cord-001116-2yvyiiuy 2013 Since those functions are associated with the hippocampus, I analyzed the global gene expression data from post-mortem hippocampal tissue of 25 old (age ≥ 60 yrs) and 15 young (age ≤ 45 yrs) cognitively intact human subjects. Having employed three different and independent methods of statistical significance, namely, ROC curve analysis, fold change, and P-value, I was able to identify 36 genes that were the most significant in terms of differential expression. The seven genes [C4A (C4B), ADORA3, MS4A7, BCL6, CD44, C3AR1, and HLA-DRB1], which are the constituent input variables of the model (F 1 super variable), and all of which are -in terms of function -inflammation or immune system activation genes (Table 1) , were all found to be over-expressed in the old subjects compared with the young subjects (Table 1) . cord-001522-82plcxv9 2015 In this study, we reviewed the data on ''''other infectious diarrhoea'''' in China from 2005-2012 obtained from CISDCP, aiming to characterize the seasonality of diarrhoea in China and identify its potential drivers, as well as explore potential opportunities for future diarrhoea control and prevention. In terms of the amplitude distribution by age and region (seasonal amplitude refers to the relative fluctuation of diarrhoea within a certain period of time, and it provides pivotal information on the possibility of diarrhoea outbreaks), we found that adults (.515 years) had much greater diarrhoea amplitudes than children (,15 years) (Figure 4 ), but the amplitude in persons .520 years declined progressively with increasing age, reaching its valley in elderly .585 years (Figure 4) , and this decreasing trend was remarkably consistent across years ( Figure S4 (supplementary material)). Demographic, economic, geographic and climate information in all 31 provinces from 2005 to 2012, including population, per capita gross regional product (PGRP), latitude, longitude, monthly average mean temperature, monthly average relative humidity, and monthly average rainfall, were collected from China Statistical Yearbook 27 to identify the putative drivers of diarrhoea seasonality. cord-001675-9717nzr7 2015 Here we demonstrate that the Tie2-agonist tetrameric peptide Vasculotide improves survival in murine models of severe influenza, even if administered as late as 72 hours after infection; the benefit was observed using three strains of the virus and two strains of mice. While the drug had no effect on human lung endothelial proliferation (Supplemental Figure 8) , it significantly attenuated lung endothelial apoptosis in vitro in response to influenza virus, as assessed by cleavage of caspase-3 (Supplemental Figure 7c ); we observed a similar reduction in cleaved caspase-3 in lungs from infected mice who received Vasculotide (Supplemental Figure 7d ). First, these data strongly implicate failure of the lung endothelial barrier as the cause of death in murine models of severe influenza, as Vasculotide conferred a significant survival benefit against multiple strains of the virus in two strains of mice. cord-001704-pdxm0iiw 2015 hmPA6 injection before or after LeTx administration protected all rats from developing anthrax (Fig. 6C) . In the present study, we developed four murine mAbs that could well neutralize LeTx in vitro, and one clone was selected to form a human/mouse chimeric antibody known as hmPA6. In the in vivo test in the present study, irrespective of whether LF was injected before or after hmPA6, the antibody protected the rats from death provided that it was administered before or simultaneously with PA. In summary, we reported a human/murine chimeric IgG, namely, hmPA6, which can specifically identify PA with high affinity, neutralize LeTx, and protect macrophages and F344 rats from anthrax-related death. In vitro and in vivo characterization of anthrax anti-protective antigen and anti-lethal factor monoclonal antibodies after passive transfer in a mouse lethal toxin challenge model to define correlates of immunity An anthrax lethal factor-neutralizing monoclonal antibody protects rats before and after challenge with anthrax toxin cord-001712-a1sbdhhn 2015 title: EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT The mechanism underlying this effect may include two processes: EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity; EGCG enhances the expression of α1-antitrypsin by regulating the PI3K/AKT pathway. In this study, we demonstrated additional contributions of inflammation to the progression of lung cancer metastasis and a novel molecular target of EGCG, human neutrophil elastase, which induces lung cancer cell migration. 