the idea of systems date: 2012-09-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/23015132/ doi: 10.1007/s11427-012-4371-2 id: cord-300122-k71s33rg author: Liu, Hung-Jen title: Retardation of cell growth by avian reovirus p17 through the activation of p53 pathway date: 2005-10-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract The second open reading frame of avian reovirus S1 gene segment encodes a 17kDa non-structural protein, named p17. The biological role of p17 is fully unknown so far. Using trypan blue dye exclusion and MTT assay, we demonstrated that the ectopic expression of p17 results in the reduction of viable cell number and cell proliferation rate of Vero, BHK, 293, and HeLa cells. Measurement of LDH activity and DNA fragmentation analysis revealed that p17 expression did not cause cell death or apoptosis. These data indicated that the p17 possessed the growth retardation function. Semi-quantitative RT-PCR and Western blotting revealed that p17-expressing cells induced the expression of CDK inhibitor p21cip1/waf1 in a time- and dose-dependent manner, but the transcripts of CDK inhibitor p15INK4b, p16INK4a, or p27kip were not altered. In the presence of p17, the p53 protein level and p53-driven reporter activity were elevated significantly. Dominant negative p53 alleviated the p21 accumulation, p53 activation, and growth inhibition effect induced by p17. Taken together, these studies revealed a possible intrinsic function of p17 in growth regulation through the activation of p53 and p21cip1/waf1. url: https://api.elsevier.com/content/article/pii/S0006291X05018656 doi: 10.1016/j.bbrc.2005.08.149 id: cord-331916-n744pymd author: Liu, Jue title: Inhibition of porcine circovirus type 2 replication in mice by RNA interference date: 2006-04-10 words: 6657.0 sentences: 350.0 pages: flesch: 52.0 cache: ./cache/cord-331916-n744pymd.txt txt: ./txt/cord-331916-n744pymd.txt summary: Specific inhibition of endogenous or pathogen mRNA by RNAi can be triggered by the introduction of 21 -23 nucleotide (nt) duplexes of RNA (siRNA) or by transcription of DNA precursor into short hairpin RNAs (shRNA) homologous to target sequences (Brummelkamp et al., 2002; Elbashir et al., 2001a; Paddison et al., 2002) , opening up possibilities for controlling replicative processes of pathogens. To further examine the ability of ORF1 shRNA to suppress viral gene expression in PCV2-infected PK15 cells, single nucleotide mutations were introduced into pSIR3 sequence as shown in Fig. 4A . As shown in Fig. 4B , a mutant with one nucleotide mutation in the 5V-end of the sense strand (pSIR3-m1) still had an effective reduction in the synthesis of ORF1 and ORF2 proteins, whereas with a nucleotide substitution at the center (pSIR3-m2) or 3V-end (pSIR3-m3) of the sense sequence, the resultant shRNAs failed to significantly suppress expression of PCV2 ORF1 and ORF2 in the transfected cells, further verifying the specificity of RNAi as demonstrated (Amarzguioui et al., 2003; Harborth et al., 2003) . abstract: Porcine circovirus type 2 (PCV2) is the primary causative agent of an emerging swine disease, postweaning multisystemic wasting syndrome (PMWS) for which no antiviral treatment is available. To exploit the possibility of using RNA interference (RNAi) as a therapeutic approach against the disease, plasmid-borne short hairpin RNAs (shRNAs) were generated to target the PCV2 genome. Transfection of these shRNAs into cultured PK15 cells caused a significant reduction in viral RNA production that was accompanied by inhibiting viral DNA replication and protein synthesis in infected cells. The effect was further tested in vivo in a mouse model that has been developed for PCV2 infection. Mice injected with shRNA before PCV2 infection showed substantially decreased microscopic lesions in inguinal lymph nodes compared to controls. In situ hybridization and immunohistochemical analyses showed that shRNA caused a significant inhibition in the level of viral DNA and protein synthesis detected in the lymph nodes of the treated mice relative to the controls. Taken together, these results indicate that shRNAs are capable of inhibiting PCV2 infection in vitro as well as in vivo and thus may constitute an effective therapeutic strategy for PCV2 infection. url: https://www.ncbi.nlm.nih.gov/pubmed/16427679/ doi: 10.1016/j.virol.2005.12.006 id: cord-022168-qautse9a author: Liu, Li title: Clinical Use of DNA Vaccines date: 2017-07-25 words: 7120.0 sentences: 321.0 pages: flesch: 38.0 cache: ./cache/cord-022168-qautse9a.txt txt: ./txt/cord-022168-qautse9a.txt summary: Specifically, the strategies that allow DNA vaccines to overcome antigenic diversity for viral infection and break immune tolerance for cancer therapy are explored. To overcome these obstacles, several approaches focusing on augmenting DNA uptake, maximizing protein expression, and enhancing antigen immunogenicity have been developed and tested in clinical trials. Therefore, one key element to improve DNA vaccine efficacy is to formulate a vaccine with an immunogenic cancer antigen so that it can prime T cells for immune responses. To date, the most successful and encouraging outcomes of using DNA vaccine in the clinical setting were obtained from treatment of malignant diseases where the etiological agent is of foreign viral origin, such as the human papillomavirus (HPV), as these viral agents can readily induce a strong immune response against cancerous cells harboring viral antigens. abstract: Owing to their unique advantages in simplicity, safety, scalability, and possibility of repeated administrations, DNA vaccines represent an appealing and competitive immunization approach for a wide array of conditions, including but not limited to infectious diseases and cancer immunotherapy. Despite the exciting efficacy observed in preclinical studies, DNA vaccines have faced challenges in inducing strong immune responses in humans. This unexpected poor immunogenicity has severely hampered the translation of DNA vaccines from investigational medications to licensed products. To overcome this obstacle, tremendous efforts have been made to improve antigen expression and enhance immunogenicity. Among these endeavors, in vivo DNA electroporation (EP) has proved to be a breakthrough technology capable of mediating efficient DNA uptake and resulting in enhanced antigen expression and vaccine immunogenicity. EP-mediated DNA delivery has become one of the major platforms used in clinical trials to evaluate DNA vaccines in humans. In this chapter, in addition to EP delivery, other progress made in DNA vaccine development including plasmid optimization, antigen design, and immunologic adjuvants is also reviewed. Finally, the use of DNA vaccines in the context of clinical trials for infectious diseases and cancer immunotherapy is summarized. Specifically, the strategies that allow DNA vaccines to overcome antigenic diversity for viral infection and break immune tolerance for cancer therapy are explored. Based on the advantages of DNA vaccines and the immense progress, led by the electroporation-mediated vaccine delivery, DNA vaccines appear to have the potential to fundamentally transform the vaccine field, providing important benefits for preventing and curing diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153459/ doi: 10.1007/978-3-319-32886-7_106 id: cord-301167-101lnq4f author: Liu, Quanjun title: Microarray-in-a-Tube for Detection of Multiple Viruses date: 2007-02-01 words: 3248.0 sentences: 177.0 pages: flesch: 48.0 cache: ./cache/cord-301167-101lnq4f.txt txt: ./txt/cord-301167-101lnq4f.txt summary: Methods: We developed a novel PCR assay, the microarray-in-a-tube system, which integrates multiple PCR processes and DNA microarrays for multiple virus detection. A 5 × 5 oligonucleotide microarray for detecting 4 respiratory tract viruses (severe acute respiratory syndrome–associated coronavirus, influenza A virus, influenza B virus, and enterovirus) with inner controls was arranged on the inner surface of a specially designed Eppendorf cap with a flat, optically transparent window. We aimed to develop a microarray-in-a-tube that integrates RT-PCR and a DNA microarray for detecting and distinguishing 4 viruses causing human acute respiratory tract infection, SARS coronavirus, influenza A and B viruses, and enterovirus. The system (Fig. 1 ) has 3 parts, which include an optically transparent plastic cap with an oligonucleotide microarray on the inner surface, a black inner vessel that contains hybridization solution, and the body of the Eppendorf tube. abstract: Background: The detection of multiple viruses is important for pathogenic diagnosis and disease control. Microarray detection is a good method, but requires complex procedures for multiple virus detection. Methods: We developed a novel PCR assay, the microarray-in-a-tube system, which integrates multiple PCR processes and DNA microarrays for multiple virus detection. A 5 × 5 oligonucleotide microarray for detecting 4 respiratory tract viruses (severe acute respiratory syndrome–associated coronavirus, influenza A virus, influenza B virus, and enterovirus) with inner controls was arranged on the inner surface of a specially designed Eppendorf cap with a flat, optically transparent window. Results: We were able to perform all detection processes in the encapsulated system without opening the cap. The 4 viruses were successfully amplified by one-step reverse transcription–PCR in the encapsulated tube. After the PCR process, the microarray-in-a-tube was inverted, and the fluorescence-labeled PCR products were directly hybridized on the microarray. Hybridization signals were obtained with an ordinary fluorescent microscope. The sensitivity of the system for virus detection reached 10(2) copies/μL. With the help of inner controls, the system provided reliable results without false negatives and false positives. Conclusions: The microarray-in-a-tube system is a rapid, labor-saving tool for multiple virus detection with several advantages, such as convenience, prevention of cross-contamination of the PCR products, and potential for multiple-gene detection. url: https://www.ncbi.nlm.nih.gov/pubmed/17158198/ doi: 10.1373/clinchem.2006.071720 id: cord-013614-j6h338qa author: Liu, Xiaojing title: ERCC6L2 promotes DNA orientation-specific recombination in mammalian cells date: 2020-04-30 words: 8200.0 sentences: 576.0 pages: flesch: 55.0 cache: ./cache/cord-013614-j6h338qa.txt txt: ./txt/cord-013614-j6h338qa.txt summary: To identify potentially new NHEJ factors, we combined chemical perturbation screens on 36 compounds with focused CRISPRknockout screens on 414 genes in the CH12 B cell line ( Fig. 1a ; Supplementary information, Table S1 , see Materials and Methods for details). ERCC6L2 clusters with other NHEJ factors Next, we clustered all 414 DNA repair genes by their z-scores across the 36 chemicals used, which categorized genes into three major groups depending on their impact on cell growth (Supplementary information, Fig. S1a ). Furthermore, the helicase catalytic-dead (DEAH > AAAH) mutant did not promote CSR ( Fig. 3a ; Supplementary information, Fig. S4b ), indicating that ERCC6L2''s predicted catalytic activity is required for DNA end-joining. To bypass the B cell development defect of core-NHEJ factor deficiencies and quickly access the directional CSR, we deleted the non-productive IgH allele in CH12F3 cells as previous described 18 (Supplementary information, Fig. S8c , named CH12-NCDel cells) and perform HTGTS assay with endogenous AID Sμ baits. abstract: Programmed DNA recombination in mammalian cells occurs predominantly in a directional manner. While random DNA breaks are typically repaired both by deletion and by inversion at approximately equal proportions, V(D)J and class switch recombination (CSR) of immunoglobulin heavy chain gene overwhelmingly delete intervening sequences to yield productive rearrangement. What factors channel chromatin breaks to deletional CSR in lymphocytes is unknown. Integrating CRISPR knockout and chemical perturbation screening we here identify the Snf2-family helicase-like ERCC6L2 as one such factor. We show that ERCC6L2 promotes double-strand break end-joining and facilitates optimal CSR in mice. At the cellular levels, ERCC6L2 rapidly engages in DNA repair through its C-terminal domains. Mechanistically, ERCC6L2 interacts with other end-joining factors and plays a functionally redundant role with the XLF end-joining factor in V(D)J recombination. Strikingly, ERCC6L2 controls orientation-specific joining of broken ends during CSR, which relies on its helicase activity. Thus, ERCC6L2 facilitates programmed recombination through directional repair of distant breaks. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608219/ doi: 10.1038/s41422-020-0328-3 id: cord-331641-u27ohm5p author: Liu, Xiaonan title: A direct isothermal amplification system adapted for rapid SNP genotyping of multifarious sample types date: 2018-09-15 words: 3850.0 sentences: 186.0 pages: flesch: 51.0 cache: ./cache/cord-331641-u27ohm5p.txt txt: ./txt/cord-331641-u27ohm5p.txt summary: In this study, we devised a Direct-LAMP procedure, amplifying nucleic acids with various samples (including whole blood, dried blood spot, buccal swab and saliva) without DNA purification, which is essential for conventional nucleic acid detection methods. To evaluate the performance of the Direct-LAMP, a serial dilution of the target concentrations of whole blood sample and saliva sample with two different genotypes (wild type and homozygous mutation which confirmed by sequencing) of MTHFR C677T and ALDH2 Glu504Lys, respectively, were used to determine the detection limit. Here, we have established a rapid, easy-to-use and accurate SNP detection platform using Direct-LAMP, which enables us to use whole blood, dried blood spot, buccal swab or saliva as samples for genotyping without DNA purification. In this study, we presented a Direct-LAMP for SNP detection by using whole blood, dried blood spot, buccal swab or saliva as samples without DNA purification. abstract: Genotyping of single nucleotide polymorphisms (SNPs) in point-of-care (POC) settings could be further improved through simplifying the treatment of samples. In this study, we devised an accurate, rapid and easy-to-use SNP detection system based on direct loop-mediated isothermal amplification (LAMP) without DNA extraction, known as Direct-LAMP. Samples from various sources (including whole blood, dried blood spot, buccal swab and saliva), treated with NaOH, can be used directly in amplification. The turnaround time was about 30 min from sample collection to provision of results. The accuracy was evaluated by assessing the polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and aldehyde dehydrogenase-2 (ALDH2) Glu504Lys, which are better known for their critical role in folate and ethanol metabolism, respectively. Completely consistent genotyping results reveal that Direct-LAMP is generally concordant with sequencing. This system can serve as a very promising platform in the fields of disease predisposition, drug metabolism and personalized medicine. url: https://doi.org/10.1016/j.bios.2018.05.021 doi: 10.1016/j.bios.2018.05.021 id: cord-346965-0oq2n0af author: Liu, Zhi-Ping title: Bridging protein local structures and protein functions date: 2008-04-18 words: 14491.0 sentences: 810.0 pages: flesch: 44.0 cache: ./cache/cord-346965-0oq2n0af.txt txt: ./txt/cord-346965-0oq2n0af.txt summary: The characteristics between interface and noninterface portions of a protein surface, such as sequence conservation, proportions of amino acids, secondary structure, solvent accessibility and side-chain conformational entropy, are often used to distinguish the specificity of local structures relating to protein binding function. The method relies on a simplified representation of the chemical groups found in amino acid side-chains to identify functional sites from a single protein structure and a number of its sequence homologs. (2006) improved previous approaches by combining two known measures of ''functionality'' in proteins, i.e. cleft volume and residue conservation, to develop a method for identifying the location of ligand-binding pockets in proteins. (2006) applied an SVM method to predict DNA-binding sites using the features including amino acid sequence, profile of evolutionary conservation of sequence positions, and low-resolution structural information. (2006) developed a method to predict both protein-protein binding site location and interface type (obligate or non-obligate) using a Bayesian network in combination with surface patch analysis. abstract: One of the major goals of molecular and evolutionary biology is to understand the functions of proteins by extracting functional information from protein sequences, structures and interactions. In this review, we summarize the repertoire of methods currently being applied and report recent progress in the field of in silico annotation of protein function based on the accumulation of vast amounts of sequence and structure data. In particular, we emphasize the newly developed structure-based methods, which are able to identify locally structural motifs and reveal their relationship with protein functions. These methods include computational tools to identify the structural motifs and reveal the strong relationship between these pre-computed local structures and protein functions. We also discuss remaining problems and possible directions for this exciting and challenging area. url: https://www.ncbi.nlm.nih.gov/pubmed/18421562/ doi: 10.1007/s00726-008-0088-8 id: cord-338164-pyam9yn3 author: Livingston, Andrew D title: Biochip sensors for the rapid and sensitive detection of viral disease date: 2005-05-26 words: 3506.0 sentences: 175.0 pages: flesch: 41.0 cache: ./cache/cord-338164-pyam9yn3.txt txt: ./txt/cord-338164-pyam9yn3.txt summary: Recent advances in DNA and protein microarray methodology and the emerging technology of cell-based sensors have massively increased the speed and sensitivity with which we can detect viral infections. Recent advances in DNA and protein microarray methodology and the emerging technology of cellbased sensors have massively increased the speed and sensitivity with which we can detect viral infections. We therefore need a rapid, sensitive approach that is capable of identifying multiple viruses in parallel; this need is being addressed by the development of DNA and protein microarrays specifically designed for virus detection and identification. The authors [4] described the use of viral DNA microarrays to produce hybridization signatures of viral sequences that effectively serve as ''viral barcodes'' for the identification of known, related or novel viruses. Cellular systems, such as the light-emitting B cells engineered by the Rider group [19] , while individually not having the parallel capabilities of the array, provide an extremely rapid detection system. abstract: Recent advances in DNA and protein microarray methodology and the emerging technology of cell-based sensors have massively increased the speed and sensitivity with which we can detect viral infections. The advantages of the multi-parameter microarray technologies could be combined with the speed and sensitivity of cell-based systems to give 'cell-omic' sensors. url: https://www.ncbi.nlm.nih.gov/pubmed/15960809/ doi: 10.1186/gb-2005-6-6-112 id: cord-298051-ej8qxkce author: Louten, Jennifer title: Detection and Diagnosis of Viral Infections date: 2016-05-06 words: 11204.0 sentences: 602.0 pages: flesch: 57.0 cache: ./cache/cord-298051-ej8qxkce.txt txt: ./txt/cord-298051-ej8qxkce.txt summary: Cell lines can be infected with patient samples to allow viral replication within the cells; observable cytopathic effects can help to identify the identity of the virus. Infected cells can also be used for immunofluorescence assays, which use fluorescently labeled virus-specific antibodies to identify viruses in fixed cells or tissues. In the process of PCR, DNA (including any viral DNA present) is isolated from the clinical specimen, generally blood cells or tissue, and added to a tube containing primers, DNA polymerase, and nucleotides ( Fig. 7.14) . The diagnostic techniques described in this chapter identify the presence of a virus in a sample, or even the amount of viral nucleic acid, but these assays cannot determine the amount of virus present that is capable of productively infecting cells. Fluorescently labeled antibodies bind to viral antigens present in infected cells. abstract: Diagnostic tests are paramount in determining the etiology of viral infections. Direct diagnostic methods assay for the presence of the virus, while indirect methods test for effects of the virus. Cell culture is the process of growing cells or tissues in the laboratory. Cell lines can be infected with patient samples to allow viral replication within the cells; observable cytopathic effects can help to identify the identity of the virus. Infected cells can also be used for immunofluorescence assays, which use fluorescently labeled virus-specific antibodies to identify viruses in fixed cells or tissues. A variety of diagnostic immunoassays exist, including enzyme-linked immunosorbent assays/enzyme immunoassays, western blots, lateral flow immunoassays, and agglutination reactions. Assays that detect viral nucleic acids are based upon the principles of PCR or nucleic acid hybridization, are extremely sensitive, and are specific for a particular virus. url: https://api.elsevier.com/content/article/pii/B9780128009475000077 doi: 10.1016/b978-0-12-800947-5.00007-7 id: cord-009376-a35a92gh author: Lovatt, Archie title: Applications of quantitative PCR in the biosafety and genetic stability assessment of biotechnology products date: 2002-01-07 words: 9214.0 sentences: 523.0 pages: flesch: 48.0 cache: ./cache/cord-009376-a35a92gh.txt txt: ./txt/cord-009376-a35a92gh.txt summary: Applications of Q-PCR within biotechnology are discussed with particular emphasis on the following areas of biosafety and genetic stability testing: (a) determination of the biodistribution of gene therapy vectors in animals; (b) quantification of the residual DNA in final product therapeutics; (c) detection of viral and bacterial nucleic acid in contaminated cell banks and final products; (d) quantification of the level of virus removal in process validation viral clearance studies; (e) specific detection of retroviral RT activity in vaccines with high sensitivity; and (f) transgene copy number determination for monitoring genetic stability during production. We are developing Q-PCR assays for these repeat regions for rodent and primate residual DNA to obtain sensitivity in the fg range, however, one advantage of using a gene such as ␤-actin is gene stability, as this target should not undergo copy number changes within a stable cell line. abstract: High throughput screening, increased accuracy and the coupling of real-time quantitative PCR (Q-PCR) to robotic set-up systems are beginning to revolutionise biotechnology. Applications of Q-PCR within biotechnology are discussed with particular emphasis on the following areas of biosafety and genetic stability testing: (a) determination of the biodistribution of gene therapy vectors in animals; (b) quantification of the residual DNA in final product therapeutics; (c) detection of viral and bacterial nucleic acid in contaminated cell banks and final products; (d) quantification of the level of virus removal in process validation viral clearance studies; (e) specific detection of retroviral RT activity in vaccines with high sensitivity; and (f) transgene copy number determination for monitoring genetic stability during production. Methods employed for Q-PCR assay validation as required in ICH Topic Q2A Validation of Analytical Methods: Definitions and Terminology (1st June 1995) are also reviewed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148957/ doi: 10.1016/s1389-0352(01)00043-5 id: cord-023727-ahbnchj9 author: Low, K. Brooks title: Genetic Recombination: A Brief Overview date: 2012-12-02 words: 4931.0 sentences: 290.0 pages: flesch: 46.0 cache: ./cache/cord-023727-ahbnchj9.txt txt: ./txt/cord-023727-ahbnchj9.txt summary: In rare instances, rearrangements of DNA molecules have been observed to result from an apparent end-to-end fusion process or else a chromosomal crossover which does not appear to involve extensive homology or site-specificity. Examples of irregular recombination events include apparent end-toend fusion events in bacteria (Guyer et ai, 1977; Horowitz and Deonier, 1985) ; recombination involving an origin of replication (Kilbane and Malamy, 1980; Michel and Ehrlich, 1986) ; nonrandom crossovers involving extremely small (if any) regions of homology (e.g., 5-10 base pairs) (King et al, 1982d; Linn et ai, 1979; Mertz and Berg, 1974; Nakano et al., 1984; Schmid and Roth, 1983) ; end-joining of DNA transfected into animal cells Wilson, 1985, 1986) ; and nonhomologous joining of phage λ and plasmid pBR322 (Ikeda, 1986) . abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173541/ doi: 10.1016/b978-0-12-456270-7.50006-0 id: cord-252838-av7ducrk author: Lucchi, Naomi W. title: Real-Time Fluorescence Loop Mediated Isothermal Amplification for the Diagnosis of Malaria date: 2010-10-29 words: 4913.0 sentences: 250.0 pages: flesch: 52.0 cache: ./cache/cord-252838-av7ducrk.txt txt: ./txt/cord-252838-av7ducrk.txt summary: In this study, we attempted to improve this method for malaria diagnosis by using a simple and portable device capable of performing both the amplification and detection (by fluorescence) of LAMP in one platform. reported a species specific LAMP diagnostic method; using clinical samples and a conventional DNA extraction method, they demonstrated sensitivity and specificity of 98.5% and 94.3% respectively compared to microscopy and a nested PCR [14] . We refer to this method as RealAmp. We demonstrate the utility of this method for the diagnosis of malaria by using published Plasmodium genus specific primers and comparing it to microscopy and a nested PCR method as described by Singh et al [18] . As summarized in Table 5 , results from the RealAmp method were comparable to the previously reported malaria LAMP assays [13] [14] [15] [16] [17] demonstrating reasonable sensitivity and specificity profiles when compared to microscopy and nested PCR. abstract: BACKGROUND: Molecular diagnostic methods can complement existing tools to improve the diagnosis of malaria. However, they require good laboratory infrastructure thereby restricting their use to reference laboratories and research studies. Therefore, adopting molecular tools for routine use in malaria endemic countries will require simpler molecular platforms. The recently developed loop-mediated isothermal amplification (LAMP) method is relatively simple and can be improved for better use in endemic countries. In this study, we attempted to improve this method for malaria diagnosis by using a simple and portable device capable of performing both the amplification and detection (by fluorescence) of LAMP in one platform. We refer to this as the RealAmp method. METHODOLOGY AND SIGNIFICANT FINDINGS: Published genus-specific primers were used to test the utility of this method. DNA derived from different species of malaria parasites was used for the initial characterization. Clinical samples of P. falciparum were used to determine the sensitivity and specificity of this system compared to microscopy and a nested PCR method. Additionally, directly boiled parasite preparations were compared with a conventional DNA isolation method. The RealAmp method was found to be simple and allowed real-time detection of DNA amplification. The time to amplification varied but was generally less than 60 minutes. All human-infecting Plasmodium species were detected. The sensitivity and specificity of RealAmp in detecting P. falciparum was 96.7% and 91.7% respectively, compared to microscopy and 98.9% and 100% respectively, compared to a standard nested PCR method. In addition, this method consistently detected P. falciparum from directly boiled blood samples. CONCLUSION: This RealAmp method has great potential as a field usable molecular tool for diagnosis of malaria. This tool can provide an alternative to conventional PCR based diagnostic methods for field use in clinical and operational programs. url: https://doi.org/10.1371/journal.pone.0013733 doi: 10.1371/journal.pone.0013733 id: cord-282618-tjvjlyn9 author: Luke, J M title: Improved antibiotic-free plasmid vector design by incorporation of transient expression enhancers date: 2010-11-25 words: 6241.0 sentences: 336.0 pages: flesch: 43.0 cache: ./cache/cord-282618-tjvjlyn9.txt txt: ./txt/cord-282618-tjvjlyn9.txt summary: To maintain a low risk of insertional mutagenesis-mediated gene activation, expression-augmenting sequences would ideally function to improve transgene expression from transiently transfected intact plasmid, but not from spurious genomically integrated vectors. A neomycin resistance gene (NeoR) without an upstream Kozak sequence was cloned downstream of an enhanced green fluorescent protein (EGFP) transgene in different configurations similar to that used with PREs. Quantifiable neoR translation products were present in all tested configurations, as was biologically active neoR protein after plasmid transfection into both HEK293 and CHO cell lines (Supplementary Table S1 ). The assay was in the same format as in (a), except for the fact that Pol III inhibitor-treated cells were transfected with EGFP plasmids containing the CMV-HTLV-I R promoter with or without VA1; (c) Inhibition of PKR, not of adenosine deaminase acting on RNA (ADAR) or RNA interference (RNAI), was required for VA1 expression enhancement effect. abstract: Methods to improve plasmid-mediated transgene expression are needed for gene medicine and gene vaccination applications. To maintain a low risk of insertional mutagenesis-mediated gene activation, expression-augmenting sequences would ideally function to improve transgene expression from transiently transfected intact plasmid, but not from spurious genomically integrated vectors. We report herein the development of potent minimal, antibiotic-free, high-manufacturing-yield mammalian expression vectors incorporating rationally designed additive combinations of expression enhancers. The SV40 72 bp enhancer incorporated upstream of the cytomegalovirus (CMV) enhancer selectively improved extrachromosomal transgene expression. The human T-lymphotropic virus type I (HTLV-I) R region, incorporated downstream of the CMV promoter, dramatically increased mRNA translation efficiency, but not overall mRNA levels, after transient transfection. A similar mRNA translation efficiency increase was observed with plasmid vectors incorporating and expressing the protein kinase R-inhibiting adenoviral viral associated (VA)1 RNA. Strikingly, HTLV-I R and VA1 did not increase transgene expression or mRNA translation efficiency from plasmid DNA after genomic integration. The vector platform, when combined with electroporation delivery, further increased transgene expression and improved HIV-1 gp120 DNA vaccine-induced neutralizing antibody titers in rabbits. These antibiotic-free vectors incorporating transient expression enhancers are safer, more potent alternatives to improve transgene expression for DNA therapy or vaccination. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/gt.2010.149) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/21107439/ doi: 10.1038/gt.2010.149 id: cord-313161-07iwwsfz author: Lundstrom, Kenneth title: Alphavirus-Based Vaccines date: 2014-06-16 words: 6844.0 sentences: 322.0 pages: flesch: 30.0 cache: ./cache/cord-313161-07iwwsfz.txt txt: ./txt/cord-313161-07iwwsfz.txt summary: Furthermore, sequential immunization with SIN and VEE replicon particles expressing the type 1 HIV gp140 envelope (Env) and trimeric Env protein in MF59 adjuvant provided partial protection in macaques against intravenous challenges with high doses of simian-human immunodeficiency virus (SHIV) [61] . In another study, chimeric VEE/SIN replicon particles were applied for the expression of measles virus hemagglutinin (H) and fusion (F) proteins, which elicited high-titer neutralizing antibody and IFNɤ-producing T-cells in macaques after intradermal vaccination [48] . Furthermore, vaccination with recombinant particles expressing the P1A gene [105] and the human papilloma virus (HPV) E7 gene [89] from SFV and VEE vectors, respectively, provided protection against further tumor development in mice. When TRAMP mice were prophylactically immunized with a prostate stem cell antigen (PSCA) DNA plasmid followed by VEE-PSCA particle administration, a specific immune response and anti-tumor protection were observed in 90% of vaccinated animals [102] . abstract: Alphavirus vectors have demonstrated high levels of transient heterologous gene expression both in vitro and in vivo and, therefore, possess attractive features for vaccine development. The most commonly used delivery vectors are based on three single-stranded encapsulated alphaviruses, namely Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus. Alphavirus vectors have been applied as replication-deficient recombinant viral particles and, more recently, as replication-proficient particles. Moreover, in vitro transcribed RNA, as well as layered DNA vectors have been applied for immunization. A large number of highly immunogenic viral structural proteins expressed from alphavirus vectors have elicited strong neutralizing antibody responses in multispecies animal models. Furthermore, immunization studies have demonstrated robust protection against challenges with lethal doses of virus in rodents and primates. Similarly, vaccination with alphavirus vectors expressing tumor antigens resulted in prophylactic protection against challenges with tumor-inducing cancerous cells. As certain alphaviruses, such as Chikungunya virus, have been associated with epidemics in animals and humans, attention has also been paid to the development of vaccines against alphaviruses themselves. Recent progress in alphavirus vector development and vaccine technology has allowed conducting clinical trials in humans. url: https://doi.org/10.3390/v6062392 doi: 10.3390/v6062392 id: cord-341521-dntkdwkj author: Luo, Yi-Ran title: Porcine Epidemic Diarrhoea Virus Induces Cell-cycle Arrest through the DNA Damage-signalling Pathway date: 2020-03-24 words: 4077.0 sentences: 168.0 pages: flesch: 52.0 cache: ./cache/cord-341521-dntkdwkj.txt txt: ./txt/cord-341521-dntkdwkj.txt summary: MATERIAL AND METHODS: We observed the effect of the PEDV SHpd/2012 strain on an infected Vero cell cycle through flow cytometry and Western blot, investigating the interrelationships of cell-cycle arrest, the DNA damage–signalling pathway caused by PEDV and the phosphorylation levels of the key molecules Chk.2 and H2A.X involved upstream and downstream in this pathway. We used inhibitors of ATM and Chk.2 to block the DNA damage-signalling pathway and to confirm whether PEDV infection can lead to cell-cycle arrest. We also treated cells with chemical inhibitors of ATM and Chk.2 to determine if cell-cycle arrest after PEDV infection was linked with activation of the DNA damage-signalling pathway. These results revealed that cell-cycle arrest after infection of Vero cells with PEDV was caused by activation of the DNA damage-signalling pathway. abstract: INTRODUCTION: Porcine epidemic diarrhoea virus (PEDV) infection causes watery diarrhoea, vomiting, anorexia, and weight loss, especially among neonatal piglets, inflicting on them morbidity and mortality potentially reaching 90%–100%. Despite it being known that certain mammalian cell phases are arrested by PEDV, the mechanisms have not been elucidated, and PEDV pathogenesis is poorly understood. This study determined the effect of an epidemic PEDV strain on cell cycle progression. MATERIAL AND METHODS: We observed the effect of the PEDV SHpd/2012 strain on an infected Vero cell cycle through flow cytometry and Western blot, investigating the interrelationships of cell-cycle arrest, the DNA damage–signalling pathway caused by PEDV and the phosphorylation levels of the key molecules Chk.2 and H2A.X involved upstream and downstream in this pathway. RESULTS: PEDV induced Vero cell-cycle arrest at the G1/G0 phase. The phosphorylation levels of Chk.2 and H2A.X increased with the prolongation of PEDV infection, and no significant cell-cycle arrest was observed after treatment with ATM or Chk.2 inhibitors. The proliferation of PEDV was also inhibited by treatment with ATM or Chk.2 inhibitors. CONCLUSION: PEDV-induced cell-cycle arrest is associated with activation of DNA damage–signalling pathways. Our findings elucidate the molecular basis of PEDV replication and provide evidence to support further evaluation of PEDV pathogenesis. url: https://doi.org/10.2478/jvetres-2020-0024 doi: 10.2478/jvetres-2020-0024 id: cord-271504-t3y1w9ef author: Luo, Zichao title: Combating the Coronavirus Pandemic: Early Detection, Medical Treatment, and a Concerted Effort by the Global Community date: 2020-06-16 words: 14361.0 sentences: 795.0 pages: flesch: 42.0 cache: ./cache/cord-271504-t3y1w9ef.txt txt: ./txt/cord-271504-t3y1w9ef.txt summary: A confirmed case should have at least one of the following criteria: (i) a positive result for 2019-nCoV nucleic acid, using real-time PCR tests from respiratory or blood samples; (ii) a high homogeneity between viral gene sequencing from respiratory or blood samples and known 2019-nCoV; and (iii) serum samples positive for IgM or IgG to 2019-nCoV, or seroconversion in IgG, or a fourfold or more significant increase in IgG antibody titer to 2019-nCoV in the recovery phase than in the acute phase [25] . Using blood samples taken from alleged COVID-19 patients, the researchers detected antibodies targeting the spike protein that prevented the virus from killing cells in laboratory tests. showed a promising in vitro inhibitory effect of this serine protease inhibitor in SARS-CoV and 2019-nCoV on human lung cells, showing potential as a viable option for COVID-19 treatment [113] . Given that antiviral drugs have previously demonstrated reasonable inhibition of coronaviruses and therapeutic efficacy against coronavirus outbreaks, umifenovir, chloroquine, hydroxychloroquine, lopinavir-ritonavir, and ribavirin have been recommended in the latest guidelines for diagnosis and treatment of COVID-19, updated on 17 February 2020 [189] . abstract: The World Health Organization (WHO) has declared the outbreak of 2019 novel coronavirus, known as 2019-nCoV, a pandemic, as the coronavirus has now infected over 2.6 million people globally and caused more than 185,000 fatalities as of April 23, 2020. Coronavirus disease 2019 (COVID-19) causes a respiratory illness with symptoms such as dry cough, fever, sudden loss of smell, and, in more severe cases, difficulty breathing. To date, there is no specific vaccine or treatment proven effective against this viral disease. Early and accurate diagnosis of COVID-19 is thus critical to curbing its spread and improving health outcomes. Reverse transcription-polymerase chain reaction (RT-PCR) is commonly used to detect the presence of COVID-19. Other techniques, such as recombinase polymerase amplification (RPA), loop-mediated isothermal amplification (LAMP), clustered regularly interspaced short palindromic repeats (CRISPR), and microfluidics, have allowed better disease diagnosis. Here, as part of the effort to expand screening capacity, we review advances and challenges in the rapid detection of COVID-19 by targeting nucleic acids, antigens, or antibodies. We also summarize potential treatments and vaccines against COVID-19 and discuss ongoing clinical trials of interventions to reduce viral progression. url: https://www.ncbi.nlm.nih.gov/pubmed/32607499/ doi: 10.34133/2020/6925296 id: cord-016144-280kwlev author: Maan, Sushila title: Novel Molecular Diagnostics and Therapeutic Tools for Livestock Diseases date: 2018-04-26 words: 6526.0 sentences: 364.0 pages: flesch: 45.0 cache: ./cache/cord-016144-280kwlev.txt txt: ./txt/cord-016144-280kwlev.txt summary: Further, modifications in PCR-based molecular detection techniques have generated a vast array of fast, reliable and specific assays which have widespread applications in veterinary diagnostics. The sensitivity of any genome detection-based method can be enhanced to a very high degree by manipulating any of the three pillars of the assay, i.e. by amplification of target, signal and probe. Common real-time PCRs include (1) SYBR green method where the fluorescent dye SYBR green binds to random dsDNA and can also give nonspecific amplification and (2) dual dyelabelled probe method which involves the use of sequence-specific DNA probes that are labelled with a fluorescent reporter, permitting specific detection after hybridization of the probe with its complementary sequence. To overcome these limitations and to increase efficiency comparable to symmetric PCRs, linear after the exponential (LATE)-PCR was developed based on primer pairs purposely designed for use at unequal concentrations to yield specific single-stranded DNA products in a robust way (Pierce et al. abstract: Recent novelties in diverse diagnostics and therapeutic tools in animal health sector have paved a brighter and clearer way ahead. These are proved to be better in detection, management, control and eradication of animal sufferings caused by various infectious and non-infectious diseases. These innovations have potential impact that extends beyond the animal health and welfare. The advancements have significantly contributed towards improvement in the economy of the country as well as food security. In the present competitive era of evolution, the organisms have inculcated a number of new strategies for survival and spread. Therefore, science needs to continuously evolve more sensitive, specific and high-throughput tools to overcome pathogen cleverness to escape from host immune surveillance. For visible or remarkable changes, it is necessary to use full potential of these advanced molecular techniques into current animal health standards and practices. Under ‘One Health’ concept, the health of animals and humans has to be taken care simultaneously. At present, these advanced molecular diagnostic methods play a significant role in the detection of new and emerging pathogens of livestock. The acquired information also helps to study the interrelationships of pathogens, their hosts and their surroundings. Additionally new vaccines bridging human and animal health development may be discovered. Latest developments in the field of diagnostics and vaccine design through genomics approach have also laid the foundation to enhance the diagnosis and surveillance and in turn helped in the control of infectious diseases. Latest high-throughput DNA sequencing platforms are currently being used for identification and detailed analysis of both disease pathogen and host genomes. The high-throughput data generated using these platforms need to be analysed adopting the bioinformatics and computational genomics that have taken a very high pace nowadays. In the context of animal health, the data analysis may provide some key opportunities for the development of better diagnostic and therapeutic tools for emerging or re-emerging diseases. Such novel and potent technologies put forward a significantly new scenario of disease knowledge, which enables more accurate predictions leading to faster and greater management responses to combat potentially devastating disease crises. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120337/ doi: 10.1007/978-981-10-4702-2_14 id: cord-322240-z8zkl2xh author: Maeda, Ken title: Isolation of Novel Adenovirus from Fruit Bat (Pteropus dasymallus yayeyamae) date: 2008-02-17 words: 1686.0 sentences: 95.0 pages: flesch: 51.0 cache: ./cache/cord-322240-z8zkl2xh.txt txt: ./txt/cord-322240-z8zkl2xh.txt summary: To date, only 1 case of disseminated infection has been reported in a solid-organ (kidney) transplant recipient; the diagnosis was made by molecular identifi cation in isolates from blood and marrow cultures. As a fi rst step in investigating unidentifi ed pathogens in bats and to help forecast the potential threat of emerging infectious diseases, we tried to isolate and characterize viruses that persistently infect bats. However, no viral nucleic acid sequence was detected from an RNA sample in the RV1-infected BKT1 cells. In addition, our success in DNA virus isolation might have resulted from usage of the adult animal latently and persistently infected with DNA viruses such as adenovirus and herpesvirus. Although its pathogenicity for humans is still unknown, knowledge of RV1 will be useful in epidemiologic studies of infectious diseases emerging from bats because persistently infecting viruses might be isolated together with primary pathogens. abstract: Isolation of Novel Adenovirus from Fruit Bat url: https://doi.org/10.3201/eid1402.070932 doi: 10.3201/eid1402.070932 id: cord-312001-8p7scli8 author: Majzoub, Karim title: The Innate Antiviral Response in Animals: An Evolutionary Perspective from Flagellates to Humans date: 2019-08-16 words: 10056.0 sentences: 548.0 pages: flesch: 46.0 cache: ./cache/cord-312001-8p7scli8.txt txt: ./txt/cord-312001-8p7scli8.txt summary: Consequently, animal cells have evolved devoted pathways which (1) sense and recognize pathogen-associated molecular patterns (PAMPs) and, more particularly, virus-associated molecular signatures; (2) initiate signaling cascades stemming from the site of detection, translocating the information to the nucleus; and (3) induce a transcriptional program that confers an antiviral state to the host ( Figure 1 ). While the cytosolic recognition of viral RNA is almost exclusively mediated by RLRs, several proteins have been proposed to play a role in DNA sensing and triggering innate immune responses, such as the DNA-dependent activator of IFN-regulatory factors (DAI), DDX41, RNA polymerase III, IFI16 and DNA-PK [62] [63] [64] [65] [66] [67] . Although the pathway leading to the transcriptional activation of Vago is still poorly understood in insects, these studies established that DExD/H-box helicase containing proteins, like Dicer and RLRs, may represent an evolutionarily conserved set of viral nucleic acid sensors that direct antiviral responses in animals [159] . abstract: Animal cells have evolved dedicated molecular systems for sensing and delivering a coordinated response to viral threats. Our understanding of these pathways is almost entirely defined by studies in humans or model organisms like mice, fruit flies and worms. However, new genomic and functional data from organisms such as sponges, anemones and mollusks are helping redefine our understanding of these immune systems and their evolution. In this review, we will discuss our current knowledge of the innate immune pathways involved in sensing, signaling and inducing genes to counter viral infections in vertebrate animals. We will then focus on some central conserved players of this response including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs) and cGAS-STING, attempting to put their evolution into perspective. To conclude, we will reflect on the arms race that exists between viruses and their animal hosts, illustrated by the dynamic evolution and diversification of innate immune pathways. These concepts are not only important to understand virus-host interactions in general but may also be relevant for the development of novel curative approaches against human disease. url: https://doi.org/10.3390/v11080758 doi: 10.3390/v11080758 id: cord-297790-tpjxt0w5 author: Mandl, Judith N. title: Going to Bat(s) for Studies of Disease Tolerance date: 2018-09-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A majority of viruses that have caused recent epidemics with high lethality rates in people, are zoonoses originating from wildlife. Among them are filoviruses (e.g., Marburg, Ebola), coronaviruses (e.g., SARS, MERS), henipaviruses (e.g., Hendra, Nipah) which share the common features that they are all RNA viruses, and that a dysregulated immune response is an important contributor to the tissue damage and hence pathogenicity that results from infection in humans. Intriguingly, these viruses also all originate from bat reservoirs. Bats have been shown to have a greater mean viral richness than predicted by their phylogenetic distance from humans, their geographic range, or their presence in urban areas, suggesting other traits must explain why bats harbor a greater number of zoonotic viruses than other mammals. Bats are highly unusual among mammals in other ways as well. Not only are they the only mammals capable of powered flight, they have extraordinarily long life spans, with little detectable increases in mortality or senescence until high ages. Their physiology likely impacted their history of pathogen exposure and necessitated adaptations that may have also affected immune signaling pathways. Do our life history traits make us susceptible to generating damaging immune responses to RNA viruses or does the physiology of bats make them particularly tolerant or resistant? Understanding what immune mechanisms enable bats to coexist with RNA viruses may provide critical fundamental insights into how to achieve greater resilience in humans. url: https://doi.org/10.3389/fimmu.2018.02112 doi: 10.3389/fimmu.2018.02112 id: cord-102370-5uy8dq18 author: Marano, Jeffrey M. title: Rolling Circle Amplification is a high fidelity and efficient alternative to plasmid preparation for the rescue of infectious clones date: 2020-06-23 words: 4116.0 sentences: 225.0 pages: flesch: 53.0 cache: ./cache/cord-102370-5uy8dq18.txt txt: ./txt/cord-102370-5uy8dq18.txt summary: The traditional approach to rescuing virus from an infectious cDNA clone requires propagating large amounts of plasmids in bacteria, which can result in unwanted mutations in the viral genome due to bacterial toxicity or recombination and requires specialized equipment and knowledge to propagate the bacteria. We have developed an alternative method of preparing large quantities of DNA that can be directly transfected to recover infectious virus without the need for bacteria by amplifying the infectious cDNA clone plasmid using rolling circle amplification (RCA). Typically, the propagation of infectious cDNA clones before viral rescue requires the generation of high concentration plasmid stocks from bacteria, which is not only cumbersome and time-consuming but also presents an opportunity for the introduction of unwanted mutations during amplification in bacteria. To ensure that the above results were not restricted to a specific RCA kit, Vero cells were transfected in triplicate in two independent replicates with RCA product produced using both the Evomics SuperPhi Kit and the GE GenomiPhi Kit or plasmid DNA (Fig. 4) . abstract: Alphaviruses (genus Alphavirus; family Togaviridae) are a medically relevant family of viruses that include chikungunya virus, Eastern equine encephalitis virus, and the emerging Mayaro virus. Infectious cDNA clones of these viruses are necessary molecular tools to understand viral biology and to create effective vaccines. The traditional approach to rescuing virus from an infectious cDNA clone requires propagating large amounts of plasmids in bacteria, which can result in unwanted mutations in the viral genome due to bacterial toxicity or recombination and requires specialized equipment and knowledge to propagate the bacteria. Here, we present an alternative to the bacterial-based plasmid platform that uses rolling circle amplification (RCA), an in vitro technology that amplifies plasmid DNA using only basic equipment. We demonstrate that the use of RCA to amplify plasmid DNA is comparable to the use of a midiprepped plasmid in terms of viral yield, albeit with a slight delay in virus recovery kinetics. RCA, however, has lower cost and time requirements and amplifies DNA with high fidelity and with no chance of unwanted mutations due to toxicity. We show that sequential RCA reactions do not introduce mutations into the viral genome and, thus, can replace the need for glycerol stocks or bacteria entirely. These results indicate that RCA is a viable alternative to traditional plasmid-based approaches to viral rescue. Importance The development of infectious cDNA clones is critical to studying viral pathogenesis and for developing vaccines. The current method for propagating clones in bacteria is limited by the toxicity of the viral genome within the bacterial host, resulting in deleterious mutations in the viral genome, which can only be detected through whole-genome sequencing. These mutations can attenuate the virus, leading to lost time and resources and potentially confounding results. We have developed an alternative method of preparing large quantities of DNA that can be directly transfected to recover infectious virus without the need for bacteria by amplifying the infectious cDNA clone plasmid using rolling circle amplification (RCA). Our results indicate that viral rescue from an RCA product produces a viral yield equal to bacterial-derived plasmid DNA, albeit with a slight delay in replication kinetics. The RCA platform, however, is significantly more cost and time-efficient compared to traditional approaches. When the simplicity and costs of RCA are combined, we propose that a shift to an RCA platform will benefit the field of molecular virology and could have significant advantages for recombinant vaccine production. url: https://doi.org/10.1101/2020.06.22.165241 doi: 10.1101/2020.06.22.165241 id: cord-002844-jv42o789 author: Marcos-Villar, Laura title: Epigenetic control of influenza virus: role of H3K79 methylation in interferon-induced antiviral response date: 2018-01-19 words: 6091.0 sentences: 308.0 pages: flesch: 43.0 cache: ./cache/cord-002844-jv42o789.txt txt: ./txt/cord-002844-jv42o789.txt summary: These results indicate that epigenetic modifications induced by influenza virus infection mainly target the histone component of host cell chromatin, with H3K79 residue methylation the most frequently modified. Dot1L inhibition caused an increase in viral replication, higher in cells infected with the natural isolates, which suggests a general role of H3K79 methylation in control of the influenza virus life cycle. At 8 h, we found a weak increase on IFNβ, IFN-stimulated gene 56 (ISG56) and interferon-induced protein Mx1 (Mx1) RNA levels after IFNαβ addition or influenza virus infection, and Dot1L inhibitor treatment did not significantly decreased their accumulation (Fig. 6B,C) . Given the role of H3K79 methylation in the control of IFN signaling, we analyzed the effect of Dot1L inhibitor on influenza virus replication in cells with normal or deficient IFN responses. Since H3K79 methylation does not affect influenza virus replication in cells with impaired IFN signaling, we analyzed the effect of Dot1L inhibitor in subsequent stages of viral infection. abstract: Influenza virus stablishes a network of virus-host functional interactions, which depends on chromatin dynamic and therefore on epigenetic modifications. Using an unbiased search, we analyzed the epigenetic changes at DNA methylation and post-translational histone modification levels induced by the infection. DNA methylation was unaltered, while we found a general decrease on histone acetylation, which correlates with transcriptional inactivation and may cooperate with the impairment of cellular transcription that causes influenza virus infection. A particular increase in H3K79 methylation was observed and the use of an inhibitor of the specific H3K79 methylase, Dot1L enzyme, or its silencing, increased influenza virus replication. The antiviral response was reduced in conditions of Dot1L downregulation, since decreased nuclear translocation of NF-kB complex, and IFN-β, Mx1 and ISG56 expression was detected. The data suggested a control of antiviral signaling by methylation of H3K79 and consequently, influenza virus replication was unaffected in IFN pathway-compromised, Dot1L-inhibited cells. H3K79 methylation also controlled replication of another potent interferon-inducing virus such as vesicular stomatitis virus, but did not modify amplification of respiratory syncytial virus that poorly induces interferon signaling. Epigenetic methylation of H3K79 might have an important role in controlling interferon-induced signaling against viral pathogens. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775356/ doi: 10.1038/s41598-018-19370-6 id: cord-311349-145kwny3 author: Mariani, Stefano title: Surface plasmon resonance applications in clinical analysis date: 2014-02-25 words: 13425.0 sentences: 630.0 pages: flesch: 39.0 cache: ./cache/cord-311349-145kwny3.txt txt: ./txt/cord-311349-145kwny3.txt summary: In the last 20 years, surface plasmon resonance (SPR) and its advancement with imaging (SPRi) emerged as a suitable and reliable platform in clinical analysis for label-free, sensitive, and real-time monitoring of biomolecular interactions. The advantages brought about by current SPR technology include real-time monitoring of the analyte/molecular markers, label free and parallel analysis (with SPRi), minimal sample pretreatment, quantitative response, and very good sensitivity and reproducibility, (reported detection limits are in atto-or femtomolar ranges and coefficient of variations below 10 %). Preventing nonspecific adsorption of biomolecules (e.g., protein) on the SPR sensing surface is another key-step for the development of specific biosensor, with real application to clinical diagnostics where complex matrices (such as serum, blood, and urine) are analyzed. abstract: In the last 20 years, surface plasmon resonance (SPR) and its advancement with imaging (SPRi) emerged as a suitable and reliable platform in clinical analysis for label-free, sensitive, and real-time monitoring of biomolecular interactions. Thus, we report in this review the state of the art of clinical target detection with SPR-based biosensors in complex matrices (e.g., serum, saliva, blood, and urine) as well as in standard solution when innovative approaches or advanced instrumentations were employed for improved detection. The principles of SPR-based biosensors are summarized first, focusing on the physical properties of the transducer, on the assays design, on the immobilization chemistry, and on new trends for implementing system analytical performances (e.g., coupling with nanoparticles (NPs). Then we critically review the detection of analytes of interest in molecular diagnostics, such as hormones (relevant also for anti-doping control) and biomarkers of interest in inflammatory, cancer, and heart failure diseases. Antibody detection is reported in relation to immune disorder diagnostics. Subsequently, nucleic acid targets are considered for revealing genetic diseases (e.g., point mutation and single nucleotides polymorphism, SNPs) as well as new emerging clinical markers (microRNA) and for pathogen detection. Finally, examples of pathogen detection by immunosensing were also analyzed. A parallel comparison with the reference methods was duly made, indicating the progress brought about by SPR technologies in clinical routine analysis. url: https://www.ncbi.nlm.nih.gov/pubmed/24566759/ doi: 10.1007/s00216-014-7647-5 id: cord-330581-g5r2b043 author: Marini, Elena title: HIV‐1 matrix protein p17 binds to monocytes and selectively stimulates MCP‐1 secretion: role of transcriptional factor AP‐1 date: 2007-10-26 words: 8241.0 sentences: 419.0 pages: flesch: 52.0 cache: ./cache/cord-330581-g5r2b043.txt txt: ./txt/cord-330581-g5r2b043.txt summary: C. AP-1 protein family profiling for DNA-binding activity of an ELISA-based transcription factor assay kit using nuclear extracts (4 mg per sample) from human monocytes cultured for 1 h in the presence or absence of p17-and AP-1-specific oligonucleotides immobilized to a 96-well plate. Due to the large number of primary monocytes required for the analysis of transcription factor DNA-binding activity in protein nuclear extracts, we further investigated the involvement of AP-1 transcription factor in p17-induced MCP-1 transcriptional events using the monocytic cell line THP-1, which constitutively expresses p17Rs on its surface (data not shown). Among these, the HIV-1 matrix protein p17 has been recently identified as a critical determinant in AIDS pathogenesis as it binds to a cellular receptor expressed on immune cells and enhances viral replication and infectivity (De Francesco et al., 1998) , through a combination of different effector functions (De Francesco et al., 2002; Vitale et al., 2003) . abstract: HIV‐1 matrix protein p17 activates a variety of cell responses which play a critical role in viral replication and infection. Its activity depends on the expression of p17 receptors (p17R) on the surface of target cells. Whether p17 also plays a role in stimulating human monocytes, a major HIV‐1 reservoir, is not known. Here we show that human monocytes constitutively express p17Rs and that p17 selectively triggers these cells to produce MCP‐1. The effect of p17 on MCP‐1 expression was observed at the transcriptional level and was primarily dependent on the activation of the transcription factor AP‐1. p17 increased the binding activity of AP‐1 complexes in a time‐ and dose‐dependent manner. Deletion of the AP‐1 binding sites in the MCP‐1 promoter resulted in the lack of p17‐induced MCP‐1 transcription. In particular, the P3 binding site located between −69 and −63 position seems to be essential to MCP‐1 mRNA induction in p17‐treated monocytes. An ever increasing amount of evidences shows a tight link between biologically dysregulated monocytes, AP‐1 activation, MCP‐1 release and HIV‐1 pathogenesis. Overall our results suggest that p17 may play a critical role in the monocyte‐mediated inflammatory processes, which are suspected to be major precipitating events in AIDS‐defining diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/18042260/ doi: 10.1111/j.1462-5822.2007.01073.x id: cord-022177-j0qcjbxg author: Markl, Jürgen title: Genome date: 2018-10-12 words: 3467.0 sentences: 425.0 pages: flesch: 51.0 cache: ./cache/cord-022177-j0qcjbxg.txt txt: ./txt/cord-022177-j0qcjbxg.txt summary: Das Projekt profitierte von der Entwicklung vieler neuer und bahnbrechender Methoden, die zuerst bei der Sequenzierung kleinerer Genome angewendet wurden -von Prokaryoten und einfach gebauten Eukaryoten, etwa von den Modellorganismen, denen Sie in vorangegangenen Kapiteln dieses Buches bereits begegnet sind. RNA-Gene, etwa für rRNA, tRNA und kleine nucleäre RNA (snRNA) und mikroRNA andere nichtcodierende Sequenzen, die verschiedenen Kategorien zugeordnet werden können, beispielsweise Centromer-oder Telomerregionen, Transposons und weitere Sequenzwiederholungen Sequenzinformationen werden auch in der vergleichenden Genomik genutzt, also für den Vergleich eines neu sequenzierten Genoms (oder von Teilen daraus) mit den Sequenzen von anderen Organismen. Wenn man die Genome von Prokaryoten und Eukaryoten vergleicht, drängt sich eine interessante Schlussfolgerung auf: Bestimmte Gene sind universell, also bei allen Lebewesen vorhanden. Mithilfe der DNA-Sequenzierung kann man die Genome von Prokaryoten untersuchen, von denen viele für den Menschen und bestimmte Ökosysteme von Bedeutung sind. abstract: Canis lupus familiaris, der Haushund, wurde vor rund 15.000 Jahren von den Menschen domestiziert. Obwohl es viele verschiedene Varianten von Wölfen gibt, ähneln sich diese ziemlich stark, doch das trifft auf den „besten Freund des Menschen“ nicht zu. Die Fédération Cynologique Internationale (FCI), weltweit größter Dachverband der Hundezüchter, erkennt über 300 Hunderassen an. Genetiker gehen von rund 100 echten Hunderassen aus, der Rest seien Varietäten. Hunderassen sehen nicht nur recht unterschiedlich aus, sondern sie unterscheiden sich auch stark in ihrer Körpergröße. So wiegt beispielsweise ein durchschnittlicher Chihuahua nur 1,5 kg, während ein Schottischer Jagdhund 70 kg auf die Waage bringt. Kein anderes Säugetier zeigt eine so starke phänotypische Variabilität. Außerdem gibt es Hunderte von genetisch bedingten Krankheiten bei Hunden, und für viele davon findet sich auch ein Gegenstück bei Menschen. Das Hundegenomprojekt begann in den späten 1990er-Jahren, um herauszufinden, welche Gene für die genetische Variabilität verantwortlich sind und welche Zusammenhänge zwischen Genen und Krankheiten bestehen. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153743/ doi: 10.1007/978-3-662-58172-8_17 id: cord-012461-v8d91fdo author: Marnissi, Boutheina title: Generation of ssDNA aptamers as diagnostic tool for Newcastle avian virus date: 2020-08-13 words: 6108.0 sentences: 304.0 pages: flesch: 54.0 cache: ./cache/cord-012461-v8d91fdo.txt txt: ./txt/cord-012461-v8d91fdo.txt summary: Top aptameric sequences were used to develop a sandwich enzymatic linked aptamer assay (ELAA) for rapid and sensitive detection of NDV in farm samples. Following optimization of the sandwich ELAA method, the results demonstrated that both selected aptamers Apt_NDV01 and Apt_NDV03 with dissociation constant values of 31 nM and 78.1 nM, respectively, showed the highest specificity and affinity for NDV detection. The output of the SELEX was amplified by symmetric (S1 Fig in S1 File) and asymmetric PCR, and the final PCR products were incubated with the virus immobilized on a nitrocellulose membrane, using an immune-blot test to monitor the enrichment of target-binding aptamers. The specificity of the five selected aptamers, Apt_NDV01-05, against NDV was evaluated by testing their affinities against various avian viruses besides NDV-LaSota vaccine strain, including H120-IBV, IBDV-Gomboro, 1133 reovirus, avian influenza-H9N2, and a naïve library which was used as a negative control. abstract: Aptamers are short single-stranded DNA (ssDNA), RNA or synthetic XNA molecules, which are used as a class of affinity binders recognizing target molecules with a very high affinity and specificity. The aim of this study was to generate and characterize ssDNA aptamers for the detection of Newcastle disease virus (NDV). These aptamers were selected using systematic evolution of ligands by exponential enrichment (SELEX) in combination with quantitative high-throughput DNA sequencing. After three rounds of selections, a highly enriched ssDNA pool was sequenced, and the results were analyzed using FASTAptamer Toolkit. Sequencing reads were sorted by copy numbers and clustered into groups, according to their sequence homology. Top aptameric sequences were used to develop a sandwich enzymatic linked aptamer assay (ELAA) for rapid and sensitive detection of NDV in farm samples. The selected aptamers have an affinity within the nanomolar range, and a high specificity with no cross-reactivity towards other avian viruses. Following optimization of the sandwich ELAA method, the results demonstrated that both selected aptamers Apt_NDV01 and Apt_NDV03 with dissociation constant values of 31 nM and 78.1 nM, respectively, showed the highest specificity and affinity for NDV detection. The ELAA results were verified by quantitative real-time PCR, demonstrating strong concordance, and showing outstanding accuracy for detection of NDV in field sample. In summary, combination of SELEX with high-throughput DNA sequencing allowed rapid screening and selection of aptamers. The selected aptamers allowed recognition of NDV with high affinities. This is the first report that uses a validated sandwich ELAA for rapid and specific detection of NDV in poultry samples. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425888/ doi: 10.1371/journal.pone.0237253 id: cord-342782-xty16m8w author: Marrugal-Lorenzo, José A. title: Repositioning salicylanilide anthelmintic drugs to treat adenovirus infections date: 2019-01-09 words: 5099.0 sentences: 267.0 pages: flesch: 47.0 cache: ./cache/cord-342782-xty16m8w.txt txt: ./txt/cord-342782-xty16m8w.txt summary: Data suggests that the studied salicylanilide anthelmintic drugs could be suitable for further clinical evaluation for the development of new antiviral drugs to treat infections by adenovirus in immunosuppressed patients and in immunocompetent individuals with community-acquired pneumonia. The three salicylanilide anthelmintic drugs showed a dose-dependent anti-HAdV activity against both HAdV5 and HAdV16, with 100% inhibition of plaques formation at 1.25, 5 and 2.5 μM for NIC, OXY and RAF, respectively ( Fig. 2a,b) . The CC 50 values for these molecules were in all cases significantly higher than the IC 50 concentrations required for inhibition in our antiviral activity and mechanistic assays for both 293β5 cells (Table 1 ) and A549 cells (22.9 ± 9.8 µM, 76.1 ± 14.4 µM and 80.6 ± 34.7 µM for NIC, OXY and RAF, respectively). The aim of this study was to evaluate the anti-HAdV activity of NIC, a salicylanilide anthelmintic drug of human use to set the basis for its further experimental and clinical development as a potential new treatment for HAdV infections. abstract: The repositioning of drugs already approved by regulatory agencies for other indications is an emerging alternative for the development of new antimicrobial therapies. The repositioning process involves lower risks and costs than the de novo development of novel antimicrobial drugs. Currently, infections by adenovirus show a steady increment with a high clinical impact in immunosuppressed and immunocompetent patients. The lack of a safe and efficacious drug to treat these infections supports the search for new antiviral drugs. Here we evaluated the anti-adenovirus activity of niclosanide, oxyclozanide, and rafoxanide, three salicylanilide anthelmintic drugs. Also, we carried out the cytotoxicity evaluation and partial characterization of the mechanism of action of these drugs. The salicylanilide anthelmintic drugs showed significant anti-adenovirus activity at low micromolar concentrations with little cytotoxicity. Moreover, our mechanistic assays suggest differences in the way the drugs exert anti-adenovirus activity. Niclosamide and rafoxanide target transport of the HAdV particle from the endosome to the nuclear envelope, whilst oxyclozanide specifically targets adenovirus immediately early gene E1A transcription. Data suggests that the studied salicylanilide anthelmintic drugs could be suitable for further clinical evaluation for the development of new antiviral drugs to treat infections by adenovirus in immunosuppressed patients and in immunocompetent individuals with community-acquired pneumonia. url: https://www.ncbi.nlm.nih.gov/pubmed/30626902/ doi: 10.1038/s41598-018-37290-3 id: cord-006068-w3if1hns author: Marshak-Rothstein, Ann title: Toll-like receptors in systemic autoimmune disease date: 2006 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Toll-like receptors (TLRs) have a crucial role in the early detection of pathogen-associated molecular patterns and the subsequent activation of the adaptive immune response. Whether TLRs also have an important role in the recognition of endogenous ligands has been more controversial. Numerous in vitro studies have documented activation of both autoreactive B cells and plasmacytoid dendritic cells by mammalian TLR ligands. The issue of whether these in vitro observations translate to an in vivo role for TLRs in either the initiation or the progression of systemic autoimmune disease is a subject of intense research; data are beginning to emerge showing that this is the case. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097510/ doi: 10.1038/nri1957 id: cord-347992-coby2m6e author: Marton, Soledad title: In Vitro and Ex Vivo Selection Procedures for Identifying Potentially Therapeutic DNA and RNA Molecules date: 2010-06-28 words: 10035.0 sentences: 535.0 pages: flesch: 45.0 cache: ./cache/cord-347992-coby2m6e.txt txt: ./txt/cord-347992-coby2m6e.txt summary: Although ribozymes and DNAzymes have been extensively assayed as potential therapeutic agents, and different clinical trials have already tested their efficiency against various diseases [49] [50] [51] [52] , very few reports have described the direct application of in vitro selection strategies in the development of potentially therapeutic catalytic nucleic acids. Molecular studies have shown that this aptamer binds to the cell surface protein nucleolin and inhibits the activity of NF-KB, a ubiquitous transcription factor, through intracellular complex formation [108] . In a different approach, SELEX has been performed with the E2F1 protein to find in vitro selected RNA aptamers that bind to and inhibit E2F activity. Astier-Gi''s group described the characterization of two DNA aptamers (27v and 127v) that specifically bind to hepatitis C virus (HCV) RNA polymerase (NS5B), inhibiting its activity in vitro [146] . In vitro selection procedures for identifying DNA and RNA aptamers targeted to nucleic acids and proteins abstract: It was only relatively recently discovered that nucleic acids participate in a variety of biological functions, besides the storage and transmission of genetic information. Quite apart from the nucleotide sequence, it is now clear that the structure of a nucleic acid plays an essential role in its functionality, enabling catalysis and specific binding reactions. In vitro selection and evolution strategies have been extremely useful in the analysis of functional RNA and DNA molecules, helping to expand our knowledge of their functional repertoire and to identify and optimize DNA and RNA molecules with potential therapeutic and diagnostic applications. The great progress made in this field has prompted the development of ex vivo methods for selecting functional nucleic acids in the cellular environment. This review summarizes the most important and most recent applications of in vitro and ex vivo selection strategies aimed at exploring the therapeutic potential of nucleic acids. url: https://www.ncbi.nlm.nih.gov/pubmed/20657381/ doi: 10.3390/molecules15074610 id: cord-313957-hviv5zar author: Masucci, Maria Grazia title: Viral Ubiquitin and Ubiquitin-Like Deconjugases—Swiss Army Knives for Infection date: 2020-08-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Posttranslational modifications of cellular proteins by covalent conjugation of ubiquitin and ubiquitin-like polypeptides regulate numerous cellular processes that are captured by viruses to promote infection, replication, and spreading. The importance of these protein modifications for the viral life cycle is underscored by the discovery that many viruses encode deconjugases that reverse their functions. The structural and functional characterization of these viral enzymes and the identification of their viral and cellular substrates is providing valuable insights into the biology of viral infections and the host’s antiviral defense. Given the growing body of evidence demonstrating their key contribution to pathogenesis, the viral deconjugases are now recognized as attractive targets for the design of novel antiviral therapeutics. url: https://doi.org/10.3390/biom10081137 doi: 10.3390/biom10081137 id: cord-254646-psolkrom author: Matsui, Mary S. title: Vitamin D Update date: 2020-10-14 words: 5106.0 sentences: 236.0 pages: flesch: 42.0 cache: ./cache/cord-254646-psolkrom.txt txt: ./txt/cord-254646-psolkrom.txt summary: This review will briefly summarize fundamental, well-established aspects of vitamin D and human health and then will also discuss (a) some of the most recent work related to vitamin D and non-skeletal-associated health issues; (b) the complexity of establishing meaningful vitamin D measurement metrics and assessing vitamin D status; c)decisionmaking for obtaining vitamin D through diet, supplements, or sun exposure; (d) the impact of skin type, pigmentation, and sunscreen on vitamin D levels; and (e) evidence for a potential influence of vitamin D on the mortality and morbidity of COVID-19 through modulation of the pro-inflammatory cytokine response and respiratory response to the virus. To some extent, this is because relevant factors vary: vitamin D food fortification regulations, the strength of ambient ultraviolet radiation (UVR), levels of smog, culture and ethnicity, skin phototype, chronological age, and ease and accuracy of specific clinical laboratory measurements. abstract: PURPOSE: The goal of this review is to provide an update in the field of vitamin D, in particular, the role of vitamin D in non-skeletal health, the complexity of providing patient guidance regarding obtaining sufficient vitamin D, and the possible involvement of vitamin D in morbidity and mortality due to SARS-CoV-2 (COVID-19). RECENT FINDINGS: In addition to bone health, vitamin D may play a role in innate immunity, cardiovascular disease, and asthma. Although rickets is often regarded as an historical disease of the early twentieth century, it appears to be making a comeback worldwide, including “first-world” countries. Broad-spectrum sunscreens (with high UVA filters) that prevent erythema are unlikely to compromise vitamin D status in healthy populations. SUMMARY: New attention is now focused on the role of vitamin D in a variety of diseases, and more individualized patient recommendation schemes are being considered that take into account more realistic and achievable goals for achieving sufficient vitamin D through diet, supplements, and sun behavior. url: https://doi.org/10.1007/s13671-020-00315-0 doi: 10.1007/s13671-020-00315-0 id: cord-259412-l8uta7du author: Mattossovich, Rosanna title: O(6)-alkylguanine-DNA Alkyltransferases in Microbes Living on the Edge: From Stability to Applicability date: 2020-04-20 words: 7475.0 sentences: 352.0 pages: flesch: 42.0 cache: ./cache/cord-259412-l8uta7du.txt txt: ./txt/cord-259412-l8uta7du.txt summary: The reaction mechanism of AGTs is based on the recognition of the damaged nucleobase on DNA [5] , followed by a one-step SN 2 -like mechanism, in which the alkyl group of the damaged guanine is irreversibly transferred to a cysteine residue in its active site [5] [6] [7] [8] (Figure 1 , blue path). These compounds mimic damaged guanine on DNA and react with the protein by the covalent transfer of the alkyl adduct to the active site cysteine residue, thus irreversibly inactivating the enzyme (Figure 1 , red path). Concerning biotechnology, the use of a modified hMGMT as protein tag opened the possibility to generalise this method-a targeted mutagenesis on a thermostable OGT by following a rational approach led to the characterization of SsOGT-H 5 , applicable to in vitro harsh reaction conditions and to in vivo (hyper)thermophilic model organisms. abstract: The genome of living cells is continuously exposed to endogenous and exogenous attacks, and this is particularly amplified at high temperatures. Alkylating agents cause DNA damage, leading to mutations and cell death; for this reason, they also play a central role in chemotherapy treatments. A class of enzymes known as AGTs (alkylguanine-DNA-alkyltransferases) protects the DNA from mutations caused by alkylating agents, in particular in the recognition and repair of alkylated guanines in O(6)-position. The peculiar irreversible self-alkylation reaction of these enzymes triggered numerous studies, especially on the human homologue, in order to identify effective inhibitors in the fight against cancer. In modern biotechnology, engineered variants of AGTs are developed to be used as protein tags for the attachment of chemical ligands. In the last decade, research on AGTs from (hyper)thermophilic sources proved useful as a model system to clarify numerous phenomena, also common for mesophilic enzymes. This review traces recent progress in this class of thermozymes, emphasizing their usefulness in basic research and their consequent advantages for in vivo and in vitro biotechnological applications. url: https://www.ncbi.nlm.nih.gov/pubmed/32326075/ doi: 10.3390/ijms21082878 id: cord-006664-ykfvbypo author: McLaughlin, R. title: The role of apoptotic cell death in cardiovascular disease date: 2001 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Programmed cell death, or apoptesis, is a distinct, managed form of cell death. It is fundamentally different from necrosis. It is a genetically controlled, energy-dependent method of cellular deletion without inflammation. In the cardiovascular system, apoptosis occurs as a primary and secondary event in disease pathogenesis. This review addresses our current understanding of the initiation, propagation and significance of apoptosis in the cardiovascular system, as well as assessing therapeutic potentials arising therefrom. METHODS: A Medline search was performed and relevant publications reviewed. Further articles were obtained from the references of these publications. RESULTS AND CONCLUSIONS: Apoptotic cell death is a key element in the pathogenesis and progression of ischaemia-reperfusion (IR) injury, cardiac failure, myocardial infarction, atherosclerosis, endothelial dysfunction and the clinical syndromes which these situations produce. Our increased understanding of the role of apoptosis in the pathogenesis of cardiovascular disease offers potential to develop new therapeutic strategies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102203/ doi: 10.1007/bf03168827 id: cord-000104-3b8b8p61 author: McWhirter, Sarah M. title: A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP date: 2009-08-31 words: 8572.0 sentences: 499.0 pages: flesch: 56.0 cache: ./cache/cord-000104-3b8b8p61.txt txt: ./txt/cord-000104-3b8b8p61.txt summary: The potency of cytosolic signaling induced by c-di-GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, nuclear factor κB, and MAP kinases. Cell type-specific responses to cytosolic DNA and c-di-GMP Collectively, these results suggest that there are strong similarities in the signaling pathways triggered by the cytosolic presence of c-di-GMP and other nucleic acids, such as DNA and RNA. These results suggest that at least one component of the host signaling pathway responding to c-di-GMP is distinct from that used for responses to cytosolic RNA or DNA, and is differentially expressed in different cell types. abstract: The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells. Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics. The cyclic dinucleotide cyclic-di–guanosine monophosphate (c-di-GMP) is a recently appreciated second messenger that plays critical regulatory roles in many species of bacteria but is not produced by eukaryotic cells. In vivo and in vitro studies have previously suggested that c-di-GMP is a potent immunostimulatory compound recognized by mouse and human cells. We provide evidence that c-di-GMP is sensed in the cytosol of mammalian cells via a novel immunosurveillance pathway. The potency of cytosolic signaling induced by c-di-GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, nuclear factor κB, and MAP kinases. However, the cytosolic pathway that senses c-di-GMP appears to be distinct from all known nucleic acid–sensing pathways. Our results suggest a novel mechanism by which host cells can induce an inflammatory response to a widely produced bacterial ligand. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737161/ doi: 10.1084/jem.20082874 id: cord-017493-zro9cna3 author: Mcnamee, James P. title: Cytogenetic and Carcinogenic Effects of Exposure to Radiofrequency Radiation date: 2007 words: 12182.0 sentences: 514.0 pages: flesch: 48.0 cache: ./cache/cord-017493-zro9cna3.txt txt: ./txt/cord-017493-zro9cna3.txt summary: (2004b) found no evidence of increased DNA damage, as determined by the alkaline comet assay, in either mouse C3H 10T1/2 fibroblasts or human glioblastoma U87MG cells following in vitro exposure for 2-24 h to 835 MHz-2.45 GHz RFR at a variety of modulations in the SAR range of 0.6-5.1 W/kg. This was followed by a series of highly publicized studies by Lai and Singh (1995 , who reported increased levels of primary DNA damage (which may have included DNA single-strand and double-strand breaks, alkali-labile sites and DNA cross-links) in rat brain cells at 0-4 h after a 2-h in vivo exposure to 2.45 GHz CW or pulse-modulated RFR at SARs of 0.6-1.2 W/kg. More recently, Paulraj and Behari (2006) reported increased DNA damage in brain cells of Wistar rats following exposure to 2.45 or 16.5 GHz RFR for 35 days at 2 h/day at SARs of approximately 1.0 and 2.0 W/kg, respectively. abstract: Radiofrequency radiation (RFR) is a portion of the electromagnetic spectrum with frequencies of 3 kHz–300 GHz. RFR is produced by many man-made sources, including mobile phones and base stations, television and radio broadcasting facilities, radar, medical equipment, microwave ovens, radiofrequency heaters as well as a diverse variety of other electronic devices within our living and working environments. Owing to ongoing public concern and the increasing prevalence of RFR-emitting devices, a great deal of research has been conducted over the past 50 years to evaluate the biological and/or health effects of thermalizing and non-thermalizing RFR exposures. In the absence of decisive epidemiological evidence to support or refute an association between RFR exposure and cancer risk, laboratory studies of possible mechanisms of carcinogenesis by RFR are important. The scientific literature on this subject is full of conflicting results and the question of whether RFR exposure can contribute to cancer risk remains unresolved. This chapter contains a literature review of the evidence for RFR-induced cytogenetic effects, but also a critique of the literature, highlighting deficiencies in the design of some studies that should be taken into account when assessing the health risk of RFR. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122069/ doi: 10.1007/978-3-540-71414-9_28 id: cord-315164-nidgnvvi author: Medkour, Hacène title: Adenovirus Infections in African Humans and Wild Non-Human Primates: Great Diversity and Cross-Species Transmission date: 2020-06-18 words: 6818.0 sentences: 359.0 pages: flesch: 58.0 cache: ./cache/cord-315164-nidgnvvi.txt txt: ./txt/cord-315164-nidgnvvi.txt summary: Non-human primates (NHPs) are known hosts for adenoviruses (AdVs), so there is the possibility of the zoonotic or cross-species transmission of AdVs. As with humans, AdV infections in animals can cause diseases that range from asymptomatic to fatal. The aim of this study was to investigate the occurrence and diversity of AdVs in: (i) fecal samples of apes and monkeys from different African countries (Republic of Congo, Senegal, Djibouti and Algeria), (ii) stool of humans living near gorillas in the Republic of Congo, in order to explore the potential zoonotic risks. Samples were screened by real-time and standard PCRs, followed by the sequencing of the partial DNA polymerase gene in order to identify the AdV species. In the present study, we sought to investigate the presence and molecular diversity of AdVs in wild African NHPs, including great apes (gorillas and chimpanzees), macaques and other monkeys (baboons, green monkeys), living in close proximity to or outside human settlements. abstract: Non-human primates (NHPs) are known hosts for adenoviruses (AdVs), so there is the possibility of the zoonotic or cross-species transmission of AdVs. As with humans, AdV infections in animals can cause diseases that range from asymptomatic to fatal. The aim of this study was to investigate the occurrence and diversity of AdVs in: (i) fecal samples of apes and monkeys from different African countries (Republic of Congo, Senegal, Djibouti and Algeria), (ii) stool of humans living near gorillas in the Republic of Congo, in order to explore the potential zoonotic risks. Samples were screened by real-time and standard PCRs, followed by the sequencing of the partial DNA polymerase gene in order to identify the AdV species. The prevalence was 3.3 folds higher in NHPs than in humans. More than 1/3 (35.8%) of the NHPs and 1/10 (10.5%) of the humans excreted AdVs in their feces. The positive rate was high in great apes (46%), with a maximum of 54.2% in chimpanzees (Pan troglodytes) and 35.9% in gorillas (Gorilla gorilla), followed by monkeys (25.6%), with 27.5% in Barbary macaques (Macaca sylvanus) and 23.1% in baboons (seven Papio papio and six Papio hamadryas). No green monkeys (Chlorocebus sabaeus) were found to be positive for AdVs. The AdVs detected in NHPs were members of Human mastadenovirus E (HAdV-E), HAdV-C or HAdV-B, and those in the humans belonged to HAdV-C or HAdV-D. HAdV-C members were detected in both gorillas and humans, with evidence of zoonotic transmission since phylogenetic analysis revealed that gorilla AdVs belonging to HAdV-C were genetically identical to strains detected in humans who had been living around gorillas, and, inversely, a HAdV-C member HAdV type was detected in gorillas. This confirms the gorilla-to-human transmission of adenovirus. which has been reported previously. In addition, HAdV-E members, the most often detected here, are widely distributed among NHP species regardless of their origin, i.e., HAdV-E members seem to lack host specificity. Virus isolation was successful from a human sample and the strain of the Mbo024 genome, of 35 kb, that was identified as belonging to HAdV-D, exhibited close identity to HAdV-D members for all genes. This study provides information on the AdVs that infect African NHPs and the human populations living nearby, with an evident zoonotic transmission. It is likely that AdVs crossed the species barrier between different NHP species (especially HAdV-E members), between NHPs and humans (especially HAdV-C), but also between humans, NHPs and other animal species. url: https://www.ncbi.nlm.nih.gov/pubmed/32570742/ doi: 10.3390/v12060657 id: cord-010443-4jblod8j author: Meduri, Gianfranco Umberto title: General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections date: 2020-04-22 words: 18827.0 sentences: 815.0 pages: flesch: 23.0 cache: ./cache/cord-010443-4jblod8j.txt txt: ./txt/cord-010443-4jblod8j.txt summary: In critical illness, NF-κB-driven systemic inflammation, also known as a "cytokine storm" (14) , activates a multi-system response that includes at least three major domains: (i) the stress system composed by the hypothalamic-pituitary-adrenal (HPA) axis and the locus caeruleus-norepinephrine/sympathetic nervous system activated to provide sufficient energy and hemodynamic stability to overcome the initial phase of critical illness (15) ; (ii) the acute-phase reaction (APR), which has several adaptive functions, including increasing the production of procoagulant factors in preparation for possible tissue damage (16) ; and (iii) the tissue defense response (TDR) of the target organs [ Figure 1 ; (11, 17) ]. In patients with septic shock (170, 171) or ARDS (172, 173) , prolonged glucocorticoid (hydrocortisone or methylprednisolone) treatment resulted in the following: (i) increased plasma activated protein C levels (173); (ii) reduction in markers of endothelial injury such as sICAM-1 (35); (iii) rapid and consistent improvement in capillary perfusion, independently of the cortisol response to ACTH (170) ; and (iv) improvement in alveolar-capillary (172) and renal (171) endothelial permeability. abstract: In critical illness, homeostatic corrections representing the culmination of hundreds of millions of years of evolution, are modulated by the activated glucocorticoid receptor alpha (GRα) and are associated with an enormous bioenergetic and metabolic cost. Appreciation of how homeostatic corrections work and how they evolved provides a conceptual framework to understand the complex pathobiology of critical illness. Emerging literature place the activated GRα at the center of all phases of disease development and resolution, including activation and re-enforcement of innate immunity, downregulation of pro-inflammatory transcription factors, and restoration of anatomy and function. By the time critically ill patients necessitate vital organ support for survival, they have reached near exhaustion or exhaustion of neuroendocrine homeostatic compensation, cell bio-energetic and adaptation functions, and reserves of vital micronutrients. We review how critical illness-related corticosteroid insufficiency, mitochondrial dysfunction/damage, and hypovitaminosis collectively interact to accelerate an anti-homeostatic active process of natural selection. Importantly, the allostatic overload imposed by these homeostatic corrections impacts negatively on both acute and long-term morbidity and mortality. Since the bioenergetic and metabolic reserves to support homeostatic corrections are time-limited, early interventions should be directed at increasing GRα and mitochondria number and function. Present understanding of the activated GC-GRα's role in immunomodulation and disease resolution should be taken into account when re-evaluating how to administer glucocorticoid treatment and co-interventions to improve cellular responsiveness. The activated GRα interdependence with functional mitochondria and three vitamin reserves (B1, C, and D) provides a rationale for co-interventions that include prolonged glucocorticoid treatment in association with rapid correction of hypovitaminosis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189617/ doi: 10.3389/fendo.2020.00161 id: cord-280429-4fota9rl author: Medvedev, Kirill E. title: Functional and evolutionary analysis of viral proteins containing a Rossmann‐like fold date: 2018-06-13 words: 7468.0 sentences: 465.0 pages: flesch: 49.0 cache: ./cache/cord-280429-4fota9rl.txt txt: ./txt/cord-280429-4fota9rl.txt summary: 10 However, structural analyses of virion architecture and coat protein topology have revealed unexpected similarities, not visible in sequence comparisons, suggesting a common origin for viruses that infect hosts residing in different domains of life. In this current work, we provide functional and evolutionary analysis of viral proteins containing a Rossmann-like fold that can be found in the Evolutionary Classification of protein Domains (ECOD) database developed in our lab. The structures represented gene products from 21 viral taxonomical families with host ranges from all kingdoms of life (http://prodata.swmed.edu/rossmann_fold/viruses/). Our analysis detected 14 different bacterial virus structure topology types defined by ECOD T-groups that contain a Rossmann-like fold (Fig. 2, 12 topology groups shown). Like the bacterial and eukaryotic branches in the tree of life, the Archea are host to a multitude of Functional and Evolutionary Analysis of Viral Proteins viruses. 61 Among viral protein structures containing the minimal Rossmann fold, 14 protein families are known helicases (http://prodata.swmed.edu/ross-mann_fold/viruses/). abstract: Viruses are the most abundant life form and infect practically all organisms. Consequently, these obligate parasites are a major cause of human suffering and economic loss. Rossmann‐like fold is the most populated fold among α/β‐folds in the Protein Data Bank and proteins containing Rossmann‐like fold constitute 22% of all known proteins 3D structures. Thus, analysis of viral proteins containing Rossmann‐like domains could provide an understanding of viral biology and evolution as well as could propose possible targets for antiviral therapy. We provide functional and evolutionary analysis of viral proteins containing a Rossmann‐like fold found in the evolutionary classification of protein domains (ECOD) database developed in our lab. We identified 81 protein families of bacterial, archeal, and eukaryotic viruses in light of their evolution‐based ECOD classification and Pfam taxonomy. We defined their functional significance using enzymatic EC number assignments as well as domain‐level family annotations. url: https://www.ncbi.nlm.nih.gov/pubmed/29722076/ doi: 10.1002/pro.3438 id: cord-299731-sis9952k author: Mehmel, Mario title: Nicotinamide Riboside—The Current State of Research and Therapeutic Uses date: 2020-05-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Nicotinamide riboside (NR) has recently become one of the most studied nicotinamide adenine dinucleotide (NAD(+)) precursors, due to its numerous potential health benefits mediated via elevated NAD(+) content in the body. NAD(+) is an essential coenzyme that plays important roles in various metabolic pathways and increasing its overall content has been confirmed as a valuable strategy for treating a wide variety of pathophysiological conditions. Accumulating evidence on NRs’ health benefits has validated its efficiency across numerous animal and human studies for the treatment of a number of cardiovascular, neurodegenerative, and metabolic disorders. As the prevalence and morbidity of these conditions increases in modern society, the great necessity has arisen for a rapid translation of NR to therapeutic use and further establishment of its availability as a nutritional supplement. Here, we summarize currently available data on NR effects on metabolism, and several neurodegenerative and cardiovascular disorders, through to its application as a treatment for specific pathophysiological conditions. In addition, we have reviewed newly published research on the application of NR as a potential therapy against infections with several pathogens, including SARS-CoV-2. Additionally, to support rapid NR translation to therapeutics, the challenges related to its bioavailability and safety are addressed, together with the advantages of NR to other NAD(+) precursors. url: https://doi.org/10.3390/nu12061616 doi: 10.3390/nu12061616 id: cord-253115-ekgdsv4f author: Mehta, Meenu title: Oligonucleotide therapy: An emerging focus area for drug delivery in chronic inflammatory respiratory diseases date: 2019-08-01 words: 7317.0 sentences: 457.0 pages: flesch: 39.0 cache: ./cache/cord-253115-ekgdsv4f.txt txt: ./txt/cord-253115-ekgdsv4f.txt summary: Commonly used drug delivery systems for respiratory diseases are polymer-based, lipid-based and peptide-based, and among these three, the lipid-based carriers are the most commonly used vectors for delivering RNAi. They include solid lipid nanoparticles, cationic liposomes, lipidoids, solid nanostructured lipid carriers and pH-responsive lipids [26] . The effective delivery of the drug and siRNA induced cell death of lung tumor cells by targeted gene silencing [56] . Glud et al., investigated pulmonary gene silencing effect of small interfering locked nucleic acid (siLNAs), targeting enhanced-greenfluorescent-protein (EGFP) in lung bronchoepithelium upon intravenous delivery of naked siLNAs and intranasal delivery of naked siLNA or chitosan based siLNA mucoadhesive nanoparticles. This study demonstrated that SAMiRNA nanoparticle is a stable siRNA silencing platform with less toxicity for effective in vivo targeting of genes involved in the pathogenesis of respiratory diseases [96] . Overcoming cisplatin resistance in non-small cell lung cancer with Mad2 silencing siRNA delivered systemically using EGFR-targeted chitosan nanoparticles abstract: Abstract Oligonucleotide-based therapies are advanced novel interventions used in the management of various respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). These agents primarily act by gene silencing or RNA interference. Better methodologies and techniques are the need of the hour that can deliver these agents to tissues and cells in a target specific manner by which their maximum potential can be reached in the management of chronic inflammatory diseases. Nanoparticles play an important role in the target-specific delivery of drugs. In addition, oligonucleotides also are extensively used for gene transfer in the form of polymeric, liposomal and inorganic carrier materials. Therefore, the current review focuses on various novel dosage forms like nanoparticles, liposomes that can be used efficiently for the delivery of various oligonucleotides such as siRNA and miRNA. We also discuss the future perspectives and targets for oligonucleotides in the management of respiratory diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/31136735/ doi: 10.1016/j.cbi.2019.05.028 id: cord-010056-zfin4bko author: Mejia, Rojelio title: Impact of intestinal parasites on microbiota and cobalamin gene sequences: a pilot study date: 2020-04-19 words: 4092.0 sentences: 260.0 pages: flesch: 41.0 cache: ./cache/cord-010056-zfin4bko.txt txt: ./txt/cord-010056-zfin4bko.txt summary: RESULTS: For Giardia-only infected children compared to uninfected children, DNA sequencing data showed a decrease in microbiota biodiversity that correlated with increasing Giardia burden and was statistically significant using Shannon''s alpha diversity (Giardia-only > 1 fg/µl 2.346; non-infected group 3.253, P = 0.0317). CONCLUSION: The study results may provide evidence for an effect of parasitic infections enabling the permissive growth of anaerobic bacteria such as Prevotella, suggesting an altered capacity of vitamin B12 (cobalamin) biosynthesis and potential impact on growth and development in children [Image: see text]. There are few studies attributing gut microbiome changes to giardiasis [17] [18] [19] and no published studies showing the impact on the human intestinal microbiome using multi-parallel real-time quantitative (qPCR) to detect the presence of Giardia and quantitating the burden of infection [20] . In this pilot study, parasite qPCR and next-generation DNA sequencing was used to explore whether quantitative burden of specific parasites (Giardia duodenalis and soil-transmitted helminths) influence the composition of intestinal microbial communities. abstract: BACKGROUND: Approximately 30% of children worldwide are infected with gastrointestinal parasites. Depending on the species, parasites can disrupt intestinal bacterial microbiota affecting essential vitamin biosynthesis. METHODS: Stool samples were collected from 37 asymptomatic children from a previous cross-sectional Argentinian study. A multi-parallel real-time quantitative PCR was implemented for Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Trichuris trichiura, Cryptosporidium spp., Entamoeba histolytica and Giardia duodenalis. In addition, whole-genome sequencing analysis was conducted for bacterial microbiota on all samples and analyzed using Livermore Metagenomic Analysis Toolkit and DIAMOND software. Separate analyses were carried out for uninfected, Giardia-only, Giardia + helminth co-infections, and helminth-only groups. RESULTS: For Giardia-only infected children compared to uninfected children, DNA sequencing data showed a decrease in microbiota biodiversity that correlated with increasing Giardia burden and was statistically significant using Shannonʼs alpha diversity (Giardia-only > 1 fg/µl 2.346; non-infected group 3.253, P = 0.0317). An increase in diversity was observed for helminth-only infections with a decrease in diversity for Giardia + helminth co-infections (P = 0.00178). In Giardia-only infections, microbiome taxonomy changed from Firmicutes towards increasing proportions of Prevotella, with the degree of change related to the intensity of infection compared to uninfected (P = 0.0317). The abundance of Prevotella bacteria was decreased in the helminths-only group but increased for Giardia + helminth co-infections (P = 0.0262). Metagenomic analysis determined cobalamin synthesis was decreased in the Giardia > 1 fg/µl group compared to both the Giardia < 1 fg/µl and the uninfected group (P = 0.0369). Giardia + helminth group also had a decrease in cobalamin CbiM genes from helminth-only infections (P = 0.000754). CONCLUSION: The study results may provide evidence for an effect of parasitic infections enabling the permissive growth of anaerobic bacteria such as Prevotella, suggesting an altered capacity of vitamin B12 (cobalamin) biosynthesis and potential impact on growth and development in children [Image: see text]. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168842/ doi: 10.1186/s13071-020-04073-7 id: cord-273993-rkqijcxn author: Menchaca, A. title: CRISPR in livestock: From editing to printing date: 2020-01-29 words: 6877.0 sentences: 331.0 pages: flesch: 42.0 cache: ./cache/cord-273993-rkqijcxn.txt txt: ./txt/cord-273993-rkqijcxn.txt summary: When applied in large animals, CRISPR involves timeand cost-consuming projects, and it is mandatory not only to choose the best approach for genome editing, but also for embryo production, zygote microinjection or electroporation, cryopreservation and embryo transfer. In addition, we discuss some CRISPR applications to enhance livestock production in the context of a growing global demand of food, in terms of increasing efficiency, reducing the impact of farming on the environment, enhancing pest control, animal welfare and health. The wide range of CRISPR applications in large animals include improving productive traits, enhancing animal welfare through adaptation and resilience, conferring resistance to infectious and transmissible diseases, generating animal models for biomedical research, and suppressing other species considered as pests for livestock. Genome editing mediated by SCNT is applied by some laboratories in some kind of projects (e.g., multiplex editing), but the high efficiency of CRISPR after direct microinjection into zygotes has allowed an easier approach (sheep: [6, 7, 15, 16] ; goats: [9, 17] ; pigs: [11, 13] ). abstract: Precise genome editing of large animals applied to livestock and biomedicine is nowadays possible since the CRISPR revolution. This review summarizes the latest advances and the main technical issues that determine the success of this technology. The pathway from editing to printing, from engineering the genome to achieving the desired animals, does not always imply an easy, fast and safe journey. When applied in large animals, CRISPR involves time- and cost-consuming projects, and it is mandatory not only to choose the best approach for genome editing, but also for embryo production, zygote microinjection or electroporation, cryopreservation and embryo transfer. The main technical refinements and most frequent questions to improve this disruptive biotechnology in large animals are presented. In addition, we discuss some CRISPR applications to enhance livestock production in the context of a growing global demand of food, in terms of increasing efficiency, reducing the impact of farming on the environment, enhancing pest control, animal welfare and health. The challenge is no longer technical. Controversies and consensus, opportunities and threats, benefits and risks, ethics and science should be reconsidered to enter into the CRISPR era. url: https://www.ncbi.nlm.nih.gov/pubmed/32088034/ doi: 10.1016/j.theriogenology.2020.01.063 id: cord-015678-9b3eazd4 author: Merzendorfer, Hans title: Chitin/Chitosan: Versatile Ecological, Industrial, and Biomedical Applications date: 2019-03-07 words: 29015.0 sentences: 1474.0 pages: flesch: 35.0 cache: ./cache/cord-015678-9b3eazd4.txt txt: ./txt/cord-015678-9b3eazd4.txt summary: A plethora of chemical chitosan derivatives have been synthesized yielding improved materials with suggested or effective applications in water treatment, biosensor engineering, agriculture, food processing and storage, textile additives, cosmetics fabrication, and in veterinary and human medicine. Chitosan and its derivatives have many desirable properties such as antioxidative and antimicrobial effects, mucoadhesiveness, biodegradability, and biocompatibility and can be manufactured in various formulations including hydrogels, films, membranes, porous sponges, nanoparticles, and nanofibers. Recyclable composite microspheres composed of cross-linked chitosan grafted with glutamic acid and having a core of Fe 3 O 4 nanoparticles coated with silica adsorb cationic dyes like methylene blue, crystal violet, and light yellow 7GL (Yan et al. While chitosan-based materials have been commercially launched as packaging and coating material in food industry, as an ingredient in cosmetics, and as ion exchanger in water treatment and are approved for human dietary use and wound dressing, their commercial applications in medicine as drug delivery systems or scaffold for tissue engineering are pending. abstract: Chitin is a linear polysaccharide of N-acetylglucosamine, which is highly abundant in nature and mainly produced by marine crustaceans. Chitosan is obtained by hydrolytic deacetylation. Both polysaccharides are renewable resources, simply and cost-effectively extracted from waste material of fish industry, mainly crab and shrimp shells. Research over the past five decades has revealed that chitosan, in particular, possesses unique and useful characteristics such as chemical versatility, polyelectrolyte properties, gel- and film-forming ability, high adsorption capacity, antimicrobial and antioxidative properties, low toxicity, and biocompatibility and biodegradability features. A plethora of chemical chitosan derivatives have been synthesized yielding improved materials with suggested or effective applications in water treatment, biosensor engineering, agriculture, food processing and storage, textile additives, cosmetics fabrication, and in veterinary and human medicine. The number of studies in this research field has exploded particularly during the last two decades. Here, we review recent advances in utilizing chitosan and chitosan derivatives in different technical, agricultural, and biomedical fields. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115017/ doi: 10.1007/978-3-030-12919-4_14 id: cord-353297-jizitnfl author: Meyer, R.F. title: Viruses and Bioterrorism date: 2008-07-30 words: 3817.0 sentences: 184.0 pages: flesch: 43.0 cache: ./cache/cord-353297-jizitnfl.txt txt: ./txt/cord-353297-jizitnfl.txt summary: The requirements for an ideal biological warfare agent include availability, ease of production, stability after production, a susceptible population, absence of specific treatment, ability to incapacitate or kill the host, appropriate particle size in aerosol so that the virus can be carried long distances by prevailing winds and inhaled deeply into the lungs of unsuspecting victims, ability to be disseminated via food or water, and the availability of a vaccine to protect certain groups. Instead, the ectromelia virus vector expressing IL-4 altered the host''s immune response to this virus resulting in lethal infections in normally genetically Classification of viral agents that are considered to be of concern for bioterrorism and biowarfare and those that have been weaponized or studied for offensive or defensive purposes as part of former or current national biological weapons programs resistant mice (e.g., C57BL/6). abstract: The use of viral agents for biological warfare has a long history, which predates their recognition and isolation by culture. Advances in viral culture and virus stabilization made during the second half of the twentieth century raised the level of concern by facilitating the large-scale production of viral agents for aerosol dissemination. Furthermore, the nucleic acid of many viruses, including some that are currently not threats, can be manipulated in the laboratory. Thus, the potential for genetic engineering and misuse of biotechnology is a serious threat. An effective defense against viral agents requires a comprehensive approach including restricting access to viral stocks, detecting deliberately induced disease outbreaks, rapid laboratory identification of viral agents in clinical specimens, preventing person-to-person transmission, using reliable decontamination procedures, and developing effective vaccines and antiviral drugs. url: https://api.elsevier.com/content/article/pii/B9780123744104005495 doi: 10.1016/b978-012374410-4.00549-5 id: cord-329155-ddpfox68 author: Mindikoglu, Ayse L. title: Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome date: 2020-10-27 words: 8186.0 sentences: 379.0 pages: flesch: 43.0 cache: ./cache/cord-329155-ddpfox68.txt txt: ./txt/cord-329155-ddpfox68.txt summary: Our results showed that 30-day intermittent fasting from dawn to sunset, the human activity phase, was associated with an anticancer serum proteome response and upregulated several key regulatory proteins that play a key role in tumor suppression, DNA repair, insulin signaling, glucose, and lipid metabolism, circadian clock, cytoskeletal remodeling, immune system, and cognitive function 15 . In accord with the findings of these murine and human studies 13,25 , we found a significant fold increase in the levels of specific tumor suppressor/anticancer proteins at the end of 4th week during 4-week intermittent fasting from dawn to sunset and/or 1 week after 4-week intermittent fasting from dawn to sunset, including CALR, CALU, INTS6, KIT, CROCC, PIGR, IGFBP4, and SEMA4B that are downregulated in several cancers resulting in cancer metastasis and poor prognosis (Table 2, Fig. 2 ). abstract: Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry. We found a significant fold increase in the levels of several tumor suppressor and DNA repair gene protein products (GP)s at the end of 4th week during 4-week intermittent fasting (CALU, INTS6, KIT, CROCC, PIGR), and 1 week after 4-week intermittent fasting (CALU, CALR, IGFBP4, SEMA4B) compared with the levels before 4-week intermittent fasting. We also found a significant reduction in the levels of tumor promoter GPs at the end of 4th week during 4-week intermittent fasting (POLK, CD109, CAMP, NIFK, SRGN), and 1 week after 4-week intermittent fasting (CAMP, PLAC1) compared with the levels before 4-week intermittent fasting. Fasting from dawn to sunset for four weeks also induced an anti-diabetes proteome response by upregulating the key regulatory proteins of insulin signaling at the end of 4th week during 4-week intermittent fasting (VPS8, POLRMT, IGFBP-5) and 1 week after 4-week intermittent fasting (PRKCSH), and an anti-aging proteome response by upregulating H2B histone proteins 1 week after 4-week intermittent fasting. Subjects had a significant reduction in body mass index, waist circumference, and improvement in blood pressure that co-occurred with the anticancer, anti-diabetes, and anti-aging serum proteome response. These findings suggest that intermittent fasting from dawn to sunset actively modulates the respective genes and can be an adjunct treatment in metabolic syndrome. Further studies are needed to test the intermittent fasting from dawn to sunset in the prevention and treatment of metabolic syndrome-induced cancers. url: https://www.ncbi.nlm.nih.gov/pubmed/33110154/ doi: 10.1038/s41598-020-73767-w id: cord-323691-5s5almd2 author: Mishin, Vasiliy P title: A ‘minimal’ approach in design of flavivirus infectious DNA date: 2001-12-04 words: 5060.0 sentences: 255.0 pages: flesch: 49.0 cache: ./cache/cord-323691-5s5almd2.txt txt: ./txt/cord-323691-5s5almd2.txt summary: Abstract The ''infectious DNA'' approach, which is based on in vivo transcription of (+)RNA virus genome cDNA cassettes from eukaryotic promoters in transfected cells, became a popular alternative to the classical scheme in the infectious clone methodology. Substantial difficulties, however, were encountered in design of flavivirus ''infectious DNA'', requiring either modification of the viral genome cassette (Yamshchikov et al., 2001) to prevent unwanted expression of viral genome segments encoding toxic for Escherichia coli products, or deletion of the structural protein region (Varnavski et al., 2000) . For this reason we sought to investigate if the stability of constructs containing an unmodified virus genome cassette can be improved by preventing its deleterious expression at the transcriptional level, i.e. by minimizing spurious transcription from eukaryotic promoters in E. abstract: Abstract The ‘infectious DNA’ approach, which is based on in vivo transcription of (+)RNA virus genome cDNA cassettes from eukaryotic promoters in transfected cells, became a popular alternative to the classical scheme in the infectious clone methodology. Its use, however, is often limited by the instability of plasmids due to a transcriptional activity of eukaryotic promoters in Escherichia coli resulting in synthesis of products toxic for the bacterial host. Using a highly unstable representative infectious clone of Japanese encephalitis (JE) flavivirus, we tested a new approach in design of such problematic ‘infectious DNA’ constructs, which is based on minimizing unwanted transcription in the bacterial host. A plasmid containing full genome size JE cDNA under control of the minimal cytomegalovirus (CMV) promoter can be propagated in E. coli with growth and stability characteristics similar to that of constructs controlled by the T7 promoter. Transfection of this plasmid into susceptible cells leads to the establishment of a productive infectious cycle. Reinsertion of the CMV enhancer at the 3′-end of the JE cassette substantially increased the specific infectivity without affecting the stability and growth characteristics of the construct. This approach can be useful when stabilization of infectious clones by modification of a viral cDNA cassette is not the feasible or suitable alternative. url: https://www.ncbi.nlm.nih.gov/pubmed/11682130/ doi: 10.1016/s0168-1702(01)00371-9 id: cord-018437-yjvwa1ot author: Mitchell, Michael title: Taxonomy date: 2013-08-26 words: 9283.0 sentences: 561.0 pages: flesch: 48.0 cache: ./cache/cord-018437-yjvwa1ot.txt txt: ./txt/cord-018437-yjvwa1ot.txt summary: Classifi cation is based on the genomic nucleic acid used by the virus (DNA or RNA), strandedness (single or double stranded), and method of replication. The nucleocapsids of some viruses are surrounded by envelopes composed of lipid bilayers and host-or viral-encoded proteins. The sequence of negative-sense ssRNA is complementary to the coding sequence for translation, so mRNA must be synthesized by RNA polymerase, typically carried within the virion, before translation into viral proteins. Among the families of viruses able to infect humans and other vertebrate hosts, there are many species that target and cause disease in the lung. The nucleocapsid is surrounded by an envelope derived from host-cell membrane and viral envelope proteins, including hepatitis B surface antigen. The genome of human parainfl uenza viruses is ~15 kb in length with an organization and six reading frames (N, P, M, F, HN, L) typical of the Paramyxoviridae (Karron and Collins 2007 ) . abstract: This chapter addresses the classification and taxonomy of viruses with special attention to viruses that show pneumotropic properties. Information provided in this chapter supplements that provided in other chapters in Parts II–V of this volume that discuss individual viral pathogens. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123310/ doi: 10.1007/978-3-642-40605-8_3 id: cord-324944-ixh3ykrc author: Mitsakakis, Konstantinos title: Diagnostic tools for tackling febrile illness and enhancing patient management date: 2018-12-05 words: 20805.0 sentences: 961.0 pages: flesch: 45.0 cache: ./cache/cord-324944-ixh3ykrc.txt txt: ./txt/cord-324944-ixh3ykrc.txt summary: This review gives an overview of diagnostic technologies featuring a platform based approach: (i) assay (nucleic acid amplification technologies are examined); (ii) cartridge (microfluidic technologies are presented); (iii) instrument (various detection technologies are discussed); and at the end proposes a way that such technologies can be interfaced with electronic clinical decision-making algorithms towards a broad and complete diagnostic ecosystem. In studies that have recorded the clinical presentation of patients (and not only their laboratory results), the causes of fever in outpatients could be classified into four main syndromes: 1) acute respiratory infections (ARI, of any type); 2) diarrhea (gastroenteritis); 3) fever with another clear focus (e.g. meningitis or skin infection); and 4) non-specific fevers [13] (each diagnostic platform described in Section 5 focuses on at least one of the aforementioned cases). abstract: Most patients with acute infectious diseases develop fever, which is frequently a reason to visit health facilities in resource-limited settings. The symptomatic overlap between febrile diseases impedes their diagnosis on clinical grounds. Therefore, the World Health Organization promotes an integrated management of febrile illness. Along this line, we present an overview of endemic and epidemic etiologies of fever and state-of-the-art diagnostic tools used in the field. It becomes evident that there is an urgent need for the development of novel technologies to fulfill end-users' requirements. This need can be met with point-of-care and near-patient diagnostic platforms, as well as e-Health clinical algorithms, which co-assess test results with key clinical elements and biosensors, assisting clinicians in patient triage and management, thus enhancing disease surveillance and outbreak alerts. This review gives an overview of diagnostic technologies featuring a platform based approach: (i) assay (nucleic acid amplification technologies are examined); (ii) cartridge (microfluidic technologies are presented); (iii) instrument (various detection technologies are discussed); and at the end proposes a way that such technologies can be interfaced with electronic clinical decision-making algorithms towards a broad and complete diagnostic ecosystem. url: https://www.sciencedirect.com/science/article/pii/S0167931718304556 doi: 10.1016/j.mee.2018.10.001 id: cord-273347-eyxc4rt0 author: Mohammadinejad, Reza title: In vivo gene delivery mediated by non-viral vectors for cancer therapy date: 2020-07-04 words: 7777.0 sentences: 485.0 pages: flesch: 39.0 cache: ./cache/cord-273347-eyxc4rt0.txt txt: ./txt/cord-273347-eyxc4rt0.txt summary: We will also highlight the in vivo gene delivery mediated by non-viral vectors to treat cancer in different tissue and organs including brain, breast, lung, liver, stomach, and prostate. Since various routes of administration have been used to transfer non-viral delivery systems for gene therapy, it seems that the route is highly dependent on the characteristics of the carrier and nucleic acids as well the prepared complex and the final formulation. Synthesis and Application of a Novel Gene Delivery Vector for Non-Small-Cell Lung Cancer Therapy Chloroquine in combination with aptamer-modified nanocomplexes for tumor vessel normalization and efficient erlotinib/Survivin shRNA co-delivery to overcome drug resistance in EGFR-mutated non-small cell lung cancer Enhanced delivery of siRNA to triple negative breast cancer cells in vitro and in vivo through functionalizing lipid-coated calcium phosphate nanoparticles with dual target ligands Highly efficient cationic hydroxyethylated cholesterol-based nanoparticle-mediated gene transfer in vivo and in vitro in prostate carcinoma PC-3 cells abstract: Gene therapy by expression constructs or down-regulation of certain genes has shown great potential for the treatment of various diseases. The wide clinical application of nucleic acid materials dependents on the development of biocompatible gene carriers. There are enormous various compounds widely investigated to be used as non-viral gene carriers including lipids, polymers, carbon materials, and inorganic structures. In this review, we will discuss the recent discoveries on non-viral gene delivery systems. We will also highlight the in vivo gene delivery mediated by non-viral vectors to treat cancer in different tissue and organs including brain, breast, lung, liver, stomach, and prostate. Finally, we will delineate the state-of-the-art and promising perspective of in vivo gene editing using non-viral nano-vectors. url: https://www.ncbi.nlm.nih.gov/pubmed/32634464/ doi: 10.1016/j.jconrel.2020.06.038 id: cord-340503-zwdewiu1 author: Mokhtarzadeh, Ahad title: Nanomaterial-based biosensors for detection of pathogenic virus date: 2017-10-13 words: 7710.0 sentences: 401.0 pages: flesch: 42.0 cache: ./cache/cord-340503-zwdewiu1.txt txt: ./txt/cord-340503-zwdewiu1.txt summary: Electron microscopy Viral particle Hours Broad spectrum; rapid method Necessity for presence of around 10 6 virus particles/mL for detection; similarity of morphologies [11] Hemagglutination assay Viral protein Hours Easy; inexpensive Poor sensitivity; necessity for fresh reagents [12] ELISA Viral protein Hours Only one incubation step; no hook effect at high analyte concentrations Limited concentration range in which the analyte can be quantified without sample dilution; and that the antigen or antibody produce the same response and not distinguishable in a one step [13] PCR Viral nucleic acid Hours Extremely high sensitivity; Easy to set up Extremely liable to contamination; Not easy to quantitate results; High degree of operator skill required [14] As an example for HIV, a type of virus that gradually attacks the immune system and makes it harder to fight off infections and diseases in infected body, a QDs-based rapid capture and imaging system was developed by Kim et al. abstract: Viruses are real menace to human safety that cause devastating viral disease. The high prevalence of these diseases is due to improper detecting tools. Therefore, there is a remarkable demand to identify viruses in a fast, selective and accurate way. Several biosensors have been designed and commercialized for detection of pathogenic viruses. However, they present many challenges. Nanotechnology overcomes these challenges and performs direct detection of molecular targets in real time. In this overview, studies concerning nanotechnology-based biosensors for pathogenic virus detection have been summarized, paying special attention to biosensors based on graphene oxide, silica, carbon nanotubes, gold, silver, zinc oxide and magnetic nanoparticles, which could pave the way to detect viral diseases and provide healthy life for infected patients. url: https://doi.org/10.1016/j.trac.2017.10.005 doi: 10.1016/j.trac.2017.10.005 id: cord-325750-x7jpsnxg author: Mokili, John L title: Metagenomics and future perspectives in virus discovery date: 2012-01-20 words: 8742.0 sentences: 463.0 pages: flesch: 40.0 cache: ./cache/cord-325750-x7jpsnxg.txt txt: ./txt/cord-325750-x7jpsnxg.txt summary: In this article, we review virus discovery techniques with a focus on metagenomic approaches that employ high-throughput sequencing technologies to characterize novel viruses. This method lacks sufficient sensitivity to detect viruses when the viral burden is low or when the DNA sequence of the suspected etiological agent is not clearly distinguishable from the control sample [31] . The following items should be included in any report on viral metagenomic studies: firstly, the sequencing platform and its version number; secondly, raw sequence data accession numbers in a public database; thirdly, details about the bioinformatic analysis, including the homology search tool and the database being used to assign the taxonomy, and their versions; fourthly, a list of known and previously unknown viruses found, clearly showing if the ''novel'' viruses are new strains of a previously described species or completely different viruses; and fifthly, causality evidence if any. abstract: Monitoring the emergence and re-emergence of viral diseases with the goal of containing the spread of viral agents requires both adequate preparedness and quick response. Identifying the causative agent of a new epidemic is one of the most important steps for effective response to disease outbreaks. Traditionally, virus discovery required propagation of the virus in cell culture, a proven technique responsible for the identification of the vast majority of viruses known to date. However, many viruses cannot be easily propagated in cell culture, thus limiting our knowledge of viruses. Viral metagenomic analyses of environmental samples suggest that the field of virology has explored less than 1% of the extant viral diversity. In the last decade, the culture-independent and sequence-independent metagenomic approach has permitted the discovery of many viruses in a wide range of samples. Phylogenetically, some of these viruses are distantly related to previously discovered viruses. In addition, 60–99% of the sequences generated in different viral metagenomic studies are not homologous to known viruses. In this review, we discuss the advances in the area of viral metagenomics during the last decade and their relevance to virus discovery, clinical microbiology and public health. We discuss the potential of metagenomics for characterization of the normal viral population in a healthy community and identification of viruses that could pose a threat to humans through zoonosis. In addition, we propose a new model of the Koch's postulates named the ‘Metagenomic Koch's Postulates’. Unlike the original Koch's postulates and the Molecular Koch's postulates as formulated by Falkow, the metagenomic Koch's postulates focus on the identification of metagenomic traits in disease cases. The metagenomic traits that can be traced after healthy individuals have been exposed to the source of the suspected pathogen. url: https://doi.org/10.1016/j.coviro.2011.12.004 doi: 10.1016/j.coviro.2011.12.004 id: cord-291749-revhbd0q author: Mongan, Arthur Elia title: Portable sequencer in the fight against infectious disease date: 2019-10-03 words: 3735.0 sentences: 222.0 pages: flesch: 40.0 cache: ./cache/cord-291749-revhbd0q.txt txt: ./txt/cord-291749-revhbd0q.txt summary: Diagnosis can be upheld by observing the cause of disease under the microscope or detecting the presence of nucleic acid and proteins of the pathogens. Sequencing of PCR amplicons or whole pathogen genomic DNA can be applied to comprehensively screen for infecting agents and their drug resistance phenotype, if exists, at the same time. Sequencing ensures detection of DNA composition unique to an organism, the presence of antimicrobials-destroying genes, or mutation that can change the function or conformation of proteins related to drug resistance. Targeted sequencing with MinION is powerful and fast to detect pathogens in clinical samples. A novel diagnostic method for malaria using loopmediated isothermal amplification (LAMP) and MinION TM nanopore sequencer Rapid metagenomic identification of viral pathogens in clinical samples by real-time nanopore sequencing analysis MinION nanopore sequencing of multiple displacement amplified Mycobacteria DNA direct from sputum. abstract: Infectious disease is still a major threat in the world today. Five decades ago, it was considered soon to be eradicated, but the adaptation of pathogens to environmental pressure, such as antimicrobials, encouraged the emergence and reemergence of infectious disease. The fight with infectious disease starts with prevention, diagnosis, and treatment. Diagnosis can be upheld by observing the cause of disease under the microscope or detecting the presence of nucleic acid and proteins of the pathogens. The molecular techniques span from classical polymerase chain reaction (PCR) to sequencing the nucleic acid composition. Here, we are reviewing the works have been undertaken to utilize a portable sequencer, MinION, in various aspects of infectious disease management. url: https://www.ncbi.nlm.nih.gov/pubmed/31582773/ doi: 10.1038/s10038-019-0675-4 id: cord-304188-1nm1tbig author: Moody, M. Anthony title: Modulation of HIV-1 immunity by adjuvants date: 2014-04-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: PURPOSE OF REVIEW: To summarize the role of adjuvants in eliciting desirable antibody responses against HIV-1 with particular emphasis on both historical context and recent developments. RECENT FINDINGS: Increased understanding of the role of pattern recognition receptors such as Toll-like receptors in recruiting and directing the immune system has increased the variety of adjuvant formulations being tested in animal models and humans. Across all vaccine platforms, adjuvant formulations have been shown to enhance desirable immune responses such as higher antibody titers and increased functional activity. Although no vaccine formulation has yet succeeded in eliciting broad neutralizing antibodies against HIV-1, the ability of adjuvants to direct the immune response to immunogens suggests they will be critically important in any successful HIV-1 vaccine. SUMMARY: The parallel development of adjuvants along with better HIV-1 immunogens will be needed for a successful AIDS vaccine. Additional comparative testing will be required to determine the optimal adjuvant and immunogen regimen that can elicit antibody responses capable of blocking HIV-1 transmission. url: https://doi.org/10.1097/coh.0000000000000052 doi: 10.1097/coh.0000000000000052 id: cord-104030-eb29t38n author: Morales-Nebreda, Luisa title: Aging imparts cell-autonomous dysfunction to regulatory T cells during recovery from influenza pneumonia date: 2020-06-05 words: 3960.0 sentences: 175.0 pages: flesch: 36.0 cache: ./cache/cord-104030-eb29t38n.txt txt: ./txt/cord-104030-eb29t38n.txt summary: Using heterochronic (age-mismatched) adoptive Treg cell transfer experiments and molecular profiling in mice, we sought to determine whether the age-related impairment in repair following influenza-induced lung injury is intrinsic to Treg cells. Our data support a paradigm in which aged Treg cells fail to upregulate youthful reparative programs, activate maladaptive responses and consequently exhibit a cell-autonomous impairment in pro-recovery function, which delays resolution from viralinduced lung injury in aged hosts. Gene set enrichment analysis of these genes demonstrated that this methylation-regulated gene expression program was associated with pro-recovery processes and was significantly skewed toward young Treg cells ( Figure 6C) . Combined, these results show that age-related DNA methylation regulates the pro-reparative transcriptional regulatory network during recovery from influenza-induced lung injury. What are the molecular mechanisms underpinning the age-associated Treg cell gain or loss-of pro-reparative function in the lung following influenza infection? abstract: Regulatory T (Treg) cells orchestrate resolution and repair of acute lung inflammation and injury following viral pneumonia. Compared with younger patients, older individuals experience impaired recovery and worse clinical outcomes after severe viral infections, including influenza and the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whether age is a key determinant of Treg cell pro-repair function following lung injury remains unknown. Here, we show that aging results in a cell-autonomous impairment of reparative Treg cell function following experimental influenza pneumonia. Transcriptional and DNA methylation profiling of sorted Treg cells provide insight into the mechanisms underlying their age-related dysfunction, with Treg cells from aged mice demonstrating both loss of reparative programs and gain of maladaptive programs. Novel strategies that restore youthful Treg cell functional programs could be leveraged as therapies to improve outcomes among older individuals with severe viral pneumonia. url: https://doi.org/10.1101/2020.06.05.135194 doi: 10.1101/2020.06.05.135194 id: cord-328633-c31xsyeo author: Moser, Michael J. title: Thermostable DNA Polymerase from a Viral Metagenome Is a Potent RT-PCR Enzyme date: 2012-06-04 words: 7868.0 sentences: 441.0 pages: flesch: 54.0 cache: ./cache/cord-328633-c31xsyeo.txt txt: ./txt/cord-328633-c31xsyeo.txt summary: Most RT-PCR protocols rely on two DNA polymerase (Pol) enzymes; a retroviral reverse transcriptase (RT) to copy RNA into cDNA and a thermostable DNA Pol to amplify the target sequence. Despite their wide use and general reliability, existing twoenzyme RT-PCR systems have several documented performance problems attributed to deficiencies inherent in retroviral RTs: 1) poor reagent stability, 2) low fidelity, 3) frequent rearrangements during cDNA synthesis, 4) secondary enzymatic activities (i.e. RNase H and strand switching), 5) bias for specific primers and templates, and 6) inhibition of PCR Pol enzymes [3, 4, 5, 6, 7] . We describe the discovery and biochemical attributes of one of these, 3173 Pol, its inherent RT activity and its incorporation into a single-enzyme PyroScriptH 2X RT-PCR Master Mix. The sensitivity, specificity and overall performance of this mix were compared to available one-and two-enzyme systems using a control MS2 RNA bacteriophage template, the clinically-relevant influenza A RNA and commonly used reference mRNA transcripts. abstract: Viral metagenomic libraries are a promising but previously untapped source of new reagent enzymes. Deep sequencing and functional screening of viral metagenomic DNA from a near-boiling thermal pool identified clones expressing thermostable DNA polymerase (Pol) activity. Among these, 3173 Pol demonstrated both high thermostability and innate reverse transcriptase (RT) activity. We describe the biochemistry of 3173 Pol and report its use in single-enzyme reverse transcription PCR (RT-PCR). Wild-type 3173 Pol contains a proofreading 3′-5′ exonuclease domain that confers high fidelity in PCR. An easier-to-use exonuclease-deficient derivative was incorporated into a PyroScript RT-PCR master mix and compared to one-enzyme (Tth) and two-enzyme (MMLV RT/Taq) RT-PCR systems for quantitative detection of MS2 RNA, influenza A RNA, and mRNA targets. Specificity and sensitivity of 3173 Pol-based RT-PCR were higher than Tth Pol and comparable to three common two-enzyme systems. The performance and simplified set-up make this enzyme a potential alternative for research and molecular diagnostics. url: https://doi.org/10.1371/journal.pone.0038371 doi: 10.1371/journal.pone.0038371 id: cord-260705-huyyw5z6 author: Moshe, Adi title: Virus-Induced Aggregates in Infected Cells date: 2012-10-17 words: 5063.0 sentences: 265.0 pages: flesch: 39.0 cache: ./cache/cord-260705-huyyw5z6.txt txt: ./txt/cord-260705-huyyw5z6.txt summary: During infection, many viruses induce cellular remodeling, resulting in the formation of insoluble aggregates/inclusions, usually containing viral structural proteins. The aggregates are utilized by viruses to house a large complex of proteins of both viral and host origin to promote virus replication, translation, intraand intercellular transportation. In plant cells, both RNA and DNA viruses are associated with large inclusions detected in the cytoplasm and nucleus, however, their role in virus propagation or oppositely in virus restraint is less investigated than in infected mammalian cells. In general, mammalian and plant viruses make use of aggregates as scaffolds for anchoring the replication complex, increasing the local concentration of viral and host components required for replication and assembly, and shielding the process of replication from host defense. abstract: During infection, many viruses induce cellular remodeling, resulting in the formation of insoluble aggregates/inclusions, usually containing viral structural proteins. Identification of aggregates has become a useful diagnostic tool for certain viral infections. There is wide variety of viral aggregates, which differ by their location, size, content and putative function. The role of aggregation in the context of a specific virus is often poorly understood, especially in the case of plant viruses. The aggregates are utilized by viruses to house a large complex of proteins of both viral and host origin to promote virus replication, translation, intra- and intercellular transportation. Aggregated structures may protect viral functional complexes from the cellular degradation machinery. Alternatively, the activation of host defense mechanisms may involve sequestration of virus components in aggregates, followed by their neutralization as toxic for the host cell. The diversity of virus-induced aggregates in mammalian and plant cells is the subject of this review. url: https://www.ncbi.nlm.nih.gov/pubmed/23202461/ doi: 10.3390/v4102218 id: cord-285982-1a5u7uux author: Moss, Ronald B title: Prospects for control of emerging infectious diseases with plasmid DNA vaccines date: 2009-09-07 words: 4227.0 sentences: 202.0 pages: flesch: 42.0 cache: ./cache/cord-285982-1a5u7uux.txt txt: ./txt/cord-285982-1a5u7uux.txt summary: The rapid manufacturing capabilities of DNA vaccines may be particularly important for emerging infectious diseases including the current novel H1N1 Influenza A pandemic, where pre-existing immunity is limited. Development in this area has greatly advanced over the years and human clinical trials of DNA vaccines have now been conducted against various infectious pathogens including the malaria parasite, dengue viruses, cytomegalovirus (CMV), Ebola virus, seasonal influenza viruses, avian or pandemic influenza viruses, West Nile virus (WMV), SARS coronavirus, hepatitis B virus, and HIV. Because the process of antigen production by host cells after DNA vaccination mimics the production of antigens during a natural infection, the resulting immune response is thought to be similar to the type induced by pathogens. Lastly, the first human clinical trial of a DNA vaccine formulated with Vaxfectin ® has been completed with plasmids that encode pandemic influenza virus antigens (H5N1). abstract: Experiments almost 20 years ago demonstrated that injections of a sequence of DNA encoding part of a pathogen could stimulate immunity. It was soon realized that "DNA vaccination" had numerous potential advantages over conventional vaccine approaches including inherent safety and a more rapid production time. These and other attributes make DNA vaccines ideal for development against emerging pathogens. Recent advances in optimizing various aspects of DNA vaccination have accelerated this approach from concept to reality in contemporary human trials. Although not yet licensed for human use, several DNA vaccines have now been approved for animal health indications. The rapid manufacturing capabilities of DNA vaccines may be particularly important for emerging infectious diseases including the current novel H1N1 Influenza A pandemic, where pre-existing immunity is limited. Because of recent advances in DNA vaccination, this approach has the potential to be a powerful new weapon in protecting against emerging and potentially pandemic human pathogens. url: https://www.ncbi.nlm.nih.gov/pubmed/19735569/ doi: 10.1186/1476-8518-7-3 id: cord-279827-921kvrrz author: Murata, Takayuki title: Growth behavior of bovine herpesvirus-1 in permissive and semi-permissive cells date: 1999-06-11 words: 7150.0 sentences: 368.0 pages: flesch: 65.0 cache: ./cache/cord-279827-921kvrrz.txt txt: ./txt/cord-279827-921kvrrz.txt summary: MDBK or HmLu-1 cells in 35 mm dishes were incubated with 1.0× 10 5 , 1.0 ×10 4 or 1.0 × 10 3 plaque forming unit (pfu) of BHV-1 at a multiplicity of infection (moi) of 0.1, 0.01 or 0.001, respectively, at 4°C for 2 h to allow the virus to be adsorbed into the cells. MDBK or HmLu-1 cells in 60 mm dishes were infected with BHV-1/RSV/p32 at 4°C for 1 h, washed three times with ice-cold PBS and incubated at 37°C in the medium containing 400 mg/ml phosphonoacetic acid (PAA). Confluent monolayer cultures of MDBK cells or HmLu-1 cells were infected with BHV-1 at an moi of 5 and at 3, 6, 12, 24, and 48 h p.i., DNA was extracted as described in Section 2. The MDBK or HmLu-1 cells were infected with BHV-1/RSV/p32 at 4°C for 1 h, washed extensively with cold PBS and incubated with medium at 37°C for 0, 1, 2, and 5 h. abstract: Bovine herpesvirus-1 (BHV-1) can replicate well in bovine-derived cell lines such as Madin Darby bovine kidney (MDBK) but grows poorly in hamster lung (HmLu-1). Virus replication, DNA synthesis, and immediate-early gene expression are severely restricted in HmLu-1. We compared adsorption and penetration of BHV-1 in permissive MDBK and semi-permissive HmLu-1 cells. At a low multiplicity of infection, BHV-1 attached to permissive MDBK cells twice as much as to HmLu-1. The presence of heparin inhibited the attachment of BHV-1 to MDBK cells by about 60%, but over 90% of the attachment was inhibited in HmLu-1. To investigate the penetration of BHV-1, we performed the quantitative measurement of viral DNA by quantitative competitive (QC)PCR in infected cells. In MDBK cells, virions attached to the cell surface, penetrated into the cells and were transported to the nucleus. However in HmLu-1, only a small fraction of the virions attached to the cell surface were allowed to penetrate. Our results indicated that the replication of BHV-1 in semi-permissive HmLu-1 was not dramatically restricted at one certain point but at some various stages including adsorption and penetration. url: https://www.ncbi.nlm.nih.gov/pubmed/10426207/ doi: 10.1016/s0168-1702(99)00023-4 id: cord-264746-gfn312aa author: Muse, Spencer title: GENOMICS AND BIOINFORMATICS date: 2012-03-29 words: 10976.0 sentences: 583.0 pages: flesch: 58.0 cache: ./cache/cord-264746-gfn312aa.txt txt: ./txt/cord-264746-gfn312aa.txt summary: The success of this project (it came in almost 3 years ahead of time and 10% under budget, while at the same time providing more data than originally planned) depended on innovations in a variety of areas: breakthroughs in basic molecular biology to allow manipulation of DNA and other compounds; improved engineering and manufacturing technology to produce equipment for reading the sequences of DNA; advances in robotics and laboratory automation; development of statistical methods to interpret data from sequencing projects; and the creation of specialized computing hardware and software systems to circumvent massive computational barriers that faced genome scientists. Although the list of important biotechnologies changes on an almost daily basis, there are three prominent data types in today''s environment: (1) genome sequences provide the starting point that allows scientists to begin understanding the genetic underpinnings of an organism; (2) measurements of gene expression levels facilitate studies of gene regulation, which, among other things, help us to understand how an organism''s genome interacts with its environment; and (3) genetic polymorphisms are variations from individual to individual within species, and understanding how these variations correlate with phenotypes such as disease susceptibility is a crucial element of modern biomedical research. abstract: This chapter discusses the basic principles of molecular biology regarding genome science and describes the major types of data involved in genome projects, including technologies for collecting them. Genome science is heavily driven by new technological advances that allow for rapid and inexpensive collection of various types of data. The emergence of genomic science has not simply provided a rich set of tools and data for studying molecular biology. It has been the catalyst for an astounding burst of interdisciplinary research, and it has challenged long-established hierarchies found in most institutions of higher learning. The next generation of biologists needs to be as comfortable at a computer workstation as they are at the lab bench. Recognizing this fact, many universities have already reorganized their departments and their curricula to accommodate the demands of genomic science.The chapter discusses practical applications and uses of genomic data. For example, in the foreseeable future, are gene therapies that can repair genetic defects. url: https://api.elsevier.com/content/article/pii/B978012238662650015X doi: 10.1016/b978-0-12-238662-6.50015-x id: cord-103892-v6gkubd4 author: Mäkinen, Janne J. title: The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases date: 2020-07-01 words: 8442.0 sentences: 418.0 pages: flesch: 51.0 cache: ./cache/cord-103892-v6gkubd4.txt txt: ./txt/cord-103892-v6gkubd4.txt summary: Overall, these data demonstrated that the enhanced or diminished capabilities of the variant RNAPs to utilize 2''dGTP in the SNA assays reflected, in qualitative terms, their capabilities to utilize all four 2''dNTPs. The role of the β''Arg425 in selectively promoting the binding of NTPs was easy to explain because the β''Arg425 interacts with the 2''OH of the NTP analogues in several RNAP structures (Supplementary Table 5 , Fig. 1c, 4a, b) . We further hypothesized and demonstrated by in silico docking experiments that the 3''OH could move to within the hydrogen bond distance of the β''Arg425 if the deoxyribose moiety adopted a 2''-endo conformation (Supplementary Fig. 8 To test this hypothesis in crystallo, we solved the X-ray crystal structure of the initially transcribing complexes containing T. Overall, the comparative analysis of RNAP structures with CMPCPP, 2''dCTP and 3''dCTP suggested that the β''Arg425 inhibited the incorporation of 2''dNTPs by interacting with their 3''OH group and favoring the 2''-endo conformation of the deoxyribose moiety. abstract: RNA polymerases (RNAPs) synthesize RNA from NTPs, whereas DNA polymerases synthesize DNA from 2’dNTPs. DNA polymerases select against NTPs by using steric gates to exclude the 2’ OH, but RNAPs have to employ alternative selection strategies. In single-subunit RNAPs, a conserved Tyr residue discriminates against 2’dNTPs, whereas selectivity mechanisms of multi-subunit RNAPs remain hitherto unknown. Here we show that a conserved Arg residue uses a two-pronged strategy to select against 2’dNTPs in multi-subunit RNAPs. The conserved Arg interacts with the 2’OH group to promote NTP binding, but selectively inhibits incorporation of 2’dNTPs by interacting with their 3’OH group to favor the catalytically-inert 2’-endo conformation of the deoxyribose moiety. This deformative action is an elegant example of an active selection against a substrate that is a substructure of the correct substrate. Our findings provide important insights into the evolutionary origins of biopolymers and the design of selective inhibitors of viral RNAPs. url: https://doi.org/10.1101/2020.06.30.179606 doi: 10.1101/2020.06.30.179606 id: cord-304794-z2kx314h author: Métifiot, Mathieu title: G-quadruplexes in viruses: function and potential therapeutic applications date: 2014-11-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: G-rich nucleic acids can form non-canonical G-quadruplex structures (G4s) in which four guanines fold in a planar arrangement through Hoogsteen hydrogen bonds. Although many biochemical and structural studies have focused on DNA sequences containing successive, adjacent guanines that spontaneously fold into G4s, evidence for their in vivo relevance has recently begun to accumulate. Complete sequencing of the human genome highlighted the presence of ∼300 000 sequences that can potentially form G4s. Likewise, the presence of putative G4-sequences has been reported in various viruses genomes [e.g., Human immunodeficiency virus (HIV-1), Epstein–Barr virus (EBV), papillomavirus (HPV)]. Many studies have focused on telomeric G4s and how their dynamics are regulated to enable telomere synthesis. Moreover, a role for G4s has been proposed in cellular and viral replication, recombination and gene expression control. In parallel, DNA aptamers that form G4s have been described as inhibitors and diagnostic tools to detect viruses [e.g., hepatitis A virus (HAV), EBV, cauliflower mosaic virus (CaMV), severe acute respiratory syndrome virus (SARS), simian virus 40 (SV40)]. Here, special emphasis will be given to the possible role of these structures in a virus life cycle as well as the use of G4-forming oligonucleotides as potential antiviral agents and innovative tools. url: https://doi.org/10.1093/nar/gku999 doi: 10.1093/nar/gku999 id: cord-023844-3flfngu0 author: Mülhardt, Cornel title: Was bitte ist denn »Molekularbiologie«? date: 2013 words: 2802.0 sentences: 358.0 pages: flesch: 69.0 cache: ./cache/cord-023844-3flfngu0.txt txt: ./txt/cord-023844-3flfngu0.txt summary: Der Molekularbiologe, auch Molli genannt, hantiert die meiste Zeit mit winzigen Mengen zumeist klarer, farbloser Lösungen -keine Spur vom wildgewordenen Forscher, wie man ihn aus den Filmen kennt, der inmitten von wabernden, dampfenden, knallbunten Flüssigkeiten steht und dabei offensichtlich viel Spaß hat. Die Natur -wen immer man sich darunter vorstellen mag -hat aus einer seltsamen Laune heraus die Eigenschaften von Nucleinsäuren optimal genutzt, um daraus eine verwirrende Vielfalt von Leben zu schaffen, und das geht so: Weil sich die Basen paaren, kann man zu einer einzelsträngigen DNA einen komplementären Strang synthetisieren, zu dem man ebenfalls wieder einen komplementären Strang synthetisieren kann, der mit dem ersten Strang identisch ist. Sie liegen wie eine zweite Haut an, sind aber leider allergen, vor allem die gepuderte Variante, von der man entschieden abraten muss, weil sich im Laufe der Monate und Jahre bei den meisten Leuten Hautprobleme einstellen. abstract: In diesen Zeiten Molekularbiologie zu betreiben ist aufregend. Es bedeutet »Gentechnik« und »Klonieren« und hat etwas Göttliches. Beim einen Teil der Bevölkerung wird man, wenn man verrät, womit man seinen lieben langen Arbeitstag verbringt, grenzenlose Bewunderung hervorrufen, beim anderen grenzenlose Ablehnung – man sollte sich daher genauestens überlegen, mit wem man es gerade zu tun hat, bevor man den Mund aufmacht. Am besten, man erwähnt keiner der Gruppen gegenüber, mit wieviel Problemen und Frust man in Wahrheit täglich kämpft, weil der erste Teil dann desillusioniert wäre und der zweite, vielleicht zurecht, unweigerlich die Frage stellen würde: »Wozu machst du das dann überhaupt?« url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176190/ doi: 10.1007/978-3-642-34636-1_1 id: cord-003674-3ajyr5e4 author: NAGAO, Konomu title: Development of a fluorescent loop-mediated isothermal amplification assay for rapid and simple diagnosis of bovine leukemia virus infection date: 2019-03-27 words: 2565.0 sentences: 130.0 pages: flesch: 53.0 cache: ./cache/cord-003674-3ajyr5e4.txt txt: ./txt/cord-003674-3ajyr5e4.txt summary: title: Development of a fluorescent loop-mediated isothermal amplification assay for rapid and simple diagnosis of bovine leukemia virus infection A fluorescent loop-mediated isothermal amplification (fLAMP) assay targeting BLV env sequences was developed and used to evaluate 100 bovine blood samples. Fluorescent (fLAMP) reagents are commercially available, and this real-time amplification approach allows extremely rapid and accurate diagnosis through the use of an improved chain replacement enzyme and annealing analysis compared with tLAMP [4, 6, 17] . Here we used 100 bovine blood samples obtained from farms in the Kagoshima, Miyazaki and Oita prefectures in Japan to develop an fLAMP assay that we compared with a published real-time PCR assay. We used 100 bovine clinical blood samples, comprising 80 ELISA-positive and 20 ELISA-negative samples, to evaluate the performance of the BLV specific fLAMP assay. Development of loop-mediated isothermal amplification method for diagnosis of bovine leukemia virus infection abstract: Bovine leukemia virus (BLV) causes enzootic bovine leukosis (EBL), a condition that threatens the sustainability of the livestock industry. A fluorescent loop-mediated isothermal amplification (fLAMP) assay targeting BLV env sequences was developed and used to evaluate 100 bovine blood samples. Compared with a conventional real-time PCR (rPCR) assay, the fLAMP assay achieved 87.3% (62/71) sensitivity and 100% (29/29) specificity. The rPCR assay took 65 min, while the fLAMP assay took 8 min to 30 min from the beginning of DNA amplification to final judgement with a comparable limit of detection. The fLAMP is a potential tool for the rapid and simple diagnosis of BLV infection to supplement ELISA testing and can be used by local laboratories and slaughterhouses without special equipment. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541838/ doi: 10.1292/jvms.19-0009 id: cord-027654-k0uby99n author: Nabel, Gary J. title: The development of gene-based vectors for immunization date: 2020-06-22 words: 6550.0 sentences: 321.0 pages: flesch: 37.0 cache: ./cache/cord-027654-k0uby99n.txt txt: ./txt/cord-027654-k0uby99n.txt summary: The advantages of their ability to induce cellular immunity, immunogenicity, safety, mode of antigen presentation, and other attractive features are countered by limitations in knowledge about clinical effi cacy, production methodologies, DNA vaccination as the initial vaccine constituent and replication-defective viral vectors, including modifi ed vaccinia Ankara virus (MVA), 21,28 rAd 22,23,27,29 or proteins to boost the initial response. 31, 32 In addition, the development of improved enhancer/ promoter regions can allow for even higher expression 5 and these vaccines have advanced into multiple human Phase I studies, alone or in combination with other gene-based vectors. Depending on their ability to target antigen presenting cells, ability to develop packaging lines, inherent immunogenicity of both the vector and insert, and other factors (Table 62 -2), these viral vectors are helping to improve vaccine effi cacy in a variety of infectious disease models. Comparative immunogenicity in rhesus monkeys of DNA plasmid, recombinant vaccinia virus, and replication-defective adenovirus vectors expressing a human immunodefi ciency virus type 1 gag gene abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310921/ doi: 10.1016/b978-1-4160-3611-1.50066-0 id: cord-000826-nuwvge0t author: Nagels Durand, Astrid title: A MultiSite Gateway(TM )vector set for the functional analysis of genes in the model Saccharomyces cerevisiae date: 2012-09-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Recombinatorial cloning using the Gateway(TM) technology has been the method of choice for high-throughput omics projects, resulting in the availability of entire ORFeomes in Gateway(TM) compatible vectors. The MultiSite Gateway(TM) system allows combining multiple genetic fragments such as promoter, ORF and epitope tag in one single reaction. To date, this technology has not been accessible in the yeast Saccharomyces cerevisiae, one of the most widely used experimental systems in molecular biology, due to the lack of appropriate destination vectors. RESULTS: Here, we present a set of three-fragment MultiSite Gateway(TM) destination vectors that have been developed for gene expression in S. cerevisiae and that allow the assembly of any promoter, open reading frame, epitope tag arrangement in combination with any of four auxotrophic markers and three distinct replication mechanisms. As an example of its applicability, we used yeast three-hybrid to provide evidence for the assembly of a ternary complex of plant proteins involved in jasmonate signalling and consisting of the JAZ, NINJA and TOPLESS proteins. CONCLUSION: Our vectors make MultiSite Gateway(TM) cloning accessible in S. cerevisiae and implement a fast and versatile cloning method for the high-throughput functional analysis of (heterologous) proteins in one of the most widely used model organisms for molecular biology research. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519679/ doi: 10.1186/1471-2199-13-30 id: cord-340781-z348xbn0 author: Namvar, Ali title: In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine date: 2019-10-23 words: 6646.0 sentences: 357.0 pages: flesch: 50.0 cache: ./cache/cord-340781-z348xbn0.txt txt: ./txt/cord-340781-z348xbn0.txt summary: Moreover, in vivo studies indicated that the combination of L1 and L2 DNA constructs without any adjuvant or delivery system induced effective immune responses, and protected mice against C3 tumor cells (the percentage of tumor-free mice: ~66.67%). The framework begins with conservancy analysis of all 13 high-risk HPV strains following with (1) B-cell epitope mapping, (2) T-cell epitope mapping (CD4 + and CD8 + ), (3) allergenicity assessment, (4) tap transport and proteasomal cleavage, (5) population coverage, (6) global and template-based docking and (7) data collection, analysis, and design of the L1 and L2 DNA constructs. In this study, for the first time, comprehensively integrated methods (using sequence-based tools in combination with flexible peptide-protein docking) were used to design highly immunogenic and protective vaccine candidates which were able to boost both humoral and cellular Table 12 . abstract: Human papillomavirus (HPV) is the most common sexually transmitted infection in the world and the main cause of cervical cancer. Nowadays, the virus-like particles (VLPs) based on L1 proteins have been considered as the best candidate for vaccine development against HPV infections. Two commercial HPV (Gardasil and Cervarix) are available. These HPV VLP vaccines induce genotype-limited protection. The major impediments such as economic barriers especially gaps in financing obstructed the optimal delivery of vaccines in developing countries. Thus, many efforts are underway to develop the next generation of vaccines against other types of high-risk HPV. In this study, we developed DNA constructs (based on L1 and L2 genes) that were potentially immunogenic and highly conserved among the high-risk HPV types. The framework of analysis include (1) B-cell epitope mapping, (2) T-cell epitope mapping (i.e., CD4(+) and CD8(+) T cells), (3) allergenicity assessment, (4) tap transport and proteasomal cleavage, (5) population coverage, (6) global and template-based docking, and (7) data collection, analysis, and design of the L1 and L2 DNA constructs. Our data indicated the 8-epitope candidates for helper T-cell and CTL in L1 and L2 sequences. For the L1 and L2 constructs, combination of these peptides in a single universal vaccine could involve all world population by the rate of 95.55% and 96.33%, respectively. In vitro studies showed high expression rates of multiepitope L1 (~57.86%) and L2 (~68.42%) DNA constructs in HEK-293T cells. Moreover, in vivo studies indicated that the combination of L1 and L2 DNA constructs without any adjuvant or delivery system induced effective immune responses, and protected mice against C3 tumor cells (the percentage of tumor-free mice: ~66.67%). Thus, the designed L1 and L2 DNA constructs would represent promising applications for HPV vaccine development. url: https://www.ncbi.nlm.nih.gov/pubmed/31645650/ doi: 10.1038/s41598-019-51679-8 id: cord-321762-7kiahjyy author: Nandy, Ashesh title: Chapter 5 The GRANCH Techniques for Analysis of DNA, RNA and Protein Sequences date: 2015-12-31 words: 9780.0 sentences: 392.0 pages: flesch: 46.0 cache: ./cache/cord-321762-7kiahjyy.txt txt: ./txt/cord-321762-7kiahjyy.txt summary: We presented our scheme at the First Indo-US Workshop on Mathematical Chemistry in Shantiniketan, West Bengal, India in 1998 [10] where we reported, as stated in the abstract, that "Geometrisation of macromolecular sequences in the form of a graphical representation provides one … technique where the nucleotides in a gene sequence can be viewed as objects in a 4-dimensional space; the method can be extended, in principle, to include, say proteins, in a 20-dimensional space. This review is a brief introduction to the readers of this new and exciting field of research on graphical representation and numerical characterization (GRANCH) of bio-molecular sequences, based on the talk I presented at the Second Mathematical Chemistry Workshop of the Americas in Bogota, Colombia, in July 2010 [13] . abstract: Abstract: The very rapid growth in molecular sequence data from the daily accretion of large gene and protein sequencing projects have led to issues regarding viewing and analyzing the massive amounts of data. Graphical representation and numerical characterization of DNA, RNA and protein sequences have exhibited great potential to address these concerns. We review here in brief several different formulations of these representations and examples of applications to diverse problems based on what this author had presented at the Second Mathematical Chemistry Workshop of the Americas in Bogota, Colombia in 2010. In particular, we note several insights that were gained from such representations, and the applications to the bio-medicinal field. url: https://api.elsevier.com/content/article/pii/B9781681080536500053 doi: 10.1016/b978-1-68108-053-6.50005-3 id: cord-252871-qfrpuy3t author: Nasir, Arshan title: Investigating the Concept and Origin of Viruses date: 2020-11-03 words: 5153.0 sentences: 298.0 pages: flesch: 46.0 cache: ./cache/cord-252871-qfrpuy3t.txt txt: ./txt/cord-252871-qfrpuy3t.txt summary: We propose a new definition of viruses that is not restricted to the presence or absence of any genetic or physical feature, detail a scenario for how viruses likely originated from ancient cells, and explain technical and conceptual biases that limit our understanding of virus evolution. We propose a new definition of viruses that is not restricted to the presence or absence of any genetic or physical feature, detail a scenario for how viruses likely originated from ancient cells, and explain technical and conceptual biases that limit our understanding of virus evolution. In turn, the origin of archaeoviruses from Archaea, bacterioviruses from Bacteria, and eukaryoviruses from Eukarya also seems less likely as these viruses share several conserved protein folds involved in virion synthesis and other functions, indicating that they may have evolved prior to the diversification of LUCA into modern cells. abstract: The ongoing COVID-19 pandemic has piqued public interest in the properties, evolution, and emergence of viruses. Here, we discuss how these basic questions have surprisingly remained disputed despite being increasingly within the reach of scientific analysis. We review recent data-driven efforts that shed light into the origin and evolution of viruses and explain factors that resist the widespread acceptance of new views and insights. We propose a new definition of viruses that is not restricted to the presence or absence of any genetic or physical feature, detail a scenario for how viruses likely originated from ancient cells, and explain technical and conceptual biases that limit our understanding of virus evolution. We note that the philosophical aspects of virus evolution also impact the way we might prepare for future outbreaks. url: https://api.elsevier.com/content/article/pii/S0966842X20302304 doi: 10.1016/j.tim.2020.08.003 id: cord-341029-49360l2a author: Nasir, Arshan title: A phylogenomic data-driven exploration of viral origins and evolution date: 2015-09-25 words: 14410.0 sentences: 794.0 pages: flesch: 49.0 cache: ./cache/cord-341029-49360l2a.txt txt: ./txt/cord-341029-49360l2a.txt summary: Viruses harboring different replicon types and infecting distantly related hosts shared many metabolic and informational protein structural domains of ancient origin that were also widespread in cellular proteomes. Here, we analyzed a total of 5080 completely sequenced proteomes from cells and viruses and assigned FSF domains to their proteins using structure-based hidden Markov models (HMMs) defined by the SUPER-FAMILY database (version 1.75) (20) . Viral supergroup behaves similarly to cellular superkingdoms in terms of FSF sharing patterns A total of 1995 significant FSF domains (E < 0.0001) were detected iñ 11 million proteins of 5080 proteomes sampled from cells and viruses. It also suggests that viruses are very ancient and most likely infected the last common ancestor of each superkingdom because viral FSFs were present in a diverse array of cellular organisms ranging from small microbes to large eukaryotes. abstract: The origin of viruses remains mysterious because of their diverse and patchy molecular and functional makeup. Although numerous hypotheses have attempted to explain viral origins, none is backed by substantive data. We take full advantage of the wealth of available protein structural and functional data to explore the evolution of the proteomic makeup of thousands of cells and viruses. Despite the extremely reduced nature of viral proteomes, we established an ancient origin of the “viral supergroup” and the existence of widespread episodes of horizontal transfer of genetic information. Viruses harboring different replicon types and infecting distantly related hosts shared many metabolic and informational protein structural domains of ancient origin that were also widespread in cellular proteomes. Phylogenomic analysis uncovered a universal tree of life and revealed that modern viruses reduced from multiple ancient cells that harbored segmented RNA genomes and coexisted with the ancestors of modern cells. The model for the origin and evolution of viruses and cells is backed by strong genomic and structural evidence and can be reconciled with existing models of viral evolution if one considers viruses to have originated from ancient cells and not from modern counterparts. url: https://www.ncbi.nlm.nih.gov/pubmed/26601271/ doi: 10.1126/sciadv.1500527 id: cord-319884-d8n0aokl author: Natesan, Mohan title: Protein Microarrays and Biomarkers of Infectious Disease date: 2010-12-16 words: 7088.0 sentences: 359.0 pages: flesch: 36.0 cache: ./cache/cord-319884-d8n0aokl.txt txt: ./txt/cord-319884-d8n0aokl.txt summary: Fluorescencebased detection of protein interactions is similar to gene array methods, and data analysis often employs approaches previously developed for genome and transcription studies. A standard assay for measuring antibody interactions with proteins of the vaccinia proteome microarray was first developed with a pool of therapeutic human sera collected from vaccinia-immune individuals (VIg) and this data was compared to results obtained from individuals vaccinated against smallpox using Dryvax. Results from this study suggested that antibodies from vaccination recognized a small number of proteins shared with pathogenic viral strains, while recovery from infection also involved humoral immunity to antigens uniquely recognized within the monkeypox virus proteome (unpublished data). For example, a protein array produced from the outer membrane proteins of Pseudomonas aeruginosa was constructed [38] to study the immune response in patients, and several antibody-binding antigens were identified by this group as potential diagnostic markers. abstract: Protein microarrays are powerful tools that are widely used in systems biology research. For infectious diseases, proteome microarrays assembled from proteins of pathogens will play an increasingly important role in discovery of diagnostic markers, vaccines, and therapeutics. Distinct formats of protein microarrays have been developed for different applications, including abundance-based and function-based methods. Depending on the application, design issues should be considered, such as the need for multiplexing and label or label free detection methods. New developments, challenges, and future demands in infectious disease research will impact the application of protein microarrays for discovery and validation of biomarkers. url: https://doi.org/10.3390/ijms11125165 doi: 10.3390/ijms11125165 id: cord-312522-mymgnf8z author: Nelson, Megan M. title: Rapid molecular detection of macrolide resistance date: 2019-02-12 words: 5135.0 sentences: 277.0 pages: flesch: 42.0 cache: ./cache/cord-312522-mymgnf8z.txt txt: ./txt/cord-312522-mymgnf8z.txt summary: METHODS: We use Recombinase Polymerase Assay (RPA) to detect the antimicrobial resistance gene mef(A) from raw lysates without nucleic acid purification. We show that detection of mef(A) accurately predicts real antimicrobial resistance assessed by traditional culture methods, and that the assay is robust to high levels of spiked-in non-specific nucleic acid contaminant. In this study, we developed and tested a novel RPA assay for the detection of the Macrolide Efflux A, or mef(A) gene, an efflux pump rendering host bacteria resistant to 14-and 15-membered macrolide antibiotics (including erythromycin A and azithromycin) [33, 34] . Our RPA assay uncovered an unexpected occurrence of the mef(A) gene within commensal Streptococcus salivarius strain, and subsequent laboratory testing confirmed that this strain has genuine antimicrobial resistance. To assess assay sensitivity we ran a serial dilution of DNA derived from mef(A)-positive Streptococcus pyogenes serotype M6 strain MGAS10394 [39] and found that confident detection was around 2000 genome copies (Fig. 1b) . abstract: BACKGROUND: Emerging antimicrobial resistance is a significant threat to human health. However, methods for rapidly diagnosing antimicrobial resistance generally require multi-day culture-based assays. Macrolide efflux gene A, mef(A), provides resistance against erythromycin and azithromycin and is known to be laterally transferred among a wide range of bacterial species. METHODS: We use Recombinase Polymerase Assay (RPA) to detect the antimicrobial resistance gene mef(A) from raw lysates without nucleic acid purification. To validate these results we performed broth dilution assays to assess antimicrobial resistance to erythromycin and ampicillin (a negative control). RESULTS: We validate the detection of mef(A) in raw lysates of Streptococcus pyogenes, S. pneumoniae, S. salivarius, and Enterococcus faecium bacterial lysates within 7–10 min of assay time. We show that detection of mef(A) accurately predicts real antimicrobial resistance assessed by traditional culture methods, and that the assay is robust to high levels of spiked-in non-specific nucleic acid contaminant. The assay was unaffected by single-nucleotide polymorphisms within divergent mef(A) gene sequences, strengthening its utility as a robust diagnostic tool. CONCLUSIONS: This finding opens the door to implementation of rapid genomic diagnostics in a clinical setting, while providing researchers a rapid, cost-effective tool to track antibiotic resistance in both pathogens and commensal strains. url: https://doi.org/10.1186/s12879-019-3762-4 doi: 10.1186/s12879-019-3762-4 id: cord-017137-6pmts7ui author: Nema, Vijay title: Microbial Forensics: Beyond a Fascination date: 2018-07-12 words: 4463.0 sentences: 227.0 pages: flesch: 42.0 cache: ./cache/cord-017137-6pmts7ui.txt txt: ./txt/cord-017137-6pmts7ui.txt summary: When leftover microbes in the biological material or objects used by the culprit or the person in question are used to correlate the identity of the individual, it takes us to the new field of science—"microbial forensics." Technological advances in the field of forensics, molecular biology, and microbiology have all helped to refine the techniques of collecting and processing of the samples for microbiological identification using DNA-based methods followed by its inference in the form of evidence. Herein the microbial forensics could be defined as "the discipline of applying scientific methods to the analysis of evidence related to bioterrorism, biocrimes, hoaxes, or the accidental release of a biological agent or toxin for attribution purposes" [21] . Microbial forensics has a role in such cases by applying scientific methods for the analysis of evidence from such a bioterrorism attack. The most reliable technique till date for microbial forensics is metagenomics-a culture-independent approach for identifying and enumerating microbes. abstract: Microbiology has seen a great transition from culture-based identification of microbes using various biochemical and microscopic observations to identify and functionally characterize the microbes by just collecting the DNA and sequencing it. This advancement has not only moved in and around microbiology but has found its applications in fields which were earlier considered to be the remote ones. Forensics is one such field, where tracing the leftover evidence on a crime scene can lead to the identification and prosecution of the culprit. When leftover microbes in the biological material or objects used by the culprit or the person in question are used to correlate the identity of the individual, it takes us to the new field of science—“microbial forensics.” Technological advances in the field of forensics, molecular biology, and microbiology have all helped to refine the techniques of collecting and processing of the samples for microbiological identification using DNA-based methods followed by its inference in the form of evidence. Studies have supported the assumption that skin or surface microflora of an individual is somewhat related with the microflora found on the objects used by that individual and efforts are ongoing to see if this is found consistently in various surroundings and with different individuals. Once established, this technique would facilitate accurate identification and differentiation of an individual or suspect to guide investigations along with conventional evidence. Legal investigations are not only the field where microbial forensic could help. Agriculture, defense, public health, tourism, etc. are the fields wherein microbial forensics with different names based on the fields are helping out and have potential to further support other fields. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121623/ doi: 10.1007/978-981-13-1583-1_17 id: cord-025251-evnfvc0l author: Nemunaitis, John title: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection: let the virus be its own demise date: 2020-05-26 words: 7308.0 sentences: 397.0 pages: flesch: 38.0 cache: ./cache/cord-025251-evnfvc0l.txt txt: ./txt/cord-025251-evnfvc0l.txt summary: Herein we describe the rationale and potential of repurposing a dual plasmid, Vigil (pbi-shRNA(furin)-GM-CSF), now in Phase III cancer trials, for the treatment of and, in certain circumstances, enhancement of the immune response to SARS-CoV-2. A recent publication from Nankai University (Tianjin, China) on SARS-CoV-2 reported that genome sequence analysis revealed a section of genes that was not present in SARS-CoV that had a cleavage site similar to HIV and Ebola which carry viral proteins necessary for fusogenic activity of viral species to the human cell membrane. Another immunotherapeutic intervention would be to increase the pulmonary expression of GM-CSF, which, in vivo, redirects macrophages from an M1 state of activation to an M2 activation state and enhances expression of anti-inflammatory mediators and perhaps allow more time for patients to mount an effective immune response against SARS-CoV-2 [25] . Similar to SARS-CoV-2, alveolar epithelial cells are the primary target of influenza virus (IV) and are the first site of entry and support for viral propagation and replication. abstract: There has been a collaborative global effort to construct novel therapeutic and prophylactic approaches to SARS-CoV-2 management. Although vaccine development is crucial, acute management of newly infected patients, especially those with severe acute respiratory distress syndrome, is a priority. Herein we describe the rationale and potential of repurposing a dual plasmid, Vigil (pbi-shRNA(furin)-GM-CSF), now in Phase III cancer trials, for the treatment of and, in certain circumstances, enhancement of the immune response to SARS-CoV-2. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249572/ doi: 10.2217/fvl-2020-0068 id: cord-253466-7gpije5d author: Netherton, Christopher title: A Guide to Viral Inclusions, Membrane Rearrangements, Factories, and Viroplasm Produced During Virus Replication date: 2007-08-31 words: 26372.0 sentences: 1363.0 pages: flesch: 45.0 cache: ./cache/cord-253466-7gpije5d.txt txt: ./txt/cord-253466-7gpije5d.txt summary: Significantly, Poliovirus infection causes enrichment of GEFs in membranes containing replicase proteins, and this would provide a mechanism for increasing levels of Arf1-GTP at sites of virus replication. There is evidence that Tobacco mosaic virus also uses the ER as a site of replication because the replicase enzyme and viral RNA are located on the ER of infected cells, and infection causes major changes in ER morphology (Reichel and Beachy, 1998) , including ER aggregation and formation of lamella structures. Even though these viruses infect a diverse range of hosts from different phyla, including vertebrates [poxviruses, African swine fever virus (ASFV)], arthropods (entomopox, ASFV, chloriridoviruses), amphibians and fish (Ranavirus, Megalocytivirus, and Lymphocystivirus genera of the Iridoviridae family), marine algae (phycodnaviruses), and protozoa (mimivirus), they all generate cytoplasmic factories as major sites of virus assembly and replication (illustrated in Fig. 4 ). Formation of DNA replication structures in herpes virus-infected cells requires a viral DNA binding protein abstract: Virus replication can cause extensive rearrangement of host cell cytoskeletal and membrane compartments leading to the “cytopathic effect” that has been the hallmark of virus infection in tissue culture for many years. Recent studies are beginning to redefine these signs of viral infection in terms of specific effects of viruses on cellular processes. In this chapter, these concepts have been illustrated by describing the replication sites produced by many different viruses. In many cases, the cellular rearrangements caused during virus infection lead to the construction of sophisticated platforms in the cell that concentrate replicase proteins, virus genomes, and host proteins required for replication, and thereby increase the efficiency of replication. Interestingly, these same structures, called virus factories, virus inclusions, or virosomes, can recruit host components that are associated with cellular defences against infection and cell stress. It is possible that cellular defence pathways can be subverted by viruses to generate sites of replication. The recruitment of cellular membranes and cytoskeleton to generate virus replication sites can also benefit viruses in other ways. Disruption of cellular membranes can, for example, slow the transport of immunomodulatory proteins to the surface of infected cells and protect against innate and acquired immune responses, and rearrangements to cytoskeleton can facilitate virus release. url: https://www.sciencedirect.com/science/article/pii/S0065352707700040 doi: 10.1016/s0065-3527(07)70004-0 id: cord-016293-pyb00pt5 author: Newell-McGloughlin, Martina title: The flowering of the age of Biotechnology 1990–2000 date: 2006 words: 22402.0 sentences: 943.0 pages: flesch: 47.0 cache: ./cache/cord-016293-pyb00pt5.txt txt: ./txt/cord-016293-pyb00pt5.txt summary: In the course of the project, especially in the early years, the plan stated that "much new technology will be developed that will facilitate biomedical and a broad range of biological research, bring down the cost of many experiments (mapping and sequencing), and finding applications in numerous other fields." The plan built upon the 1988 reports of the Office of Technology Assessment and the National Research Council on mapping and sequencing the human genome. These DNA chips have broad commercial applications and are now used in many areas of basic and clinical research including the detection of drug resistance mutations in infectious organisms, direct DNA sequence comparison of large segments of the human genome, the monitoring of multiple human genes for disease associated mutations, the quantitative and parallel measurement of mRNA expression for thousands of human genes, and the physical and genetic mapping of genomes. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120537/ doi: 10.1007/1-4020-5149-2_4 id: cord-018145-kssjdn8y author: Niemann, Heiner title: Transgenic Farm Animals: Current Status and Perspectives for Agriculture and Biomedicine date: 2009 words: 9160.0 sentences: 503.0 pages: flesch: 40.0 cache: ./cache/cord-018145-kssjdn8y.txt txt: ./txt/cord-018145-kssjdn8y.txt summary: Guidelines developed by the Food and Drug Administration (FDA) of the USA require monitoring the animals'' health in a specific pathogen free (SPF) facility, sequence validation of the gene construct, characterization of the isolated recombinant protein, and monitoring the genetic stability of the transgenic animals over several generations. Some gene constructs have failed to produce economically significant amounts of protein in the milk of transgenic animals indicating that the technology needs further refinement to insure consistent high-level expression. The use of somatic nuclear transfer will accelerate production of transgenic animals for mammary gland specific synthesis of recombinant proteins. In the pig, increased transgenic expression of a bovine lactalbumin construct in the mammary gland resulted in increased lactose content and increased milk production which resulted in improved survival and development of the piglets (Wheeler et al. abstract: The first transgenic livestock were produced in 1985 by microinjection of foreign DNA into zygotic pronuclei. This was the method of choice for more than 20 years, but more efficient protocols are now available, based on somatic cell nuclear transfer (SCNT) which permits targeted genetic modifications. Although the efficiency of transgenic animal production by microinjection technology is low, many animals with agriculturally important transgenic traits were produced. Typical applications included improved carcass composition, lactational performance, and wool production as well as enhanced disease resistance and reduced environmental impact. Transgenic animal production for biomedical applications has found broad acceptance. In 2006 the European Medicines Agency (EMEA) approved the commercialization of the first recombinant protein drug produced by transgenic animals. Recombinant antithrombin III, produced in the mammary gland of transgenic goats, was launched as ATryn® for prophylactic treatment of patients with congenital antithrombin deficiency. Pigs expressing human immunomodulatory genes have contributed to significant progress in xenotransplantation research with survival periods of non-human primates receiving transgenic porcine hearts or kidneys approaching six months. Lentiviral vectors and small interfering ribonucleic acid (siRNA) technology are also emerging as important tools for transgenesis. As the genome sequencing projects for various farm animal species progress, it has become increasingly practical to target the removal or modification of individual genes. We anticipate that this approach to animal breeding will be instrumental in meeting global challenges in agricultural production in the future and will open new horizons in biomedicine. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122947/ doi: 10.1007/978-3-540-85843-0_1 id: cord-032183-yqqqe325 author: Ning, Qin title: Antiviral Therapy for AECHB and Severe Hepatitis B (Liver Failure) date: 2019-05-21 words: 32675.0 sentences: 1658.0 pages: flesch: 43.0 cache: ./cache/cord-032183-yqqqe325.txt txt: ./txt/cord-032183-yqqqe325.txt summary: Patients awaiting liver transplantation because of HBV-related end-stage liver disease or liver cancer should be given nucleoside analogues with strong HBV inhibition and low drug-resistance, or nucleotides analogues combination treatment, in order to reduce viral load and prevent graft re-infection. The objective of antiviral treatment for HBV-ACLF is to reduce viral load at an appreciably high rate, thereby promoting reduction in hepatocyte cell death and improved survival outcomes by prevention of decompensation related multiorgan complications in this group of severely ill patients. Response-Guided Therapy 4006 study [126] suggested continuous treatment with LAM (10 years) delayed clinical progression in patients with chronic hepatitis and advanced fibrosis by significantly reducing the incidence of the risk of hepatocellular carcinoma and hepatic decompensation. abstract: This chapter describes the principles of antiviral therapy, treatment strategies, medications and recommendations for AECHB, HBV-ACLF, HBV-related liver cirrhosis, HBV-related HCC, and liver transplantation. 1. Severe exacerbation of chronic hepatitis B is closely related to continuous HBV replication. Therefore, inhibiting HBV replication to reduce viral load may block disease progression and improve the quality of life of these patients. ETV or TDF has been recommend first-line drug for the treatment of AECHB. 2. A hyperactive immune response due to continuous HBV replication is the main mechanism for development of severe hepatitis B. In addition to comprehensive treatment, early administration of potent nucleoside analogs can rapidly reduce HBV DNA concentration, relieve immune injury induced by HBV, and reduce liver inflammation and patient mortality. Antiviral agents have become important in the treatment of severe exacerbation of chronic hepatitis B. 3. Long-term antiviral treatment with nucleoside analogs can delay or reverse the progress of liver cirrhosis. Virologic response, viral resistance and adverse drug reactions should be closely monitored during treatment. The treatment should be optimized for maximum effect based on each patient’s responses. 4. Effective antiviral therapy can suppress HBV replication and reduce the incidence of HBV-related HCC. Patients with HBV-related HCC should receive individualized and optimal multidisciplinary comprehensive treatment. Anti-viral drugs with high efficacy, low resistance and low adverse drug reactions should be selected to improve the patient’s quality of life and prolong survival time. 5. Methods to prevent HBV reinfection after liver transplantation include passive immunization (HBIG), antiviral treatment (nucleoside analogs) and active immunization (hepatitis B vaccine). 6. Clinical trials involving sequential combination therapy with NUC and Peg-IFN have shown statistically significant decline in HBsAg levels on treatment and high rates of sustained post-treatment serologic response. Combination therapy with novel DAA and immunotherapeutic approach may hold promise to overcome both cccDNA persistence and immune escape, representing a critical step towards HBV cure. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498919/ doi: 10.1007/978-94-024-1603-9_5 id: cord-344321-fjer281d author: Ning, Yi title: Aptamers used for biosensors and targeted therapy date: 2020-10-20 words: 16947.0 sentences: 1045.0 pages: flesch: 49.0 cache: ./cache/cord-344321-fjer281d.txt txt: ./txt/cord-344321-fjer281d.txt summary: Aptamers, first raised by two research groups independently in 1990 [1, 2] , are single-stranded DNA (ssDNA) or RNA sequences obtained through systematic evolution of ligands by exponential enrichment (SELEX) that can fold into secondary and three-dimensional shapes, enabling them to recognize various target molecules with high specificity and affinity, including proteins [3, 4] , small molecules [5, 6] , metal ions [7, 8] , bacterial cells [9, 10] , viruses [11, 12] , cancer cells [13, 14] , and even tissues [15] . developed a novel QD-Apt conjugate to be loaded with Dox for the targeted delivery of drugs to PC cells based on the mechanism of binary (Bi)-FRET (Fig. 15A) [215] . The Apt-Dox-Lip complex showed selective internalization and enhanced cytotoxicity to MCF-7 breast cancer cells and xenograft MCF-7 breast tumors in nude mice, suggesting that AS1411 aptamer-functionalized liposomes can specifically bind nucleolin overexpressed on the MCF-7 cell surface, and implement drug delivery with high selectivity. abstract: Aptamers are single-stranded nucleic acid sequences that can bind to target molecules with high selectivity and affinity. Most aptamers are screened in vitro by a combinatorial biology technique called systematic evolution of ligands by exponential enrichment (SELEX). Since aptamers were discovered in the 1990s, they have attracted considerable attention and have been widely used in many fields owing to their unique advantages. In this review, we present an overview of the advancements made in aptamers used for biosensors and targeted therapy. For the former, we will discuss multiple aptamer-based biosensors with different principles detected by various signaling methods. For the latter, we will focus on aptamer-based targeted therapy using aptamers as both biotechnological tools for targeted drug delivery and as targeted therapeutic agents. Finally, challenges and new perspectives associated with these two regions were further discussed. We hope that this review will help researchers interested in aptamer-related biosensing and targeted therapy research. url: https://www.ncbi.nlm.nih.gov/pubmed/33096353/ doi: 10.1016/j.biopha.2020.110902 id: cord-009655-ekc2p7k9 author: Norbäck, D. title: Dampness, indoor mould, fungal DNA and respiratory health – molecular methods in indoor epidemiology date: 2015-04-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162140/ doi: 10.1111/cea.12524 id: cord-018039-dw2xblyr author: Norbäck, Dan title: Microbial Agents in the Indoor Environment: Associations with Health date: 2019-08-08 words: 7024.0 sentences: 396.0 pages: flesch: 44.0 cache: ./cache/cord-018039-dw2xblyr.txt txt: ./txt/cord-018039-dw2xblyr.txt summary: Keywords Mould · Bacteria · Endotoxin · Beta-1-3-glucan · Muramic acid Fungal DNA · Microbial volatile organic compounds (MVOC) · Mycotoxins Asthma · Respiratory symptoms Endotoxin: A cell-wall compound found in gram-negative bacteria (endotoxin can have different chain length of the 3-hydroxy acids in the molecule) Muramic acid (MuA): A cell-wall compound found mainly in gram-positive bacteria Ergosterol: A cell-wall compound found in mould (but also in plant materials) Beta 1-3 glucans: A group of cell-wall compounds in mould (but also in pollen)t Fungal DNA: DNA sequences specific for mould (general or species specific sequences) Bacterial DNA: DNA sequences specific for bacteria (general or species specific sequences) MVOC: Volatile organic compounds produced by microorganisms (but can have non-microbial sources as well) Secondary microbial metabolites: Chemical compounds produced by the secondary metabolism of microorganisms Mycotoxins: Chemical compounds with toxic properties produced by mould (a subgroup of secondary microbial metabolites) They concluded that there is sufficient evidence of a causal association between outdoor culturable fungal exposure and exacerbation in asthmatics sensitised to fungi. abstract: There is international consensus that damp buildings and indoor mould can increase the risk of asthma, rhinitis, bronchitis and respiratory tract infections but we do not know which types of microbial agents that are causing the observed adverse health effects. Microbial indoor exposure is a broader concept than microbial growth in buildings. Other sources of indoor microbial exposure include the outdoor environment, humans (crowdedness) and furry pet keeping. Microbial exposure can have different health effects depending on the dose, different exposure route, genetic disposition and the timing of exposure. Microbial stimulation linked to large microbial diversity in early life can protect against disease development, especially for allergic asthma and atopy. Protective effects are more often reported for bacterial exposure and adverse health effects are more often linked to mould exposure. There are many studies on health associations for indoor exposure to endotoxin, mainly from homes. The risk of getting atopic asthma may be less if you are exposed to endotoxin in childhood but the risk of non-atopic asthma may increase if exposed to endotoxin especially in adulthood. Moreover, genetic disposition modifies health effects of endotoxin. Epidemiological studies on muramic acid (from gram-positive bacteria) or ergosterol (from mould) are few. Studies on health effects of indoor exposure to beta-1-3-glucan (from mould) have conflicting results (positive as well as negative associations). Epidemiological studies on health effects of indoor exposure to mycotoxins are very few. Some studies have reported health associations for MVOC, but it is unclear to what extent MVOC has microbial sources in indoor environments. Many studies have reported health associations for fungal DNA, especially as a risk factor for childhood asthma at home. Since most studies on health effects of indoor exposure to mould, bacteria and microbial agents are cross-sectional, it is difficult to draw conclusions on causality. More prospective studies on indoor microbial exposure are needed and studies should include other indoor environments than homes, such as day care centers, schools, hospitals and offices. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122805/ doi: 10.1007/978-981-32-9182-9_9 id: cord-256130-zhlvvuj4 author: Nordén, Rickard title: Quantification of Torque Teno Virus and Epstein-Barr Virus Is of Limited Value for Predicting the Net State of Immunosuppression After Lung Transplantation date: 2018-03-06 words: 4853.0 sentences: 230.0 pages: flesch: 47.0 cache: ./cache/cord-256130-zhlvvuj4.txt txt: ./txt/cord-256130-zhlvvuj4.txt summary: Here, we evaluated quantification of torque teno virus (TTV) and Epstein-Barr virus (EBV) as biomarkers for defining the net state of immunosuppression in lung-transplanted patients. The aim of the present study was to evaluate levels of TTV and EBV in relation to the frequency of infectious events and acute rejections over time in a prospective manner in a single-center cohort of lung-transplanted patients. The total nucleic acid content was isolated from serum or whole blood samples and analyzed for TTV-, EBV-, and CMV-DNA load by real-time PCR. Comparison of TTV-and EBV-DNA levels in lung transplant recipients who received either Tacrolimus-or Cyclosporinebased therapy revealed that Cyclosporine-treated patients had significantly lower TTV-DNA levels in serum at month 6 post-LTx and onwards, compared with the Tacrolimustreated patients (Figure 1 ). However, we found no association between either TTV-or EBV-DNA load and infectious events or acute rejections, which suggests a limited clinical applicability as biomarkers predicting short-term outcomes related to the net state of immunosuppression. abstract: BACKGROUND: Major hurdles for survival after lung transplantation are rejections and infectious complications. Adequate methods for monitoring immune suppression status are lacking. Here, we evaluated quantification of torque teno virus (TTV) and Epstein-Barr virus (EBV) as biomarkers for defining the net state of immunosuppression in lung-transplanted patients. METHODS: This prospective single-center study included 98 patients followed for 2 years after transplantation. Bacterial infections, fungal infections, viral respiratory infections (VRTI), cytomegalovirus (CMV) viremia, and acute rejections, as well as TTV and EBV levels, were monitored. RESULTS: The levels of torque teno virus DNA increased rapidly after transplantation, likely due to immunosuppressive treatment. A modest increase in levels of Epstein-Barr virus DNA was also observed after transplantation. There were no associations between either TTV or EBV and infectious events or acute rejection, respectively, during follow-up. When Tacrolimus was the main immunosuppressive treatment, TTV DNA levels were significantly elevated 6–24 months after transplantation as compared with Cyclosporine treatment. CONCLUSIONS: Although replication of TTV, but not EBV, appears to reflect the functionality of the immune system, depending on the type of immunosuppressive treatment, quantification of TTV or EBV as biomarkers has limited potential for defining the net state of immune suppression. url: https://www.ncbi.nlm.nih.gov/pubmed/29644247/ doi: 10.1093/ofid/ofy050 id: cord-103563-7a3wdduq author: Nunez-Bajo, Estefania title: Ultra-Low-Cost Integrated Silicon-based Transducer for On-Site, Genetic Detection of Pathogens date: 2020-03-25 words: 4535.0 sentences: 211.0 pages: flesch: 44.0 cache: ./cache/cord-103563-7a3wdduq.txt txt: ./txt/cord-103563-7a3wdduq.txt summary: Unlike other silicon-based technologies, TriSilix can be produced at wafer-scale in a standard laboratory; we have developed a series of methodologies based on metal-assisted chemical (wet) etching, electroplating, thermal bonding and laser-cutting to enable a cleanroom-free low-cost fabrication that does not require processing in an advanced semiconductor foundry. To create an ultra-low-cost device, the architecture proposed exploits the intrinsic properties of silicon and integrates three modes of operation in a single chip: i) electrical (Joule) heater, ii) temperature sensor (i.e. thermistor) with a negative temperature coefficient that can provide the precise temperature of the sample solution during reaction and iii) electrochemical sensor for detecting target NA. Using TriSilix, the sample solution can be maintained at a single, specific temperature (needed for isothermal amplification of NA such as Recombinase Polymerase Amplification (RPA) or cycled between different temperatures (with a precision of ±1.3°C) for Polymerase Chain Reaction (PCR) while the exact concentration of amplicons is measured quantitatively and in real-time electrochemically. abstract: Rapid screening and low-cost diagnosis play a crucial role in choosing the correct course of intervention e.g., drug therapy, quarantine, no action etc. when dealing with highly infectious pathogens. This is especially important if the disease-causing agent has no effective treatment, such as the novel coronavirus SARS-CoV-2 (the pathogen causing COVID-19), and shows no or similar symptoms to other common infections. We report a silicon-based integrated Point-of-Need (PoN) transducer (TriSilix) that can chemically-amplify and detect pathogen-specific sequences of nucleic acids (NA) quantitatively in real-time. Unlike other silicon-based technologies, TriSilix can be produced at wafer-scale in a standard laboratory; we have developed a series of methodologies based on metal-assisted chemical (wet) etching, electroplating, thermal bonding and laser-cutting to enable a cleanroom-free low-cost fabrication that does not require processing in an advanced semiconductor foundry. TriSilix is, therefore, resilient to disruptions in the global supply chain as the devices can be produced anywhere in the world. To create an ultra-low-cost device, the architecture proposed exploits the intrinsic properties of silicon and integrates three modes of operation in a single chip: i) electrical (Joule) heater, ii) temperature sensor (i.e. thermistor) with a negative temperature coefficient that can provide the precise temperature of the sample solution during reaction and iii) electrochemical sensor for detecting target NA. Using TriSilix, the sample solution can be maintained at a single, specific temperature (needed for isothermal amplification of NA such as Recombinase Polymerase Amplification (RPA) or cycled between different temperatures (with a precision of ±1.3°C) for Polymerase Chain Reaction (PCR) while the exact concentration of amplicons is measured quantitatively and in real-time electrochemically. A single 4-inch Si wafer yields 37 TriSilix chips of 10×10×0.65 mm in size and can be produced in 7 hours, costing ~US $0.35 per device. The system is operated digitally, portable and low power – capable of running up to 35 tests with a 4000 mAh battery (a typical battery capacity of a modern smartphone). We were able to quantitatively detect a 563-bp fragment (Insertion Sequence IS900) of the genomic DNA of M. avium subsp. paratuberculosis (extracted from cultured field samples) through PCR in real-time with a Limit-of-Detection of 20 fg, equivalent to a single bacterium, at the 30th cycle. Using TriSilix, we also detected the cDNA from SARS-CoV-2 (1 pg), through PCR, with high specificity against SARS-CoV (2003). url: https://doi.org/10.1101/2020.03.23.002931 doi: 10.1101/2020.03.23.002931 id: cord-298136-mel9fxw8 author: O'Malley, Maureen A. title: Whole-genome patenting date: 2005-05-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Gene patenting is now a familiar commercial practice, but there is little awareness that several patents claim ownership of the complete genome sequence of a prokaryote or virus. When these patents are analysed and compared to those for other biological entities, it becomes clear that genome patents seek to exploit the genome as an information base and are part of a broader shift towards intangible intellectual property in genomics. url: https://www.ncbi.nlm.nih.gov/pubmed/15883589/ doi: 10.1038/nrg1613 id: cord-252198-gs52k4lq author: Onions, David title: Validation of the safety of MDCK cells as a substrate for the production of a cell-derived influenza vaccine date: 2010-09-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Cell culture-based production methods may assist in meeting increasing demand for seasonal influenza vaccines and developing production flexibility required for addressing influenza pandemics. MDCK-33016PF cells are used in propagation of a cell-based seasonal influenza vaccine (Optaflu®); but, like most continuous cell lines, can grow in immunocompromised mice to produce tumors. It is, therefore, essential that no residual cells remain within the vaccine, that cell lysates or DNA are not oncogenic, and that the cell substrate does not contain oncogenic viruses or oncogenic DNA. Multiple, redundant processes ensure the safety of influenza vaccines produced in MDCK-33016PF cells. The probability of a residual cell being present in a dose of vaccine is approximately 1 in 1034. Residual MDCK-DNA is ≤10ng per dose and the ß-propiolactone used to inactivate influenza virus results in reduction of detectable DNA to less than 200base pairs (bp). Degenerate PCR and specific PCR confirm exclusion of oncogenic viruses. The manufacturing process has been validated for its capacity to remove and inactivate viruses. We conclude that the theoretical risks arising from manufacturing seasonal influenza vaccine using MDCK-33016PF cells are reduced to levels that are effectively zero by the multiple, orthogonal processes used during production. url: https://api.elsevier.com/content/article/pii/S1045105610000989 doi: 10.1016/j.biologicals.2010.04.003 id: cord-016187-58rqc0cg author: Opal, S. M. title: The Challenge of Emerging Infections and Progressive Antibiotic Resistance date: 2006 words: 6617.0 sentences: 330.0 pages: flesch: 37.0 cache: ./cache/cord-016187-58rqc0cg.txt txt: ./txt/cord-016187-58rqc0cg.txt summary: Community and nosocomial outbreaks of multidrug resistant pathogens as evidenced by methicillin and vancomycin resistance [17] in Staphylococcus aureus and resistance to the new anti-viral neuraminidase inhibitors [18, 19] by recent infl uenza isolates are cause for real concern. Beta-lactam antibiotics have been known for almost 80 years and their widespread use has created selection pressures on bacterial pathogens to resist their inhibitory actions. These investigators discovered that the resistant strain had acquired a new methylase gene that blocked the binding site for inhibition by aminoglycosides on a specifi c sequence on 16S ribosomal RNA. Mutations resulting in the loss of specifi c porins can occur in clinical isolates and determine increased resistance to beta-lactam antibiotics. If we could discover new targets for future antimicrobial drugs it may be possible to keep pace or even exceed the rate of antibiotic resistance gene development by microbial pathogens. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120399/ doi: 10.1007/3-540-29730-8_6 id: cord-342015-bz2vab6e author: Ouadfeul, Sid-Ali title: Multifractal Analysis of SARS-CoV-2 Coronavirus genomes using the wavelet transform date: 2020-08-16 words: 1386.0 sentences: 86.0 pages: flesch: 58.0 cache: ./cache/cord-342015-bz2vab6e.txt txt: ./txt/cord-342015-bz2vab6e.txt summary: In this paper, the 1D Wavelet Transform Modulus Maxima lines (WTMM) method is used to investigate the Long-Range Correlation (LRC) and to estimate the so-called Hurst exponent of 21 isolate RNA sequence downloaded from the NCBI database of patients infected by SARS-CoV-2, Coronavirus, the Knucleotidic, Purine, Pyramidine, Ameno, Keto and GC DNA coding are used. Arneodo et al (1996) published a paper deals with the study of the Long-Range Correlation (LRC) character of DNA sequences using the 1D continuous wavelet transform method. Audit et al (2004) published a paper deals with wavelet Analysis of DNA bending profiles reveals structural constraints on the evolution of genomic sequences, Voss (1996) published a paper deals with the evolution of Long-Range fractal correlations and 1/f noise in DNA base sequences. In this paper the 1D Wavelet Transform Modulus Maxima Lines (WTMM) method is used to demonstrate the monofractal behavior of SARS-CoV-2 RNA sequences downloaded from the NCBI database and to estimate the so-called Hurst exponent, the goal is to investigate the LRC character in these sequences. abstract: In this paper, the 1D Wavelet Transform Modulus Maxima lines (WTMM) method is used to investigate the Long-Range Correlation (LRC) and to estimate the so-called Hurst exponent of 21 isolate RNA sequence downloaded from the NCBI database of patients infected by SARS-CoV-2, Coronavirus, the Knucleotidic, Purine, Pyramidine, Ameno, Keto and GC DNA coding are used. Obtained results show the LRC character in the most sequences; except some sequences where the anti-correlated or the Classical Brownian motion character is observed. Obtained results demonstrate show that the SARS-Cov2 coronavirus undergoes mutation from a country to another or in the same country. url: https://doi.org/10.1101/2020.08.15.252411 doi: 10.1101/2020.08.15.252411 id: cord-029462-jm5qwxhz author: Ouidir, Marion title: Concentrations of persistent organic pollutants in maternal plasma and epigenome-wide placental DNA methylation date: 2020-07-13 words: 6383.0 sentences: 353.0 pages: flesch: 45.0 cache: ./cache/cord-029462-jm5qwxhz.txt txt: ./txt/cord-029462-jm5qwxhz.txt summary: We performed an epigenome-wide association study (EWAS) to identify placental DNA methylation associated with maternal plasma concentration of POPs in early gestation (10 weeks 0 days to 13 weeks 6 days) among 260 pregnant women participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development''s (NICHD) Fetal Growth Studies-Singletons cohort (which comprised 2802 pregnant women from 12 clinic sites within the USA). In total, maternal early pregnancy plasma concentrations of POPs were significantly associated with placental DNA methylation at 214 CpG sites annotated to 205 genes (BACON-corrected false discovery rate (FDR) p values < 0.05, nominal p values ranging from 2.61 × 10 −21 to 2.11 10 −7 , Supplementary Table S3 ). The correlations between DNA methylation at the POPs-associated CpG sites and neonatal anthropometry suggest that placental epigenetic mechanisms may underlie the influence of specific maternal plasma POP concentrations on fetal growth. abstract: BACKGROUND: Prenatal maternal plasma persistent organic pollutant (POP) concentrations have been associated with neonatal outcomes. However, the underlying mechanisms remain unknown. Placental epigenetic mechanisms may be involved, but no prior epigenome-wide studies have investigated the impact of maternal POPs on placental DNA methylation. We studied the association between maternal plasma POP concentration in early pregnancy and epigenome-wide placental DNA methylation among 260 pregnant women from the NICHD Fetal Growth Studies. RESULTS: Our analysis focused on POPs with more than 80% plasma concentrations above the limit of quantification, including 3 organochlorine pesticides (hexachlorobenzene, trans-nonachlor, p,p’-dichlorodiphenyldichloroethylene), 1 polybrominated diphenyl ether (PBDE 47), 3 polychlorinated biphenyls (138/158, 153, 180), and 6 poly- and perfluorinated alkyl substances (PFASs) (perfluorodecanoic acid, perfluorohexanesulfonic acid, perfluorononanoic acid, perfluorooctanesulfonic acid, perfluoroundecanoic acid (PFUnDA)). Using 5% false discovery rate, POPs were associated with a total of 214 differentially methylated CpG sites (nominal p values ranging from 2.61 × 10(−21) to 2.11 × 10(−7)). Out of the 214 CpG sites, 24 (11%) were significantly correlated with placental expression of 21 genes. Notably, higher PFUnDA was associated with increased methylation at 3 CpG sites (cg13996963, cg12089439, cg18145877) annotated to TUSC3, and increased methylation at those 3 CpG sites was correlated with decreased expression of TUSC3 in the placenta. Increased methylation at cg18145877 (TUSC3) and decreased expression of TUSC3 were correlated with shorter birth length. Out of the 214 CpG sites, methylation at 44 CpG sites was correlated (p value < 0.10) with at least one neonatal anthropometry measure (i.e., birth weight, birth length, and head circumference). Seven CpG sites mediated (p value < 0.05) the association between PBDE 47 and neonatal anthropometry measures. Genes annotating the top differentially methylated CpG sites were enriched in pathways related to differentiation of embryonic cells (PBDE 47) and in pathways related to brain size and brain morphology (PFASs). CONCLUSIONS: DNA methylation changes in the placenta were significantly associated with maternal plasma POPs concentration. The findings suggest that placental DNA methylation and gene expression mechanism may be involved in the prenatal toxicity of POPs and their association with neonatal anthropometry measures. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371466/ doi: 10.1186/s13148-020-00894-6 id: cord-334082-fyxn0g3v author: O’Carroll, I.P. title: Viral Nucleic Acids date: 2015-08-20 words: 5495.0 sentences: 271.0 pages: flesch: 54.0 cache: ./cache/cord-334082-fyxn0g3v.txt txt: ./txt/cord-334082-fyxn0g3v.txt summary: This scheme in turn places two requirements on the nucleic acid: it must be replicated in the virus-producing cell, to provide the genetic material encased in the progeny virus particles; and it must encode the proteins needed for the production of the progeny particles, including at a minimum the structural proteins from which the particles will be assembled. The DNAs of ssDNA viruses are replicated by a mechanism similar to ''rolling circle'' replication, involving synthesis of dsDNA intermediates containing multiple tandem copies of the viral genome. These viruses are unique in that their genomic RNA is translated immediately upon infection; that is, the virus particle is simply a package that introduces an mRNA molecule into the cell. When the particle infects a new host cell, the RNA-dependent DNA polymerase or ''reverse transcriptase'' in the virus copies this RNA into dsDNA. abstract: Viral genomes exhibit extraordinary diversity with respect to nucleic acid type, size, complexity, and the information transfer pathways they follow. Thus, viral nucleic acids can be DNA or RNA, double-stranded or single-stranded, monopartite or multipartite, linear or circular, as short as 2 kb or up to 2500 kb long. The goal of a virus is to replicate itself. To do so, viruses have evolved various strategies to replicate their genomes and produce the structural and catalytic proteins needed for the formation of new viruses. This article is a brief introduction to viral genomes and viral replication. url: https://www.sciencedirect.com/science/article/pii/B9780123944474100616 doi: 10.1016/b978-0-12-394447-4.10061-6 id: cord-026025-xqj877en author: PETRAS, ROBERT E. title: Large Intestine (Colon) date: 2009-10-30 words: 48309.0 sentences: 3034.0 pages: flesch: 42.0 cache: ./cache/cord-026025-xqj877en.txt txt: ./txt/cord-026025-xqj877en.txt summary: 27, 28 These guidelines consider colonoscopic polypectomy definitive treatment for a patient with a malignant polyp if the following criteria are fulfilled: (1) the polyp is considered completely excised at endoscopy, (2) the specimen is properly processed by the pathology laboratory, (3) the cancer is not poorly differentiated, (4) no histologic evidence of vascular or lymphatic involvement exists, and (5) the resection margin is not involved by carcinoma. Pathologic features of colorectal cancer that suggest MSI/Lynch''s syndrome include right-sided location, synchronous or metachronous large bowel cancers, large and bulky polypoid tumors with circumscribed pushing margins, tumors showing prominent lymphoid infiltrate, and cancers of poor differentiation (medullary or undifferentiated carcinoma) or mucinous and signet ring cell histologic pattern (Figs. [352] [353] [354] [355] The trauma-type histologic features can be seen in the solitary rectal ulcer syndrome, localized colitis cystica profunda, inflammatory cloacogenic polyp, the mucosa adjacent to orifices of colonic diverticula, 356 and inflammatory cap polyposis 357 and are frequent findings adjacent to neoplasia and in the vicinity of the ileocecal valve. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271214/ doi: 10.1016/b978-1-4160-3966-2.00023-0 id: cord-345712-gmzue6lj author: Palazzo, Luca title: ADP‐ribosylation: new facets of an ancient modification date: 2017-04-26 words: 6641.0 sentences: 389.0 pages: flesch: 42.0 cache: ./cache/cord-345712-gmzue6lj.txt txt: ./txt/cord-345712-gmzue6lj.txt summary: Altogether, ADPribosylation is a widespread modification that controls a vast number of cellular processes, including DNA damage repair, transcription, cell-cycle progression, cell division, unfolded protein response, aging, nitrogen fixation, microbial pathogenicity, cell death and many others [7, 14, [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] . As a consequence, macrodomain-containing proteins are involved in a diverse set of cellular functions, such as chromatin remodelling and DNA-damage repair, oxidative stress response, metabolic processes and pathogenic mechanisms [3,5,10-13,30,37, 53, 54, [59] [60] [61] . Studies looking either at the genomic context of ADPribosylating systems or their evolution in bacteria suggest that ADP-ribosylation might be involved in the regulation of many crucial cellular processes including bacterial persistence, oxidative stress response and adaptation to the host environment in general [5, 9, 49, 154] . abstract: Rapid response to environmental changes is achieved by uni‐ and multicellular organisms through a series of molecular events, often involving modification of macromolecules, including proteins, nucleic acids and lipids. Amongst these, ADP‐ribosylation is of emerging interest because of its ability to modify different macromolecules in the cells, and its association with many key biological processes, such as DNA‐damage repair, DNA replication, transcription, cell division, signal transduction, stress and infection responses, microbial pathogenicity and aging. In this review, we provide an update on novel pathways and mechanisms regulated by ADP‐ribosylation in organisms coming from all kingdoms of life. url: https://doi.org/10.1111/febs.14078 doi: 10.1111/febs.14078 id: cord-332654-nav15g8k author: Paniri, Alireza title: Molecular effects and retinopathy induced by hydroxychloroquine during SARS-CoV-2 therapy: Role of CYP450 isoforms and epigenetic modulations date: 2020-08-04 words: 5712.0 sentences: 341.0 pages: flesch: 47.0 cache: ./cache/cord-332654-nav15g8k.txt txt: ./txt/cord-332654-nav15g8k.txt summary: The major focus of the present review is to discuss about the pharmacokinetic and pharmacodynamic properties of CQ and HCQ that may be influenced by epigenetic mechanisms, and consequently cause several side effects especially retinopathy during SARS-CoV-2 therapy. Furthermore, growing body of evidence demonstrated that several factors including CYP450 single nucleotide polymorphisms (SNPs), and epigenetic molecules such as non-coding RNAs (ncRNAs), DNA methylation and histone acetylation influenced the expression levels of CYP450, and consequently might influence HCQ metabolism. The major purpose of this review is to discuss the pharmacokinetic and pharmacodynamic characteristics of CQ and HCQ that may be influenced by epigenetic mechanisms including ncRNAs and CYP2D6 SNPs, and thereby cause several side effects such as cardiotoxicity, prolonged QT interval, gastrointestinal problems (like dyspepsia and abdominal cramps), central nervous system or skin disorders, and especially retinopathy. abstract: Antimalaria drugs such as chloroquine (CQ) and hydroxychloroquine (HCQ) have been administered to several inflammatory diseases including rheumatoid arthritis and systemic lupus erythematosus, and infectious diseases such as acquired immune deficiency syndrome and influenza. Recently, several patients infected with novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were given HCQ, and showed a discrepant response. HCQ inhibits SARS-CoV-2 cell entry, and inflammatory cascade by interfering with lysosomal and endosomal activities, and autophagy, impeding virus-membrane fusion, and inhibiting cytokine production resulted from inflammatory pathways activation. Despite ongoing administration of HCQ in a wide spectrum of disorders, there are some reports about several side effects, especially retinopathy in some patients treated with HCQ. Cytochrome P450 (CYP450) and its isoforms are the main metabolizers of HCQ and CQ. Pharmacokinetic properties of CYP enzymes are influenced by CYP polymorphism, non-coding RNAs, and epigenetic mechanisms such as DNA methylation, and histone acetylation. Accumulating evidence about side effects of HCQ in some patients raise the possibility that different response of patients to HCQ might be due to difference in their genome. Therefore, CYP450 genotyping especially for CYP2D6 might be helpful to refine HCQ dosage. Also, regular control of retina should be considered for patients under HCQ treatment. The major focus of the present review is to discuss about the pharmacokinetic and pharmacodynamic properties of CQ and HCQ that may be influenced by epigenetic mechanisms, and consequently cause several side effects especially retinopathy during SARS-CoV-2 therapy. url: https://api.elsevier.com/content/article/pii/S001429992030546X doi: 10.1016/j.ejphar.2020.173454 id: cord-352891-ljmkqdzx author: Parang, Keykavous title: Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs against Human Coronavirus 229E (HCoV-229E) date: 2020-05-17 words: 3165.0 sentences: 182.0 pages: flesch: 52.0 cache: ./cache/cord-352891-ljmkqdzx.txt txt: ./txt/cord-352891-ljmkqdzx.txt summary: title: Comparative Antiviral Activity of Remdesivir and Anti-HIV Nucleoside Analogs against Human Coronavirus 229E (HCoV-229E) Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5′-O-fatty acylated anti-HIV nucleoside conjugates. Therefore, HCoV-229E may be a good initial model for the evaluation of antiviral compounds that could have potential applications against other coronaviruses, such as SARS-COV-2, the coronavirus that causes COVID-19. We have previously shown that the conjugation of certain fatty acids to the anti-HIV NRTIs, such as FLT, 3TC and FTC, enhanced activity against X4, R5, cell-associated, and/or multi-drug resistant virus when compared with their parent nucleosides [24] [25] [26] [27] . A series of anti-HIV nucleosides and their fatty acyl derivatives were compared with remdesivir for antiviral activity against HCoV-229E in MRC-5 cells. abstract: Remdesivir is a nucleotide prodrug that is currently undergoing extensive clinical trials for the treatment of COVID-19. The prodrug is metabolized to its active triphosphate form and interferes with the action of RNA-dependent RNA polymerase of SARS-COV-2. Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5′-O-fatty acylated anti-HIV nucleoside conjugates. The anti-HIV nucleosides interfere with HIV RNA-dependent DNA polymerase and/or act as chain terminators. Normal human fibroblast lung cells (MRC-5) were used to determine the cytotoxicity of the compounds. The study revealed that remdesivir exhibited an EC(50) value of 0.07 µM against HCoV-229E with TC(50) of > 2.00 µM against MRC-5 cells. Parent NRTIs were found to be inactive against (HCoV-229E) at tested concentrations. Among all the NRTIs and 5′-O-fatty acyl conjugates of NRTIs, 5′-O-tetradecanoyl ester conjugate of FTC showed modest activity with EC(50) and TC(50) values of 72.8 µM and 87.5 µM, respectively. These data can be used for the design of potential compounds against other coronaviruses. url: https://www.ncbi.nlm.nih.gov/pubmed/32429580/ doi: 10.3390/molecules25102343 id: cord-320005-i30t7cvr author: Pardo, A. title: The Human Genome and Advances in Medicine: Limits and Future Prospects date: 2004-03-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.sciencedirect.com/science/article/pii/S1579212906700787 doi: 10.1016/s1579-2129(06)70078-7 id: cord-324094-23kzr8rq author: Parida, M. M. title: Rapid and real-time detection technologies for emerging viruses of biomedical importance date: 2008-11-01 words: 5709.0 sentences: 243.0 pages: flesch: 46.0 cache: ./cache/cord-324094-23kzr8rq.txt txt: ./txt/cord-324094-23kzr8rq.txt summary: We have developed two real-time assays ie., SYBR green I based real time reverse transcription polymerase chain reaction (RT-PCR) and RT-loop-mediated isothermal amplification (LAMP) assay for rapid detection as well as typing of some of the emerging viruses of biomedical importance viz. We have developed two real-time assays ie., SYBR green I based real time reverse transcription polymerase chain reaction (RT-PCR) and RT-loop-mediated isothermal amplifi cation (LAMP) assay for rapid detection as well as typing of some of the emerging viruses of biomedical importance viz. A one-step single tube real-time accelerated reverse transcription loop mediated isothermal amplifi cation (RT-LAMP) assays for rapid detection of some of the recently emerged human viral pathogens viz. Rapid detection and differentiation of dengue virus serotypes by a real-time reverse transcription-loop-mediated isothermal amplifi cation assay Development and evaluation of reverse transcription Loop mediated isothermal amplifi cation assay for rapid and Real-time detection of Japanese encephalitis virus abstract: The development of technologies with rapid and sensitive detection capabilities and increased throughput have become crucial for responding to greater number threats posed by emerging and re-emerging viruses in the recent past. The conventional identification methods require time-consuming culturing, and/ or detection of antibodies, which are not very sensitive and specific. The recent advances in molecular biology techniques in the field of genomics and proteomics greatly facilitate the rapid identification with more accuracy. We have developed two real-time assays ie., SYBR green I based real time reverse transcription polymerase chain reaction (RT-PCR) and RT-loop-mediated isothermal amplification (LAMP) assay for rapid detection as well as typing of some of the emerging viruses of biomedical importance viz. dengue, Japanese encephalitis, chikungunya, west Nile, severe acute respiratory syndrome virus (SARS) etc. Both these techniques are capable of detection and differentiation as well as quantifying viral load with higher sensitivity, rapidity, specificity. One of the most important advantages of LAMP is its field applicability, without requirement of any sophisticated equipments. Both these assays have been extensively evaluated and validated with clinical samples of recent epidemics from different parts of India. The establishment of these real time molecular assays will certainly facilitate the rapid detection of viruses with high degree of precision and accuracy in future. url: https://www.ncbi.nlm.nih.gov/pubmed/19208986/ doi: 10.1007/s12038-008-0079-7 id: cord-001254-y2knt8g0 author: Parkhomenko, Taisiya A. title: Comparison of DNA-Hydrolyzing Antibodies from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis date: 2014-04-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: It was found that high-affinity anti-DNA antibodies were one of the major components of the intrathecal IgG response in multiple sclerosis (MS) patients [Williamson et al., PNAS, 2001]. Recently we have shown that IgGs from the sera of MS patients are active in the hydrolysis of DNA. Here we have shown, for the first time, that average concentration of total proteins (132-fold), total IgGs (194-fold) and anti-DNA antibodies (200-fold) in the sera is significantly higher than that in the cerebrospinal fluid (CSF) of fifteen MS patients. The relative activities of total protein from sera and CSFs varied remarkably from patient to patient. It was surprising that the specific DNase activity of the total protein of CSF reparations were 198-fold higher than the serum ones. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We present first evidence showing that IgGs from CSF not only bind but efficiently hydrolyze DNA and that average specific DNase activity of homogeneous antibodies from CSF is unpredictably ∼49-fold higher than that from the sera of the same MS patients. Some possible reasons of these findings are discussed. We suggest that DNase IgGs of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and MS pathogenesis development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988009/ doi: 10.1371/journal.pone.0093001 id: cord-010680-lc1onm53 author: Patel, Ami title: In Vivo Delivery of Nucleic Acid-Encoded Monoclonal Antibodies date: 2020-03-10 words: 13044.0 sentences: 659.0 pages: flesch: 41.0 cache: ./cache/cord-010680-lc1onm53.txt txt: ./txt/cord-010680-lc1onm53.txt summary: Some of these hurdles may be overcome through transient in vivo gene delivery platforms, such as non-viral synthetic plasmid DNA and messenger RNA vectors that are engineered to encode optimized mAb genes. In this review, we focus on nucleic acid delivery of antibody employing synthetic plasmid DNA vector platforms, and RNA delivery, these being important approaches that are advancing simple, rapid, in vivo expression and having an impact in animal models of infectious diseases and cancer, among others. The original studies surrounding in vivo antibody gene delivery focused primarily on gene delivery using recombinant viral vectors such as AAV and adenovirus (Ad), which were advanced clinically, building on work in the traditional gene therapy-based field. Additional studies to help evaluate fully human pDNA-mAbs in mouse models would be highly informative for both non-viral and viral delivery and provide an important path forward for preclinical evaluation of in vivo-delivered antibodies [109] . abstract: Antibody immunotherapy is revolutionizing modern medicine. The field has advanced dramatically over the past 40 years, driven in part by major advances in isolation and manufacturing technologies that have brought these important biologics to the forefront of modern medicine. However, the global uptake of monoclonal antibody (mAb) biologics is impeded by biophysical and biochemical liabilities, production limitations, the need for cold-chain storage and transport, as well as high costs of manufacturing and distribution. Some of these hurdles may be overcome through transient in vivo gene delivery platforms, such as non-viral synthetic plasmid DNA and messenger RNA vectors that are engineered to encode optimized mAb genes. These approaches turn the body into a biological factory for antibody production, eliminating many of the steps involved in bioprocesses and providing several other significant advantages, and differ from traditional gene therapy (permanent delivery) approaches. In this review, we focus on nucleic acid delivery of antibody employing synthetic plasmid DNA vector platforms, and RNA delivery, these being important approaches that are advancing simple, rapid, in vivo expression and having an impact in animal models of infectious diseases and cancer, among others. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211204/ doi: 10.1007/s40259-020-00412-3 id: cord-321640-kx3t81yh author: Patrone, Paul N. title: Affine analysis for quantitative PCR measurements date: 2020-09-20 words: 7625.0 sentences: 458.0 pages: flesch: 57.0 cache: ./cache/cord-321640-kx3t81yh.txt txt: ./txt/cord-321640-kx3t81yh.txt summary: Application to reverse-transcriptase qPCR measurements of a SARS-CoV-2 RNA construct points to the usefulness of this approach for improving confidence and reducing limits of detection in diagnostic testing of emerging diseases. Using this, we develop a data analysis approach employing constrained optimization to determine if an amplification curve exhibits characteristics that are representative of a true signal. We illustrate the validity of this approach on experimental data and demonstrate how it can improve interpretation of late-cycle amplification curves corresponding to low initial DNA concentrations [4] . Our data analysis leverages a universal property of qPCR, which states that under very general conditions, all amplification curves are the same up to an affine transformation, i.e. a multiplicative factor and horizontal shift. To demonstrate that optimization of the transformation parameters does not generate false positives, we performed the analysis described above on 17 non-template control (NTC) datasets that were baseline-corrected according to the same procedure used on the amplification curves. abstract: Motivated by the current COVID-19 health crisis, we consider data analysis for quantitative polymerase chain-reaction (qPCR) measurements. We derive a theoretical result specifying the conditions under which all qPCR amplification curves (including their plateau phases) are identical up to an affine transformation, i.e. a multiplicative factor and horizontal shift. We use this result to develop a data analysis procedure for determining when an amplification curve exhibits characteristics of a true signal. The main idea behind this approach is to invoke a criterion based on constrained optimization that assesses when a measurement signal can be mapped to a master reference curve. We demonstrate that this approach: (i) can decrease the fluorescence detection threshold by up to a decade; and (ii) simultaneously improve confidence in interpretations of late-cycle amplification curves. Moreover, we demonstrate that the master curve is transferable reference data that can harmonize analyses between different labs and across several years. Application to reverse-transcriptase qPCR measurements of a SARS-CoV-2 RNA construct points to the usefulness of this approach for improving confidence and reducing limits of detection in diagnostic testing of emerging diseases. [Figure: see text] url: https://doi.org/10.1007/s00216-020-02930-z doi: 10.1007/s00216-020-02930-z id: cord-027309-8siz9rb8 author: Paul, Debjani title: Developing a Point-of-Care Molecular Test to Detect SARS-CoV-2 date: 2020-06-19 words: 2269.0 sentences: 136.0 pages: flesch: 51.0 cache: ./cache/cord-027309-8siz9rb8.txt txt: ./txt/cord-027309-8siz9rb8.txt summary: The recent pandemic of COVID-19 caused by the novel coronavirus (SARS-CoV-2) has drawn attention to the need for developing rapid and accurate diagnostic tests. The widespread use of these immunodiagnostic tests in clinical settings, in spite of their shortcomings, emphasizes the need for developing rapid and point-of-care (POC) tests that are based on molecular diagnostics (i.e., tests that detect the viral RNA directly in a manner similar to RT-PCR). We believe we can build on our past experience with isothermal DNA amplification techniques and paperfluidic devices to develop an isothermal amplification-based molecular diagnostic test for COVID-19 that can be deployed more easily. The ID NOW COVID-19 assay from Abbott, which recently got an emergency use authorization (EUA) from the US government for clinical use, detects SARS-CoV-2 RNA using an isothermal amplification test and can enable a clinical decision in as early as 13 min (ID NOWTM Covid-19 2020). abstract: There is a need for widespread testing in India to stop the spread of the novel coronavirus in the population. While RT-PCR is the recommended diagnostic technique, its use is limited to well-equipped laboratories due to the need for specialized instrumentation, reagents and trained personnel. Immunodiagnostic tests are not yet recommended by the WHO for diagnosing active infections. There is a strong need for developing point-of-care molecular tests. Based on our past experience with paperfluidic devices for diagnosing bacterial infections by molecular tests, we propose the development of a diagnostic test for COVID-19. As a platform technology, it could be adapted to other viral outbreaks in future. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303936/ doi: 10.1007/s41403-020-00127-5 id: cord-007506-swx3kqob author: Paul, Prem S. title: Applications of nucleic acid probes in veterinary infectious diseases date: 2002-11-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Nucleic acid probe technology is increasingly being used in basic research in veterinary microbiology and in diagnosis of infectious diseases of veterinary importance. This review presents an overview of nucleic acid probe methodology and its applications in veterinary infectious diseases. The major applications of nucleic acid probes include detection of pathogens in clinical samples, especially those organisms which are fastidious and difficult to cultivate, differentiation of virulent from a virulent organisms and vaccine strains from wild type isolates, typing of microorganisms mapping genes, screening libraries of cloned DNA for specific genes, detection of latently infected or carrier animals, study of mechanisms of pathogenesis, epidemiological studies and food safety. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7117517/ doi: 10.1016/0378-1135(90)90187-z id: cord-352619-s2x53grh author: Payne, Natalie title: Novel Circoviruses Detected in Feces of Sonoran Felids date: 2020-09-15 words: 3263.0 sentences: 177.0 pages: flesch: 45.0 cache: ./cache/cord-352619-s2x53grh.txt txt: ./txt/cord-352619-s2x53grh.txt summary: Genomes from several families of circular Rep-encoding single-stranded DNA viruses (CRESS-DNA viruses) are part of the phylum Cressdnaviricota [22] and have been identified in fecal samples of other mammals, including domestic cats [23, 24] , bobcats, African lions [25] , capybaras [26] , and Tasmanian devils [27] . Here we used a metagenomic approach to identify novel circoviruses in the feces of two species of Sonoran felids, the puma and bobcat; although not endangered, knowledge of viral threats facing these species could help prevent future population decline, as well as indicate potential threats to the endangered ocelot and jaguar. Based on the species-demarcation threshold for circoviruses which is 80% genome-wide identity [28] , both of these belong to a new species which we refer to as Sonfela (derived from Sonoran felid associated) circovirus 1. As the viral genomes were derived from scat samples, the circoviruses could have infected the bobcat prey species or the felids themselves or be environmentally derived. abstract: Sonoran felids are threatened by drought and habitat fragmentation. Vector range expansion and anthropogenic factors such as habitat encroachment and climate change are altering viral evolutionary dynamics and exposure. However, little is known about the diversity of viruses present in these populations. Small felid populations with lower genetic diversity are likely to be most threatened with extinction by emerging diseases, as with other selective pressures, due to having less adaptive potential. We used a metagenomic approach to identify novel circoviruses, which may have a negative impact on the population viability, from confirmed bobcat (Lynx rufus) and puma (Puma concolor) scats collected in Sonora, Mexico. Given some circoviruses are known to cause disease in their hosts, such as porcine and avian circoviruses, we took a non-invasive approach using scat to identify circoviruses in free-roaming bobcats and puma. Three circovirus genomes were determined, and, based on the current species demarcation, they represent two novel species. Phylogenetic analyses reveal that one circovirus species is more closely related to rodent associated circoviruses and the other to bat associated circoviruses, sharing highest genome-wide pairwise identity of approximately 70% and 63%, respectively. At this time, it is unknown whether these scat-derived circoviruses infect felids, their prey, or another organism that might have had contact with the scat in the environment. Further studies should be conducted to elucidate the host of these viruses and assess health impacts in felids. url: https://doi.org/10.3390/v12091027 doi: 10.3390/v12091027 id: cord-294712-kvvxmvqo author: Pelosse, Martin title: MultiBac: from protein complex structures to synthetic viral nanosystems date: 2017-10-30 words: 5379.0 sentences: 272.0 pages: flesch: 38.0 cache: ./cache/cord-294712-kvvxmvqo.txt txt: ./txt/cord-294712-kvvxmvqo.txt summary: The MultiBac baculovirus/insect cell expression vector system was conceived as a user-friendly, modular tool-kit for producing multiprotein complexes for structural biology applications. We then turned our attention to eukaryotic methods, specifically an expression vector system relying on a recombinant baculovirus, to infect insect cell cultures for producing the complexes in which we had interest. This particular feature, and the-at least conceptually-relative ease of manipulating baculovirus in the laboratory by non-expert users, was exciting and led us on to the development of MultiBac: a baculovirus/insect cell system specifically engineered for expressing functional multiprotein complexes in the quality and quantity required for high-resolution structural and mechanistic studies [7] [8] [9] [10] [11] . The introduced genome alterations resulted in a virus that exhibited delayed lysis of the insect cells, allowing the production of recombinant protein complexes at very high levels while the cells seemingly remained intact [11] . The MultiBac baculovirus/insect cell expression vector system for producing complex protein biologics abstract: The MultiBac baculovirus/insect cell expression vector system was conceived as a user-friendly, modular tool-kit for producing multiprotein complexes for structural biology applications. MultiBac has allowed the structure and function of many molecular machines to be elucidated, including previously inaccessible high-value drug targets. More recently, MultiBac developments have shifted to customized baculoviral genomes that are tailored for a range of applications, including synthesizing artificial proteins by genetic code expansion. We review some of these developments, including the ongoing rewiring of the MultiBac system for mammalian applications, notably CRISPR/Cas9-mediated gene editing. url: https://doi.org/10.1186/s12915-017-0447-6 doi: 10.1186/s12915-017-0447-6 id: cord-015946-biu5zxd1 author: Peng, Daizhi title: Research Advances in Biomarker for Sepsis date: 2016-11-16 words: 5100.0 sentences: 242.0 pages: flesch: 40.0 cache: ./cache/cord-015946-biu5zxd1.txt txt: ./txt/cord-015946-biu5zxd1.txt summary: Most commonly proposed sepsis and infection biomarkers including C-reactive protein (CRP), procalcitonin (PCT) [5, 6] , cytokines (TNF-α, IL-1, IL-6, IL-10, osteopontin) [7, 8] , chemokines [macrophage migration inhibitory factor (MIF), high-mobility-group box 1 (HMGB1)] [9, 10] , soluble receptor [soluble triggering receptor expressed on myeloid cells 1 (sTREM-1), soluble urokinase-type plasminogen activator receptor (suPAR)] [11, 12] etc. When it comes to sepsis, by using genome-wide miRNA profiling with microarray in peripheral blood leukocytes and quantitative RT-PCR, Vasilescu [71] found that miR-150 levels were significantly reduced in both leukocytes and plasma of sepsis patients and had a negative correlation with the level of disease severity measured by the Sequential Organ Failure Assessment (SOFA) score, which made it a biomarker of early sepsis. As they were significantly correlated with disease severity, classical markers of inflammation and bacterial infection, as well as organ failure, high miR-133a levels were considered as independent biomarkers for unfavorable prognosis of critically ill patients. abstract: Sepsis is one of the most common causes of death in severely injured patients worldwide. The early detection of sepsis still has to be solved in clinical practice. The delayed diagnosis often contributes to inappropriate antimicrobial treatment and subsequent high mortality. Sepsis biomarkers are produced during the host response to infection. Traditional biomarkers are polypeptides and/or proteins derived from this response. Omics-based biomarkers are screening out from all kinds of molecules of host response while high-throughout omics technologies are emerging. This review describes traditional and potential omics-based sepsis biomarkers from currently available literatures. The combination of these biomarkers would refine the identification of sepsis for further clinical and experimental sepsis studies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120075/ doi: 10.1007/978-981-10-2425-2_15 id: cord-030369-4dn02a35 author: Peng, Liang title: Clinical Manifestations and Laboratory Tests of AECHB and Severe Hepatitis (Liver Failure) date: 2019-05-21 words: 35858.0 sentences: 1603.0 pages: flesch: 38.0 cache: ./cache/cord-030369-4dn02a35.txt txt: ./txt/cord-030369-4dn02a35.txt summary: Once pulmonary infection is present, the disease condition will likely deteriorate, directly causing death; (3) a majority of infections are nosocomial infection, and pathogens are usually resistant to common antibiotics, making therapy challenging; (4) the pathogens causing infection are diverse but mainly Gram-negative bacteria, although the incidence of Gram-positive and fungal infections is increasing; (5) infection is closely related to the prognosis for liver failure patients. Although their clinical manifestation differ significantly, the "coexistence of acute and chronic failures" is shared by failures of all those organs; (2) CLF classification has been generally recognized at home and abroad, and the necessity of classification are further proved by the difference between CLF and the other three types; (3) CLF cases are relatively large in proportion (nearly 30%), which is still increasing (since the proportion of ALF/SALF are lowering); (4) Complications of CLF are common and are found in various forms, with bad prognosis; (5) In CLF patients with correlation to HBV, virus replication are commonly found, which is closely related to decompensation. abstract: This chapter describes the clinical symptoms and signs of AECHB and HBV ACLF, classification, grading of HBV ACLF and their features, diagnostic principles and standards in liver pathology, biochemistry, and virology of HBV ACLF. 1. Liver failure is defined as serious damage to the liver cause by a variety of etiologies, leading to liver function disorder or even decompensation, and clinical syndromes with coagulopathy, jaundice, hepatic encephalopathy, and ascites. 2. Severe hepatitis B can be indicated pathologically by apparent hepatocellular necrosis, including extensive multifocal, confluent, bridging, sub-massive or massive necrosis. 3. Laboratory tests during the course of severe exacerbation of chronic hepatitis B can reflect pathological changes and liver function in a timely manner, providing objective and informative reference data for evaluation of disease severity and treatment efficacy. Among the most important laboratory tests are those for prothrombin activity, international normalized ratio, and increases in total bilirubin concentration. 4. Severe hepatitis B is associated with interactions between the virus and host factors. Detection of HBV DNA, HBV genotype, quasispecies and HBV mutation can provide important theoretical bases for the prevention, control or mitigation of the progress of severe hepatitis B. 5. Noninvasive imaging modalities can be used to visualize the entire liver and parts of it. Measuring liver volume to evaluate liver size and liver reserve capacity is regarded as important in diagnosis, surgical approach and prognostic evaluation of patients with severe exacerbation of chronic hepatitis B and liver failure. 6. Model for End-Stage Liver Disease (MELD) is the first quantitative method developed to assess whether a patient with liver failure requires a liver transplant. The predictive value of the MELD model has been improved by the MELD-Na, iMELD, and MESO models. Several other valuable prognostic models have been developed. For example, for patients with HBV-ACLF, the established TPPM scoring system was found to be more predictive than MELD score. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418529/ doi: 10.1007/978-94-024-1603-9_1 id: cord-018159-ycg6waay author: Peng, Xiaolei title: Plasmofluidics for Biosensing and Medical Diagnostics date: 2018-01-23 words: 9124.0 sentences: 499.0 pages: flesch: 40.0 cache: ./cache/cord-018159-ycg6waay.txt txt: ./txt/cord-018159-ycg6waay.txt summary: With their capability of controlling light at the nanoscale beyond the diffraction limit, surface plasmons such as surface plasmon polaritons (SPPs) and localized surface plasmon resonances (LSPRs) [8] are effective at optically manipulating, sensing, and analyzing biological cells and molecules [9] [10] [11] . Using simple optics to create the trapping force, plasmonic tweezers can be readily incorporated into microfluidic systems to design novel plasmofluidic chips with functionalities such as single-particle trapping [57, 62] , parallel trapping [58] , co-trapping [63] , and kinetic detection of biological objects [61, 64] . Plasmonic nanotechnologies such as plasmonic arrays [87, 88, [101] [102] [103] and SPRI [104, 105] and innovative microfluidic techniques such as integrated concentration gradient generator [104] and multi-well fluidic measurement [106] have been intensely pursued to detect and quantify cancer biomarkers with enhanced sensitivity, robustness, integrity, high throughput, and multiplexity. achieved label-free imaging, detection, and mass/size measurement of single viral particles with high-resolution surface plasmon resonance spectroscopy [121] . abstract: Plasmofluidics, an extension of optofluidics into the nanoscale regime, merges plasmonics and micro-/nanofluidics for highly integrated and multifunctional lab on a chip. In this chapter, we focus on the applications of plasmofluidics in the versatile manipulation and sensing of biological cell, organelles, molecules, and nanoparticles, which underpin advanced biomedical diagnostics. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122966/ doi: 10.1007/978-3-662-56333-5_5 id: cord-332379-340wczmq author: Pennington, Matthew R. title: Disparate Entry of Adenoviruses Dictates Differential Innate Immune Responses on the Ocular Surface date: 2019-09-13 words: 11584.0 sentences: 604.0 pages: flesch: 36.0 cache: ./cache/cord-332379-340wczmq.txt txt: ./txt/cord-332379-340wczmq.txt summary: These findings suggest that adenoviruses may stimulate specific pattern recognition receptors in an entry/trafficking-dependent manner, leading to distinct immune responses dependent on the virus/cell type combination. Additional work is needed to understand the specific connections between adenoviral entry and the stimulation of innate immune responses by the various cell types present on the ocular surface. Innate immune responses to adenoviruses rely on the detection of pathogen-associated molecular patterns (PAMPs): distinct ligands present on the external surfaces, and nucleic acids of pathogens (but absent in the host) that feature molecular signatures able to be recognized by pattern recognition receptors (PRR) on or in infected host cells [43] [44] [45] [46] . Innate immune responses to adenoviruses rely on the detection of pathogen-associated molecular patterns (PAMPs): distinct ligands present on the external surfaces, and nucleic acids of pathogens (but absent in the host) that feature molecular signatures able to be recognized by pattern recognition receptors (PRR) on or in infected host cells [43] [44] [45] [46] . abstract: Human adenovirus infection of the ocular surface is associated with severe keratoconjunctivitis and the formation of subepithelial corneal infiltrates, which may persist and impair vision for months to years following infection. Long term pathology persists well beyond the resolution of viral replication, indicating that the prolonged immune response is not virus-mediated. However, it is not clear how these responses are sustained or even initiated following infection. This review discusses recent work from our laboratory and others which demonstrates different entry pathways specific to both adenovirus and cell type. These findings suggest that adenoviruses may stimulate specific pattern recognition receptors in an entry/trafficking-dependent manner, leading to distinct immune responses dependent on the virus/cell type combination. Additional work is needed to understand the specific connections between adenoviral entry and the stimulation of innate immune responses by the various cell types present on the ocular surface. url: https://doi.org/10.3390/microorganisms7090351 doi: 10.3390/microorganisms7090351 id: cord-256201-vjzfzshh author: Pereira-Gómez, Marianoel title: Effect of mismatch repair on the mutation rate of bacteriophage ϕX174 date: 2015-09-10 words: 6108.0 sentences: 284.0 pages: flesch: 54.0 cache: ./cache/cord-256201-vjzfzshh.txt txt: ./txt/cord-256201-vjzfzshh.txt summary: Finally, the mutation rate reduction afforded by GATC sites is fully reverted under stress conditions, which up-regulate repair pathways and expression of error-prone host polymerases such as heat and treatment with the base analog 5-fluorouracil, suggesting that access to repair renders the phage sensitive to stress-induced mutagenesis. Finally, we found that the mutation rate reduction afforded by the twenty GATC motifs was fully reverted at 42 C and in the presence of the base analog 5-fluorouracil (5-FU), two stress factors that promote overexpression of repair-associated error prone polymerases (Layton and Foster 2005; Malkova and Haber 2012) , thus suggesting that addition of GATC motifs renders the phage sensitive to stress-induced mutagenesis. We have shown that introduction of GATC sites in the /X174 genome can reduce the spontaneous mutation rate of the phage by up to fiftyfold, indicating that phage DNA can undergo MMR if the required sequence motifs are present. abstract: Viral mutation rates vary widely in nature, yet the mechanistic and evolutionary determinants of this variability remain unclear. Small DNA viruses mutate orders of magnitude faster than their hosts despite using host-encoded polymerases for replication, which suggests these viruses may avoid post-replicative repair. Supporting this, the genome of bacteriophage ϕX174 is completely devoid of GATC sequence motifs, which are required for methyl-directed mismatch repair in Escherichia coli. Here, we show that restoration of the randomly expected number of GATC sites leads to an eightfold reduction in the rate of spontaneous mutation of the phage, without severely impairing its replicative capacity over the short term. However, the efficacy of mismatch repair in the presence of GATC sites is limited by inefficient methylation of the viral DNA. Therefore, both GATC avoidance and DNA under-methylation elevate the mutation rate of the phage relative to that of the host. We also found that the effects of GATC sites on the phage mutation rate vary extensively depending on their specific location within the phage genome. Finally, the mutation rate reduction afforded by GATC sites is fully reverted under stress conditions, which up-regulate repair pathways and expression of error-prone host polymerases such as heat and treatment with the base analog 5-fluorouracil, suggesting that access to repair renders the phage sensitive to stress-induced mutagenesis. url: https://www.ncbi.nlm.nih.gov/pubmed/27774282/ doi: 10.1093/ve/vev010 id: cord-305973-i3raopi6 author: Perley, Casey C. title: Anti-HFRS Human IgG Produced in Transchromosomic Bovines Has Potent Hantavirus Neutralizing Activity and Is Protective in Animal Models date: 2020-05-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We explored an emerging technology to produce anti-Hantaan virus (HTNV) and anti-Puumala virus (PUUV) neutralizing antibodies for use as pre- or post-exposure prophylactics. The technology involves hyperimmunization of transchomosomic bovines (TcB) engineered to express human polyclonal IgG antibodies with HTNV and PUUV DNA vaccines encoding G(n)G(c) glycoproteins. For the anti-HTNV product, TcB was hyperimmunized with HTNV DNA plus adjuvant or HTNV DNA formulated using lipid nanoparticles (LNP). The LNP-formulated vaccine yielded fivefold higher neutralizing antibody titers using 10-fold less DNA. Human IgG purified from the LNP-formulated animal (SAB-159), had anti-HTNV neutralizing antibody titers >100,000. SAB-159 was capable of neutralizing pseudovirions with monoclonal antibody escape mutations in G(n) and G(c) demonstrating neutralization escape resistance. SAB-159 protected hamsters from HTNV infection when administered pre- or post-exposure, and limited HTNV infection in a marmoset model. An LNP-formulated PUUV DNA vaccine generated purified anti-PUUV IgG, SAB-159P, with a neutralizing antibody titer >600,000. As little as 0.33 mg/kg of SAB-159P protected hamsters against PUUV infection for pre-exposure and 10 mg/kg SAB-159P protected PUUV-infected hamsters post-exposure. These data demonstrate that DNA vaccines combined with the TcB-based manufacturing platform can be used to rapidly produce potent, human, polyclonal, escape-resistant anti-HTNV, and anti-PUUV neutralizing antibodies that are protective in animal models. url: https://www.ncbi.nlm.nih.gov/pubmed/32508764/ doi: 10.3389/fmicb.2020.00832 id: cord-023830-w218ogsk author: Perlin, David title: Rapid Detection of Bioterrorism Pathogens date: 2008-09-10 words: 6048.0 sentences: 292.0 pages: flesch: 38.0 cache: ./cache/cord-023830-w218ogsk.txt txt: ./txt/cord-023830-w218ogsk.txt summary: The inadequacy of phenotypic-based diagnostic assays is illustrated graphically by the ''''gold standard'''' public health laboratory-testing algorithm that was in place for positive identification of Bacillus anthracis from environmental samples during the October 2001 anthrax outbreak (Fig. 16.1a) . Genomic differences between microbes offer an alternative to culturing for detection and identification of pathogens by providing species-specific DNA targets that can be accurately resolved by molecular methodology. Polymerase chain reaction (PCR)-based amplification of highly conserved ribosomal RNA (rRNA) genes, intergenic sequences, and specific toxin genes is currently the most reliable approach for identification of bacterial, fungal and many viral pathogenic agents. Most importantly, these genetic probing systems offer rapid turn around time (1-6 h) and are suitable for high throughput, automated multiplex operations critical for use in clinical diagnostic laboratories. Rapid diagnostic assays in the genomic biology era: detection and identification of infectious disease and biological weapon agents abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176176/ doi: 10.1007/978-1-59745-326-4_16 id: cord-102219-d3gkfo7s author: Perzel Mandell, Kira A. title: Characterizing the dynamic and functional DNA methylation landscape in the developing human cortex date: 2019-10-30 words: 5038.0 sentences: 231.0 pages: flesch: 47.0 cache: ./cache/cord-102219-d3gkfo7s.txt txt: ./txt/cord-102219-d3gkfo7s.txt summary: In the present report, we describe the use of whole genome bisulfite sequencing (WGBS) to capture an unbiased map of the DNAm landscape, and to characterize both CpG and CpH methylation during prenatal brain development. We performed whole genome bisulfite sequencing (WGBS) to better characterize the shifting DNAm landscape in the developing human dorsolateral prefrontal cortex (DLPFC) in 20 prenatal samples during the second trimester in utero (Table S1 ). We found that DNAm changes were abundant even during this relatively restricted period in prenatal development, with 36,546 CpG sites differentially methylated across the ages of 14-20 post-conception weeks (PCW, at FDR < 0.05, Table S3 ). The top biological processes associated with genes containing differentially methylated CpGs across age were related to axon development and guidance, and regulation of neuron projection ( Figure S4 , Table S8 ). abstract: DNA methylation (DNAm) is a key epigenetic regulator of gene expression across development. The developing prenatal brain is a highly dynamic tissue, but our understanding of key drivers of epigenetic variability across development is limited. We therefore assessed genomic methylation at over 39 million sites in the prenatal cortex using whole genome bisulfite sequencing and found loci and regions in which methylation levels are dynamic across development. We saw that DNAm at these loci was associated with nearby gene expression and enriched for enhancer chromatin states in prenatal brain tissue. Additionally, these loci were enriched for genes associated with psychiatric disorders and genes involved with neurogenesis. We also found autosomal differences in DNAm between the sexes during prenatal development, though these have less clear functional consequences. We lastly confirmed that the dynamic methylation at this critical period is specifically CpG methylation, with very low levels of CpH methylation. Our findings provide detailed insight into prenatal brain development as well as clues to the pathogenesis of psychiatric traits seen later in life. url: https://doi.org/10.1101/823781 doi: 10.1101/823781 id: cord-252586-fuaoelgb author: Phillips, Sandra title: Alisporivir Inhibition of Hepatocyte Cyclophilins Reduces HBV Replication and Hepatitis B Surface Antigen Production date: 2014-10-08 words: 5530.0 sentences: 296.0 pages: flesch: 47.0 cache: ./cache/cord-252586-fuaoelgb.txt txt: ./txt/cord-252586-fuaoelgb.txt summary: METHODS: Liver-derived cell lines producing full-length HBV and HBsAg particles, owing to stable (HepG2215) or transient (HuH-7) transfection, or infected with HBV (HepaRG cells; Invitrogen [Carlsbad, CA]), were incubated with alisporivir or NIM811 alone, or alisporivir in combination with a direct antiviral (telbivudine). Alisporivir treatment of HepG2215 cells resulted in a progressive reduction of secreted and intracellular, nucleocapsid-associated HBV DNA dependent on both drug concentration and time of drug exposure ( Figure 1A and B). NIM811 treatment of HepG2215 and of HepaRG cells also reduced the secreted and intracellular nucleocapsidassociated HBV DNA, however, its antiviral effect was lower than alisporivir (Supplementary Figure 3) . As stated earlier, alisporivir at 5 mg/mL reduced intracellular HBV-DNA levels by 73% and 58% in HuH-7 and HepG2215 cells, respectively, after 72 hours of treatment ( Figure 1B and D) . abstract: BACKGROUND & AIMS: Cyclophilins are host factors required for hepatitis C virus replication. Cyclophilin inhibitors such as alisporivir have shown strong anti–hepatitis C virus activity in vitro and in clinical studies. However, little is known about whether hepatocyte cyclophilins are involved in the hepatitis B virus (HBV) life cycle. We investigated the effects of 2 cyclophilin inhibitors (alisporivir and NIM811) on HBV replication and hepatitis B surface antigen (HBsAg) production in cell lines. METHODS: Liver-derived cell lines producing full-length HBV and HBsAg particles, owing to stable (HepG2215) or transient (HuH-7) transfection, or infected with HBV (HepaRG cells; Invitrogen [Carlsbad, CA]), were incubated with alisporivir or NIM811 alone, or alisporivir in combination with a direct antiviral (telbivudine). The roles of individual cyclophilins in drug response was evaluated by small interfering RNA knockdown of cyclophilin (CYP)A, CYPC, or CYPD in HepG2215 cells, or CYPA knockdown in HuH-7 cells. The kinetics of antiviral activity were assessed based on levels of HBV DNA and HBsAg and Southern blot analysis. RESULTS: In HepG2215, HuH-7, and HepaRG cells, alisporivir reduced intracellular and secreted HBV DNA, in a dose-dependent manner. Knockdown of CYPA, CYPC, or CYPD (reduced by 80%) significantly reduced levels of HBV DNA and secreted HBsAg. Knockdown of CYPA significantly reduced secretion of HBsAg, leading to accumulation of intracellular HBsAg; the addition of alisporivir greatly reduced levels of HBsAg in these cells. The combination of alisporivir and telbivudine had greater antiviral effects than those of telbivudine or alisporivir alone. CONCLUSIONS: Alisporivir inhibition of cyclophilins in hepatocyte cell lines reduces replication of HBV DNA and HBsAg production and secretion. These effects are potentiated in combination with direct antiviral agents that target HBV-DNA polymerase. url: https://api.elsevier.com/content/article/pii/S0016508514011998 doi: 10.1053/j.gastro.2014.10.004 id: cord-103830-pu6v53oy author: Pichon, Fabien title: Analysis and annotation of genome-wide DNA methylation patterns in two nonhuman primate species using the Infinium Human Methylation 450K and EPIC BeadChips date: 2020-05-10 words: 5439.0 sentences: 225.0 pages: flesch: 47.0 cache: ./cache/cord-103830-pu6v53oy.txt txt: ./txt/cord-103830-pu6v53oy.txt summary: In the present study, we evaluated the use of the Infinium 450K and Infinium EPIC BeadChips for genome-wide DNA methylation analyses in samples from Chlorocebus sabaeus and Macaca mulatta and conducted an in-depth analysis of the available probes for these two old world monkey genomes. We provide for each species and each microarray a list of annotated probes that can be used by the scientific community for genome-wide DNA methylation studies in Chlorocebus sabaeus or Macaca mulatta. We then mapped all the 50 bp probe sequences targeting CpG positions in the human genome from the Infinium 450K and EPIC arrays to Chlorocebus sabaeus (CS) and Macaca mulatta (MM) genomes, consecutively, using Bowtie [39], allowing only a unique position on the respective genome and up to 3 mismatches. abstract: The Infinium Human Methylation450 and Methylation EPIC BeadChips are useful tools for the study of the methylation state of hundreds of thousands of CpG across the human genome at affordable cost. However, in a wide range of experimental settings in particular for studies in infectious or brain-related diseases, human samples cannot be easily obtained. Hence, due to their close developmental, immunological and neurological proximity with humans, non-human primates are used in many research fields of human diseases and for preclinical research. Few studies have used DNA methylation microarrays in simian models. Microarrays designed for the analysis of DNA methylation patterns in the human genome could be useful given the genomic proximity between human and nonhuman primates. However, there is currently information lacking about the specificity and usability of each probe for many nonhuman primate species, including rhesus macaques (Macaca mulatta), originating from Asia, and African green monkeys originating from West-Africa (Chlorocebus sabaeus). Rhesus macaques and African green monkeys are among the major nonhuman primate models utilized in biomedical research. Here, we provide a precise evaluation and re-annotation of the probes of the two microarrays for the analysis of genome-wide DNA methylation patterns in these two Cercopithecidae species. We demonstrate that up to 162,000 of the 450K and 255,000 probes of the EPIC BeadChip can be reliably used in Macaca mulatta or Chlorocebus sabaeus. The annotation files are provided in a format compatible with a variety of preprocessing, normalization and analytical pipelines designed for data analysis from 450K/EPIC arrays, facilitating high-throughput DNA methylation analyses in Macaca mulatta and Chlorocebus sabaeus. They provide the opportunity to the research community to focus their analysis only on those probes identified as reliable. The described analytical workflow leaves the choice to the user to balance coverage versus specificity and can also be applied to other Cercopithecidae species. url: https://doi.org/10.1101/2020.05.09.081547 doi: 10.1101/2020.05.09.081547 id: cord-347221-g98q9cga author: Piyush, Ravikant title: Nucleic acid-based therapy for coronavirus disease 2019 date: 2020-09-19 words: 4217.0 sentences: 246.0 pages: flesch: 50.0 cache: ./cache/cord-347221-g98q9cga.txt txt: ./txt/cord-347221-g98q9cga.txt summary: This review mainly focuses on various nucleic acid-based biologically active molecules and their therapeutic potentials in developing vaccines for SARS-CoV-2. This review mainly focuses on various nucleic acid-based biologically active molecules and their therapeutic potentials in developing vaccines for SARS-CoV-2. This phenomenon of producing an effective immunity is particularly important in their use against the development of nucleic acid based therapeutic drugs for the treatment of SARS-CoV-2. Nucleic acid-based therapies, especially, RNA therapies including RNAi (RNA interference), siRNAs (small interfering RNA) and RNA aptamers, Ribozymes and ASOs (antisense oligonucleotides) target and neutralize the crucial components of the virus-like specific mRNA molecules, viral proteins like E (envelope), M (membrane), or N (nucleocapsid), or SARS helicase, etc. The nucleic acid-based vaccination technologies involve the use of RNA (mRNA) [34] or plasmid DNA, which encodes for antigen. abstract: The coronavirus disease 2019 (COVID-19), the pandemic that originated in China has already spread into more than 190 countries, resulting in huge loss of human life and many more are at the stake of losing it; if not intervened with the best therapeutics to contain the disease. For that aspect, various scientific groups are continuously involved in the development of an effective line of treatment to control the novel coronavirus from spreading rapidly. Worldwide scientists are evaluating various biomolecules and synthetic inhibitors against COVID-19; where the nucleic acid-based molecules may be considered as potential drug candidates. These molecules have been proved potentially effective against SARS-CoV, which shares high sequence similarity with SARS-CoV-2. Recent advancements in nucleic acid-based therapeutics are helpful in targeted drug delivery, safely and effectively. The use of nucleic acid-based molecules also known to regulate the level of gene expression inside the target cells. This review mainly focuses on various nucleic acid-based biologically active molecules and their therapeutic potentials in developing vaccines for SARS-CoV-2. url: https://doi.org/10.1016/j.heliyon.2020.e05007 doi: 10.1016/j.heliyon.2020.e05007 id: cord-291960-1is0rv6c author: Piñana, José Luis title: Pulmonary cytomegalovirus (CMV) DNA shedding in allogeneic hematopoietic stem cell transplant recipients: Implications for the diagnosis of CMV pneumonia date: 2019-02-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: OBJECTIVES: To date no definitive cut-off value for cytomegalovirus (CMV) DNA load in bronchoalveolar lavage (BAL) fluid specimens has been established to discriminate between CMV pneumonia and pulmonary CMV DNA shedding in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. METHODS: The current retrospective study is aimed at assessing the range of CMV DNA loads quantified in BAL fluid specimens from allo-HSCT patients with pneumonia in which different microorganisms were causally involved. RESULTS: A total of 144 BAL specimens from 123 patients were included. CMV DNA was detected in 56 out of 144 BAL fluid specimens and the median CMV DNA load from patients in whom CMV pneumonia was unlikely or could be tentatively ruled out was 1210 (31–68, 920) IU/ml. The frequency of CMV DNA detection and median CMV DNA loads were comparable, irrespective of the attributable cause of pneumonia. Detection of CMV DNA loads in BAL fluid specimens >500 IU/ml was independently associated with pneumonia-attributable mortality. CONCLUSIONS: The current study highlights the difficulty in establishing universal CMV DNA load thresholds in BAL fluid specimens for distinguishing between CMV pneumonia and pulmonary CMV DNA shedding, and suggests that the presence of CMV DNA in BAL fluid specimens beyond a certain level may have a deleterious impact on patient outcome. url: https://api.elsevier.com/content/article/pii/S0163445319300581 doi: 10.1016/j.jinf.2019.02.009 id: cord-276335-e1xlwcvc author: Poh, W.P. title: Characterization of cytotoxic T‐lymphocyte epitopes and immune responses to SARS coronavirus spike DNA vaccine expressing the RGD‐integrin‐binding motif date: 2009-05-27 words: 6046.0 sentences: 326.0 pages: flesch: 52.0 cache: ./cache/cord-276335-e1xlwcvc.txt txt: ./txt/cord-276335-e1xlwcvc.txt summary: Significant cell‐mediated immune responses were characterized by cytotoxic T‐lymphocyte (51)Cr release assay and interferon‐gamma secretion ELISPOT assay against RMA‐S target cells presenting predicted MHC class I H2‐Kb epitopes, including those spanning residues 884–891 and 1116–1123 within the S2 subunit of SARS‐CoV spike protein. The production of antigen-specific antibody induced by the SARS-CoV spike DNA vaccinations was assessed For the MHC-peptide binding assay, the mean fluorescence increase (MFI) was calculated as the ratio of the fluorescence of peptide-loaded RMA-S cells to the fluorescence of unloaded RMA-S cells. Mouse IFN-g ELISPOT for splenocytes of C57BL/6 mice immunized with selected S-His and S-RGD/His DNA vaccines to confirm T-cell epitopes of spike protein. This study demonstrated that prime-boost immunization of mice with SARS-CoV spike DNA vaccine constructs S-His and S-RGD/His induced significant antigen-specific cellular immune responses, IFN-g stimulation, and CTL activation. abstract: Integrins are critical for initiating T‐cell activation events. The integrin‐binding motif Arg‐Gly‐Asp (RGD) was incorporated into the pcDNA 3.1 mammalian expression vector expressing the codon‐optimized extracellular domain of SARS coronavirus (SARS‐CoV) spike protein, and tested by immunizing C57BL/6 mice. Significant cell‐mediated immune responses were characterized by cytotoxic T‐lymphocyte (51)Cr release assay and interferon‐gamma secretion ELISPOT assay against RMA‐S target cells presenting predicted MHC class I H2‐Kb epitopes, including those spanning residues 884–891 and 1116–1123 within the S2 subunit of SARS‐CoV spike protein. DNA vaccines incorporating the Spike‐RGD/His motif or the Spike‐His construct generated robust cell‐mediated immune responses. Moreover, the Spike‐His DNA vaccine construct generated a significant antibody response. Immunization with these DNA vaccine constructs elicited significant cellular and humoral immune responses. Additional T‐cell epitopes within the SARS‐CoV spike protein that may contribute to cell‐mediated immunity in vivo were also identified. J. Med. Virol. 81:1131–1139, 2009. © 2009 Wiley‐Liss, Inc. url: https://www.ncbi.nlm.nih.gov/pubmed/19475608/ doi: 10.1002/jmv.21571 id: cord-315616-pvt0amth author: Poole, Anthony title: Methyl-RNA: an evolutionary bridge between RNA and DNA? date: 2004-06-17 words: 5623.0 sentences: 281.0 pages: flesch: 54.0 cache: ./cache/cord-315616-pvt0amth.txt txt: ./txt/cord-315616-pvt0amth.txt summary: Ribonucleotide reductase itself, which synthesises deoxyribonucleotides from ribonucleotides, requires complex protein radical chemistry, and RNA world genomes may have reached their limits of coding capacity well before such complex enzymes had evolved. Even with this gap in the RNA world model, current knowledge suggests the RNA organism that evolved protein synthesis was likely to have been dangerously close to the Eigen limit for RNA, and probably emIn the ¢rst step, a radical is generated at some distance from the active site. By virtue of its non-speci¢c dsRNA methylating activity, this enzyme is hypothesised to have been recruited into methylation of genomic RNA, improving the stability of the genetic material prior to the origin of DNA. The predicted stabilising effect of 2P-O-methylation on genomic RNA argues that the coding capacity of the genome would have increased suf¢ciently for genuinely catalytic proteins such as RNA polymerase, and later ribonucleotide reductase, to arise, paving the way to the DNA world (Figure 4) . abstract: Given the apparent limitation of double-stranded RNA (dsRNA) genomes to about 30 kb, together with the complexity of DNA synthesis, it appears difficult for a dsRNA genome to encode all the information required before the transition from an RNA to a DNA genome. Ribonucleotide reductase itself, which synthesises deoxyribonucleotides from ribonucleotides, requires complex protein radical chemistry, and RNA world genomes may have reached their limits of coding capacity well before such complex enzymes had evolved. The transition from RNA to DNA thus appears to require intermediate steps, and we suggest that the naturally occurring 2′-O-methylated RNA, with chemical properties intermediate between RNA and DNA, is a suitable candidate. url: https://www.ncbi.nlm.nih.gov/pubmed/11137821/ doi: 10.1016/s1074-5521(00)00042-9 id: cord-297078-pxggjaby author: Poole, Anthony M. title: Modern mRNA Proofreading and Repair: Clues that the Last Universal Common Ancestor Possessed an RNA Genome? date: 2005-03-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: RNA repair has now been demonstrated to be a genuine biological process and appears to be present in all three domains of life. In this article, we consider what this might mean for the transition from an early RNA-dominated world to modern cells possessing genetically encoded proteins and DNA. There are significant gaps in our understanding of how the modern protein-DNA world could have evolved from a simpler system, and it is currently uncertain whether DNA genomes evolved once or twice. Against this backdrop, the discovery of RNA repair in modern cells is timely food for thought and brings us conceptually one step closer to understanding how RNA genomes were replaced by DNA genomes. We have examined the available literature on multisubunit RNA polymerase structure and function and conclude that a strong case can be made that the Last Universal Common Ancestor (LUCA) possessed a repair-competent RNA polymerase, which would have been capable of acting on an RNA genome. However, while this lends credibility to the proposal that the LUCA had an RNA genome, the alternative, that LUCA had a DNA genome, cannot be completely ruled out. url: https://www.ncbi.nlm.nih.gov/pubmed/15774424/ doi: 10.1093/molbev/msi132 id: cord-309642-wwaa6ls0 author: Potgieter, Leon N.D. title: Pathogenesis of Viral Infections date: 1986-11-30 words: 10859.0 sentences: 770.0 pages: flesch: 40.0 cache: ./cache/cord-309642-wwaa6ls0.txt txt: ./txt/cord-309642-wwaa6ls0.txt summary: 7 · 18 · 84 · 133 Such restrictions function at the cellular level either as the presence or absence of appropriate cell surface receptors (in some instances, they have been shown to be inherited as dominant alleles in a Mendelian manner) 9 · 18 · 26 · 46 · 68 · 97 ·u 9 · 120 or the intracellular hospitality of the cell (several genetic host restrictions on virus replication have been identified).18·32·59·80·82·108·109·120·126 Restricted growth of several DNA viruses in some cells results in transformation without production of progeny viruses. 112 The phenomenon appears to be mediated by virus-induced receptors on the surface membrane of cells and may be one mechanism of the often-encountered secondary bacterial infections associated with viral diseases. 51 · 52 · 104 Viral respiratory tract disease is a consequence of mechanical and biochemical injury to epithelial cells and alveolar macrophages, which can, in the most severe instances, result in secondary bacterial infection, pneumonia, and death. abstract: The article considers factors that influence pathogenesis, initiation of infection, dissemination of virus within a host, lytic viral infections, viral immunosuppression, viral immunopathology, and viral oncogenesis. url: https://api.elsevier.com/content/article/pii/S0195561686501297 doi: 10.1016/s0195-5616(86)50129-7 id: cord-004515-x22q1f21 author: Pottecher, Julien title: Protocol for TRAUMADORNASE: a prospective, randomized, multicentre, double-blinded, placebo-controlled clinical trial of aerosolized dornase alfa to reduce the incidence of moderate-to-severe hypoxaemia in ventilated trauma patients date: 2020-03-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Acute respiratory distress syndrome continues to drive significant morbidity and mortality after severe trauma. The incidence of trauma-induced, moderate-to-severe hypoxaemia, according to the Berlin definition, could be as high as 45%. Its pathophysiology includes the release of damage-associated molecular patterns (DAMPs), which propagate tissue injuries by triggering neutrophil extracellular traps (NETs). NETs include a DNA backbone coated with cytoplasmic proteins, which drive pulmonary cytotoxic effects. The structure of NETs and many DAMPs includes double-stranded DNA, which prevents their neutralization by plasma. Dornase alfa is a US Food and Drug Administration-approved recombinant DNase, which cleaves extracellular DNA and may therefore break up the backbone of NETs and DAMPs. Aerosolized dornase alfa was shown to reduce trauma-induced lung injury in experimental models and to improve arterial oxygenation in ventilated patients. METHODS: TRAUMADORNASE will be an institution-led, multicentre, double-blinded, placebo-controlled randomized trial in ventilated trauma patients. The primary trial objective is to demonstrate a reduction in the incidence of moderate-to-severe hypoxaemia in severe trauma patients during the first 7 days from 45% to 30% by providing aerosolized dornase alfa as compared to placebo. The secondary objectives are to demonstrate an improvement in lung function and a reduction in morbidity and mortality. Randomization of 250 patients per treatment arm will be carried out through a secure, web-based system. Statistical analyses will include a descriptive step and an inferential step using fully Bayesian techniques. The study was approved by both the Agence Nationale de la Sécurité du Médicament et des Produits de Santé (ANSM, on 5 October 2018) and a National Institutional Review Board (CPP, on 6 November 2018). Participant recruitment began in March 2019. Results will be published in international peer-reviewed medical journals. DISCUSSION: If early administration of inhaled dornase alfa actually reduces the incidence of moderate-to-severe hypoxaemia in patients with severe trauma, this new therapeutic strategy may be easily implemented in many clinical trauma care settings. This treatment may facilitate ventilator weaning, reduce the burden of trauma-induced lung inflammation and facilitate recovery and rehabilitation in severe trauma patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03368092. Registered on 11 December 2017. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079402/ doi: 10.1186/s13063-020-4141-6 id: cord-290617-45be6gxe author: Poulain, Florian title: Footprint of the host restriction factors APOBEC3 on the genome of human viruses date: 2020-08-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: APOBEC3 enzymes are innate immune effectors that introduce mutations into viral genomes. These enzymes are cytidine deaminases which transform cytosine into uracil. They preferentially mutate cytidine preceded by thymidine making the 5’TC motif their favored target. Viruses have evolved different strategies to evade APOBEC3 restriction. Certain viruses actively encode viral proteins antagonizing the APOBEC3s, others passively face the APOBEC3 selection pressure thanks to a depleted genome for APOBEC3-targeted motifs. Hence, the APOBEC3s left on the genome of certain viruses an evolutionary footprint. The aim of our study is the identification of these viruses having a genome shaped by the APOBEC3s. We analyzed the genome of 33,400 human viruses for the depletion of APOBEC3-favored motifs. We demonstrate that the APOBEC3 selection pressure impacts at least 22% of all currently annotated human viral species. The papillomaviridae and polyomaviridae are the most intensively footprinted families; evidencing a selection pressure acting genome-wide and on both strands. Members of the parvoviridae family are differentially targeted in term of both magnitude and localization of the footprint. Interestingly, a massive APOBEC3 footprint is present on both strands of the B19 erythroparvovirus; making this viral genome one of the most cleaned sequences for APOBEC3-favored motifs. We also identified the endemic coronaviridae as significantly footprinted. Interestingly, no such footprint has been detected on the zoonotic MERS-CoV, SARS-CoV-1 and SARS-CoV-2 coronaviruses. In addition to viruses that are footprinted genome-wide, certain viruses are footprinted only on very short sections of their genome. That is the case for the gamma-herpesviridae and adenoviridae where the footprint is localized on the lytic origins of replication. A mild footprint can also be detected on the negative strand of the reverse transcribing HIV-1, HIV-2, HTLV-1 and HBV viruses. Together, our data illustrate the extent of the APOBEC3 selection pressure on the human viruses and identify new putatively APOBEC3-targeted viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/32797103/ doi: 10.1371/journal.ppat.1008718 id: cord-029957-q7v5gli8 author: Prabhu, D. title: In silico Functional Annotation and Characterization of Hypothetical Proteins from Serratia marcescens FGI94 date: 2020-07-31 words: 5796.0 sentences: 311.0 pages: flesch: 42.0 cache: ./cache/cord-029957-q7v5gli8.txt txt: ./txt/cord-029957-q7v5gli8.txt summary: Two proteins AGB81206.1 and AGB83112.1 were predicted as a member of the exonuclease-endonuclease-phosphate domain super family which plays a crucial role in the intracellular signaling activities in bacteria (Dlakic, 2000) . The observed function of the HPs helps to understand the crucial role of new proteins in bacterial growth and can be targeted as a potential targets for drug discovery. The protein AGB80728.1 was predicted as Translocation and Assembly Module (TAM), which plays a major role in outer membrane biogenesis and virulence mechanisms in bacterial kingdom (Josts et al., 2017) . This kind of proteins are found in wide variety of prokaryotic and eukaryotic organisms and plays an vital role in cell processes and associated with virulence mechanisms of bacterial pathogens (Cerveny et al., 2013) . Various types of enzymes, transporters, cell division, binding proteins were characterized which play an essential role in the growth, survival virulence and pathogenesis of S. abstract: Serratia marcescens, rod-shaped Gram-negative bacteria is classified as an opportunistic pathogen in the family Enterobacteriaceae. It causes a wide variety of infections in humans, including urinary, respiratory, ocular lens and ear infections, osteomyelitis, endocarditis, meningitis and septicemia. Unfortunately, over the past decade, antibiotic resistance has become a serious health care issue; the effective means to control and dissemination of S. marcescens resistance is the need of hour. The whole genome sequencing of S. marcescens FGI94 strain contains 4434 functional proteins, among which 690 (15.56%) proteins were classified under hypothetical. In the present study, we applied the power of various bioinformatics tools on the basis of protein family comparison, motifs, functional properties of amino acids and genome context to assign the possible functions for the HPs. The pseudo sequences (protein sequence that contain ≤100 amino acid residues) are eliminated from the study. Although we have successfully predicted the function for 483 proteins, we were able to infer the high level of confidence only for 108 proteins. The predicted HPs were classified into various classes such as enzymes, transporters, binding proteins, cell division, cell regulatory and other proteins. The outcome of the study could be helpful to understand the molecular mechanism in bacterial pathogenesis and also provide an insight into the identification of potential targets for drug and vaccine development. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394047/ doi: 10.1134/s1062359020300019 id: cord-346890-4vozhns4 author: Prajapati, Deepak G. title: Progress in the Development of Intrinsically Conducting Polymer Composites as Biosensors date: 2019-04-23 words: 14599.0 sentences: 806.0 pages: flesch: 39.0 cache: ./cache/cord-346890-4vozhns4.txt txt: ./txt/cord-346890-4vozhns4.txt summary: Similarly, intrinsically conducting polymers (ICPs) and their composites have lured immense interest in bio‐sensing due to their various attributes like compatibility with biological molecules, efficient electron transfer upon biochemical reactions, loading of bio‐reagent, and immobilization of biomolecules. Amperometric biosensor relies on determining the current produced by electrochemical redox reaction of electro-active species, as a function of time, with a fixed applied potential on the electrode surface, most commonly an ICP. [255] Graphene in combination with ICP created a surface with superior electrical conductivity that resulted in a selective and sensitive biosensor and AuNP provided high affinity toward DNA for immobilization. The sensitive and selective biosensor exhibited excellent conductivity, high surface area, and many functional groups that aided in excellent immobilization of antibodies with low detection limit of 3.7 fg mL −1 . abstract: Biosensors are analytical devices which find extensive applications in fields such as the food industry, defense sector, environmental monitoring, and in clinical diagnosis. Similarly, intrinsically conducting polymers (ICPs) and their composites have lured immense interest in bio‐sensing due to their various attributes like compatibility with biological molecules, efficient electron transfer upon biochemical reactions, loading of bio‐reagent, and immobilization of biomolecules. Further, they are proficient in sensing diverse biological species and compounds like glucose (detection limit ≈0.18 nm), DNA (≈10 pm), cholesterol (≈1 µm), aptamer (≈0.8 pm), and also cancer cells (≈5 pm mL(−1)) making them a potential candidate for biological sensing functions. ICPs and their composites have been extensively exploited by researchers in the field of biosensors owing to these peculiarities; however, no consolidated literature on the usage of conducting polymer composites for biosensing functions is available. This review extensively elucidates on ICP composites and doped conjugated polymers for biosensing functions of copious biological species. In addition, a brief overview is provided on various forms of biosensors, their sensing mechanisms, and various methods of immobilizing biological species along with the life cycle assessment of biosensors for various biosensing applications, and their cost analysis. url: https://doi.org/10.1002/macp.201800561 doi: 10.1002/macp.201800561 id: cord-282610-zim7nond author: Proal, Amy title: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity date: 2018-12-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The illness ME/CFS has been repeatedly tied to infectious agents such as Epstein Barr Virus. Expanding research on the human microbiome now allows ME/CFS-associated pathogens to be studied as interacting members of human microbiome communities. Humans harbor these vast ecosystems of bacteria, viruses and fungi in nearly all tissue and blood. Most well-studied inflammatory conditions are tied to dysbiosis or imbalance of the human microbiome. While gut microbiome dysbiosis has been identified in ME/CFS, microbes and viruses outside the gut can also contribute to the illness. Pathobionts, and their associated proteins/metabolites, often control human metabolism and gene expression in a manner that pushes the body toward a state of illness. Intracellular pathogens, including many associated with ME/CFS, drive microbiome dysbiosis by directly interfering with human transcription, translation, and DNA repair processes. Molecular mimicry between host and pathogen proteins/metabolites further complicates this interference. Other human pathogens disable mitochondria or dysregulate host nervous system signaling. Antibodies and/or clonal T cells identified in patients with ME/CFS are likely activated in response to these persistent microbiome pathogens. Different human pathogens have evolved similar survival mechanisms to disable the host immune response and host metabolic pathways. The metabolic dysfunction driven by these organisms can result in similar clusters of inflammatory symptoms. ME/CFS may be driven by this pathogen-induced dysfunction, with the nature of dysbiosis and symptom presentation varying based on a patient's unique infectious and environmental history. Under such conditions, patients would benefit from treatments that support the human immune system in an effort to reverse the infectious disease process. url: https://doi.org/10.3389/fped.2018.00373 doi: 10.3389/fped.2018.00373 id: cord-341062-k3vjqumq author: Pruitt, Hawley C. title: Roles of N‐Myc and STAT interactor in cancer: From initiation to dissemination date: 2016-03-11 words: 6635.0 sentences: 409.0 pages: flesch: 47.0 cache: ./cache/cord-341062-k3vjqumq.txt txt: ./txt/cord-341062-k3vjqumq.txt summary: N‐myc & STAT Interactor, NMI, is a protein that has mostly been studied for its physical interactions with transcription factors that play critical roles in tumor growth, progression and metastasis. The physical interactions of NMI with its binding partners have been linked to many aspects of tumor biology including DNA damage response, cell death, epithelial‐to‐mesenchymal transition and stemness. 45 NMI expression reversed mesenchymal phenotypes of highly invasive breast cancer cells through enhancing STAT5-mediated transcription of SMAD7. Tri-complex formation leads to the stabilization of cytosolic b-catenin, a transcriptional co-factor that can enter the nucleus, bind to a member of the TCF/LEF protein family and subsequently activate transcription of Wnt target genes. Stably expressing NMI in MDA-MB-231 and MDA-MB-435 cancer cell lines led to increased levels of DKK1 and concomitantly reduced levels of b-catenin and c-Myc, known downstream targets of Wnt signaling. abstract: N‐myc & STAT Interactor, NMI, is a protein that has mostly been studied for its physical interactions with transcription factors that play critical roles in tumor growth, progression and metastasis. NMI is an inducible protein, thus its intracellular levels and location can vary dramatically, influencing a diverse array of cellular functions in a context‐dependent manner. The physical interactions of NMI with its binding partners have been linked to many aspects of tumor biology including DNA damage response, cell death, epithelial‐to‐mesenchymal transition and stemness. Thus, discovering more details about the function(s) of NMI could reveal key insights into how transcription factors like c‐Myc, STATs and BRCA1 are contextually regulated. Although a normal, physiological function of NMI has not yet been discovered, it has potential roles in pathologies ranging from viral infection to cancer. This review provides a timely perspective of the unfolding roles of NMI with specific focus on cancer progression and metastasis. url: https://doi.org/10.1002/ijc.30043 doi: 10.1002/ijc.30043 id: cord-261134-zarq507s author: Pulford, David title: Amplification refractory mutation system PCR assays for the detection of variola and Orthopoxvirus date: 2004-02-13 words: 3799.0 sentences: 215.0 pages: flesch: 50.0 cache: ./cache/cord-261134-zarq507s.txt txt: ./txt/cord-261134-zarq507s.txt summary: PCR assays that can identify the presence of variola virus (VARV) sequences in an unknown DNA sample were developed using principles established for the amplification refractory mutation system (ARMS). When a variola virus specific primer was used with a consensus primer in an ARMS assay with different Orthopoxvirus genomes, a PCR product was only amplified from variola virus DNA. Incorporating a second consensus primer into the assay produced a multiplex PCR that provided Orthopoxvirus generic and variola-specific products with variola virus DNA. The variola virus specific primers did not produce amplicons with either assay format when tested with 50 other Orthopoxvirus DNA samples. These multiplex assays employ three primers; two consensus primers generate an amplicon diagnostic of an Old World Orthopoxvirus and the third primer simultaneously binds to a variola-specific polymorphism and initiates extension of a shorter PCR product to detect the presence of variola virus. abstract: PCR assays that can identify the presence of variola virus (VARV) sequences in an unknown DNA sample were developed using principles established for the amplification refractory mutation system (ARMS). The assay’s specificity utilised unique single nucleotide polymorphisms (SNP) identified among Orthopoxvirus (OPV) orthologs of the vaccinia virus Copenhagen strain A13L and A36R genes. When a variola virus specific primer was used with a consensus primer in an ARMS assay with different Orthopoxvirus genomes, a PCR product was only amplified from variola virus DNA. Incorporating a second consensus primer into the assay produced a multiplex PCR that provided Orthopoxvirus generic and variola-specific products with variola virus DNA. We tested two single nucleotide polymorphisms with a panel of 43 variola virus strains, collected over 40 years from countries across the world, and have shown that they provide reliable markers for variola virus identification. The variola virus specific primers did not produce amplicons with either assay format when tested with 50 other Orthopoxvirus DNA samples. Our analysis shows that these two polymorphisms were conserved in variola virus genomes and provide a reliable signature of Orthopoxvirus species identification. url: https://www.ncbi.nlm.nih.gov/pubmed/15019263/ doi: 10.1016/j.jviromet.2004.01.001 id: cord-004181-exbs3tz7 author: Pumchan, Ansaya title: Novel Chimeric Multiepitope Vaccine for Streptococcosis Disease in Nile Tilapia (Oreochromis niloticus Linn.) date: 2020-01-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Streptococcus agalactiae is a causative agent of streptococcosis disease in various fish species, including Nile tilapia (Oreochromis niloticus Linn.). Vaccination is an effective disease prevention and control method, but limitations remain for protecting against catastrophic mortality of fish infected with different strains of streptococci. Immunoproteomics analysis of S. agalactiae was used to identify antigenic proteins and construct a chimeric multiepitope vaccine. Epitopes from five antigenic proteins were shuffled in five helices of a flavodoxin backbone, and in silico analysis predicted a suitable RNA and protein structure for protein expression. 45F2 and 42E2 were identified as the best candidates for a chimeric multiepitope vaccine. Recombinant plasmids were constructed to produce a recombinant protein vaccine and DNA vaccine system. Overexpressed proteins were determined to be 30 kDa and 25 kDa in the E. coli and TK1 systems, respectively. The efficacy of the chimeric multiepitope construct as a recombinant protein vaccine and DNA vaccine was evaluated in Nile tilapia, followed by S. agalactiae challenge at 1 × 10(7) CFU/mL. Relative percentage survival (RPS) and cumulative mortality were recorded at approximately 57–76% and 17–30%, respectively. These chimeric multiepitope vaccines should be applied in streptococcosis disease control and developed into a multivalent vaccine to control multiple diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969146/ doi: 10.1038/s41598-019-57283-0 id: cord-312757-58p5b2vw author: Pérez-Montoto, Lázaro G. title: Scoring function for DNA–drug docking of anticancer and antiparasitic compounds based on spectral moments of 2D lattice graphs for molecular dynamics trajectories date: 2009-11-30 words: 4825.0 sentences: 256.0 pages: flesch: 53.0 cache: ./cache/cord-312757-58p5b2vw.txt txt: ./txt/cord-312757-58p5b2vw.txt summary: Abstract We introduce here a new class of invariants for MD trajectories based on the spectral moments πk (L) of the Markov matrix associated to lattice network-like (LN) graph representations of Molecular Dynamics (MD) trajectories. We propose this new model as a scoring function to guide DNA-docking studies in the drug design of new coumarins for anticancer or antiparasitic PUVA therapy. In addition, predicting drug activity we can use 3D drugtarget QSAR/QSBR models as scoring function to guide the search of optimal drug-target interaction geometries in drug-target docking studies [42] [43] [44] . The new model is also QSBR that has potential applications as scoring function for DNA-furocoumarin docking studies. The DNA-drug docking molecular dynamics trajectories or energetic profiles of all the starting intercalation complexes were obtained by means of the Monte Carlo [155] method, using the HyperChem package. We can obtain new types of 2D graph theoretical representation for Molecular Dynamics (MD) trajectories that resemble LNs used for DNA and protein sequences. abstract: Abstract We introduce here a new class of invariants for MD trajectories based on the spectral moments πk (L) of the Markov matrix associated to lattice network-like (LN) graph representations of Molecular Dynamics (MD) trajectories. The procedure embeds the MD energy profiles on a 2D Cartesian coordinates system using simple heuristic rules. At the same time, we associate the LN with a Markov matrix that describes the probabilities of passing from one state to other in the new 2D space. We construct this type of LNs for 422 MD trajectories obtained in DNA–drug docking experiments of 57 furocoumarins. The combined use of psoralens+ultraviolet light (UVA) radiation is known as PUVA therapy. PUVA is effective in the treatment of skin diseases such as psoriasis and mycosis fungoides. PUVA is also useful to treat human platelet (PTL) concentrates in order to eliminate Leishmania spp. and Trypanosoma cruzi. Both are parasites that cause Leishmaniosis (a dangerous skin and visceral disease) and Chagas disease, respectively; and may circulate in blood products collected from infected donors. We included in this study both lineal (psoralens) and angular (angelicins) furocoumarins. In the study, we grouped the LNs on two sets; set1: DNA–drug complex MD trajectories for active compounds and set2: MD trajectories of non-active compounds or no-optimal MD trajectories of active compounds. We calculated the respective πk (L) values for all these LNs and used them as inputs to train a new classifier that discriminate set1 from set2 cases. In training series the model correctly classifies 79 out of 80 (specificity=98.75%) set1 and 226 out of 238 (Sensitivity=94.96%) set2 trajectories. In independent validation series the model correctly classifies 26 out of 26 (specificity=100%) set1 and 75 out of 78 (sensitivity=96.15%) set2 trajectories. We propose this new model as a scoring function to guide DNA-docking studies in the drug design of new coumarins for anticancer or antiparasitic PUVA therapy. url: https://www.sciencedirect.com/science/article/pii/S022352340900333X doi: 10.1016/j.ejmech.2009.06.011 id: cord-031970-7szpo4zx author: Qiao, Yu title: Tumorigenic and Immunogenic Properties of Induced Pluripotent Stem Cells: a Promising Cancer Vaccine date: 2020-09-16 words: 6938.0 sentences: 377.0 pages: flesch: 39.0 cache: ./cache/cord-031970-7szpo4zx.txt txt: ./txt/cord-031970-7szpo4zx.txt summary: Finally, the review will discuss the expanding application of iPSC technology in cancer immunotherapy as a potential cancer vaccine and its advantages in auxiliary treatment compared with oncofetal antigen-based and embryonic stem cell (ESC)-based vaccines. While the core pluripotent factors like Oct4, Sox2, Klf4, c-Myc, Nanog and Lin28 are promoting the somatic reprogramming process, one of the vital tumor suppressor gene -P53 acts like a barrier to impede this. Abnormal epigenetic modification accumulated in the iPSCs from reprogramming to prolonged culture also contributes to the risk of tumorigenic potential colon cancer cell line reduced colony formation not because of apoptosis induction, but due to its role in mediating p53dependent cell cycle arrest [66] . Another parallel study demonstrated that iPSC had similar gene expression patterns with lung adenocarcinoma stem cells and could provoke anti-tumor immunity in humanized mice model [154] . Humanized mice reveal differential immunogenicity of cells derived from autologous induced pluripotent stem cells abstract: Induced pluripotent stem cells (iPSCs) are mainly characterized by their unlimited proliferation abilities and potential to develop into almost any cell type. The creation of this technology has been of great interest to many scientific fields, especially regenerative biology. However, concerns about the safety of iPSC application in transplantation have arisen due to the tumorigenic and immunogenic properties of iPSCs. This review will briefly introduce the developing history of somatic reprogramming and applications of iPSC technology in regenerative medicine. In addition, the review will highlight two challenges to the efficient usage of iPSCs and the underlying mechanisms of these challenges. Finally, the review will discuss the expanding application of iPSC technology in cancer immunotherapy as a potential cancer vaccine and its advantages in auxiliary treatment compared with oncofetal antigen-based and embryonic stem cell (ESC)-based vaccines. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494249/ doi: 10.1007/s12015-020-10042-5 id: cord-000010-prsvv6l9 author: Qin, Jian title: Studying copy number variations using a nanofluidic platform date: 2008-08-18 words: 4986.0 sentences: 250.0 pages: flesch: 51.0 cache: ./cache/cord-000010-prsvv6l9.txt txt: ./txt/cord-000010-prsvv6l9.txt summary: Copy number variations (CNVs) in the human genome are conventionally detected using high-throughput scanning technologies, such as comparative genomic hybridization and high-density single nucleotide polymorphism (SNP) microarrays, or relatively low-throughput techniques, such as quantitative polymerase chain reaction (PCR). We have developed a new technology to study copy numbers using a platform known as the digital array, a nanofluidic biochip capable of accurately quantitating genes of interest in DNA samples. Other existing technologies, such as quantitative polymerase chain reaction (PCR), are limited because of their inability to reliably distinguish less than a twofold difference in copy number of a particular gene in DNA samples (11) (12) (13) . In this study we demonstrate the use of a unique integrated nanofluidic system, the digital array, in the study of CNVs. The digital array (14, 15) is able to accurately quantitate DNA samples based on the fact that single DNA molecules are randomly distributed in more than 9000 reaction chambers and then PCR amplified. abstract: Copy number variations (CNVs) in the human genome are conventionally detected using high-throughput scanning technologies, such as comparative genomic hybridization and high-density single nucleotide polymorphism (SNP) microarrays, or relatively low-throughput techniques, such as quantitative polymerase chain reaction (PCR). All these approaches are limited in resolution and can at best distinguish a twofold (or 50%) difference in copy number. We have developed a new technology to study copy numbers using a platform known as the digital array, a nanofluidic biochip capable of accurately quantitating genes of interest in DNA samples. We have evaluated the digital array's performance using a model system, to show that this technology is exquisitely sensitive, capable of differentiating as little as a 15% difference in gene copy number (or between 6 and 7 copies of a target gene). We have also analyzed commercial DNA samples for their CYP2D6 copy numbers and confirmed that our results were consistent with those obtained independently using conventional techniques. In a screening experiment with breast cancer and normal DNA samples, the ERBB2 gene was found to be amplified in about 35% of breast cancer samples. The use of the digital array enables accurate measurement of gene copy numbers and is of significant value in CNV studies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2566873/ doi: 10.1093/nar/gkn518 id: cord-311328-k751tehv author: Rabti, Amal title: DNA markers and nano-biosensing approaches for tuberculosis diagnosis date: 2020-06-19 words: 7738.0 sentences: 340.0 pages: flesch: 35.0 cache: ./cache/cord-311328-k751tehv.txt txt: ./txt/cord-311328-k751tehv.txt summary: The latter use carbonaceous nanomaterials (graphene and carbon nanotubes), noble metals (silver and gold), semi-conducting (metal oxides, magnetic beads, and quantum dots) in order to reveal and/or to amplify the signal after the recognition of target DNA biomarker. developed a sandwich-type of Mtb DNA biosensor based on the use of polyaniline-reduced graphene oxide, which was decorated with DNA label immobilized onto gold nanoparticles ( Fig. 13.1 ) [17] . In fact, hybridization of IS6110 amplified DNA target sequence, modified at 3′ end with AuNPs as mass enhancement, to the probe oligonucleotide immobilized onto gold electrode of the quartz crystal were studied through the changes in QCM frequency, which indicated that the developed biosensor could detect serial dilution of Mtb DNA limited to 5 pg of genomic DNA. An electrochemical DNA biosensor for the detection of Mycobacterium tuberculosis, based on signal amplification of graphene and a gold nanoparticle-polyaniline nanocomposite Reduced graphene oxide nanoribbon immobilized gold nanoparticles based electrochemical DNA biosensor for detection of Mycobacterium tuberculosis abstract: According to WHO 2018 report, 10 million people developed tuberculosis and 1.3 million died from it making it 1 of 10 deadliest diseases worldwide. Tuberculosis is caused by infection with the bacillus Mycobacterium tuberculosis (Mtb). WHO recommends using a specific diagnostic kit Xpert MTB/RIF developed by Cepheid (California, United States). An alarming number of new cases (ca. 558,000) of rifampicin-resistant tuberculosis was diagnosticated in 2017. In recent years, new diagnosis tools targeting the Mtb DNA biomarkers have emerged using a plethora of nanomaterials capable of delivering new technological approaches for the rapid diagnostics of TB and rifampicin-resistant TB (RR-TB). In this chapter, we summarized the state-of-the-art of the current available DNA biomarkers and the potential applications for the development of new diagnosis nanotechnology-based devices. The latter use carbonaceous nanomaterials (graphene and carbon nanotubes), noble metals (silver and gold), semi-conducting (metal oxides, magnetic beads, and quantum dots) in order to reveal and/or to amplify the signal after the recognition of target DNA biomarker. The readout techniques such as colorimetry, fluorescence, surface plasmon resonance, and electrochemical methods were also reviewed. Future is bright for point-of-care diagnostics with a sample-in answer-out approach that hampers user-error through miniaturization of biochip technology to the nanoscale range, which will enable their use by nonspecialized personnel. url: https://api.elsevier.com/content/article/pii/B9780128198117000138 doi: 10.1016/b978-0-12-819811-7.00013-8 id: cord-290550-u8x9drva author: Radford, Alan D. title: Application of next-generation sequencing technologies in virology date: 2012-09-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The progress of science is punctuated by the advent of revolutionary technologies that provide new ways and scales to formulate scientific questions and advance knowledge. Following on from electron microscopy, cell culture and PCR, next-generation sequencing is one of these methodologies that is now changing the way that we understand viruses, particularly in the areas of genome sequencing, evolution, ecology, discovery and transcriptomics. Possibilities for these methodologies are only limited by our scientific imagination and, to some extent, by their cost, which has restricted their use to relatively small numbers of samples. Challenges remain, including the storage and analysis of the large amounts of data generated. As the chemistries employed mature, costs will decrease. In addition, improved methods for analysis will become available, opening yet further applications in virology including routine diagnostic work on individuals, and new understanding of the interaction between viral and host transcriptomes. An exciting era of viral exploration has begun, and will set us new challenges to understand the role of newly discovered viral diversity in both disease and health. url: https://doi.org/10.1099/vir.0.043182-0 doi: 10.1099/vir.0.043182-0 id: cord-017297-q3qtgrfc author: Rajagopal, Vaishnavi title: Viral Helicases date: 2008-11-01 words: 11546.0 sentences: 654.0 pages: flesch: 52.0 cache: ./cache/cord-017297-q3qtgrfc.txt txt: ./txt/cord-017297-q3qtgrfc.txt summary: In a recent study on HSV-1 UL9 helicase, mutational analysis of the residues in the Ia motif implicated in DNA binding resulted in moderate to severe defects in single-stranded nucleic-acids binding and ssNA stimulated ATPase activity, while retaining the intrinsic ATPase activity similar to that of wildtype enzyme (Marintcheva and Weller 2003) . Thus, in order to understand the mechanism of helicase catalyzed unwinding reactions, it is important to understand all the individual steps to it, namely: nucleic-acid binding, NTP binding and hydrolysis, single-stranded translocation, and then finally the strand-separation function. Two early genes of bacteriophage T5 encode proteins containing an NTP-binding sequence motif and probably involved in DNA replication, recombination and repair Bacteriophage T7 helicase/primase proteins form rings around single-stranded DNA that suggest a general structure for hexameric helicases A functional interaction of ICP8, the herpes simplex virus single-stranded DNA-binding protein, and the helicase-primase complex that is dependent on the presence of the UL8 subunit abstract: Helicases are motor proteins that use the free energy of NTP hydrolysis to catalyze the unwinding of duplex nucleic acids. Helicases participate in almost all processes involving nucleic acids. Their action is critical for replication, recombination, repair, transcription, translation, splicing, mRNA editing, chromatin remodeling, transport, and degradation (Matson and Kaiser-Rogers 1990; Matson et al. 1994; Mendonca et al. 1995; Luking et al. 1998). url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121818/ doi: 10.1007/b135974_20 id: cord-346280-7sw30bsz author: Ramos Venancio, D. B. title: Biomathematical models for genetic diversity analyses in complete genomes of SARS-CoV-2 date: 2020-10-02 words: 4036.0 sentences: 254.0 pages: flesch: 52.0 cache: ./cache/cord-346280-7sw30bsz.txt txt: ./txt/cord-346280-7sw30bsz.txt summary: In this work, we evaluated the levels of genetic diversity in 38 complete genomes of SARS-CoV-2, publicly available on the National Center for Biotechnology Information (NCBI) platform and from six countries in South America (Brazil, Chile, Peru, Colombia, Uruguay and Venezuela with 16, 11, 1, 1, 1, 7 haplotypes, respectively), all with an extension of 29,906 bp and Phred values [≥] 40. The specific methodologies for Paired FST estimators, Molecular Variance (AMOVA), Genetic Distance, mismatch, demographic and spatial expansion analyses, molecular diversity and evolutionary divergence time analyses, were obtained using 20,000 random permutation. This stage is the most used in the LaBECom protocols because it allows to know the genetic structure of populations measuring their variances, this methodology, first defined by Cockerham in 1969 and and, later adapted by other researchers, is essentially similar to other approaches based on analyses of gene frequency variance, but takes into account the number of mutations between haplotypes. abstract: In this work, we evaluated the levels of genetic diversity in 38 complete genomes of SARS-CoV-2, publicly available on the National Center for Biotechnology Information (NCBI) platform and from six countries in South America (Brazil, Chile, Peru, Colombia, Uruguay and Venezuela with 16, 11, 1, 1, 1, 7 haplotypes, respectively), all with an extension of 29,906 bp and Phred values [≥] 40. These haplotypes were previously used for phylogenetic analyses, following the alignment protocols of the MEGA X software; where all gaps and unconserved sites were extracted for the construction of phylogenetic trees. The specific methodologies for Paired FST estimators, Molecular Variance (AMOVA), Genetic Distance, mismatch, demographic and spatial expansion analyses, molecular diversity and evolutionary divergence time analyses, were obtained using 20,000 random permutation. url: http://medrxiv.org/cgi/content/short/2020.10.01.20205120v1?rss=1 doi: 10.1101/2020.10.01.20205120 id: cord-336659-qddjqiw9 author: Ramos, Jheneffer Sonara Aguiar title: Multi-biomarker responses to pesticides in an agricultural population from Central Brazil date: 2020-08-21 words: 3842.0 sentences: 201.0 pages: flesch: 48.0 cache: ./cache/cord-336659-qddjqiw9.txt txt: ./txt/cord-336659-qddjqiw9.txt summary: Our findings demonstrate that pesticides can exert various deleterious effects on human health by damaging the DNA as well as by influencing the immune system in the case of both direct or indirect exposure and these issues are associated to age, gender, intoxication and the nonuse of PPE. In this context, agricultural workers and their families and individuals who reside close to fields where pesticides are applied are considered to be the group that will receive the most considerable exposure at the highest risk for adverse health outcomes (Gangemi et al., 2016; Docea et al. This is the first study from Central Brazil that demonstrated how genetic and immune biomarkers are associated to the exposure of a complex mixture of pesticides Also, families of farmworkers are often environmentally exposed to multiple pesticides, either by living near crops or by having contact with contaminated clothes and work tools without personal protection (Damalas and Eleftherohorinos, 2011; Parks, 2016; Doğanlar et al. abstract: Abstract We evaluated farmworkers exposed to pesticides and individuals with no history of occupational exposure to pesticides. It was performed the comet assay to evaluate DNA damage. The immunophenotyping of TCD4+ lymphocyte subpopulations in peripheral blood was performed by flow cytometry. The single nucleotide polymorphisms (SNPs) in PON1, XRCC1, IL6, IL6R, TNF-α, and MIR137 genes were evaluated by real-time PCR. The exposed group was composed mostly by males (69.44%), with direct exposure to pesticides (56%) and with an average age range of 46 ± 13.89 years, being that 58.3% of farmworkers directly exposed to pesticides and reported the full use of personal protective equipment (PPE). DNA damage was greater in the exposed group (p < 0.05), reinforced by the use of PPE to denote a lower degree of DNA damage (p = 0.002). In this context, in the exposed group, we demonstrated that the use of PPE, age, gender and intoxication events were the variables that most contributed to increase DNA damage (p < 0.0001). Besides, the exposed group showed a significant increase in the subpopulations of T lymphocytes CD3+ CD4+ (p = 0.04) and CD3+ CD4+ CD25+ (p < 0.0001). SNPs in the TNF-α (rs361525) gene presented a difference in the genotype distribution between the groups (p = 0.002). The genotype distribution of TNF-α (rs361525) was also positively correlated with the DNA damage of the exposed group (r = 0.19; p = 0.01), demonstrating a higher risk of DNA damage in the farmworkers presenting the A mutated allele. Our findings demonstrate that pesticides can exert various deleterious effects on human health by damaging the DNA as well as by influencing the immune system in the case of both direct or indirect exposure and these issues are associated to age, gender, intoxication and the nonuse of PPE. url: https://www.ncbi.nlm.nih.gov/pubmed/32920385/ doi: 10.1016/j.scitotenv.2020.141893 id: cord-292031-weiwksh6 author: Ramírez-Castillo, Flor Yazmín title: Waterborne Pathogens: Detection Methods and Challenges date: 2015-05-21 words: 7358.0 sentences: 378.0 pages: flesch: 36.0 cache: ./cache/cord-292031-weiwksh6.txt txt: ./txt/cord-292031-weiwksh6.txt summary: Quantitative microbial risk assessment (QMRA) is a helpful tool to evaluate the scenarios for pathogen contamination that involve surveillance, detection methods, analysis and decision-making. Molecular techniques, such as nucleic acid amplification procedures, offer sensitive and analytical tools for detecting a variety of pathogens, including new emerging strains, present the possibility of automation, and real-time analysis to provide information for microbial risk assessment purposes [33] . Limitations of DNA based methods such as PCR include the inability to discriminate between viable from non-viable cells that both contain DNA, the low concentration of several pathogens in water such as Cryptosporidium, Giardia and viruses, and the lack of data to indicate the real infectious risk to a population. Oligonucleotide microarrays are a powerful genomic technology that is widely utilized to monitor gene expression under different cell growth conditions, detecting specific mutations in DNA sequences and characterizing microorganisms in environmental samples [76] . abstract: Waterborne pathogens and related diseases are a major public health concern worldwide, not only by the morbidity and mortality that they cause, but by the high cost that represents their prevention and treatment. These diseases are directly related to environmental deterioration and pollution. Despite the continued efforts to maintain water safety, waterborne outbreaks are still reported globally. Proper assessment of pathogens on water and water quality monitoring are key factors for decision-making regarding water distribution systems’ infrastructure, the choice of best water treatment and prevention waterborne outbreaks. Powerful, sensitive and reproducible diagnostic tools are developed to monitor pathogen contamination in water and be able to detect not only cultivable pathogens but also to detect the occurrence of viable but non-culturable microorganisms as well as the presence of pathogens on biofilms. Quantitative microbial risk assessment (QMRA) is a helpful tool to evaluate the scenarios for pathogen contamination that involve surveillance, detection methods, analysis and decision-making. This review aims to present a research outlook on waterborne outbreaks that have occurred in recent years. This review also focuses in the main molecular techniques for detection of waterborne pathogens and the use of QMRA approach to protect public health. url: https://www.ncbi.nlm.nih.gov/pubmed/26011827/ doi: 10.3390/pathogens4020307 id: cord-000050-tfcerilc author: Rao, Srinivas title: Multivalent HA DNA Vaccination Protects against Highly Pathogenic H5N1 Avian Influenza Infection in Chickens and Mice date: 2008-06-18 words: 5605.0 sentences: 256.0 pages: flesch: 44.0 cache: ./cache/cord-000050-tfcerilc.txt txt: ./txt/cord-000050-tfcerilc.txt summary: METHODOLOGY / PRINCIPAL FINDINGS: The ability of DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. After optimization of injection conditions, alternative multivalent DNA vaccine regimens were analyzed and compared for magnitude and breadth of neutralizing antibodies, as well as protective efficacy after challenge in mouse and chicken models of HPAI H5N1 infection. The ability of chickens to generate specific antibodies was assessed with three strains that showed broad cross protection in mouse studies (A/Vietnam/1203/2004, A/Anhui/ 1/2005 and A/Indonesia/05/2005), administered individually or in combination, by different injection methods. abstract: BACKGROUND: Sustained outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in avian species increase the risk of reassortment and adaptation to humans. The ability to contain its spread in chickens would reduce this threat and help maintain the capacity for egg-based vaccine production. While vaccines offer the potential to control avian disease, a major concern of current vaccines is their potency and inability to protect against evolving avian influenza viruses. METHODOLOGY / PRINCIPAL FINDINGS: The ability of DNA vaccines encoding hemagglutinin (HA) proteins from different HPAI H5N1 serotypes was evaluated for its ability to elicit neutralizing antibodies and to protect against homologous and heterologous HPAI H5N1 strain challenge in mice and chickens after DNA immunization by needle and syringe or with a pressure injection device. These vaccines elicited antibodies that neutralized multiple strains of HPAI H5N1 when given in combinations containing up to 10 HAs. The response was dose-dependent, and breadth was determined by the choice of the influenza virus HA in the vaccine. Monovalent and trivalent HA vaccines were tested first in mice and conferred protection against lethal H5N1 A/Vietnam/1203/2004 challenge 68 weeks after vaccination. In chickens, protection was observed against heterologous strains of HPAI H5N1 after vaccination with a trivalent H5 serotype DNA vaccine with doses as low as 5 µg DNA given twice either by intramuscular needle injection or with a needle-free device. CONCLUSIONS/SIGNIFICANCE: DNA vaccines offer a generic approach to influenza virus immunization applicable to multiple animal species. In addition, the ability to substitute plasmids encoding different strains enables rapid adaptation of the vaccine to newly evolving field isolates. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2657001/ doi: 10.1371/journal.pone.0002432 id: cord-331557-8axi74nn author: Raoult, Didier title: What does the future hold for clinical microbiology? date: 2004 words: 6513.0 sentences: 328.0 pages: flesch: 35.0 cache: ./cache/cord-331557-8axi74nn.txt txt: ./txt/cord-331557-8axi74nn.txt summary: When PCR is used to detect DNA in clinical specimens, microarrays can then be used to identify the amplified products by hybridization to an array that is composed of pathogen-specific probes. Kits are available for the detection and quantification of DNA and RNA in clinical samples, and the technique has been specifically developed to enable the follow-up of patients with HIV and hepatitis C infections (Amplitech AME Bioscience; Bayer Diagnostics; Roche Diagnostics). Mass-spectrometry analysis of base-specific fragmentation patterns of PCRamplified DNA has recently been studied as a technique for the rapid identification of bacterial isolates and for the detection of specific 16S rRNA gene fragments that are amplified from complex environmental samples 35 . These automated microarrays will be suitable both for mass screening of sera in epidemiology studies and in blood banks, and for diagnostics that are carried out on single serum samples in clinical microbiology laboratories. abstract: In the past decade, clinical microbiology laboratories have undergone important changes with the introduction of molecular biology techniques and laboratory automation. In the future, there will be a need for more rapid diagnoses, increased standardization of testing and greater adaptability to cope with new threats from infectious microorganisms, such as agents of bioterrorism and emerging pathogens. The combination of the new tools that are now being developed in research laboratories, the general reorganization of clinical laboratories and improved communication between physicians and clinical microbiologists should lead to profound changes in the way that clinical microbiologists work. url: https://www.ncbi.nlm.nih.gov/pubmed/15040262/ doi: 10.1038/nrmicro820 id: cord-348860-zaimorg0 author: Ratra, Ruchi title: Functional genomics as a tool in virus research date: 2008-06-01 words: 3379.0 sentences: 171.0 pages: flesch: 39.0 cache: ./cache/cord-348860-zaimorg0.txt txt: ./txt/cord-348860-zaimorg0.txt summary: The genomics era has revolutionized the biological sciences and has heralded the emergence of new ''omics'' methodologies such as transcriptomics (study of the gene expression and expression levels of mRNAs at a given time and condition), proteomics (study of the entire protein content of a cell/tissue under various conditions, their structure and functions), metabolomics (study of the metabolite profi le of different cellular processes), phosphoproteomics (a branch of proteomics that characterizes proteins that are phosphorylated), interactomics/system biology (a science that unifi es transcriptomics, proteomics and metabolomics to look at the organism as a whole) and so on. DNA microarrays, proteomics and bioinformatic analysis are routinely used to analyze changes in host and viral gene and protein expression that occur in a virus infected cell [25] . abstract: Genomics is the study of an organism’s entire genome. It started out as a great scientific endeavor in the 1990s which aimed to sequence the complete genomes of certain biological species. However viruses are not new to this field as complete viral genomes have routinely been sequenced since the past thirty years. The ‘genomic era’ has been said to have revolutionized biology. This knowledge of full genomes has created the field of functional genomics in today’s post-genomic era, which, is in most part concerned with the studies on the expression of the organism’s genome under different conditions. This article is an attempt to introduce its readers to the application of functional genomics to address and answer several complex biological issues in virus research. url: https://www.ncbi.nlm.nih.gov/pubmed/23100713/ doi: 10.1007/s12088-008-0032-3 id: cord-350807-qdq96723 author: Reckziegel, Maria title: Viruses and atypical bacteria in the respiratory tract of immunocompromised and immunocompetent patients with airway infection date: 2020-05-27 words: 4655.0 sentences: 283.0 pages: flesch: 44.0 cache: ./cache/cord-350807-qdq96723.txt txt: ./txt/cord-350807-qdq96723.txt summary: Samples were tested by PCR for the presence of herpesviruses (HSV-1/-2; VZV; CMV; HHV6; EBV), adenoviruses, bocaviruses, entero-/rhinoviruses (HRV), parechoviruses, coronaviruses, influenza viruses (IV), parainfluenza viruses as well as for pneumoviruses (HMPV and RSV), and atypical bacteria (Mycoplasma pneumoniae, M.p.; Chlamydia pneumoniae, C.p.). Furthermore, particularly transplant patients are at risk for reactivation of diverse herpesviruses (herpes simplex virus-1/-2, HSV-1/-2; varicella zoster virus, VZV; cytomegalovirus, CMV; human herpesvirus 6, HHV-6; Epstein-Barr virus, EBV) [12, 15, [17] [18] [19] [20] . In this monocentric study, genome equivalents of viruses and M.p. were frequently detected in immunocompromised (66.7%) and immunocompetent (69.2%) patients with respiratory symptoms (Table 1) . Same authors indicated a mean age of 1.8 years Table 2 Detection of multiple pathogens in the respiratory tract of the overall study population (a) as well as of immunocompromised (b) and immunocompetent (c) patients. abstract: Respiratory tract infections (RTI) can take a serious course under immunosuppression. Data on the impact of the underlying pathogens are still controversial. Samples from the upper (n = 322) and lower RT (n = 169) were collected from 136 children and 355 adults; 225 among them have been immunocompromised patients. Exclusion criteria were presence of relevant cultivable microorganisms, C-reactive protein > 20 mg/dl, or procalcitonin > 2.0 ng/ml. Samples were tested by PCR for the presence of herpesviruses (HSV-1/-2; VZV; CMV; HHV6; EBV), adenoviruses, bocaviruses, entero-/rhinoviruses (HRV), parechoviruses, coronaviruses, influenza viruses (IV), parainfluenza viruses as well as for pneumoviruses (HMPV and RSV), and atypical bacteria (Mycoplasma pneumoniae, M.p.; Chlamydia pneumoniae, C.p.). Viral/bacterial genome equivalents were detected in more than two-thirds of specimens. Under immunosuppression, herpesviruses (EBV 30.9%/14.6%, p < 0.001; CMV 19.6%/7.9%, p < 0.001; HSV-1: 14.2%/7.1%, p = 0.012) were frequently observed, mainly through their reactivation in adults. Immunocompromised adults tended to present a higher RSV prevalence (6.4%/2.4%, p = 0.078). Immunocompetent patients were more frequently tested positive for IV (15.0%/5.8%, p = 0.001) and M.p. (6.4%/0.4%, p < 0.001), probably biased due to the influenza pandemic of 2009 and an M.p. epidemic in 2011. About 41.8% of samples were positive for a single pathogen, and among them EBV (19.9%) was most prevalent followed by HRV (18.2%) and IV (16.6%). HSV-2 and C.p. were not found. Marked seasonal effects were observed for HRV, IV, and RSV. Differences in pathogen prevalence were demonstrated between immunocompetent and immunocompromised patients. The exact contribution of some herpesviruses to the development of RTI remains unclear. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-020-03878-9) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/32462500/ doi: 10.1007/s10096-020-03878-9 id: cord-007047-7ty9mxa9 author: Reller, L. Barth title: Implications of New Technology for Infectious Diseases Practice date: 2006-11-15 words: 4095.0 sentences: 190.0 pages: flesch: 38.0 cache: ./cache/cord-007047-7ty9mxa9.txt txt: ./txt/cord-007047-7ty9mxa9.txt summary: Problems with currently available molecular assays include a lack of knowledge about the extent of microbial nucleic acid in "normal" hosts, concentration of agent material in small volume samples, lack of microbiologist expertise, lack of adequate reimbursement, and difficulty with validation based on conventional methods. Infectious diseases clinicians have relied on these expert workers, and Reliable molecular diagnostic tests are not readily available for many infectious agents Commercial tests should only be used for validated specimen types Transportation problems, low concentrations of infectious agent, primer binding site genetic changes, final assay volume, inhibition, contamination, nonspecific amplification, and operator error lead to false-negative and false-positive amplification results Genomic bacterial sequencing is subject to error because of sequence homology among different bacteria, database problems, and mutations A number of nucleic acid hybridization and amplification methods are now in use, including direct probe hybridization (AdvanDx FISH for Staphylococcus aureus [AdvanDx] and GenProbe for group A streptococci [GenProbe]), hybrid capture (Digene for human papillomavirus; Digene), PCR, branched-chain DNA (bDNA; Bayer Diagnostics), and transcription-mediated amplification (Probe-Tec for Chlamydia and N. abstract: New assays for the diagnosis of infectious diseases—particularly those that use molecular technologies—will revolutionize infectious diseases practices, but the fulfillment of the promise is several years away. Problems with currently available molecular assays include a lack of knowledge about the extent of microbial nucleic acid in “normal” hosts, concentration of agent material in small volume samples, lack of microbiologist expertise, lack of adequate reimbursement, and difficulty with validation based on conventional methods. Clinicians must appreciate the shortcomings of new technology to use it effectively and appropriately. However, we are realizing tangible progress in our ability to detect new etiological agents; the availability of rapid, accurate diagnostic tests for previously difficult infections; and advances into new, human response—based paradigms for diagnostic testing. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107913/ doi: 10.1086/508536 id: cord-254115-hwy962a4 author: Reslova, Nikol title: xMAP Technology: Applications in Detection of Pathogens date: 2017-01-25 words: 11354.0 sentences: 530.0 pages: flesch: 40.0 cache: ./cache/cord-254115-hwy962a4.txt txt: ./txt/cord-254115-hwy962a4.txt summary: xMAP multiplex assays are currently available in various nucleic acid and immunoassay formats, enabling simultaneous detection and typing of pathogenic viruses, bacteria, parasites and fungi and also antigen or antibody interception. High-throughput multiplex detection techniques are designed for the rapid, sensitive and specific testing of large numbers of analytes (nucleic acid assays, immunoassays, enzyme assays, or receptor-ligands) in a single biological sample. Although PCR allows multiplex amplification of several targets in a single run xMAP as a methodology represents a significant step forward, and was designed with the aim of creating a high-throughput bioassay platform, enabling rapid, cost-effective, and simultaneous analysis of multiple analytes within a single biological sample. In direct DNA hybridization (DDH), allele-specific primer extension (ASPE), single base chain extension (SBCE), and Oligonucleotide ligation assay (OLA) all the target DNA sequences are amplified in multiplex PCR prior to hybridization to microspheres. abstract: xMAP technology is applicable for high-throughput, multiplex and simultaneous detection of different analytes within a single complex sample. xMAP multiplex assays are currently available in various nucleic acid and immunoassay formats, enabling simultaneous detection and typing of pathogenic viruses, bacteria, parasites and fungi and also antigen or antibody interception. As an open architecture platform, the xMAP technology is beneficial to end users and therefore it is used in various pharmaceutical, clinical and research laboratories. The main aim of this review is to summarize the latest findings and applications in the field of pathogen detection using microsphere-based multiplex assays. url: https://www.ncbi.nlm.nih.gov/pubmed/28179899/ doi: 10.3389/fmicb.2017.00055 id: cord-330800-s91zfzfi author: Reta, Daniel Hussien title: Molecular and Immunological Diagnostic Techniques of Medical Viruses date: 2020-09-04 words: 10548.0 sentences: 574.0 pages: flesch: 43.0 cache: ./cache/cord-330800-s91zfzfi.txt txt: ./txt/cord-330800-s91zfzfi.txt summary: e nucleic acid amplification tests are very popular in the diagnosis of viral infections caused by several viruses, including hepatitis C virus (HCV), human immunodeficiency virus (HIV), dengue virus, Epstein-Barr virus (EBV), influenza viruses, Zika virus (ZIKV), Ebola virus, and coronavirus [26] [27] [28] [29] [30] [31] [32] . Owing to high sensitivity and specificity, short turnaround time for results, and ease of performance [33, 61] , most laboratories across the globe employ real-time PCR for the detection and quantification of medical DNA and RNA viruses in clinical specimens. For example, Co-Diagnostics (Salt Lake City, USA) has developed real-time RT-PCR kit (Logix Smart COVID-19 test) for qualitative detection of nucleic acid from the SARS-CoV-2 in lower respiratory samples (e.g., bronchoalveolar lavage, sputum, and tracheal aspirate) and upper respiratory specimens (e.g., oropharyngeal swabs, nasal swabs, and nasopharyngeal swabs). LAMP is another isothermal nucleic acid amplification method that is extensively utilized for sensitive, specific, rapid, and cost-effective detection of both DNA and RNA viruses in human specimens. abstract: Viral infections are causing serious problems in human population worldwide. The recent outbreak of coronavirus disease 2019 caused by SARS-CoV-2 is a perfect example how viral infection could pose a great threat to global public health and economic sectors. Therefore, the first step in combating viral pathogens is to get a timely and accurate diagnosis. Early and accurate detection of the viral presence in patient sample is crucial for appropriate treatment, control, and prevention of epidemics. Here, we summarize some of the molecular and immunological diagnostic approaches available for the detection of viral infections of humans. Molecular diagnostic techniques provide rapid viral detection in patient sample. They are also relatively inexpensive and highly sensitive and specific diagnostic methods. Immunological-based techniques have been extensively utilized for the detection and epidemiological studies of human viral infections. They can detect antiviral antibodies or viral antigens in clinical samples. There are several commercially available molecular and immunological diagnostic kits that facilitate the use of these methods in the majority of clinical laboratories worldwide. In developing countries including Ethiopia where most of viral infections are endemic, exposure to improved or new methods is highly limited as these methods are very costly to use and also require technical skills. Since researchers and clinicians in all corners of the globe are working hard, it is hoped that in the near future, they will develop good quality tests that can be accessible in low-income countries. url: https://www.ncbi.nlm.nih.gov/pubmed/32908530/ doi: 10.1155/2020/8832728 id: cord-005048-9fs1ienf author: Retief, E. title: Potential Inoculum Sources of Phaeomoniellachlamydospora in South African Grapevine Nurseries date: 2006-06-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Petri disease of grapevine is primarily caused by Phaeomoniella chlamydospora. This pathogen affects mostly young grapevines, but is also implicated in esca disease of older grapevines. Little is known about the disease cycle of this fungus. Infected propagation material was identified as a major means of dissemination of the pathogen. Recently, the pathogen was also detected from soil in South Africa and airborne conidia have been found in vineyards. The aim of this study was to use a molecular detection technique to test different samples collected from nurseries in South Africa at different nursery stages for the presence of P. chlamydospora. A one-tube nested-PCR technique was optimised for detecting P. chlamydospora in DNA extracted from soil, water, callusing medium and grapevine wood. The one-tube nested-PCR was sensitive enough to detect as little as 1 fg of P. chlamydospora genomic DNA from water and 10 fg from wood, callusing medium and soil. PCR analyses of the different nursery samples revealed the presence of several putative 360 bp P. chlamydospora specific bands. Subsequent sequence analyses and/or restriction enzyme digestions of all 360 bp PCR bands confirmed that all bands were P. chlamydospora specific, except for five bands obtained from callusing media and one from water. Phaeomoniella chlamydospora was positively detected in 25% of rootstock cane sections collected from mother blocks, 42% of rootstock cuttings and 16% of scion cuttings collected during grafting, 40% of water samples collected after pre-storage hydration, 67% of water samples collected during grafting, 8% of callusing medium samples and 17% of soil samples collected from mother blocks. These media can therefore be considered as possible inoculum sources of the pathogen during the nursery stages. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088137/ doi: 10.1007/s10658-006-9025-4 id: cord-345903-ggkn1w5y author: Revathidevi, Sundaramoorthy title: APOBEC: A molecular driver in cervical cancer pathogenesis date: 2020-10-07 words: 7008.0 sentences: 366.0 pages: flesch: 44.0 cache: ./cache/cord-345903-ggkn1w5y.txt txt: ./txt/cord-345903-ggkn1w5y.txt summary: In general, APOBEC3 enzymes play a pivotal role in the deamination of cytidines to uracil in DNA and RNA to control diverse biological processes such as regulation of protein expression, innate immunity, and embryonic development. Innate antiviral activity of the APOBEC3 family members restrict retroviruses, endogenous retro-element, and DNA viruses including the HPV that is the leading risk factor for cervical cancer. Most HPV infections are cleared within months by the immune system but a few high-risk subtypes like HPV16 and HPV18 persist and express viral oncogenes E6 and E7 which lead to increased genomic instability, accumulation of somatic mutations, and integration of HPV into the host genome resulting in cervical cancer [3] . In relevance to persistent HPV infection and cervical carcinogenesis, a family of APOBEC enzymes with DNA/RNA editing capability has been analyzed as they are involved in various immune functions including restriction of viral replication, antigen presentation, and maturation of host immune receptors and are highly polymorphic in nature [79] . abstract: Cervical cancer is one of the foremost common cancers in women. Human papillomavirus (HPV) infection remains a major risk factor of cervical cancer. In addition, numerous other genetic and epigenetic factors also are involved in the underlying pathogenesis of cervical cancer. Recently, it has been reported that apolipoprotein B mRNA editing enzyme catalytic polypeptide like (APOBEC), DNA-editing protein plays an important role in the molecular pathogenesis of cancer. Particularly, the APOBEC3 family was shown to induce tumor mutations by aberrant DNA editing mechanism. In general, APOBEC3 enzymes play a pivotal role in the deamination of cytidines to uracil in DNA and RNA to control diverse biological processes such as regulation of protein expression, innate immunity, and embryonic development. Innate antiviral activity of the APOBEC3 family members restrict retroviruses, endogenous retro-element, and DNA viruses including the HPV that is the leading risk factor for cervical cancer. This review briefly describes the pathogenesis of cervical cancer and discusses in detail the recent findings on the role of APOBEC in the molecular pathogenesis of cervical cancer. url: https://doi.org/10.1016/j.canlet.2020.10.004 doi: 10.1016/j.canlet.2020.10.004 id: cord-001732-4eyn7pjq author: Riede, O title: Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine date: 2015-04-30 words: 6339.0 sentences: 336.0 pages: flesch: 49.0 cache: ./cache/cord-001732-4eyn7pjq.txt txt: ./txt/cord-001732-4eyn7pjq.txt summary: Evaluation of single-dose and repeated-dose toxicity of the vaccine candidate after i.d. administration to naive, non-infected mice did not reveal any safety concerns. To assess toxicity of LEISHDNAVAX in naive mice, sterile phosphate-buffered saline (PBS, placebo) and ascending doses of the vaccine were injected either once or five times in weekly intervals (Table 1) . Twenty-four hour after single or repeated injection, MIDGE-Th1 vector DNA was detected in almost all organs and tissues examined, suggesting that it was distributed systemically, most likely via the lymphatic system and the blood stream. Groups of 10 BALB/c mice (5 male, 5 female) were immunized i.d. at the tail base five times in weekly intervals with either PBS or LEISHDNAVAX (10, 50 or 100 μg per dose). In summary, we have shown here that LEISHDNAVAX, a novel DNA vaccine candidate against leishmaniasis is safe and well tolerated in both naive and Leishmania-infected mice. abstract: The leishmaniases are a complex of vector-borne diseases caused by protozoan parasites of the genus Leishmania. LEISHDNAVAX is a multi-antigen, T-cell epitope-enriched DNA vaccine candidate against human leishmaniasis. The vaccine candidate has been proven immunogenic and showed prophylactic efficacy in preclinical studies. Here, we describe the safety testing of LEISHDNAVAX in naive mice and rats, complemented by the demonstration of tolerability in Leishmania-infected mice. Biodistribution and persistence were examined following single and repeated intradermal (i.d.) administration to rats. DNA vectors were distributed systemically but did not accumulate upon repeated injections. Although vector DNA was cleared from most other tissues within 60 days after the last injection, it persisted in skin at the site of injection and in draining lymph nodes. Evaluation of single-dose and repeated-dose toxicity of the vaccine candidate after i.d. administration to naive, non-infected mice did not reveal any safety concerns. LEISHDNAVAX was also well tolerated in Leishmania-infected mice. Taken together, our results substantiate a favorable safety profile of LEISHDNAVAX in both naive and infected animals and thus, support the initiation of clinical trials for both preventive and therapeutic applications of the vaccine. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530203/ doi: 10.1038/gt.2015.35 id: cord-009261-97qegnlo author: Rieux, Charlotte title: Thiopurine Derivative-Induced Fpg/Nei DNA Glycosylase Inhibition: Structural, Dynamic and Functional Insights date: 2020-03-17 words: 11719.0 sentences: 574.0 pages: flesch: 52.0 cache: ./cache/cord-009261-97qegnlo.txt txt: ./txt/cord-009261-97qegnlo.txt summary: Among forty compounds, four TXn were better inhibitors than 2TX for Fpg. Unexpectedly, but very interestingly, two dithiolated derivatives more selectively and efficiently inhibit the zincless finger (ZnLF)-containing enzymes (human and mimivirus Neil1 DNA glycosylases hNeil1 and MvNei1, respectively). The crystal structure of LlFpg bound to 14-mer [8-oxoG:C] DNA duplex (which differs from that used in this study only by the damaged nature present in the duplex: an 8-oxoG lesion in place of THF) revealed that the second Fpg molecule can bind to the overhanging base positioned at the 5 end of the damaged strand ( Figure S5b ) [38] . Similar to the 2TX-containing crystal structure, the intramolecular disulfide bridge Cys245-S-S-Cys265 is also formed in the presence of TXn. Not observed previously, one 2TX molecule that is non-covalently bound to the enzyme is inserted at the protein-DNA interface in the vicinity of the ZnF loop and the H2TH motif (Figure 10a,b) , the two DNA binding domains that characterize the Fpg/Nei DNA glycosylase superfamily [29] . abstract: DNA glycosylases are emerging as relevant pharmacological targets in inflammation, cancer and neurodegenerative diseases. Consequently, the search for inhibitors of these enzymes has become a very active research field. As a continuation of previous work that showed that 2-thioxanthine (2TX) is an irreversible inhibitor of zinc finger (ZnF)-containing Fpg/Nei DNA glycosylases, we designed and synthesized a mini-library of 2TX-derivatives (TXn) and evaluated their ability to inhibit Fpg/Nei enzymes. Among forty compounds, four TXn were better inhibitors than 2TX for Fpg. Unexpectedly, but very interestingly, two dithiolated derivatives more selectively and efficiently inhibit the zincless finger (ZnLF)-containing enzymes (human and mimivirus Neil1 DNA glycosylases hNeil1 and MvNei1, respectively). By combining chemistry, biochemistry, mass spectrometry, blind and flexible docking and X-ray structure analysis, we localized new TXn binding sites on Fpg/Nei enzymes. This endeavor allowed us to decipher at the atomic level the mode of action for the best TXn inhibitors on the ZnF-containing enzymes. We discovered an original inhibition mechanism for the ZnLF-containing Fpg/Nei DNA glycosylases by disulfide cyclic trimeric forms of dithiopurines. This work paves the way for the design and synthesis of a new structural class of inhibitors for selective pharmacological targeting of hNeil1 in cancer and neurodegenerative diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139703/ doi: 10.3390/ijms21062058 id: cord-007613-g4s0v8ra author: Rimstad, Espen title: Cloning, expression and characterization of biologically active feline tumour necrosis factor-α date: 2000-03-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We report the cloning, expression and characterization of biologically active feline tumour necrosis factor-α (fTNF-α). Messenger RNA was extracted from feline peritoneal macrophage cultures and used to synthesize cDNA for polymerase chain reaction (PCR) amplification. The PCR products were cloned into the plasmid vector pCRII and sequenced, showing 99.3% homology with a published fTNF-α gene sequence. Subcloning into the vector pGEX-2T and subsequent expression resulted in a 43 kDa fusion protein of fTNF-α and glutathione S-transferase (GST). Thrombin cleavage of the fusion protein yielded a 17 kDa protein. This protein cross-reacted with a monoclonal anti-human TNF-α antibody in Western blotting, but not with a polyclonal anti-murine TNF-α serum. Recombinant fTNF-α (rfTNF-α) and rfTNF-α-GST had a CD(50) of 15 ng ml(−1) and 230 ng ml(−1), respectively, in the L929 cytotoxicity assay. Cats given rfTNF-α-GST intravenously manifested the typical biological effects of TNF-α, including fever, depression, and piloerection. The rfTNF-α-GST upregulated IL-2 receptor and MHC-II antigen expression on peripheral blood mononuclear cells stimulated in vitro, but had no effect on TNF-α receptor and MHC-I antigen expression. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119607/ doi: 10.1016/0165-2427(94)05345-s id: cord-022336-zqnczjpp author: Robertson, Hugh D. title: Virus Origins: Conjoined RNA Genomes as Precursors to DNA Genomes date: 2007-09-02 words: 6163.0 sentences: 229.0 pages: flesch: 47.0 cache: ./cache/cord-022336-zqnczjpp.txt txt: ./txt/cord-022336-zqnczjpp.txt summary: The chapter also outlines the significance of work on viroid-like pathogens, circular RNA replication, and their potential relation to early RNA; and relates the early emergence of RNA mosaics to developments leading to today''s DNA-based systems of viral gene expression. Recent work to be reviewed below shows that there is one class of primitive life forms-the viroid-like pathogens -whose properties today could help us to understand how primitive RNA-based self-replication may have been compatible with expansion to produce more complex RNAs. In summary, the causative agent for human hepatitis delta contains two specialized domains, one concerned with replication and the other encoding a single protein (Branch et al., 1989; Purcell and Gerin, 1996; Taylor, 1996) . It is evident that if RNA conjunction leading to delta-like RNA mosaics with both replicating and functionally translatable protein-coding domains has taken place, we need to consider the consequences both for the evolution of primitive RNA systems, yielding today''s DNA-based cellular information system, and for presentday RNA-level events. abstract: RNA's unprecedented ability to act both as a template for information storage and as an enzymatic molecule has led to the proposal that primitive living systems were based on RNA, with protein synthesis and DNA templates for information storage added later. This chapter reviews the current knowledge about RNA rearrangement and recombination in viruses, and cites evidence for various mechanisms catalyzing these events. RNA recombination can occur in a spontaneous manner, and such a potential, even at low frequency, would expand opportunities for RNA conjunction. The chapter also outlines the significance of work on viroid-like pathogens, circular RNA replication, and their potential relation to early RNA; and relates the early emergence of RNA mosaics to developments leading to today's DNA-based systems of viral gene expression. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155586/ doi: 10.1016/b978-012220360-2/50003-9 id: cord-350019-4nlbu54e author: Robinson, Elektra K. title: The how and why of lncRNA function: An innate immune perspective() date: 2019-09-02 words: 13173.0 sentences: 715.0 pages: flesch: 44.0 cache: ./cache/cord-350019-4nlbu54e.txt txt: ./txt/cord-350019-4nlbu54e.txt summary: Using this extensively studied biological system, we identified the first example of a TLR-stimulated lncRNA, lincRNA-Cox2, which was capable of positively and negatively regulating distinct types of innate immune genes [42] [43] [44] [45] [46] . The majority of lncRNAs studied in immunity were initially identified following RNA-sequencing to examine their expression profiles in specific cell lines or tissues during inflammatory activation. Hence future studies may opt to target TF binding sites, secondary structure and/or polyadenylation sites as a way to more finely dissect the functional portions of lncRNAs. The ease in which Cas9 can be targeted to specific genomic regions sparked the development of a modified (catalytically inactivated) version of the protein fused to the KRAB (Krüppel associated box) chromatin-silencing domain termed CRISPRi [174, 175] (Fig. 3C) . Genome-wide screening for functional long noncoding RNAs in human cells by Cas9 targeting of splice sites abstract: Next-generation sequencing has provided a more complete picture of the composition of the human transcriptome indicating that much of the “blueprint” is a vastness of poorly understood non-protein-coding transcripts. This includes a newly identified class of genes called long noncoding RNAs (lncRNAs). The lack of sequence conservation for lncRNAs across species meant that their biological importance was initially met with some skepticism. LncRNAs mediate their functions through interactions with proteins, RNA, DNA, or a combination of these. Their functions can often be dictated by their localization, sequence, and/or secondary structure. Here we provide a review of the approaches typically adopted to study the complexity of these genes with an emphasis on recent discoveries within the innate immune field. Finally, we discuss the challenges, as well as the emergence of new technologies that will continue to move this field forward and provide greater insight into the biological importance of this class of genes. This article is part of a Special Issue entitled: ncRNA in control of gene expression edited by Kotb Abdelmohsen. url: https://www.ncbi.nlm.nih.gov/pubmed/31487549/ doi: 10.1016/j.bbagrm.2019.194419 id: cord-293421-0ksn0fc7 author: Rodriguez, J. M. title: Detection of animal pathogens by using the polymerasechain reaction (PCR) date: 1997-05-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Summary The polymerase chain reaction (PCR) is a nucleic acid-based technique that enables the rapid and sensitive detection of specific micro-organisms. Although this technique is widely used in veterinary research, it has not yet found applications in routine microbiological analysis of veterinary clinical samples. However, advances in sample preparation together with the increasing availability of specific gene sequences will probably lead to the more widespread diagnostic use of PCR in the future. PCR is likely to have a strong impact in the epidemiology, treatment and prevention of animal infectious diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/9232118/ doi: 10.1016/s1090-0233(97)80063-9 id: cord-258623-9evwcs32 author: Roembke, Benjamin T. title: Nucleic acid detection using G-quadruplex amplification methodologies date: 2013-12-15 words: 4218.0 sentences: 235.0 pages: flesch: 58.0 cache: ./cache/cord-258623-9evwcs32.txt txt: ./txt/cord-258623-9evwcs32.txt summary: Willner and co-workers also reported nucleic acid detection using a symmetric split G-quadruplex probe but instead of DAB, the Willner group used luminol as a reductant for a luminescent readout (Fig. 3 ) [22] . Wang and co-workers have described an interesting ''''split'''' molecular beacon G-quadruplex probe that can be used to detect DNA or thrombin (a dual probe, Fig. 12 ) [31] . When there is no target DNA, and both molecular beacons are intact, the probe can form a complete G-quadruplex, resulting in an active DNAzyme peroxidase. To create a turn on probe the authors used the blocker DNA in a twostep amplification process, in which the blocker DNA would lose affinity for the MB and bind the DNA analyte of interest resulting in the molecular beacon refolding and forming an active G-quadruplex peroxidase. Willner and co-workers showed that upon binding of a target to a MB G-quadruplex probe that was attached to a gold electrode, a G-quadruplex forms. abstract: Abstract In the last decade, there has been an explosion in the use of G-quadruplex labels to detect various analytes, including DNA/RNA, proteins, metals and other metabolites. In this review, we focus on strategies for the detection of nucleic acids, using G-quadruplexes as detection labels or as enzyme labels that amplify detection signals. Methods to detect other analytes are briefly mentioned. We highlight various strategies, including split G-quadruplex, hemin–G-quadruplex conjugates, molecular beacon G-quadruplex or inhibited G-quadruplex probes. The tandem use of G-quadruplex labels with various DNA-modifying enzymes, such as polymerases (used for rolling circle amplification), exonucleases and endonucleases, is also discussed. Some of the detection modalities that are discussed in this review include fluorescence, colorimetric, chemiluminescence, and electrochemical methods. url: https://www.sciencedirect.com/science/article/pii/S104620231300399X doi: 10.1016/j.ymeth.2013.10.003 id: cord-307909-7vbxyns0 author: Ronda, Luca title: Rational Design of a User-Friendly Aptamer/Peptide-Based Device for the Detection of Staphylococcus aureus date: 2020-09-02 words: 9356.0 sentences: 417.0 pages: flesch: 43.0 cache: ./cache/cord-307909-7vbxyns0.txt txt: ./txt/cord-307909-7vbxyns0.txt summary: We coupled the selectivity and affinity of aptamers, short nucleic acids sequences able to recognize specific epitopes on bacterial surface, immobilized at high density on a nanostructured zirconium dioxide surface, with the rational design of specifically interacting fluorescent peptides to assemble an easy-to-use detection device. λ-Cro is a 66 aa protein that plays a pivotal role in the switch from lysogenic to lytic phase in the growth cycle of phage λ and represented a suitable scaffold for several reasons: (i) the availability of threedimensional structures both in the presence and absence of its cognate DNA (PDB ID: 6cro [60] and 5cro [80] , respectively) allows detailed structural evaluations; (ii) the helix-turn-helix motif of the DNA binding domain is relatively small and all the interactions between the nucleobases of the consensus sequence and the peptidic backbone are well characterized; (iii) the minimum functional portion of the consensus sequence is quite short and made by contiguous nucleobases along the two strands of the DNA target; (iv) previous works reported successful examples of Cro reprogramming for binding consensus sequences that differ from the wild type [79] . abstract: The urgent need to develop a detection system for Staphylococcus aureus, one of the most common causes of infection, is prompting research towards novel approaches and devices, with a particular focus on point-of-care analysis. Biosensors are promising systems to achieve this aim. We coupled the selectivity and affinity of aptamers, short nucleic acids sequences able to recognize specific epitopes on bacterial surface, immobilized at high density on a nanostructured zirconium dioxide surface, with the rational design of specifically interacting fluorescent peptides to assemble an easy-to-use detection device. We show that the displacement of fluorescent peptides upon the competitive binding of S. aureus to immobilized aptamers can be detected and quantified through fluorescence loss. This approach could be also applied to the detection of other bacterial species once aptamers interacting with specific antigens will be identified, allowing the development of a platform for easy detection of a pathogen without requiring access to a healthcare environment. url: https://www.ncbi.nlm.nih.gov/pubmed/32887407/ doi: 10.3390/s20174977 id: cord-347472-n6811ens author: Rosebrock, Adam P. title: Patient DNA cross-reactivity of the CDC SARS-CoV-2 extraction control leads to an inherent potential for false negative results date: 2020-05-15 words: 6252.0 sentences: 344.0 pages: flesch: 51.0 cache: ./cache/cord-347472-n6811ens.txt txt: ./txt/cord-347472-n6811ens.txt summary: The US Centers for Disease Control and Prevention (CDC) have specified and given emergency use authorization (EUA) for a SARS-CoV-2 molecular diagnostic used to detect viral RNA in clinical samples (2) . Genomic DNA is co-purified in quantities sufficient to generate strong positive signals for the CDC-specified extraction control during work-up of clinical RNA specimens. To test for the presence of control-affecting DNA, qPCR reactions lacking reverse transcriptase were performed on SARS-CoV-2-positive clinical samples using the CDC-specified RP primer and probe. All clinical samples tested generated unambiguous extraction control positive signals in the absence of reverse transcription, a reaction context that could not have detected virus an RNA virus ( Fig. 2A) Single-digit copies of genomic DNA are sufficient to generate a positive control signal using the CDC-designed assay. Due to the presence of co-purifying genomic DNA in clinical samples, loss of RNA integrity leads to false-negative results using the CDC-specified control. abstract: Testing for RNA viruses such as SARS-CoV-2 requires careful handling of inherently labile RNA during sample collection, clinical processing, and molecular analysis. Tests must include fail-safe controls that affirmatively report the presence of intact RNA and demonstrate success of all steps of the assay. A result of “no virus signal” is insufficient for clinical interpretation: controls must also say “The reaction worked as intended and would have found virus if present.” Unfortunately, a widely used test specified by the US Centers for Disease Control and Prevention (CDC) incorporates a control that does not perform as intended and claimed. Detecting SARS-CoV-2 with this assay requires both intact RNA and successful reverse transcription. The CDC-specified control does not require either of these, due to its inability to differentiate human genomic DNA from reverse-transcribed RNA. Patient DNA is copurified from nasopharyngeal swabs during clinically-approved RNA extraction and is sufficient to return an “extraction control success” signal using the CDC design. As such, this assay fails-unsafe: truly positive patient samples return a false-negative result of “no virus detected, control succeeded” following any of several readily-encountered mishaps. This problem affects tens-of-millions of patients worth of shipped assays, but many of these flawed reagents have not yet been used. There is an opportunity to improve this important diagnostic tool. As demonstrated here, a re-designed transcript-specific control correctly monitors sample collection, extraction, reverse transcription, and qPCR detection. This approach can be rapidly implemented and will help reduce truly positive patients from being incorrectly given the all-clear. One Sentence Summary A widely-used COVID-19 diagnostic is mis-designed and generates false-negative results, dangerously confusing “No” with “Don’t know” – but it’s fixable url: https://doi.org/10.1101/2020.05.13.094839 doi: 10.1101/2020.05.13.094839 id: cord-030028-s6sxi8uj author: Rubio, Luis title: Detection of Plant Viruses and Disease Management: Relevance of Genetic Diversity and Evolution date: 2020-07-17 words: 14687.0 sentences: 698.0 pages: flesch: 40.0 cache: ./cache/cord-030028-s6sxi8uj.txt txt: ./txt/cord-030028-s6sxi8uj.txt summary: This technique has been used to differentiate isolates of some plant viruses, such as prunus necrotic ringspot virus (PNRSV), TYLCV and CTV (Gillings et al., 1993; Hammond et al., 1998; Font et al., 2007) ; iii) Single-strand conformation polymorphism (SSCP) analysis is based on electrophoresis of denatured dsDNA in non-denaturing gels so migration of single-stranded DNA depends on its conformation determined by its nucleotide sequence and the electrophoretic conditions. This technique followed by sequencing of the different haplotypes detected has been used to evaluate the genetic variation of some plant viruses, such as cucumber mosaic virus (CMV), citrus psorosis virus (CPsV) and CTV (Rubio et al., 1996; Rubio et al., 1999; Vives et al., 2002; Lin et al., 2003; Martıń et al., 2006) . Procedures to detect and identify various viruses or virus strains in a single assay simultaneously reduce time and cost of the analysis (see Pallaś et al., 2018 for a comprehensive review), and are especially suitable for evaluating mixed infections in individual plants. abstract: Plant viruses cause considerable economic losses and are a threat for sustainable agriculture. The frequent emergence of new viral diseases is mainly due to international trade, climate change, and the ability of viruses for rapid evolution. Disease control is based on two strategies: i) immunization (genetic resistance obtained by plant breeding, plant transformation, cross-protection, or others), and ii) prophylaxis to restrain virus dispersion (using quarantine, certification, removal of infected plants, control of natural vectors, or other procedures). Disease management relies strongly on a fast and accurate identification of the causal agent. For known viruses, diagnosis consists in assigning a virus infecting a plant sample to a group of viruses sharing common characteristics, which is usually referred to as species. However, the specificity of diagnosis can also reach higher taxonomic levels, as genus or family, or lower levels, as strain or variant. Diagnostic procedures must be optimized for accuracy by detecting the maximum number of members within the group (sensitivity as the true positive rate) and distinguishing them from outgroup viruses (specificity as the true negative rate). This requires information on the genetic relationships within-group and with members of other groups. The influence of the genetic diversity of virus populations in diagnosis and disease management is well documented, but information on how to integrate the genetic diversity in the detection methods is still scarce. Here we review the techniques used for plant virus diagnosis and disease control, including characteristics such as accuracy, detection level, multiplexing, quantification, portability, and designability. The effect of genetic diversity and evolution of plant viruses in the design and performance of some detection and disease control techniques are also discussed. High-throughput or next-generation sequencing provides broad-spectrum and accurate identification of viruses enabling multiplex detection, quantification, and the discovery of new viruses. Likely, this technique will be the future standard in diagnostics as its cost will be dropping and becoming more affordable. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380168/ doi: 10.3389/fpls.2020.01092 id: cord-271241-w1q46y63 author: Ruggiero, Emanuela title: Viral G-quadruplexes: New frontiers in virus pathogenesis and antiviral therapy date: 2020-05-18 words: 8912.0 sentences: 495.0 pages: flesch: 45.0 cache: ./cache/cord-271241-w1q46y63.txt txt: ./txt/cord-271241-w1q46y63.txt summary: Since the genomes of viruses are remarkably variable, high conservation rates strongly suggest a crucial role of G4s in the viral replication cycle and evolution, emphasizing the possibility of targeting viral G4s as a new pharmacological approach in antiviral therapy. 1 In the past few decades, pharmaceutical and biotechnological advance has succeeded in developing new therapeutics for the management of different viral diseases: for example, anti-retroviral therapy against the human immunodeficiency virus (HIV), or the pan-genotypic direct-acting antiviral drugs used for hepatitis C (HCV) management. In addition, such PQSs are highly conserved, despite the high recombination rates that characterize viruses, suggesting a crucial role for G4s in viral evolution and replication, and corroborating their targeting as a valid pharmacological approach for antiviral therapy. abstract: Viruses are the most abundant organisms on our planet, affecting all living beings: some of them are responsible for massive epidemics that concern health, national economies and the overall welfare of societies. Although advances in antiviral research have led to successful therapies against several human viruses, still some of them cannot be eradicated from the host and most of them do not have any treatment available. Consequently, innovative antiviral therapies are urgently needed. In the past few years, research on G-quadruplexes (G4s) in viruses has boomed, providing powerful evidence for the regulatory role of G4s in key viral steps. Comprehensive bioinformatics analyses have traced putative G4-forming sequences in the genome of almost all human viruses, showing that their distribution is statistically significant and their presence highly conserved. Since the genomes of viruses are remarkably variable, high conservation rates strongly suggest a crucial role of G4s in the viral replication cycle and evolution, emphasizing the possibility of targeting viral G4s as a new pharmacological approach in antiviral therapy. Recent studies have demonstrated the formation and function of G4s in pathogens responsible for serious diseases, such as HIV-1, Hepatitis B and C, Ebola viruses, to cite a few. In this chapter, we present the state of the art on the structural and functional characterization of viral G4s in RNA viruses, DNA viruses and retroviruses. We also present the G4 ligands that provide further details on the viral G4 role and which, showing promising antiviral activity, which could be exploited for the development of innovative antiviral agents. url: https://api.elsevier.com/content/article/pii/S0065774320300142 doi: 10.1016/bs.armc.2020.04.001 id: cord-319116-2ts6zpdb author: Ruggiero, Emanuela title: G-quadruplexes and G-quadruplex ligands: targets and tools in antiviral therapy date: 2018-04-20 words: 9124.0 sentences: 410.0 pages: flesch: 42.0 cache: ./cache/cord-319116-2ts6zpdb.txt txt: ./txt/cord-319116-2ts6zpdb.txt summary: Since the number of reports describing the presence of G4s in virus genomes has boomed in the past 2 years and treatment with several G4 ligands has shown potentially interesting therapeutic activity, we here aim at presenting, organizing and discussing an up-to-date close-up of the literature on G4s in viruses and the classes of molecules that have shown antiviral activity by viral G4 targeting. The research of G4s in the HIV-1 genome has been quite productive, concerning not only the two RNA viral genome copies, but also the integrated proviral genome, specifically For each virus the following information is shown: virion structure and dimension, genome size and organization; schematic representation of the G4 (red dots) location in the viral genomes or in the mRNA and G4 binding proteins; number of G4s assessed through bioinformatics analysis, according to the corresponding references; G4 ligands reported to date to display antiviral effect and corresponding references. abstract: G-quadruplexes (G4s) are non-canonical nucleic acids secondary structures that form within guanine-rich strands of regulatory genomic regions. G4s have been extensively described in the human genome, especially in telomeres and oncogene promoters; in recent years the presence of G4s in viruses has attracted increasing interest. Indeed, G4s have been reported in several viruses, including those involved in recent epidemics, such as the Zika and Ebola viruses. Viral G4s are usually located in regulatory regions of the genome and implicated in the control of key viral processes; in some cases, they have been involved also in viral latency. In this context, G4 ligands have been developed and tested both as tools to study the complexity of G4-mediated mechanisms in the viral life cycle, and as therapeutic agents. In general, G4 ligands showed promising antiviral activity, with G4-mediated mechanisms of action both at the genome and transcript level. This review aims to provide an updated close-up of the literature on G4s in viruses. The current state of the art of G4 ligands in antiviral research is also reported, with particular focus on the structural and physicochemical requirements for optimal biological activity. The achievements and the to-dos in the field are discussed. url: https://www.ncbi.nlm.nih.gov/pubmed/29554280/ doi: 10.1093/nar/gky187 id: cord-274080-884x48on author: Rumlová, Michaela title: In vitro methods for testing antiviral drugs date: 2018-06-30 words: 17989.0 sentences: 941.0 pages: flesch: 41.0 cache: ./cache/cord-274080-884x48on.txt txt: ./txt/cord-274080-884x48on.txt summary: For the majority of animal viruses, the activation of these fusion or penetration mechanisms occurs through conformational changes and structural rearrangements in viral surface proteins and/or the whole virion shell that may destabilize the capsid core. D: Three mechanisms (I.-III.) of DNA viruses replication are shown: (I): Following entry and uncoating, the DNA genome is transported to the nucleus; products of early genes (regulatory proteins, transcription factors) regulate the synthesis of viral enzymes (e.g. DNA polymerase) required for genome replication; expression of late genes encoding structural capsid proteins in the cytosol, they are then transported into nucleus where packaging and pre-assembly take place; preassembled procapsids exit the nucleus and leave the cell (e.g. Herpesviruses). Here, we provide an overview of in vitro methods, including cell-based assays, that may be suitable for screening of antivirotics that interfere with the key steps of viral life cycles and target either virus or cell-encoded proteins required for the infectivity. abstract: Abstract Despite successful vaccination programs and effective treatments for some viral infections, humans are still losing the battle with viruses. Persisting human pandemics, emerging and re-emerging viruses, and evolution of drug-resistant strains impose continuous search for new antiviral drugs. A combination of detailed information about the molecular organization of viruses and progress in molecular biology and computer technologies has enabled rational antivirals design. Initial step in establishing efficacy of new antivirals is based on simple methods assessing inhibition of the intended target. We provide here an overview of biochemical and cell-based assays evaluating the activity of inhibitors of clinically important viruses. url: https://www.ncbi.nlm.nih.gov/pubmed/29292156/ doi: 10.1016/j.biotechadv.2017.12.016 id: cord-302880-sizk6mk6 author: Rummun, Nawraj title: Terminalia bentzoë, a Mascarene Endemic Plant, Inhibits Human Hepatocellular Carcinoma Cells Growth In Vitro via G0/G1 Phase Cell Cycle Arrest date: 2020-10-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Tropical forests constitute a prolific sanctuary of unique floral diversity and potential medicinal sources, however, many of them remain unexplored. The scarcity of rigorous scientific data on the surviving Mascarene endemic taxa renders bioprospecting of this untapped resource of utmost importance. Thus, in view of valorizing the native resource, this study has as its objective to investigate the bioactivities of endemic leaf extracts. Herein, seven Mascarene endemic plants leaves were extracted and evaluated for their in vitro antioxidant properties and antiproliferative effects on a panel of cancer cell lines, using methyl thiazolyl diphenyl-tetrazolium bromide (MTT) and clonogenic cell survival assays. Flow cytometry and comet assay were used to investigate the cell cycle and DNA damaging effects, respectively. Bioassay guided-fractionation coupled with liquid chromatography mass spectrometry (MS), gas chromatography-MS, and nuclear magnetic resonance spectroscopic analysis were used to identify the bioactive compounds. Among the seven plants tested, Terminalia bentzoë was comparatively the most potent antioxidant extract, with significantly (p < 0.05) higher cytotoxic activities. T. bentzoë extract further selectively suppressed the growth of human hepatocellular carcinoma cells and significantly halted the cell cycle progression in the G0/G1 phase, decreased the cells’ replicative potential and induced significant DNA damage. In total, 10 phenolic compounds, including punicalagin and ellagic acid, were identified and likely contributed to the extract’s potent antioxidant and cytotoxic activities. These results established a promising basis for further in-depth investigations into the potential use of T. bentzoë as a supportive therapy in cancer management. url: https://doi.org/10.3390/ph13100303 doi: 10.3390/ph13100303 id: cord-020969-lh2ergpm author: STRAUSS, JAMES H. title: Gene Therapy date: 2012-07-27 words: 11793.0 sentences: 597.0 pages: flesch: 52.0 cache: ./cache/cord-020969-lh2ergpm.txt txt: ./txt/cord-020969-lh2ergpm.txt summary: Together with methods for cloning and manipulating viral genomes, this information has made possible the use of viruses as vectors to express foreign genes. The use of minus-strand RNA viruses as vectors was delayed because the virion RNA itself is not infectious, but recent developments has made it possible to rescue virus from cloned DNA by using coexpression of the appropriate viral proteins in a transfected cell. It is also possible to transfect cells with the E1 or E3 expression cassette together with DNA clones encoding the rest of the adenovirus genome, in which case homologous recombination results in the production of virus. Because the poliovirus replicon lacks a full complement of the structural genes (it is a suicide vector), packaging to produce particles requires infection of a cell that expresses the polioviral structural proteins by some mechanism. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148746/ doi: 10.1016/b978-0-12-373741-0.50014-3 id: cord-341634-mpk8mmp8 author: Sadana, Ajit title: Detection of Analytes on Arrays/Microarrays/DNA Chips date: 2010-09-02 words: 11089.0 sentences: 563.0 pages: flesch: 62.0 cache: ./cache/cord-341634-mpk8mmp8.txt txt: ./txt/cord-341634-mpk8mmp8.txt summary: In this chapter we use fractal analysis to analyze (a) the binding and dissociation (hybridization) of different targets (400 nM) in solution to a probe immobilized on a DNA chip surface (Fiche et al., 2007) , (b) binding (hybridization) of different concentrations (in nM) of free-DNA in solution to a 22-mer strand (bound DNA) immobilized via a phenylene-diisocyanate linker molecule on a glass substrate (Michel et al., 2007) , (c) binding (hybridization) of SA-HRP (streptavidin-horseradish peroxide) in solution to a capture probe on a QCM (quartz crystal microbalance) electrode along with a detection probe (Feng et al., 2007) , (d) binding (hybridization) of a complementary and a noncomplementary (three-base mismatch strand) DNA in solution to a 30-mer 3 0 -thiolated DNA strand immobilized on an electrochemical enzymatic genosensor (Abad-Valle et al., 2007a,b) , (e) binding (hybridization) of (i) a perfectly matched oligonucleotide (ODN-P) and (ii) a noncomplementary ODN (ODN-N) to an electrochemical sensor with a EST2-A34 reporter (Wang et al., 2007) , (f) binding and dissociation during PNA-DNA hybridization-binding of different concentrations (in mM) of target DNA complementary to CYP2C9*2 (target DNA2) to CYP2C9*2 as a probe PNA immobilized on a ionsensitive field-effect transistor (IS-FET)-based biosensor (Uno et al., 2007) , (g) binding and dissociation during PNA-DNA hybridization-binding of different concentrations (in mM) of target DNA complementary to CYP2C9*2 (target DNA2) to CYP2C9*2 as a probe PNA immobilized on an IS-FET-based biosensor (Uno et al., 2007) , (h) binding and dissociation of RNA synthesized on a (i) 42 nM template and a (ii) 420 nM template (Blair et al., 2007) , and (i) binding (hybridization) of different concentrations of ss DNA in solution preincubated with prehybridized 22-nt FQ duplex to a "broken beacon" immobilized on a sensor surface (Blair et al., 2007) . abstract: Microarrays/arrays/DNA chips are frequently being used to detect different analytes in biosensors. This chapter analyzes the detection of different analytes on microarrays/arrays/DNA chips and analyzes the kinetics of binding and dissociation (hybridization) in such biosensors through fractal analysis. Both single- and dual-fractal analysis are used to analyze binding (hybridization) of different targets (400 nM) in solution to a probe immobilized on a DNA chip surface, binding (hybridization) of different concentrations of free-DNA in solution to a 22-mer strand (bound DNA) immobilized via a phenylene-diisocyanate linker molecule on a glass substrate, SA-HRP (streptavidin-horseradish peroxide) in solution to a capture probe on a QCM (quartz crystal microbalance) electrode along with a detection probe, a complementary and a noncomplementary (three-base mismatch strand) DNA in solution to a 30-mer 30-thiolated DNA strand immobilized on an electrochemical enzymatic genosensor, binding (hybridization) of a perfectly matched oligonucleotide (ODN-P) and a noncomplementary ODN (ODN-N) to an electrochemical sensor with an EST2-A34 reporter. Fractal analyses are also used to discuss the binding and dissociation during PNA–DNA hybridization, PNA–DNA hybridization, and binding (hybridization) of different concentrations of ss DNA in solution preincubated with prehybridized 22-nt FQ duplex to a “broken beacon” immobilized on a sensor surface. Fractal analysis can be considered as an alternate method of analyzing the kinetics of binding and dissociation during hybridization in these types of analyte–receptor reactions occurring on biosensor surfaces. url: https://api.elsevier.com/content/article/pii/B9780444532626000115 doi: 10.1016/b978-0-444-53262-6.00011-5 id: cord-015850-ef6svn8f author: Saitou, Naruya title: Eukaryote Genomes date: 2013-08-22 words: 7424.0 sentences: 484.0 pages: flesch: 53.0 cache: ./cache/cord-015850-ef6svn8f.txt txt: ./txt/cord-015850-ef6svn8f.txt summary: General overviews of eukaryote genomes are first discussed, including organelle genomes, introns, and junk DNAs. We then discuss the evolutionary features of eukaryote genomes, such as genome duplication, C-value paradox, and the relationship between genome size and mutation rates. Most of the protein coding genes of melon mitochondrial DNAs are highly similar to those of its congeneric species, which are watermelon and squash whose mitochondrial genome sizes are 119 kb and 125 kb, respectively. There are various genomic features that are specifi c to eukaryotes other than existence of introns and junk DNAs, such as genome duplication, RNA editing, C-value paradox, and the relationship between genome size and mutation rates. The Perigord black truffl e ( Tuber melanosporum ), shown as A i n Fig. 8.9 , has the largest genome size (~125 Mb) among the 88 fungi species whose genome sequences were so far determined, yet the number of genes is only ~7,500 [ 81 ] . abstract: General overviews of eukaryote genomes are first discussed, including organelle genomes, introns, and junk DNAs. We then discuss the evolutionary features of eukaryote genomes, such as genome duplication, C-value paradox, and the relationship between genome size and mutation rates. Genomes of multicellular organisms, plants, fungi, and animals are then briefly discussed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119937/ doi: 10.1007/978-1-4471-5304-7_8 id: cord-033054-qaj1f6qq author: Samad, Abdus title: Computational assessment of MCM2 transcriptional expression and identification of the prognostic biomarker for human breast cancer date: 2020-10-01 words: 5008.0 sentences: 247.0 pages: flesch: 42.0 cache: ./cache/cord-033054-qaj1f6qq.txt txt: ./txt/cord-033054-qaj1f6qq.txt summary: Therefore, we aimed to analyze the MCM2 expression and the associated outcome in breast cancer (BC) patients based on the publicly available online databases. In this study, server-based gene expression analyses indicate the upregulation of MCM2 (p < 10(−6); fold change>2.0) in various BC subtypes as compared to the respective normal tissues. The GEPIA2 database contains data from 1,085 tumors and 291 normal tissues related to BC where the type of cancers can be predicted by the query sample based on the intensity of gene expression. The mRNA expression of the MCM2 gene in BC patients was analyzed based on their clinicopathological characteristics in TCGA datasets with the UALCAN server [29, 30] . The results exhibit enhanced expression of MCM2 irrespective of individual cancer stages, patient''s race, gender, age, major subclass with and without different TNBC-type, menopause status, tumor histology, and nodal metastasis depicted in Figure 3 and listed in Table 2 . abstract: Minichromosome maintenance protein 2 (MCM2) is a highly conserved protein from the MCM protein family that plays an important role in eukaryotic DNA replication as well as in cell cycle progression. In addition, it maintains the ploidy level consistency in eukaryotic cells, hence, mutations or alteration of this protein could result in the disintegration of the fine-tuned molecular machinery that can lead to uncontrolled cell proliferation. Moreover, MCM2 has been found to be an important marker for progression and prognosis in different cancers. Therefore, we aimed to analyze the MCM2 expression and the associated outcome in breast cancer (BC) patients based on the publicly available online databases. In this study, server-based gene expression analyses indicate the upregulation of MCM2 (p < 10(−6); fold change>2.0) in various BC subtypes as compared to the respective normal tissues. Besides, the evaluation of histological sections from healthy and cancer tissues showed strong staining signals indicating higher expression of MCM2 protein. The overexpression of MCM2 was significantly correlated to promoter methylation and was related to patients' clinical features. Further, mutation analysis suggested missense as the predominant type of mutation (71.4%) with 18 copy-number alterations and 0.2% mutation frequency in the MCM2 gene. This study revealed a significant correlation (Cox p ≤ 0.05) between the higher MCM2 expression and lower patient survival. Finally, we identified the co-expressed genes with gene ontological features and signaling pathways associated in BC development. We believe that this study will provide a basis for MCM2 to be a significant biomarker for human BC prognosis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530310/ doi: 10.1016/j.heliyon.2020.e05087 id: cord-299943-wzkh04dv author: Santhanam, Manikandan title: DNA/RNA Electrochemical Biosensing Devices a Future Replacement of PCR Methods for a Fast Epidemic Containment date: 2020-08-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Pandemics require a fast and immediate response to contain potential infectious carriers. In the recent 2020 Covid-19 worldwide pandemic, authorities all around the world have failed to identify potential carriers and contain it on time. Hence, a rapid and very sensitive testing method is required. Current diagnostic tools, reverse transcription PCR (RT-PCR) and real-time PCR (qPCR), have its pitfalls for quick pandemic containment such as the requirement for specialized professionals and instrumentation. Versatile electrochemical DNA/RNA sensors are a promising technological alternative for PCR based diagnosis. In an electrochemical DNA sensor, a nucleic acid hybridization event is converted into a quantifiable electrochemical signal. A critical challenge of electrochemical DNA sensors is sensitive detection of a low copy number of DNA/RNA in samples such as is the case for early onset of a disease. Signal amplification approaches are an important tool to overcome this sensitivity issue. In this review, the authors discuss the most recent signal amplification strategies employed in the electrochemical DNA/RNA diagnosis of pathogens. url: https://www.ncbi.nlm.nih.gov/pubmed/32824787/ doi: 10.3390/s20164648 id: cord-324137-nau83mjv author: Saranathan, Nandhini title: G-Quadruplexes: More Than Just a Kink in Microbial Genomes date: 2018-09-14 words: 6722.0 sentences: 379.0 pages: flesch: 42.0 cache: ./cache/cord-324137-nau83mjv.txt txt: ./txt/cord-324137-nau83mjv.txt summary: Several reports convincingly demonstrate antimicrobial activity of quadruplex-binding ligands against clinically challenging pathogens, including HIV-1, HCV, Ebola virus, Plasmodium falciparum, and Mycobacterium tuberculosis. An earlier study reports that, following concatemeric replication of HHV-1, the cleavage of unit length genomes and their encapsidation is achieved by the binding of virus proteins to a DNA secondary structure formed by a DNA packaging sequence (pac-1) [50] . G4s have been shown to inhibit the transcription or translation of structural and nonstructural proteins in viruses, deleteriously affecting the virus loads and their pathogenicity; the stabilization of these quadruplexes with ligands has been investigated as a potential mechanism for targeting viruses. Negative regulation of virus transcription, translation or replication by quadruplex motifs in virus genomes forms the basis of using G4-binding ligands as antiviral agents. G-quadruplex forming structural motifs in the genome of Deinococcus radiodurans and their regulatory roles in promoter functions abstract: G-quadruplexes (G4s) are noncanonical nucleic acid secondary structures formed by guanine-rich DNA and RNA sequences. In this review we aim to provide an overview of the biological roles of G4s in microbial genomes with emphasis on recent discoveries. G4s are enriched and conserved in the regulatory regions of microbes, including bacteria, fungi, and viruses. Importantly, G4s in hepatitis B virus (HBV) and hepatitis C virus (HCV) genomes modulate genes crucial for virus replication. Recent studies on Epstein–Barr virus (EBV) shed light on the role of G4s within the microbial transcripts as cis-acting regulatory signals that modulate translation and facilitate immune evasion. Furthermore, G4s in microbial genomes have been linked to radioresistance, antigenic variation, recombination, and latency. G4s in microbial genomes represent novel therapeutic targets for antimicrobial therapy. url: https://api.elsevier.com/content/article/pii/S0966842X18301951 doi: 10.1016/j.tim.2018.08.011 id: cord-279229-2226jnfl author: Savan, R title: Loop‐mediated isothermal amplification: an emerging technology for detection of fish and shellfish pathogens date: 2005-11-22 words: 4188.0 sentences: 230.0 pages: flesch: 45.0 cache: ./cache/cord-279229-2226jnfl.txt txt: ./txt/cord-279229-2226jnfl.txt summary: In this paper, we review a novel method of DNA amplification known as loop-mediated isothermal amplification (LAMP) of a target nucleic acid. Screening for KHV has become very important as trade of fancy carp is an easy route for geographical spread of the virus and a rapid and efficient system like LAMP is very Figure 2 Loop-mediated isothermal amplification reaction amplifying the haemolysin gene from Edwardsiella tarda isolates. Rapid detection of a fish iridovirus using loop-mediated isothermal amplification (LAMP) Rapid diagnosis of Tetracapsuloides bryosalmonae, the causative agent of proliferative kidney disease (PKD) in salmonid fish by a novel DNA amplification method, loop-mediated isothermal amplification (LAMP) Rapid diagnosis of herpes simplex virus infection by a loop-mediated isothermal amplification method A loop mediated isothermal amplification (LAMP) method for detection of infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss) Rapid diagnosis of human herpesvirus 6 infection by a novel DNA amplification method, loop-mediated isothermal amplification abstract: Fish and shellfish diseases are a constant threat to the sustainability and economic viability of aquaculture. Early diagnosis plays a vital role in management of fish and shellfish diseases. Traditionally, various biochemical and serological tests have been used for fish disease diagnosis. However, the time and expertise required for such diagnoses makes it difficult for aquaculturists to easily adopt them under production conditions. Polymerase chain reaction and probe‐based nucleic acid detection have become increasingly popular in fish and shellfish diagnostics. Recently, a novel technique called loop‐mediated isothermal amplification (LAMP) has been developed, which is highly sensitive and rapid. LAMP has been used for the detection of bacterial, viral, fungal and parasitic diseases in both animal and plants. In aquaculture, LAMP‐based detection of pathogens like Edwardsiella tarda, E. ictaluri, Nocardia seriolae, Tetracapsuloides bryosalmonae, white spot syndrome virus and infectious haematopoietic necrosis virus have been reported. In this review, the application of LAMP for the detection of aquaculture‐associated pathogens is discussed. url: https://www.ncbi.nlm.nih.gov/pubmed/16302951/ doi: 10.1111/j.1365-2761.2005.00670.x id: cord-285077-okwck5sv author: Sayahi, Tofigh title: Airborne Aerosolized Mouse Cytomegalovirus From Common Otolaryngology Procedures: Implications for COVID-19 Infection date: 2020-09-15 words: 4973.0 sentences: 300.0 pages: flesch: 49.0 cache: ./cache/cord-285077-okwck5sv.txt txt: ./txt/cord-285077-okwck5sv.txt summary: CONCLUSION: Coblation and electrocautery procedures generate >100-fold increases in aerosol concentrations over background; only coblation and drilling produce aerosolized viral DNA. Coblation and electrocautery procedures generate .100-fold increases in aerosol concentrations over background; only coblation and drilling produce aerosolized viral DNA. 10, 11 We proposed to build on these studies by measuring particle size and concentration and by trying to detect aerosolized viral DNA and viable virus during common otolaryngology procedures, using a murine model for cytomegalovirus (CMV) infection. The results also indicated that drilling and microdebrider did not cause statistically significant increases in aerosol concentrations and total counts when compared with background (.870 \ Tukey-adjusted P value \ .930; Figures 2 and 3 , Table 3 ). The results from our study demonstrate that a number of these procedures can generate relatively large concentrations of aerosolized particles and that a significant percentage are small enough to pass unimpeded through conventional surgical and even N95 masks. abstract: OBJECTIVES: To determine whether common otolaryngology procedures generate viable aerosolized virus through a murine cytomegalovirus (mCMV) model for infection. STUDY DESIGN: mCMV model of infection. SETTING: University of Utah laboratory. METHODS: Three-day-old BALB/c mice were inoculated with mCMV or saline. Five days later, each mouse underwent drilling, microdebrider, coblation, and electrocautery procedures. Particle size distribution and PM(2.5) (particulate matter <2.5 µm) concentration were determined with a scanning mobility particle sizer and an aerosol particle sizer in the range of 15 nm to 32 µm. Aerosolized samples from these procedures were collected with an Aerosol Devices BioSpot sampler for viral titer based on polymerase chain reaction and for viable virus through viral culture. RESULTS: As compared with the background aerosol concentrations, coblation and electrocautery showed statistically significant increases in airborne aerosols (Tukey-adjusted P value <.040), while microdebrider and drilling at 30,000 rpm did not (.870 < Tukey-adjusted P value < .930). We identified viral DNA in samples from coblation and drilling procedures, although we did not identify viable viruses in aerosol samples from any of the 4 procedures. CONCLUSION: Coblation and electrocautery procedures generate >100-fold increases in aerosol concentrations over background; only coblation and drilling produce aerosolized viral DNA. The high concentration of aerosols from coblation and electrocautery suggests the need for appropriate safeguards against particle exposure to health care workers. The presence of viral DNA from drilling and coblation procedures warrants the need for appropriate protection against droplet and aerosol exposure. url: https://www.ncbi.nlm.nih.gov/pubmed/32928037/ doi: 10.1177/0194599820957966 id: cord-288879-rj03dsib author: Schein, Catherine H. title: Polyglutamine Repeats in Viruses date: 2018-09-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: This review explores the presence and functions of polyglutamine (polyQ) in viral proteins. In mammals, mutations in polyQ segments (and CAG repeats at the nucleotide level) have been linked to neural disorders and ataxias. PolyQ regions in normal human proteins have documented functional roles, in transcription factors and, more recently, in regulating autophagy. Despite the high frequency of polyQ repeats in eukaryotic genomes, little attention has been given to the presence or possible role of polyQ sequences in virus genomes. A survey described here revealed that polyQ repeats occur rarely in RNA viruses, suggesting that they have detrimental effects on virus replication at the nucleotide or protein level. However, there have been sporadic reports of polyQ segments in potyviruses and in reptilian nidoviruses (among the largest RNA viruses known). Conserved polyQ segments are found in the regulatory control proteins of many DNA viruses. Variable length polyQ tracts are found in proteins that contribute to transmissibility (cowpox A-type inclusion protein (ATI)) and control of latency (herpes viruses). New longer-read sequencing methods, using original biological samples, should reveal more details on the presence and functional role of polyQ in viruses, as well as the nucleotide regions that encode them. Given the known toxic effects of polyQ repeats, the role of these segments in neurovirulent and tumorigenic viruses should be further explored. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-018-1269-4) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/30182336/ doi: 10.1007/s12035-018-1269-4 id: cord-335490-p63qlcnx author: Schenk, Thomas title: Disseminated Bocavirus Infection after Stem Cell Transplant date: 2007-09-17 words: 1928.0 sentences: 103.0 pages: flesch: 46.0 cache: ./cache/cord-335490-p63qlcnx.txt txt: ./txt/cord-335490-p63qlcnx.txt summary: To the Editor: Human bocavirus (HBoV) (1) is increasingly recognized as a cause of respiratory infections worldwide. Retrospectively, the same NPA sample was reanalyzed for HBoV DNA by real-time PCR (7) and showed a viral load of 4.6 × 10 7 copies/mL (online Appendix Figure) ; specifi city was confi rmed by sequencing. Diarrheic stool samples obtained on day 21 and, after resolution of respiratory symptoms, on day 75 showed substantial HBoV DNA (2.5 × 10 6 and 6.0 × 10 5 copies/mg, respectively; online Appendix Figure) . Drug-induced PRCA is a rare blood disorder in adults and has already been reported in isoniazid-treated patients (3) (4) (5) . This hypothesis is supported by previously reported cases in which PRCA relapses occurred when treatment with isoniazid was resumed (3, 5) . Detection of human bocavirus in Japanese children with lower respiratory tract infections Human bocavirus DNA detected by quantitative real-time PCR in two children hospitalized for lower respiratory tract infection abstract: nan url: https://doi.org/10.3201/eid1309.070318 doi: 10.3201/eid1309.070318 id: cord-018371-16zhx0ai author: Schomburg, Dietmar title: DNA helicase 3.6.4.12 date: 2013 words: 13038.0 sentences: 1289.0 pages: flesch: 67.0 cache: ./cache/cord-018371-16zhx0ai.txt txt: ./txt/cord-018371-16zhx0ai.txt summary: The enzyme utilizes the energy of ATP hydrolysis to translocate along one strand of the duplex and unwind the complementary strand [43] ; <3,48> gonadotropin-regulated testicular he-licase (GRTH/DDX25), a target of gonadotropin and androgen action, is a post-transcriptional regulator of key spermatogenesis genes [36] ; <20> helicase UvrD protein plays an important role in nucleotide excision repair, mismatch repair, rolling circular plasmid replication, and in DNA replication [16] ; <39> helicases play an essential role in nearly all the nucleic acid metabolic processes, catalyzing the transient opening of the duplex nucleic acids in an ATP-dependent manner [18] ; <32> involved in DNA recombination, repair and genome stability maintenance [56] ; <22> meiosis-specific MER3 protein is required for crossing over, which ensures faithful segregation of homologous chromosomes at the first meiotic division [30] ; <41> PcrA is a chromosomally encoded DNA helicase of gram-positive bacteria involved in replication of rolling circle replicating plasmids [21] ; <43> the ability of CeWRN-1 to unwind DNA structures may improve the access for DNA repair and replication proteins that are important for preventing the accumulation of abnormal structures, contributing to genomic stability [9] ; <12> the C-terminal portion of hepatitis C virus nonstructural protein 3 (NS3) forms a three domain polypeptide that possesses the ability to travel along RNA or single-stranded DNA (ssDNA) in a 3'' to 5'' direction. abstract: EC number 3.6.4.12 Systematic name ATP phosphohydrolase (DNA helix unwinding) Recommended name DNA helicase Synonyms 3’ to 5’ DNA helicase <28> [35] 3’-5’ DNA helicase <11> [55] 3’-5’ PfDH <11> [55] 5’ to 3’ DNA helicase <26,27> [19,42] AvDH1 <47> [37] BACH1 helicase <19> [34] BLM <3> [28] BLM protein <3> [28] BRCA1-associated C-terminal helicase <19> [34] BcMCM <8> [52] CeWRN-1 <43> [9] DDX25 <3,48> [36] DNA helicase 120 <7> [15] DNA helicase A <4> [8] DNA helicase E <5> [44] DNA helicase II <9> [7] DNA helicase III <4> [27] DNA helicase RECQL5β <44> [17] DNA helicase VI <3> [45] Dbp9p <46> (<46> a member of the DEAD box protein family [24]) [24] DmRECQ5 <1> [50] DnaB helicase <29> [23] E1 helicase <17> [58] GRTH/DDX25 <3,48> [36] HCoV SF1 helicase <23> [3] HCoV helicase <23> [3] HDH IV <3> [45] Hel E <5> [44] Hmi1p <40> [60] MCM helicase <6,5,38> [43,54] MCM protein <6,35> [43] MER3 helicase <22> [30] MER3 protein <22> [30] MPH1 <28> [35] NS3 <12,50> (<12,50> ambiguous [38,65,66]) [38,65,66] NS3 NTPase/helicase <14> (<14> ambiguous [67]) [67] NS3 protein <12> (<12> ambiguous [63]) [63] NTPase/helicase <12,16> (<12> ambiguous [61]) [61,64] PDH120 <7> [15] PIF1 <33> [51] PIF1 helicase <33> [51,53] PcrA <37> [20] PcrA helicase <37,41,49> [20,21,39] PcrASpn <41> [21] PfDH A <11> [55] Pfh1p <27> [42] RECQ5 <1> [49,50] RECQ5 helicase <1> (<1> small isoform [49]) [49] RECQL5b <44> [17] REcQ <31> [13] RSF1010 RepA <30> [5] RecG <45> [6] RecQ helicase <32> [56] RecQsim <32> [56] Rep52 <24> [40] Rrm3p <26> [19] Sgs1 <36> [29] Sgs1 DNA helicase <36> [29] TWINKLE <21> [33] Tth UvrD <20> [16] UvrD <20,42> [16,22] UvrD helicase <39> [18] WRN <18> [31] WRN RecQ helicase <18> [12] WRN helicase <18> [12] WRN protein <18> [12] WRN-1 RecQ helicase <43> [9] Werner Syndrome helicase <18> [31] Werner syndrome RecQ helicase <18> [12] dheI I <1> [46] dnaB <29> [23] hPif1 <33> [53] helicase DnaB <2> [10] helicase II <25> [25] helicase PcrA <49> [39] helicase UvrD <20> [16] helicase domain of bacteriophage T7 gene 4 protein <10> [47] non structural protein 3 <12> (<12> ambiguous [61,62]) [61,62] nonstructural protein 3 <12,14,50,51> (<12,14,50> ambiguous [38,63,65,66,67]; <51> ambigous [4]) [4,38,63,65,66,67] protein NS3 <12> (<12> ambiguous [62]) [62] scHelI <4> [26] urvD <25> [25] url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123227/ doi: 10.1007/978-3-642-36260-6_24 id: cord-103813-w2sb6h94 author: Schumacher, Garrett J. title: Genetic information insecurity as state of the art date: 2020-07-10 words: 6459.0 sentences: 358.0 pages: flesch: 35.0 cache: ./cache/cord-103813-w2sb6h94.txt txt: ./txt/cord-103813-w2sb6h94.txt summary: Therefore, human genetic information is a uniquely confidential form of data that requires increased security controls and scrutiny. Sensitive genetic information, which includes both biological material and digital genetic data, is the primary asset of concern, and associated assets, such as metadata, electronic health records and intellectual property, are also vulnerable within this ecosystem. ❖ Private Sensitive Genetic Information can be expected to cause a moderate level of risk to a nation, ethnic group, individual, or stakeholder if it is disclosed, modified, or destroyed without authorization. The genetic information ecosystem is a distributed cyber-physical system containing numerous stakeholders (Supplementary Material, Appendix 1), personnel, and devices for computing and networking purposes. Genetic information security is a shared responsibility between sequencing laboratories and device vendors, as well as all other involved stakeholders. Examples include biorepositories, DNA sequencing laboratories, researchers, cloud and other service providers, and supply chain entities responsible for devices, software and materials. abstract: Genetic information is being generated at an increasingly rapid pace, offering advances in science and medicine that are paralleled only by the threats and risk present within the responsible ecosystem. Human genetic information is identifiable and contains sensitive information, but genetic data security is only recently gaining attention. Genetic data is generated in an evolving and distributed cyber-physical ecosystem, with multiple systems that handle data and multiple partners that utilize the data. This paper defines security classifications of genetic information and discusses the threats, vulnerabilities, and risk found throughout the entire genetic information ecosystem. Laboratory security was found to be especially challenging, primarily due to devices and protocols that were not designed with security in mind. Likewise, other industry standards and best practices threaten the security of the ecosystem. A breach or exposure anywhere in the ecosystem can compromise sensitive information. Extensive development will be required to realize the potential of this emerging field while protecting the bioeconomy and all of its stakeholders. url: https://doi.org/10.1101/2020.07.08.192666 doi: 10.1101/2020.07.08.192666 id: cord-012418-6ralcn8p author: Schwanke, Hella title: Of Keeping and Tipping the Balance: Host Regulation and Viral Modulation of IRF3-Dependent IFNB1 Expression date: 2020-07-07 words: 15685.0 sentences: 761.0 pages: flesch: 38.0 cache: ./cache/cord-012418-6ralcn8p.txt txt: ./txt/cord-012418-6ralcn8p.txt summary: Due to its key role during the induction of the initial IFN response, the activity of the transcription factor interferon regulatory factor 3 (IRF3) is tightly regulated by the host and fiercely targeted by viral proteins at all conceivable levels. The crucial role of IRF3 and the posttranslational changes it undergoes upon viral infection were first reported more than 20 years ago: Upon stimulation, IRF3 gets phosphorylated and accumulates in the nucleus where it interacts with the coactivators CREB-binding protein (CBP)/p300 to specifically bind to virus-inducible enhancer elements and exerts transcriptional activation of the IFNB1 gene [21, [36] [37] [38] (Figure 2 ). The crucial role of IRF3 and the posttranslational changes it undergoes upon viral infection were first reported more than 20 years ago: Upon stimulation, IRF3 gets phosphorylated and accumulates in the nucleus where it interacts with the coactivators CREB-binding protein (CBP)/p300 to specifically bind to virus-inducible enhancer elements and exerts transcriptional activation of the IFNB1 gene [21, [36] [37] [38] (Figure 2 ). abstract: The type I interferon (IFN) response is a principal component of our immune system that allows to counter a viral attack immediately upon viral entry into host cells. Upon engagement of aberrantly localised nucleic acids, germline-encoded pattern recognition receptors convey their find via a signalling cascade to prompt kinase-mediated activation of a specific set of five transcription factors. Within the nucleus, the coordinated interaction of these dimeric transcription factors with coactivators and the basal RNA transcription machinery is required to access the gene encoding the type I IFN IFNβ (IFNB1). Virus-induced release of IFNβ then induces the antiviral state of the system and mediates further mechanisms for defence. Due to its key role during the induction of the initial IFN response, the activity of the transcription factor interferon regulatory factor 3 (IRF3) is tightly regulated by the host and fiercely targeted by viral proteins at all conceivable levels. In this review, we will revisit the steps enabling the trans-activating potential of IRF3 after its activation and the subsequent assembly of the multi-protein complex at the IFNβ enhancer that controls gene expression. Further, we will inspect the regulatory mechanisms of these steps imposed by the host cell and present the manifold strategies viruses have evolved to intervene with IFNβ transcription downstream of IRF3 activation in order to secure establishment of a productive infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411613/ doi: 10.3390/v12070733 id: cord-319799-h9kot3og author: Schäfer, Alexandra title: Epigenetic Landscape during Coronavirus Infection date: 2017-02-15 words: 10080.0 sentences: 465.0 pages: flesch: 33.0 cache: ./cache/cord-319799-h9kot3og.txt txt: ./txt/cord-319799-h9kot3og.txt summary: By combining measures of epigenome reorganization with RNA and proteomic datasets, we articulate a spatial-temporal data integration approach to identify regulatory genomic clusters and regions that play a crucial role in the host''s innate immune response, thereby defining a new viral antagonism mechanism following emerging coronavirus infection. By utilizing Calu3 cells, we have developed a robust human model platform to study innate immune regulatory control and epigenetics following emerging coronavirus and influenza virus infections as well as other highly pathogenic viruses ( Figure 6 ). Utilizing these model systems, we aim to study genome-wide histone modifications, DNA methylation patterns, and the chromatin landscape after virus infection across different cell types in the lung, revealing cell type-specific regulatory features that function to regulate infection outcomes. Utilizing these model systems, we aim to study genome-wide histone modifications, DNA methylation patterns, and the chromatin landscape after virus infection across different cell types in the lung, revealing cell type-specific regulatory features that function to regulate infection outcomes. abstract: Coronaviruses (CoV) comprise a large group of emerging human and animal pathogens, including the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) strains. The molecular mechanisms regulating emerging coronavirus pathogenesis are complex and include virus–host interactions associated with entry, replication, egress and innate immune control. Epigenetics research investigates the genetic and non-genetic factors that regulate phenotypic variation, usually caused by external and environmental factors that alter host expression patterns and performance without any change in the underlying genotype. Epigenetic modifications, such as histone modifications, DNA methylation, chromatin remodeling, and non-coding RNAs, function as important regulators that remodel host chromatin, altering host expression patterns and networks in a highly flexible manner. For most of the past two and a half decades, research has focused on the molecular mechanisms by which RNA viruses antagonize the signaling and sensing components that regulate induction of the host innate immune and antiviral defense programs upon infection. More recently, a growing body of evidence supports the hypothesis that viruses, even lytic RNA viruses that replicate in the cytoplasm, have developed intricate, highly evolved, and well-coordinated processes that are designed to regulate the host epigenome, and control host innate immune antiviral defense processes, thereby promoting robust virus replication and pathogenesis. In this article, we discuss the strategies that are used to evaluate the mechanisms by which viruses regulate the host epigenome, especially focusing on highly pathogenic respiratory RNA virus infections as a model. By combining measures of epigenome reorganization with RNA and proteomic datasets, we articulate a spatial-temporal data integration approach to identify regulatory genomic clusters and regions that play a crucial role in the host’s innate immune response, thereby defining a new viral antagonism mechanism following emerging coronavirus infection. url: https://www.ncbi.nlm.nih.gov/pubmed/28212305/ doi: 10.3390/pathogens6010008 id: cord-009894-iciaa829 author: Scott‐Taylor, Tim H. title: Detection of enteric adenoviruses with synthetic oligonucleotide probes date: 2005-12-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The abilities of hybridization probes to detect all human adenovirus types and to identify enteric adenovirus types were evaluated. The efficiency of hybridization was compared to other tests currently in routine laboratory use on clinical specimens from young children with gastroenteritis, Probes were derived from various regions of the adenovirus types 2 and 41 genomes, and were evaluated by hybridization with a series of DNA quantities from 1 μg to 10 pg of one adenovirus type from each human subgenus, lambda phage, and HEp 2 cells. The sensitivity of hybridization with the HPII probe (92.7%), containing the conserved hexon gene, compared well with EM (54.6%), culture and neutralization (45.5%), and enzyme immunoassay (61.8%). The sensitivity of detection of enteric adenovirus isolates by the cloned Bg/II D fragment probe (92.9%) and by a synthetic probe (85.7%), manufactured from type‐specific sequences of the Ad41 hexon gene were comparable to Ad40/Ad41 specific enzyme immunoassay (84.6%). Hybridization was found to be a sensitive method of adenovirus detection in comparison to traditional methods of laboratory diagnosis. Synthetic oligonucleotides enable specific detection of individual enteric adenovirus types. Hybridization had additional advantages over other tests in identifying cases of infection with more than one adenovirus type and in allowing an estimate of the concentration of adenovirus in the specimen. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166767/ doi: 10.1002/jmv.1890410414 id: cord-253894-4u5yt7b7 author: Senkevich, Tatiana G. title: Vaccinia virus F16 protein, a predicted catalytically inactive member of the prokaryotic serine recombinase superfamily, is targeted to nucleoli date: 2011-09-01 words: 6253.0 sentences: 286.0 pages: flesch: 44.0 cache: ./cache/cord-253894-4u5yt7b7.txt txt: ./txt/cord-253894-4u5yt7b7.txt summary: VACV, by far the most intensively studied poxvirus, replicates entirely in the cytoplasm of infected cells and encodes many of the proteins required for its growth as well as numerous proteins modulating virus-host interactions. Here we provide a detailed computational analysis of the F16 protein indicating that it is unlikely to have serine recombinase activity, and experimental data showing that the F16L gene is not required for virus growth in cell culture. F16-3xflag was detected by Western blotting at 2 h after infection, only slightly increased in amount between 4 and 24 h, and accumulated in the presence of cytosine arabinoside (araC), an inhibitor of DNA synthesis that prevents VACV intermediate and late gene expression. Two other VAC proteins, I3 and B1, containing a C-terminal 3xflag tag and expressed from a transfected plasmid under the control of the CMV promoter were analyzed in parallel with F16-3xflag, and no nucleolar or nuclear membrane staining was detected (not shown). abstract: The F16L gene of vaccinia virus (VACV) is conserved in all chordopoxviruses except avipoxviruses. The crocodile poxvirus F16 protein ortholog has highly significant similarity to prokaryotic serine recombinases and contains all amino acids that comprise the catalytic site. In contrast, F16 orthologs encoded by other poxviruses show only marginally significant similarity to serine recombinases, lack essential amino acids of the active site and are most likely inactive derivatives of serine recombinases. Nevertheless, the conservation of F16L in non-avian poxviruses suggested an important function. However, a VACV mutant with the F16L gene knocked out replicated normally in dividing and quiescent cells. The F16 protein was synthesized early after infection and detected in virus cores. When expressed in infected or uninfected cells, F16 accumulated in nucleoli depending on the level of expression and confluency of cells. Evidence was obtained that F16 forms multimers, which might regulate concentration-dependent intracellular localization. url: https://www.ncbi.nlm.nih.gov/pubmed/21752417/ doi: 10.1016/j.virol.2011.06.017 id: cord-102206-mb0qcd0b author: Seymour, Elif title: Configurable Digital Virus Counter on Robust Universal DNA Chips date: 2020-10-22 words: 5898.0 sentences: 284.0 pages: flesch: 52.0 cache: ./cache/cord-102206-mb0qcd0b.txt txt: ./txt/cord-102206-mb0qcd0b.txt summary: Here, we demonstrate real-time multiplexed virus detection by applying DNA-directed antibody immobilization technique to a single-particle interferometric reflectance imaging sensor (SP-IRIS). We also show that this method can be modified to produce a single-step, homogeneous assay format by mixing the antibody-DNA conjugates with the virus sample in solution phase prior to flowing in the microfluidic cartridge, eliminating the antibody immobilization step. 16 SP-IRIS has been utilized for detecting viruses in complex media using antibody microarrays by imaging chips both dry (dried after sample incubation and wash steps) and in liquid using disposable microfluidic cartridges. To demonstrate the feasibility of using the homogeneous assay in combination with the passive flow cartridge and to compare its performance to the directly immobilized antibody assay, an SP-IRIS chip was printed with anti-EBOV mAb, A'' probe, and a negative DNA sequence, and washed as described previously. abstract: Here, we demonstrate real-time multiplexed virus detection by applying DNA-directed antibody immobilization technique to a single-particle interferometric reflectance imaging sensor (SP-IRIS). In this technique, the biosensor chip surface spotted with different DNA sequences is converted to a multiplexed antibody array by flowing antibody-DNA conjugates and allowing specific DNA-DNA hybridization. The resulting antibody array is shown to detect three different recombinant Vesicular Stomatitis Viruses (rVSVs) genetically engineered to express surface glycoproteins of Ebola, Marburg, and Lassa viruses in real-time in a disposable microfluidic cartridge. We also show that this method can be modified to produce a single-step, homogeneous assay format by mixing the antibody-DNA conjugates with the virus sample in solution phase prior to flowing in the microfluidic cartridge, eliminating the antibody immobilization step. This homogenous approach achieved detection of the model Ebola virus, rVSV-EBOV, at a concentration of 100 PFU/ml in 1 hour. Finally, we demonstrate the feasibility of this homogeneous technique as a rapid test using a passive microfluidic cartridge. A concentration of 104 PFU/ml was detectable under 10 minutes for the rVSV-Ebola virus. Utilizing DNA microarrays for antibody-based diagnostics is an alternative approach to antibody microarrays and offers advantages such as configurable sensor surface, long-term storage ability, and decreased antibody use. We believe these properties will make SP-IRIS a versatile and robust platform for point-of-care diagnostics applications. url: https://doi.org/10.1101/2020.10.22.350579 doi: 10.1101/2020.10.22.350579 id: cord-339522-jm2xpn1w author: Sharma, Nidhi title: Recombinase‐Based Isothermal Amplification of Nucleic Acids with Self‐Avoiding Molecular Recognition Systems (SAMRS) date: 2014-09-10 words: 3873.0 sentences: 219.0 pages: flesch: 55.0 cache: ./cache/cord-339522-jm2xpn1w.txt txt: ./txt/cord-339522-jm2xpn1w.txt summary: In contrast, with the primers containing SAMRS components, clean amplification products (amplicons) of the correct identity (as judged by length) were produced if the reaction mixture contained the target DNA (Figure 3 A, lane 2) . Real-time amplification with STD primers resulted in a nonspecific signal that does not depend on the amount of target template added to the reaction mixtures (Figure 4 B, left) . Once again, STD primers amplified unwanted products in the negative control (Figure 5 A) , giving a background signal that obscured the desired amplicons when lower concentrations of viral RNA template was used in the RT-RPA reaction. These experiments show that, at least for these three cases, adding SAMRS nucleotides to primers used in RPA isothermal amplification eliminates assay artifacts, allows for readout by using real-time fluorescence signal, and increases the robustness of the assay with respect to using different target sequences. abstract: Recombinase polymerase amplification (RPA) is an isothermal method to amplify nucleic acid sequences without the temperature cycling that classical PCR uses. Instead of using heat to denature the DNA duplex, RPA uses recombination enzymes to swap single‐stranded primers into the duplex DNA product; these are then extended using a strand‐displacing polymerase to complete the cycle. Because RPA runs at low temperatures, it never forces the system to recreate base‐pairs following Watson–Crick rules, and therefore it produces undesired products that impede the amplification of the desired product, complicating downstream analysis. Herein, we show that most of these undesired side products can be avoided if the primers contain components of a self‐avoiding molecular recognition system (SAMRS). Given the precision that is necessary in the recombination systems for them to function biologically, it is surprising that they accept SAMRS. SAMRS‐RPA is expected to be a powerful tool within the range of amplification techniques available to scientists. url: https://doi.org/10.1002/cbic.201402250 doi: 10.1002/cbic.201402250 id: cord-021966-5m21bsrw author: Shaw, Alan R. title: Vaccines date: 2009-05-15 words: 21170.0 sentences: 897.0 pages: flesch: 33.0 cache: ./cache/cord-021966-5m21bsrw.txt txt: ./txt/cord-021966-5m21bsrw.txt summary: Because a number of proteins produced in isolation by recombinant methods have been observed to elicit lower immune responses than do natural infections or live attenuated vaccines, the development and use of adjuvants to optimize recombinant vaccine immunogenicity represent an important parallel area for future exploration. Modern molecular biology and biochemistry have provided numerous options for vaccine immunogen presentation, including recombinant proteins (and recombinant virus-like particles (VLPs)), synthetic proteins, protein-polysaccharide conjugates, and gene delivery systems (recombinant viral vectors, or DNA vaccines) >> Is the antigen of interest sufficiently immunogenic on its own, or is augmentation of the desired immune response by conjugation to a specific carrier or addition of an adjuvant necessary to elicit a sufficient and sufficiently durable immune response in individuals in the target population for vaccination? abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152278/ doi: 10.1016/b978-0-323-04404-2.10092-2 id: cord-337867-hqmf6r7t author: Shim, Byoung-Shik title: Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses date: 2010-12-31 words: 3762.0 sentences: 221.0 pages: flesch: 54.0 cache: ./cache/cord-337867-hqmf6r7t.txt txt: ./txt/cord-337867-hqmf6r7t.txt summary: title: Intranasal immunization with plasmid DNA encoding spike protein of SARS-coronavirus/polyethylenimine nanoparticles elicits antigen-specific humoral and cellular immune responses RESULTS: In the present study, the immune responses of BALB/c mice immunized via intranasal (i.n.) route with SARS DNA vaccine (pci-S) in a PEI/pci-S complex form have been examined. The result showed that SARS S-specific IgA antibody response was significantly (P < 0.01) increased in lung wash from mice immunized with PEI/pci-S complexes ( Figure 2B ). B220 + cells from mice immunized with PEI/pci-S complexes were highly proliferated after in vitro re-stimulation with SARS-CoV S protein ( Figure 2C ). The surface expression of CD80 and CD86 co-stimulatory molecules were significantly (P < 0.05) higher on DCs from mice treated with PEI/pci-S complexes than those from SARS-CoV DNA S vaccine alone ( Figure 3 ). DNA vaccine encoding full-length S protein has shown to induce humoral, cellular and protective immune responses against SARS-CoV [6] . abstract: BACKGROUND: Immunization with the spike protein (S) of severe acute respiratory syndrome (SARS)-coronavirus (CoV) in mice is known to produce neutralizing antibodies and to prevent the infection caused by SARS-CoV. Polyethylenimine 25K (PEI) is a cationic polymer which effectively delivers the plasmid DNA. RESULTS: In the present study, the immune responses of BALB/c mice immunized via intranasal (i.n.) route with SARS DNA vaccine (pci-S) in a PEI/pci-S complex form have been examined. The size of the PEI/pci-S nanoparticles appeared to be around 194.7 ± 99.3 nm, and the expression of the S mRNA and protein was confirmed in vitro. The mice immunized with i.n. PEI/pci-S nanoparticles produced significantly (P < 0.05) higher S-specific IgG1 in the sera and mucosal secretory IgA in the lung wash than those in mice treated with pci-S alone. Compared to those in mice challenged with pci-S alone, the number of B220(+ )cells found in PEI/pci-S vaccinated mice was elevated. Co-stimulatory molecules (CD80 and CD86) and class II major histocompatibility complex molecules (I-A(d)) were increased on CD11c(+ )dendritic cells in cervical lymph node from the mice after PEI/pci-S vaccination. The percentage of IFN-γ-, TNF-α- and IL-2-producing cells were higher in PEI/pci-S vaccinated mice than in control mice. CONCLUSION: These results showed that intranasal immunization with PEI/pci-S nanoparticles induce antigen specific humoral and cellular immune responses. url: https://www.ncbi.nlm.nih.gov/pubmed/21194475/ doi: 10.1186/1471-2172-11-65 id: cord-018944-du42ho11 author: Shin, Jeong Hwan title: Nucleic Acid Extraction and Enrichment date: 2018-11-10 words: 6857.0 sentences: 355.0 pages: flesch: 41.0 cache: ./cache/cord-018944-du42ho11.txt txt: ./txt/cord-018944-du42ho11.txt summary: [6, 7] as follows: (1) extraction should be simple and rapid and should show high sensitivity and specificity; (2) it is preferred that there be no requirements for specialized equipment or special knowledge and skills; (3) the final nucleic acid should be pure and easy to modify for various amplification techniques; (4) the reagents and their product should be harmless; and (5) the process of preparation should resist contamination with other specimens. Although the phenolchloroform method is relatively easy compared with the CsCl/EtBr gradient and is very useful for the extraction of nucleic acids, it also is problematic for the clinical microbiology laboratory because phenol has important limitations due to its being toxic, caustic, and flammable [5, 15, 16] . In recent years, it has become possible to extract viral nucleic acid from clinical specimens having cellular components, and there have been trials of these commercially available kits to detect various clinically important viruses [30] [31] [32] . abstract: Nucleic acid extraction is the first step of any amplification experiment no matter what kind of amplification is used to detect a specific pathogen. Efficient nucleic acid extraction is essential to obtain good results using any molecular test. The optimal extraction method should fulfill the following conditions: speed, short working time, cost-effectiveness, high sensitivity and specificity, good reproducibility, and safety. The methods can be divided into solution or column based according to differences of their principles. The automated extraction instruments have many advantages, and these have proven to be very useful. Moreover, in recent years, fully automated instruments combining NA extraction and amplification have been commercially available. However, the method itself does not provide assurance, and the DNA recovery can be different among various kits or instruments that use the similar principles. Therefore, it is important to carefully evaluate the performance of any extraction method used in the clinical microbiology laboratory even though manufacturers may have reported good validation results with specific organisms. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123959/ doi: 10.1007/978-3-319-33900-9_13 id: cord-003764-141u6ax7 author: Shrestha, Ashish C. title: Cytolytic Perforin as an Adjuvant to Enhance the Immunogenicity of DNA Vaccines date: 2019-04-30 words: 6292.0 sentences: 309.0 pages: flesch: 42.0 cache: ./cache/cord-003764-141u6ax7.txt txt: ./txt/cord-003764-141u6ax7.txt summary: The ability of a DNA vaccine to elicit T cell immunity is thus dependent on activating APCs to present antigen: MHC complexes to T cells [31] and adjuvants can serve as an important costimulatory factor to enhance this process. The use of fusogenic membrane glycoprotein (FMG) gene from VSV vaccine encoding the H7 protein of human papillomavirus type 16 was shown to enhance ell responses and effectively control growth of tumors [87] . The use of fusogenic membrane glycoprotein (FMG) gene from VSV in a DNA vaccine encoding the H7 protein of human papillomavirus type 16 was shown to enhance CD8 + T cell responses and effectively control growth of tumors [87] . This cytolytic DNA vaccine is unique as it is based on a bicistronic plasmid with the ability to coexpress antigen and PRF in a balanced mechanism causing necrosis of vaccine-transduced cells, followed by increased activation of immune cells and cross presentation of vaccine immunogen. abstract: DNA vaccines present one of the most cost-effective platforms to develop global vaccines, which have been tested for nearly three decades in preclinical and clinical settings with some success in the clinic. However, one of the major challenges for the development of DNA vaccines is their poor immunogenicity in humans, which has led to refinements in DNA delivery, dosage in prime/boost regimens and the inclusion of adjuvants to enhance their immunogenicity. In this review, we focus on adjuvants that can enhance the immunogenicity of DNA encoded antigens and highlight the development of a novel cytolytic DNA platform encoding a truncated mouse perforin. The application of this innovative DNA technology has considerable potential in the development of effective vaccines. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630607/ doi: 10.3390/vaccines7020038 id: cord-005377-36io7zsm author: Sidoti, Francesca title: Alternative Molecular Tests for Virological Diagnosis date: 2012-04-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Several nucleic acid amplification techniques (NAATs), particularly PCR and real-time PCR, are currently used in the routine clinical laboratories. Such approaches have allowed rapid diagnosis with a high degree of sensitivity and specificity. However, conventional PCR methods have several intrinsic disadvantages such as the requirement for temperature cycling apparatus, and sophisticated and costly analytical equipments. Therefore, amplification at a constant temperature is an attractive alternative method to avoid these requirements. A new generation of isothermal amplification techniques are gaining a wide popularity as diagnostic tools due to their simple operation, rapid reaction and easy detection. The main isothermal methods reviewed here include loop-mediated isothermal amplification, nucleic acid sequence-based amplification, and helicase-dependent amplification. In this review, design criteria, potential of amplification, and application of these alternative molecular tests will be discussed and compared to conventional NAATs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091206/ doi: 10.1007/s12033-012-9533-8 id: cord-265764-h4zg0q8x author: Singh, Kamaljit title: Synthesis of 4-aminoquinoline–pyrimidine hybrids as potent antimalarials and their mode of action studies date: 2013-06-10 words: 4082.0 sentences: 219.0 pages: flesch: 49.0 cache: ./cache/cord-265764-h4zg0q8x.txt txt: ./txt/cord-265764-h4zg0q8x.txt summary: On the other hand, pyrimidine-based compounds are well known for their wide range of promising antiviral [22] , antitubercular [23] , anti-AIDS [24] , antinociceptive [25] , antifungal [26] , antitumor [27] and antimalarial activities [28] apart from their role in the nucleic acid synthesis. The in vitro antimalarial screening of the new synthesized compounds 5aeg revealed good to moderate activities in nM range against both the tested Dd2 (CQ S ) and D10 strains (CQ R ) of P. Analysis of the activity of the compounds recorded in Table 1 reveals that replacing C-5 ethyl ester of the previously reported [29] decrease in antimalarial activity against both the chloroquine sensitive and chloroquine resistant strains of P. In this study, we have evaluated the mechanism of antimalarial activity of the most potent compound 5b of the series by studying its binding with heme (Fig. 4) . abstract: One of the most viable options to tackle the growing resistance to the antimalarial drugs such as artemisinin is to resort to synthetic drugs. The multi-target strategy involving the use of hybrid drugs has shown promise. In line with this, new hybrids of quinoline with pyrimidine have been synthesized and evaluated for their antiplasmodial activity against both CQ(S) and CQ(R) strains of Plasmodium falciparum. These depicted activity in nanomolar range and were found to bind to heme as well as AT rich pUC18 DNA. url: https://www.ncbi.nlm.nih.gov/pubmed/23811093/ doi: 10.1016/j.ejmech.2013.05.046 id: cord-304375-l5gvpat3 author: Singh, Kamaljit title: 2-Aminopyrimidine based 4-aminoquinoline anti-plasmodial agents. Synthesis, biological activity, structure–activity relationship and mode of action studies date: 2012-03-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: 2-Aminopyrimidine based 4-aminoquinolines were synthesized using an efficacious protocol. Some of the compounds showed in vitro anti-plasmodial activity against drug-sensitive CQ(S) (3D7) and drug-resistant CQ(R) (K1) strains of Plasmodium falciparum in the nM range. In particular, 5-isopropyloxycarbonyl-6-methyl-4-(2-nitrophenyl)-2-[(7-chloroquinolin-4-ylamino)butylamino] pyrimidine depicted the lowest IC(50) (3.6 nM) value (56-fold less than CQ) against CQ(R) strain. Structure–activity profile and binding with heme, μ-oxo-heme have been studied. Binding assays with DNA revealed better binding with target parasite type AT rich pUC18 DNA. Most compounds were somewhat cytotoxic, but especially cytostatic. Molecular docking analysis with Pf DHFR allowed identification of stabilizing interactions. url: https://api.elsevier.com/content/article/pii/S0223523412001511 doi: 10.1016/j.ejmech.2012.03.007 id: cord-335839-wgdqu1s1 author: Singh, Meharban title: Pediatrics in 21(st) Century and Beyond date: 2016-08-10 words: 4423.0 sentences: 218.0 pages: flesch: 47.0 cache: ./cache/cord-335839-wgdqu1s1.txt txt: ./txt/cord-335839-wgdqu1s1.txt summary: Availability of totipotent stem cells and developments in transplant technology are likely to revolutionize the management of a variety of hematologic cancers and life-threatening genetic disorders. Availability of totipotent stem cells and developments in transplant technology are likely to revolutionize the management of a variety of hematologic cancers and life-threatening genetic disorders. The availability of newer vaccines by recombinant technology for emerging infective and for non-infective lifestyle diseases is likely to improve survival and quality of life. The availability of newer vaccines by recombinant technology for emerging infective and for non-infective lifestyle diseases is likely to improve survival and quality of life. There is going to be a greater focus on the Bpatient^having the disease rather than Bdisease^per se by practicing holistic pediatrics by effective utilization of alternative or complementary strategies for health care. The concept of functional foods is being increasingly exploited to prevent illness, promote health and improve quality of life. abstract: Pediatrics is a dynamic discipline and there is awareness and hope for actualizing outstanding achievements in the field of child health in 21(st) century and beyond. Improved lifestyle and quality of children’s health is likely to reduce the burden of adult diseases and enhance longevity because seeds of most adult diseases are sown in childhood. Identification and decoding of human genome is expected to revolutionize the practice of pediatrics. The day is not far off when a patient will walk into doctor’s chamber with an electronic or digital health history on a CD or palmtop and a decoded genomic constitution. There will be reduced burden of genetic diseases because of selective abortions of “defective” fetuses and replacement of “bad” genes with “good” ones by genetic engineering. Availability of totipotent stem cells and developments in transplant technology are likely to revolutionize the management of a variety of hematologic cancers and life-threatening genetic disorders. The possibility of producing flawless designer babies by advances in assisted reproductive technologies (ARTs) is likely to be mired by several ethical and legal issues. The availability of newer vaccines by recombinant technology for emerging infective and for non-infective lifestyle diseases is likely to improve survival and quality of life. There is going to be a greater focus on the “patient” having the disease rather than “disease” per se by practicing holistic pediatrics by effective utilization of alternative or complementary strategies for health care. Due to advances in technology, pediatrics may get further dehumanized. A true healer cannot simply rely on technology; there must be a spiritual bond between the patient and the physician by exploiting the concept of psycho-neuro-immunology and body-mind interactions. In the years to come, physicians are likely to play “god” but medicine can’t achieve immortality because anything born must die in accordance with nature’s recycling blueprint. The medical science is likely to improve longevity but our goal should be to improve the quality of life. url: https://www.ncbi.nlm.nih.gov/pubmed/27510612/ doi: 10.1007/s12098-016-2206-z id: cord-028729-vhpuvp4g author: Singh, Simranjeet title: Biological Biosensors for Monitoring and Diagnosis date: 2020-07-08 words: 4791.0 sentences: 291.0 pages: flesch: 34.0 cache: ./cache/cord-028729-vhpuvp4g.txt txt: ./txt/cord-028729-vhpuvp4g.txt summary: It also has immense applications in the detection of different contaminants in the food industry, environmental monitoring, disease diagnosis, etc. Biosensors are devices comprising of a biological and physicochemical component to detect an analyte by producing a signal which can be measured (Mishra et al. It is used for the detection of a pathogen in water and food by measuring the change in optical density or color of the test sample upon a chemical reaction (Park et al. Biosensors exhibit numerous promising applications in various fields such as environmental monitoring, molecular diagnostics, pathogen detection, food industries, etc. Majority of the biosensors developed for detecting pathogens involved in causing infectious disease are based on the principle of electrochemical reaction. On the other hand, different electrochemical biosensors have also been developed to detect the microbes in contaminated food. Electrochemical DNA sensors based on the use of gold nanoparticles: a review on recent developments abstract: Quantification and detection of various contaminants in the ecosystem have become critically important in the past few decades due to their exhaustive use in soil and aquatic ecosystems. The contamination by both organic and inorganic contaminants in the ecosystem has drawn attention due to their persistence, biological accumulation, and toxicity. Organic contaminants reach the air, water, food, soil, and other systems through drift mechanism and have detrimental effect on various life systems after entering the food chain, thus interfering the normal biological process of the ecosystem. Inorganic contaminants have less solubility, primarily get adsorbed, and accumulate on lower sediments. The sources of both organic and inorganic contaminants include anthropogenic activities which dispose industrial and sewage effluent directly into water bodies. Most of the contaminants are very much toxic and have tumorigenic, carcinogenic, and mutagenic effect on various life-forms. Biosensors have various prospective and existing applications in the detection of these compounds in the environment by transducing a signal. It also has immense applications in the detection of different contaminants in the food industry, environmental monitoring, disease diagnosis, etc. where reliable and precise analyses are required. This chapter points out a comprehensive glimpse on different biosensors and their characteristics, operating principles, and their designs, based on transduction types and biological components. Efforts have been made to summarize various applications of biosensors in food industry, environmental monitoring, drug delivery systems, and clinical diagnostics etc. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340096/ doi: 10.1007/978-981-15-2817-0_14 id: cord-016588-f8uvhstb author: Sintchenko, Vitali title: Informatics for Infectious Disease Research and Control date: 2009-10-03 words: 8186.0 sentences: 393.0 pages: flesch: 36.0 cache: ./cache/cord-016588-f8uvhstb.txt txt: ./txt/cord-016588-f8uvhstb.txt summary: The goal of infectious disease informatics is to optimize the clinical and public health management of infectious diseases through improvements in the development and use of antimicrobials, the design of more effective vaccines, the identification of biomarkers for life-threatening infections, a better understanding of host-pathogen interactions, and biosurveillance and clinical decision support. "New Age" infectious disease informatics rests on advances in microbial genomics, the sequencing and comparative study of the genomes of pathogens, and proteomics or the identification and characterization of their protein related properties and reconstruction of metabolic and regulatory pathways (Bansal 2005) . The figure was produced using Artemis software (The Wellcome Trust Sanger Institute, UK) 1 Informatics for Infectious Disease Research and Control evidence-based gene calling or translating alignments of the DNA sequence to known proteins; and (3) aligning cDNAs from the same or related species. abstract: The goal of infectious disease informatics is to optimize the clinical and public health management of infectious diseases through improvements in the development and use of antimicrobials, the design of more effective vaccines, the identification of biomarkers for life-threatening infections, a better understanding of host-pathogen interactions, and biosurveillance and clinical decision support. Infectious disease informatics can lead to more targeted and effective approaches for the prevention, diagnosis and treatment of infections through a comprehensive review of the genetic repertoire and metabolic profiles of a pathogen. The developments in informatics have been critical in boosting the translational science and in supporting both reductionist and integrative research paradigms. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120928/ doi: 10.1007/978-1-4419-1327-2_1 id: cord-016417-3cwwmyv9 author: Sluijter, J. P. G. title: Quantitative Real-Time PCR date: 2006 words: 3110.0 sentences: 174.0 pages: flesch: 53.0 cache: ./cache/cord-016417-3cwwmyv9.txt txt: ./txt/cord-016417-3cwwmyv9.txt summary: In this chapter, we focus on the newest advancements in reverse transcription polymerase chain reaction (rt-pcr) technology, the real-time PCR or quantitative PCR, using small amounts of RNA to determine expression levels.We discuss the technique in general and describe two different approaches. Traditional methods to quantify mRNA expression levels are Northern blotting, in situ hybridization, ribonuclease protection, cDNA arrays, and reverse transcription polymerase chain reaction (rt-pcr). PCR amplification of your target DNA will increase the number of probes that hybridize with the complementary template. Accumulation of the released reporter molecules during the amplification cycles results in an increasing fluorescent signal and is correlated to the amount of the target DNA present. When the probe binds to the target sequence this will result in a separation of the reporter and quencher molecule and the fluorescent signal can be monitored. Amplification in a real-time PCR will increase the target DNA and therefore also the observed fluorescent signal. abstract: Changes in mRNA expression levels occur during physiological and pathological processes in the cardiovascular system. An increase inDNAtranscription results in increasedmRNAlevels and will subsequently result in increased protein levels that regulate processes inside and outside the cell. To determine alterations in mRNA levels, traditional methods such as Northern blot and ribonuclease protection assay can be used; however, large amounts of RNA are necessary and the methods are very labor intensive. In this chapter, we focus on the newest advancements in reverse transcription polymerase chain reaction (rt-pcr) technology, the real-time PCR or quantitative PCR, using small amounts of RNA to determine expression levels.We discuss the technique in general and describe two different approaches. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120686/ doi: 10.1007/0-387-23329-6_4 id: cord-291349-tq2n4mx3 author: Smith, Kevin R title: Gene transfer in higher animals: theoretical considerations and key concepts date: 2002-10-09 words: 12232.0 sentences: 661.0 pages: flesch: 45.0 cache: ./cache/cord-291349-tq2n4mx3.txt txt: ./txt/cord-291349-tq2n4mx3.txt summary: The prospects for germline transgenesis via nuclear transfer (NT) are very significant: transgenes can be introduced to donor cells in vitro, permitting the production of genetically modified animals by NT . However, although retroviral-mediated gene therapy has been used successfully for (nonhuman) germline modifications, the most used */and to date the most useful */method for germline transgenesis is microinjection, reviewed in the following section. Because there are no special problems with microinjecting large transgene constructs, it is possible to incorporate structural gene-plus-promoter (plus other potentially useful sequences such as enhancers) combinations into the host genome. Therefore, the use of germline gene targeting as a means to avoiding transgene expression problems awaits progress in ES cell technology and NT technology. Following liposome-mediated gene transfer, amongst transgene molecules reaching the nucleus, only a minority integrate into the host cell chromosomes. abstract: Gene transfer technology provides the ability to genetically manipulate the cells of higher animals. Gene transfer permits both germline and somatic alterations. Such genetic manipulation is the basis for animal transgenesis goals and gene therapy attempts. Improvements in gene transfer are required in terms of transgene design to permit gene targeting, and in terms of transfection approaches to allow improved transgene uptake efficiencies. url: https://www.ncbi.nlm.nih.gov/pubmed/12204554/ doi: 10.1016/s0168-1656(02)00105-0 id: cord-341287-i1hyk962 author: Smith, Trevor R. F. title: Immunogenicity of a DNA vaccine candidate for COVID-19 date: 2020-05-20 words: 7803.0 sentences: 446.0 pages: flesch: 54.0 cache: ./cache/cord-341287-i1hyk962.txt txt: ./txt/cord-341287-i1hyk962.txt summary: Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. In subjects immunized with INO-4700 (MERS-CoV S protein DNA vaccine) durable neutralizing antibodies (nAbs) and T cell immune responses were measured, and a seroconversion rate of 96% was observed and immunity was followed for 60 weeks in most study volunteers 9 . We followed the induction of immunity by the selected immunogen in mice and guinea pigs, measuring SARS-CoV-2 S protein-specific antibody levels in serum and in the lung fluid, and antibody functionality through competitive inhibition of ACE2 binding, pseudovirus and live virus neutralization. In summary, humoral immunogenicity testing in both mice and guinea pigs revealed the COVID-19 vaccine candidate, INO-4800, was capable of eliciting functional blocking antibody responses to SARS-CoV-2 spike protein. abstract: The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study. url: https://www.ncbi.nlm.nih.gov/pubmed/32433465/ doi: 10.1038/s41467-020-16505-0 id: cord-015935-r2wd1yfa author: Sokol, Deborah K. title: The Genetics of Autism date: 2011-02-10 words: 11276.0 sentences: 598.0 pages: flesch: 45.0 cache: ./cache/cord-015935-r2wd1yfa.txt txt: ./txt/cord-015935-r2wd1yfa.txt summary: Another offshoot of microarray technology is submicroscopic chromosome copy number variation (CNV) analysis, in which deletions or duplications involving > 1-kb DNA have been detected in patients with mental retardation, autism, and multiple congenital anomalies. Technology compatible with this approach includes cytogenetics (including karyotyping and FISH), gene association studies (analysis of genes and protein system from less complex genetic syndromes similar to autism such as Rett and fragile X syndromes), linkage studies (including genome screens in affected sibling pairs), microarray technology, and CNV analysis. Cytogenetic approaches provided the first evidence for an autism gene 40 years ago when Lubs (1969) identified an abnormal or "fragile" site on the long arm of chromosome X in four males with mental retardation, leading to the recognition of fragile X syndrome (FXS). As chromosome 7q has been discussed in section "Cytogenetics: Rare Mutations," chromosome 2 and then 17q11 will follow the description of how linkage studies led to the discovery of the gene loci for a syndromic form of autism: tuberous sclerosis complex (TSC). abstract: This chapter is written to make the fast-paced, expanding field of the genetics of autism accessible to those practitioners who help children with autism. New genetic knowledge and technology have quickly developed over the past 30 years, particularly within the past decade, and have made many optimistic about our ability to explain autism. Among these advances include the sequencing of the human genome (Lander et al., 2001) and the identification of common genetic variants via the HapMap project (International HapMap Consortium, 2005), and the development of cost-efficient genotyping and analysis technologies (Losh, Sullivan, Trembath, & Piven, 2008). Improvement in technology has led to improved visualization of chromosomal abnormality down to the molecular level. The four most common syndromes associated with autism include fragile X syndrome, tuberous sclerosis, 15q duplications, and untreated phenylketonuria (PKU; Costa e Silva, 2008). FXS and 15q duplications are discussed within the context of cytogenetics. TSC is illustrated within the description of linkage analysis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120060/ doi: 10.1007/978-1-4419-8065-6_6 id: cord-012654-m8nlsutd author: Song, Zhiquan title: Genome-wide identification of DNA-PKcs-associated RNAs by RIP-Seq date: 2019-07-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799803/ doi: 10.1038/s41392-019-0057-6 id: cord-305024-343l2ha7 author: Sonntag, Michael title: New Adenovirus in Bats, Germany date: 2009-12-17 words: 1686.0 sentences: 82.0 pages: flesch: 44.0 cache: ./cache/cord-305024-343l2ha7.txt txt: ./txt/cord-305024-343l2ha7.txt summary: We performed an extensive search for unknown viruses in 55 German vespertilionid bats based on both generic PCR assays and virus isolation techniques, as part of a broader study investigating histopathologic changes in German bats in association with infectious pathogens. The obtained sequence of a fragment of the DNA polymerase gene (≈550 bp) indicated that the viruses were a novel virus type within the genus Mastadenovirus and was tentatively named bat adenovirus 2 (bat AdV-2) strain P. Although viruses were not detected by various generic PCR assays from homogenized frozen tissue samples, we isolated a novel virus from a hibernating insectivorous bat species. The acquired partial sequence of the bat AdV-2 DNA polymerase with the closest relation to canine adenovirus (only 74% at the nucleic acid level) and the isolation from a new animal host suggests that this virus is a new adenovirus species within the genus Mastadenovirus. abstract: We tested 55 deceased vespertilionid bats of 12 species from southern Germany for virus infections. A new adenovirus was isolated from tissue samples of 2 Pipistrellus pipistrellus bats, which represents the only chiropteran virus isolate found in Europe besides lyssavirus (rabies virus). Evidence was found for adenovirus transmission between bats. url: https://www.ncbi.nlm.nih.gov/pubmed/19961700/ doi: 10.3201/eid1512.090646 id: cord-336636-xgfw21hk author: Spezia, Pietro Giorgio title: Redondovirus DNA in human respiratory samples date: 2020-08-15 words: 1889.0 sentences: 110.0 pages: flesch: 48.0 cache: ./cache/cord-336636-xgfw21hk.txt txt: ./txt/cord-336636-xgfw21hk.txt summary: Abstract Background Redondovirus (ReDoV) is a recently discovered circular, Rep-encoding single-stranded DNA (CRESS-DNA) virus in humans. While attempting to study human virome in bronchoalveolar lavage (BAL) samples of lung transplant patients [1, 2] , Abbas and colleagues identified sequence reads that aligned with low-coverage to a poorly characterized circovirus, named porcine stool-associated circular virus-5 (PoSCV-5) [3] . These observations suggest that ReDoV is not part of the normal oral and/or respiratory microflora of humans, differently to other circular single-stranded DNA viruses [5, 15] and that its infection might be involved in clinically relevant disorders. Redondoviridae, a family of small, circular DNA viruses of the human oro-respiratory tract associated with periodontitis and critical illness Identification and genetic characterization of a novel circular single-stranded DNA virus in a human upper respiratory tract sample abstract: Abstract Background Redondovirus (ReDoV) is a recently discovered circular, Rep-encoding single-stranded DNA (CRESS-DNA) virus in humans. Its pathogenesis and clinical associations are still completely unknown. Methods The presence of ReDoV DNA was investigated in biological specimens of 543 Italian subjects by in-house developed PCR assays. Results The overall ReDoV prevalence was about 4% (23 of 543 samples). The virus was detected in 22 of 209 (11 %) respiratory samples. One stool sample was also ReDoV positive. Viral DNA was not found in blood samples from immunocompetent and immunosuppressed subjects and cerebrospinal fluids from patients with neurological diseases. Genomic nucleotide differences were detected among the ReDoV isolates by sequencing a 582-nucleotide fragment of the capsid gene of the viral genome. Conclusions The results demonstrate that ReDoV is mainly present in the respiratory tract of infected people. Further investigations are needed to reveal possible clinical implications of this new CRESS-DNA virus in humans. url: https://www.ncbi.nlm.nih.gov/pubmed/32841923/ doi: 10.1016/j.jcv.2020.104586 id: cord-006331-s2qf98lj author: Spiridonova, V. A. title: Molecular recognition elements: DNA/RNA-aptamers to proteins date: 2010-05-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The review summarizes data on DNA/RNA aptamers, a novel class of molecular recognition elements. Special attention is paid to the aptamers to proteins involved into pathogenesis of wide spread human diseases. These include aptamers to serine proteases, cytokines, influenza viral proteins, immune deficiency virus protein and nucleic acid binding proteins. High affinity and specific binding of aptamers to particular protein targets make them attractive as direct protein inhibitors. They can inhibit pathogenic proteins and data presented here demonstrate that the idea that nucleic acid aptamers can regulate (inhibit) activity of protein targets has been transformed from the stage of basic developments into the stage of realization of practical tasks. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101625/ doi: 10.1134/s1990750810020046 id: cord-269124-oreg7rnj author: Spyrou, Maria A. title: Ancient pathogen genomics as an emerging tool for infectious disease research date: 2019-04-05 words: 11932.0 sentences: 518.0 pages: flesch: 42.0 cache: ./cache/cord-269124-oreg7rnj.txt txt: ./txt/cord-269124-oreg7rnj.txt summary: Examples of tools that have shown their effectiveness with ancient metagenomic DNA include the widely used Basic Local Alignment Search Tool (BLAST) 68 ; the MEGAN Alignment Tool (MALT) 41 , which involves a taxonomic binning algorithm that can use whole genome databases (such as the National Center for Biotechnical Information (NCBI) Reference Sequence (RefSeq) database 69 ); Metagenomic Phylogenetic Analysis (MetaPhlAn) 70 , which is also integrated into the metagenomic pipeline MetaBIT 71 and uses thousands (or millions) of marker genes for the distinction of specific microbial clades; or Kraken 72 , an alignment free sequence classifier that is based on k-mer matching of a query to a constructed database. Similar limitations can arise when the evolutionary history of a microorganism is vastly affected by recombination, as observed for HBV 44, 53 , although HBV molecular dating was recently attempted using a different genomic data set and suggested that the currently explored diversity of Old and New World pri mate lineages (including all human genotypes) may have emerged within the last 20,000 years 43 . abstract: Over the past decade, a genomics revolution, made possible through the development of high-throughput sequencing, has triggered considerable progress in the study of ancient DNA, enabling complete genomes of past organisms to be reconstructed. A newly established branch of this field, ancient pathogen genomics, affords an in-depth view of microbial evolution by providing a molecular fossil record for a number of human-associated pathogens. Recent accomplishments include the confident identification of causative agents from past pandemics, the discovery of microbial lineages that are now extinct, the extrapolation of past emergence events on a chronological scale and the characterization of long-term evolutionary history of microorganisms that remain relevant to public health today. In this Review, we discuss methodological advancements, persistent challenges and novel revelations gained through the study of ancient pathogen genomes. url: https://doi.org/10.1038/s41576-019-0119-1 doi: 10.1038/s41576-019-0119-1 id: cord-259929-02765q5j author: Stanley, Philip M. title: Decoding DNA data storage for investment date: 2020-09-28 words: 5978.0 sentences: 308.0 pages: flesch: 47.0 cache: ./cache/cord-259929-02765q5j.txt txt: ./txt/cord-259929-02765q5j.txt summary: Moving forward, the concerted efforts of academia, large corporates, innovative startup companies together with venture capital investment will be required to propel DNA data storage to commercial scale. Interdisciplinary efforts spanning molecular biology, computer science, and information technology are required to reach a complete DNA data storage workflow and in the following paragraphs, several of these approaches are discussed in more depth. First, the past seven years have seen a rapid increase in total capital invested in companies developing DNA data storage-enabling technologies (Figure 3a) , averaging a 44% compound annual growth rate (CAGR). Given DNA data storage"s technology maturity time-scale, venture capital firms companies investing in this space (see 4.) would already be operating with a long-term view and longer timelines than are typical for other fields of investment. abstract: While DNA's perpetual role in biology and life science is well documented, its burgeoning digital applications are beginning to garner significant interest. As the development of novel technologies requires continuous research, product development, startup creation, and financing, this work provides an overview of each respective area and highlights current trends, challenges, and opportunities. These are supported by numerous interviews with key opinion leaders from across academia, government agencies and the commercial sector, as well as investment data analysis. Our findings illustrate the societal and economic need for technological innovation and disruption in data storage, paving the way for nature's own time-tested, advantageous, and unrivaled solution. We anticipate a significant increase in available investment capital and continuous scientific progress, creating a ripe environment on which DNA data storage-enabling startups can capitalize to bring DNA data storage into daily life. url: https://www.sciencedirect.com/science/article/pii/S0734975020301415?v=s5 doi: 10.1016/j.biotechadv.2020.107639 id: cord-286684-2xmd3jfo author: Stefanetti, Valentina title: Retrospective Biomolecular Investigation of Coxiella burnetii and Leptospira spp. DNA in Cases of Abortion, Stillbirth and Neonatal Mortality in Dogs and Cats date: 2018-08-20 words: 3428.0 sentences: 183.0 pages: flesch: 50.0 cache: ./cache/cord-286684-2xmd3jfo.txt txt: ./txt/cord-286684-2xmd3jfo.txt summary: Leptospira interrogans sensu lato is able to cause abortion or stillbirth in several animal species and its abortigenic role has occasionally been described in bitches and queens. DNA in a retrospective series of 103 cases of canine and feline abortion, stillbirth, and neonatal mortality submitted for the identification of possible infectious agents. DNA in a retrospective series of cases of canine and feline abortion, stillbirth, and neonatal mortality submitted to a diagnostic laboratory of infectious diseases. biflexa serovar patoc, type Patoc), and unrelated bacteria (Streptococcus spp.; Eschericia coli; Klebsiella pneumoniae; Pseudomonas aeruginosa; Staphylococcus intermedius; Proteus vulgaris; Enterococcus faecalis), as well as DNA from bovine and caprine faeces and clinical specimens from animals with previously diagnosed Leptospira infection, were used to test the specificity of the protocol. burnetii and Leptospira has been previously reported in the same geographical area and time frame in which this study was conducted, although in different animal species; leptospiral DNA was found in equine abortion and stillbirth, 25 whereas C. abstract: Abortion and neonatal mortality are events that can occur in breeding bitches and queens. It has been reported that up to 55% and 33% of these cases remain without a known cause, respectively, in canine and feline pregnancies. Unusual abortigenic and potentially zoonotic agents, including Coxiella burnetii and Leptospira spp., may be involved in these cases. C. burnetii is able to cause reproductive disorders in cattle, sheep and goats, and cases of abortion have been observed in dogs and cats. Moreover, several outbreaks of C. burnetii infection in humans have been caused by delivering bitches and queens, and some of these animals experienced abortion. Leptospira interrogans sensu lato is able to cause abortion or stillbirth in several animal species and its abortigenic role has occasionally been described in bitches and queens. The aim of this study was to search for C. burnetii and Leptospira spp. DNA in a retrospective series of 103 cases of canine and feline abortion, stillbirth, and neonatal mortality submitted for the identification of possible infectious agents. One hundred and fifty-one specimens were tested using PCR assays and found negative for C. burnetii and Leptospira DNA. However, in 49 samples (47.6%) other infectious causes of abortion, stillbirth, and neonatal mortality were identified. These results showed that C. burnetii and Leptospira spp. are probably not common abortigenic agents or causes of neonatal deaths in dogs. However, given the potential abortigentic and zoonotic role of these agents, surveillance of canine and feline abortion, stillbirth, and neonatal mortality could be advisable for a systematic investigation of these events. url: https://www.ncbi.nlm.nih.gov/pubmed/30502862/ doi: 10.1053/j.tcam.2018.08.005 id: cord-027865-p1epjn51 author: Sterchi, Diane L. title: Molecular pathology date: 2020-06-22 words: 13228.0 sentences: 841.0 pages: flesch: 54.0 cache: ./cache/cord-027865-p1epjn51.txt txt: ./txt/cord-027865-p1epjn51.txt summary: ISH is a method of localizing and detecting specific mRNA sequences in preserved tissue sections or cell preparations by hybridizing the complementary strand of a nucleotide probe to the sequence of interest. (See Data Sheet Kappa and Lambda Probe ISH Kit, Novacastra.) (Fig. 21.3.) Chromogenic in situ hybridization (CISH) is a method ''that enables the detection of gene expression in the nucleus using a conventional histochemical reaction'' (White 2005) ; it is used for the detection of abnormal genes and to identify a gene therapy treatment direction. However, FISH still has an advantage over chromogenic methods for labeling specific nucleic acid sequences in cells and tissues. This may be done by using the normal detection procedure for the ISH method on dots of labeled nucleic acid sequence and a labeled control applied at matching descending concentrations on a positively charged nylon membrane. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315333/ doi: 10.1016/b978-0-7020-4226-3.00021-4 id: cord-352172-g0jiaenw author: Stoevesandt, Oda title: Protein microarrays: high-throughput tools for proteomics date: 2014-01-09 words: 7464.0 sentences: 373.0 pages: flesch: 32.0 cache: ./cache/cord-352172-g0jiaenw.txt txt: ./txt/cord-352172-g0jiaenw.txt summary: While conventionally made by the spotting of purified proteins, recent advances in technology have made it possible to produce protein microarrays through in situ cell-free synthesis directly from corresponding DNA arrays. Protein microarray technology has rapidly developed into one of the most active areas in biotechnology today, and is being increasingly applied for the high-throughput discovery of molecular interactions, profiling of protein expression and monitoring of protein modifications. While genome sequencing and annotations provide comprehensive information on protein-encoding genes, and DNA arrays analyze gene expression at the mRNA level, these technologies need to be complemented by functional proteomic studies in order to better understand protein activities, expression levels and interactions at the system level. A reverse-phase micro array approach has been successfully applied to discover distinct pathway-activation differences among breast cancer cell lines, demonstrating the use of array-based ana lysis for multiple pharmacodynamic biomarkers responding to targeted kinase inhibitors [108] . abstract: Protein microarrays are versatile tools for parallel, miniaturized screening of binding events involving large numbers of immobilized proteins in a time- and cost-effective manner. They are increasingly applied for high-throughput protein analyses in many research areas, such as protein interactions, expression profiling and target discovery. While conventionally made by the spotting of purified proteins, recent advances in technology have made it possible to produce protein microarrays through in situ cell-free synthesis directly from corresponding DNA arrays. This article reviews recent developments in the generation of protein microarrays and their applications in proteomics and diagnostics. url: https://www.ncbi.nlm.nih.gov/pubmed/19385942/ doi: 10.1586/epr.09.2 id: cord-009615-xcz8m9a7 author: Stoner, Gerald L. title: Polyomavirus Models of Brain Infection and the Pathogenesis of Multiple Sclerosis date: 2008-01-28 words: 6395.0 sentences: 329.0 pages: flesch: 44.0 cache: ./cache/cord-009615-xcz8m9a7.txt txt: ./txt/cord-009615-xcz8m9a7.txt summary: Animal models of viral demyelination and studies showing that JC virus (JCV), the polyomavirus which causes progressive multifocal leukoencephalopathy (PML), may be latent in some normal human brains suggest another possibility. It is thought that an MS virus could be one of two basic types: 1) A rare agent which infects relatively few individuals but is frequently pathogenic, or 2) A common agent which infects a majority of the population and perhaps a significant number of normal brains, but, in which the virus expression and the host response to the infection ( Immunocytochemical studies in our laboratory indicate that perivascular cellular infiltration, apparently due to immunological reactivity to SV40 antigens, occurs in this model (Fig. 1) . Thus, simian immunodeficiency virus (S1V)-infected macaques should be observed regularly for the possible occurrence of MS-like signs with demyelination attributable to mononuclear cell infiltration in response to abortively infected glial cells, rather twa-stage process of deletion and duplication known as "brain adaptation" to generate the progressive multifocal leukoencephalopathy (PML)-type viral genome capable of replicating in glial cells of the human brain. abstract: Multiple sclerosis (MS) is generally considered to be an autoimmune disorder with myelin as the target and with several unidentified viruses playing ancillary roles, possibly through molecular mimicry. Although this paradigm has led to important progress on potential mechanisms of myelin loss, neither a target antigen in myelin nor a triggering mechanism has yet been identified, leaving the etiology of MS still unknown. Animal models of viral demyelination and studies showing that JC virus (JCV), the polyomavirus which causes progressive multifocal leukoencephalopathy (PML), may be latent in some normal human brains suggest another possibility. A host immune response targeting proteins expressed at low levels from viral DNA latent in the central nervous system (CNS) might underlie a focal demyelinating disease such as MS. A shift from autoimmunity to a latent‐virus model is not a trivial substitution of target antigens. This shift would expand the search for a definitive laboratory test for MS and could lead to improved therapeutic and preventive approaches. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161790/ doi: 10.1111/j.1750-3639.1993.tb00748.x id: cord-309083-ew9cwiw0 author: Su, Hang title: Cyprinid viral diseases and vaccine development date: 2018-09-07 words: 11167.0 sentences: 585.0 pages: flesch: 43.0 cache: ./cache/cord-309083-ew9cwiw0.txt txt: ./txt/cord-309083-ew9cwiw0.txt summary: In this review, authors summarized six major cyprinid viral diseases, including koi herpesvirus disease (KHVD), spring viraemia of carp (SVC), grass carp hemorrhagic disease (GCHD), koi sleepy disease (KSD), carp pox disease (CPD) and herpesviral haematopoietic necrosis (HPHN). Challenge experiment reveals that the oral recombinant subunit vaccine can protect 50%-60% grass carp from infection and generate immunity against GCRV [199] . Oral vaccination is an effective way to induce mucosal immunity [215] and this strategy has shown a successful induction of the antiviral responses against viral diseases in different fish species [165] . Gene expression analysis of common carp (Cyprinus carpio L.) lines during cyprinid herpesvirus 3 infection yields insights into differential immune responses Recombinant lactobacillus expressing G protein of spring viremia of carp virus (SVCV) combined with ORF81 protein of koi herpesvirus (KHV): a promising way to induce protective immunity against SVCV and KHV infection in cyprinid fish via oral vaccination abstract: In the past decades, global freshwater fish production has been rapidly growing, while cyprinid takes the largest portion. Along with the rapid rise of novel forms of intensive aquaculture, increased global aquatic animal movement and various anthropogenic stress to aquatic ecosystems during the past century, freshwater fish farming industry encounter the emergence and breakout of many diseases, especially viral diseases. Because of the ability to safely and effectively prevent aquaculture diseases, vaccines have become the mainstream technology for prevention and control of aquatic diseases in the world. In this review, authors summarized six major cyprinid viral diseases, including koi herpesvirus disease (KHVD), spring viraemia of carp (SVC), grass carp hemorrhagic disease (GCHD), koi sleepy disease (KSD), carp pox disease (CPD) and herpesviral haematopoietic necrosis (HPHN). The present review described the characteristics of these diseases from epidemiology, pathology, etiology and diagnostics. Furthermore, the development of specific vaccines respective to these diseases is stated according to preparation methods and immunization approaches. It is hoped that the review could contribute to aquaculture in prevention and controlling of cyprinid viral diseases, and serve the healthy and sustainable development of aquaculture industry. url: https://api.elsevier.com/content/article/pii/S1050464818305394 doi: 10.1016/j.fsi.2018.09.003 id: cord-335864-392xmrq0 author: Sun, Yu-Meng title: Principles and innovative technologies for decrypting noncoding RNAs: from discovery and functional prediction to clinical application date: 2020-08-10 words: 13942.0 sentences: 786.0 pages: flesch: 45.0 cache: ./cache/cord-335864-392xmrq0.txt txt: ./txt/cord-335864-392xmrq0.txt summary: With recent developments in sequencing methods and information analysis, an increasing number of novel ncRNAs have been identified, including long noncoding RNAs (lncRNAs) [5, 6] , circular RNAs (circRNAs) [7, 8] , and novel small ncRNAs [9] [10] [11] . Most circRNAs derived from mRNA back-splicing lose translational capacity because of the lack of effective ORFs or ribosome entry approaches, while a few circRNAs from coding or Sno-lncRNAs maintain their stability by their classical stem-loop structures of snoRNAs. c Alternative splicing within circRNAs. d A number of novel small ncRNAs derived from rRNAs (rRFs), tRNAs (tsRNAs), and snoRNAs (sdRNAs) have also been found to be enriched in RNA-induced silencing complexes (RISCs) and function in a miRNA-like pathway This approach can provide in-depth analysis of transcripts from target regions of genome. abstract: Noncoding RNAs (ncRNAs) are a large segment of the transcriptome that do not have apparent protein-coding roles, but they have been verified to play important roles in diverse biological processes, including disease pathogenesis. With the development of innovative technologies, an increasing number of novel ncRNAs have been uncovered; information about their prominent tissue-specific expression patterns, various interaction networks, and subcellular locations will undoubtedly enhance our understanding of their potential functions. Here, we summarized the principles and innovative methods for identifications of novel ncRNAs that have potential functional roles in cancer biology. Moreover, this review also provides alternative ncRNA databases based on high-throughput sequencing or experimental validation, and it briefly describes the current strategy for the clinical translation of cancer-associated ncRNAs to be used in diagnosis. url: https://doi.org/10.1186/s13045-020-00945-8 doi: 10.1186/s13045-020-00945-8 id: cord-017188-d3xg05ty author: Swartz, H.M. title: Free Radicals and Medicine date: 2005 words: 15533.0 sentences: 799.0 pages: flesch: 45.0 cache: ./cache/cord-017188-d3xg05ty.txt txt: ./txt/cord-017188-d3xg05ty.txt summary: Examples described include pulmonary free radical damage, free radicals and sickle cell disease, free radicals in amyotrophic lateral sclerosis, melanin and free radicals and the potential role of oxidative stress in the induction of cancer. The potential limiting factors for such studies include the technical problems of carrying out EPR measurements in human subjects and‚ for techniques that involve the administration of spin traps or other substances‚ the complex and difficult process for obtaining permission to administer substances to human subjects (Swartz‚ 2003) . The first in vivo spin trapping evidence for increased free radical formation was provided using the SOD1-G93A transgenic mouse model for FALS (Gurney et al.‚ 1998) . In conclusion‚ in vitro and in vivo experiments suggest that nitrone spin traps can potentially mitigate oxidative stress in FALS mutant overexpressing cells and mice and protect against progressive motor neuron death. abstract: EPR has been employed in attempts to understand the basis of specific pathophysiologies in which free radicals have a postulated role. Examples described include pulmonary free radical damage, free radicals and sickle cell disease, free radicals in amyotrophic lateral sclerosis, melanin and free radicals and the potential role of oxidative stress in the induction of cancer. The final section of the chapter describes the use of NMR as the spectroscopic measure of spin-trapped radicals, after they have reacted further to form diamagnetic species. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121688/ doi: 10.1007/0-387-26741-7_3 id: cord-282062-h9smg0w9 author: Takano, Tomomi title: Novel single-stranded, circular DNA virus identified in cats in Japan date: 2018-09-14 words: 1942.0 sentences: 124.0 pages: flesch: 56.0 cache: ./cache/cord-282062-h9smg0w9.txt txt: ./txt/cord-282062-h9smg0w9.txt summary: We detected a novel feline stool-associated circular DNA virus (FeSCV) in fecal samples from cats with diarrhea using consensus primers matching those of circovirus and cyclovirus. Feline cyclovirus was identified by next-generation sequencing analysis in which the viral gene was detected in a pooled fecal sample collected from 4-5 healthy cats. In this study, we performed nested PCR using Circoviridae family consensus primers and detected novel CRESS DNA viruses in several cats with diarrhea symptoms. However, we concluded that FeSCV is a circular DNA virus based on the following: 1) No Giardia intestinalis was detected in the fecal test, and 2) the complete genome of FeSCV was amplified using the rolling-circle amplification and inverse PCR assays. We detected a novel CRESS DNA virus, FeSCV, in fecal samples from cats. Although it was detected using consensus primers of circovirus and cyclovirus, FeSCV was phylogenetically positioned in a clade different from that of these viruses. abstract: We detected a novel feline stool-associated circular DNA virus (FeSCV) in fecal samples from cats with diarrhea using consensus primers matching those of circovirus and cyclovirus. FeSCV is a circular DNA virus containing a genome with a total length of 2,046 nt encoding 2 open reading frames. Phylogenetic analyses indicated that FeSCV is classified into a clade different from that of circovirus and cyclovirus. Since the FeSCVs detected in several cats in the same household had genetically similar genomes, these viruses are most likely derived from the same origin. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-018-4020-6) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1007/s00705-018-4020-6 doi: 10.1007/s00705-018-4020-6 id: cord-325280-4whzcmqv author: Takizawa, Naoki title: Current landscape and future prospects of antiviral drugs derived from microbial products date: 2017-10-11 words: 6601.0 sentences: 365.0 pages: flesch: 34.0 cache: ./cache/cord-325280-4whzcmqv.txt txt: ./txt/cord-325280-4whzcmqv.txt summary: In this review, we summarize antiviral microbial products discovered by Institute of Microbial Chemistry (IMC) and discuss antiviral compounds against influenza virus and HBV, because these two viruses threaten global human health now and antiviral drug against these two viruses have been developed. THE CONTRIBUTIONS OF IMC TO ANTIVIRAL RESEARCH Nucleos(t)ide analogs are a major class of approved antiviral drugs that exert therapeutic effects through incorporation into viral DNA and RNA to inhibit virus replication. Viral polymerase complex is a promising target for the development of anti-influenza drugs, because transcription and replication are critical steps for virus propagation. Potential applications of microbial products in anti-HBV drug development Approved nucleos(t)ide analogs competitively inhibit DNA elongation of viral polymerase after the conversion to triphosphate form by cellular enzymes. abstract: Viral infections are a major global health threat. Over the last 50 years, significant efforts have been devoted to the development of antiviral drugs and great success has been achieved for some viruses. However, other virus infections, such as epidemic influenza, still spread globally and new threats continue to arise from emerging and re-emerging viruses and drug-resistant viruses. In this review, the contributions of microbial products isolated in Institute of Microbial Chemistry for antiviral research are summarized. In addition, the current state of development of antiviral drugs that target influenza virus and hepatitis B virus, and the future prospects for antivirals from natural products are described and discussed. url: https://www.ncbi.nlm.nih.gov/pubmed/29018267/ doi: 10.1038/ja.2017.115 id: cord-356291-0x1jhya6 author: Tang, Liang title: Three-dimensional structure of the bacteriophage P22 tail machine date: 2005-06-02 words: 6191.0 sentences: 300.0 pages: flesch: 60.0 cache: ./cache/cord-356291-0x1jhya6.txt txt: ./txt/cord-356291-0x1jhya6.txt summary: The three-dimensional structure of the P22 tail machine determined by electron cryo-microscopy and image reconstruction reveals how the five types of polypeptides present as 51 subunits are organized into this molecular machine through twelve-, sixand three-fold symmetry, and provides insights into molecular events during host cell attachment and phage DNA translocation. The electron cryo-microscopy (cryoEM) structure of Bacillus phage SPP1 portal in complex with head completion proteins gp15 and gp16, through which the tail is connected to the head, revealed local conformational change of the portal upon binding of gp15 and the function of gp16 as a valve (Orlova et al, 2003) . Here, we present the three-dimensional structures of the tail machine and a C-terminally truncated form of the portal protein of bacteriophage P22 determined by cryoEM and image reconstruction. abstract: The tail of the bacteriophage P22 is composed of multiple protein components and integrates various biological functions that are crucial to the assembly and infection of the phage. The three-dimensional structure of the P22 tail machine determined by electron cryo-microscopy and image reconstruction reveals how the five types of polypeptides present as 51 subunits are organized into this molecular machine through twelve-, six- and three-fold symmetry, and provides insights into molecular events during host cell attachment and phage DNA translocation. url: http://europepmc.org/articles/pmc1150889?pdf=render doi: 10.1038/sj.emboj.7600695 id: cord-259738-yuqc6dk0 author: Tang, Mengjun title: Enhancement of the immunogenicity of an infectious bronchitis virus DNA vaccine by a bicistronic plasmid encoding nucleocapsid protein and interleukin-2 date: 2008-03-07 words: 3841.0 sentences: 209.0 pages: flesch: 49.0 cache: ./cache/cord-259738-yuqc6dk0.txt txt: ./txt/cord-259738-yuqc6dk0.txt summary: title: Enhancement of the immunogenicity of an infectious bronchitis virus DNA vaccine by a bicistronic plasmid encoding nucleocapsid protein and interleukin-2 A DNA vaccine against infectious bronchitis virus (IBV) can induce specific humoral and cell-mediated immunity. When chickens were challenged with a virulent strain of IBV, the protective efficacy could be enhanced significantly after immunization with bicistronic DNA vaccine. In the present study, a bicistronic plasmid encoding the nucleocapsid protein and immune-stimulatory interleukin-2 has been constructed and its immunogenicity and protective effect in chickens has been evaluated. These recombinant plasmids were inoculated in chickens and tested in a protection-challenge experiment, demonstrating that vaccination with the co-expression plasmid pIRES-N/IL2 can induce stronger immune response than vaccination with pIRES-N. These results suggested that vaccination with the co-expression plasmid of N protein gene and IL-2 may have increased the protection rate against challenge. Partial protection against infectious bursal disease virus through DNA-mediated vaccination with the VP2 capsid protein and chicken IL-2 genes abstract: A DNA vaccine against infectious bronchitis virus (IBV) can induce specific humoral and cell-mediated immunity. However, compared to conventional vaccines, DNA vaccines usually induce poor antibody responses. To develop a more potent IBV DNA vaccine formulations, a monocistronic vector encoding the nucleocapsid protein of IBV and a bicistronic vector separately encoding the nucleocapsid protein and immune-stimulatory interleukin-2 were constructed. When the DNA vaccines were administered to the quadriceps muscle of chickens, the induced humoral and cellular responses were evaluated. There was a significant difference in ELISA antibody levels elicited by either monocistronic or bicistronic DNA vaccines. The percentage of CD3(+), CD3(+)CD8(+) and CD3(+)CD4(+) subgroups of peripheral blood T-lymphocytes in chickens immunized with bicistronic DNA vaccine were higher than those in chickens immunized with monocistronic DNA vaccine. When chickens were challenged with a virulent strain of IBV, the protective efficacy could be enhanced significantly after immunization with bicistronic DNA vaccine. These results demonstrated that bicistronic DNA vaccine is an effective approach to increase IBV DNA vaccine immunogenicity. url: https://www.ncbi.nlm.nih.gov/pubmed/18329109/ doi: 10.1016/j.jviromet.2008.01.017 id: cord-296967-qiil3gqk author: Tatlow, Dean title: A novel concept for treatment and vaccination against Covid‐19 with an inhaled chitosan‐coated DNA vaccine encoding a secreted spike protein portion date: 2020-08-08 words: 2262.0 sentences: 143.0 pages: flesch: 52.0 cache: ./cache/cord-296967-qiil3gqk.txt txt: ./txt/cord-296967-qiil3gqk.txt summary: A novel concept in DNA vaccine design is the creation of an inhaled DNA plasmid construct containing a portion of the coronavirus spike protein for treatment and vaccination. An inhaled plasmid DNA vaccine replicates the route of lung infection taken by coronavirus with transfected cells secreting spike protein portions to induce immunity. 3 These findings of the identified spike proteins in the SARS-CoV-2 receptor binding domain and ACE2 region may provide useful information for treatment or vaccine development. 5 In this paper a series of inhaled plasmid DNA vaccine construct containing various forms of the coronavirus spike protein sequence may provide potential treatment and vaccine options as revealed by Yu et al. 3 Once in the lower respiratory tract or alveolar region of the lung deposited plasmid DNA will be taken up and expression of coronavirus spike proteins by host cells such as pneumocytes will occur. abstract: A novel concept in DNA vaccine design is the creation of an inhaled DNA plasmid construct containing a portion of the coronavirus spike protein for treatment and vaccination. The secretion of a spike protein portion will function as a competitive antagonist by interfering with the binding of coronavirus to the angiotensin‐converting enzyme 2 (ACE2) receptor. The secreted protein binding to the ACE2 receptor provides a unique mechanism of action for treatment to all strains of coronavirus in naïve patients, by blocking the ACE2 receptor site. An inhaled plasmid DNA vaccine replicates the route of lung infection taken by coronavirus with transfected cells secreting spike protein portions to induce immunity. Unlike most DNA vaccines with intracellular antigen presentation through MHC I, the current vaccine relies on the secreted proteins presentation through MHC II as well as MHC I to induce immunity. Lung specific production of vaccine particles by inhaled plasmid DNA is appealing since it may have limited systemic side‐effects, and may induce both humoral and cytotoxic immunity. Finally, the ease and ability to rapidly produce this plasmid construct makes this an ideal solution for managing the emerging threat of coronavirus. url: https://www.ncbi.nlm.nih.gov/pubmed/32881059/ doi: 10.1111/1440-1681.13393 id: cord-290284-aw8p35c5 author: Tatsis, Nia title: Adenoviruses as vaccine vectors date: 2016-12-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Adenoviruses have transitioned from tools for gene replacement therapy to bona fide vaccine delivery vehicles. They are attractive vaccine vectors as they induce both innate and adaptive immune responses in mammalian hosts. Currently, adenovirus vectors are being tested as subunit vaccine systems for numerous infectious agents ranging from malaria to HIV-1. Additionally, they are being explored as vaccines against a multitude of tumor-associated antigens. In this review we describe the molecular biology of adenoviruses as well as ways the adenovirus vectors can be manipulated to enhance their efficacy as vaccine carriers. We describe methods of evaluating immune responses to transgene products expressed by adenoviral vectors and discuss data on adenoviral vaccines to a selected number of pathogens. Last, we comment on the limitations of using human adenoviral vectors and provide alternatives to circumvent these problems. This field is growing at an exciting and rapid pace, thus we have limited our scope to the use of adenoviral vectors as vaccines against viral pathogens. url: https://www.sciencedirect.com/science/article/pii/S1525001604013425 doi: 10.1016/j.ymthe.2004.07.013 id: cord-320501-xqgqq55q author: Theobald, Nigel title: Emerging vaccine delivery systems for COVID-19: Functionalised silica nanoparticles offer a potentially safe and effective alternative delivery system for DNA/RNA vaccines and may be useful in the hunt for a COVID-19 vaccine date: 2020-06-24 words: 1203.0 sentences: 58.0 pages: flesch: 47.0 cache: ./cache/cord-320501-xqgqq55q.txt txt: ./txt/cord-320501-xqgqq55q.txt summary: title: Emerging vaccine delivery systems for COVID-19: Functionalised silica nanoparticles offer a potentially safe and effective alternative delivery system for DNA/RNA vaccines and may be useful in the hunt for a COVID-19 vaccine Liposomal encapsulation of drugs with bioavailability issues was a proven approach in small molecule pharma, and it was apparent to biopharma R&D scientists that LNPs could meet the basic requirements of an RNA/DNA delivery system too, namely to protect nucleic acid from in vivo digestion as it travels to the target. As scientists looked to alternative carriers that could be adapted to encapsulate and protect nucleic acids, mesoporous silica nanoparticles (MSNs)silica-based nanostructured materials with excellent biocompatibility and chemical stability This surface simply and effectively traps and protects nucleic acids (such as mRNA/pDNA) from nuclease enzymes as it travels to the cells. Once inside the cell, the DNA/RNA is released and will result in synthesis of the foreign/target protein which will activate the immune system, leading to both a cellular and humoral immune response. abstract: nan url: https://doi.org/10.1016/j.drudis.2020.06.020 doi: 10.1016/j.drudis.2020.06.020 id: cord-002982-zwvesrct author: Thiessen, Lindsey D. title: Development of a quantitative loop-mediated isothermal amplification assay for the field detection of Erysiphe necator date: 2018-04-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Plant pathogen detection systems have been useful tools to monitor inoculum presence and initiate management schedules. More recently, a loop-mediated isothermal amplification (LAMP) assay was successfully designed for field use in the grape powdery mildew pathosystem; however, false negatives or false positives were prevalent in grower-conducted assays due to the difficulty in perceiving the magnesium pyrophosphate precipitate at low DNA concentrations. A quantitative LAMP (qLAMP) assay using a fluorescence resonance energy transfer-based probe was assessed by grape growers in the Willamette Valley of Oregon. Custom impaction spore samplers were placed at a research vineyard and six commercial vineyard locations, and were tested bi-weekly by the lab and by growers. Grower-conducted qLAMP assays used a beta-version of the Smart-DART handheld LAMP reaction devices (Diagenetix, Inc., Honolulu, HI, USA), connected to Android 4.4 enabled, Bluetooth-capable Nexus 7 tablets for output. Quantification by a quantitative PCR assay was assumed correct to compare the lab and grower qLAMP assay quantification. Growers were able to conduct and interpret qLAMP results; however, the Erysiphe necator inoculum quantification was unreliable using the beta-Smart-DART devices. The qLAMP assay developed was sensitive to one spore in early testing of the assay, but decreased to >20 spores by the end of the trial. The qLAMP assay is not likely a suitable management tool for grape powdery mildew due to losses in sensitivity and decreasing costs and portability for other, more reliable molecular tools. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5912203/ doi: 10.7717/peerj.4639 id: cord-023928-9a1w174h author: Thomas, Neal J. title: Genetic Predisposition to Critical Illness in the Pediatric Intensive Care Unit date: 2011-12-16 words: 12255.0 sentences: 510.0 pages: flesch: 46.0 cache: ./cache/cord-023928-9a1w174h.txt txt: ./txt/cord-023928-9a1w174h.txt summary: authors: Thomas, Neal J.; Dahmer, Mary K.; Quasney, Michael W. Examples of the infl uence of genetic variations in proteins involved in recognition of pathogens on the severity of infections include polymorphisms in the genes coding for mannose binding Individual variability in the susceptibility to and outcome from critical care diseases has long been observed, and advances in genomic medicine now gives an opportunity to understand these differences. abstract: Much progress has been made in the past decade in the understanding of the genetic contribution to the development of human disease in general, and critical care illness specifically. With the mapping of the human genome and on-going mapping of genetic polymorphisms and haplotypes in humans, the field of critical care is now in prime position to study the impact of genetics on common illnesses that affect children who require critical care, to examine how differences of the host defense response lead to variable outcomes in outwardly appearing similar disease states, and to study how genetic differences in response to therapy will help practitioners tailor therapeutic interventions to an individual child’s genetic composition. While we are still years away from true individualized medicine, we are now closer than ever to understanding why two might children respond to the same environmental insult in vastly different ways. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178837/ doi: 10.1007/978-0-85729-923-9_11 id: cord-008613-tysyq6o4 author: Thomas, Sheila M. title: Two mRNAs that differ by two nontemplated nucleotides encode the amino coterminal proteins P and V of the paramyxovirus SV5 date: 1988-09-09 words: 8410.0 sentences: 433.0 pages: flesch: 60.0 cache: ./cache/cord-008613-tysyq6o4.txt txt: ./txt/cord-008613-tysyq6o4.txt summary: Simian virus 5 (SV5), a prototype paramyxovirus, has a single-stranded, negative sense genomic RNA (vRNA) approximately 15,000 nucleotides in chain length that is transcribed in infected cells by the virion-associated RNA transcriptase to yield virus-specific mRNAs. The SV5 "P" gene has been shown to encode both the P protein (Mr = 44,000), and protein V (Mr = 24,000) by the arrest of translation in vitro of both P and V using a cDNA clone derived from SV5-specific mRNAs (Paterson et al., 1984) . Antigenic Region Mapping of the P and V Monoclonal Antibodies on the P and V Gene Using T7 RNA Polymerase Runoff Transcripts, In Vitro Translation, and Immunoprecipitation The full-length P203-1 DNA insert cloned using Xbal linkers (XX) and a Hindlll to Xbal fragment (HX) containing the 3'' two-thirds of the P203-1 DNA were placed under the control of the T7 promoter in the plasmid pGEM-2. abstract: The “P≓ gene of the paramyxovirus SV5 encodes two known proteins, P (M(r) ≈ 44,000) and V (M(r) ≈ 24,000). The complete nucleotide sequence of the “P≓ gene has been obtained and is found to contain two open reading frames, neither of which is large enough to encode the P protein. We have shown that the P and V proteins are translated from two mRNAs that differ by the presence of two nontemplated G residues in the P mRNA. These two additional nucleotides convert the two open reading frames to one of 392 amino acids. The P and V proteins are amino coterminal and have 164 amino acids in common. The unique C terminus of V consists of a cysteine-rich region that resembles a cysteine-rich metal binding domain. An open reading frame that contains this cysteine-rich region exists in all other paramyxovirus “P≓ gene sequences examined, which suggests that it may have important biological significance. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133244/ doi: 10.1016/s0092-8674(88)91285-8 id: cord-017543-60q9iecq author: Tian, Wei-Chang title: Microfluidic Applications in Biodefense date: 2008-08-23 words: 16557.0 sentences: 831.0 pages: flesch: 37.0 cache: ./cache/cord-017543-60q9iecq.txt txt: ./txt/cord-017543-60q9iecq.txt summary: Sections cover microscale sample preparation methods; immunomagnetic separations and immunoassays; proteomics; polymerase chain reaction (PCR), quantitative PCR (qPCR) and other nucleic acid amplification methods; DNA microarrays, microelectrophoresis, and finally integrated Lab-on-a-Chip systems. The intent of JBAIDS Block III, Next Generation Diagnostics (NGD), is to establish a new system incorporating the capabilities of Block I and Block II capabilities (Table 10 .1) and adding immunoassay capabilities and the ability to identify up to 50 agents including toxins in 15 minutes using automated, miniaturized sample preparation integrated with analysis for nucleic acids and proteins, in a hand held or smaller format. They will need to be completely automated or simple to use; incorporate advanced technologies including sample preparation starting from primary samples (aerosols, blood, etc.), molecular detection, automation, microfluidics, and bioinformatics; reduce reagent consumption and space requirements; and provide cost and performance advantages compared to present systems. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122129/ doi: 10.1007/978-0-387-09480-9_10 id: cord-343775-tcljwdlo author: Tiee, Madeline S. title: Ghosts of infections past: using archival samples to understand a century of monkeypox virus prevalence among host communities across space and time date: 2018-01-31 words: 5321.0 sentences: 249.0 pages: flesch: 45.0 cache: ./cache/cord-343775-tcljwdlo.txt txt: ./txt/cord-343775-tcljwdlo.txt summary: Here, we screened over 1000 museum specimens collected over the past 120 years to examine the historical distribution and prevalence of monkeypox virus (MPXV) in five species of African rope squirrel (Funisciurus sp.) collected across Central Africa. Here, we screened over 1000 museum specimens collected over the past 120 years to examine the historical distribution and prevalence of monkeypox virus (MPXV) in five species of African rope squirrel (Funisciurus sp.) collected across Central Africa. As long as the assumptions inherent to these methods are acknowledged and when possible controlled for (such as sampling bias or the effects of specimen preparation and preservation methodology on DNA quality and amplification), museum sampling can be valuable for identifying potential host species and understanding broad geographical and temporal patterns of disease, especially in regions difficult to sample. abstract: Infectious diseases that originate from multiple wildlife hosts can be complex and problematic to manage. A full understanding is further limited by large temporal and spatial gaps in sampling. However, these limitations can be overcome, in part, by using historical samples, such as those derived from museum collections. Here, we screened over 1000 museum specimens collected over the past 120 years to examine the historical distribution and prevalence of monkeypox virus (MPXV) in five species of African rope squirrel (Funisciurus sp.) collected across Central Africa. We found evidence of MPXV infections in host species as early as 1899, half a century earlier than the first recognized case of MPXV in 1958, supporting the suggestion that historic pox-like outbreaks in humans and non-human primates may have been caused by MPXV rather than smallpox as originally thought. MPX viral DNA was found in 93 of 1038 (9.0%) specimens from five Funisciurus species (F. anerythrus, F. carruthersi, F. congicus, F. lemniscatus and F. pyrropus), of which F. carruthersi and pyrropus had not previously been identified as potential MPXV hosts. We additionally documented relative prevalence rates of infection in museum specimens of Funisciurus and examined the spatial and temporal distribution of MPXV in these potential host species across nearly a hundred years (1899–1993). url: https://www.ncbi.nlm.nih.gov/pubmed/29410823/ doi: 10.1098/rsos.171089 id: cord-011053-gza05hsv author: Tiew, Pei Yee title: The Mycobiome in Health and Disease: Emerging Concepts, Methodologies and Challenges date: 2020-01-01 words: 10936.0 sentences: 561.0 pages: flesch: 30.0 cache: ./cache/cord-011053-gza05hsv.txt txt: ./txt/cord-011053-gza05hsv.txt summary: In this state-of-the-art review, we discuss current diagnostic and therapeutic challenges associated with fungal disease and provide key examples where the application of sequencing technologies has potential diagnostic application in assessing the human ''mycobiome''. Despite their natural environmental abundance, few fungi are human pathogens, and while fulminant fungal infection is uncommon in the healthy individuals, invasive fungal disease is a concern in the immuno-compromised host with significant associated morbidity and mortality [2] . Increasing numbers of patients are at risk of invasive fungal disease including those with human immunodeficiency virus (HIV), malignancy and transplant recipients on immunosuppressive or immunomodulatory therapies, each contributing to the rising global trend of fungal infections among susceptible populations. Despite treatment, mortality rates for invasive fungal disease remain high with factors contributing to poor prognosis including delayed diagnosis and initiation of antifungal treatment, host factors, site of infection, emerging antifungal resistance and drug toxicity. abstract: Fungal disease is an increasingly recognised global clinical challenge associated with high mortality. Early diagnosis of fungal infection remains problematic due to the poor sensitivity and specificity of current diagnostic modalities. Advances in sequencing technologies hold promise in addressing these shortcomings and for improved fungal detection and identification. To translate such emerging approaches into mainstream clinical care will require refinement of current sequencing and analytical platforms, ensuring standardisation and consistency through robust clinical benchmarking and its validation across a range of patient populations. In this state-of-the-art review, we discuss current diagnostic and therapeutic challenges associated with fungal disease and provide key examples where the application of sequencing technologies has potential diagnostic application in assessing the human ‘mycobiome’. We assess how ready access to fungal sequencing may be exploited in broadening our insight into host–fungal interaction, providing scope for clinical diagnostics and the translation of emerging mycobiome research into clinical practice. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223441/ doi: 10.1007/s11046-019-00413-z id: cord-254942-g51mjj2b author: Touati, Rabeb title: New methodology for repetitive sequences identification in human X and Y chromosomes date: 2020-10-19 words: 7712.0 sentences: 513.0 pages: flesch: 52.0 cache: ./cache/cord-254942-g51mjj2b.txt txt: ./txt/cord-254942-g51mjj2b.txt summary: In this paper, we propose an efficient algorithm based on the signal and image processing tools to localize repetitive DNA sequences. Fig. 3 shows an example of the FCGS 2 signal, the correspondent scalogram in a 3D representation and the energy wavelet of a sequence located in chromosome X of the human genome. For each DNA image into the repeat-Data database, we aim to identify a DNA-reference sequence, to which corresponds the existing repetitive pattern in the scalogram. In the first result block, we provide the scalogram representation of the DNA sequence we have located at the X chromosome of the human genome (Xp22.33, position: [321001:322000bp]). Location of repetitive intronic satellites sequence "Rseq7" and the corresponding exonic modified sequences in different chromosomes of the human genome. These repetitive sequences are also located at the same position in intronic region within the DHRSX gene in the Y chromosome of the human genome. abstract: Repetitive DNA sequences occupy the major proportion of DNA in the human genome and even in the other species’ genomes. The importance of each repetitive DNA type depends on many factors: structural and functional roles, positions, lengths and numbers of these repetitions are clear examples. Conserving such DNA sequences or not in different locations in the chromosome remains a challenge for researchers in biology. Detecting their location despite their great variability and finding novel repetitive sequences remains a challenging task. To side-step this problem, we developed a new method based on signal and image processing tools. In fact, using this method we could find repetitive patterns in DNA images regardless of the repetition length. This new technique seems to be more efficient in detecting new repetitive sequences than bioinformatics tools. In fact, the classical tools present limited performances especially in case of mutations (insertion or deletion). However, modifying one or a few numbers of pixels in the image doesn’t affect the global form of the repetitive pattern. As a consequence, we generated a new repetitive patterns database which contains tandem and dispersed repeated sequences. The highly repetitive sequences, we have identified in X and Y chromosomes, are shown to be located in other human chromosomes or in other genomes. The data we have generated is then taken as input to a Convolutional neural network classifier in order to classify them. The system we have constructed is efficient and gives an average of 94.4% as recognition score. url: https://www.ncbi.nlm.nih.gov/pubmed/33101452/ doi: 10.1016/j.bspc.2020.102207 id: cord-317213-vhprfb1o author: Tram, Dai Thien Nhan title: Advances in nanomaterials and their applications in point of care (POC) devices for the diagnosis of infectious diseases date: 2016-09-26 words: 11575.0 sentences: 794.0 pages: flesch: 48.0 cache: ./cache/cord-317213-vhprfb1o.txt txt: ./txt/cord-317213-vhprfb1o.txt summary: This review presents an overview on how the POC-associated nanotechnology, currently applied for the identification of nucleic acids, proteins and antibodies, might be further exploited for the detection of infectious pathogens: although still premature, future integrations of nanoparticles with biological markers that target specific microorganisms will enable timely therapeutic intervention against life-threatening infectious diseases. • no tagging is required • about two orders of magnitude more sensitive than some common colorimetric techniques • selectivity down to the level of single-base mismatch • quantitative signal intensity varied with the length of target RNA sequence (Nam et al., 2004) Analyte: nucleotide sequence indicative of anthrax lethal factor Sample size: 30 μl Assay time: 3-4 h Detection range: 500 zM-5 fM Performance: abstract: Nanotechnology has gained much attention over the last decades, as it offers unique opportunities for the advancement of the next generation of sensing tools. Point-of-care (POC) devices for the selective detection of biomolecules using engineered nanoparticles have become a main research thrust in the diagnostic field. This review presents an overview on how the POC-associated nanotechnology, currently applied for the identification of nucleic acids, proteins and antibodies, might be further exploited for the detection of infectious pathogens: although still premature, future integrations of nanoparticles with biological markers that target specific microorganisms will enable timely therapeutic intervention against life-threatening infectious diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/27686397/ doi: 10.1016/j.biotechadv.2016.09.003 id: cord-017999-saxwqc2j author: Travers, Andrew A. title: Gene Regulation by HMGA and HMGB Chromosomal Proteins and Related Architectural DNA-Binding Proteins date: 2005 words: 6332.0 sentences: 294.0 pages: flesch: 48.0 cache: ./cache/cord-017999-saxwqc2j.txt txt: ./txt/cord-017999-saxwqc2j.txt summary: The eukaryotic abundant high mobility group HMGA and HMGB proteins can act as architectural transcription factors by promoting the assembly of higher-order protein-DNA complexes which can either activate or repress gene expression. Similarly rat SSRPl has been shown to facilitate the DNA binding of serum response factor and human SSRPl is associated with the y isoform of p63 in vivo at the endogenous MDM22inAp2nfl''"^^ promoters.