14 demonstrated that the natural polyphenol product curcumin inhibits tumor proliferation induced by neutrophil elastase via the upregulation of AAT in lung cancer. These results indicated that treatment with EGCG at a concentration between 10 and 20 μ M induces a substantial anti-migratory effect without affecting the proliferation of A549 cells exposed to neutrophil elastase. Our results showed that the neutrophil elastase-induced decrease in IRS-1 expression was significantly inhibited by EGCG in A549 cells. cord-001823-v60vv99o 2015 By fitting the model to reported cumulative cases and deaths in Guinea, Sierra Leone and Liberia until March 22, 2015, we estimate the basic reproduction number in these countries as 1.2552, 1.6093 and 1.7994, respectively. The objective of this paper is to assess the effect of all possible intervention strategies (isolation, media impact, safe burial, and vaccination) on controlling the spread of Ebola virus in Guinea, Sierra Leone, Liberia. Using the model, we evaluate the potential effect of increasing the fraction of latent individuals prior to symptoms onset, shortening the duration between symptoms onset and isolation, improving media coverage, following restrict burial procedures, and administrating timely vaccine on the epidemic of Ebola infection. If the effectiveness of isolation increases to 80%, i.e., the relative transmissibility  of isolated individuals decreases to 20% (magenta lines in Fig. 5 ), then about 35%, 65%, 60% of pre-symptomatic patients need to be detected in Guinea, Sierra Leone and Liberia to control the disease. cord-001829-rwnbxmt4 2015 Genome-wide association studies performed on diverse patient populations have identified polymorphisms near the interferon-λ 3 (IFNL3; formerly IL28B) gene that predict the efficacy of interferon-based therapy for chronic infection. The differential effects on mRNA versus protein levels strongly suggest that the IFNL3 3′ UTR regulates gene expression by repressing the efficiency of mRNA translation rather than mRNA abundance in HeLa cells. We used polysome profiling to examine whether the variant IFNL3 reporter mRNAs were differentially associated with translating ribosomes in stable HeLa cell lines. Although rs4803217 is not independently associated with patient phenotypes in the cohort we analyzed, this SNP occurs in the 3′ UTR of IFNL3 and showed clear functional effects on reporter gene expression, suggesting a role for this variant in control of HCV infection. cord-001852-c79vwr6t 2015 In conclusion, our results found that a history of recurrent wheezing may be a risk factor for the detection of EV-D68 and viral-induced asthma exacerbation may be a clinical feature of EV-D68 infection. In a previous hospital-based viral surveillance study of RTI cases in Chongqing, China, from 2009 to 2012, the detection rate of EV-D68 was 0.4% (7/1565) 11 . In our study, most children infected with EV-D68 had a history of recurrent wheezing or asthma and a diagnosis of acute asthma exacerbation. Our study found that a history of recurrent wheezing or asthma may be a risk factor for the detection of EV-D68 and viral-induced acute asthma exacerbation may be a clinical feature of EV-D68 infection in Chongqing area. A history of recurrent wheezing or asthma appeared to be a risk factor for the detection of EV-D68 and viral-induced acute asthma exacerbation might be a clinical feature of EV-D68 infection. cord-001858-nmi39n6h 2015 title: Reference gene selection for normalization of RT-qPCR gene expression data from Actinidia deliciosa leaves infected with Pseudomonas syringae pv. Primer sequence (5′-3′) BestKeeper and the deltaCt method) were used to evaluate the stability of expression of selected RGs. The analyses were performed for three comparison groups considering both low-and high-dose bacterial inocula in the leaves and their combined dataset. In kiwifruit leaves with a high dose of bacterial inoculum, BestKeeper revealed that only the expression of TUB overcame the stability threshold; CYP and GAPDH were considered to be the most stable genes, with SD values of 0.50 and 0.61, respectively (Table 3 ). The expression of three genes encoding the reactive oxygen species (ROS) scavenging enzymes ascorbate peroxidase (APX), superoxide dismutase (SOD) and catalase (CAT), induced during the systemic infection of kiwifruit leaves with PSA, were chosen