^^ In most of these cases, the interaction of the HMG protein with the transcription factor has been detected in vitro and could, in principle, serve as the mechanism for recruitment of HMGB 1 or 2 to particular DNA sites. abstract: The eukaryotic abundant high mobility group HMGA and HMGB proteins can act as architectural transcription factors by promoting the assembly of higher-order protein-DNA complexes which can either activate or repress gene expression. The structural organisation of both classes of protein is similar with either a single or repeated DNA binding domain preceding a short negatively charged C-terminal tail. In the HMGB class of proteins the HMG DNA-binding domain binds non-specifically and introduces a sharp bend into DNA whereas the AT-hook in the HMGA protein binds preferentially to A/T rich regions of DNA and stabilises a B-DNA structure. The acidic tails are hypothesised to facilitate the interaction of the proteins with nudeosomes by binding to the positively charged histone tails. Both classes of protein also interact with a large number of transcription factors that bind to specific DNA sequences. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122717/ doi: 10.1007/0-387-29148-2_11 id: cord-289535-srrfr1es author: Tregoning, J. S. title: Vaccines for COVID‐19 date: 2020-10-18 words: 14329.0 sentences: 793.0 pages: flesch: 44.0 cache: ./cache/cord-289535-srrfr1es.txt txt: ./txt/cord-289535-srrfr1es.txt summary: One concern with vaccine development for SARS-CoV-2 is that the immune response can cause disease, often in the act of clearing the infection. Preclinical animal studies have demonstrated that DNA vaccines encoding the M, N, 3a or S proteins of the SARS-CoV-1 virus could elicit immune responses [180] [181] [182] . The S protein is the target of the only SARS-CoV-1 DNA vaccine to progress to Phase I clinical trial, delivered by bio-injector, and it was safe and induced neutralizing antibody responses [183] . T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial abstract: Since the emergence of COVID‐19, caused by the SARS‐CoV‐2 virus at the end of 2019, there has been an explosion of vaccine development. By 24 September 2020, a staggering number of vaccines (more than 200) had started preclinical development, of which 43 had entered clinical trials, including some approaches that have not previously been licensed for human vaccines. Vaccines have been widely considered as part of the exit strategy to enable the return to previous patterns of working, schooling and socializing. Importantly, to effectively control the COVID‐19 pandemic, production needs to be scaled‐up from a small number of preclinical doses to enough filled vials to immunize the world’s population, which requires close engagement with manufacturers and regulators. It will require a global effort to control the virus, necessitating equitable access for all countries to effective vaccines. This review explores the immune responses required to protect against SARS‐CoV‐2 and the potential for vaccine‐induced immunopathology. We describe the profile of the different platforms and the advantages and disadvantages of each approach. The review also addresses the critical steps between promising preclinical leads and manufacturing at scale. The issues faced during this pandemic and the platforms being developed to address it will be invaluable for future outbreak control. Nine months after the outbreak began we are at a point where preclinical and early clinical data are being generated for the vaccines; an overview of this important area will help our understanding of the next phases. url: https://www.ncbi.nlm.nih.gov/pubmed/32935331/ doi: 10.1111/cei.13517 id: cord-031565-mos619wp author: Troedsson, Christofer title: Quantification of copepod gut content by differential length amplification quantitative PCR (dla-qPCR) date: 2009-02-01 words: 4215.0 sentences: 211.0 pages: flesch: 47.0 cache: ./cache/cord-031565-mos619wp.txt txt: ./txt/cord-031565-mos619wp.txt summary: Recently, molecular based methods have demonstrated that DNA from prey species can be used to identify zooplankton gut contents, and further, quantitative gut content estimates by quantitative PCR (qPCR) assays targeted to the 18S rRNA gene have been used to estimate feeding rates in appendicularians and copepods. The assay utilizes multiple primer sets that amplify different sized fragments of the prey 18S rRNA gene and, based on the differential amplification of these fragments, the degree of digestion is estimated and corrected for. Recently, our group developed a PCR based assay for detection of prey content in the gut of the calanoid copepod Calanus finmarchicus (Nejstgaard et al. We refer to this method as ''''differential length amplification quantitative polymerase chain reaction'''' (dla-qPCR), and by amplifying different sized fragments of the same prey target gene extracted from copepod guts, we hypothesize that it would be possible to generate a digestion profile of a target prey species consumed by a copepod. abstract: Quantification of feeding rates and selectivity of zooplankton is vital for understanding the mechanisms structuring marine ecosystems. However, methodological limitations have made many of these studies difficult. Recently, molecular based methods have demonstrated that DNA from prey species can be used to identify zooplankton gut contents, and further, quantitative gut content estimates by quantitative PCR (qPCR) assays targeted to the 18S rRNA gene have been used to estimate feeding rates in appendicularians and copepods. However, while standard single primer based qPCR assays were quantitative for the filter feeding appendicularian Oikopleura dioica, feeding rates were consistently underestimated in the copepod Calanus finmarchicus. In this study, we test the hypothesis that prey DNA is rapidly digested after ingestion by copepods and describe a qPCR-based assay, differential length amplification qPCR (dla-qPCR), to account for DNA digestion. The assay utilizes multiple primer sets that amplify different sized fragments of the prey 18S rRNA gene and, based on the differential amplification of these fragments, the degree of digestion is estimated and corrected for. Application of this approach to C. finmarchicus fed Rhodomonas marina significantly improved quantitative feeding estimates compared to standard qPCR. The development of dla-qPCR represents a significant advancement towards a quantitative method for assessing in situ copepod feeding rates without involving cultivation-based manipulation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477863/ doi: 10.1007/s00227-008-1079-8 id: cord-339152-wfakzb6w author: Trovato, Maria title: Viral Emerging Diseases: Challenges in Developing Vaccination Strategies date: 2020-09-03 words: 12000.0 sentences: 540.0 pages: flesch: 38.0 cache: ./cache/cord-339152-wfakzb6w.txt txt: ./txt/cord-339152-wfakzb6w.txt summary: Ebola and Marburg hemorrhagic fevers, Lassa fever, Dengue fever, Yellow fever, West Nile fever, Zika, and Chikungunya vector-borne diseases, Swine flu, Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the recent Coronavirus disease 2019 (COVID-19) are examples of zoonoses that have spread throughout the globe with such a significant impact on public health that the scientific community has been called for a rapid intervention in preventing and treating emerging infections. The occurrence of significant disease outbreaks-such as SARS (severe acute respiratory syndrome) originating in China in 2002 (8) , the 2009 H1N1 swine flu pandemic from Mexico (9) , MERS (Middle East respiratory syndrome) that occurred in Saudi Arabia in 2012 (10) , the West African outbreak of Ebola virus (EBOV) in late 2013 (11) , the Zika virus (ZIKV) outbreak originating in Brazil in 2015 (12) , the 2018 health emergence in Nigeria caused by Lassa virus (13) , and the ongoing Coronavirus disease 2019 (COVID19) pandemic (14) -has renewed interests in developing strategies to faster prevent, treat, and/or control emerging and re-emerging viruses with high epidemic potential. abstract: In the last decades, a number of infectious viruses have emerged from wildlife or re-emerged, generating serious threats to the global health and to the economy worldwide. Ebola and Marburg hemorrhagic fevers, Lassa fever, Dengue fever, Yellow fever, West Nile fever, Zika, and Chikungunya vector-borne diseases, Swine flu, Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the recent Coronavirus disease 2019 (COVID-19) are examples of zoonoses that have spread throughout the globe with such a significant impact on public health that the scientific community has been called for a rapid intervention in preventing and treating emerging infections. Vaccination is probably the most effective tool in helping the immune system to activate protective responses against pathogens, reducing morbidity and mortality, as proven by historical records. Under health emergency conditions, new and alternative approaches in vaccine design and development are imperative for a rapid and massive vaccination coverage, to manage a disease outbreak and curtail the epidemic spread. This review gives an update on the current vaccination strategies for some of the emerging/re-emerging viruses, and discusses challenges and hurdles to overcome for developing efficacious vaccines against future pathogens. url: https://www.ncbi.nlm.nih.gov/pubmed/33013898/ doi: 10.3389/fimmu.2020.02130 id: cord-265173-70wyecwj author: Trujillo-Uscanga, Adrian title: Host cell p53 associates with the feline calicivirus major viral capsid protein VP1, the protease-polymerase NS6/7, and the double-stranded RNA playing a role in virus replication date: 2020-08-27 words: 5671.0 sentences: 282.0 pages: flesch: 53.0 cache: ./cache/cord-265173-70wyecwj.txt txt: ./txt/cord-265173-70wyecwj.txt summary: title: Host cell p53 associates with the feline calicivirus major viral capsid protein VP1, the protease-polymerase NS6/7, and the double-stranded RNA playing a role in virus replication Viruses modulate p53 functions in different manners: single-stranded RNA viruses such as the human coronavirus NL63 (HCoV-NL63) induces its degradation of p53 (Yuan et al., 2015) to ensure viral growth in infected cells (Ma-Lauer et al., 2016) , Zika (ZIKV) and West Nile (WNV) activate p53 to facilitate their replication (El Ghouzzi et al., 2016) (Teng et al., 2017) (Yang et al., 2008) while Adenovirus Even though p53 is implicated in the induction of apoptosis and in many viral infections, its role during calicivirus infection has not been studied. Here we found that p53 interacts with FCV dsRNA, the protease-polymerase NS6/7, and VP1 in the RC; moreover, knockdown of p53 resulted in a significant reduction of the NS viral protein synthesis and virus production, indicating its role for efficient viral replication. abstract: p53 is implicated in several cellular pathways such as induction of cell-cycle arrest, differentiation, senescence, and apoptosis. p53 is activated by a broad range of stress signals, including viral infections. While some viruses activate p53, others induce its inactivation, and occasionally p53 is differentially modulated during the replicative cycle. During calicivirus infections, apoptosis is required for virus exit and spread into the host; yet, the role of p53 during infection is unknown. By confocal microscopy, we found that p53 associates with FCV VP1, the protease-polymerase NS6/7, and the dsRNA. This interaction was further confirmed by proximity ligation assays, suggesting that p53 participates in the FCV replication. Knocked-down of p53 expression in CrFK cells before infection, resulted in a strong reduction of the non-structural protein levels and a decrease of the viral progeny production. These results indicate that p53 is associated with the viral replication complex and is required for an efficient FCV replication. url: https://api.elsevier.com/content/article/pii/S0042682220301616 doi: 10.1016/j.virol.2020.08.008 id: cord-343470-w215pzdc author: Tsai, Kevin title: Epigenetic and epitranscriptomic regulation of viral replication date: 2020-06-12 words: 9761.0 sentences: 452.0 pages: flesch: 41.0 cache: ./cache/cord-343470-w215pzdc.txt txt: ./txt/cord-343470-w215pzdc.txt summary: Eukaryotic gene expression is regulated not only by genomic enhancers and promoters, but also by covalent modifications added to both chromatin and RNAs. Whereas cellular gene expression may be either enhanced or inhibited by specific epigenetic modifications deposited on histones (in particular, histone H3), these epigenetic modifications can also repress viral gene expression, potentially functioning as a potent antiviral innate immune response in DNA virus-infected cells. First, the viral protein VP16, which is packaged into the tegument layer of incoming virions, recruits host proteins, including host-cell factor 1 (HCF-1) and octamer-binding factor (Oct-1), in order to form a complex that recruits the histone demethylases lysine-specific demethylase 1 (LSD1) and Jumonji domain 2 (JMJD2) family members as a means to remove repressive H3K9 marks from viral immediate early promoters 42 Upon entry into the cell nucleus, the DNA of many viruses initiates the replication process adjacent to subnuclear structures called pro-myelocytic leukaemia nuclear bodies (PML-NBs). abstract: Eukaryotic gene expression is regulated not only by genomic enhancers and promoters, but also by covalent modifications added to both chromatin and RNAs. Whereas cellular gene expression may be either enhanced or inhibited by specific epigenetic modifications deposited on histones (in particular, histone H3), these epigenetic modifications can also repress viral gene expression, potentially functioning as a potent antiviral innate immune response in DNA virus-infected cells. However, viruses have evolved countermeasures that prevent the epigenetic silencing of their genes during lytic replication, and they can also take advantage of epigenetic silencing to establish latent infections. By contrast, the various covalent modifications added to RNAs, termed epitranscriptomic modifications, can positively regulate mRNA translation and/or stability, and both DNA and RNA viruses have evolved to utilize epitranscriptomic modifications as a means to maximize viral gene expression. As a consequence, both chromatin and RNA modifications could serve as novel targets for the development of antivirals. In this Review, we discuss how host epigenetic and epitranscriptomic processes regulate viral gene expression at the levels of chromatin and RNA function, respectively, and explore how viruses modify, avoid or utilize these processes in order to regulate viral gene expression. url: https://www.ncbi.nlm.nih.gov/pubmed/32533130/ doi: 10.1038/s41579-020-0382-3 id: cord-001090-qg2r691d author: Twin, Jimmy title: The Potential of Metatranscriptomics for Identifying Screening Targets for Bacterial Vaginosis date: 2013-09-27 words: 3944.0 sentences: 201.0 pages: flesch: 44.0 cache: ./cache/cord-001090-qg2r691d.txt txt: ./txt/cord-001090-qg2r691d.txt summary: BACKGROUND: The ribosomal RNA content of a sample collected from a woman with bacterial vaginosis (BV) was analysed to determine the active microbial community, and to identify potential targets for further screening. Prevotella amnii was chosen as an example target, being the most metabolically active species present in the single patient with BV, and was found to be detected at a high concentration by qPCR in 31% of cohort with BV, with an association with both oral and penile-vaginal sex. An amplicon-based metagenomic library was generated from the extracted DNA using the universal bacterial PCR primers 27F and 338R that target the V1-V2 hypervariable regions of the 16S rRNA gene as previously described [15] . Comparison of cDNA to DNA from Nugent 10 patient All of the predominant bacteria with .1% total abundance identified in the cDNA library were also detected using the 16S rRNA gene amplicon-based approach on extracted DNA. abstract: BACKGROUND: The ribosomal RNA content of a sample collected from a woman with bacterial vaginosis (BV) was analysed to determine the active microbial community, and to identify potential targets for further screening. METHODOLOGY/PRINCIPAL FINDINGS: The sample from the BV patient underwent total RNA extraction, followed by physical subtraction of human rRNA and whole transcriptome amplification. The metatranscriptome was sequenced using Roche 454 titanium chemistry. The bioinformatics pipeline MG-RAST and desktop DNA analysis platforms were utilised to analyse results. Bacteria of the genus Prevotella (predominately P. amnii) constituted 36% of the 16S rRNA reads, followed by Megasphaera (19%), Leptotrichia/Sneathia (8%) and Fusobacterium (8%). Comparison of the abundances of several bacteria to quantitative PCR (qPCR) screening of extracted DNA revealed comparable relative abundances. This suggests a correlation between what was present and transcriptionally active in this sample: however distinct differences were seen when compared to the microbiome determined by 16S rRNA gene amplicon sequencing. To assess the presence of P. amnii in a larger pool of samples, 90 sexually active women were screened using qPCR. This bacterium was found to be strongly associated with BV (P<0.001, OR 23.3 (95%CI:2.9–190.7)) among the 90 women. CONCLUSIONS/SIGNIFICANCE: This study highlighted the potential of metatranscriptomics as a tool for characterising metabolically active microbiota and identifying targets for further screening. Prevotella amnii was chosen as an example target, being the most metabolically active species present in the single patient with BV, and was found to be detected at a high concentration by qPCR in 31% of cohort with BV, with an association with both oral and penile-vaginal sex. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785445/ doi: 10.1371/journal.pone.0076892 id: cord-010564-7c9h16bi author: Unolt, Marta title: Pathogenic variants in CDC45 on the remaining allele in patients with a chromosome 22q11.2 deletion result in a novel autosomal recessive condition date: 2019-09-02 words: 4682.0 sentences: 274.0 pages: flesch: 44.0 cache: ./cache/cord-010564-7c9h16bi.txt txt: ./txt/cord-010564-7c9h16bi.txt summary: Based on the clinical presentation of these patients and on the recurrent phenotype of the patients with pathogenic variants in the CDC45 gene (Table 1) , reported by Fenwick et al., 5 we further expanded the atypical findings spectrum, to include rare gastrointestinal anomalies, such as intestinal malrotation, imperforate/anteriorly displaced anus and congenital diaphragmatic hernia and short stature (in absence of any endocrine or metabolic cause) and patellar anomalies. 5 identified biallelic pathogenic variants in the CDC45 gene in patients with a recurrent phenotype ( Table 1 ) they reported to be consistent with Meier-Gorlin syndrome (MGS, MIM 224690), a rare autosomal recessive primordial dwarfism disorder, characterized by microtia, short stature, and absent or hypoplastic patellae. Importantly, we suggest that a pathogenic variant in CDC45 should now be considered in every patient with a 22q11.2 deletion who presents with the following findings: craniosynostosis, anorectal anomalies/intestinal malrotation, short stature, upper limb anomalies, and cleft lip and palate. abstract: PURPOSE: The 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion in humans, with highly variable phenotypic expression. Whereas congenital heart defects, palatal anomalies, immunodeficiency, hypoparathyroidism, and neuropsychiatric conditions are observed in over 50% of patients with 22q11DS, a subset of patients present with additional “atypical” findings such as craniosynostosis and anorectal malformations. Recently, pathogenic variants in the CDC45 (Cell Division Cycle protein 45) gene, located within the LCR22A–LCR22B region of chromosome 22q11.2, were noted to be involved in the pathogenesis of craniosynostosis. METHODS: We performed next-generation sequencing on DNA from 15 patients with 22q11.2DS and atypical phenotypic features such as craniosynostosis, short stature, skeletal differences, and anorectal malformations. RESULTS: We identified four novel rare nonsynonymous variants in CDC45 in 5/15 patients with 22q11.2DS and craniosynostosis and/or other atypical findings. CONCLUSION: This study supports CDC45 as a causative gene in craniosynostosis, as well as a number of other anomalies. We suggest that this association results in a condition independent of Meier–Gorlin syndrome, perhaps representing a novel condition and/or a cause of features associated with Baller–Gerold syndrome. In addition, this work confirms that the phenotypic variability observed in a subset of patients with 22q11.2DS is due to pathogenic variants on the nondeleted chromosome. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197230/ doi: 10.1038/s41436-019-0645-4 id: cord-257802-vgizgq2y author: Uttamchandani, Mahesh title: Applications of microarrays in pathogen detection and biodefence date: 2008-11-12 words: 6568.0 sentences: 305.0 pages: flesch: 35.0 cache: ./cache/cord-257802-vgizgq2y.txt txt: ./txt/cord-257802-vgizgq2y.txt summary: Advances in miniaturizing this initial PCR step, for instance the development of Review Glossary Biodefence: defensive measures against biological threats, including natural/ emerging pathogens and bioterror agents, that have significant potential to endanger public health Detection: identifying the presence of target pathogen(s) from clinical or environmental samples. (b) Antibody microarrays can be used to detect pathogen proteins or antigens that might be present in environmental samples as an indication of contamination or for diagnostic purposes to determine pathogen infection in human tissues. fabricated a customized Affymetrix microarray containing 53 660 probes to detect DNA amplified from 18 different pathogenic microorganisms simultaneously, including pathogens from the US CDC''s list of bioterrorism agents, such as Bacillus anthracis (which causes anthrax), Clostridium botulinum (which generates the botulinum toxin), Yersinia pestis (which causes bubonic plague) and the Ebola virus [17] . abstract: The microarray is a platform with wide-ranging potential in biodefence. Owing to the high level of throughput attainable through miniaturization, microarrays have accelerated the ability to respond in an epidemic or crisis. Extending beyond diagnostics, recent studies have applied microarrays as a research tool towards understanding the etiology and pathogenicity of dangerous pathogens, as well as in vaccine development. The original emphasis was on DNA microarrays, but the range now includes protein, antibody and carbohydrate microarrays, and research groups have exploited this diversity to further extend microarray applications in the area of biodefence. Here, we discuss the impact and contributions of the growing range of microarrays and emphasize the concepts that might shape the future of biodefence research. url: https://doi.org/10.1016/j.tibtech.2008.09.004 doi: 10.1016/j.tibtech.2008.09.004 id: cord-306904-8iteddug author: Uversky, Vladimir N title: Unreported intrinsic disorder in proteins: Building connections to the literature on IDPs date: 2014-12-12 words: 18422.0 sentences: 1012.0 pages: flesch: 48.0 cache: ./cache/cord-306904-8iteddug.txt txt: ./txt/cord-306904-8iteddug.txt summary: 86 Figure 8C represents the results of the computational disorder analysis in human APC (UniProt ID: P04070) and shows that mentioned loops enriched in basic residues are predicted to be disordered or very flexible, thereby providing an interesting mechanistic plane for the molecular basis of APC recognition and binding of FVIII. 96 Figure 8E shows that although human PECAM-1 (UniProt ID: P16284) is predicted to be mostly ordered, the residues, phosphorylation of which is crucial for its function (Y 663 and Y 686 ), are located within the highly disordered C-terminal tail. 210 Figure 14C represents the results of the disorder analysis of human AMSH (UniProt ID: O95630) and shows that this protein contains a long IDPR (residues 90-250) thereby illustrating that the N-terminal part of the analyzed catalytic domain is predicted to be disordered. [222] [223] [224] Figure 14D shows that human Purb protein (UniProt ID: O35295) is predicted to possess significant amount of functionally important intrinsic disorder. abstract: This review opens a new series entitled “Unreported intrinsic disorder in proteins.” The goal of this series is to bring attention of researchers to an interesting phenomenon of missed (or overlooked, or ignored, or unreported) disorder. This series serves as a companion to “Digested Disorder” which provides a quarterly review of papers on intrinsically disordered proteins (IDPs) found by standard literature searches. The need for this alternative series results from the observation that there are numerous publications that describe IDPs (or hybrid proteins with ordered and disordered regions) yet fail to recognize many of the key discoveries and publications in the IDP field. By ignoring the body of work on IDPs, such publications often fail to relate their findings to prior discoveries or fail to explore the obvious implications of their work. Thus, the goal of this series is not only to review these very interesting and important papers, but also to point out how each paper relates to the IDP field and show how common tools in the IDP field can readily take the findings in new directions or provide a broader context for the reported findings. url: https://doi.org/10.4161/21690693.2014.970499 doi: 10.4161/21690693.2014.970499 id: cord-102661-lh7992rl author: Valentine, Charles C. title: Direct Quantification of in vivo Mutagenesis and Carcinogenesis Using Duplex Sequencing date: 2020-11-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The ability to accurately measure mutations is critical for basic research and identification of potential drug and chemical carcinogens. Current methods for in vivo quantification of mutagenesis are limited because they rely on transgenic rodent systems that are low-throughput, expensive, prolonged, and don’t fully represent other species such as humans. Next generation sequencing (NGS) is a conceptually attractive alternative for mutation detection in the DNA of any organism, however, the limit of resolution for standard NGS is poor. Technical error rates (~1×10−3) of NGS obscure the true abundance of somatic mutations, which can exist at pernucleotide frequencies ≤1×10−7. Using Duplex Sequencing, an extremely accurate error-corrected NGS (ecNGS) technology, we were able to detect mutations induced by 3 carcinogens in 5 tissues of 2 strains of mice within 31 days following exposure. We observed a strong correlation between mutation induction measured by Duplex Sequencing and the gold-standard transgenic rodent mutation assay. We identified exposure-specific mutation spectra of each compound through trinucleotide patterns of base substitution. We observed variation in mutation susceptibility by genomic region, as well as by DNA strand. We also identified the primordial signs of carcinogenesis in a cancer-predisposed strain of mice, as evidenced by clonal expansions of cells carrying an activated oncogene, less than a month after carcinogen exposure. These findings demonstrate that ecNGS is a powerful method for sensitively detecting and characterizing mutagenesis and the early clonal evolutionary hallmarks of carcinogenesis. Duplex Sequencing can be broadly applied to chemical safety testing, basic mutational research, and related clinical uses. SIGNIFICANCE STATEMENT Error-corrected next generation sequencing (ecNGS) can be used to rapidly detect and quantify the in vivo mutagenic impact of environmental exposures or endogenous processes in any tissue, from any species, at any genomic location. The greater speed, higher scalability, richer data outputs, as well as cross-species and cross-locus applicability of ecNGS compared to existing methods make it a powerful new tool for mutational research, regulatory safety testing, and emerging clinical applications. url: https://doi.org/10.1101/2020.06.28.176685 doi: 10.1101/2020.06.28.176685 id: cord-270637-4zphlpks author: Van Rompay, An R title: Substrate specificity and phosphorylation of antiviral and anticancer nucleoside analogues by human deoxyribonucleoside kinases and ribonucleoside kinases date: 2003-11-04 words: 11595.0 sentences: 702.0 pages: flesch: 47.0 cache: ./cache/cord-270637-4zphlpks.txt txt: ./txt/cord-270637-4zphlpks.txt summary: (2001) , there are 3 general mechanisms of resistance to NAs that have been described in cell lines and clinical samples: (1) insufficient intracellular concentrations of NA-TPs, which might be due to inefficient cellular uptake, decreased levels of activating enzymes, increased catabolism by elevated levels of 5V -NT or deaminases, or expansion of dNTP pools; (2) inability to achieve sufficient alterations in DNA strands or dNTP pools, which might result from altered interactions with DNA polymerases, lack of inhibition of RR, or inadequate p53 exonuclease activity; and (3) defective induction of apoptosis. In human leukemia cell lines is CAFdA, a more efficient substrate for dCK, and the active form is more stable due to higher phosphorylation and longer retention time compared with CdA, but the mechanisms leading to acquired resistance to CAFdA seem to be similar to those for CdA (Lotfi et al., 1999; Månsson et al., 2003) . abstract: Structural analogues of nucleosides, nucleoside analogues (NA), are used in the treatment of cancer and viral infections. Antiviral NAs inhibit replication of the viral genome, whereas anticancer NAs inhibit cellular DNA replication and repair. NAs are inactive prodrugs that are dependent on intracellular phosphorylation to their pharmacologically active triphosphate form. The deoxyribonucleoside kinases (dNK) and ribonucleoside kinases (rNK) catalyze the first phosphorylation step, converting deoxyribonucleosides and ribonucleosides to their corresponding monophosphate form. The dNKs have been studied intensively, whereas the rNKs have not been as thoroughly investigated. This overview is focused on the substrate specificity, tissue distribution, and subcellular location of the mammalian dNKs and rNKs and their role in the activation of NAs. url: https://www.sciencedirect.com/science/article/pii/S0163725803001190 doi: 10.1016/j.pharmthera.2003.07.001 id: cord-298998-n5rhhzc9 author: Vashee, Sanjay title: Cloning, Assembly, and Modification of the Primary Human Cytomegalovirus Isolate Toledo by Yeast-Based Transformation-Associated Recombination date: 2017-10-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Genetic engineering of cytomegalovirus (CMV) currently relies on generating a bacterial artificial chromosome (BAC) by introducing a bacterial origin of replication into the viral genome using in vivo recombination in virally infected tissue culture cells. However, this process is inefficient, results in adaptive mutations, and involves deletion of viral genes to avoid oversized genomes when inserting the BAC cassette. Moreover, BAC technology does not permit the simultaneous manipulation of multiple genome loci and cannot be used to construct synthetic genomes. To overcome these limitations, we adapted synthetic biology tools to clone CMV genomes in Saccharomyces cerevisiae. Using an early passage of the human CMV isolate Toledo, we first applied transformation-associated recombination (TAR) to clone 16 overlapping fragments covering the entire Toledo genome in Saccharomyces cerevisiae. Then, we assembled these fragments by TAR in a stepwise process until the entire genome was reconstituted in yeast. Since next-generation sequence analysis revealed that the low-passage-number isolate represented a mixture of parental and fibroblast-adapted genomes, we selectively modified individual DNA fragments of fibroblast-adapted Toledo (Toledo-F) and again used TAR assembly to recreate parental Toledo (Toledo-P). Linear, full-length HCMV genomes were transfected into human fibroblasts to recover virus. Unlike Toledo-F, Toledo-P displayed characteristics of primary isolates, including broad cellular tropism in vitro and the ability to establish latency and reactivation in humanized mice. Our novel strategy thus enables de novo cloning of CMV genomes, more-efficient genome-wide engineering, and the generation of viral genomes that are partially or completely derived from synthetic DNA. IMPORTANCE The genomes of large DNA viruses, such as human cytomegalovirus (HCMV), are difficult to manipulate using current genetic tools, and at this time, it is not possible to obtain, molecular clones of CMV without extensive tissue culture. To overcome these limitations, we used synthetic biology tools to capture genomic fragments from viral DNA and assemble full-length genomes in yeast. Using an early passage of the HCMV isolate Toledo containing a mixture of wild-type and tissue culture-adapted virus. we directly cloned the majority sequence and recreated the minority sequence by simultaneous modification of multiple genomic regions. Thus, our novel approach provides a paradigm to not only efficiently engineer HCMV and other large DNA viruses on a genome-wide scale but also facilitates the cloning and genetic manipulation of primary isolates and provides a pathway to generating entirely synthetic genomes. url: https://www.ncbi.nlm.nih.gov/pubmed/28989973/ doi: 10.1128/mspheredirect.00331-17 id: cord-261028-sxux2ujo author: Vatner, Ralph E. title: STING, DCs and the link between innate and adaptive tumor immunity date: 2017-12-20 words: 10018.0 sentences: 475.0 pages: flesch: 44.0 cache: ./cache/cord-261028-sxux2ujo.txt txt: ./txt/cord-261028-sxux2ujo.txt summary: Dendritic cells (DCs) are a heterogeneous population of professional antigen-presenting cells (APCs) from hematopoietic origin that serve as a key link between the innate and adaptive immune systems, and are the lynchpin in generating anti-tumor immunity (Steinman and Idoyaga, 2010) . More recently, type I IFN production and signaling through the STING pathway has been identified as having an essential role in the development of anti-tumor immunity in response to tumor derived DNA. DNA sensing by STING is the upstream link that triggers type I IFN production by DCs and facilitates effective cross-priming of tumor specific CD8+ T cells. This DNA is likely derived from stressed and dying cancer cells, and is introduced into the DC cytosol through a yet unknown mechanism where it binds to cGAS, which initiates STING mediated type I IFN transcription (Fig. 2) . abstract: Cancer and the immune system are intimately related. Much of the bulk of tumors is comprised of stromal leukocytes with immune functions, which serve to both promote and inhibit tumor growth, invasion and metastasis. The T lymphocytes of the adaptive immune system are essential for tumor immunity, and these T cells are generated by cross-priming against tumor associated antigens. Dendritic cells (DCs) are essential in this process, serving as the cellular link between innate and adaptive immunity. As a prerequisite for priming of adaptive immune responses, DCs must take up tumor antigens, process them and present them in the context of the major histocompatibility complex (MHC). DCs also serve as sensors of innate activation signals from cancer that are necessary for their activation and effective priming of cancer specific T cells. Here we discuss the role of DCs in the sensing of cancer and in priming the adaptive response against tumors. Furthermore, we present the essential role of the Stimulator of Interferon Genes (STING) signaling pathway in producing type I interferons (IFNs) that are essential in this process. url: https://doi.org/10.1016/j.molimm.2017.12.001 doi: 10.1016/j.molimm.2017.12.001 id: cord-282251-r4on3lpr author: Veggiani, Gianluca title: Emerging drug development technologies targeting ubiquitination for cancer therapeutics date: 2019-03-07 words: 11388.0 sentences: 580.0 pages: flesch: 41.0 cache: ./cache/cord-282251-r4on3lpr.txt txt: ./txt/cord-282251-r4on3lpr.txt summary: Within the span of 20 years, high-throughput technologies further advanced to include feats in protein engineering such as proteolysis-targeting chimeras (PROTACs) derived from the ubiquitination pathway (Zhou, Bogacki, McReynolds, & Howley, 2000) , streamlined phage display approaches that include Ub variants (UbV) to target protein-protein interactions in the UPS (Brown et al., 2016; Ernst et al., 2013; Ernst & Sidhu, 2013; Gabrielsen et al., 2017; Ordureau et al., 2018; Zhang et al., 2016; Zhang et al., 2017; Zhang et al., 2017; Zhang & Sidhu, 2018) and cell-based pharmacological HTS assays to enhance oncolytic virus cancer-cell-killing efficiency through viral sensitizer screens (Bourgeois-Daigneault et al., 2016; Diallo et al., 2010) (Fig. 2) . abstract: Development of effective cancer therapeutic strategies relies on our ability to interfere with cellular processes that are dysregulated in tumors. Given the essential role of the ubiquitin proteasome system (UPS) in regulating a myriad of cellular processes, it is not surprising that malfunction of UPS components is implicated in numerous human diseases, including many types of cancer. The clinical success of proteasome inhibitors in treating multiple myeloma has further stimulated enthusiasm for targeting UPS proteins for pharmacological intervention in cancer treatment, particularly in the precision medicine era. Unfortunately, despite tremendous efforts, the paucity of potent and selective UPS inhibitors has severely hampered attempts to exploit the UPS for therapeutic benefits. To tackle this problem, many groups have been working on technology advancement to rapidly and effectively screen for potent and specific UPS modulators as intracellular probes or early-phase therapeutic agents. Here, we review several emerging technologies for developing chemical- and protein-based molecules to manipulate UPS enzymatic activity, with the aim of providing an overview of strategies available to target ubiquitination for cancer therapy. url: https://doi.org/10.1016/j.pharmthera.2019.03.003 doi: 10.1016/j.pharmthera.2019.03.003 id: cord-262353-iips79vo author: Veltkamp, Henk-Willem title: Disposable DNA Amplification Chips with Integrated Low-Cost Heaters † date: 2020-02-25 words: 9618.0 sentences: 540.0 pages: flesch: 57.0 cache: ./cache/cord-262353-iips79vo.txt txt: ./txt/cord-262353-iips79vo.txt summary: Based on the analysis of the milling process, metal adhesion studies, and COMSOL MultiPhysics heat transfer simulations, the first batch of chips has been fabricated and successful multiple displacement amplification reactions are performed inside these chips. The work presented at the 4th Microfluidic Handling Systems conference and which is extended in this paper aims at the development of a disposable, polymer-based DNA amplification lab-on-chip system with integrated resistive heater based on the World Health Organization (WHO) Sexually Transmitted Diseases Diagnostics Initiative (SDI) ASSURED criteria. The aim of this study was to fabricate biocompatible, low-cost, and disposable chips with integrated heater, which should be able to perform DNA amplification, and possible in situ fluorescence detection in the near future. The integrated resistive heaters on the chips were characterized and showed a temperature stability of ±2 • C over a time period of 25 h, which is at least twelve-fold longer than the required operating times for DNA amplification reactions [6, [8] [9] [10] [11] . abstract: Fast point-of-use detection of, for example, early-stage zoonoses, e.g., Q-fever, bovine tuberculosis, or the Covid-19 coronavirus, is beneficial for both humans and animal husbandry as it can save lives and livestock. The latter prevents farmers from going bankrupt after a zoonoses outbreak. This paper describes the development of a fabrication process and the proof-of-principle of a disposable DNA amplification chip with an integrated heater. Based on the analysis of the milling process, metal adhesion studies, and COMSOL MultiPhysics heat transfer simulations, the first batch of chips has been fabricated and successful multiple displacement amplification reactions are performed inside these chips. This research is the first step towards the development of an early-stage zoonoses detection device. Tests with real zoonoses and DNA specific amplification reactions still need to be done. url: https://www.ncbi.nlm.nih.gov/pubmed/32106462/ doi: 10.3390/mi11030238 id: cord-015933-x5cq4k4x author: Verbrugh, H.A. title: 1 Micro-organismen, de mens en het ontstaan van infectieziekten: algemene principes date: 2011 words: 19354.0 sentences: 1625.0 pages: flesch: 54.0 cache: ./cache/cord-015933-x5cq4k4x.txt txt: ./txt/cord-015933-x5cq4k4x.txt summary: Virussen vormen een geheel aparte groep biologische agentia die ziekte bij de mens kunnen veroorzaken; hun meest karakteristieke eigenschap is dat zij voor hun vermeerdering afhankelijk zijn van levende gastheercellen. Dit duidt er dus tevens op dat een micro-organisme over een complex geheel van genetische eigenschappen moet beschikken, wil het pathogene betekenis voor de mens krijgen; dergelijke eigenschappen worden ook wel virulentiefactoren genoemd. Een aantal virussen staat bekend als tumorvirus omdat zij een permanente maligne transformatie in hun gastheercel kunnen teweegbrengen; het virus beïnvloedt dan de transcriptie van specifieke cellulaire oncogenen of andere gastheergenen, genen die betrokken zijn bij de regulatie van celdeling of spontane celdood (apoptose). Hoewel sommige micro-organismen (stafylokokken) zich direct aan dergelijke kunststoffen kunnen hechten, is het in de praktijk zo dat het oppervlak ervan snel door neerslag met bovengenoemde matrixeiwitten als fibronectine wordt bedekt, een proces dat ook wel conditionering van het biomateriaal wordt genoemd. abstract: Infectieziekten zijn te beschouwen als een aparte groep ziekten van de mens. Steeds gaat het om ziekten die het gevolg zijn van een interactie tussen de mens en een ander biologisch agens: een micro-organisme. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120058/ doi: 10.1007/978-90-313-7944-6_1 id: cord-285505-8norumv6 author: Vere Hodge, R. Anthony title: Meeting report: 27th International conference on antiviral research, in Raleigh, NC, USA date: 2014-09-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The 27th International Conference on Antiviral Research (ICAR) was held in Raleigh, North Carolina, USA from May 12 to 16, 2014. This article summarizes the principal invited lectures. John Drach (Elion Award) described the early days of antiviral drugs and their novel modes of action. Piet Herdewijn (Holý Award) used evolutionary pressure to select DNA polymerases that accept nucleoside analogs. Replacing thymine by 5-chlorouracil led to the generation of a new form of Escherichia coli. Adrian Ray (Prusoff Award) demonstrated how prodrugs can markedly improve both the efficacy and safety of potential drugs. The keynote addresses, by David Margolis and Myron Cohen, tackled two emerging areas of HIV research, to find an HIV “cure” and to prevent HIV transmission, respectively. These topics were discussed further in other presentations – a cure seems to be a distant prospect but there are exciting developments for reducing HIV transmission. TDF-containing vaginal rings and GSK-744, as a long-lasting injection, offer great hope. There were three mini-symposia. Although therapy with TDF/FTC gives excellent control of HBV replication, there are only a few patients who achieve a functional cure. Myrcludex, an entry inhibitor, is active against both HBV and HDV. The recent progress with HBV replication in cell cultures has transformed the search for new antiviral compounds. The HBV capsid protein has been recognized as key player in HBV DNA synthesis. Unexpectedly, compounds which enhance capsid formation, markedly reduce HBV DNA synthesis. The development of BCX4430, which is active against Marburg and Ebola viruses, is of great current interest. url: https://api.elsevier.com/content/article/pii/S0166354214002460 doi: 10.1016/j.antiviral.2014.08.009 id: cord-016095-jop2rx61 author: Vignais, Pierre V. title: Challenges for Experimentation on Living Beings at the Dawn of the 21(st) Century date: 2010-06-08 words: 42843.0 sentences: 1503.0 pages: flesch: 43.0 cache: ./cache/cord-016095-jop2rx61.txt txt: ./txt/cord-016095-jop2rx61.txt summary: Instead of setting out to discover unknown mechanisms by analyzing effects that are dependent on specific causes, with some uncertainty as to the possible success of the enterprise being undertaken, which is the foundation stone of the Bernardian paradigm of the experimental method, many current research projects give themselves achievable and programmable objectives that depend upon the means available to them: sequencing of genomes with a view to comparing them, recognition of sequence similarities in proteins coded for by genes belonging to different species, with the aim of putting together phylogenetic trees, synthesis of interesting proteins in transgenic animals and plants, analysis of the three-dimensional structure of proteins, in order to find sites that are likely to fix medicinal substances, and synthesis of molecular species able to recognize pathogenic targets. abstract: “We can talk endlessly about moral progress, about social progress, about poetic progress, about progress made in happiness; nevertheless, there is a type of progress that defies any discussion, and that is scientific progress, as soon as we judge it within the hierarchy of knowledge, from a specifically intellectual point of view.” url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120277/ doi: 10.1007/978-90-481-3767-1_5 id: cord-264884-ydkigome author: Villarreal, Luis P. title: The Widespread Evolutionary Significance of Viruses date: 2008-07-05 words: 23138.0 sentences: 1203.0 pages: flesch: 47.0 cache: ./cache/cord-264884-ydkigome.txt txt: ./txt/cord-264884-ydkigome.txt summary: For example, common structural motifs from phage to eukaryotic DNA viruses (T4 and herpesvirus) suggest very ancient links in virus evolution that span all domains of life (see below). On an evolutionary time-scale, the majority of viral lineages tend to exist as species-specifi c persistent (aka temperate, latent, and chronic) infections in which individual hosts will be colonized by mostly silent (asymptomatic) viruses for the duration of their life . It has distinct genetic, fi tness, and evolutionary characteristics that require intimate, host (tissue)-specifi c viral strategies and precise gene functions to attain stable maintenance in the presence of immunity and to allow biologically controlled reactivation. Thus, the phycodnaviruses appear to represent a basal but diverse viral lineage that has both acute and persistent lifestyle and have some clear relationships to most large eukaryotic DNA viruses and many phage. abstract: In the last 30 years, the study of virus evolution has undergone a transformation. Originally concerned with disease and its emergence, virus evolution had not been well integrated into the general study of evolution. This chapter reviews the developments that have brought us to this new appreciation for the general significance of virus evolution to all life. We now know that viruses numerically dominate all habitats of life, especially the oceans. Theoretical developments in the 1970s regarding quasispecies, error rates, and error thresholds have yielded many practical insights into virus–host dynamics. The human diseases of HIV-1 and hepatitis C virus cannot be understood without this evolutionary framework. Yet recent developments with poliovirus demonstrate that viral fitness can be the result of a consortia, not one fittest type, a basic Darwinian concept in evolutionary biology. Darwinian principles do apply to viruses, such as with Fisher population genetics, but other features, such as reticulated and quasispecies-based evolution distinguish virus evolution from classical studies. The available phylogenetic tools have greatly aided our analysis of virus evolution, but these methods struggle to characterize the role of virus populations. Missing from many of these considerations has been the major role played by persisting viruses in stable virus evolution and disease emergence. In many cases, extreme stability is seen with persisting RNA viruses. Indeed, examples are known in which it is the persistently infected host that has better survival. We have also recently come to appreciate the vast diversity of phage (DNA viruses) of prokaryotes as a system that evolves by genetic exchanges across vast populations (Chapter 10). This has been proposed to be the “big bang” of biological evolution. In the large DNA viruses of aquatic microbes we see surprisingly large, complex and diverse viruses. With both prokaryotic and eukaryotic DNA viruses, recombination is the main engine of virus evolution, and virus host co-evolution is common, although not uniform. Viral emergence appears to be an unending phenomenon and we can currently witness a selective sweep by retroviruses that infect and become endogenized in koala bears. url: https://api.elsevier.com/content/article/pii/B9780123741530000217 doi: 10.1016/b978-0-12-374153-0.00021-7 id: cord-277318-cwuls6xs author: Visscher, Koen title: −1 Programmed Ribosomal Frameshifting as a Force-Dependent Process date: 2016-02-02 words: 8568.0 sentences: 455.0 pages: flesch: 48.0 cache: ./cache/cord-277318-cwuls6xs.txt txt: ./txt/cord-277318-cwuls6xs.txt summary: 13 A recent single-molecule experiment indicates that ribosome helicase action during the translational elongation cycle may be twofold: it destabilizes the helical junction at the mRNA entry site favoring an open conformation, and it appears to pull mRNA strands apart during the translocation step when relatively large structural rearrangements occur on the ribosome. 26 We will review methods and experiments that apply force to the single molecules to determine the mechanical properties of codon-anticodon interaction at the slippery site, the stability of downstream mRNA structure motifs that give rise to −1 PRF, and elastic properties of the ssRNA elasticity bridging those elements. 104, 105 Single-molecule assays that probe the codon-anticodon dynamics at the slippery sequence and investigate the force dependence of the translation elongational cycle (discussed later in the chapter; see Fig. 8 ) should be fit to answer these questions and allow unfolding of −1 PRF mRNA structure motifs held at the ribosome''s entry site. abstract: −1 Programmed ribosomal frameshifting is a translational recoding event in which ribosomes slip backward along messenger RNA presumably due to increased tension disrupting the codon–anticodon interaction at the ribosome's coding site. Single-molecule physical methods and recent experiments characterizing the physical properties of mRNA's slippery sequence as well as the mechanical stability of downstream mRNA structure motifs that give rise to frameshifting are discussed. Progress in technology, experimental assays, and data analysis methods hold promise for accurate physical modeling and quantitative understanding of −1 programmed ribosomal frameshifting. url: https://doi.org/10.1016/bs.pmbts.2015.11.003 doi: 10.1016/bs.pmbts.2015.11.003 id: cord-021532-6hmn90ac author: Von Seggern, Dan J. title: ADENOVIRAL VECTORS FOR PROTEIN EXPRESSION date: 2007-09-02 words: 12536.0 sentences: 580.0 pages: flesch: 43.0 cache: ./cache/cord-021532-6hmn90ac.txt txt: ./txt/cord-021532-6hmn90ac.txt summary: Many features of this viral system, including the ability to infect a wide variety of nondividing cells, a large capacity for insertion of DNA, ease of production and stability of the viral particles, and the high viral titers that can be produced, make Ad-based vectors especially useful in gene transfer. Recombinant adenoviruses have been used to express foreign proteins for a number of years, and the recent explosion of interest in gene therapy has led to the development both of improved adenoviral vectors and of more efficient techniques for generating them. Once constructed, a single vector can be used for in vitro protein expression and purification, studies of the effect of the gene product on cell biology, or in vivo studies in many tissue types and a number of different species. Viral vectors deleted for the corresponding sequences will have a higher capacity for insertion of DNA and should be useful for expressing large proteins such as dystrophin or combinations of genes (perhaps multisubunit enzyme complexes). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150134/ doi: 10.1016/b978-012253840-7/50006-7 id: cord-010784-khvrklqt author: Waki, Kayoko title: Integrity of plasma DNA is inversely correlated with vaccine-induced antitumor immunity in ovarian cancer patients date: 2020-05-11 words: 3076.0 sentences: 173.0 pages: flesch: 50.0 cache: ./cache/cord-010784-khvrklqt.txt txt: ./txt/cord-010784-khvrklqt.txt summary: Here, we investigated the potential utility of the circulating cell-free DNA (cfDNA) integrity—a ratio of necrotic cell-derived, longer DNA fragments versus apoptotic cell-derived shorter fragments of Alu gene—as a biomarker of vaccine therapy for patients with ovarian cancer. We analyzed plasma samples from 39 patients with advanced or recurrent ovarian cancer enrolled in clinical trials for personalized peptide vaccinations. We conducted the present study to investigate the possibility of using the circulating cfDNA integrity as a biomarker of vaccine therapy for patients with ovarian cancer. Frozen plasma samples from 39 patients with advanced or recurrent ovarian cancer who were enrolled in clinical trials of the personalized peptide vaccination during the period from January 2009 to July 2012 were used in this study [6] . We analyzed the circulating cfDNA integrity of 39 patients with advanced or recurrent ovarian cancer who were treated with a personalized peptide vaccination in a clinical trial [6] . abstract: Cancer immunotherapy including vaccine therapy is a promising modality for cancer treatment, but few patients show its clinical benefits currently. The identification of biomarkers that can identify patients who will benefit from cancer immunotherapy is thus important. Here, we investigated the potential utility of the circulating cell-free DNA (cfDNA) integrity—a ratio of necrotic cell-derived, longer DNA fragments versus apoptotic cell-derived shorter fragments of Alu gene—as a biomarker of vaccine therapy for patients with ovarian cancer. We analyzed plasma samples from 39 patients with advanced or recurrent ovarian cancer enrolled in clinical trials for personalized peptide vaccinations. We observed that (1) the cfDNA integrity was decreased after the first cycle of vaccination, and (2) the decreased levels of cfDNA integrity were correlated with vaccine-induced immune responses; i.e., decreased cfDNA integrity was observed in 91.7% and 59.3% of the IgG-positive and negative patients, respectively (p = 0.0445). Similarly, decreased cfDNA integrity was observed in 92.9% and 56.0% of CTL response-positive and negative patients, respectively (p = 0.0283). These results suggest that the circulating cfDNA integrity is a possible biomarker for cancer vaccine therapy. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222063/ doi: 10.1007/s00262-020-02599-4 id: cord-004133-32w6g7qk author: Walker, Faye M. title: Advances in Directly Amplifying Nucleic Acids from Complex Samples date: 2019-09-30 words: 13585.0 sentences: 664.0 pages: flesch: 42.0 cache: ./cache/cord-004133-32w6g7qk.txt txt: ./txt/cord-004133-32w6g7qk.txt summary: Studies were included if they involved direct amplification and detection of genetic material from one of six representative sample types: blood, dried blood spot, serum and plasma, saliva and sputum, swabs, urine, and stool. However, it is important to note that the sensitivity does not necessarily suffer in much more concentrated samples-in Liu et al.''s highly robust two-step amplification process with direct hairpin assembly and HCR-based detection of SNP DNA sequences in 50% (v/v) serum, they achieved a very low LOD of 100 pg [119] . However, it is important to note that the sensitivity does not necessarily suffer in much more concentrated samples-in Liu et al.''s highly robust two-step amplification process with direct hairpin assembly and HCR-based detection of SNP DNA sequences in 50% (v/v) serum, they achieved a very low LOD of 100 pg [119] . abstract: Advances in nucleic acid amplification technologies have revolutionized diagnostics for systemic, inherited, and infectious diseases. Current assays and platforms, however, often require lengthy experimental procedures and multiple instruments to remove contaminants and inhibitors from clinically-relevant, complex samples. This requirement of sample preparation has been a bottleneck for using nucleic acid amplification tests (NAATs) at the point of care (POC), though advances in “lab-on-chip” platforms that integrate sample preparation and NAATs have made great strides in this space. Alternatively, direct NAATs—techniques that minimize or even bypass sample preparation—present promising strategies for developing POC diagnostic tools for analyzing real-world samples. In this review, we discuss the current status of direct NAATs. Specifically, we surveyed potential testing systems published from 1989 to 2017, and analyzed their performances in terms of robustness, sensitivity, clinical relevance, and suitability for POC diagnostics. We introduce bubble plots to facilitate our analysis, as bubble plots enable effective visualization of the performances of these direct NAATs. Through our review, we hope to initiate an in-depth examination of direct NAATs and their potential for realizing POC diagnostics, and ultimately transformative technologies that can further enhance healthcare. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955841/ doi: 10.3390/bios9040117 id: cord-306798-f28264k3 author: Walsh, Geraldine M. title: Blood-Borne Pathogens: A Canadian Blood Services Centre for Innovation Symposium date: 2016-02-23 words: 15308.0 sentences: 723.0 pages: flesch: 45.0 cache: ./cache/cord-306798-f28264k3.txt txt: ./txt/cord-306798-f28264k3.txt summary: Transfusion services can employ indirect measures such as surveillance, hemovigilance, and donor questioning (defense), protein-, or nucleic acid based direct testing (detection), or pathogen inactivation of blood products (destruction) as strategies to mitigate the risk of transmission-transmitted infection. Cost concerns make it likely that pathogen inactivation will be contemplated by blood operators through the lens of health economics and risk-based decision making, rather than in zero-risk paradigms previously embraced for transfusable products. Dr Margaret Fearon, CBS Medical Director, Medical Microbiology, and Assistant Professor, University of Toronto, discussed the current prevalence of classical transfusion-transmissible infections (TTIs) in CBS blood donors, new and emerging infectious diseases, how CBS prepares for and manages new risks, and also addressed new paradigms for risk management. Other transfusion-transmissible diseases are currently being monitored as potential emerging threats to the safety of the blood supply, including babesiosis, hepatitis E, CHIKV, and dengue virus. abstract: Testing donations for pathogens and deferring selected blood donors have reduced the risk of transmission of known pathogens by transfusion to extremely low levels in most developed countries. Protecting the blood supply from emerging infectious threats remains a serious concern in the transfusion medicine community. Transfusion services can employ indirect measures such as surveillance, hemovigilance, and donor questioning (defense), protein-, or nucleic acid based direct testing (detection), or pathogen inactivation of blood products (destruction) as strategies to mitigate the risk of transmission-transmitted infection. In the North American context, emerging threats currently include dengue, chikungunya, and hepatitis E viruses, and Babesia protozoan parasites. The 2003 SARS and 2014 Ebola outbreaks illustrate the potential of epidemics unlikely to be transmitted by blood transfusion but disruptive to blood systems. Donor-free blood products such as ex vivo generated red blood cells offer a theoretical way to avoid transmission-transmitted infection risk, although biological, engineering, and manufacturing challenges must be overcome before this approach becomes practical. Similarly, next generation sequencing of all nucleic acid in a blood sample is currently possible but impractical for generalized screening. Pathogen inactivation systems are in use in different jurisdictions around the world, and are starting to gain regulatory approval in North America. Cost concerns make it likely that pathogen inactivation will be contemplated by blood operators through the lens of health economics and risk-based decision making, rather than in zero-risk paradigms previously embraced for transfusable products. Defense of the blood supply from infectious disease risk will continue to require innovative combinations of surveillance, detection, and pathogen avoidance or inactivation. url: https://doi.org/10.1016/j.tmrv.2016.02.003 doi: 10.1016/j.tmrv.2016.02.003 id: cord-259748-x7dq1sy4 author: Wan, Dongshan title: Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response date: 2020-04-28 words: 14147.0 sentences: 850.0 pages: flesch: 41.0 cache: ./cache/cord-259748-x7dq1sy4.txt txt: ./txt/cord-259748-x7dq1sy4.txt summary: Double-stranded DNA (dsDNA) sensor cyclic-GMP-AMP synthase (cGAS) along with the downstream stimulator of interferon genes (STING) acting as essential immune-surveillance mediators have become hot topics of research. The intrinsic function of the cGAS-STING pathway facilitates type-I interferon (IFN) inflammatory signaling responses and other cellular processes such as autophagy, cell survival, senescence. In 2008, several research teams discovered a new protein on the endoplasmic reticulum (ER) which can be activated by immune-stimulatory DNA (ISD) and initiate type-I interferon (IFN) responses, which was named "stimulator of interferon genes" (STING, also known as MITA, ERIS) (2) (3) (4) . Mitochondrial outer membrane permeabilization (MOMP) activation, which is executed by BCL-2-associated X protein (BAX) and BCL-2 antagonist or killer (BAK), is a highly controlled conserved process in regulated cell FIGURE 3 | Interaction of the cGAS-STING pathway with other DNA-sensing pathways and its role in cell survival. Human plasmacytoid dentritic cells elicit a Type I interferon response by sensing DNA via the cGAS-STING signaling pathway abstract: Double-stranded DNA (dsDNA) sensor cyclic-GMP-AMP synthase (cGAS) along with the downstream stimulator of interferon genes (STING) acting as essential immune-surveillance mediators have become hot topics of research. The intrinsic function of the cGAS-STING pathway facilitates type-I interferon (IFN) inflammatory signaling responses and other cellular processes such as autophagy, cell survival, senescence. cGAS-STING pathway interplays with other innate immune pathways, by which it participates in regulating infection, inflammatory disease, and cancer. The therapeutic approaches targeting this pathway show promise for future translation into clinical applications. Here, we present a review of the important previous works and recent advances regarding the cGAS-STING pathway, and provide a comprehensive understanding of the modulatory pattern of the cGAS-STING pathway under multifarious pathologic states. url: https://www.ncbi.nlm.nih.gov/pubmed/32411126/ doi: 10.3389/fimmu.2020.00615 id: cord-347710-ff64y6ef author: Wan, Qianya title: Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development date: 2020-07-13 words: 36567.0 sentences: 2487.0 pages: flesch: 46.0 cache: ./cache/cord-347710-ff64y6ef.txt txt: ./txt/cord-347710-ff64y6ef.txt summary: hnRNPs involve in a large number of cellular processes, including chromatin remodelling, transcription regulation, RNP assembly and stabilization, RNA export, virus replication, histone-like nucleoid structuring, and even intracellular immunity. 6, 13 It is well known that Hsp90 not only interacts and contributes to RNA polymerase assembly and nuclear import of some (−) ssRNA viruses (e.g., PB2 of influenza virus), but plays crucial roles in the folding process of viral capsid proteins and virion assemblies as well. 17, 18 As a critical component of cellular protein surveillance, the ATP-dependent molecular chaperone protects cells from damage caused by stress and takes part in a number of folding processes, including folding of newly synthesized polypeptides, recognition and refolding of misfolded or aggregated proteins, solubilization or degradation of proteins, transporting proteins, assembly or disassembly of oligomeric protein complexes, and the regulation of certain natively folded proteins. abstract: Stress proteins (SPs) including heat-shock proteins (HSPs), RNA chaperones, and ER associated stress proteins are molecular chaperones essential for cellular homeostasis. The major functions of HSPs include chaperoning misfolded or unfolded polypeptides, protecting cells from toxic stress, and presenting immune and inflammatory cytokines. Regarded as a double-edged sword, HSPs also cooperate with numerous viruses and cancer cells to promote their survival. RNA chaperones are a group of heterogeneous nuclear ribonucleoproteins (hnRNPs), which are essential factors for manipulating both the functions and metabolisms of pre-mRNAs/hnRNAs transcribed by RNA polymerase II. hnRNPs involve in a large number of cellular processes, including chromatin remodelling, transcription regulation, RNP assembly and stabilization, RNA export, virus replication, histone-like nucleoid structuring, and even intracellular immunity. Dysregulation of stress proteins is associated with many human diseases including human cancer, cardiovascular diseases, neurodegenerative diseases (e.g., Parkinson’s diseases, Alzheimer disease), stroke and infectious diseases. In this review, we summarized the biologic function of stress proteins, and current progress on their mechanisms related to virus reproduction and diseases caused by virus infections. As SPs also attract a great interest as potential antiviral targets (e.g., COVID-19), we also discuss the present progress and challenges in this area of HSP-based drug development, as well as with compounds already under clinical evaluation. url: https://www.ncbi.nlm.nih.gov/pubmed/32661235/ doi: 10.1038/s41392-020-00233-4 id: cord-292794-okh6i4l1 author: Wang, Bin title: Protective efficacy of a broadly cross-reactive swine influenza DNA vaccine encoding M2e, cytotoxic T lymphocyte epitope and consensus H3 hemagglutinin date: 2012-06-27 words: 4776.0 sentences: 235.0 pages: flesch: 44.0 cache: ./cache/cord-292794-okh6i4l1.txt txt: ./txt/cord-292794-okh6i4l1.txt summary: Results demonstrated that there was no detectable virus load in all the vaccine-immunized mice, while empty vector control group showed high lung viral titers ( Figure 4 ). Results indicated that all the mice that had been vaccinated with MHa had a detectable virus level, although showed a reduction in mean viral titers in both challenge groups compared with vector control, the reduction did not reach significance (p = 0.06 for rPan09 group and p = 0.67 for G11 group, Figure 4 ). The present study lays the foundation for universal swine influenza vaccine development, and call for further investigations in which the heterologous immune response should be further enhanced, such as the addition of molecular adjuvants [31, 32] and/or more copies of conserved viral protein encoding genes [33] , and the usage of DNA-prime protein/virus-boost immunization schedule [34, 35] . abstract: BACKGROUND: Pigs have been implicated as mixing reservoir for the generation of new pandemic influenza strains, control of swine influenza has both veterinary and public health significance. Unlike human influenza vaccines, strains used for commercially available swine influenza vaccines are not regularly replaced, making the vaccines provide limited protection against antigenically diverse viruses. It is therefore necessary to develop broadly protective swine influenza vaccines that are efficacious to both homologous and heterologous virus infections. In this study, two forms of DNA vaccines were constructed, one was made by fusing M2e to consensus H3HA (MHa), which represents the majority of the HA sequences of H3N2 swine influenza viruses. Another was made by fusing M2e and a conserved CTL epitope (NP147-155) to consensus H3HA (MNHa). Their protective efficacies against homologous and heterologous challenges were tested. RESULTS: BALB/c mice were immunized twice by particle-mediated epidermal delivery (gene gun) with the two DNA vaccines. It was shown that the two vaccines elicited substantial antibody responses, and MNHa induced more significant T cell-mediated immune response than MHa did. Then two H3N2 strains representative of different evolutional and antigenic clusters were used to challenge the vaccine-immunized mice (homosubtypic challenge). Results indicated that both of the DNA vaccines prevented homosubtypic virus infections completely. The vaccines’ heterologous protective efficacies were further tested by challenging with a H1N1 swine influenza virus and a reassortant 2009 pandemic strain. It was found that MNHa reduced the lung viral titers significantly in both challenge groups, histopathological observation showed obvious reduction of lung pathogenesis as compared to MHa and control groups. CONCLUSIONS: The combined utility of the consensus HA and the conserved M2e and CTL epitope can confer complete and partial protection against homologous and heterologous challenges, respectively, in mouse model. This may provide a basis for the development of universal swine influenza vaccines. url: https://www.ncbi.nlm.nih.gov/pubmed/22738661/ doi: 10.1186/1743-422x-9-127 id: cord-312278-rin733w4 author: Wang, Yung‐Chih title: Current diagnostic tools for coronaviruses–From laboratory diagnosis to POC diagnosis for COVID‐19 date: 2020-08-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The Coronavirus‐2019 (COVID‐19) pandemic has put tremendous strain on healthcare systems worldwide. It is challenging for clinicians to differentiate COVID‐19 from other acute respiratory tract infections via clinical symptoms because those who are infected display a wide range of symptoms. An effective, point‐of‐care (POC) diagnostic tool could mitigate healthcare system strain, protect healthcare professionals, and support quarantine efforts. We believe that a POC tool can be developed that would be rapid, easy to use, and inexpensive. It could be used in the home, in resource‐limited areas, and even in clinical settings. In this article, we summarize the current state of POC tools and propose an all‐in‐one, highly sensitive POC assay that integrates antibody detection, protein detection, and serum cytokine detection to diagnose COVID‐19 infection. We believe this article will provide insight into the current state of POC diagnostics for COVID‐19, and promote additional research and tool development that could be exceptionally impactful. url: https://doi.org/10.1002/btm2.10177 doi: 10.1002/btm2.10177 id: cord-035173-6974gw6j author: Wang, Zhuo title: Effects of Low-Dose X-Ray on Cell Growth, Membrane Permeability, DNA Damage and Gene Transfer Efficiency date: 2020-10-28 words: 5527.0 sentences: 262.0 pages: flesch: 56.0 cache: ./cache/cord-035173-6974gw6j.txt txt: ./txt/cord-035173-6974gw6j.txt summary: title: Effects of Low-Dose X-Ray on Cell Growth, Membrane Permeability, DNA Damage and Gene Transfer Efficiency BACKGROUND: We aimed to reveal if low dose X-rays would induce harmful or beneficial effect or dual response on biological cells and whether there are conditions the radiation can enhance gene transfer efficiency and promote cell growth but without damage to the cells. METHOD: A systematic study was performed on the effects of Kilo-V and Mega-V X-rays on the cell morphology, viability, membrane permeability, DNA damage, and gene transfection of 293 T and CHO cells. RESULTS: The Kilo-V X-rays of very low doses from 0.01 to 0.04 Gray in principle didn''t induce any significant change in cell morphology, growth, membrane permeability, and cause DNA damage. We have shown that the very low doses KV X-ray irradiation (doses from 0.01-0.04 Gy) didn''t induce any significant change in CHO cells on cell morphology, cell viability, membrane permeability, DNA structure, and GFP transfection. abstract: BACKGROUND: We aimed to reveal if low dose X-rays would induce harmful or beneficial effect or dual response on biological cells and whether there are conditions the radiation can enhance gene transfer efficiency and promote cell growth but without damage to the cells. METHOD: A systematic study was performed on the effects of Kilo-V and Mega-V X-rays on the cell morphology, viability, membrane permeability, DNA damage, and gene transfection of 293 T and CHO cells. RESULTS: The Kilo-V X-rays of very low doses from 0.01 to 0.04 Gray in principle didn’t induce any significant change in cell morphology, growth, membrane permeability, and cause DNA damage. The Mega-V X-ray had a damage threshold between 1.0 and 1.5 Gray. The 0.25 Gray Mega-V-X-ray could promote cell growth and gene transfer, while the 1.5 Gray Mega-V X-ray damaged cells. CONCLUSION: The very low dose of KV X-rays is safe to cells, while the effects of Mega-V-X-rays are dose-dependent. Mega-V-X-rays with a dose higher than the damage threshold would be harmful, that between 1.0 -1.5 Gray can evoke dual effects, whereas 0.25 Gray MV X-ray is beneficial for both cell growth and gene transfer, thus would be suitable for radiation-enhanced gene transfection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597563/ doi: 10.1177/1559325820962615 id: cord-354000-jxqskt4k author: Warren, Cody J. title: The Antiviral Restriction Factors IFITM1, 2 and 3 Do Not Inhibit Infection of Human Papillomavirus, Cytomegalovirus and Adenovirus date: 2014-05-14 words: 4420.0 sentences: 265.0 pages: flesch: 47.0 cache: ./cache/cord-354000-jxqskt4k.txt txt: ./txt/cord-354000-jxqskt4k.txt summary: Here, we demonstrate that IFN-α or -β treatment of keratinocytes substantially decreases human papillomavirus 16 (HPV16) infection while robustly inducing IFITM1, 2 and 3 expression. IFITM protein expression induced by type I IFN inhibits infection of many RNA viruses [22] [23] [24] [25] [26] [27] [28] [29] [30] . Therefore, we analyzed induction of IFITM1, 2 and 3 expression by IFN-b treatment in human keratinocytes, the natural host cells for HPV. To determine the effect of IFITMs on HPV16 entry, HeLa cells stably expressing c-Myc-tagged IFITM1, 2 or 3 or with vector alone ( Fig. 2A-B) were infected with HPV16-LucF. Using various epithelial cell lines and primary keratinocytes expressing IFITMs, we show that HPV infection is surprisingly enhanced by IFITM1 and IFITM3 overexpression (Fig. 2) . Taken together, our results suggest that HPV and other DNA viruses may have evolved to avoid IFITM1, 2 and 3 restriction during entry into host cells. abstract: Type I interferons (IFN-α and β) induce dynamic host defense mechanisms to inhibit viral infections. It has been recently recognized that the interferon-inducible transmembrane proteins (IFITM) 1, 2 and 3 can block entry of a broad spectrum of RNA viruses. However, no study to date has focused on the role of IFITM proteins in DNA virus restriction. Here, we demonstrate that IFN-α or -β treatment of keratinocytes substantially decreases human papillomavirus 16 (HPV16) infection while robustly inducing IFITM1, 2 and 3 expression. However, IFITM1, 2 and 3 overexpression did not inhibit HPV16 infection; rather, IFITM1 and IFITM3 modestly enhanced HPV16 infection in various cell types including primary keratinocytes. Moreover, IFITM1, 2 and 3 did not inhibit infection by two other DNA viruses, human cytomegalovirus (HCMV) and adenovirus type 5 (Ad5). Taken together, we reveal that the entry of several DNA viruses, including HPV, HCMV, and Ad5 is not affected by IFITM1, 2 and 3 expression. These results imply that HPV, and other DNA viruses, may bypass IFITM restriction during intracellular trafficking. url: https://doi.org/10.1371/journal.pone.0096579 doi: 10.1371/journal.pone.0096579 id: cord-328947-3l9ydspz author: Webb, L. G. title: Chikungunya virus antagonizes cGAS-STING mediated type-I interferon responses by degrading cGAS date: 2020-10-15 words: 9857.0 sentences: 544.0 pages: flesch: 51.0 cache: ./cache/cord-328947-3l9ydspz.txt txt: ./txt/cord-328947-3l9ydspz.txt summary: CHIKV is no exception, the type-I interferon (IFN) response has been demonstrated to be key in controlling CHIKV infection [21] [22] [23] [24] [25] [26] and primary sensing of the virus is via the pattern recognition receptor (PRR) retinoic acid-inducible gene I (RIG-I)-mitochondrial antiviral signaling protein (MAVS) axis [24, 26] . The lack of cGAS degradation seen in the exogenous expression system when compared to the infected cells shows that although there is a clear interaction of cGAS with nsP4, the degradation of cGAS observed is not mediated by the non-structural proteins of CHIKV, but must require other viral or host factors. Chikungunya virus inhibits DNA sensing by degrading cGAS both mock and infected cells by 4 hpi suggesting that the stress produced during the process of infection (mock or CHIKV) in HFF-1s stimulates increased translation at early timepoints ( Fig 4D, lanes 2 and 5) . abstract: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus known to cause epidemics resulting in predominantly symptomatic infections, which in rare cases cause long term debilitating arthritis and arthralgia. Significant progress has been made in understanding the roles of canonical RNA sensing pathways in the host recognition of CHIKV; however, less is known regarding antagonism of CHIKV by cytosolic DNA sensing pathways like that of cyclic GMP-AMP synthase (cGAS) and Stimulator of Interferon Genes (STING). With the use of cGAS or STING null cells we demonstrate that the pathway restricts CHIKV replication in fibroblasts and immune cells. We show that DNA accumulates in the cytoplasm of infected cells and that CHIKV blocks DNA dependent IFN-β transcription. This antagonism of DNA sensing is via an early autophagy-mediated degradation of cGAS and expression of the CHIKV capsid protein is sufficient to induce cGAS degradation. Furthermore, we identify an interaction of CHIKV nsP1 with STING and map the interaction to 23 residues in the cytosolic loop of the adaptor protein. This interaction stabilizes the viral protein and increases the level of palmitoylated nsP1 in cells. Together, this work supports previous publications highlighting the relevance of the cGAS-STING pathway in the early detection of (+)ssRNA viruses and provides direct evidence that CHIKV interacts with and antagonizes cGAS-STING signaling. url: https://doi.org/10.1371/journal.ppat.1008999 doi: 10.1371/journal.ppat.1008999 id: cord-023389-ilrp8vb7 author: Wefer, J. title: Protective DNA Vaccination Against MOG(91‐108)‐Induced Experimental Autoimmune Encephalomyelitis Involves Induction of IFNβ date: 2008-06-28 words: 16845.0 sentences: 866.0 pages: flesch: 46.0 cache: ./cache/cord-023389-ilrp8vb7.txt txt: ./txt/cord-023389-ilrp8vb7.txt summary: We demonstrate that Cw6 þ psoriasis patients had significant CD8 þ T-cell IFN-g responses to peptides from K17 and M6 protein selected on the basis of sequence homology and predicted HLA-Cw*0602 binding. The uptake of MBP by B cells and the presentation of MBP-derive peptides to T helper (Th) cells by B cells may be promoted by the formation of complement (C) activating immune complexes (ICs) between MBP and natural autoantibodies in healthy individuals and disease-associated anti-MBP antibodies in MS patients, respectively. While MBP did not induce measurable proliferation of B cells nor CD4 þ T cells, we observed the production of TNF-a, IFN-g and IL-10 by PBMC in response to incubation with MBP in the presence of sera from healthy controls as well as sera from MS patients. In conclusion, the results of this study suggest an involvement of the ASMase in the activation, expansion or maturation of virus-specific CD8 þ T cells during the acute infection of mice with the LCM virus. abstract: DNA vaccine coding for the encephalitogenic peptide MOG(91‐108) protects LEW.1AV1 from subsequent development of experimental autoimmune encephalomyelitis (EAE). Protection is associated with a type 1 immune response and is dependent on the presence of CpG DNA motifs. The mechanisms underlying the observed reduction of EAE development in protected rats have not been fully clarified. We investigated immunological characteristics of lymphocytes after DNA vaccinaton and subsequent EAE induction. We confirm that protection was not associated with suppression of T1 cells, as transcription of the novel molecule rat T‐cell immunoglobulin‐ and mucin‐domain‐containing molecule (TIM‐3), reported to be exclusively expressed on differentiated T1 cells, was not altered by DNA vaccination. We did not note any clonal deletion upon tolerization, but detected an antigen‐specific lymphocyte population upregulating IFNγ upon recall stimulation 3 weeks after protective DNA vaccination. In protected rats, we observed (1) no alterations in antigen‐specific Th2 or Th3 responses, (2) reduced MHC II expression on splenocytes early after EAE induction, (3) antigen‐specific upregulation of IFNβ upon recall stimulation and (4) reduced IL‐12Rβ2 on lymphocytes. We thus demonstrate an association of the protective effect of DNA vaccination with expression of IFNβ. We are currently investigating the cellular mechanisms behind this IFNβ‐mediated protection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169512/ doi: 10.1111/j.0300-9475.2004.01423j.x id: cord-311839-61djk4bs author: Wei, Dan title: A novel hierarchical clustering algorithm for gene sequences date: 2012-07-23 words: 8033.0 sentences: 496.0 pages: flesch: 61.0 cache: ./cache/cord-311839-61djk4bs.txt txt: ./txt/cord-311839-61djk4bs.txt summary: We propose a new alignment-free algorithm, mBKM, based on a new distance measure, DMk, for clustering gene sequences. DMk shows better performance than the k-tuple distance in our experiments, and mBKM outperforms SL, CL, AL, BKM and KM when tested on public gene sequence datasets. In this paper we propose a new alignment-free similarity measure, DMk, based on which we developed mBKM to cluster gene sequences. To evaluate the proposed similarity measure, we test DMk on gene sequence data sets and compare it with the k-tuple distance. Moreover, we use our method, mBKM with similarity measure DMk, in phylogenetic analysis to show how well the genes are grouped together and how well the resulting trees agree with existing phylogenies. In order to illustrate the efficiency of mBKM in gene sequence clustering, we ran mBKM with the k-tuple distance and DMk on real data sets listed in Table 1 . abstract: BACKGROUND: Clustering DNA sequences into functional groups is an important problem in bioinformatics. We propose a new alignment-free algorithm, mBKM, based on a new distance measure, DMk, for clustering gene sequences. This method transforms DNA sequences into the feature vectors which contain the occurrence, location and order relation of k-tuples in DNA sequence. Afterwards, a hierarchical procedure is applied to clustering DNA sequences based on the feature vectors. RESULTS: The proposed distance measure and clustering method are evaluated by clustering functionally related genes and by phylogenetic analysis. This method is also compared with BlastClust, CD-HIT-EST and some others. The experimental results show our method is effective in classifying DNA sequences with similar biological characteristics and in discovering the underlying relationship among the sequences. CONCLUSIONS: We introduced a novel clustering algorithm which is based on a new sequence similarity measure. It is effective in classifying DNA sequences with similar biological characteristics and in discovering the relationship among the sequences. url: https://doi.org/10.1186/1471-2105-13-174 doi: 10.1186/1471-2105-13-174 id: cord-265237-sxh2nqre author: Weile, Jan title: Current applications and future trends of molecular diagnostics in clinical bacteriology date: 2009-04-18 words: 4555.0 sentences: 226.0 pages: flesch: 35.0 cache: ./cache/cord-265237-sxh2nqre.txt txt: ./txt/cord-265237-sxh2nqre.txt summary: Improvements and new approaches in technology now open the possibility for the development of multiparameter assays using microarrays, multiplex nucleic acid amplification techniques, or mass spectrometry, while the introduction of closed-tube systems has resulted in rapid microbial diagnostics with a subsequently reduced contamination risk. We mainly focus this review on nucleic-acid-based molecular techniques for identification and resistance determination in clinical bacteriology, giving a brief overview of currently used modern bacterial diagnostics and providing an outlook on future technologies, especially dealing with the multiparametric detection of infectious disease-related determinants. With exception of molecular tests such as nucleic acid amplification techniques (NAT), direct microscopy of the specimen, culturing, and direct antigen detection represent the sole possibilities to detect an acute infection as early as possible, facing either a lack of sensitivity, specificity or long time periods until results are available. abstract: Molecular diagnostics of infectious diseases, in particular, nucleic-acid-based methods, are the fastest growing field in clinical laboratory diagnostics. These applications are stepwise replacing or complementing culture-based, biochemical, and immunological assays in microbiology laboratories. The first-generation nucleic acid assays were monoparametric such as conventional tests, determining only a single parameter. Improvements and new approaches in technology now open the possibility for the development of multiparameter assays using microarrays, multiplex nucleic acid amplification techniques, or mass spectrometry, while the introduction of closed-tube systems has resulted in rapid microbial diagnostics with a subsequently reduced contamination risk. Whereas the first assays were focused on the detection and identification of microbial pathogens, these new technologies paved the way for the parallel determination of multiple antibiotic resistance determinants or to perform microbial epidemiology and surveillance on a genetic level. url: https://doi.org/10.1007/s00216-009-2779-8 doi: 10.1007/s00216-009-2779-8 id: cord-306175-p5rtp31m author: Weissbrich, Benedikt title: Frequent detection of bocavirus DNA in German children with respiratory tract infections date: 2006-07-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: In a substantial proportion of respiratory tract diseases of suspected infectious origin, the etiology is unknown. Some of these cases may be caused by the recently described human bocavirus (hBoV). The aim of this study was to investigate the frequency and the potential clinical relevance of hBoV in pediatric patients. METHODS: We tested 835 nasopharyngeal aspirates (NPA) obtained between 2002 and 2005 from pediatric in-patients with acute respiratory tract diseases at the University of Würzburg, Germany, for the presence of hBoV DNA. The specificity of positive PCR reactions was confirmed by sequencing. RESULTS: HBoV DNA was found in 87 (10.3 %) of the NPAs. The median age of the infants and children with hBoV infection was 1.8 years (mean age 2.0 years; range 18 days – 8 years). Infections with hBoV were found year-round, though most occurred in the winter months. Coinfections were found in 34 (39.1 %) of the hBoV positive samples. RSV, influenza A, and adenoviruses were most frequently detected as coinfecting agents. Sequence determination of the PCR products in the NP-1 region revealed high identity (99 %) between the nucleotide sequences obtained in different years and in comparison to the Swedish viruses ST1 and ST2. An association of hBoV with a distinct respiratory tract manifestation was not apparent. CONCLUSION: HBoV is frequently found in NPAs of hospitalized infants and children with acute respiratory tract diseases. Proving the clinical relevance of hBoV is challenging, because application of some of Koch's revised postulates is not possible. Because of the high rate of coinfections with hBoV and other respiratory tract pathogens, an association between hBoV and respiratory tract diseases remains unproven. url: https://www.ncbi.nlm.nih.gov/pubmed/16834781/ doi: 10.1186/1471-2334-6-109 id: cord-008333-1wepke2o author: Weisz, Ora A. title: Chapter 7 Use of Recombinant Vaccinia Virus Vectors for Cell Biology date: 2008-02-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: This chapter describes the use of several of the recombinant vaccinia expression systems, focuses on the systems that are most useful for cell biologists, and discusses their advantages and limitations. Vaccinia-mediated expression can be used for assessing cellular localization, posttranslational modifications, oligomerization, and transport and turnover rates. The system provides a rapid method for screening mutant proteins for expression and targeting. It is an excellent way of quickly deciding which mutant proteins might be worth further studying using stable expression systems. Expression of foreign genes using Vaccinia virus is based on recombinant viruses constructed by insertion of complementary DNA (cDNA) into the nonessential thymidine kinase (TK) gene. Both direct and indirect methods of expression are possible. The foreign gene can be inserted into the vaccinia genome by homologous recombination using a plasmid with flanking regions of vaccinia DNA. The recombinant virus is selected, expanded, and used to infect cells, which then express high levels of the foreign protein. Recombinant vaccinia viruses are generated by subcloning the foreign gene into a plasmid transfer vector so it is flanked by DNA from the vaccinia (TK) gene, which is nonessential for growth of the virus in tissue culture. This plasmid is then transfected into vaccinia-infected cells. Homologous recombination of the plasmid and the vaccinia genome generates a recombinant virus with an inactive TK gene. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7130382/ doi: 10.1016/s0091-679x(08)60602-0 id: cord-267671-ys43n672 author: Whary, Mark T. title: Biology and Diseases of Mice date: 2015-07-10 words: 63666.0 sentences: 3678.0 pages: flesch: 40.0 cache: ./cache/cord-267671-ys43n672.txt txt: ./txt/cord-267671-ys43n672.txt summary: Clinical Signs MCMV causes subclinical infection in adult immunocompetent mice, but experimental inoculation of neonates can cause lethal disease due to multisystemic necrosis and inflammation. Diagnosis Because infected mice do not manifest signs or lesions and the virus is very difficult to propagate in cell culture, detection and diagnosis rely on serology and molecular methods. Differential Diagnosis Reovirus infection must be differentiated from other diarrheal diseases of infant mice, including those caused by mouse coronaviruses, EDIM virus, Salmonella spp., or Clostridium piliforme. Epizootiology EDIM virus appears to be infectious only for mice and occurs episodically in mouse colonies, and infection is probably widespread geographically (Livingston and Riley, 2003; Pritchett-Corning LABORATORY ANIMAL MEDICINE et al., 2009) . Sentinel mouse surveillance, using soiled bedding, is an effective strategy for detecting MNV (Manuel et al., 2008) Differential Diagnosis The mild change in fecal consistency associated with MNV in adult mice may mimic rotavirus, coronavirus, Helicobacter spp., Citrobacter rodentium, or other enteric diseases. abstract: Today’s laboratory mouse, Mus musculus, has its origins as the ‘house mouse’ of North America and Europe. Beginning with mice bred by mouse fanciers, laboratory stocks (outbred) derived from M. musculus musculus from eastern Europe and M. m. domesticus from western Europe were developed into inbred strains. Since the mid-1980s, additional strains have been developed from Asian mice (M. m. castaneus from Thailand and M. m. molossinus from Japan) and from M. spretus which originated from the western Mediterranean region. url: https://api.elsevier.com/content/article/pii/B9780124095274000031 doi: 10.1016/b978-0-12-409527-4.00003-1 id: cord-286243-ddpemgqt author: Whitaker, Amy M. title: APE1: A skilled nucleic acid surgeon date: 2018-11-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Before a deleterious DNA lesion can be replaced with its undamaged counterpart, the lesion must first be removed from the genome. This process of removing and replacing DNA lesions is accomplished by the careful coordination of several protein factors during DNA repair. One such factor is the multifunctional enzyme human apurinic/apyrimidinic endonuclease 1 (APE1), known best for its DNA backbone cleavage activity at AP sites during base excision repair (BER). APE1 preforms AP site incision with surgical precision and skill, by sculpting the DNA to place the cleavage site in an optimal position for nucleophilic attack within its compact protein active site. APE1, however, has demonstrated broad surgical expertise, and applies its DNA cleavage activity to a wide variety of DNA and RNA substrates. Here, we discuss what is known and unknown about APE1 cleavage mechanisms, focusing on structural and mechanistic considerations. Importantly, disruptions in the biological functions associated with APE1 are linked to numerous human maladies, including cancer and neurodegenerative diseases. The continued elucidation of APE1 mechanisms is required for rational drug design towards novel and strategic ways to target its associated repair pathways. url: https://www.ncbi.nlm.nih.gov/pubmed/30170830/ doi: 10.1016/j.dnarep.2018.08.012 id: cord-000269-v4jochbe author: Wittekindt, Nicola E. title: Nodeomics: Pathogen Detection in Vertebrate Lymph Nodes Using Meta-Transcriptomics date: 2010-10-18 words: 5886.0 sentences: 314.0 pages: flesch: 44.0 cache: ./cache/cord-000269-v4jochbe.txt txt: ./txt/cord-000269-v4jochbe.txt summary: cDNA libraries from five individuals and two pools of samples were prepared from retropharyngeal lymph node RNA enriched for polyadenylated RNA and sequenced using Roche-454 Life Sciences technology. Representatives of all bacterial phyla were detected in the seven libraries based on protein-coding transcripts indicating that viable microbiota were present in lymph nodes. Based on detection of both rRNA and protein-coding transcripts, we identified two new proteobacterial species; a Helicobacter closely related to Helicobacter cetorum in the Helicobacter pylori/Helicobacter acinonychis complex and an Acinetobacter related to Acinetobacter schindleri. The microbial community of mule deer lymph nodes Detection of protein-coding and ribosomal RNA transcripts provides strong support for the presence of viable and replicating microorganisms. As an alternative approach to identifying bacterial microorganisms present in lymph node tissue, we utilized amplicon DNA library sequencing technology. abstract: The ongoing emergence of human infections originating from wildlife highlights the need for better knowledge of the microbial community in wildlife species where traditional diagnostic approaches are limited. Here we evaluate the microbial biota in healthy mule deer (Odocoileus hemionus) by analyses of lymph node meta-transcriptomes. cDNA libraries from five individuals and two pools of samples were prepared from retropharyngeal lymph node RNA enriched for polyadenylated RNA and sequenced using Roche-454 Life Sciences technology. Protein-coding and 16S ribosomal RNA (rRNA) sequences were taxonomically profiled using protein and rRNA specific databases. Representatives of all bacterial phyla were detected in the seven libraries based on protein-coding transcripts indicating that viable microbiota were present in lymph nodes. Residents of skin and rumen, and those ubiquitous in mule deer habitat dominated classifiable bacterial species. Based on detection of both rRNA and protein-coding transcripts, we identified two new proteobacterial species; a Helicobacter closely related to Helicobacter cetorum in the Helicobacter pylori/Helicobacter acinonychis complex and an Acinetobacter related to Acinetobacter schindleri. Among viruses, a novel gamma retrovirus and other members of the Poxviridae and Retroviridae were identified. We additionally evaluated bacterial diversity by amplicon sequencing the hypervariable V6 region of 16S rRNA and demonstrate that overall taxonomic diversity is higher with the meta-transcriptomic approach. These data provide the most complete picture to date of the microbial diversity within a wildlife host. Our research advances the use of meta-transcriptomics to study microbiota in wildlife tissues, which will facilitate detection of novel organisms with pathogenic potential to human and animals. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956653/ doi: 10.1371/journal.pone.0013432 id: cord-003656-7mzsaz7a author: Wium, Martha title: DNA Vaccines Against Mycoplasma Elicit Humoral Immune Responses in Ostriches date: 2019-05-14 words: 5575.0 sentences: 308.0 pages: flesch: 53.0 cache: ./cache/cord-003656-7mzsaz7a.txt txt: ./txt/cord-003656-7mzsaz7a.txt summary: Currently there are no commercially available vaccines against ostrich-infecting mycoplasmas and this study therefore set out to develop and evaluate the use of a DNA vaccine against mycoplasma infections in ostriches using an OppA protein as antigen. The ability of the DNA vaccines to elicit an anti-OppA antibody response was evaluated by ELISA using the recombinant OppA protein of Ms03 as coating antigen. In this study we report, for the first time, that a DNA vaccine can elicit a humoral immune response in ostriches using OppA as antigen. The controls were serum samples representing the week 0, 3, 6, and 9 sampling points of a single ostrich, randomly selected from the pCI-neo_oppA 1,200 µg group based on high titers produced after vaccination. In this study, DNA vaccines were developed for ostriches using the oppA gene of an ostrich-infecting mycoplasma (Ms03) as vaccine antigen. abstract: In ostriches, the population densities resulting from intensive rearing increases susceptibility to pathogens such as mycoplasmas. In addition to good management practices, vaccination offers an attractive alternative for controlling mycoplasma infections in food animals, instead of using antibiotics, which often leave unacceptable residues. The use of live attenuated vaccines, however, carry the concern of reversion to virulence or genetic recombination with field strains. Currently there are no commercially available vaccines against ostrich-infecting mycoplasmas and this study therefore set out to develop and evaluate the use of a DNA vaccine against mycoplasma infections in ostriches using an OppA protein as antigen. To this end, the oppA gene of “Mycoplasma nasistruthionis sp. nov.” str. Ms03 was cloned into two DNA vaccine expression vectors after codon correction by site-directed mutagenesis. Three-months-old ostriches were then vaccinated intramuscularly at different doses followed by a booster vaccination after 6 weeks. The ability of the DNA vaccines to elicit an anti-OppA antibody response was evaluated by ELISA using the recombinant OppA protein of Ms03 as coating antigen. A statistically significant anti-OppA antibody response could be detected after administration of a booster vaccination indicating that the OppA protein was successfully immunogenic. The responses were also both dose and vector dependent. In conclusion, the DNA vaccines were able to elicit an immune response in ostriches and can therefore be viewed as an option for the development of vaccines against mycoplasma infections. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527592/ doi: 10.3389/fimmu.2019.01061 id: cord-325915-dw989txm author: Wolf, Michael W title: Downstream processing of cell culture-derived virus particles date: 2014-01-09 words: 11861.0 sentences: 655.0 pages: flesch: 34.0 cache: ./cache/cord-325915-dw989txm.txt txt: ./txt/cord-325915-dw989txm.txt summary: The number of publications [24, [38] [39] [40] [41] [42] [43] [44] [45] [46] and patents [301] [302] [303] describing the purification or concentration of virus particles by centrifugation methods demonstrates that these procedures are extensively used at industrial-and small-scale levels for viral vectors and vaccine production processes. In summary, the main advantages of ultrafiltration compared with other methods are their high-throughput and (for the concentration of active virus particles) the gentle processing at optimal operating conditions [43, 47] that results in improved efficacies for purification of viral vectors for gene therapy. Considering a complete purification train for the production of vaccines or gene therapy vectors (Figure 1) , current improvements of the dynamic binding capacities in chromatography media might facilitate the removal of the initial concentration step within the downstream process. abstract: Manufacturing of cell culture-derived virus particles for vaccination and gene therapy is a rapidly growing field in the biopharmaceutical industry. The process involves a number of complex tasks and unit operations ranging from selection of host cells and virus strains for the cultivation in bioreactors to the purification and formulation of the final product. For the majority of cell culture-derived products, efforts focused on maximization of bioreactor yields, whereas design and optimization of downstream processes were often neglected. Owing to this biased focus, downstream procedures today often constitute a bottleneck in various manufacturing processes and account for the majority of the overall production costs. For efficient production methods, particularly in sight of constantly increasing economic pressure within human healthcare systems, highly productive downstream schemes have to be developed. Here, we discuss unit operations and downstream trains to purify virus particles for use as vaccines and vectors for gene therapy. url: https://doi.org/10.1586/erv.11.111 doi: 10.1586/erv.11.111 id: cord-266670-jxgywvwx author: Wong, Mark title: Chapter 13 Recent Advances and Future Needs in Environmental Virology date: 2007-09-06 words: 5842.0 sentences: 333.0 pages: flesch: 39.0 cache: ./cache/cord-266670-jxgywvwx.txt txt: ./txt/cord-266670-jxgywvwx.txt summary: The standard method of detection of viral pathogens in environmental samples uses assays in mammalian cell culture. The standard method of detection of viral pathogens in environmental samples uses assays in mammalian cell culture. When realtime PCR quantitative results for adenoviruses in environmental samples were compared with conventional cell culture results, it was concluded that the real-time PCR method demonstrated higher quantities of adenoviruses in comparison with conventional techniques. Detection of astroviruses, enteroviruses, and adenovirus types 40 and 41 in surface waters collected and evaluated by the information collection rule and an integrated cell culture-nested PCR procedure Application of Real-Time PCR and Tissue Culture Assay for Adenovirus Detection in Two Southern California Urban Rivers Rapid and quantitative detection of human adenovirus DNA by real-time PCR Use of cell culture-PCR assay based on combination of A549 and BGMK cell lines and molecular identification as a tool to monitor infectious adenoviruses and enteroviruses in river water abstract: The detection of viruses in water and other environmental samples constitutes special challenges. The standard method of detection of viral pathogens in environmental samples uses assays in mammalian cell culture. The infected cell cultures undergo observable morphological changes called cytopathogenic effects (CPEs) that are used for the detection of viruses. Even though many viruses are culturable in several cell lines and are thus detectable by the development of CPEs in cell culture, there are several viruses, like enteric waterborne adenoviruses types 40 and 41, which are difficult to culture and do not produce clear and consistent CPE. Other viruses, like waterborne caliciviruses, have not yet been successfully grown in cell cultures. Conventional cell culture assays for the detection of viruses in environmental samples have limited sensitivity and can be labor-intensive and timeconsuming. Two advances, the PCR and microarrays, have spurred the study of viruses and should be further applied to the field of environmental virology. The ability of both DNA viruses and RNA viruses to rapidly evolve means new and emerging viral pathogens will need to be addressed. Pathogen discovery and characterization, occurrence in the environment, exposure pathways, and health outcomes via environmental exposure need to be addressed. This will likely follow a new microbial risk framework that will require focused research on some important properties of viral disease transmission. The future will require models that examine community risks and provide explicit links between the models currently under development for environmental exposure and infectious disease. url: https://api.elsevier.com/content/article/pii/S0168706907170130 doi: 10.1016/s0168-7069(07)17013-0 id: cord-010037-1bpc8g6n author: Wu, Hui title: A high frequency of allopolyploid speciation in the gymnospermous genus Ephedra and its possible association with some biological and ecological features date: 2016-02-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The origin and evolution of polyploids have been studied extensively in angiosperms and ferns but very rarely in gymnosperms. With the exception of three species of conifers, all natural polyploid species of gymnosperms belong to Ephedra, in which more than half of the species show polyploid cytotypes. Here, we investigated the origin and evolution of polyploids of Ephedra distributed in the Qinghai–Tibetan Plateau (QTP) and neighbouring areas. Flow cytometry (FCM) was used to measure the ploidy levels of the sampled species that are represented by multiple individuals from different populations, and then, two single‐copy nuclear genes (LFY and DDB2) and two chloroplast DNA fragments were used to unravel the possible origins and maternal donors of the polyploids. The results indicate that the studied polyploid species are allopolyploids, and suggest that allotetraploidy is a dominant mode of speciation in Ephedra. The high percentage of polyploids in the genus could be related to some of its biological attributes such as vegetative propagation, a relatively high rate of unreduced gamete formation, and a small genome size relative to most other gymnosperms. Significant ecological divergences between allotetraploids and their putative progenitors were detected by PCAs and anova and Tukey's tests, with the exception of E. saxatilis. The overlap of geographical distributions and ecological niches of some diploid species could have provided opportunities for interspecific hybridization and allopolyploid speciation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168403/ doi: 10.1111/mec.13538 id: cord-342629-mzi0krja author: Wu, Q. title: An Activated GOPS‐poly‐L‐Lysine‐ Coated Glass Surface for the Immobilization of 60mer Oligonucleotides date: 2005-11-16 words: 2086.0 sentences: 118.0 pages: flesch: 49.0 cache: ./cache/cord-342629-mzi0krja.txt txt: ./txt/cord-342629-mzi0krja.txt summary: To explore a method for enhancing the immobilization and hybridization efficiency of oligonucleotides on DNA microarrays, conventional protocols of poly‐L‐lysine coating were modified by means of surface chemistry, namely, the slides were prepared by the covalently coupling of poly‐L‐lysine to a glycidoxy‐modified glass surface. The modified slides were then used to print microarrays for the detection of the SARS coronavirus by means of 60mer oligonucleotide probes. With the development of the DNA microarray technology, many reports on the modification of glass surfaces and the immobilization of oligonucleotides onto solid supports by covalent linkage have appeared [8±12]. In this paper, the process of slide surface chemistry based on conventional protocols for poly-L-lysine coating was improved [6, 13] in order to immobilize 60mer oligonucleotides by deposition technology. Oligo microarrays printed on an activated GOPS-PLL slide could undergo hybridization stripping cycles for at least three cycles. Preparation of SARS 60mer oligonucleotide probes for microarray printing abstract: To explore a method for enhancing the immobilization and hybridization efficiency of oligonucleotides on DNA microarrays, conventional protocols of poly‐L‐lysine coating were modified by means of surface chemistry, namely, the slides were prepared by the covalently coupling of poly‐L‐lysine to a glycidoxy‐modified glass surface. The modified slides were then used to print microarrays for the detection of the SARS coronavirus by means of 60mer oligonucleotide probes. The characteristics of the modified slides concerning immobilization efficiency, hybridization dynamics, and probe stripping cycles were determined. The improved surface exhibited high immobilization efficiency, a good quality uniformity, and satisfactory hybridization dynamics. The spotting concentration of 10 μmol/L can meet the requirements of detection; the spots were approximately 170 nm in diameter; the mean fluorescence intensity of the SARS spots were between 3.2 × 10(4) and 5.0 × 10(4) after hybridization. Furthermore, the microarrays prepared by this method demonstrated more resistance to consecutive probe stripping cycles. The activated GOPS‐PLL slide could undergo hybridization stripping cycles for at least three cycles, and the highest loss in fluorescence intensity was found to be only 11.9 % after the third hybridization. The modified slides using the above‐mentioned method were superior to those slides treated with conventional approaches, which theoretically agrees with the fact that modification by surface chemistry attaches the DNA covalently firmly to the slides. This protocol may have great promise in the future for application in large‐scale manufacture. url: https://doi.org/10.1002/elsc.200520097 doi: 10.1002/elsc.200520097 id: cord-268122-74nj66vb author: Xie, Na title: NAD(+) metabolism: pathophysiologic mechanisms and therapeutic potential date: 2020-10-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Nicotinamide adenine dinucleotide (NAD(+)) and its metabolites function as critical regulators to maintain physiologic processes, enabling the plastic cells to adapt to environmental changes including nutrient perturbation, genotoxic factors, circadian disorder, infection, inflammation and xenobiotics. These effects are mainly achieved by the driving effect of NAD(+) on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction reactions. Besides, multiple NAD(+)-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA, RNA and proteins, or releasing second messenger cyclic ADP-ribose (cADPR) and NAADP(+). Prolonged disequilibrium of NAD(+) metabolism disturbs the physiological functions, resulting in diseases including metabolic diseases, cancer, aging and neurodegeneration disorder. In this review, we summarize recent advances in our understanding of the molecular mechanisms of NAD(+)-regulated physiological responses to stresses, the contribution of NAD(+) deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention. url: https://doi.org/10.1038/s41392-020-00311-7 doi: 10.1038/s41392-020-00311-7 id: cord-026518-xv03vpji author: Xie, Peng title: Immune effect of a Newcastle disease virus DNA vaccine with IL-12 as a molecular adjuvant delivered by electroporation date: 2020-06-09 words: 5771.0 sentences: 280.0 pages: flesch: 52.0 cache: ./cache/cord-026518-xv03vpji.txt txt: ./txt/cord-026518-xv03vpji.txt summary: An additional 52 14-day-old SPF chickens were randomly divided into four equal groups (N = 13) to investigate the effect of chIL-12 used as an adjuvant to the F gene DNA vaccine. Two weeks after booster vaccination, the birds were challenged with NDV and mortality for 14 days was evaluated the two delivery methods might induce different immune responses in chickens. Oladele and colleagues constructed a DNA vaccine based on the HA gene of H5N1 avian influenza virus and found that EP delivery could enhance the antibody response, significantly reduce morbidity, and protect chickens from fatal NDV attack [25] . However, although all of the chickens in the pCAG-F/EP group survived, they did not all have detectable neutralizing antibodies, indicating that antibodies may not be essential for protection and that cell mediated immunity might play an important role in plasmid DNA-induced protection against NDV challenge. abstract: Newcastle disease (ND), caused by virulent Newcastle disease virus (NDV) strains, has been one of the most problematic diseases affecting the poultry industry worldwide. Conventional vaccines provide effective protection for birds to survive ND outbreaks, but they may not completely suppress NDV shedding. NDV strains circulate on farms for a long time after the initial infection and cause potential risks. A new vaccine with fast clearance ability and low viral shedding is needed. In this study, we used interleukin-12 (IL-12) as an adjuvant and electroporation (EP) as an advanced delivery system to improve a DNA vaccine candidate. The fusion (F) protein gene from an NDV strain of the prevalent genotype VII.1.1 was cloned to prepare the vaccine. Chickens immunized with the F gene DNA vaccine co-delivered with an IL-12-expressing plasmid DNA showed higher neutralizing antibody levels and stronger concanavalin-A-induced lymphocyte proliferation than those treated with the F gene DNA vaccine alone. The co-delivered vaccine provided 100% protection, and less viral shedding and a shorter release time were observed in challenged chickens than when the F gene DNA vaccine was administered alone. The use of F gene DNA combined with IL-12 delivered by electroporation is a promising approach for vaccination against ND. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282469/ doi: 10.1007/s00705-020-04669-5 id: cord-000575-g1ob16b9 author: Xie, Xiao-li title: Protein sequence analysis based on hydropathy profile of amino acids date: 2012-01-27 words: 2178.0 sentences: 116.0 pages: flesch: 48.0 cache: ./cache/cord-000575-g1ob16b9.txt txt: ./txt/cord-000575-g1ob16b9.txt summary: A new method to analyze the similarity/dissimilarity of protein sequence was proposed based on the conditional probability of the protein sequence. Based on the graphical representation, it is possible to numerically characterize DNA sequence and further quantitatively measure similarity of different DNA sequences. This is mainly because extension of DNA graphical representation to protein sequences would enormously increase the number of possible alternative assignments for the 20 amino acids. The graphical representation of protein sequence cannot only describe amino acid sequence, but also measure similarity/ dissimilarity of different protein sequences. In this paper, we converted a protein sequence into three-letter sequence based on hydropathy profile of amino acid and defined the three curves to represent different hydropathy features. The method is based on the graphical representation and conditional probability taken as the numerical characterization of the protein sequence. Similarity/dissimilarity studies of protein sequences based on a new 2D graphical representation abstract: Biology sequence comparison is a fundamental task in computational biology. According to the hydropathy profile of amino acids, a protein sequence is taken as a string with three letters. Three curves of the new protein sequence were defined to describe the protein sequence. A new method to analyze the similarity/dissimilarity of protein sequence was proposed based on the conditional probability of the protein sequence. Finally, the protein sequences of ND6 (NADH dehydrogenase subunit 6) protein of eight species were taken as an example to illustrate the new approach. The results demonstrated that the method is convenient and efficient. url: http://europepmc.org/articles/pmc3274743?pdf=render doi: 10.1631/jzus.b1100052 id: cord-003596-6dg7i06i author: Xiong, Qingqing title: Biomedical applications of mRNA nanomedicine date: 2018-07-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: As an attractive alternative to plasmid DNA, messenger RNA (mRNA) has recently emerged as a promising class of nucleic acid therapeutics for biomedical applications. Advances in addressing the inherent shortcomings of mRNA and in the development of nanoparticle-based delivery systems have prompted the development and clinical translation of mRNA-based medicines. In this review, we discuss the chemical modification strategies of mRNA to improve its stability, minimize immune responses, and enhance translational efficacy. We also highlight recent progress in nanoparticle-based mRNA delivery. Considerable attention is given to the increasingly widespread applications of mRNA nanomedicine in the biomedical fields of vaccination, protein-replacement therapy, gene editing, and cellular reprogramming and engineering. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472920/ doi: 10.1007/s12274-018-2146-1 id: cord-026729-hn0q0sbv author: Xu, Jun title: Functional investigation of the chromosomal ccdAB and hipAB operon in Escherichia coli Nissle 1917 date: 2020-06-13 words: 8851.0 sentences: 494.0 pages: flesch: 54.0 cache: ./cache/cord-026729-hn0q0sbv.txt txt: ./txt/cord-026729-hn0q0sbv.txt summary: Biofilm and persister formation of EcN controlled by the ccdAB and hipAB were associated with the expression of genes involved in DNA synthesis, SOS response, and stringent response. coli, more than ten kinds of type II TASs have been studied, of which the F-plasmid-based ccdAB and high persistence allele hipAB are two of the best characterized and identified that are mainly responsible for the plasmid maintenance and persister formation, respectively (Ogura and Hiraga 1983; Semanjski et al. The results showed that the inhibited expression of either ccdAB or hipAB significantly reduced the biofilm formation of EcN compared with that of control groups (wildtype and non-induced group), with the value of OD 540 /OD 620 decreased from 1.87 to 1.49, and 1.94 to 1.62, Fig. 3 Comparative and phylogenetic analysis of HipAB among different E. By CRISPRi, ccdAB and hipAB were shown to be involved in the formation of biofilm and persister cells in EcN. abstract: Toxin-antitoxin systems (TASs) have attracted much attention due to their important physiological functions. These small genetic factors have been widely studied mostly in commensal Escherichia coli strains, whereas the role of TASs in the probiotic E. coli Nissle 1917 (EcN) is still elusive. Here, the physiological role of chromosomally encoded type II TASs in EcN was examined. We showed that gene pair ECOLIN_00240-ECOLIN_00245 and ECOLIN_08365-ECOLIN_08370 were two functional TASs encoding CcdAB and HipAB, respectively. The homologs of CcdAB and HipAB were more conserved in E. coli species belonging to pathogenic groups, suggesting their important roles in EcN. CRISPRi-mediated repression of ccdAB and hipAB significantly reduced the biofilm formation of EcN in the stationary phase. Moreover, ccdAB and hipAB were shown to be responsible for the persister formation in EcN. Biofilm and persister formation of EcN controlled by the ccdAB and hipAB were associated with the expression of genes involved in DNA synthesis, SOS response, and stringent response. Besides, CRISPRi was proposed to be an efficient tool in annotating multiple TASs simultaneously. Collectively, our results advance knowledge and understanding of the role of TASs in EcN, which will enhance the utility of EcN in probiotic therapy. Key points • Two TASs in EcN were identified as hipAB and ccdAB. • Knockdown of HipAB and CcdAB resulted in decreased biofilm formation of EcN. • Transcriptional silencing of hipAB and ccdAB affected the persister formation of EcN. • An attractive link between TASs and stress response was unraveled in EcN. • CRISPRi afforded a fast and in situ annotation of multiple TASs simultaneously. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-020-10733-6) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293176/ doi: 10.1007/s00253-020-10733-6 id: cord-293072-giakcaki author: Xu, Wan-Xiang title: A simpler and more cost-effective peptide biosynthetic method using the truncated GST as carrier for epitope mapping date: 2017-10-12 words: 5303.0 sentences: 227.0 pages: flesch: 52.0 cache: ./cache/cord-293072-giakcaki.txt txt: ./txt/cord-293072-giakcaki.txt summary: The protocol involves the following core steps: (i) design of plus and minus strands of DNA fragments encoding overlapping 8/18mer peptides; (ii) chemical synthesis of the designed DNA fragments; (iii) development of r-clones using pXXGST-3 vector expressing each 8/18mer peptide fused with truncated GST188 protein; (iv) screening r-clones by running the cell pellets from each induced clone on SDS-PAGE gel followed by sequencing of inserted DNA fragments for each verified r-clone; and (v) Western blotting with either monoclonal antibodies or polyclonal antibodies. abstract: There is a need to develop better methods for epitope mapping and/or identification of antibody-recognizing motifs. Here, we describe improved biosynthetic peptide (BSP) method using a newly developed plasmid pXXGST-3 as vector, which has a viral E7 gene in the cloning sites of pXXGST-1. It is crucial to employ pXXGST-3 instead of pXXGST-1, since it makes use of the BSP method simpler and easier to perform, and more cost-effective for epitope mapping. These merits are embodied in two aspects: i) convenient recovery of double enzyme-digested product due to the existence of 315 bp inserted between BamH I and Sal I sites, and thus greatly reducing the production of self-ligation clones, and ii) no longer requiring control protein when screening recombinant (r-) clones expressing 8/18mer peptides by running polyacrylamide gel electrophoresis. The protocol involves the following core steps: (i) design of plus and minus strands of DNA fragments encoding overlapping 8/18mer peptides; (ii) chemical synthesis of the designed DNA fragments; (iii) development of r-clones using pXXGST-3 vector expressing each 8/18mer peptide fused with truncated GST188 protein; (iv) screening r-clones by running the cell pellets from each induced clone on SDS-PAGE gel followed by sequencing of inserted DNA fragments for each verified r-clone; and (v) Western blotting with either monoclonal antibodies or polyclonal antibodies. This improved GST188-BSP method provides a powerful alternative tool for epitope mapping. url: https://doi.org/10.1371/journal.pone.0186097 doi: 10.1371/journal.pone.0186097 id: cord-103422-ys846i99 author: Xu, Xinhui title: CRISPR-Assisted DNA Detection, a novel dCas9-based DNA detection technique date: 2020-05-13 words: 4258.0 sentences: 308.0 pages: flesch: 60.0 cache: ./cache/cord-103422-ys846i99.txt txt: ./txt/cord-103422-ys846i99.txt summary: In this detection, DNA sample is incubated with a pair of capture sgRNAs (sgRNAa and sgRNAb) specific to a target DNA, dCas9, a signal readout-related probe, and an oligo-coated solid support beads or microplate at room temperature for 15 min. When target DNA is bound by a pair of dCas9-sgRNA complexes, the dCas9-sgRNA-DNA complex will be captured on surface of beads or microplate via annealing between an oligonucleotide coupled on solid supports and capture sequence of sgRNAa. Then the captured dCas9-sgRNA-DNA complex is reported by a kind of signal reporter captured by the capture sequence of sgRNAb. This method was validated by detecting DNA of bacteria, cancer cell and virus. We compared the HPV detection results of these 31 clinical samples tested by Beads-HCR CADD and PCR-reverse dot hybridization method that was performed by Jinling Hospital (Fig. 4C ). These results indicate that Beads-HCR CADD can be used to detect hrHPV infections in clinical samples with high sensitivity and specificity. abstract: Nucleic acid detection techniques are always critical to diagnosis, especially in the background of the present COVID-19 pandemic. The simple and rapid detection techniques with high sensitivity and specificity are always urgently needed. However, the current nucleic acid detection techniques are still limited the traditional amplification and hybridization. To overcome the limitation, we here develop a CRISPR/Cas9-assisted DNA detection (CADD). In this detection, DNA sample is incubated with a pair of capture sgRNAs (sgRNAa and sgRNAb) specific to a target DNA, dCas9, a signal readout-related probe, and an oligo-coated solid support beads or microplate at room temperature for 15 min. During this incubation, the dCas9-sgRNA-DNA complex is formed and captured on solid support by the capture sequence of sgRNAa and the signal readout-related probe is captured by the capture sequence of sgRNAb. Finally the detection result is reported by a fluorescent or colorimetric signal readout. This detection was verified by detecting DNA of bacteria, cancer cell and virus. Especially, by designing a set of sgRNAs specific to 15 high-risk human papillomaviruses (HPVs), the HPV infection in 64 clinical cervical samples were successfully detected by the method. All detections can be finished in 30 minutes at room temperature. This detection holds promise for rapid on-the-spot detection or point-of-care testing (POCT). url: https://doi.org/10.1101/2020.05.13.093062 doi: 10.1101/2020.05.13.093062 id: cord-296886-0bma2749 author: Xu, Yingying title: Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives date: 2014-07-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT). Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV) etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents. url: https://www.ncbi.nlm.nih.gov/pubmed/25014738/ doi: 10.3390/pharmaceutics6030378 id: cord-014908-jys1y0k9 author: Yadav, Rakesh title: Trends and Perspectives of Biosensors for Food and Environmental Virology date: 2010-05-19 words: 5113.0 sentences: 259.0 pages: flesch: 32.0 cache: ./cache/cord-014908-jys1y0k9.txt txt: ./txt/cord-014908-jys1y0k9.txt summary: Unluckily, the PCR-based tools do not persistently amplify nucleic acids if viruses are found in infected food or environmental samples at critically low level. Another successful innovative biosensor with combined microfluidics and biosensing capabilities, furnish real time and automated affinity bioanalysis (e.g. for antigen-antibody assays) through surface plasmon resonance (SPR)-based original optical transduction mechanism. Since molecular recognition trait is central in the biosensing systems, all the structural components can be targeted to device a biosensor for detection of the specific virion particles present in food and environment samples. Molecular nanotechnology-based new nanostructures/nanomaterials such as aptamers are capable for developing highly specific biosensor for target elements detection. DNA-based biosensors have great applications in food and environmental analysis including determination of the pathogenic bacteria , and virus DNA sequence such as that of SARS virus (Abad-Valle et al. Quartz crystal microbalance (QCM)-based piezoelectric sensors can detect the hybridized viral DNA and also the capsid protein-ligand interactions. abstract: Food and environmental virology has become a very important and interesting area of research because of food safety and public health concerns. During the last few decades, increasing foodborne diseases and environmental generated illnesses are considered to be highly challenging issues. Biosensor technology holds great promise for the healthcare market, and the security sector. Similar to clinical diagnostic tools, biosensors are being developed for the rapid, reliable, yet inexpensive identification and enumeration of pathogenic viruses which are adulterating environment, food and feed commodities. In this modern era, bio-and nano-technologies play a pivotal role in virological diagnostics of food industry, environmental and veterinary samples. This review covers the recent advances and future prospects of nanotechnology-based bioanalytical microsystems for food and environmental virology. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090531/ doi: 10.1007/s12560-010-9034-5 id: cord-010621-d1utt8j3 author: Yamamoto, N. title: Assessing allergenic fungi in house dust by floor wipe sampling and quantitative PCR date: 2011-08-09 words: 5414.0 sentences: 250.0 pages: flesch: 48.0 cache: ./cache/cord-010621-d1utt8j3.txt txt: ./txt/cord-010621-d1utt8j3.txt summary: Abstract In the present study, we modified an existing surface wipe sampling method for lead and other heavy metals to create a protocol to collect fungi in floor dust followed by real‐time quantitative PCR (qPCR)‐based detection. Combined field and laboratory results suggested this modified new wipe sampling method, in conjunction with growth‐independent qPCR, shows potential to improve human exposure and health studies for fungal pathogens and allergens in dust in homes of susceptible, vulnerable population subgroups. Abstract In the present study, we modified an existing surface wipe sampling method for lead and other heavy metals to create a protocol to collect fungi in floor dust followed by real-time quantitative PCR (qPCR)-based detection. Combined field and laboratory results suggested this modified new wipe sampling method, in conjunction with growth-independent qPCR, shows potential to improve human exposure and health studies for fungal pathogens and allergens in dust in homes of susceptible, vulnerable population subgroups. abstract: Abstract In the present study, we modified an existing surface wipe sampling method for lead and other heavy metals to create a protocol to collect fungi in floor dust followed by real‐time quantitative PCR (qPCR)‐based detection. We desired minimal inconvenience for participants in residential indoor environmental quality and health studies. Accuracy, precision, and method detection limits (MDLs) were investigated. Overall, MDLs ranged from 0.6 to 25 cell/cm(2) on sampled floors. Overall measurement precisions expressed as the coefficient of variation because of sample processing and qPCR ranged 6–63%. Median and maximum fungal concentrations in house dust in study homes in Visalia, Tulare County, California, were 110 and 2500 cell/cm(2), respectively, with universal fungal primers (allergenic and nonallergenic species). The field study indicated samplings in multiple seasons were necessary to characterize representative whole‐year fungal concentrations in residential microenvironments. This was because significant temporal variations were observed within study homes. Combined field and laboratory results suggested this modified new wipe sampling method, in conjunction with growth‐independent qPCR, shows potential to improve human exposure and health studies for fungal pathogens and allergens in dust in homes of susceptible, vulnerable population subgroups. PRACTICAL IMPLICATIONS: Fungi are ubiquitous in indoor and outdoor environments, and many fungi are known to cause allergic reactions and exacerbate asthma attacks. This study established—by modifying an existing—a wipe sampling method to collect fungi in floor dust followed by real‐time quantitative PCR (qPCR)‐based detection methodologies. Results from this combined laboratory and field assessment suggested the methodology’s potential to inform larger human exposure studies for fungal pathogens and allergens in house dust as well as epidemiologic studies of children with asthma and older adults with chronic respiratory diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201893/ doi: 10.1111/j.1600-0668.2011.00732.x id: cord-025232-5itrsfmk author: Yan, Yuqian title: Construction and Characterization of a Novel Recombinant Attenuated and Replication-Deficient Candidate Human Adenovirus Type 3 Vaccine: “Adenovirus Vaccine Within an Adenovirus Vector” date: 2020-05-26 words: 5669.0 sentences: 312.0 pages: flesch: 45.0 cache: ./cache/cord-025232-5itrsfmk.txt txt: ./txt/cord-025232-5itrsfmk.txt summary: The strategy of using a clinically approved and replication-defective HAdV-5 vector provides a novel approach to develop universal adenovirus vaccine candidates against all the other types of adenoviruses causing ARDs and perhaps other adenovirus-associated diseases. In this study, the commercially-available and gene therapy use approved replication-defective HAdV-5 vector was used to construct a recombinant attenuated human adenovirus type 3 vaccine (Ginn et al. The complete hexon gene of HAdV-3 GZ01 was cloned into the AdEasy TM Adenoviral Vector, and this type-specific antigen was expressed when the recombinant adenovirus vaccine was inoculated into mice. The recombinant vaccine is expected to be used in the prevention of ARD outbreaks caused by HAdV-3 infections, and to serve as a model using adenovirus vectors for the construction of other vaccines against additional important serotypes of adenoviral respiratory pathogens. Mice were either inoculated with HAdV-3 wild-type strain GZ01 or immunized with the rAd3H recombinant vaccine by either the intranasal route or intramuscular route, respectively, to assess the antibody titer. abstract: Human adenoviruses (HAdVs) are highly contagious and result in large number of acute respiratory disease (ARD) cases with severe morbidity and mortality. Human adenovirus type 3 (HAdV-3) is the most common type that causes ARD outbreaks in Asia, Europe, and the Americas. However, there is currently no vaccine approved for its general use. The hexon protein contains the main neutralizing epitopes, provoking strong and lasting immunogenicity. In this study, a novel recombinant and attenuated adenovirus vaccine candidate against HAdV-3 was constructed based on a commercially-available replication-defective HAdV-5 gene therapy and vaccine vector. The entire HAdV-3 hexon gene was integrated into the E1 region of the vector by homologous recombination using a bacterial system. The resultant recombinants expressing the HAdV-3 hexon protein were rescued in AD293 cells, identified and characterized by RT-PCR, Western blots, indirect immunofluorescence, and electron microscopy. This potential vaccine candidate had a similar replicative efficacy as the wild-type HAdV-3 strain. However, and importantly, the vaccine strain had been rendered replication-defective and was incapable of replication in A549 cells after more than twenty-generation passages in AD293 cells. This represents a significant safety feature. The mice immunized both intranasally and intramuscularly by this vaccine candidate raised significant neutralizing antibodies against HAdV-3. Therefore, this recombinant, attenuated, and safe adenovirus vaccine is a promising HAdV-3 vaccine candidate. The strategy of using a clinically approved and replication-defective HAdV-5 vector provides a novel approach to develop universal adenovirus vaccine candidates against all the other types of adenoviruses causing ARDs and perhaps other adenovirus-associated diseases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248191/ doi: 10.1007/s12250-020-00234-1 id: cord-316434-mz4y5am2 author: Yang, Benjamin title: Co-administration with DNA encoding papillomavirus capsid proteins enhances the antitumor effects generated by therapeutic HPV DNA vaccination date: 2015-06-25 words: 5792.0 sentences: 269.0 pages: flesch: 46.0 cache: ./cache/cord-316434-mz4y5am2.txt txt: ./txt/cord-316434-mz4y5am2.txt summary: In the current study, we aim to introduce an approach to elicit potent CD4(+) T cell help for the enhancement of antigen-specific CD8(+) T cell immune responses generated by CRT/E7 DNA vaccination by using co-administration of a DNA vector expressing papillomavirus major and minor capsid antigens, L1 and L2. Co-administration with vectors encoding papillomavirus L1 or L2 significantly enhances the antigen-specific CD8 + T cell immune responses generated by CRT/E7 or OVA DNA vaccination In order to characterize the antigen-specific CD8 + T cell immune responses generated by vaccination with CRT/ E7 or OVA DNA in combination with vectors containing codon-optimized BPV1 L1 or L2 DNA, C57BL/6 mice (five per group) were vaccinated intradermally via gene gun with CRT/E7 or OVA DNA with or without BPV1 L1 or L2 DNA twice at 1-week intervals. abstract: BACKGROUND: DNA vaccines have emerged as attractive candidates for the control of human papillomavirus (HPV)-associated malignancies. However, DNA vaccines suffer from limited immunogenicity and thus strategies to enhance DNA vaccine potency are needed. We have previously demonstrated that for DNA vaccines encoding HPV-16 E7 antigen (CRT/E7) linkage with calreticulin (CRT) linked enhances both the E7-specific CD8(+) T cell immune responses and antitumor effects against E7-expressing tumors. In the current study, we aim to introduce an approach to elicit potent CD4(+) T cell help for the enhancement of antigen-specific CD8(+) T cell immune responses generated by CRT/E7 DNA vaccination by using co-administration of a DNA vector expressing papillomavirus major and minor capsid antigens, L1 and L2. RESULT: We showed that co-administration of vectors containing codon-optimized bovine papillomavirus type 1 (BPV-1) L1 and L2 in combination with DNA vaccines could elicit enhanced antigen-specific CD8(+) in both CRT/E7 and ovalbumin (OVA) antigenic systems. We also demonstrated that co-administration of vectors expressing BPV-1 L1 and/or L2 DNA with CRT/E7 DNA led to the generation of L1/L2-specific CD4(+) T cell immune responses and L1-specific neutralizing antibodies. Furthermore, we showed that co-administration with DNA encoding BPV1 L1 significantly enhances the therapeutic antitumor effects generated by CRT/E7 DNA vaccination. In addition, the observed enhancement of CD8(+) T cell immune responses by DNA encoding L1 and L2 was also found to extend to HPV-16 L1/L2 system. CONCLUSION: Our strategy elicits both potent neutralizing antibody and therapeutic responses and may potentially be extended to other antigenic systems beyond papillomavirus for the control of infection and/or cancer. url: https://doi.org/10.1186/s13578-015-0025-y doi: 10.1186/s13578-015-0025-y id: cord-318609-211m5b79 author: Yang, Chen title: Accurate, rapid and low-cost diagnosis of Mycoplasma pneumoniae via fast narrow-thermal-cycling denaturation bubble-mediated strand exchange amplification date: 2020-10-11 words: 4723.0 sentences: 192.0 pages: flesch: 41.0 cache: ./cache/cord-318609-211m5b79.txt txt: ./txt/cord-318609-211m5b79.txt summary: Furthermore, ASEA exhibited excellent performance in clinical specimen analysis, with sensitivity and specificity of 96.2% and 100%, respectively, compared with the "gold standard" real-time PCR. pneumoniae nucleic acid testing of clinical specimens to verify the accuracy of this novel method by comparison with real-time PCR, the current "gold standard." The objective was to provide a rapid, low-cost and sensitive detection method with conventional instruments and easily available commercial polymerase for early diagnosis of M. The ASEA reaction was performed in 20 μL amplification mixture containing 2 μL of the relevant templates, 3.0 × 10 −6 M primers F and R, 2 μL ISO buffer, 0.5 μL EvaGreen, 0.2 μL Bst 2.0 WarmStart DNA polymerase and 1.6 μL dNTPs. The amplification mixture was subjected to rapid thermal cycles between a first temperature (T 1 ) and a second temperature (T 2 ) using the CFX Connect™ Real-Time PCR System (Bio-Rad, CA, USA). abstract: Mycoplasma pneumoniae is a strong infectious pathogen that may cause severe respiratory infections. Since this pathogen may possess a latent period after infection, which sometimes leads to misdiagnosis by traditional diagnosis methods, the establishment of a rapid and sensitive diagnostic method is crucial for transmission prevention and timely treatment. Herein, a novel detection method was established for M. pneumoniae detection. The method, which improves upon a denaturation bubble-mediated strand exchange amplification (SEA) that we developed in 2016, is called accelerated SEA (ASEA). The established ASEA achieved detection of 1% M. pneumoniae genomic DNA in a DNA mixture from multiple pathogens, and the limit of detection (LOD) of ASEA was as low as 1.0 × 10(−17) M (approximately 6.0 × 10(3) copies/mL). Considering that the threshold of an asymptomatic carriage is normally recommended as 1.0 × 10(4) copies/mL, this method was able to satisfy the requirement for practical diagnosis of M. pneumoniae. Moreover, the detection process was finished within 20.4 min, significantly shorter than real-time PCR and SEA. Furthermore, ASEA exhibited excellent performance in clinical specimen analysis, with sensitivity and specificity of 96.2% and 100%, respectively, compared with the “gold standard” real-time PCR. More importantly, similar to real-time PCR, ASEA requires only one pair of primers and ordinary commercial polymerase, and can be carried out using a conventional fluorescence real-time PCR instrument, which makes this method low-cost and easy to accomplish. Therefore, ASEA has the potential for wide use in the rapid detection of M. pneumoniae or other pathogens in large numbers of specimens. [Figure: see text] url: https://www.ncbi.nlm.nih.gov/pubmed/33040157/ doi: 10.1007/s00216-020-02977-y id: cord-335607-gv96hlw6 author: Yang, Dayong title: Novel DNA materials and their applications date: 2010-08-20 words: 9048.0 sentences: 526.0 pages: flesch: 47.0 cache: ./cache/cord-335607-gv96hlw6.txt txt: ./txt/cord-335607-gv96hlw6.txt summary: One-dimensional (1D) DNA materials, including nanotubes and nanowires, can be fabricated through the programed self-assembly of DNA tiles, which have the potential to template the growth of nanowires 19, 49, 50 and induce alignment of membrane proteins. These connectors allowed planar DNA tiles to assemble into 2D array structures by taking advantage of the geometry of the 2.5 helical turns between two DNA tiles ( Figure 2 strand of DNA, 53 which resembled the self-assembly of natural protein nanofilaments. Mao and coworkers developed a concept in which DNA sequence symmetry could be used to design DNA building blocks for larger self-assembled structures. 23, 74 In contrast to the conventional crossover strategy, which creates single building blocks that self-assemble into larger structures in a ''two-step'' process, DNA origami provides a versatile and simple ''one-pot'' method using numerous short single strands of DNA (staple strands) to direct the folding of a long, single strand of DNA into the desired shape ( Figure 3 (g)). abstract: The last two decades have witnessed the exponential development of DNA as a generic material instead of just a genetic material. The biological function, nanoscale geometry, biocompatibility, biodegradability, and molecular recognition capacity of DNA make it a promising candidate for the construction of novel functional nanomaterials. As a result, DNA has been recognized as one of the most appealing and versatile nanomaterial building blocks. Scientists have used DNA in this way to construct various amazing nanostructures, such as ordered lattices, origami, supramolecular assemblies, and even three‐dimensional objects. In addition, DNA has been utilized as a guide and template to direct the assembly of other nanomaterials including nanowires, free‐standing membranes, and crystals. Furthermore, DNA can also be used as structural components to construct bulk materials such as DNA hydrogels, demonstrating its ability to behave as a unique polymer. Overall, these novel DNA materials have found applications in various areas in the biomedical field in general, and nanomedicine in particular. In this review, we summarize the development of DNA assemblies, describe the innovative progress of multifunctional and bulk DNA materials, and highlight some real‐world nanomedical applications of these DNA materials. We also show our insights throughout this article for the future direction of DNA materials. WIREs Nanomed Nanobiotechnol 2010 2 648–669 1.. Diagnostic Tools > Biosensing; 2.. Nanotechnology Approaches to Biology > Cells at the Nanoscale; 3.. Implantable Materials and Surgical Technologies > Nanomaterials and Implants; 4.. Nanotechnology Approaches to Biology > Nanoscale Systems in Biology. url: https://doi.org/10.1002/wnan.111 doi: 10.1002/wnan.111 id: cord-348104-7662q8dg author: Yang, Xiaoyun title: Molecular basis for the MacroD1-mediated hydrolysis of ADP-ribosylation date: 2020-06-22 words: 4314.0 sentences: 254.0 pages: flesch: 53.0 cache: ./cache/cord-348104-7662q8dg.txt txt: ./txt/cord-348104-7662q8dg.txt summary: Taken together, our study provides structural and functional insights into the molecular mechanism of MacroD1-mediated ADPR hydrolysis and its role in DNA damage repair. Combining with our structural analysis and ADPR hydrolyzation assay, it suggests that distinct catalytic residues are responsible for the MacroD1-mediated ADPR hydrolysis, rather than the catalytic residues Asn 174 , Asp 184 and His 188 in the deacetylation of OAADPr. It is observed that Phe 272 adopts a significant conformational change in the catalytic pocket of MacroD1 upon ADPR binding, and that the corresponding phenyl group is evolutionarily conserved among macro domain hydrolases. In contrast, the structure of ADPR bound to the MacroH2A1.1 macro domain (inactive) reveals that the corresponding residue for MacroD1 Phe 272 is Asn 316 , and the disappearance of steric hindrance, which is generated by phenyl group, makes the distal ribose in a relatively extended conformation, in which its C1″ atom is far away from the catalytic water ( Fig. S3) (38) . abstract: MacroD1 is an enzyme that hydrolyzes protein mono-ADP-ribosylation. However, the key catalytic residues of MacroD1 in these biochemical reactions remain elusive. Here, we present the crystal structure of MacroD1 in a complex with ADP-ribose (ADPR). The β5-α10-loop functions as a switch loop to mediate substrate recognition and right orientation. The conserved Phe(272) in the β5-α10-loop plays a crucial role in the orientation of ADPR distal ribose, and a conserved hydrogen-bond network contributes significantly to hold and orient the catalytic water12, which mediates ADPR hydrolysis. Moreover, we found that MacroD1 was recruited to the sites of DNA damage via recognition of ADP-ribosylation at DNA lesions. The MacroD1-mediated ADPR hydrolysis is essential for DNA damage repair. Taken together, our study provides structural and functional insights into the molecular mechanism of MacroD1-mediated ADPR hydrolysis and its role in DNA damage repair. url: https://doi.org/10.1016/j.dnarep.2020.102899 doi: 10.1016/j.dnarep.2020.102899 id: cord-291174-rym84kni author: Yang, Yazhi title: A label-free electrochemical assay for coronavirus IBV H120 strain quantification based on equivalent substitution effect and AuNPs-assisted signal amplification date: 2020-10-23 words: 3577.0 sentences: 234.0 pages: flesch: 51.0 cache: ./cache/cord-291174-rym84kni.txt txt: ./txt/cord-291174-rym84kni.txt summary: title: A label-free electrochemical assay for coronavirus IBV H120 strain quantification based on equivalent substitution effect and AuNPs-assisted signal amplification According to the differences of S1 protein in various infectious bronchitis virus (IBV) strains, a target DNA sequence that can specifically recognize H120 RNA forming a DNA-RNA hybridized double-strand structure has been designed. Therefore, developing a rapid and sensitive method for identification and quantification of different IBV strains based on hypervariable region of S1 gene can effectively solve the problem, which plays important roles in IB early diagnosis and control, especially for vaccine production. Herein, a label-free electrochemical assay based on equivalent substitution effect and AuNPs-assisted signal amplification is developed for identification and quantification detection of IBV H120 strain. In this work, we designed the sequence of the target DNA based on the hypervariable region in the S1 gene between different IBV strains, then, constructed the standard plasmid containing characteristic sequence of S1 gene in H120 strain, Fig. 2 Real-time fluorescence quantitative PCR plot. abstract: A label-free electrochemical strategy is proposed combining equivalent substitution effect with AuNPs-assisted signal amplification. According to the differences of S1 protein in various infectious bronchitis virus (IBV) strains, a target DNA sequence that can specifically recognize H120 RNA forming a DNA-RNA hybridized double-strand structure has been designed. Then, the residual single-stranded target DNA is hydrolyzed by S1 nuclease. Therefore, the content of target DNA becomes equal to the content of virus RNA. After equivalent coronavirus, the target DNA is separated from DNA-RNA hybridized double strand by heating, which can partly hybridize with probe 2 modified on the electrode surface and probe 1 on AuNPs’ surface. Thus, AuNPs are pulled to the surface of the electrode and the abundant DNA on AuNPs’ surface could adsorb a large amount of hexaammineruthenium (III) chloride (RuHex) molecules, which produce a remarkably amplified electrochemical response. The voltammetric signal of RuHex with a peak near − 0.28 V vs. Ag/AgCl is used as the signal output. The proposed method shows a detection range of 1.56e(−9) to 1.56e(−6) μM with the detection limit of 2.96e(−10) μM for IBV H120 strain selective quantification detection, exhibiting good accuracy, stability, and simplicity, which shows a great potential for IBV detection in vaccine research and avian infectious bronchitis diagnosis. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00604-020-04582-3) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1007/s00604-020-04582-3 doi: 10.1007/s00604-020-04582-3 id: cord-282106-7k088cqv author: Yang, Zhi-yong title: A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice date: 2004 words: 3739.0 sentences: 193.0 pages: flesch: 48.0 cache: ./cache/cord-282106-7k088cqv.txt txt: ./txt/cord-282106-7k088cqv.txt summary: Here, we show that a DNA vaccine encoding the spike (S) glycoprotein of the SARS-CoV induces T cell and neutralizing antibody responses, as well as protective immunity, in a mouse model. Here, we show that a DNA vaccine encoding the spike (S) glycoprotein of the SARS-CoV induces T cell and neutralizing antibody responses, as well as protective immunity, in a mouse model. Viral replication was reduced by more than six orders of magnitude in the lungs of mice vaccinated with these S plasmid DNA expression vectors, and protection was mediated by a humoral but not a T-cell-dependent immune mechanism. Immunization and challenge were performed in mice as described previously 18 , and viral replication (mean log 10 TCID 50 per g tissue with standard error) in the lower (a) and upper (b) respiratory tract after challenge with SARS-CoV was measured for five immunized animals inoculated with SDCD, SDTM or empty plasmid vector control. abstract: Public health measures have successfully identified and contained outbreaks of the severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV)(1,2,3,4,5), but concerns remain over the possibility of future recurrences. Finding a vaccine for this virus therefore remains a high priority. Here, we show that a DNA vaccine encoding the spike (S) glycoprotein of the SARS-CoV induces T cell and neutralizing antibody responses, as well as protective immunity, in a mouse model. Alternative forms of S were analysed by DNA immunization. These expression vectors induced robust immune responses mediated by CD4 and CD8 cells, as well as significant antibody titres, measured by enzyme-linked immunosorbent assay. Moreover, antibody responses in mice vaccinated with an expression vector encoding a form of S that includes its transmembrane domain elicited neutralizing antibodies. Viral replication was reduced by more than six orders of magnitude in the lungs of mice vaccinated with these S plasmid DNA expression vectors, and protection was mediated by a humoral but not a T-cell-dependent immune mechanism. Gene-based vaccination for the SARS-CoV elicits effective immune responses that generate protective immunity in an animal model. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature02463) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/15024391/ doi: 10.1038/nature02463 id: cord-004170-ri5qsarz author: Yashima, Nozomi title: Leukocyte-derived extracellular DNA contributes to abnormal pressure elevation in the extracorporeal circulation circuit date: 2020-01-16 words: 3584.0 sentences: 234.0 pages: flesch: 44.0 cache: ./cache/cord-004170-ri5qsarz.txt txt: ./txt/cord-004170-ri5qsarz.txt summary: title: Leukocyte-derived extracellular DNA contributes to abnormal pressure elevation in the extracorporeal circulation circuit Abnormal in-circuit elevation in pressure was associated with deposition of extracellular DNA on the outlet surface of the filter. In-circuit pressure was elevated at the oxygenator if heparin was administered in whole blood that was stored for 7 days (Fig. S1B) . Then, we examined whether leukocyte stimulation results in elevation of in-circuit pressure since previous studies have suggested that stimulated leukocytes are prone to releasing DNA into the extracellular space 13 . Our study showed that leukocyte-derived extracellular DNA induced an elevation of in-circuit pressure. Our study suggested that extracellular DNA from disrupted leukocytes contributed to elevation of in-circuit pressure. In conclusion, our study shows that leukocyte-derived extracellular DNA contributes to abnormal in-circuit elevation of pressure in an ex vivo circuit. abstract: An abnormal elevation in pressure is a serious complication involving the extracorporeal circulation circuit. Clot formation might be associated with this complication, but the precise mechanism of an abnormal elevation in pressure has not been identified. We investigated sufficient conditions for in-circuit elevation in pressure using an ex vivo re-circulation circuit with porcine blood. Specifically, we investigated the effect of blood conditions, the type of anticoagulation, and pro-inflammatory stimulation on in-circuit pressure. We also examined the cause of an abnormal elevation of in-circuit pressure by specifically degrading DNA, RNA, or protein components of an obstructed filter and by using immunofluorescent techniques. Neither a change in temperature nor change in pH in the blood increased in-circuit pressure. In contrast, long-term storage of blood, pro-inflammatory stimulation by phorbol myristate acetate, and heparin administration significantly increased in-circuit pressure. Abnormal in-circuit elevation in pressure was associated with deposition of extracellular DNA on the outlet surface of the filter. Administration of DNase resulted in a rapid decline of in-circuit pressure. In an ex vivo re-circulation circuit system, extracellular DNA deposition on the filter is responsible for an abnormal in-circuit elevation in pressure. Senescent leukocytes, stimulated leukocytes, and heparin exposure are associated with extracellular DNA deposition. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965310/ doi: 10.1038/s41598-019-57173-5 id: cord-275232-0sg0hv9w author: Yeung, Siu-Wai title: A DNA biochip for on-the-spot multiplexed pathogen identification date: 2006-09-25 words: 3241.0 sentences: 162.0 pages: flesch: 41.0 cache: ./cache/cord-275232-0sg0hv9w.txt txt: ./txt/cord-275232-0sg0hv9w.txt summary: The DNA-based identification of the two model pathogens involved a number of steps including a thermal lysis step, magnetic particle-based isolation of the target genomes, asymmetric PCR, and electrochemical sequence-specific detection using silver-enhanced gold nanoparticles. The assay involves the following steps: (i) sample preparation using thermal cell lysis and magnetic particle-based target genome isolation; (ii) target DNA amplification by the PCR; (iii) hybridization of the amplicons to their complementary oligonucleotide capture probes immobilized onto individual detection electrode surfaces and (iv) electrochemical transduction of the recognition event via gold nanoparticles with signal amplification using electrocatalytic silver deposition (10) . The three main steps were (A) sample preparation: thermal cell lysis and magnetic particle-based isolation of specific genomic DNAs; (B) target DNA amplification: generation of single-stranded rich amplicons by asymmetric PCR; (C) product detection: gold nanoparticle labeling, electrocatalytic silver deposition, and electrochemical silver dissolution. abstract: Miniaturized integrated DNA analysis systems have largely been based on a multi-chamber design with microfluidic control to process the sample sequentially from one module to another. This microchip design in connection with optics involved hinders the deployment of this technology for point-of-care applications. In this work, we demonstrate the implementation of sample preparation, DNA amplification, and electrochemical detection in a single silicon and glass-based microchamber and its application for the multiplexed detection of Escherichia coli and Bacillus subtilis cells. The microdevice has a thin-film heater and temperature sensor patterned on the silicon substrate. An array of indium tin oxide (ITO) electrodes was constructed within the microchamber as the transduction element. Oligonucleotide probes specific to the target amplicons are individually positioned at each ITO surface by electrochemical copolymerization of pyrrole and pyrrole−probe conjugate. These immobilized probes were stable to the thermal cycling process and were highly selective. The DNA-based identification of the two model pathogens involved a number of steps including a thermal lysis step, magnetic particle-based isolation of the target genomes, asymmetric PCR, and electrochemical sequence-specific detection using silver-enhanced gold nanoparticles. The microchamber platform described here offers a cost-effective and sample-to-answer technology for on-site monitoring of multiple pathogens. url: https://www.ncbi.nlm.nih.gov/pubmed/17000638/ doi: 10.1093/nar/gkl702 id: cord-283249-pk5sc2ca author: Yoshida, Wataru title: Homogeneous DNA sensing using enzyme-inhibiting DNA aptamers date: 2006-09-15 words: 5356.0 sentences: 235.0 pages: flesch: 56.0 cache: ./cache/cord-283249-pk5sc2ca.txt txt: ./txt/cord-283249-pk5sc2ca.txt summary: The structural change of the enzyme-inhibiting aptamer site induces a change in the inhibitory activity of the AES, which enables us to detect a target molecule by measuring the enzymatic activity of the whole aptameric complex in a homogeneous solution without bound/free separation. The stem-and-loop structure bearing the probe DNA sequence was inserted into the 3 0 -end T-T loop of the G-quartet structure of the 31-mer thrombin-inhibiting aptamer. We also inserted two additional T bases between the thrombin-inhibiting aptamer and the stem-and-loop structure in all AESs except AES 1, since the diameter of the DNA double helix is different from the distance between two Gs of the G-quartet structure (approximately 17 and 20 Å , respectively). For the measurement of the CD spectra of AES SARS 1, a stem-and-loop structure to be inserted into the 31-mer thrombin-inhibiting aptamer on AES SARS 1 was synthesized. abstract: Abstract A novel aptameric enzyme subunit (AES) which can detect target DNAs has been developed. AES is an enzyme-inhibiting aptamer bearing a target-molecule binding site which can allosterically control enzymatic activity. The thrombin-inhibiting aptamer bearing a G-quartet structure was chosen as the enzyme-inhibiting aptamer. The stem-and-loop structure, which contains a strand complementary to the target DNA, was inserted into the G-quartet structure of the thrombin-inhibiting aptamer to disrupt the G-quartet structure through the hybridization of the target DNA with the complementary strand in the AES. The disruption of the G-quartet structure led to a decrease of the inhibitory activity of the whole aptameric complex. Using this designed aptamer, we were able to detect target DNAs by measuring the thrombin activity in a homogeneous solution without bound/free separation, and the lower detection limit was 20nM. url: https://www.sciencedirect.com/science/article/pii/S0006291X06015956 doi: 10.1016/j.bbrc.2006.07.069 id: cord-001761-yvd1n42f author: Yoshimura, Takeo title: Controlled Microwave Heating Accelerates Rolling Circle Amplification date: 2015-09-08 words: 4411.0 sentences: 223.0 pages: flesch: 48.0 cache: ./cache/cord-001761-yvd1n42f.txt txt: ./txt/cord-001761-yvd1n42f.txt summary: Analysis of the temperature profiles of each RCA component subjected to microwave heating revealed the selectivity heating of buffer components compared with primers, template DNA, dNTP, and RNase-free water. To determine the component of RCA by microwave selectivity heating, we measured the temperatures of the five components (circularized template with primers, dNTPs, ThermoPol Buffer, Bst-LF, and RNase-free water) of the RCA and MW-RCA mixtures for 10 min from 13°C to 60°C. To reveal the effect of the selectivity heating in MW-RCA, we compared the efficiency of DNA amplification in the RCA and MW-RCA reactions mixtures containing a 4-fold excess concentration of each RCA component (dNTP, template-primers, Bst-LF, Tris-HCl, KCl, (NH 4 ) 2 SO 4 , and MgSO 4 ). We performed MW-RCA reactions containing a four-fold higher concentration of each RCA component [dNTP, template-primers, Bst DNA polymerase-LF, Tris-HCl, KCl, (NH 4 ) 2 SO 4 , and MgSO 4 ] to identify a link between microwave selective heating and DNA amplification. abstract: Rolling circle amplification (RCA) generates single-stranded DNAs or RNA, and the diverse applications of this isothermal technique range from the sensitive detection of nucleic acids to analysis of single nucleotide polymorphisms. Microwave chemistry is widely applied to increase reaction rate as well as product yield and purity. The objectives of the present research were to apply microwave heating to RCA and indicate factors that contribute to the microwave selective heating effect. The microwave reaction temperature was strictly controlled using a microwave applicator optimized for enzymatic-scale reactions. Here, we showed that microwave-assisted RCA reactions catalyzed by either of the four thermostable DNA polymerases were accelerated over 4-folds compared with conventional RCA. Furthermore, the temperatures of the individual buffer components were specifically influenced by microwave heating. We concluded that microwave heating accelerated isothermal RCA of DNA because of the differential heating mechanisms of microwaves on the temperatures of reaction components, although the overall reaction temperatures were the same. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562646/ doi: 10.1371/journal.pone.0136532 id: cord-010511-eoc0ex3i author: Yousefi, Shida title: In vivo evidence for extracellular DNA trap formation date: 2020-04-30 words: 9212.0 sentences: 461.0 pages: flesch: 32.0 cache: ./cache/cord-010511-eoc0ex3i.txt txt: ./txt/cord-010511-eoc0ex3i.txt summary: The formation of extracellular DNA traps by neutrophils, eosinophils, and basophils, but also lymphocytes, has been observed in various infections of humans, mice, and additional species. The circulating autoantibodies such as anti-damaged-DNA/RNA ribonucleoprotein antibody immune complexes (RNP-ICs-Ab) can further activate neutrophils, including NET formation (not shown) 13, 73, 74 , leading to vicious cycle of chronic inflammation in genetically susceptible individuals 68, 74 , causing autoimmune diseases such as systemic lupus erythematous (SLE). Upon stimulation with antimicrobial 72 or antiribonucleoprotein (RNP) antibodies 13, 73, 74 , neutrophils from SLE patients have been shown to release self-DNA associated with antimicrobial peptides able to trigger innate plasmocytoid dendritic cell (pDC) activation via TLR9 to produce IFN-Ι (Fig. 1) . Deep vein thrombosis (DVT) has been linked to neutrophil activation and release of NETs based on studies investigating the pathogenic role of NETs in the pathogenesis of venous thromboembolism (VT) using genetically modified mice, various large animal models and human material assessing plasma markers or thrombi species 126 . abstract: Extracellular DNA trap formation is a cellular function of neutrophils, eosinophils, and basophils that facilitates the immobilization and killing of invading microorganisms in the extracellular milieu. To form extracellular traps, granulocytes release a scaffold consisting of mitochondrial DNA in association with granule proteins. As we understand more about the molecular mechanism for the formation of extracellular DNA traps, the in vivo function of this phenomenon under pathological conditions remains an enigma. In this article, we critically review the literature to summarize the evidence for extracellular DNA trap formation under in vivo conditions. Extracellular DNA traps have not only been detected in infectious diseases but also in chronic inflammatory diseases, as well as in cancer. While on the one hand, extracellular DNA traps clearly exhibit an important function in host defense, it appears that they can also contribute to the maintenance of inflammation and metastasis, suggesting that they may represent an interesting drug target for such pathological conditions. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193637/ doi: 10.1038/s41419-020-2497-x id: cord-000293-pc4x5e24 author: Yu, Chien-Hung title: Stimulation of ribosomal frameshifting by antisense LNA date: 2010-08-06 words: 3901.0 sentences: 194.0 pages: flesch: 49.0 cache: ./cache/cord-000293-pc4x5e24.txt txt: ./txt/cord-000293-pc4x5e24.txt summary: The requirements for À1 ribosomal frameshifting are the presence of a slippery heptanucleotide sequence X XXY YYZ (where X can be A, U, G or C; Y can be A or U; and Z does not equal Y; the spaces indicate the original reading frame) (8) followed by a downstream structural element, such as a pseudoknot, a hairpin or an antisense oligonucleotide duplex [for reviews, see (9) ]. We and others have demonstrated that small RNA oligonucleotides are able to mimic the function of frameshifter pseudoknots or hairpins by redirecting ribosomes into new reading frames (27, 28) . These results demonstrate that LNA modifications indeed enhance the antisense-induced frameshifting efficiency probably due to higher thermodynamic stability and RNA-like structural properties. In addition to RNA oligonucleotides, we demonstrated that LNA/DNA mix-mers are also capable of stimulating efficient À1 ribosomal frameshifting in contrast to DNA oligonucleotides. Triplex structures in an RNA pseudoknot enhance mechanical stability and increase efficiency of À1 ribosomal frameshifting abstract: Programmed ribosomal frameshifting is a translational recoding mechanism commonly used by RNA viruses to express two or more proteins from a single mRNA at a fixed ratio. An essential element in this process is the presence of an RNA secondary structure, such as a pseudoknot or a hairpin, located downstream of the slippery sequence. Here, we have tested the efficiency of RNA oligonucleotides annealing downstream of the slippery sequence to induce frameshifting in vitro. Maximal frameshifting was observed with oligonucleotides of 12–18 nt. Antisense oligonucleotides bearing locked nucleid acid (LNA) modifications also proved to be efficient frameshift-stimulators in contrast to DNA oligonucleotides. The number, sequence and location of LNA bases in an otherwise DNA oligonucleotide have to be carefully manipulated to obtain optimal levels of frameshifting. Our data favor a model in which RNA stability at the entrance of the ribosomal tunnel is the major determinant of stimulating slippage rather than a specific three-dimensional structure of the stimulating RNA element. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001050/ doi: 10.1093/nar/gkq650 id: cord-328206-iylw1bvw author: Yu, Daojun title: Simultaneous Detection and Differentiation of Human Papillomavirus Genotypes 6, 11, 16 and 18 by AllGlo Quadruplex Quantitative PCR date: 2012-11-09 words: 4070.0 sentences: 209.0 pages: flesch: 48.0 cache: ./cache/cord-328206-iylw1bvw.txt txt: ./txt/cord-328206-iylw1bvw.txt summary: In this study, applying novel AllGlo fluorescent probes, we established a quadruplex quantitative PCR method to simultaneously detect and differentiate HPV 6, 11, 16 and 18 in a single tube. So AllGlo quadruplex quantitative PCR has the advantages of relatively high throughput, good reproducibility, high sensitivity, high specificity, it is easy for designing the probes and primers of multiplex qPCR and can increase the detection throughput. Two aliquots were used for the detection of HPV6-11 and HPV16-18 mixed types by TaqMan uniplex probe fluorescence quantitative PCR (Guangzhou Da''an Diagnostic Co., Ltd., China). Single-tube AllGlo probe quadruplex fluorescence qPCR could simultaneously type HPV 6, 11, 16, and 18 and quantitatively detect the viral load of each HPV at the same time. Single-tube AllGlo probe quadruplex fluorescence qPCR could simultaneously type HPV 6, 11, 16, and 18 and quantitatively detect the viral load of each HPV at the same time. abstract: BACKGROUND: Human papillomaviruses (HPV) are classified into high-risk HPV and low-risk HPV. The most common high-risk HPV types in cervical cancer are HPV 16 and 18, and the most common low-risk types causing genital warts are HPV 6 and HPV 11. In this study, applying novel AllGlo fluorescent probes, we established a quadruplex quantitative PCR method to simultaneously detect and differentiate HPV 6, 11, 16 and 18 in a single tube. METHODS: The specificity, the sensitivity, the detection limit, the reproducibility and the standard curve of this method were examined. Finally, clinical samples that had been tested previously by TaqMan PCR and HPV GenoArray (GA) test were used to verify the accuracy and sensitivity of the method. RESULTS: The assay has a sensitivity of 10(1) to 10(2) copies/test and a linear detection range from 10(1) to 10(8) copies/test. The mean amplification efficiencies for HPV 6, 11, 16, and 18 were 0.97, 1.10, 0.93 and 1.20, respectively, and the mean correlation coefficient (r(2)) of each standard curve was above 0.99 for plasmid templates ranging from 10(3) to 10(7) copies/test. There was 100% agreement between the AllGlo quadruplex quantitative PCR, HPV GA test and TaqMan uniplex qPCR methods. CONCLUSIONS: AllGlo quadruplex quantitative PCR in a single tube has the advantages of relatively high throughput, good reproducibility, high sensitivity, high specificity, and a wide linear range of detection. The convenient single tube format makes this assay a powerful tool for the studies of mixed infections by multiple pathogens, viral typing and viral load quantification. url: https://www.ncbi.nlm.nih.gov/pubmed/23152833/ doi: 10.1371/journal.pone.0048972 id: cord-332844-2se4d1yp author: Yun, Sang-Im title: Bacterial Artificial Chromosomes: A Functional Genomics Tool for the Study of Positive-strand RNA Viruses date: 2015-12-29 words: 4793.0 sentences: 233.0 pages: flesch: 52.0 cache: ./cache/cord-332844-2se4d1yp.txt txt: ./txt/cord-332844-2se4d1yp.txt summary: Here, the present report describes the strategic considerations in creating and amplifying a genetically stable full-length infectious JEV cDNA as a bacterial artificial chromosome (BAC) using the following general experimental procedures: viral RNA isolation, cDNA synthesis, cDNA subcloning and modification, assembly of a full-length cDNA, cDNA linearization, in vitro RNA synthesis, and virus recovery. This protocol provides a general methodology applicable to cloning full-length cDNA for a range of positive-strand RNA viruses, particularly those with a genome of >10 kb in length, into a BAC vector, from which infectious RNAs can be transcribed in vitro with a bacteriophage RNA polymerase. Generation of an infectious cDNA clone is a key step in developing a reverse genetics system for RNA viruses, especially for positive-strand RNA viruses, because its genome acts as viral mRNA that is translated into proteins by host cell ribosomes. abstract: Reverse genetics, an approach to rescue infectious virus entirely from a cloned cDNA, has revolutionized the field of positive-strand RNA viruses, whose genomes have the same polarity as cellular mRNA. The cDNA-based reverse genetics system is a seminal method that enables direct manipulation of the viral genomic RNA, thereby generating recombinant viruses for molecular and genetic studies of both viral RNA elements and gene products in viral replication and pathogenesis. It also provides a valuable platform that allows the development of genetically defined vaccines and viral vectors for the delivery of foreign genes. For many positive-strand RNA viruses such as Japanese encephalitis virus (JEV), however, the cloned cDNAs are unstable, posing a major obstacle to the construction and propagation of the functional cDNA. Here, the present report describes the strategic considerations in creating and amplifying a genetically stable full-length infectious JEV cDNA as a bacterial artificial chromosome (BAC) using the following general experimental procedures: viral RNA isolation, cDNA synthesis, cDNA subcloning and modification, assembly of a full-length cDNA, cDNA linearization, in vitro RNA synthesis, and virus recovery. This protocol provides a general methodology applicable to cloning full-length cDNA for a range of positive-strand RNA viruses, particularly those with a genome of >10 kb in length, into a BAC vector, from which infectious RNAs can be transcribed in vitro with a bacteriophage RNA polymerase. url: https://www.ncbi.nlm.nih.gov/pubmed/26780115/ doi: 10.3791/53164 id: cord-104272-lczm1z5z author: Yusifov, Taleh N. title: Tear lipocalin is the major endonuclease in tears date: 2008-01-29 words: 4121.0 sentences: 244.0 pages: flesch: 54.0 cache: ./cache/cord-104272-lczm1z5z.txt txt: ./txt/cord-104272-lczm1z5z.txt summary: To determine the mode of hydrolysis, the cleaved ends of the DNA digested by tear DNases were analyzed by 3′ and 5′ end labeling using either terminal deoxynucleotidyl transferase or polynucleotide kinase with or without pretreatment with alkaline phosphatase. Both are Mg(2+) dependent enzyme endonucleases that are enhanced by Ca(2+), active at physiologic pH, inhibited by aurintricarboxylic acid, and catalyze hydrolysis of DNA to produce 3′-OH/5′P ends. Both endonucleases in tears show maximal activity in hydrolyzing plasmid DNA in 50 mM NaCl (Figure 4 ). To compare the DNA fragment sizes remaining after hydrolysis by TL and the minor endonuclease, dideoxy sequencing gel electrophoresis was performed on the digestion products ( Figure 9 ). The size variation of the final single strand hydrolysis products observed in sequencing gels for DNase I, TL, and the minor endonuclease may reflect mechanistic interactions of the DNA substrate with unique binding and cleavage sites. abstract: PURPOSE: Human endonucleases are integral to apoptosis in which unwanted or potentially harmful cells are eliminated. The rapid turnover of ocular surface epithelium and microbial colonization of the eyelids are continual sources of DNA in tears. Here, we determine the principal sources of endonuclease activity in tears. METHODS: Endonucleases in human tears were identified after Sephadex G100 gel filtration. DNA hydrolyzing activity was measured by the conversion pUC19 plasmid DNA to its circular form in agarose gels. Fractions with endonuclease activity were further isolated using a combination ConA-Sepharose DNA, oligo (dT) cellulose, and anion exchange chromatographies. The molecular weights of the DNA hydrolyzing proteins were estimated in zymograms and by calibration of size exclusion chromatography. DNase activities were characterized for activity at a variety of pH and ion concentrations as well as in the presence of inhibitors including NiCl(2), ZnCl(2), G-actin, and aurintricarboxylic acid (ATA). To determine the mode of hydrolysis, the cleaved ends of the DNA digested by tear DNases were analyzed by 3′ and 5′ end labeling using either terminal deoxynucleotidyl transferase or polynucleotide kinase with or without pretreatment with alkaline phosphatase. RESULTS: Tear lipocalin (TL) accounts for over 75% of the DNA catalytic activity in tears while a second endonuclease, ~34 kDa, is responsible for less than 24% of the activity. Both are Mg(2+) dependent enzyme endonucleases that are enhanced by Ca(2+), active at physiologic pH, inhibited by aurintricarboxylic acid, and catalyze hydrolysis of DNA to produce 3′-OH/5′P ends. However, the two enzymes can be distinguished by the inhibitory effect of NiCl(2) and the sizes of the cleaved DNA fragments. CONCLUSIONS: Two magnesium dependent extracellular endonucleases were identified in tears that are different from other major human extracellular nucleases. TL is the principal endonuclease in human tear fluid. Tear endonucleases have unique characteristics that differ from other known human endonucleases. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2254967/ doi: nan id: cord-354990-2hx7f6ny author: ZAKIAN, VIRGINIA A. title: Telomere formation in yeast date: 1989 words: 698.0 sentences: 44.0 pages: flesch: 51.0 cache: ./cache/cord-354990-2hx7f6ny.txt txt: ./txt/cord-354990-2hx7f6ny.txt summary: In two other families of viral GKS/Tcontaining proteins serine is encoded almost exclusively by UCN, with AGY occurring only once (see table) . An alternative mechanism involves the generation of a new serine codon next to the functionally important one (yielding a GKSS sequence with the two serines encoded by codons of different series) followed by deletion of the original codon. SIR-We recently demonstrated that dur-, ing formation of new telomeres in the yeast Saccharomyces cerevisiae, telomeric sequences are often transferred between DNA termini''. In a recent News and Views article'', however, Szostak suggested that the telomere resolution reaction '' (the cleavage between two blocks of telomeric sequences that are oriented as a head-tohead inverted repeat'''') can provide an alternative explanation for our data, a possibility that can be addressed definitively by DNA sequencing. Because the resolution reaction is excluded unequivocally by DNA sequence data , telomere-telomere recombination remains the only reasonable explanation for the transfer of telomeric sequences that we have observed. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/2648157/ doi: 10.1038/338468a0 id: cord-338812-q24jycgk author: Zakaryan, H. title: Nuclear remodelling during viral infections date: 2011-04-28 words: 4462.0 sentences: 226.0 pages: flesch: 37.0 cache: ./cache/cord-338812-q24jycgk.txt txt: ./txt/cord-338812-q24jycgk.txt summary: At present, we know that the nucleus contains the chromatin territories that mainly consist of DNA-protein complexes, as well as several distinct interchromosomal compartments (bodies) that support molecular activities, including replication, transcription and processing of nucleic acids (Fig. 1) . For many years the classical view of these components focused on their crucial role for the biogenesis of ribosomal subunits, but proteomic analysis of human nucleoli showed the presence of about 4500 nucleolar proteins with different functions, thus revealing the multifunctional nature of the nucleolus (Ahmad et al., 2009) . The previous decade of extensive studies implicated PML NBs in stress response (Maul et al., 1995) , gene regulation (Zhong et al., 2000) , oncogenesis (Salomoni and Pandolfi, 2002) , cell senescence (Bischof et al., 2002) , DNA damage repair (Dellaire and Bazett-Jones, 2004) , apoptosis (Takahashi et al., 2004) as well as in antiviral defence mechanisms (Everett and Chelbi-Alix, 2007) . abstract: Because of their limited coding capacity, viruses are not able to encode all proteins that are required for their replication. Therefore, they depend on a wide variety of cellular functions and structures, such as the host cell nucleus. It has been shown that DNA, as well as RNA viruses, exploit the nucleus because it provides essential machinery for viral replication. On the other hand, the nucleus undergoes significant remodelling during viral usurpation or exploitation. Moreover, it is becoming increasingly clear that some subnuclear structures, such as promyelocytic leukaemia nuclear bodies, act as an antiviral defence mechanism, and several viruses antagonize this intracellular defence by modifying subnuclear structures. This article reviews the main alterations that take place in nucleus during viral infections. url: https://www.ncbi.nlm.nih.gov/pubmed/21501365/ doi: 10.1111/j.1462-5822.2011.01596.x id: cord-328460-thx9zh11 author: Zanoli, Laura Maria title: Isothermal Amplification Methods for the Detection of Nucleic Acids in Microfluidic Devices date: 2012-12-27 words: 8972.0 sentences: 407.0 pages: flesch: 36.0 cache: ./cache/cord-328460-thx9zh11.txt txt: ./txt/cord-328460-thx9zh11.txt summary: Miniaturized isothermal amplification systems will be then illustrated including nucleic acid sequence-based amplification (NASBA), loop-mediated isothermal amplification (LAMP), helicase-dependent amplification (HDA), rolling circle amplification (RCA), multiple displacement amplification (MDA) and recombinase polymerase amplification (RPA). In addition, the use of droplet-based microfluidic systems for PCR enables the amplification and the analysis of individual target sequences to be performed in a significantly lower time as a consequence of a higher thermal cycling speed. These include nucleic acid sequence-based amplification (NASBA), loop-mediated amplification (LAMP), helicase-dependent amplification (HDA), rolling circle amplification (RCA), recombinase polymerase amplification (RPA) and multiple displacement amplification (MDA) [7] . Unlike other electrochemical techniques [56], based on the immobilization of an oligonucleotide probe onto an electrode, hybridization of a complementary target sequence, and transduction of the hybridization event [57], the microfluidic detection of LAMP amplicons [55] does not require probe immobilization and bacteria detection can be accomplished in a single chamber without DNA extraction and purification steps, since the used isothermal temperature (66 °C) provides enough thermal shock to lyse the E. abstract: Diagnostic tools for biomolecular detection need to fulfill specific requirements in terms of sensitivity, selectivity and high-throughput in order to widen their applicability and to minimize the cost of the assay. The nucleic acid amplification is a key step in DNA detection assays. It contributes to improving the assay sensitivity by enabling the detection of a limited number of target molecules. The use of microfluidic devices to miniaturize amplification protocols reduces the required sample volume and the analysis times and offers new possibilities for the process automation and integration in one single device. The vast majority of miniaturized systems for nucleic acid analysis exploit the polymerase chain reaction (PCR) amplification method, which requires repeated cycles of three or two temperature-dependent steps during the amplification of the nucleic acid target sequence. In contrast, low temperature isothermal amplification methods have no need for thermal cycling thus requiring simplified microfluidic device features. Here, the use of miniaturized analysis systems using isothermal amplification reactions for the nucleic acid amplification will be discussed. url: https://doi.org/10.3390/bios3010018 doi: 10.3390/bios3010018 id: cord-317021-o30zylrq author: Zhai, Yujia title: SmartBac, a new baculovirus system for large protein complex production date: 2019-02-10 words: 7669.0 sentences: 428.0 pages: flesch: 56.0 cache: ./cache/cord-317021-o30zylrq.txt txt: ./txt/cord-317021-o30zylrq.txt summary: Here we report SmartBac, an easy and versatile system for constructing large-sized transfer plasmids used to generate recombinant baculoviruses that express large multiprotein complexes in insect cells. The second strategy used to express multiprotein complexes is to construct a transfer plasmid carrying multiple GECs. The commercial pFastbac-Dual vector features two promoters for expression of two proteins simultaneously. In Fig. 2a , a vector is designed to express a multiprotein complex composed of eight different subunits (subunits A, B, C, D, E, F, G and H) in insect cells. Obtaining large multiprotein complexes through recombinant expression has always been challenging for researchers who need a sufficient quantity of high-purity sample for structural and biochemical studies. The key to successful protein production using the baculovirus expression system is the construction of the final transfer plasmid containing genes of multiple protein subunits. abstract: Recent revolution of cryo-electron microscopy has opened a new door to solve high-resolution structures of macromolecule complexes without crystallization while how to efficiently obtain homogenous macromolecule complex sample is therefore becoming a bottleneck. Here we report SmartBac, an easy and versatile system for constructing large-sized transfer plasmids used to generate recombinant baculoviruses that express large multiprotein complexes in insect cells. The SmartBac system integrates the univector plasmid-fusion system, Gibson assembly method and polyprotein strategy to construct the final transfer plasmid. The fluorescent proteins are designed co-expressed with the target to monitor transfection and expression efficiencies. A scheme of screening an optimal tagged subunit for efficient purification is provided. Six large multiprotein complexes including the human exocyst complex and dynactin complex were successfully expressed and purified, suggesting a great potential of SmartBac system for its wide application in the future. url: https://www.ncbi.nlm.nih.gov/pubmed/32337507/ doi: 10.1016/j.yjsbx.2019.100003 id: cord-018897-tceum2m1 author: Zhang, Anqi title: Nanowire Field-Effect Transistor Sensors date: 2016-07-27 words: 6316.0 sentences: 301.0 pages: flesch: 42.0 cache: ./cache/cord-018897-tceum2m1.txt txt: ./txt/cord-018897-tceum2m1.txt summary: Research advances exploiting SiNWs configured as FETs for biomolecule analysis have emerged as one of the most promising and powerful platforms for label-free, real-time, and sensitive electrical detection of proteins as well as many other biological species. Since the NW diameters can be similar to biomolecules such as proteins and nucleic acids, these binding events can be sensitively detected by the NW-FETs. Furthermore, incorporation of a number of NW-FET elements in a single sensor chip where the NWs are functionalized with different surface receptors allows for multiplexed electrical detection in the same assay, enabling a unique and powerful platform for chemical/biological recognition [6] . Furthermore, several methods for improving the sensitivity and/or capabilities of NW-FET sensors, including the use of branched NWs to enhance the capture efficiency of molecular analytes, operation of the FET in the subthreshold regime, increasing the analyte concentration by electrokinetic effects, and detection in physiological fluids, are briefly illustrated. abstract: Sensitive and quantitative analysis of proteins and other biochemical species are central to disease diagnosis, drug screening and proteomic studies. Research advances exploiting SiNWs configured as FETs for biomolecule analysis have emerged as one of the most promising and powerful platforms for label-free, real-time, and sensitive electrical detection of proteins as well as many other biological species. In this chapter, we first briefly introduce the fundamental principle for semiconductor NW-FET sensors. Representative examples of semiconductor NW sensors are then summarized for sensitive chemical and biomolecule detection, including proteins, nucleic acids, viruses and small molecules. In addition, this chapter discusses several electrical and surface functionalization methods for enhancing the sensitivity of semiconductor NW sensors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123897/ doi: 10.1007/978-3-319-41981-7_10 id: cord-274049-3gw65kpu author: Zhang, Han title: CRISPR Editing in Biological and Biomedical Investigation date: 2017-05-31 words: 6583.0 sentences: 333.0 pages: flesch: 40.0 cache: ./cache/cord-274049-3gw65kpu.txt txt: ./txt/cord-274049-3gw65kpu.txt summary: © 2017 Wiley Periodicals, Inc. nucleases (ZFN) and transcription activator-like effector nucleases (TALEN), have enabled the manipulation of genes by targeting DNA double-stranded breaks (DSBs) via non-homologous end-joining (NHEJ) or homology-directed repair (HDR) pathways [Rudin et al., 1989; Rouet et al., 1994; Choulika et al., 1995; Bibikova et al., 2002; Moscou and Bogdanove, 2009 ]. Overall, these studies empower a broader range of disease modeling applications via CRISPR-Cas9-mediated genome engineering, allowing researchers to uncover fundamental mechanisms in disease initiation, maintenance and procession, and explore the therapeutic potential of the CRISPR-Cas9 system to correct disease-causing mutations. Owing to its ability to completely disrupt target genes and the simplicity of designing potent sgRNAs, the CRISPR-Cas9 system has been extended to large-scale loss-of-function (LOF) genome screens in human cells [Koike-Yusa et al., 2014; Shalem et al., 2014; Wang et al., 2014; Zhou et al., 2014] . Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease abstract: The revolutionary technology for genome editing known as the clustered regularly interspaced short palindromic repeat (CRISPR)‐CRISPR‐associated protein 9 (Cas9) system has sparked advancements in biological and biomedical research. The scientific breakthrough of the development of CRISPR‐Cas9 technology has allowed us to recapitulate human diseases by generating animal models of interest ranging from zebrafish to non‐human primates. The CRISPR‐Cas9 system can also be used to delineate the mechanisms underlying the development of human disorders and to precisely correct disease‐causing mutations. Repurposing this technology enables wider applications in transcriptome and epigenome manipulation and holds promise to reach the clinic. In this review, we highlight the latest advances of the CRISPR‐Cas9 system in different platforms and discuss the hurdles and challenges this technology is facing. J. Cell. Biochem. 118: 4152–4162, 2017. © 2017 Wiley Periodicals, Inc. url: https://www.ncbi.nlm.nih.gov/pubmed/28467679/ doi: 10.1002/jcb.26111 id: cord-338942-q4neat3x author: Zhang, Haoqing title: LAMP-on-a-chip: Revising microfluidic platforms for loop-mediated DNA amplification date: 2019-01-31 words: 5757.0 sentences: 314.0 pages: flesch: 41.0 cache: ./cache/cord-338942-q4neat3x.txt txt: ./txt/cord-338942-q4neat3x.txt summary: Isothermal deoxyribonucleic acid amplification methods, such as loop-mediated isothermal amplification (LAMP), exhibit characteristics ideal for point-of-care (POC) applications, since their instrumentation is simpler in comparison with the standard method of polymerase chain reaction. Nucleic acids amplification methods are primarily required to be performed, as the original number of either DNA or ribonucleic acid (RNA) copies in the clinical sample is insufficient for their direct detection. A microfluidic disk-based LAMP chip, integrating sample preparation and detection, was developed [44] (Fig. 2B ). Loop-mediated isothermal amplification integrated on microfluidic chips for point-of-care quantitative detection of pathogens An integrated rotary microfluidic system with DNA extraction, loop-mediated isothermal amplification, and lateral flow strip based detection for point-ofcare pathogen diagnostics An integrated microfluidic loop-mediated-isothermal-amplification system for rapid sample pre-treatment and detection of viruses Development and application of a loop-mediated isothermal amplification method on rapid detection Escherichia coli O157 strains from food samples abstract: Nucleic acid amplification for the detection of infectious diseases, food pathogens, or assessment of genetic disorders require a laboratory setting with specialized equipment and technical expertise. Isothermal deoxyribonucleic acid amplification methods, such as loop-mediated isothermal amplification (LAMP), exhibit characteristics ideal for point-of-care (POC) applications, since their instrumentation is simpler in comparison with the standard method of polymerase chain reaction. Other key advantages of LAMP are robustness and the production of pyrophosphate in the presence of the target gene, enabling to detect the reaction products using the naked eye. Polymerase inhibitors, presented in clinical samples, do not affect the amplification process, making LAMP suitable for a simple sample-to-answer diagnostic systems with simplified sample preparation. In this review, we discuss the trends in miniaturized LAMP techniques, such as microfluidic, paper-based, and digital with their advantages and disadvantages, especially for POC applications alongside our opinion of the future development of miniaturized LAMP. url: https://www.ncbi.nlm.nih.gov/pubmed/32287531/ doi: 10.1016/j.trac.2019.01.015 id: cord-003516-l1lq8yga author: Zhang, Jing title: A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations date: 2019-01-31 words: 2357.0 sentences: 133.0 pages: flesch: 38.0 cache: ./cache/cord-003516-l1lq8yga.txt txt: ./txt/cord-003516-l1lq8yga.txt summary: title: A Survey of Recent Adenoviral Respiratory Pathogens in Hong Kong Reveals Emergent and Recombinant Human Adenovirus Type 4 (HAdV-E4) Circulating in Civilian Populations A signature of these "old" HAdV-E4 is the absence of a critical replication motif, NF-I, which is found in all HAdV respiratory pathogens and most HAdVs. However, our recent survey of flu-like disease in children in Hong Kong reveals that the emergent HAdV-E4 pathogens circulating in civilian populations contain NF-I, indicating recombination and reflecting host-adaptation that enables the "new" HAdV-E4 to replicate more efficiently in human cells and foretells more potential HAdV-E4 outbreaks in immune-naïve civilian populations. Recent isolates are recombinants containing this HAdV replication motif [1] , presumably permitting an expansion of the virus range into the immune-naïve populations [5] [6] [7] [21] [22] [23] , and should be noted as a molecular evolution example of a post-zoonotic, host-adaptation of a "novel" and "emergent" human pathogen. abstract: Human adenovirus type 4 (HAdV-E4), which is intriguingly limited to military populations, causes acute respiratory disease with demonstrated morbidity and mortality implications. This respiratory pathogen contains genome identity with chimpanzee adenoviruses, indicating zoonotic origins. A signature of these “old” HAdV-E4 is the absence of a critical replication motif, NF-I, which is found in all HAdV respiratory pathogens and most HAdVs. However, our recent survey of flu-like disease in children in Hong Kong reveals that the emergent HAdV-E4 pathogens circulating in civilian populations contain NF-I, indicating recombination and reflecting host-adaptation that enables the “new” HAdV-E4 to replicate more efficiently in human cells and foretells more potential HAdV-E4 outbreaks in immune-naïve civilian populations. Special attention should be paid by clinicians to this emergent and recombinant HAdV-E4 circulating in civilian populations. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410123/ doi: 10.3390/v11020129 id: cord-300061-l2pfl776 author: Zhang, Ren title: A rebuttal to the comments on the genome order index and the Z-curve date: 2011-02-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Elhaik, Graur and Josic recently commented on the genome order index (S) and the Z-curve (Elhaik et al. Biol Direct 2010, 5: 10). S is a quantity defined as S = a(2 )+ c(2 )+ g(2 )+ t(2), where a, c, g and t denote corresponding base frequencies. The Z-curve is a three dimensional curve that represents a DNA sequence in the manner that each can be uniquely reconstructed given the other. Elhaik et al. made 4 major claims. 1) In the previous mapping system with the regular tetrahedron, calculation of the radius of the inscribed sphere is "a mathematical error". 2) S follows an exponential distribution and is narrowly distributed with a range of (0.25 - 0.33). 3) Based on the Chargaff's second parity rule (PR2), "S is equivalent to H [Shannon entropy]" and they are derivable from each other. 4) Z-curve "suffers from over dimensionality", because based on the analysis of 235 bacterial genomes, x and y components contributed only less than 1% of the variance and therefore "would be of little use". RESULTS: 1) Elhaik et al. mistakenly neglected the parameter [Formula: see text] when calculating the radius of the inscribed sphere. 2) The exponential distribution of S is a restatement of our previous conclusion, and the range of (0.25 - 0.33) only paraphrases the previously suggested S range (0.25 -1/3). 3) Elhaik et al. incorrectly disregard deviations from PR2 by treating the deviations as 0 altogether, reduce S and H, both having 4 variables, a, c, g and t, into functions of one single variable, a only, and apply this treatment to all DNA sequences as the basis of their "demonstration", which is therefore invalid. 