to further validate the reliability of the selected RGs for the normalization of RT-qPCR data. cord-001862-a097byk5 2015 The proteolytic activity of nsP2 has been characterized in other alphaviruses, such as Sindbis virus (SINV), Semliki forest virus (SFV) and Venezuelan Equine Encephalitis virus (VEEV), as a papain-like cysteine protease with a cysteine-histidine catalytic dyad in the active site 11, 12, [16] [17] [18] [19] . Although the dyad residues have been identified previously in other alphavirus nsP2 proteins; in SINV, SFV and VEEV 11, 12, [16] [17] [18] , the CHIKV nsP2 protease active site has not been experimentally characterized. In performing this study a structural comparison showed that CHIKV nsP2 protease is not papain-like, and we have found what appears to be a unique feature of CHIKV nsP2 protease, in which the cysteine dyad residue can be catalytically replaced by a vicinal serine. In our study the protease inhibitors leupeptin and E-64 showed little to no effect on wild type, Cys478Ala and Ser482Ala enzyme activities for all 3 substrates (Table 2) . cord-001868-utsvsja0 2015 In this study, we focused on CARD9, a signaling adaptor known to regulate innate immune activation through multiple innate sensor proteins, and investigated its role in anti-IFV defense and lung pathogenesis in a mouse model recapitulating severe influenza pneumonia with ARDS. Our results showed that the CARD9 pathway was involved in fatal influenza pneumonia mediated by inflammatory cytokine/chemokine production, whereas it was dispensable for type-I interferon production as well as the development of anti-viral acquired immunity. adapted IFV A/PR/8/34 strain (PR8) shows similar lung pathology to human ARDS 10-12 , we intratracheally infected wild-type (WT: C57BL/6) and Card9 -/mice with a lethal dose (10 4 PFU/mouse) of PR8 to determine whether CARD9-mediated innate immune responses contributed to severe influenza pneumonia. However, no reduction in cytokine/chemokine levels was evident on day 8, indicating that a CARD9-mediated innate response controls cytokine/chemokine production at an early time point after IFV infection and influences subsequent inflammatory cell recruitment and lung pathology at a later time point. cord-001875-ulq1xqma 2015 Our results represent the first step in determining the effects of climate factors on two different virus infections in China and provide warning guidelines for the future when provinces fall into the risky windows. Previously, data have indicated that environmental factors affect the prevalence of H5N1 and H7N9, with the infection and spread of the two viruses being closely correlated with bird habitats, migration, and local climate factors (e.g., temperature and relative humidity) 17 . We collected the H5N1 and H7N9 influenza data reported on the Chinese mainland from The climate dataset contained the air temperature, ground surface temperature, relative humidity, wind speed, and atmospheric pressure of all meteorological stations in the reported provinces at the reported dates for each record. Environmental factors influencing the spread of the highly pathogenic avian influenza H5N1 virus in wild birds in cord-001901-2s6hpakk 2016 title: Anti-inflammatory effects of indirubin derivatives on influenza A virus-infected human pulmonary microvascular endothelial cells In this report, we examined the potential immunomodulatory effects of two indirubin derivatives, indirubin-3′-(2,3-dihydroxypropyl)-oximether (E804) and indirubin-3′-oxime (E231), on IAV (H9N2) infected-human pulmonary microvascular endothelial cells (HPMECs). Using specific inhibitors or small-interfering RNA, we confirmed that indirubin derivatives can suppress H9N2-induced cytokines production through MAPKs and STAT3 signaling pathways. To detect the activity of individual MAPKs after treatment with IAV and indirubin derivatives, the non-radioactive In vitro protein kinase assay kit from Cell Signaling Technology was used. In this study, we found that the infection of influenza A virus subtype A/Quali/Hong Kong/G1/97 (H9N2) on HPMECs induced excessive production of various pro-inflammatory cytokines and chemokines, including IP-10 ( In this report, we demonstrated that indirubin derivatives, particularly E804 is a potent immunomodulatory compound for IAV-infection in vitro by inhibiting intracellular signaling pathways in pulmonary endothelial cells. cord-001915-b9dk07tk 2016 title: A CRISPR/Cas9 and Cre/Lox system-based express vaccine development strategy against re-emerging Pseudorabies virus Here we present an express vaccine development strategy based on CRISPR/Cas9 and Cre/Lox system against re-emerging Pseudorabies virus, which caused the recent devastating swine pseudorabies outbreak in China. To establish an express vaccine development strategy, two highly efficient gene edit systems, CRISPR/Cas9 and Cre/Lox system were employed. Eight hours post transfection, cells were then infected with PRV HNX with different MOI (multiplicity of infection) and incubated until recombinant virus expressing red and/or green fluorescence were observed (Fig. 3b) . As shown in Fig. 4a , the Cre recombinase gene transfected HEK293T cells were infected with PRV-HNX-TK − /gE − GFP + mCherry + recombinant PRV with various MOI (0.1, 1, and 10). Here, our animal experiments in mouse and piglets validated the protective effect of this gene editing technologies based new vaccine candidate, demonstrating its potential in controlling the current pseudorabies outbreak in the swine industry. cord-001963-4wjvykx7 2016 title: Using mutagenesis to explore conserved residues in the RNA-binding groove of influenza A virus nucleoprotein for antiviral drug development By interrupting the stacking interaction between Y148 and an RNA base, we identified an influenza virus NP inhibitor, (E, E)-1,7-bis(4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5-dione; this inhibitor reduced the NP''s RNA-binding affinity and hindered viral replication. As shown in Fig. 7A , upon H7 treatment at 15μM, the M1 viral RNA synthesis in the influenza virus-infected cells was reduced by 75% at T2. NP is the most abundant RNA-binding viral protein in influenza virus-infected cells and is responsible for recognizing RNA and forming a filamentous nucleocapsid 24 . Using fluorescence titration and an SPR assay of the NPs, we identified one potential natural compound, curcumin (H7), that targets Y148 of influenza virus NP and potently interferes with its RNA-binding activity. cord-002013-rb9xdzro 2016 To investigate whether EBOV infections can be controlled by virus neutralization alone, and to prevent the possible induction of serum sickness in humans that would be administered antisera, the post-exposure efficacy of F(ab′ ) 2 (immunoglobulin treated with pepsin to remove the Fc regions of the antibody) were also investigated side-by-side with equine antisera in all experiments as a potential alternate treatment. Three horses were immunized intramuscularly (IM) with 7 injections of eVLP over 11 weeks and the hyperimmune sera were collected from each animal at specified timepoints ( Fig. 1A) to determine the serum titers by neutralization assay against a recombinant HIV-1 virus pseudotyped with EBOV GP. The observation that administering F(ab′ ) 2 at 1 dpi is more efficacious than when the same treatment was given at 30 minutes post-exposure (Fig. 5A ) was also observed in past studies with therapeutic EBOV GP-specific monoclonal antibodies 25, 26 , and suggests that virus neutralization may play a bigger role in protection at a later timepoint after EBOV challenge. cord-002019-wtnf340p 2016 We demonstrated that elevated numbers of gut-homing CD8(+) T cells (which express α4β7 and CCR9 molecules) were presented in porcine inguinal lymph nodes and were recruited to the small intestine by RA. Taken together, the cell migration assay results revealed a strong chemotactic response in T cells when activated by RA-activated DCs. These data demonstrated that RA-pretreated BMDCs could activate T cells to express high functional levels of the gut-homing receptor CCR9, as well as to migrate towards the porcine chemokine CCL25. In agreement with the migration of gut-homing CD8 + cells, our observations showed that after RA plus TGEV s.c. treatment, many CD3 + T cells were recruited to the intestinal villi and lamina propria, and these data also showed that RA-assisted antigen s.c. can establish a stronger and faster cellular immune response to defend against foreign pathogens 40 . cord-002045-m44fic4g 2016 Endogenous bornavirus-like L (EBLL) elements are inheritable sequences derived from ancient bornavirus L genes that encode a viral RNA-dependent RNA polymerase (RdRp) in many eukaryotic genomes. Furthermore, we showed that the EBLLs evolved under purifying selection and still possess functional motifs conserved among the Mononegavirales RdRps. These results strongly suggest that the EBLL elements encode functional proteins that may be RdRps. ORF screening for these elements in