4) Elhaik et al. confuse numeral smallness with biological insignificance, and disregard the distributions of purine/pyrimidine and amino/keto bases (x and y components), the variations of which, although can be less than that of GC content, contain rich information that is important and useful, such as in locating replication origins of bacterial and archaeal genomes, and in studies of gene recognition in various species. CONCLUSION: Elhaik et al. confuse S (a single number) with Z-curve (a series of 3D coordinates), which are distinct. To use S as a case study of Z-curve, by itself, is invalid. S and H are neither equivalent nor derivable from each other. The criticisms of Elhaik, Graur and Josic are wrong. REVIEWERS: This article was reviewed by Erik van Nimwegen. url: https://www.ncbi.nlm.nih.gov/pubmed/21324187/ doi: 10.1186/1745-6150-6-10 id: cord-000403-vzbh457k author: Zhang, Weijun title: Identification of CD8(+ )cytotoxic T lymphocyte epitopes from porcine reproductive and respiratory syndrome virus matrix protein in BALB/c mice date: 2011-05-30 words: 4247.0 sentences: 206.0 pages: flesch: 51.0 cache: ./cache/cord-000403-vzbh457k.txt txt: ./txt/cord-000403-vzbh457k.txt summary: Twenty-seven nanopeptides derived from the matrix (M) protein of porcine reproductive and respiratory syndrome virus (PRRSV) were screened for their ability to elicit a recall interferon-γ (IFN-γ) response from the splenocytes of BALB/c mice following DNA vaccination and a booster vaccination with recombinant vaccinia virus rWR-PRRSV-M. We screened peptides derived from the PRRSV M protein for their ability to induce interferon (IFN)-γ in splenocytes harvested from BALB/ c mice following DNA vaccination and a booster vaccination with recombinant vaccinia virus expressing M protein. In contrast, control mice vaccinated with pVAX1-only or PBS-only did not show significant increases in M protein-specific antibody titers after the booster vaccination with rWR-PRRSV-M (P > 0.05, Additional file 5, Fig. S5 ). Specific increases in the number of cells producing IFN-γ following stimulation with the peptides "K 93 FITSRCRL" and "F 57 GYMTFVHF" was observed by day 3 after the booster vaccination with rWR-PRRSV-M (Figure 1 and 2) . abstract: Twenty-seven nanopeptides derived from the matrix (M) protein of porcine reproductive and respiratory syndrome virus (PRRSV) were screened for their ability to elicit a recall interferon-γ (IFN-γ) response from the splenocytes of BALB/c mice following DNA vaccination and a booster vaccination with recombinant vaccinia virus rWR-PRRSV-M. We identified two peptides (amino acid residues K(93)FITSRCRL and F(57)GYMTFVHF) as CD8(+ )cytotoxic T lymphocyte (CTL) epitopes. These peptides elicited significant numbers of IFN-γ secreting cells, compared with other M nonapeptides and one irrelevant nonapeptide. Bioinformatics analysis showed that the former is an H-2K(d)-restricted CTL epitope, and the latter is an H-2D(d)-restricted CTL epitope. Multiple amino acid sequence alignment among different PRRSV M sequences submitted to GenBank indicated that these two CTL epitopes are strongly conserved, and they should therefore be considered for further research on the mechanisms of cellular immune responses to PRRSV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126774/ doi: 10.1186/1743-422x-8-263 id: cord-193910-7p3f3znj author: Zhang, Xiangxie title: Comparing Machine Learning Algorithms with or without Feature Extraction for DNA Classification date: 2020-11-01 words: 7724.0 sentences: 436.0 pages: flesch: 59.0 cache: ./cache/cord-193910-7p3f3znj.txt txt: ./txt/cord-193910-7p3f3znj.txt summary: In the experiments, the performances of feature extraction using primers and random DNA sequences will be compared to several other machine learning approaches. Finally, three state-of-the-art methods, namely a con-volutional neural network (CNN), a deep neural network (DNN), and an N-gram probabilistic model, which were fed the unprocessed DNA sequences without prior feature extraction, were tested. Different machine learning algorithms will be trained and tested using each set of feature vectors in the experiments. For each data set, the results of all six machine learning algorithms using the random DNA sequence feature extraction method are presented in Table ( 8) containing mean accuracy and standard deviation over the ten folds of the cross-validation. It can be concluded that the Levenshtein distance feature extraction yields the best and most consistent results across the six different machine learning algorithms when the distance between a primer and a DNA sequence is taken. abstract: The classification of DNA sequences is a key research area in bioinformatics as it enables researchers to conduct genomic analysis and detect possible diseases. In this paper, three state-of-the-art algorithms, namely Convolutional Neural Networks, Deep Neural Networks, and N-gram Probabilistic Models, are used for the task of DNA classification. Furthermore, we introduce a novel feature extraction method based on the Levenshtein distance and randomly generated DNA sub-sequences to compute information-rich features from the DNA sequences. We also use an existing feature extraction method based on 3-grams to represent amino acids and combine both feature extraction methods with a multitude of machine learning algorithms. Four different data sets, each concerning viral diseases such as Covid-19, AIDS, Influenza, and Hepatitis C, are used for evaluating the different approaches. The results of the experiments show that all methods obtain high accuracies on the different DNA datasets. Furthermore, the domain-specific 3-gram feature extraction method leads in general to the best results in the experiments, while the newly proposed technique outperforms all other methods on the smallest Covid-19 dataset url: https://arxiv.org/pdf/2011.00485v1.pdf doi: nan id: cord-260050-9ex70e1k author: Zhang, Y. Q. title: Inhibition of herpes simplex virus type 1 by small interfering RNA date: 2007-11-02 words: 2120.0 sentences: 131.0 pages: flesch: 51.0 cache: ./cache/cord-260050-9ex70e1k.txt txt: ./txt/cord-260050-9ex70e1k.txt summary: Aim. To investigate the antiviral effects of siRNA on herpes simplex virus type 1 (HSV‐1) replication in Vero cells. These results indicate that siRNA can potently inhibit HSV‐1 replication in vitro, suggesting that siRNA‐based antiviral therapy may be a potential effective therapeutic alternative for patients with HSV‐1 infection. In our experiments, we showed that the siRNA duplexes targeting VP16 and DNA polymerase genes potently inhibited HSV-1 replication. However, this is not a universal finding as no additive or synergistic effect on antiviral activity was observed in a study when using any combination between the specific siRNA targeting viral protease 2A and any other siRNAs targeting the 5¢ untranslated region, start codon and RNA polymerase 3D of coxsackie virus B3. Short interfering RNA-mediated inhibition of herpes simplex virus type 1 gene expression and function during infection of human keratinocytes abstract: Background. RNA interference, a conserved mechanism in which a sequence‐specific gene‐silencing process is mediated by small interfering RNA (siRNA), is a promising method of gene therapy in treating a variety of viral diseases. Aim. To investigate the antiviral effects of siRNA on herpes simplex virus type 1 (HSV‐1) replication in Vero cells. Methods. The antiviral effects of siRNA duplexes targeting the VP16 and DNA polymerase genes of HSV‐1 were evaluated by yield‐reduction and plaque‐reduction assays. The effect of siRNA on the expression of target genes was measured by real‐time quantitative reverse transcription PCR. Results. Two siRNA duplexes (siRNA‐1, targeting VP16, and siRNA‐4, targeting DNA polymerase), were found to be highly effective in inhibiting HSV‐1 replication. siRNA‐1 and siRNA‐4 reduced HSV‐1 replication by around 2 log(10) and 1 log(10) in the yield‐‐reduction assay and by ∼85% and ∼70% in the plaque‐reduction assay, respectively. Significant decreases in the mRNA level of VP16 and DNA polymerase genes were detected after viral infection in the Vero cells pretreated with siRNA‐1 and siRNA‐4, respectively. Conclusion. These results indicate that siRNA can potently inhibit HSV‐1 replication in vitro, suggesting that siRNA‐based antiviral therapy may be a potential effective therapeutic alternative for patients with HSV‐1 infection. url: https://www.ncbi.nlm.nih.gov/pubmed/17979991/ doi: 10.1111/j.1365-2230.2007.02543.x id: cord-288131-dwhfrgje author: Zhao, Guodong title: Aberrant DNA Methylation of SEPT9 and SDC2 in Stool Specimens as an Integrated Biomarker for Colorectal Cancer Early Detection date: 2020-06-18 words: 4309.0 sentences: 234.0 pages: flesch: 62.0 cache: ./cache/cord-288131-dwhfrgje.txt txt: ./txt/cord-288131-dwhfrgje.txt summary: A number of methylated DNA biomarkers have been found to associate with CRC and precancerous lesions in stool or plasma samples, including SEPT9 (Catherine et al., 2008; Lamb and Dhillon, 2017) , SDC2 (Barták et al., 2017; Han et al., 2019) , SFRP2 (Barták et al., 2017; Li et al., 2019) , and TFPI2 (Glöckner et al., 2009) , some of which have been developed into commercial kits for CRC early detection (Potter et al., 2014; Lamb and Dhillon, 2017; Li et al., 2019; Zhao et al., 2019) . We previously demonstrated a multiplex methylated DNA test in plasma, ColoDefense test, with high sensitivity and specificity for CRC early detection. Instead, we have demonstrated that the detection rates of plasma ColoDefense test for AA and early stage CRC were significantly improved by the combination of two biomarkers, mSEPT9 and mSDC2, with high specificity . abstract: Colorectal cancer (CRC) has become the second leading cause of new cancer cases and the fifth of cancer deaths in China, and early detection is the most effective way to reduce the incidence and mortality of CRC. A number of methylated DNA biomarkers have been found to associate with CRC and precancerous lesions in stool samples, indicating stool methylated DNA biomarkers are potential tools for CRC early detection. In this study, approximately 5 g of stool specimen was collected from 230 subjects (124 in the training set and 106 in the validation set). Stool DNA was extracted and bisulfite-converted, followed by ColoDefense test, a multiplex qPCR assay, that simultaneously detects methylated SEPT9 (mSEPT9) and methylated SDC2 (mSDC2). Youden index was employed to determine the cut-off value of ColoDefense test for stool specimens. In the training set, the optimized cut-off value of stool ColoDefense test was: mSEPT9 analyzed with 3/3 algorithm and mean mSEPT9 Ct values of <38, or mSDC2 with 2/3 algorithm. Stool ColoDefense test achieved Youden indexes of 79.9 and 57.4% in detecting CRC and advanced adenomas (AA), respectively. Its sensitivities in the training set for AA and CRC were 66.7% (95% CI: 24.1–94.0%) and 89.1% (95% CI: 77.1–95.5%) with a 90.8% (95% CI: 80.3–96.2%) specificity, and AUC was 0.956 (95% CI: 0.924–0.988). In the validation set, its sensitivities for AA and CRC were 66.7% (95% CI: 24.1–94.0%) and 92.3% (95% CI: 78.0–98.0%) with a 93.2% (95% CI: 82.7–97.8%) specificity, and AUC was 0.977 (95% CI: 0.952–1.000). Positive detection rate of stool ColoDefense test has been found to be independent of age, gender, tumor location, and tumor size. In conclusion, stool ColoDefense test demonstrated high sensitivities and specificity for the detection of AA and CRC. Therefore, it has the potential to become a low-cost, convenient, and highly effective tool for CRC early detection. url: https://www.ncbi.nlm.nih.gov/pubmed/32625237/ doi: 10.3389/fgene.2020.00643 id: cord-012802-xm2ftrw2 author: Zhao, Wu-li title: The novel quinolizidine derivate IMB-HDC inhibits STAT5a phosphorylation at 694 and 780 and promotes DNA breakage and cell apoptosis via blocking STAT5a nuclear translocation date: 2020-01-13 words: 7536.0 sentences: 330.0 pages: flesch: 50.0 cache: ./cache/cord-012802-xm2ftrw2.txt txt: ./txt/cord-012802-xm2ftrw2.txt summary: Our research reveals a novel DNA response mechanism different from general DNA-damaging agents, and that sophoridine derivate inhibits the phosphorylation of Tyr694 and Ser780 of STAT5a to induce the lessened shuttle from the cytoplasm to the nucleus, and leads to the decreased nuclear STAT5a and subsequently inhibits the expression of STAT5a target gene RAD51 that contributes to the checkpoint activation, thus inhibiting ATR activation. All the above-mentioned results demonstrated that IMB-HDC depressed STAT5a nuclear translocation, transcriptional activity, and triggers DNA breakage and apoptosis via blocking 694 and 780 phosphorylation IMB-HDC-induced proliferation inhibition depends on the decreased phosphorylation of 694 and 780 in vivo Next, in a tumor xenograft nude mouse model, we examined IMB-HDC anticancer efficacy. Our previous chip assay analysis showed that the level of several STAT5a target genes decreased; thus, we speculated that STAT5a might be implicated in IMB-HDC-induced apoptosis and DNA breakage in tumor cells. abstract: Sophoridine is a quinolizidine natural product and the exploration of its derivatives has been carried out, and the potent anticancer compound IMB-HDC was acquired. Although previous studies have revealed that some sophoridine derivatives could induce DNA breakage, the underlying mechanisms of inhibition of DNA damage repair (ATR inactivation) and the apoptosis independent of p53, have not been elucidated. Our research reveals a novel DNA response mechanism different from general DNA-damaging agents, and that sophoridine derivate inhibits the phosphorylation of Tyr694 and Ser780 of STAT5a to induce the lessened shuttle from the cytoplasm to the nucleus, and leads to the decreased nuclear STAT5a and subsequently inhibits the expression of STAT5a target gene RAD51 that contributes to the checkpoint activation, thus inhibiting ATR activation. Meanwhile, IMB-HDC that induced the diminished expression of STAT5a target gene contributes to proliferation and leads to apoptosis. More importantly, we give the first evidence that promoting the effect of Tyr694 phosphorylation on nuclear location and subsequent STAT5a target gene transcription depends on Ser780 increased or unchanged phosphorylation and was not correlated with Ser726 phosphorylation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471404/ doi: 10.1038/s41401-019-0333-6 id: cord-292757-d03byeee author: Zhou, Xianfeng title: Enhance immune response to DNA vaccine based on a novel multicomponent supramolecular assembly date: 2007-08-07 words: 4707.0 sentences: 237.0 pages: flesch: 46.0 cache: ./cache/cord-292757-d03byeee.txt txt: ./txt/cord-292757-d03byeee.txt summary: Here, a novel multicomponent supramolecular system involving the preparation of mannose-bearing chitosan oligomers microspheres with entrapping complexes of DNA vaccine and polyethylenimine was developed to mimic many of the beneficial properties of the viruses. After delivery by intramuscular immunization in BALB/c mice, the microspheres induced an enhanced serum antibody responses two orders of magnitude greater than naked DNA vaccine. Here we have designed novel mannose-bearing chitosan oligomers (MBCO) microspheres with entrapping polyethylenimine (PEI)/DNA complexes to mimic the beneficial properties of viruses: Hence, the MBCO microspheres mimic the following five desirable characteristics of a virus: (i) DNA condensation; (ii) cell entry-targeting; (iii) endosome escape; (iv) compact viral size (200-300 nm) and (v) efficient decomplexation. These studies have demonstrated that MBCO microspheres were potent delivery systems for DNA vaccines and are capable of inducing the enhanced humoral and cellular responses (about 100-fold) after i.m. immunization with HBsAg plasmid. abstract: DNA vaccination has tremendous potential for treating or preventing numerous diseases for which traditional vaccines are ineffective but the technique can be limited by low immunogenicity. Current synthetic DNA delivery systems are versatile and safe, but substantially less efficient than viruses. Here, a novel multicomponent supramolecular system involving the preparation of mannose-bearing chitosan oligomers microspheres with entrapping complexes of DNA vaccine and polyethylenimine was developed to mimic many of the beneficial properties of the viruses. After delivery by intramuscular immunization in BALB/c mice, the microspheres induced an enhanced serum antibody responses two orders of magnitude greater than naked DNA vaccine. Additionally, in contrast to naked DNA, the microspheres induced potent cytotoxic T lymphocyte responses at a low dose. Consequently, formulation of DNA vaccines into multicomponent vectors is a powerful means of increasing vaccine potency. url: https://api.elsevier.com/content/article/pii/S0142961207005248 doi: 10.1016/j.biomaterials.2007.07.002 id: cord-323973-wszo9s3d author: Zhu, Hanliang title: The vision of point-of-care PCR tests for the COVID-19 pandemic and beyond date: 2020-07-20 words: 9784.0 sentences: 493.0 pages: flesch: 50.0 cache: ./cache/cord-323973-wszo9s3d.txt txt: ./txt/cord-323973-wszo9s3d.txt summary: [9] The analysis of larger volumes of biological fluids with a low viral load is likely to reduce the risk of false-negative results, but microfluidic point-of-care (POC) devices are typically unable to handle mL-scale volumes in a short time due to the requirement of slow flow rates. [15] The PCR test on samples prepared from blood and urine specimens is capable of detecting the virus in the early stages of the disease, resulting in early diagnosis and subsequent isolation of infected patients to block transmission. The total reaction time depends on a series of parameters, such as the chip size, the PCR master mix volume determining the value of C, the thermal conductivity of the substrate (G), and the temperature cycling rate. A number of fully integrated systems have so far been developed, starting with the non-portable GenExpert from Cepheid, which was first utilized for anthrax detection by the United States Postal Service, [64] and then with different primers to perform HIV and tuberculosis diagnostics in South Africa. abstract: Infectious diseases, such as the most recent case of COVID-19, have brought the prospect of point-of-care (POC) diagnostic tests into the spotlight. A rapid, accurate, low-cost, and easy-to-use test in the field could stop epidemics before they develop into full-blown pandemics. Unfortunately, despite all the advances, it still does not exist. Here, we critically review the limited number of prototypes demonstrated to date that is based on a polymerase chain reaction (PCR) and has come close to fulfilling this vision. We summarize the requirements for the POC-PCR tests and then go on to discuss the PCR product-detection methods, the integration of their functional components, the potential applications, and other practical issues related to the implementation of lab-on-a-chip technologies. We conclude our review with a discussion of the latest findings on nucleic acid-based diagnosis. url: https://api.elsevier.com/content/article/pii/S0165993620302132 doi: 10.1016/j.trac.2020.115984 id: cord-308497-zltp8ei4 author: Zhu, Kaichun title: A continuous method for the large-scale extraction of plasmid DNA by modified boiling lysis date: 2007-01-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: This protocol describes a streamlined method of plasmid DNA extraction by continual thermal lysis, a modification of the basic boiling lysis technique, to simplify the processing of large volumes of Escherichia coli cultures. Fermented bacteria are harvested using a hollow fiber-membrane module and pre-treated with lysozyme prior to passing through a thermal exchange coil set at 70 °C to lyse the cells, and into a juxtaposed cooling coil on ice. The lysed and cooled bacteria are subsequently separated from the lysate by centrifugation and plasmid DNA is precipitated from the supernatant for further purification. The use of peristaltic pumps and two heating coils at constant temperature without the use of centrifugation enable the lysis process to become constant and controllable, providing a flow-through protocol for cell lysis and plasmid DNA extraction. Large volumes of bacterial cultures (20 l) can be processed in 2 h, yielding approximately 100 mg plasmid DNA l(−1) culture, making this an attractive protocol for consistent and large-scale preparation of plasmid DNA. url: https://www.ncbi.nlm.nih.gov/pubmed/17406572/ doi: 10.1038/nprot.2006.452 id: cord-310268-8q4tk6fd author: Zhu, Qinchang title: DNA Aptamers in the Diagnosis and Treatment of Human Diseases date: 2015-11-25 words: 8649.0 sentences: 411.0 pages: flesch: 47.0 cache: ./cache/cord-310268-8q4tk6fd.txt txt: ./txt/cord-310268-8q4tk6fd.txt summary: Nucleic acid aptamers are RNA and single-stranded (ss) DNA oligonucleotides with lengths typically ranging from 15 to 70 mers, which have the same level of target-binding affinity as monoclonal antibodies (the dissociation constant (K d ) usually ranges from 0.1 to 50 nM) [5, 6] . This SELEX is able to generate DNA aptamers that recognize the cell-surface or intracellular target protein in their native conformation, which shows great potential in cell-specific therapeutics and diagnostic applications [26] [27] [28] . Recently, modified cell-SELEX methods have been developed to select aptamers targeting specific cells like disease state cells and metastatic cells. In the era of personalized medicine, DNA aptamer-based therapeutics and diagnostics are believed to have great potential for extensive application because of their flexibility to specifically bind to any molecule targets. abstract: Aptamers have a promising role in the field of life science and have been extensively researched for application as analytical tools, therapeutic agents and as vehicles for targeted drug delivery. Compared with RNA aptamers, DNA aptamers have inherent advantages in stability and facility of generation and synthesis. To better understand the specific potential of DNA aptamers, an overview of the progress in the generation and application of DNA aptamers in human disease diagnosis and therapy are presented in this review. Special attention is given to researches that are relatively close to practical application. DNA aptamers are expected to have great potential in the diagnosis and treatment of human diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/26610462/ doi: 10.3390/molecules201219739 id: cord-305143-mqd4ioj4 author: Zmasek, Christian M. title: Classification of human Herpesviridae proteins using Domain-architecture Aware Inference of Orthologs (DAIO) date: 2019-01-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We developed a computational approach called Domain-architecture Aware Inference of Orthologs (DAIO) for the analysis of protein orthology by combining phylogenetic and protein domain-architecture information. Using DAIO, we performed a systematic study of the proteomes of all human Herpesviridae species to define Strict Ortholog Groups (SOGs). In addition to assessing the taxonomic distribution for each protein based on sequence similarity, we performed a protein domain-architecture analysis for every protein family and computationally inferred gene duplication events. While many herpesvirus proteins have evolved without any detectable gene duplications or domain rearrangements, numerous herpesvirus protein families do exhibit complex evolutionary histories. Some proteins acquired additional domains (e.g., DNA polymerase), whereas others show a combination of domain acquisition and gene duplication (e.g., betaherpesvirus US22 family), with possible functional implications. This novel classification system of SOGs for human Herpesviridae proteins is available through the Virus Pathogen Resource (ViPR, www.viprbrc.org). url: https://www.sciencedirect.com/science/article/pii/S0042682219300054 doi: 10.1016/j.virol.2019.01.005 id: cord-338633-pxxon1ni author: Zuo, Yu title: Neutrophil extracellular traps and thrombosis in COVID-19 date: 2020-11-05 words: 2782.0 sentences: 167.0 pages: flesch: 41.0 cache: ./cache/cord-338633-pxxon1ni.txt txt: ./txt/cord-338633-pxxon1ni.txt summary: We found that remnants of NETs (cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3) and neutrophil-derived S100A8/A9 (calprotectin) in patient sera were associated with higher risk of morbid thrombotic events in spite of prophylactic anticoagulation. Neutrophil-derived extracellular traps (NETs) play a pathogenic role in many thrombo-inflammatory states including sepsis [4, 5] , thrombosis [6] [7] [8] , and respiratory failure [9, 10] . Here, we describe 11 cases of thrombosis in patients hospitalized with COVID-19 and demonstrate an association with neutrophil hyperactivity and NET release. As compared with the control group, patients with a thrombotic event demonstrated significantly higher levels of calprotectin, a marker of neutrophil activation (Fig. 1a) . Finally, we asked whether there was an association between blood markers of neutrophil activation (such as calprotectin and cell-free DNA) and D-dimer within this cohort of COVID-19 patients (n = 44). abstract: Studies of patients with COVID-19 have demonstrated markedly dysregulated coagulation and a high risk of morbid arterial and venous thrombotic events. Elevated levels of blood neutrophils and neutrophil extracellular traps (NETs) have recently been described in patients with COVID-19. However, their potential role in COVID-19-associated thrombosis remains incompletely understood. In order to elucidate the potential role of hyperactive neutrophils and NET release in COVID-19-associated thrombosis, we conducted a case–control study of patients hospitalized with COVID-19 who developed thrombosis, as compared with gender- and age-matched COVID-19 patients without clinical thrombosis. We found that remnants of NETs (cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3) and neutrophil-derived S100A8/A9 (calprotectin) in patient sera were associated with higher risk of morbid thrombotic events in spite of prophylactic anticoagulation. These observations underscore the need for urgent investigation into the potential relationship between NETs and unrelenting thrombosis in COVID-19, as well as novel approaches for thrombosis prevention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11239-020-02324-z) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1007/s11239-020-02324-z doi: 10.1007/s11239-020-02324-z id: cord-284690-ogu1gmcb author: da Cunha, Nicolau B. title: The next generation of antimicrobial peptides (AMPs) as molecular therapeutic tools for the treatment of diseases with social and economic impacts date: 2016-11-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Anti-infective drugs have had a key role in the contemporary world, contributing to dramatically decrease mortality rates caused by infectious diseases worldwide. Antimicrobial peptides (AMPs) are multifunctional effectors of the innate immune system of mucosal surfaces and present antimicrobial activity against a range of pathogenic viruses, bacteria, and fungi. However, the discovery and development of new antibacterial drugs is a crucial step to overcome the great challenge posed by the emergence of antibiotic resistance. In this review, we outline recent advances in the development of novel AMPs with improved antimicrobial activities that were achieved through characteristic structural design. In addition, we describe recent progress made to overcome some of the major limitations that have hindered peptide biosynthesis. url: https://www.sciencedirect.com/science/article/pii/S1359644616304135 doi: 10.1016/j.drudis.2016.10.017 id: cord-263134-0p4zy5t2 author: de Paz, Hector David title: Molecular isothermal techniques for combating infectious diseases: towards low-cost point-of-care diagnostics date: 2014-07-23 words: 6474.0 sentences: 304.0 pages: flesch: 34.0 cache: ./cache/cord-263134-0p4zy5t2.txt txt: ./txt/cord-263134-0p4zy5t2.txt summary: This review describes the landscape of molecular isothermal diagnostic techniques for infectious diseases, their characteristics, current state of development, and available products, with a focus on new directions towards point-of-care applications. Advances in microfluidics and miniaturization of signal detectors have allowed the integration of molecular diagnostics into microscale lab-on-achip devices that perform all necessary PCR steps automatically, from sample intake to cell lysis, DNA extraction, purification and amplification. This review describes the state-ofthe-art and new directions in the development of isothermal amplification technologies for diagnosis of infectious diseases with particular focus on those susceptible to be integrated in inexpensive molecular POC tests. • Loop-mediated isothermal amplification, smart amplification process & signal mediated amplification of RNA technology, helicasedependent amplification, strand displacement amplification, recombinase polymerase amplification and nicking and extension amplification reaction are isothermal techniques with mid/high tolerance to inhibitory compounds that allow the use of raw samples without any pretreatment step, which may be an interesting feature for PCR-based point-of-care (POC) testing. abstract: Nucleic acid amplification techniques such as PCR have facilitated rapid and accurate diagnosis in central laboratories over the past years. PCR-based amplifications require high-precision instruments to perform thermal cycling reactions. Such equipment is bulky, expensive and complex to operate. Progressive advances in isothermal amplification chemistries, microfluidics and detectors miniaturisation are paving the way for the introduction and use of compact ‘sample in-results out’ diagnostic devices. However, this paradigm shift towards decentralised testing poses diverse technological, economic and organizational challenges both in industrialized and developing countries. This review describes the landscape of molecular isothermal diagnostic techniques for infectious diseases, their characteristics, current state of development, and available products, with a focus on new directions towards point-of-care applications. url: https://doi.org/10.1586/14737159.2014.940319 doi: 10.1586/14737159.2014.940319 id: cord-346450-x1u567ss author: del Fresno, Carlos title: Myeloid cells in sensing of tissue damage date: 2020-10-07 words: 4209.0 sentences: 222.0 pages: flesch: 34.0 cache: ./cache/cord-346450-x1u567ss.txt txt: ./txt/cord-346450-x1u567ss.txt summary: During tissue injury, mitochondrial DNA (mtDNA) is also released extracellularly as a pro-inflammatory DAMP [16] that is primarily recognized by the endosomal Toll-Like Receptor 9 (TLR9) upon phagocytosis by myeloid cells [17] . In a similar way, histones released upon cell death are recognized by 36 Innate immunity Inflammatory and regulatory functions of myeloid receptors and DAMPs compiled in this review. During most of the conditions described before, the recognition of DAMPs by myeloid cells triggers direct inflammatory responses by activating signaling pathways downstream certain PRRs. However, the sensing of tissue injury is not always inflammatory but can rather regulate inflammation (Figure 1, right oval) . Tissue injury conditions lead to massive release of different DAMPs. As discussed in here, the recognition of this tissue damage by myeloid cells can generate both pro-inflammatory and regulatory responses. abstract: Myeloid cells are components of the innate immune system that represent the first line of defense. Tissue damage, associated with pathological conditions such as infection, cancer or autoimmunity, leads to the exposure of the intracellular content to the extracellular environment. Myeloid cells detect ligands exposed or released by dead cells through specific receptors that signal for a diversity of responses. Inflammatory responses triggered by myeloid cells after sensing tissue injury can contribute to resolution of the damage. The signaling response following dead-cell sensing by myeloid cells can contribute either to an inflammatory or a regulatory response. We review herein some representative examples of how myeloid cells react to the recognition of cell death during specific tissue damage contexts. A deep understanding of the cellular and molecular mechanisms underlying these processes would allow to improve therapeutical interventions in pathologies associated with tissue damage. url: https://www.sciencedirect.com/science/article/pii/S0952791520300820 doi: 10.1016/j.coi.2020.08.006 id: cord-000083-3p81yr4n author: nan title: Poster Exhibition date: 2009-01-31 words: 112815.0 sentences: 7542.0 pages: flesch: 56.0 cache: ./cache/cord-000083-3p81yr4n.txt txt: ./txt/cord-000083-3p81yr4n.txt summary: R. China Background: The objective of this study was to evaluate the early virologic response for prediction of achievement of HBeAg seroconversion and hepatitis B virus (HBV) DNA negativity after two years of lamivudine treatment in chronic hepatitis B (CHB) patients. Methods: A total of 620 patients who tested positive for hepatitis B surface antigen and were referred to Chiba University Hospital between February 1985 and March 2008 were included in the study, and their following characteristics were analyzed: age, gender, the status of HBeAg, ALT, HBV-DNA level, and PLT. Methods: A total of 60 patients with chronic hepatitis B, 32 (53.3%) were HBeAg positive (group A) while 28(46.7%) were HBeAg negative (group B) were included in this study after meeting the following criteria: age 18 to 60 years, HBsAg positive for more than 6 months, serum HBV-DNA was >5 log(10) copies/mL and ALT more than two times the upper normal limit. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712310/ doi: 10.1007/s12072-009-9123-4 id: cord-000718-7whai7nr author: nan title: ESP Abstracts 2012 date: 2012-08-22 words: 166497.0 sentences: 12847.0 pages: flesch: 49.0 cache: ./cache/cord-000718-7whai7nr.txt txt: ./txt/cord-000718-7whai7nr.txt summary: Method: We analyzed consecutive gastric cancer cases in terms of AMACR immunohistochemical expression and clinical/pathological characteristics and followed patients'' postoperative history. Results: Histological, immunohistochemical and molecular examination revealed non-neoplastic lymphadenopathy with atypical paracortical T-cell hyperplasia with immunoblastic reaction in the former and burnt-out histiocytic pattern in the latter, both falling into a broad spectrum of reactive lymph node changes associated with Still''s disease. Method: We have thus collected, from our two Institutions a large number (45 cases) of cancers showing the histological definition of adenosquamous carcinomas according to the WHO criteria and performed gene analysis for k-RAS (codons 12, 13) and EGFR (codons 18, 19 and 21) mutations. Objective: We previously identified amplified fibroblast growth factor 1 (FGFR1) as a therapeutic target for small molecule inhibitor (SMI) therapy in squamous cell lung cancer (L-SCC), resulting in currently running clinical trials treating patients with stage III disease. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400751/ doi: 10.1007/s00428-012-1284-1 id: cord-001835-0s7ok4uw author: nan title: Abstracts of the 29th Annual Symposium of The Protein Society date: 2015-10-01 words: 138514.0 sentences: 6150.0 pages: flesch: 40.0 cache: ./cache/cord-001835-0s7ok4uw.txt txt: ./txt/cord-001835-0s7ok4uw.txt summary: Altogether, these results indicate that, although PHDs might be more selective for HIF as a substrate as it was initially thought, the enzymatic activity of the prolyl hydroxylases is possibly influenced by a number of other proteins that can directly bind to PHDs. Non-natural aminoacids via the MIO-enzyme toolkit Alina Filip 1 , Judith H Bartha-V ari 1 , Gergely B an oczy 2 , L aszl o Poppe 2 , Csaba Paizs 1 , Florin-Dan Irimie 1 1 Biocatalysis and Biotransformation Research Group, Department of Chemistry, UBB, 2 Department of Organic Chemistry and Technology An attractive enzymatic route to enantiomerically pure to the highly valuable a-or b-aromatic amino acids involves the use of aromatic ammonia lyases (ALs) and aminomutases (AMs). Continuing our studies of the effect of like-charged residues on protein-folding mechanisms, in this work, we investigated, by means of NMR spectroscopy and molecular-dynamics simulations, two short fragments of the human Pin1 WW domain [hPin1(14-24); hPin1(15-23)] and one single point mutation system derived from hPin1(14-24) in which the original charged residues were replaced with non-polar alanine residues. abstract: nan url: https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/pro.2823 doi: 10.1002/pro.2823 id: cord-004534-jqm1hxps author: nan title: Abstract date: 2009-06-09 words: 139023.0 sentences: 6450.0 pages: flesch: 42.0 cache: ./cache/cord-004534-jqm1hxps.txt txt: ./txt/cord-004534-jqm1hxps.txt summary: HIV-1 to efficiently complete a replication cycle has to integrate its genome into the host cellular DNA.After HIV-1 enters target cells,neosynthesized viral DNA forms along with other proteins the pre-integration complex (PIC).PICs are then transported into the nucleus where integration,catalyzed by the viral integrase,takes place.HIV-1 viral particles engineered to incorporate integrase fused to EGFP have proven effective to study PICs within nuclei of infected cells.In this study we report the live imaging analysis of nuclear PIC dynamics obtained by time-lapse microscopy.Intranuclear trajectories of IN-EGFP-labeled PIC were collected in three dimensions and examined by both mean squared displacement (MSD) and cage diameter (CD) analysis.In CD the maximum distances measured between two positions occupied by a PIC in a time window of 2 minutes were calculated while in our MSD analysis 5-minute long trajectory segments were considered.Remarkably,MSD revealed the presence of an underlying active transport mechanism.To test the possible role of actin filaments,PIC nuclear trafficking was analyzed in cells treated with latrunculin B (actin polymerization inhibitor).Preliminary results suggest that the disruption of actin function impairs the active nuclear movement of PICs. Second harmonic generation microscopy reveals sarcomere contractile dynamics of cardiomyocytes N. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079852/ doi: 10.1007/s00249-009-0478-1 id: cord-004584-bcw90f5b author: nan title: Abstracts: 8th EBSA European Biophysics Congress, August 23rd–27th 2011, Budapest, Hungary date: 2011-08-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080017/ doi: 10.1007/s00249-011-0734-z id: cord-004675-n8mlxe7p author: nan title: 2019 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference date: 2019-02-26 words: 86427.0 sentences: 5050.0 pages: flesch: 46.0 cache: ./cache/cord-004675-n8mlxe7p.txt txt: ./txt/cord-004675-n8mlxe7p.txt summary: However, the mean infusion rate per site was similar between patients aged <18 years ( XMEN disease (X-linked Immunodeficency with Magnesium defect, Epstein-Barr virus infection and Neoplasia) is a primary immune deficiency caused by mutations in MAGT1 and characterized by chronic infection with Epstein-Barr virus (EBV), EBV-driven lymphoma, CD4 T-cell lymphopenia, and dysgammaglobulinemia. We present the case of a 1-year old Hispanic infant with a pathogenic variant in MAGT1 gene that clinically manifested with early Pneumocystis jirovecii and cytomegalovirus (CMV) interstitial pneumonia, and EBV chronic infection with good response to intravenous immunoglobulins supplementation without hematopoietic stem cell transplantation or gene therapy. Chief, Laboratory of Clinical Immunology and Microbiology, IDGS, DIR, NIAID, NIH, Bethesda, MD, USA Hypomorphic Recombination Activating Gene 1 (RAG1) mutations result in residual T-and B-cell development in both humans and mice and have been found in patients presenting with delayed-onset combined immune deficiency with granulomas and/or autoimmunity (CID-G/AI). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086569/ doi: 10.1007/s10875-019-00597-5 id: cord-004879-pgyzluwp author: nan title: Programmed cell death date: 1994 words: 81677.0 sentences: 4465.0 pages: flesch: 51.0 cache: ./cache/cord-004879-pgyzluwp.txt txt: ./txt/cord-004879-pgyzluwp.txt summary: Furthermore kinetic experiments after complementation of HIV=RT p66 with KIV-RT pSl indicated that HIV-RT pSl can restore rate and extent of strand displacement activity by HIV-RT p66 compared to the HIV-RT heterodimer D66/D51, suggesting a function of the 51 kDa polypeptide, The mouse mammary tumor virus proviral DNA contains an open reading frame in the 3'' long terminal repeat which can code for a 36 kDa polypeptide with a putative transmembrane sequence and five N-linked glycosylation sites. To this end we used constructs encoding the c-fos (and c-jun) genes fused to the hormone-binding domain of the human estrogen receptor, designated c-FosER (and c-JunER), We could show that short-term activation (30 mins.) of c-FosER by estradiole (E2) led to the disruption of epithelial cell polarity within 24 hours, as characterized by the expression of apical and basolateral marker proteins. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087532/ doi: 10.1007/bf02033112 id: cord-004948-ad3i9wgj author: nan title: 7th International Congress on Amino Acids and Proteins : Vienna, Austria, August 6–10, 2001 date: 2001 words: 73534.0 sentences: 3588.0 pages: flesch: 45.0 cache: ./cache/cord-004948-ad3i9wgj.txt txt: ./txt/cord-004948-ad3i9wgj.txt summary: Specific CTL were derived by immunization of HHD mice with tumor peptide extracts loaded on antigen presenting cells and with HHD transfected human tumor cell lines CTL induced against peptides from various tumors recognized tumor peptides more effectively than peptides extracted from normal tissues and also reacted with a serie of peptides derived from overexpressed candidate proteins, identified by differential display methods (SAGE, Microarrays) Comparison of CTL derived from HHD mice to CTL induced from patient''s PBMC showed overlapping recognition of many candidate peptides. By comparison of pro-teomic cell maps from normal controls and individuals affected with lysosomal transport disorders we have selected and identified several candidate disease-causing proteins, which have to be further studied by mutation analysis and functional expression. The results of the in vitro studies available to date strongly suggest that its effects on neuronal amino acid transport processes is mediated via some novel extracellular mechanism controlling the H ϩ (and/or other ionic) concentrations of neurones. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087755/ doi: 10.1007/s007260170030 id: cord-005147-mvoq9vln author: nan title: Autorenregister date: 2017-02-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7088617/ doi: 10.1007/s11825-017-0126-6 id: cord-006229-7yoilsho author: nan title: Abstracts of the 82(nd) Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and the 18(th) Annual Meeting of the Network Clinical Pharmacology Germany (VKliPha) in cooperation with the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e.V. (AGAH) date: 2016-02-06 words: 133493.0 sentences: 6804.0 pages: flesch: 42.0 cache: ./cache/cord-006229-7yoilsho.txt txt: ./txt/cord-006229-7yoilsho.txt summary: It directly activates Protein Kinase A (PKA) or the Exchange protein directly activated by cAMP (Epac) which is a guanine exchange factor (GEF) for the small monomeric GTPase Rap. As Human umbilical vein endothelial cells (HUVEC) express both cAMP effectors (Epac1 and PKA), we investigated the role of cAMP-signaling using a spheroid based sprouting assay as an in vitro model for angiogenesis. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration Methods and Results: Here we demonstrate that dexamethasone treatment lowered S1P 1 mRNA and protein expression levels in rat mesangial cells measured by TaqMan® and Western blot analyses. The aim of this study was to investigate the relevance of IGFBP5 in cardiogenesis and cardiac remodeling and its role as a potential target for ameliorating stress-induced cardiac remodeling Methods and Results: We investigated the expression of Igfbp5 in murine cardiac tissue at different developmental stages by qPCR normalized to Tpt1 (Tumor Protein, Translationally-Controlled 1). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100641/ doi: 10.1007/s00210-016-1213-y id: cord-006230-xta38e7j author: nan title: Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date: 2012-02-22 words: 135419.0 sentences: 7042.0 pages: flesch: 43.0 cache: ./cache/cord-006230-xta38e7j.txt txt: ./txt/cord-006230-xta38e7j.txt summary: Here, we will present our analysis of Ca 2+ signaling following stimulation of the FcεRI receptor and application of secretagogues that are supposed to affect Ca 2+ -dependent mast cell activation such as adenosine, endothelin-1, substance P and compound 48/80 in BMMCs and PMCs derived from mouse lines with inactivation of TRPC1, TRPC3, TRPC4, TRPC5 or TRPC6 since specific antagonists are still lacking for these TRP channels. These data indicate that increased PP2A activity is associated with modified gene expression in TG hearts possibly affecting stress response and regulation of cell signalling. As demonstrated by qPCR and Western blot experiments, mesangial cells showed a marked time-and dose-dependent upregulation of CSE mRNA and protein levels after treatment with platelet-derived growth factor (PDGF-BB). The transcription factor cAMP response element (CRE)-binding protein (CREB) plays a critical role in regulating gene expression in response to activation of the cAMPdependent signaling pathway, which is implicated in the pathophysiology of heart failure. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100643/ doi: 10.1007/s00210-012-0736-0 id: cord-006466-e1phpqes author: nan title: 2018 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference date: 2018-04-23 words: 92230.0 sentences: 5516.0 pages: flesch: 46.0 cache: ./cache/cord-006466-e1phpqes.txt txt: ./txt/cord-006466-e1phpqes.txt summary: Whole exome sequencing revealed a heterozygous mutation, previously reported (c.1425+1G>T) Conclusions: In summary, this report emphasizes the suspicion of a combined immunodeficiency in the presence of multiple abscesses by Mycoplasma, the usefulness of rDNA 16s in order to achieve proper Objectives: We describe a 15-year-old male patient with novel heterozygous mutation of EP300 gene; his first manifestations were initially characterized by infections, cytopenia and hypogammaglobulinemia suggesting a Common Variable Immunodeficiency (CVID), but later on, persisting lymphopenia was suggestive of a combined immunodeficiency. Conclusions: Close monitoring of immune function in early life for patients with CHH and CID as well as the availability of suitable donors assists in determining management, including HSCT Introduction/Background: Leukocyte Adhesion Deficiency (LAD) represents a group of distinct inherited disorders, which inhibit the normal extravasation of neutrophils and their recruitment to sites of infection or inflammation. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101862/ doi: 10.1007/s10875-018-0485-z id: cord-006860-a3b8hyyr author: nan title: 40th Annual Meeting of the GTH (Gesellschaft für Thrombose- und Hämostaseforschung) date: 1996 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103196/ doi: 10.1007/bf00641048 id: cord-008777-i2reanan author: nan title: ECB12: 12th European Congess on Biotechnology date: 2005-07-19 words: 151383.0 sentences: 7577.0 pages: flesch: 43.0 cache: ./cache/cord-008777-i2reanan.txt txt: ./txt/cord-008777-i2reanan.txt summary: Mollerup Department of Chemical Engineering, Building 229, DTU, 2800 Lyngby, Denmark A variety of factors that govern the properties of proteins are utilized in the development of chromatographic processes for the recovery of biological products including the binding and release of protons, the non-covalent association with non-polar groups (often hydrophobic interactions), the association of small ions (ion exchange) and the highly specific antigen-antibody interaction (affinity interactions). Such fermenters will be needed in order to meet the increasing pressure on costs for low price commodity type products such as single cell protein or food and technical grade enzymes, and to meet the demands of the new wave of white biotech, in which bio-produced chemicals must be made at prices competitive with those of the traditional chemical industry. The presentation will focus on use of the sensitive sandwich hybridization technology for the quantitative analysis of process relevant marker genes in different kind of microbial cell cultures with a focus on the production of recombinant proteins. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134330/ doi: 10.1016/j.jbiotec.2005.06.005 id: cord-009571-mygj2nd4 author: nan title: Proceedings of the 42nd annual meeting of the american rheumatism association a section of the arthritis foundation june 1 & 2, 1978 new york city abstracts of papers presented date: 2005-11-23 words: 46150.0 sentences: 2284.0 pages: flesch: 49.0 cache: ./cache/cord-009571-mygj2nd4.txt txt: ./txt/cord-009571-mygj2nd4.txt summary: Levels of Ty cells as well as total T lymphocytes were measured in 19 patients with systemic lupus erythematosus (SLE), 11 with active and 8 with inactive disease, and in 47 normal subjects. The diagnosis of GC arthritis were studied for the presence of GC antigen (AG) and anti-in all seven patients was made by typical clinical presentation, body (AB) in serum and synovial fluid by counter-positive local culture for Ngonorrhoeae (NG) , and response to treatment. A retrospective study was instituted on 10 patients in the UCLA lupus nephritis clinic in an attempt to determine the ability of three serologic indicators-specifically immune complexes (IC), anti-DNA antibodies (DNA-ab), and C3-to predict the activity of SLE renal disease as indicated by changes in 24 hour proteinuria, serum creatinine, and creatinine clearance. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159665/ doi: 10.1002/art.1780210508 id: cord-009664-kb9fnbgy author: nan title: Oral presentations date: 2014-12-24 words: 71112.0 sentences: 3948.0 pages: flesch: 47.0 cache: ./cache/cord-009664-kb9fnbgy.txt txt: ./txt/cord-009664-kb9fnbgy.txt summary: Because of the conflicting reports and lack of published data from paediatric patients, we sought to assess possible MIC change over time and to compare results generated by using different methodologies including Etest, agar dilution, and broth microdilution (MicroScan) methods. Recently, in vitro and in vivo studies have shown that NO plays a key role in the eradication of the leishmania parasite Objective: To determine whether a NO donor patch (developed by electrospinning technique) is as effective as meglumine antimoniate in the treatment of CL while causing less adverse events Methods: A double-blind, randomised, placebo-controlled clinical trial was conducted with 178 patients diagnosed with CL in Santander, Colombia, South-America. To follow the development and spread of the resistance among these strains is difficult, as antibiotic susceptibility testing of clinically relevant anaerobes in different routine laboratories in Europe is less and less frequently carried out due to the fact, that clinicians treat many presumed anaerobic infections empirically. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162236/ doi: 10.1111/j.1469-0691.2009.02857.x id: cord-010027-r0tl01kq author: nan title: Dublin Pathology 2015. 8th Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland date: 2015-09-15 words: 36299.0 sentences: 2004.0 pages: flesch: 47.0 cache: ./cache/cord-010027-r0tl01kq.txt txt: ./txt/cord-010027-r0tl01kq.txt summary: Further profiling of other T cell populations may help to further understand this expression which may act as a biomarker or provide a therapeutic target Biomarkers that are able to distinguish stage II and III colon cancer patients at high risk of developing disease recurrence, who may benefit from adjuvant chemotherapy, are still lacking. *AM supported by the NIHR and the Academy of Medical Sciences ABSTRACTS S·17 Assessment of HER2 Status on Needle Core Biopsy of Breast Cancer: Impact of Histopathological Concordance P M Pigera; AHS Lee; IO Ellis; EA Rakha; Z Hodi Nottingham City Hospital, Nottingham, UK One of the key recommendations introduced in the ASCO/CAP update guideline recommendation on HER2 testing is the novel concept of "histopathological concordance." It is proposed that certain tumour morphological features such as histologic type and grade should trigger repeating a molecular test in cases of "discordance". abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168113/ doi: 10.1002/path.4631 id: cord-010092-uftc8inx author: nan title: Abstract of 29th Regional Congress of the ISBT date: 2019-06-07 words: 233304.0 sentences: 13171.0 pages: flesch: 54.0 cache: ./cache/cord-010092-uftc8inx.txt txt: ./txt/cord-010092-uftc8inx.txt summary: Prospective testing of blood donations in endemic areas of the U.S. revealed 0.38% of donors were positive for Babesia DNA or antibodies (Moritz, NEJM, 2016) Aims: -To report results of ongoing Babesia clinical trial -To explain significance of Babesia as a TT infection Methods: In cobas â Babesia for use on the cobas â 6800/8800 Systems, is a qualitative polymerase chain reaction nucleic acid amplification test, developed to detect in whole blood (WB) donor samples the 4 Babesia species that cause human disease: B. In sensitivity analyses, there were two discrepant results for HIV testing, three for HCV, and five for anti-HBc. Summary/Conclusions: Elecsys â infectious disease parameters on the cobas e 801 analyser demonstrate high specificity/sensitivity for screening first-time blood donor samples, with similar clinical performance to other commercially available assays. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169345/ doi: 10.1111/vox.12792 id: cord-010119-t1x9gknd author: nan title: Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017 date: 2017-09-04 words: 230193.0 sentences: 13234.0 pages: flesch: 55.0 cache: ./cache/cord-010119-t1x9gknd.txt txt: ./txt/cord-010119-t1x9gknd.txt summary: Conclusion: The wide distribution in the concentration of bioactive lipids among 405 stored RBC units suggests that lipid degradation is highly donor-Background/Case Studies: To ensure availability of biological products to hospitals, blood banks have developed and validated multiple storage conditions for each of their products to maximize shelf life and quality. 1 The Department of Blood Transfusion, The PLA General Hospital, 2 The Department of Blood Transfusion, Air Force General Hospital, PLA Background/Case Studies: Recently, multi researches have reported that longer term-stored red blood cells(RBCs) units were associated with increased risks of clinically adverse events, especially in critically ill patients. Weak D types 1, 2 and 3 express all the major RhD epitopes and these patients can be managed as RhD-positive, which may lead to a reduction in unnecessary Rh immunoglobulin (RhIG) administration and conservation of RhD-negative RBCs. Study Design/Method: RHD genotyping was performed on all patient samples with weaker than expected or discrepant RhD typing results, utilizing a commercially available genotyping kit manufactured by Immucor (RHD BeadChip). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169716/ doi: 10.1111/trf.14286 id: cord-014368-4nasrbs6 author: nan title: Gene Chip for Viral Discovery date: 2003-11-17 words: 10009.0 sentences: 438.0 pages: flesch: 49.0 cache: ./cache/cord-014368-4nasrbs6.txt txt: ./txt/cord-014368-4nasrbs6.txt summary: As they report in this paper, Miguel Nicolelis and colleagues have helped clarify some of the fundamental issues surrounding the programming and use of BMIs. Presenting results from a series of long-term studies in monkeys, they demonstrate that the same set of brain cells can control two distinct movements, the reaching and grasping of a robotic arm. RAG genes regulate the genetic recombination and ultimate cell surface expression of TCRs. Using chemical inhibitors and mutant human T cell lines deficient in critical signaling components involved in antigen receptor-dependent pathways, the researchers found that the loss of specific functions or specific proteins affected an unexpected set of target genes. But these studies also establish a model for investigating other signaling systems, to determine whether biologically functional basal signaling is a rare phenomenon or whether it is a fundamental cell process needed to control the profile of gene expression in the quiescent state. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC261871/ doi: 10.1371/journal.pbio.0000003 id: cord-014462-11ggaqf1 author: nan title: Abstracts of the Papers Presented in the XIX National Conference of Indian Virological Society, “Recent Trends in Viral Disease Problems and Management”, on 18–20 March, 2010, at S.V. University, Tirupati, Andhra Pradesh date: 2011-04-21 words: 35453.0 sentences: 1711.0 pages: flesch: 49.0 cache: ./cache/cord-014462-11ggaqf1.txt txt: ./txt/cord-014462-11ggaqf1.txt summary: Molecular diagnosis based on reverse transcription (RT)-PCR s.a. one step or nested PCR, nucleic acid sequence based amplification (NASBA), or real time RT-PCR, has gradually replaced the virus isolation method as the new standard for the detection of dengue virus in acute phase serum samples. Non-genetic methods of management of these diseases include quarantine measures, eradication of infected plants and weed hosts, crop rotation, use of certified virus-free seed or planting stock and use of pesticides to control insect vector populations implicated in transmission of viruses. The results of this study indicate that NS1 antigen based ELISA test can be an useful tool to detect the dengue virus infection in patients during the early acute phase of disease since appearance of IgM antibodies usually occur after fifth day of the infection. The studies showed high level of expression in case of constructed vector as compared to infected virus for the specific protein. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3639731/ doi: 10.1007/s13337-011-0027-2 id: cord-014597-66vd2mdu author: nan title: Abstracts from the 25th European Society for Animal Cell Technology Meeting: Cell Technologies for Innovative Therapies: Lausanne, Switzerland. 14-17 May 2017 date: 2018-03-15 words: 50613.0 sentences: 2624.0 pages: flesch: 46.0 cache: ./cache/cord-014597-66vd2mdu.txt txt: ./txt/cord-014597-66vd2mdu.txt summary: Irrespective of the cell culture-based system and production scale, PEIpro® and PEIpro®-HQ have led to efficient viral vector yields superior to 10 7 IG/mL and 10 9 VG/mL, respectively for lentiviruses and AAVs Background Continuous perfusion process is making a comeback as a competing upstream manufacturing technology for the production of Biopharmaceuticals compared to the standard fed batch processes. To evaluate the impact of feed-spiking compared with cultivation in basal medium only, the cell line was grown in bioreactors under controlled conditions to determine cellspecific metabolic rates, nutrient consumption, and byproduct accumulation over the process time. Through the interchangeability of signal peptides between products and even species, a large variety can be used to enhance protein expression in already existing production systems Materials and methods At first the influence of four different natural SPs (SP (7), (8), (9) and (10)) was compared on the secreted amount of an IgG4 model antibody (product A) in fed batches using a CHO DG44 host cell line. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861492/ doi: 10.1186/s12919-018-0097-x id: cord-014674-ey29970v author: nan title: Dreizehnter Bericht nach Inkrafttreten des Gentechnikgesetzes (GenTG) für den Zeitraum vom 1.1.2002 bis 31.12.2002 : Die Arbeit der Zentralen Kommission für die Biologische Sicherheit (ZKBS) im Jahr 2002 date: 2003 words: 2522.0 sentences: 181.0 pages: flesch: 62.0 cache: ./cache/cord-014674-ey29970v.txt txt: ./txt/cord-014674-ey29970v.txt summary: title: Dreizehnter Bericht nach Inkrafttreten des Gentechnikgesetzes (GenTG) für den Zeitraum vom 1.1.2002 bis 31.12.2002 : Die Arbeit der Zentralen Kommission für die Biologische Sicherheit (ZKBS) im Jahr 2002 We have closely examined the experimental data and the analyses of the nucleotide sequences presented in the report.We find that aside from problematic details of the experimental design and some erratic presentations of the data the results of the study do not provide evidence for the introgression of recombinant DNA from transgenic crop plants into the genomes of ''criollo'' maize. 3. We characterized with the help of BLAST searches those parts of the sequences of the iPCR amplification products that were denoted by Quist and Chapela in their Fig.2 as regions flanking the CMV p-35S sequence.We find that the sequence of AF434754 denoted adh1 in the K1 source of Fig. 2 does not match with the maize adh1 gene. We examined whether the identified regions in the maize genomic DNA from which PCR amplification products were obtained by the authors would perhaps be flanked by primer binding sites. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079883/ doi: 10.1007/s00103-003-0614-5 id: cord-014685-ihh30q6f author: nan title: Posters P788 - P999 date: 2005-09-21 words: 38354.0 sentences: 1784.0 pages: flesch: 45.0 cache: ./cache/cord-014685-ihh30q6f.txt txt: ./txt/cord-014685-ihh30q6f.txt summary: This study has attempted to analyse the structural properties of membrane peptides and proteins through the use of model systems that have been designed to mimic their natural counterparts: Podlubnaya 2 1 Institute of Theoretical and Experimental Biophysics RAS, 2 Pushchino State University Amyloid brils are formed by proteins or their peptides in the result of a conformational transition from alpha helix into beta-sheet structure. Analysis of the results of such studies indicate that folding of SNase fragments is dominated by developing the local and non-local nucleation sites from native-like secondary structures and by intensifying the longrange interactions of residues at nucleation sites with residues further removed in sequence. The results show that at different pH values the aggregation processes of both proteins follow different pathways determined by the variations in the native structure and by the details of the involved conformational changes. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080055/ doi: 10.1007/s00249-005-0504-x id: cord-014712-5u4e00q6 author: nan title: Selected Abstracts from the 100th J Project Meeting, Antalya, Turkey, March 12-14, 2014 date: 2014-08-02 words: 36900.0 sentences: 2254.0 pages: flesch: 49.0 cache: ./cache/cord-014712-5u4e00q6.txt txt: ./txt/cord-014712-5u4e00q6.txt summary: Ege University Faculty of Medicine, Dept of Pediatric Immunology, Izmir, Turkey Ig class switch recombination deficiencies are rare PIDs (1:500,000 births) with normal or elevated serum IgM and low IgG, IgA and IgE levels, defective or normal somatic hypermutation, defective T/B cooperation (50%), intrinsic B cell defect (50%), susceptibility to bacterial infections begining from the first year of age (impaired B cell immunity) and lack of germinal centres in secondary lymphoid organs. Great North Children''s Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, and Primary Immunodeficiency Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK Even following the introduction of biologic disease modifying antirheumatic drugs (DMARDs), a small number of children suffering from severe, refractory autoimmune (AI), rheumatic and/or autoinflammatory disorders will not get into clinical remission (CR) and will potentially further suffer from multiple side-effects of combined and long-term immunosuppressive and anti-inflammatory therapies, in particular severe infections (Marodi L, Casanova JL. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086544/ doi: 10.1007/s10875-014-0065-9 id: cord-014794-yppi30a0 author: nan title: 19th European Congress of Pathology, Ljubljana, Slovenia, September 6-11, 2003 date: 2003-07-31 words: 158059.0 sentences: 9041.0 pages: flesch: 44.0 cache: ./cache/cord-014794-yppi30a0.txt txt: ./txt/cord-014794-yppi30a0.txt summary: These parts were in a high percentage associated with fibrosis and lymphocyte rich areas and showed a higher mitotic activity than usual PTCs. Discussion The differences in the occurrence of TCV and TCmorphology between the presented series and previously reported cases might result from until now not clearly defined tall cell morphology as well as from similarities to PTCs, such as the oxyphilic variant, which is extremely rare in our series, and maybe also from often described squamous changes within PTCs. Due to these data it is not clear which tumor parts have relevance for prognosis and which tumors should be treated more aggressively than others. The aims of this study were to characterize the group of patients with BSOT and evaluate the significance of various molecular markers expression versus serous papillary ovarian carcinomas (SPOC) Material and methods We analyzed a total of 102 cases including: 64 cystadenoma, 10 borderline and 28 cystadenocarcinoma. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087991/ doi: 10.1007/s00428-003-0864-5 id: cord-014875-xhzxhwgo author: nan title: Book Reviews date: 2003 words: 7144.0 sentences: 338.0 pages: flesch: 46.0 cache: ./cache/cord-014875-xhzxhwgo.txt txt: ./txt/cord-014875-xhzxhwgo.txt summary: The last chapter in the second focused area is by Pumpens and Grens, who provide an in-depth discussion of the use of viral vectors for delivering a desirable gene into target cells for protein production. The chapters don''t cover material in great depth (and if they did, this book will be many times larger) but they provide enough information to cover what someone new to the area would need to know to get started. As described above, this book does not intend to summarize transporters related to drugs rather tried to introduce many technologies to be used in future studies for molecular cloning, structure, functionality, regulation, and sorting in various point of views by using typical experimental results on physiologically important transporter molecules. Each chapter provides a polymer-based step-bystep description of not only basic information including various classification, application, and structure-property relationships, but also very practical descriptions of synthetic and analytic techniques that are believed to be good references in research laboratories. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089263/ doi: 10.1023/b:pham.0000008097.92834.f4 id: cord-015348-qt0worsl author: nan title: Abstract date: 2010-07-30 words: 74085.0 sentences: 4714.0 pages: flesch: 45.0 cache: ./cache/cord-015348-qt0worsl.txt txt: ./txt/cord-015348-qt0worsl.txt summary: However, the application of the compounds in clinical trials has revealed promising results only when predictive procedures have been available for determining which patients will benefit from targeting therapy, so-called eligibility or predictive tests, e.g. Her2 in breast cancer, KRAS and EGFR mutations in colorectal cancer and non-small cell lung cancer. Conclusion: We report on the development of a quantitative tissue-based immunohistochemical (IHC) methodology employing activation-specific antibodies against multiple components of the BCR signaling pathway that will assess the activity of the BCR pathway in formalin-fixed paraffinembedded primary DLBCLs. This approach will identify the subset of patient tumors that are actively signaling through the BCR pathway and, therefore, will predict therapeutic responsiveness to targeted inhibition of BCR signaling. Method: In our study, we investigate 120 cases diagnosed with invasive breast carcinoma in which we established microscopic characterization, immunohistochemical profiles (expression of proliferation markers, steroid receptors and Her2) and computer-assisted morphometric profiles by determining the mean values for nuclear area, cellular area and N/C ratio with Lucia Net Software. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102354/ doi: 10.1007/s00428-010-0947-z id: cord-015368-a0qz4tb9 author: nan title: 48th Annual Meeting of the Austrian Society of Surgery, Graz, June 7–9, 2007 date: 2007 words: 86620.0 sentences: 6042.0 pages: flesch: 51.0 cache: ./cache/cord-015368-a0qz4tb9.txt txt: ./txt/cord-015368-a0qz4tb9.txt summary: Surgical treatment and evaluation, complications, short and long term patency of our patients were compared to interventional techniques and international literature. The aim of the study was to investigate: i) relevant and combined determinants of the development, management and outcome of a representative patient cohort (n ¼ 9.991) with acute appendicitis enrolled in a prospective unicenter study through a time period of 27 years (middle Europe), and ii) the frequency and impact of specific categories (e.g., characteristics of the medical history, clinical and intraoperative findings, complications), correlation and relative risk factors of the disease and its prognosis. From 01=1997 until 12=2006 198 TEM procedures were performed in 194 patients, 104 males, 90 females, mean age was 68.9 years (38-91), the median hospital stay was 8 days . No conversion to open technique had to be performed, no postoperative surgical complications were observed, one patient died 4 weeks postoperative due to liver failure following esophageal varices bleeding. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103188/ doi: 10.1007/s10353-007-0330-8 id: cord-015394-uj7fe5y6 author: nan title: Scientific Abstracts date: 2008-12-23 words: 242330.0 sentences: 15267.0 pages: flesch: 52.0 cache: ./cache/cord-015394-uj7fe5y6.txt txt: ./txt/cord-015394-uj7fe5y6.txt summary: Studies involving immunohistochemical analysis of normal ovaries have shown that granulosa cells express significantly higher levels of the activator protein-1 (AP-1) transcription factor, cFos compared to theca cells, where cFos expression is virtually absent. Following acute hypoxia (0.5% O2) for one to six hours, RhoA mRNA, total protein and activation (RhoA-GTP) levels were analysed, using semi-quantitative PCRs and western blot, and compared to normoxic non-pregnant human uterine smooth muscle control cells. Since there is an urgent need for non-invasive methods for determination of fetal (F) and placental (P) function, this study was designed to evaluate the genes differently and commonly expressed in P tissue and leukocytes in maternal (M) and F circulation.Material and Methods. The current study: 1) localized IL-6 mRNA levels in preeclamptic versus normal decidual sections; 2) evaluated mechanisms regulating IL-6 synthesis by targeting intracellular signaling pathways with specific inhibitors; 3) identified potential IL-6 targets by immunolocalizing the IL-6 receptor (IL-6R) to specific cell types in placental bed biopsies. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104449/ doi: 10.1177/19337191080150020102 id: cord-015619-msicix98 author: nan title: Virus Structure & Assembly date: 2009-02-24 words: 3302.0 sentences: 164.0 pages: flesch: 45.0 cache: ./cache/cord-015619-msicix98.txt txt: ./txt/cord-015619-msicix98.txt summary: The studies were performed with nanoindentation techniques using an Atomic Force Microscope (AFM), an approach which is becoming a standard method to measure the mechanical properties of viral particles (1, 2) . Using molecular dynamics simulations of the connector in complex with DNA, and aiming at distinguishing between these three models, we calculated mechanical properties of this system. The bacteriophage lambda is composed of an icosahedral capsid, into which a 48.5 kbp double-stranded DNA genome is packaged, and a long non-contractile tail consisting of 34 disk-like structures. The relative probabilities of fusion and endocytosis of a virus particle initially nonspecifically adsorbed on the host cell membrane are computed as functions of receptor concentration, binding strength, and number of spikes. As revealed by techniques of structural biology and single-molecule experimentation, the capsids of viruses are some of nature''s best examples of highly symmetric multiscale self-assembled structures with impressive mechanical properties of strength and elasticity. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111173/ doi: 10.1016/s0006-3495(08)79065-9 id: cord-016751-g46gs087 author: nan title: DNA, RNA und IHRE Amplifikation date: 2009-12-24 words: 3437.0 sentences: 491.0 pages: flesch: 63.0 cache: ./cache/cord-016751-g46gs087.txt txt: ./txt/cord-016751-g46gs087.txt summary: Die lange Suche nach dem Träger der Vererbung kulminierte ein erstes Mal 1944, als Avery, MacLeod und McCarty am Rockefeller Institut eindeutig nachweisen konnten, dass die bakterielle Erbinformation in hochgereinigter DNA, nicht aber in Proteinfraktionen, enthalten ist. Indem man diese Abstammungslinien zurückverfolgt, kann man sich ein Bild darüber machen, wie sich kleine Volksstämme des modernen Menschen in Afrika vor Zehntausenden von Jahren auseinanderentwickelt und in die ganze Welt ausgebreitet haben. Ihre Angehörigen haben sich vielleicht dem Clan des Mittleren Ostens (mit dem Marker M89) angeschlossen, als sie den Herden der großen Säugetiere nach Norden durch die Grasländer und Savannen des Sahara-Korridors folgten. Für einen Afro-Amerikaner aus der Haplogruppe L2 -wahrscheinlich ein Nachkomme von Westafrikanern, die im Zuge des Sklavenhandels nach Amerika gelangten -kann man nicht mit Sicherheit sagen, wo genau in Afrika die Linie entstanden ist. abstract: DNA heißt die magische Helix des Lebens — der materielle Träger der Erbsubstanz, die Desoxyribonucleinsäure (DNA, deoxyribonucleic acid) (siehe Box 6.1). url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121128/ doi: 10.1007/978-3-8274-2156-2_6 id: cord-017752-ofzm3x3a author: nan title: Theories of Carcinogenesis date: 2007 words: 12289.0 sentences: 692.0 pages: flesch: 47.0 cache: ./cache/cord-017752-ofzm3x3a.txt txt: ./txt/cord-017752-ofzm3x3a.txt summary: Others attributed the simplified enzyme patterns of cancerous cells to a regression of the tumor tissues to early embryonal stages of development. Viral DNA is frequently integrated into the cancer cells, but additional agents or factors may be involved at various stages of the progression to invasive carcinoma. The encounter with a family, in which many members developed breast or liver cancer, led Pierre Paul Broca to hypothesize, in 1866, that an inherited abnormality within the affected tissue caused the tumor development [Broca 1866 Theodor Boveri (1862 Boveri ( -1915 then proposed that defects in chromosomes lead to malignancy [Boveri 1914 ]. Any mutation of cancer associated genes can be handed on to following generations and predispose the affected cells to malignant transformation in the case of additional DNA damage. Further developments in tumor immunology have led to models of selection and evolution of cancer cells. abstract: The oldest description of human cancer, referring to eight cases of tumors of the breast, was found in the Egyptian Edwin Smith Papyrus, written around 3000–1500 BC. The oldest specimens of human cancers were detected in the remains of a female skull dating back to the Bronze Age (1900–1600 BC), and in fossilized bones of ancient Egypt. The mummified skeletal remains of Peruvian Incas, dating about 2,400 years ago, contained lesions suggestive of malignant melanoma. The term “cancer” goes back to Hippocrates (460–370 BC), who named a group of diseases καρκινοσ and καρκινομα, the ancient Greek word for crab. It is a metaphor for the hard center and spiny projections of the tumors he studied. Cancer is the Latin word for crab and its use has been traced back to Galen (AD 129–199). A snapshot of theories of carcinogenesis, devised in the course of the last two centuries, reflects the progress of insight from the cellular level via biochemistry to an understanding of damaging influences and oncogenes, and to a more wholistic approach in the regulatory theory. It shows the relative success of reductionism as well as the current need to put the insights of various research endeavors into broader paradigmatic contexts. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122402/ doi: 10.1007/978-1-4020-6016-8_1 id: cord-020010-q58x6xb0 author: nan title: 19th ICAR Abstracts: date: 2006-03-13 words: 46663.0 sentences: 2181.0 pages: flesch: 44.0 cache: ./cache/cord-020010-q58x6xb0.txt txt: ./txt/cord-020010-q58x6xb0.txt summary: In the present study we reported the antiviral activity of neuraminidase inhibitor oseltamivir against lethal H5N1 influenza virus infection in ferrets, an appropriate animal model that closely resembles clinical signs of human influenza. Earl Kern 1 , Kathy Keith 2 , Robert Jordan 2 , Dennis Hruby 2 , Debra Quenelle 2 1 Department of Pediatrics, University of Alabama School of Medicine, Birmingham, AL, USA; 2 SIGA Technologies, Inc., Corvallis, OR, USA Although cidofovir (CDV) has been approved as an investigational new drug for emergency treatment of smallpox, its lack of oral activity and dose limiting toxicity dictates a need for continued development of better therapeutic agents for this potential bioterror disease. The in vitro antiviral activity of one of the most selective compounds, i.e. CHI-033, was assessed by (i) MTS-based cytopathic effect assays, (ii) virus yield reduction assays, (iii) real-time quantitative PCR (RT-QPCR) and (iv) by monitoring viral antigen expression. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133865/ doi: 10.1016/j.antiviral.2006.02.001 id: cord-020235-stcrozdw author: nan title: Abstracts of Papers Presented at the 38th Meeting of the Deutsche Gesellschaft für Hygiene und Mikrobiologie, Virology Section, Göttingen, 5.–8.10.1981 date: 2012-03-15 words: 13494.0 sentences: 843.0 pages: flesch: 58.0 cache: ./cache/cord-020235-stcrozdw.txt txt: ./txt/cord-020235-stcrozdw.txt summary: Hepatitis A virus (HAV) was isolated directly from human stool in diploid human fibroplasrs, Viral antigen was expressed only after 210 days of incubation of the infected cultures. Univ., 0-8700 Wiirzburg Effect of Measles (SSPE) Antiserum on Viral Surface Proteins and Hormone Receptor Activity in C6/SSPE Persistently Infected Cells BARRETT, P. Inst, of Genetics, Univ., 0-5000 Co logne Virus-Cell DNA Recombinants in Human Cells Lytically Infected by Ad2 NEUMANN, R., WEYER, U., and DOERFLER, W. In vitro, however, the gag-specific peptide sequences are cleaved off upon addition of the purified viral piS protease; in the case of the replication-defective, transforming avian sarcoma virus PRC II the cleaved nongag part has a ryrosine-phosphorylaring kinase activity similar to that described for the RSV src-gene product pp60 src . f. Virologie, Univ., D·6300 Giefen, 3 A protein of a molecular weight of about 38.000 d has been found to be phosphorylated 1 h after the onset of cell transformation by Rous sarcoma virus (RSV). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134445/ doi: 10.1016/s0174-3031(82)80128-5 id: cord-022476-g826uiqx author: nan title: Eosinophils and Anti-Pathogen Host Defense date: 2012-10-12 words: 12501.0 sentences: 638.0 pages: flesch: 36.0 cache: ./cache/cord-022476-g826uiqx.txt txt: ./txt/cord-022476-g826uiqx.txt summary: Similarly, although the weight of evidence suggests that eosinophils contribute to the pathophysiology of allergy and asthma, a chronic respiratory disease in which bronchoconstriction in response to environmental triggers is typically associated with production of T h 2 cytokines and recruitment of eosinophils to the airways, asthmatic responses are obviously negative sequelae of eosinophil function that alone cannot represent a direct evolutionary advantage to the host organism. Although respiratory virus infections are not among the diseases typically associated with T h 2 lymphocyte activation and profound pulmonary eosinophilia, eosinophils and/or eosinophil granule secretory proteins have been detected in lung washings or systemically in infants in need of supplemental oxygen secondary to severe RSV infection. 55 A number of studies suggest potential detrimental roles for eosinophils and fungi in T h 2-mediated airway diseases, such as allergic bronchopulmonary aspergillosis (ABPA), severe asthma associated with fungal sensitivity (SAFS), and CRS. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156009/ doi: 10.1016/b978-0-12-394385-9.00009-2 id: cord-022501-9wnmdvg5 author: nan title: P1460 – P1884 date: 2015-12-28 words: 128256.0 sentences: 7808.0 pages: flesch: 51.0 cache: ./cache/cord-022501-9wnmdvg5.txt txt: ./txt/cord-022501-9wnmdvg5.txt summary: Methods: Using published data on (1) the prevalence of MRSA and other bacterial pathogens causing cSSSI in the US, (2) the in-vitro susceptibility rates of commonly used regimens in cSSSI in the US in relation to the most pervasive pathogens identified above, and (3) estimated costs of failure of initial, empiric treatment from a recent study of a large US multi-hospital database, we developed a model to predict the expected clinical and economic impact of increasing prevalence of MRSA. Small outbreaks of VEB-1 ESBL producing Acinetobacter baumannii in Belgian nursing homes and hospitals through cross-border transfer of patients from northern France Methods: From 01/04 to 03/05, all Belgian acute hospitals were invited to report cases of nosocomial infections/colonisations due to MDR Ab isolates presenting a resistance profile similar to the French epidemic strain (resistance to all agents except carbapenems and colistin) and to send such isolates to the reference laboratory for phenotypic confirmation and for genotypic characterization (PCR of VEB-1 and class 1 Integron, PFGE typing). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157935/ doi: 10.1111/j.1470-9465.2006.12_4_1431.x id: cord-022888-dnsdg04n author: nan title: Poster Sessions date: 2009-08-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: No Abtract url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163517/ doi: 10.1002/eji.200990224 id: cord-022940-atbjwpo5 author: nan title: Poster Sessions date: 2016-09-07 words: 241182.0 sentences: 12746.0 pages: flesch: 47.0 cache: ./cache/cord-022940-atbjwpo5.txt txt: ./txt/cord-022940-atbjwpo5.txt summary: We have studied the effect of inhibition of IRE1 (inositol requiring enzyme 1), which is a central mediator of endoplasmic reticulum stress and controls cell proliferation and tumor growth, on hypoxic regulation of the expression of different proliferation related genes in U87 glioma cells. Transient inhibition of Akt and mTOR protein kinase activation in tumor cells followed by reactivation of signaling pathway did not result in a time-dependent difference on EGFR, HER2 and HER3 expression levels. In our study we aimed to determine cytotoxic effect of RES in K562 human CML cell line and to evaluate the expressions of miRNAs that are associated with genetics of leukemia after treatment with RES; to investigate target genes of miRNAs which show significant expression alterations and molecular mechanisms of RES treatment. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164006/ doi: 10.1111/febs.13808 id: cord-023055-ntbvmssh author: nan title: Immunogenicity date: 2004-02-19 words: 64563.0 sentences: 3952.0 pages: flesch: 59.0 cache: ./cache/cord-023055-ntbvmssh.txt txt: ./txt/cord-023055-ntbvmssh.txt summary: Antigen is internalized into acidic vesicles, proteolyzed, and peptides containing T ceU antigenic determinants are transported to the APC surface where they are recognized by the antigen-specific T cell in conjunction with Ia. Most Ia-"pressing cells are competent APC, however, only B cells have antigen-specilic receptors on their surface aUowing bound antigen to be processed and presented at 1/lW the antigen concentration required by nonspecific APC Little is known about B cell antigen processing function during differentiation, or if Ig-mediated APC function is altered at different maturational stages, thus allowing regulation of B cell-helper T cell interactions. These results indicate that the poor response of murine CTL to human class I antigens is not determined by selection in the thymus, but by species-specific constraints on the interaction of MHC antigens with T-cell recognition structures. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166418/ doi: 10.1002/jcb.240410506 id: cord-023095-4dannjjm author: nan title: Research Abstract Program of the 2011 ACVIM Forum Denver, Colorado, June 15–18, 2011 date: 2011-05-03 words: 134226.0 sentences: 6834.0 pages: flesch: 51.0 cache: ./cache/cord-023095-4dannjjm.txt txt: ./txt/cord-023095-4dannjjm.txt summary: The purpose of this study was to determine the short-term effects of ivabradine on heart rate (HR), blood pressure, left ventricular (LV) systolic and diastolic function, left atrial (LA) performance, and clinical tolerance in healthy cats after repeated oral doses. The goal of this study was to investigate the relationship between heart rate and ECG time intervals to body mass in apparently healthy horses and ponies and to calculate normal ranges for different weight groups. This study aimed to investigate the prevalence of hypercoagulability in PLN dogs based on thromboelastography (TEG), and to determine whether hypercoagulability in these patients could be predicted by clinical assessments that identify systemic hypertension (systolic blood pressure 4 160 mmHg), hypoalbuminemia (serum albumin o 2.7 mg/dl), antithrombin activity (o 70%), and degree of proteinuria (urine protein:creatinine ratio [UPC] ! abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166756/ doi: 10.1111/j.1939-1676.2011.0726.x id: cord-023120-jcgf2401 author: nan title: Animal virus genetics date: 2004-06-18 words: 17801.0 sentences: 1474.0 pages: flesch: 67.0 cache: ./cache/cord-023120-jcgf2401.txt txt: ./txt/cord-023120-jcgf2401.txt summary: We suggest that, (1) c regions contain promotors for viral RNA synthesis, (2) cx contains a more efficient promotor than c" and (3) non-acute disease foliows the formation of critical viral-cell recombinants in which ( 2 ) The r e s u l t i n g CDNA i s f r a c t i o n a t e d and a l l fragments having a length g r e a t e r than 300 nucleotides are i s o l a t e d and c u t with a r e s t r i c t i o n endonuclease capable of d i g e s t i n g single-stranded DNA. Studies of the synthesis and processing of viral proteins in simian sarcoma associated virus (SSAV)infected and SSV(SSAV)transformed marmoset and human cell lines has demonstrated polyprotein precursors precipitable by anti-SSAV p30 and anti-SSAV gp70. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166955/ doi: 10.1002/jss.400140505 id: cord-023208-w99gc5nx author: nan title: Poster Presentation Abstracts date: 2006-09-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167816/ doi: 10.1002/psc.797 id: cord-023209-un2ysc2v author: nan title: Poster Presentations date: 2008-10-07 words: 111878.0 sentences: 5398.0 pages: flesch: 45.0 cache: ./cache/cord-023209-un2ysc2v.txt txt: ./txt/cord-023209-un2ysc2v.txt summary: Site-specifi c PEGylation of human IgG1-Fab using a rationally designed trypsin variant In the present contribution we report on a novel, highly selective biocatalytic method enabling C-terminal modifi cations of proteins with artifi cial functionalities under native state conditions. Recently, our group report a novel approach to a totally synthetic vaccine which consists of FMDV (Foot and Mouth Disease Virus) VP1 peptides, prepared by covalent conjugation of peptide biomolecules with membrane active carbochain polyelectrolytes In the present study, peptide epitops of VP1 protein both 135-161(P1) amino acid residues (Ser-Lys-Tyr-Ser-Thr-Thr-Gly-Glu-Arg-Thr-Arg-Thr-Arg-Gly-Asp-Leu-Gly-Ala-Leu-Ala-Ala-Arg-Val-Ala-Thr-Gln-Leu-Pro-Ala) and triptophan (Trp) containing on the N terminus 135-161 amino acid residues (Trp-135-161) (P2) were synthesized by using the microwave assisted solid-phase methods. Using as a template a peptide, already identifi ed, with agonist activity against PTPRJ(H-[Cys-His-His-Asn-Leu-Thr-His-Ala-Cys]-OH), here we report a structure-activity study carried out through endocyclic modifi cations (Ala-scan, D-substitutions, single residue deletions, substitutions of the disulfi de bridge) and the preliminary biological results of this set of compounds. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167823/ doi: 10.1002/psc.1090 id: cord-023211-kt5gt26t author: nan title: Poster Session Abstracts date: 2007-08-29 words: 221224.0 sentences: 11772.0 pages: flesch: 52.0 cache: ./cache/cord-023211-kt5gt26t.txt txt: ./txt/cord-023211-kt5gt26t.txt summary: Previous studies performed using fluorescence halide efflux measurements and short-circuit current voltage clamp have shown that treatment with PPARγ (peroxisome proliferator activated receptor gamma) agonists, such as pioglitazone and FLL (FMOC-L-leucine), resulted in an increased biosynthesis and trafficking of ∆F508-CFTR to the cell surface. Physiology, School of Medical Sciences, University of Bristol, Bristol, United Kingdom Recent progress in the development of small molecule correctors and potentiators capable of restoring CFTR function have increased the need for pre-clinical test models including cultured airway epithelial cells from human CF patients as well as CF mouse models. Clinical studies have linked increased sputum and peripheral blood neutrophil MPO activity with increased airflow obstruction in cystic fibrosis (CF) patients of the same age, gender, airway bacterial flora, and CFTR genotype. Because patients expressing low levels of normal CFTR mRNA (5-20%) have mild disease symptoms, these studies demonstrate that the incorporation of the ciliated cell-specific FOXJ1 promoter into gene therapy vectors may be useful for treatment of CF. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167830/ doi: 10.1002/ppul.20700 id: cord-023225-5quigar4 author: nan title: Posters date: 2012-08-21 words: 70251.0 sentences: 3367.0 pages: flesch: 43.0 cache: ./cache/cord-023225-5quigar4.txt txt: ./txt/cord-023225-5quigar4.txt summary: To further explore the structure-function relationship, a viable synthesis strategy for pseudodesmin A analogues was developed, based on side-chain attachment of the first amino acid to the solid support, followed by stepwise Fmoc solid-phase synthesis of the linear peptide precursor and on-resin head-to-tail cyclization. The cases when the amino acid sequence of a fragment coincided with part of the primary structure of a natural oligopeptide were recorded in the Total protein chemical synthesis requires a case by case design and optimization which is governed by factors such as the solubility of the individual peptide segments, their primary sequence and in particular the presence of "difficult" amino acid residues at ligation junctions such as proline or the location of cysteines. In this study we present synthesis of two series of peptide libraries, which were designed by substitution of Leu in the P5, P6 position of our control peptide (Ac-LLLLRVKR-AMBA) with each of nineteen amino acid residues in order to verifying its influence on activity and selectivity of the resulting analogues. abstract: No abstract is available for this article. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167970/ doi: 10.1002/psc.2449 id: cord-023346-8sqbqjm1 author: nan title: MONDAY: POSTERS date: 2005-06-08 words: 130043.0 sentences: 7330.0 pages: flesch: 54.0 cache: ./cache/cord-023346-8sqbqjm1.txt txt: ./txt/cord-023346-8sqbqjm1.txt summary: • enhancement of automation/computerisation; • process control to provide an ''error-free pathway''; • (national) surveillance and trend analysis of results, preferably based on national working standards; • significantly increased sensitivity, especially from development of antigen/antibody ''combi'' assays (e.g. for HIV, and recently, for HCV); • awareness of HBsAg vaccine-escape mutants and design of assays to cope with this; • extension of range of agents and markers tested for (varies in different countries); • increasing range of assays available for testing donors with a relevant history of exposure to malaria or Chagas'' disease infection (for retrieval of otherwise wasted blood); • European Union''s in vitro diagnostics directive: this has caused some problems and reduced flexibility. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169255/ doi: 10.1111/j.1423-0410.2005.00652.x id: cord-023354-f2ciho6o author: nan title: TUESDAY PLENARY SESSION 3 TUESDAY: POSTERS date: 2005-06-08 words: 130046.0 sentences: 7333.0 pages: flesch: 54.0 cache: ./cache/cord-023354-f2ciho6o.txt txt: ./txt/cord-023354-f2ciho6o.txt summary: • enhancement of automation/computerisation; • process control to provide an ''error-free pathway''; • (national) surveillance and trend analysis of results, preferably based on national working standards; • significantly increased sensitivity, especially from development of antigen/antibody ''combi'' assays (e.g. for HIV, and recently, for HCV); • awareness of HBsAg vaccine-escape mutants and design of assays to cope with this; • extension of range of agents and markers tested for (varies in different countries); • increasing range of assays available for testing donors with a relevant history of exposure to malaria or Chagas'' disease infection (for retrieval of otherwise wasted blood); • European Union''s in vitro diagnostics directive: this has caused some problems and reduced flexibility. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169300/ doi: 10.1111/j.1423-0410.2005.00654.x id: cord-023364-ut56gczm author: nan title: EDUCATION DAY MONDAY: PLENARY SESSION 1 MONDAY: PARALLEL SESSIONS date: 2005-06-08 words: 130049.0 sentences: 7334.0 pages: flesch: 54.0 cache: ./cache/cord-023364-ut56gczm.txt txt: ./txt/cord-023364-ut56gczm.txt summary: • enhancement of automation/computerisation; • process control to provide an ''error-free pathway''; • (national) surveillance and trend analysis of results, preferably based on national working standards; • significantly increased sensitivity, especially from development of antigen/antibody ''combi'' assays (e.g. for HIV, and recently, for HCV); • awareness of HBsAg vaccine-escape mutants and design of assays to cope with this; • extension of range of agents and markers tested for (varies in different countries); • increasing range of assays available for testing donors with a relevant history of exposure to malaria or Chagas'' disease infection (for retrieval of otherwise wasted blood); • European Union''s in vitro diagnostics directive: this has caused some problems and reduced flexibility. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169338/ doi: 10.1111/j.1423-0410.2005.00651.x id: cord-023592-w96h4rir author: nan title: Abstracts cont. date: 2015-12-28 words: 67857.0 sentences: 4136.0 pages: flesch: 52.0 cache: ./cache/cord-023592-w96h4rir.txt txt: ./txt/cord-023592-w96h4rir.txt summary: Conclusions: Although the risk of developing more serious gastric lesions increased as the number of virulence factor genes are accumulated in a given Hp strain, we did not find any significant differences or relationship in the cagA, vacA or babA2 status between the Hp isolates from patients with gastritis or peptic ulcer in this study. pneumophila at the serogroup level, it was used in two different outbreaks to demonstrate rapidly the identity of the sequences between strains responsible for severe human infection and those isolated in the hot water reservoir, suggesting a common origin. To determine the antimicrobial resistance in Salmonella and Shigella strains isolated from stool specimens during a 2-year period, from patients admitted to our clinics with a diagnosis of diarrhoea. In our study the susceptibility of 65 bacterial strains isolated in hospital environment (colonising or infecting patients or carried by German cockroaches) to antibiotics and chemical disinfectants was determined. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172567/ doi: 10.1111/j.1469-0691.2004.0902c.x id: cord-024058-afgvztwo author: nan title: Engineering a Global Response to Infectious Diseases: This paper presents a more robust, adaptable, and scalable engineering infrastructure to improve the capability to respond to infectious diseases.Contributed Paper date: 2015-02-17 words: 5592.0 sentences: 294.0 pages: flesch: 38.0 cache: ./cache/cord-024058-afgvztwo.txt txt: ./txt/cord-024058-afgvztwo.txt summary: Examples of innovative leveraging of infrastructure, technologies to enhance existing disease management strategies, engineering approaches to accelerate the rate of discovery and application of scientific, clinical, and public health information, and ethical issues that need to be addressed for implementation are presented. Because engineers contribute to the design and implementation of infrastructure, there are opportunities for innovative solutions to infectious disease response within existing systems that have utility, and therefore resources, before a public health emergency. Moving forward, addressing privacy issues will be critical so that geographic tracking of a phone''s location could be used to help inform an individual of potential contact with infected persons or animals and support automated, anonymous, electronic integration of those data to accelerate the epidemiological detective work of identifying and surveying those same individuals for public health benefit. abstract: Infectious diseases are a major cause of death and economic impact worldwide. A more robust, adaptable, and scalable infrastructure would improve the capability to respond to epidemics. Because engineers contribute to the design and implementation of infrastructure, there are opportunities for innovative solutions to infectious disease response within existing systems that have utility, and therefore resources, before a public health emergency. Examples of innovative leveraging of infrastructure, technologies to enhance existing disease management strategies, engineering approaches to accelerate the rate of discovery and application of scientific, clinical, and public health information, and ethical issues that need to be addressed for implementation are presented. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186037/ doi: 10.1109/jproc.2015.2389146 id: cord-031907-ilhr3iu5 author: nan title: ISEV2020 Abstract Book date: 2020-07-15 words: 200999.0 sentences: 11528.0 pages: flesch: 44.0 cache: ./cache/cord-031907-ilhr3iu5.txt txt: ./txt/cord-031907-ilhr3iu5.txt summary: L.M., and the National Institutes of Health (R35GM119623) to T.R.G. The addition of a size exclusion chromatography step to various urinary extracellular vesicle concentrating methods reveals differences in the small RNA profile Introduction: Urinary extracellular vesicles (EVs) and their RNA cargo are a novel source of biomarkers for various diseases, however non-vesicular RNA (e.g. associated with proteins) is also present within urine. We then evaluated efficiency of heart targeting for eAAV9 or eAAV6 and standard AAV9 or AAV6 encoding for EGFP, mCherry or firefly luciferase in different human cell lines in vitro, in black mouse and in passive immunity nude mouse model in vivo using flow cytometry, confocal microscopy, Langendorff perfusion system and Methods: HLHS patients (n = 3) after Glenn procedure and swine (n = 3) after PAB were given RV injections of allogeneic/xenogeneic MSCs. Donor-specific, HLA-I+, exosomes were isolated from plasma. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480431/ doi: 10.1080/20013078.2020.1784511 id: cord-304685-s0bfhwtn author: nan title: Susceptibility to cytotoxic T lymphocyte-induced apoptosis is a function of the proliferative status of the target date: 1994-02-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Cytotoxic T lymphocytes (CTL) kill cells by perturbing the target's plasma membrane and by inducing the disintegration of the target cell's DNA into oligonucleosomal fragments, a process characteristic of apoptosis. We show that the DNA fragmentation event is distinct from the membrane lysis event and is dependent on the state of target cell activation or commitment into the mitotic cycle. Quiescent cells were refractory to DNA fragmentation, but not to membrane lysis. Log phase growth, transformation with c-myc, or infection of quiescent G0 targets with herpes simplex virus-1, which induces a competent state for DNA synthesis, all enhanced target cell susceptibility to CTL-induced DNA fragmentation without altering the membrane lysis. These results suggest that G0 cells are resistant to CTL-induced apoptosis, but that entry into G1 or a G1-like state by growth factors, cellular transformation, or DNA virus infection renders them competent to enter the apoptotic pathway(s). url: https://www.ncbi.nlm.nih.gov/pubmed/8294885/ doi: nan id: cord-326785-le2t1l8g author: nan title: Pathological Society of Great Britain and Ireland. 163rd meeting, 3–5 July 1991 date: 2005-06-15 words: 22752.0 sentences: 2108.0 pages: flesch: 42.0 cache: ./cache/cord-326785-le2t1l8g.txt txt: ./txt/cord-326785-le2t1l8g.txt summary: The lesions (usually multlpleand each 5 mm orless m diameter) were identified in lung parenchymaat a distance from the tumour and consisted of thickened alveolar walls lined by prominent, distinctly atypical cells morphologically Slmllar to type I 1 pneumacytes and cytologically different to the associated turnour Reactive changes 8" lung involved by obstrmtive pneumonitis were not included !n thts Sews All of the associated tumwra were peripheral adenocarcinamas and all showed a pattern of alveolar wall spread at the tumour periphery Clinically 7 of the patients were female and all were smokers or ex-smokers The slgnlflcance of this lesion in the histogenesis of primary pulmonary ademcarcinoma IS. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/1681042/ doi: 10.1002/path.1711640412 id: cord-327883-s9nbr5y8 author: nan title: Section Virology date: 1990-03-31 words: 10576.0 sentences: 571.0 pages: flesch: 48.0 cache: ./cache/cord-327883-s9nbr5y8.txt txt: ./txt/cord-327883-s9nbr5y8.txt summary: By improving the enzyme-linked immunosorbent assay (ELISA) for HSV-2-antibodies and additional testing of sera by Western blot, we were able to specifically identify HSV-l-and HSV-2-antibodies in serum samples. To get some insight into the molecular basis of processes controlling the viral expression we studied the sequence-specific DNA-protein interactions within the genomic regulatory regions. for Med. Microbiology, Univ., D-5300 Bonn Semiquantitative detection of Hepatitis B Virus (HBV) DNA in sera of infected individuals has become an important means of modern serological hepatitis diagnostics. THOMSSEN 1 In the course of acute Epstein-Barr virus (EBV) infection IgM antibodies always occur against two cellular antigens that were characterized as proteins with a molecular weight of 26 kD (p26) and 29 kD (p29), respectively. The frequency and specificity of antibodies to P-gene encoded proteins of human hepatitis B virus was tested in sera of acute and chronically infected patients with and without hepatocellular carcinoma (HCC). abstract: nan url: https://www.sciencedirect.com/science/article/pii/S0934884011800393 doi: 10.1016/s0934-8840(11)80039-3 id: cord-291860-dw1sfzqx author: van Boheemen, Sander title: Retrospective Validation of a Metagenomic Sequencing Protocol for Combined Detection of RNA and DNA Viruses Using Respiratory Samples from Pediatric Patients date: 2019-12-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Viruses are the main cause of respiratory tract infections. Metagenomic next-generation sequencing (mNGS) enables unbiased detection of all potential pathogens. To apply mNGS in viral diagnostics, sensitive and simultaneous detection of RNA and DNA viruses is needed. Herein, were studied the performance of an in-house mNGS protocol for routine diagnostics of viral respiratory infections with potential for automated pan-pathogen detection. The sequencing protocol and bioinformatics analysis were designed and optimized, including exogenous internal controls. Subsequently, the protocol was retrospectively validated using 25 clinical respiratory samples. The developed protocol using Illumina NextSeq 500 sequencing showed high repeatability. Use of the National Center for Biotechnology Information’s RefSeq database as opposed to the National Center for Biotechnology Information’s nucleotide database led to enhanced specificity of classification of viral pathogens. A correlation was established between read counts and PCR cycle threshold value. Sensitivity of mNGS, compared with PCR, varied up to 83%, with specificity of 94%, dependent on the cutoff for defining positive mNGS results. Viral pathogens only detected by mNGS, not present in the routine diagnostic workflow, were influenza C, KI polyomavirus, cytomegalovirus, and enterovirus. Sensitivity and analytical specificity of this mNGS protocol were comparable to PCR and higher when considering off-PCR target viral pathogens. One single test detected all potential viral pathogens and simultaneously obtained detailed information on detected viruses. url: https://www.sciencedirect.com/science/article/pii/S1525157819304325 doi: 10.1016/j.jmoldx.2019.10.007 id: cord-007757-4mri8kyq author: van de Sluis, Bart title: Transgene Design date: 2010-10-04 words: 3791.0 sentences: 205.0 pages: flesch: 43.0 cache: ./cache/cord-007757-4mri8kyq.txt txt: ./txt/cord-007757-4mri8kyq.txt summary: Size constraints, inherent to particular cloning systems, may limit the use of native regulatory elements: if a transgene becomes too large for regular plasmid or cosmid-based vectors, or when genetic complementation is desired (e.g., with DNA fragments spanning large genomic deletions), one can switch to systems that allow cloning of very large DNA segments (see Subheading 1.3; Chapter 9). In addition, some endogenous introns appear to harbor regulatory elements with structural and functional similarities to enhancers, Locus control regions (LCRs), or Matrix attachment regions (MARs) (see Subheading 2.2) which direct transgene expression in a position-independent or cell type-specific fashion (9-17). The experimenter has a certain degree of freedom to tailor transgene design to specific requirements ((3); see also The choice of regulatory elements that drive transgene expression is broad (Fig. 2) , and is primarily determined by the aim of the model. abstract: Transgenics are powerful mouse models to understand the biological functions of genes. This chapter gives a short overview of the requirements and considerations in designing a transgene. In addition, potential important choices that have to be made in advance for the successful designing and generating a transgenic mouse model are discussed. Methods for DNA purification for microinjection are also provided in this chapter. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122210/ doi: 10.1007/978-1-60761-974-1_6 ==== make-pages.sh questions [ERIC WAS HERE] ==== make-pages.sh search /data-disk/reader-compute/reader-cord/bin/make-pages.sh: line 77: /data-disk/reader-compute/reader-cord/tmp/search.htm: No such file or directory Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/tsv2htm-search.py", line 51, in with open( TEMPLATE, 'r' ) as handle : htm = handle.read() FileNotFoundError: [Errno 2] No such file or directory: '/data-disk/reader-compute/reader-cord/tmp/search.htm' ==== make-pages.sh topic modeling corpus Zipping study carrel