several mammalian species and found an EBLL element in the bat species Eptesicus fuscus (designated efEBLL-1; accession number ALEH01013293). Notably, this element (eEBLL-1) contains a 1,718-amino acid ORF that was conserved for more than 11.8 MY and included almost all of the sequence motifs essential for the enzymatic activity of a RNA virus RdRp. To the best of our knowledge, eEBLL-1 is the first example of an RNA virus-derived RdRp encoded by the mammalian genome. cord-002072-qbh728ec 2016 Genetic and phylogenetic analyses revealed that the virus belonged to a novel genotype, which probably emerged and further reassorted with other H9 or H7 viruses in poultry before transmitting to humans. The IFN-induced transmembrane protein-3 (IFITM3) C/C genotype was reported to be associated with severe clinical outcomes, as reflected by a higher viral load, more rapid progression to ARDS, higher cytokine/chemokine levels, and an increased mortality rate after H7N9 infection 22 . Although this was a severe H7N9-infected case with cytokine storm-like appearances and multiple organ failure, the patient was eventually cured after combination therapy with antivirals, mechanical ventilation, supportive nutrition and symptomatic treatment. Clinical, virological and immunological features from patients infected with re-emergent avian-origin human H7N9 influenza disease of varying severity in Guangdong province Cytokine and chemokine levels in patients infected with the novel avian influenza A (H7N9) virus in China cord-002081-vi6rth9o 2016 In this work, a rapid one-step SNP detection method, real-time loop-mediated isothermal amplification (RT-LAMP), was first applied for CYP2C19 polymorphisms testing. The optimized method was established with specifically designed primers for target amplification by real-time detection in approximately 30 min under isothermal conditions. The successful establishment of an inexpensive, rapid and real-time LAMP protocol for CYP2C19*2 and CYP2C19*3 detection is significant for the extension of this technique for genotyping other SNPs. Our results suggest applications for this RT-LAMP assay system for both basic research and clinical diagnosis in pharmacogenomics. In this study, the successful establishment of an inexpensive, rapid and real-time LAMP protocol for CYP2C19 SNP genotyping expanded the scope of application of this technique to human gene mutation detection. In summary, as a rapid, feasible and cost-efficient point-of-care (POC) SNP detection method, we demonstrated that RT-LAMP could quantitatively detect human genomic DNA with high specificity and sensitivity in a single step. cord-002110-pbb247lp 2016 title: Membrane protein assembly: two cytoplasmic phosphorylated serine sites of Vpu from HIV-1 affect oligomerization Coarse-grained molecular dynamic simulations with models of wild-type and mutant Vpu in a hydrated lipid bilayer supported the experimental data in demonstrating that, in addition to a previously known role in downregulation of host factors, the phosphorylation sites of Vpu also modulate oligomerization. Coarse grained molecular dynamics (CGMD) simulations of Vpu proteins embedded in a planar lipid bilayer model were chosen to evaluate the oligomeric assembly under likely in vivo conditions such as an abundance of Vpu proteins in a large lipid patch and simulated over a long time period. The dynamics data was plotted as area of the peak of the higher oligomer (A P1 ), divided by the total area of A P1 and the peak area of the dimer (A P2 ), A P1 /(A P1 + A P2 ), over time for Vpu-WT with a double logarithmic growth curve (Fig. 4b , black and Table 2 ). Three-dimensional structure of the channel-forming trans-membrane domain of virus protein "u" (Vpu) from HIV-1 cord-002111-mmpijsqb 2016 title: Small Glutamine-Rich Tetratricopeptide Repeat-Containing Protein Alpha (SGTA) Ablation Limits Offspring Viability and Growth in Mice Small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) has been implicated as a co-chaperone and regulator of androgen and growth hormone receptor (AR, GHR) signalling. As some, but not all, androgen-regulated organs displayed potential signs of hyperandrogenisation during development in Sgta +/− and Sgta −/− mutants, we measured Ar mRNA expression in androgen-regulated tissues, the brain, and the prostate and testis in males, and the mammary and ovary in females (Fig. 4C) . However, the relative weights of vital and sex organs, adipose tissue, muscle and bone were not affected by a genotype* age interaction, suggesting that Sgta-null mice are not any more vulnerable to age-related stress than WT. Small glutamine-rich tetratricopeptide repeat-containing protein (SGT) interacts with the ubiquitin-dependent endocytosis (UbE) motif of the growth hormone receptor cord-002177-yyfgl9x5 2016 Furthermore, treatment of TGEV-infected IPEC-J2 cells with the NF-κB-specific inhibitor BAY 11-7082 resulted in down-regulation of pFcRn expression. We identified four NF-κB transcription factor binding sites in the promoter region of this gene using luciferase reporter system, chromatin immunoprecipitation, electromobility shift assay, and supershift analysis. In the present study, we investigated how TGEV infection activated the NF-κ B pathway in vitro and up-regulated pFcRn expression in IPEC-J2 cells. Furthermore, pFcRn expression induced by TGEV infection was strongly reduced by the NF-κ B-specific inhibitor BAY 11-7082 in IPEC-J2 cells (Fig. 3) . Transient transfection of the pFcRn promoter luciferase reporter plasmids revealed that pFcRn-luc-(1-3) plasmids resulted in increased promoter activity in the presence of TGEV infection (Fig. 4B) , further demonstrating that TGEV up-regulates pFcRn expression in IPEC-J2 cells. In summary, TGEV infection up-regulates pFcRn expression in IPEC-J2 cells, and activates the NF-κ B signaling pathway. cord-002244-5h6monh3 2016 Immunohistochemical analysis revealed that injection with PTEN overexpression vector significantly suppressed the expression of proinflammatory cytokines and osteoclastogenesis related factor such as RANKL and TRAP in joints compared to CIA mice treated with mock vector (Fig. 1D,E) . However, the differentiation of Treg cell was promoted in CIA induced mice injected with PTEN overexpression vector ( Fig. 2A) . However, the number of CD4 + p-Foxp3 + T cells in the spleen tissues of CIA induced mice was significantly upregulated compared to that in the spleen tissues of mice treated with mock vector based on immunofluorescence confocal microscopy ( Fig. 2C,D) . (A,B) Relative mRNA levels of PTEN and factors such as IL-17, RORγ t, and Foxp3 involved in the differentiation of Th17 and Treg in splenic CD4 + T cells, splenocytes, and draining lymph nodes from CIA induced WT or p53 −/− mice were assessed by real-time PCR. cord-002258-o9azey3m 2016 In this study, we evaluated the role of amino acid substitution PB2-627K or compensatory changes at PB2-591K and PB2-701N, on the tropism and replication competence of H7N9 viruses for human and swine respiratory tracts using ex vivo organ explant cultures. There were very limited influenza antigen positive cells in the rgPB2-K627E + Q591K and rgPB2-K627E + D701N inoculated ex vivo culture of human bronchus (Fig. 2C ) while more infected cells were shown in these mutant viruses infected lung tissues (Fig. 2D ). In this study, we evaluated the effects of PB2-E627K mutation as well as two mammalian adaptation markers, PB2-Q591K and D701N on H7N9 virus replication competence in ex vivo cultures of human and swine respiratory tracts and in vitro cultures of human primary ATI and PMφ . Tropism and innate host responses of a novel avian influenza A H7N9 virus: an analysis of ex-vivo and in-vitro cultures of the human respiratory tract cord-002290-wvo22jx2 2016 In this study four functional single-nucleotide polymorphisms (SNPs, H/L, X/Y, P/Q and A/B) across the MBL2 gene were genotyped by direct DNA sequencing of PCR products in a case-control population of Chinese Han origin, consisting of 1,020 patients with pulmonary TB and 1,020 controls. In 1,020 controls, this distribution was 723 (70.9%), 234 (22.9%) and 63 (6.2%), respectively (OR = 1.56, 95% CI 1.29-1.90, P = 1.4 × 10 −6 , with adjustment for age and gender; simulation number = 10,000,000; Table 2 ), implicating that the individuals bearing medium or low expression haplotype pairs had an increased risk of TB and that the MBL deficiency might play a potential role in susceptibility to TB. In this study, we investigated all of the four functional SNPs in the MBL2 gene, individually or in haplotype or haplotype pairs, in a large case-control population of Chinese Han origin, totally consisting of 1,020 patients with TB and 1,020 controls. cord-002312-jyk7f8hz 2016 Massively parallel (deep) sequencing (RNAseq) of total RNA permitted analysis of all RNA sequences in MS (n = 6) and nonMS (n = 6) white matter samples, revealing that bacterial RNA (ribosomal and non-ribosomal) sequences were detected in all nonMS and MS brain specimens, including MS patients with relapsing-remitting disease (receiving disease modifying therapy) (RR-MS, n = 3) and progressive (untreated) MS (P-MS; n = 3) ( Fig. 2A) . The current study shows the presence of bacterial RNA and DNA sequences and proteins in human brain which are disrupted in conjunction with inflammatory demyelination in patients with MS. The present studies revealed the ratio of bacterium-encoded 16s rDNA to rRNA in matched brain samples to be ~1:2 in both white matter (and cortex, data not shown) with bacterial numbers of 1200-1400 genomes/cm 3 suggesting both bacterial burden and replication were low compared to active pathogenic infections in other tissues. cord-002320-m99amd4y 2016 Systematic analysis of all CHIKV proteins using a Sf21 RNAi sensor cell line based assay revealed that non-structural proteins nsP2 and nsP3 exhibited RNAi suppressor activity. Using cell lysate of the transfected cell expressing nsP2 and nsP3, we evaluated their ability to bind double stranded RNA by using [γ 32P] labeled shRNA of GFP and running the bound complex in a 6% polyacrylamide gel (Fig. 3e) . Having confirmed that both nsP2 and nsP3 exhibit RNAi suppressor activities, efforts were taken to characterise the proteins better and to identify those specific domains that were and NS4B (dengue virus) were taken as positive controls and empty vector was used as negative control. Taken together, the current study has identified CHIKV proteins nsP2 and nsP3 to exhibit RNAi suppressor activity in the in-vitro system that was further demonstrated in its natural hosts, namely, an Aedes and mammalian cell line. cord-002369-shk4n8f6 2017 The expression of HCV proteins results in the induction of a major rearrangement of host cell membranes, thus leading to the formation of a complex membranous compartment termed the membranous web (MW), which favors viral RNA replication and assembly 3, 4 . To determine whether LC3 or the ATG5-12 conjugate modulates HCV RNA replication, we analyzed the effects of silencing these autophagy genes on viral RNA replication in Huh7 cells stably expressing the JFH1 subgenomic replicon (SGR). Because silencing of LC3 expression led to a clear inhibition of HCV RNA translation after electroporation of the viral RNA but did not significantly affect replication in JFH1-SGR cells, we sought to compare the effect of siRNA treatment before and after infection with HCVcc JFH1 (Fig. 3C) . The autophagy elongation complex proteins (ATG5-12 and ATG16L1) were also detected in the purified MW from NS4B HA replicon cells, but not in the control extract, thus indicating that the elongation complex is indeed present at the HCV replication site. cord-002373-rueg4gsj 2017 Then, analyte IgG proteins in increasing concentrations were added to a set of buffer solutions containing antibody-conjugated GO. As the number density of the binding sites was limited on the modified GO, more adsorbed analyte IgG proteins resulted in a stronger fluorescence signal from free IgG-FITCs in the solutions. Therefore, there is a positive and quantitative correlation between the analyte IgG concentration and the fluorescence intensity of free IgG-FITCs. According to this principle, our assay relies on the effectiveness of GO as an energy acceptor to provide efficient fluorescence quenching. The experiment was repeated 4 times, and the average of the results was plotted in Fig. 4(a) , from which we can see the assay''s fluorescence signal increased readily with the increasing analyte IgG concentration. We established an immunosensor platform based on quantitative fluorescence quenching between fluorescein-labelled antigens and antibody-conjugated GO nanosheets, a process controlled quantitatively by the concentration of analyte proteins. cord-002389-k86hzbbx 2017 As all stages of Ebola entry (binding to and internalization from the cell surface, as well as trafficking to and fusion with the limiting membrane of endolysosome) are mediated by trimeric GP spikes arrayed around the Ebola particles 29, 30 , so the pseudovirion model with Ebola GP can simulate the stages of wild-type Ebola entry, and several groups have studied the Ebola entry mechanism and screened the anti-Ebola entry drugs with Ebola pseudovirion model 3, 6, 31, 32 . To determine whether endolysosomal calcium is involved in the mechanism of Ebola entry inhibition, we treated HepG2 cell line with a high-affinity Rhod-dextran to chelate intraluminal calcium, and infected the cells with Ebola, WSN, or VSV pseudovirions. cord-002408-bbtslrrt 2017 We demonstrate that this urban area is not a single, perfectly mixed ecology, but is in fact comprised of a set of more basic, relatively independent pathogen transmission units, which we term here Local Transmission Zones, LTZs. By identifying these LTZs, and using the dynamic pathogen-content information contained within them, we are able to differentiate between disease-causes at the individual patient level often with near-perfect predictive accuracy. To investigate the possibility of LTZs in a large regional area, we analyze clinical data from a healthcare medical center in the city of Jerusalem, containing the clinical test results for Influenza virus and Respiratory Syncytial Virus (RSV) from patients presenting with ILI symptoms. Our analysis finds that while Influenza and RSV incidences tend to overlap and show more or less equal number of cases over the whole region, individual LTZs show a far more homogeneous disease content at most given times, with some being dominated by RSV while others by Influenza. cord-002411-iiw878w8 2017 The enhanced TLR3 up-regulation in AMΦ augmented the expression of cytokines and chemokines in response to sequential challenges with LPS and Poly I:C, a TLR3 ligand, which was physiologically associated with amplified AMΦ-induced PMN migration into lung alveoli. To address the effect of LPS/TLR4-mediated activation of TLR3 in AMΦ on inflammatory cytokines, we assessed TNF-α and IL-6 in the serum and BALF, as well as the chemokines MIP-2 and MCP-1 in the BALF, following sequential intratracheal challenges with LPS and Poly I:C. This cross talk between TLR4 and TLR3 in AMΦ resulted in the amplification of cytokine (IL-6, TNF-α ) and chemokine (MIP-2, MCP-1) expression in response to LPS and Poly I:C, which activate TLR4 and TLR3, respectively, and subsequently led to enhanced PMN sequestration into the lung, which was found to be correlated with ALI based on the assessment of alveolar-capillary permeability and histological sections of lung tissue. cord-002474-2l31d7ew 2017 title: Actual measurement, hygrothermal response experiment and growth prediction analysis of microbial contamination of central air conditioning system in Dalian, China Based on the data of Cladosporium in hygrothermal response experiment, this paper used the logistic equation and the Gompertz equation to fit the growth predictive model of Cladosporium genera in different temperature and relative humidity conditions, and the square root model was fitted based on the two environmental factors. Besides, according to the tested microbial density and the identified genome sequence of collected microorganisms, the hygrothermal response experiment of dominant fungal was detected, and the fitting analysis was carried out based on the prediction model, followed by a series of statistical analysis. The unit A showed the obvious microbial contamination status, though all components and airborne microorganism meet the Hygienic specification of central air conditioning ventilation system in public buildings of China 22 . cord-002490-kw8psrmz 2017 We present the structure of the surface Ebola virus (EBOV) trimeric glycoprotein (GP) spike at 11 Å resolution, in situ within the viral plasma membrane of purified virus particles. In addition, 29,976 images were selected for reference-free analysis of the half-diameter of EBOV to investigate the spatial distribution of the GP spikes, as well as the periodicity and symmetrical relationships between GP and the matrix protein VP40 in the envelope, and the underlying nucleocapsid layer (Figs 1c and S3) . The spike structure of Beniac et al imaged within the virus-like particles was somehow clipped, since this should have included the mucin-like domains: in addition, tomography was combined with single-particle analysis, which may have distorted the results 4 . The structure that we report here is based entirely on the well-accepted method of single-particle analysis using projection matching, and is broadly similar to that published of expressed GP in virus-like particles using tomography 28, 29 : there are noticeable differences in shape and size of the spike, as well as in resolution (Fig. 4) . cord-002644-yzan95du 2017 Thus, our study reveals that the NLRP3 inflammasome is deleterious for the host during H7N9 infection in mice, which is due to an overwhelming inflammatory response via caspase-1 activation and associated IL-1 signal. To note, the production of above mentioned cytokines and chemokines from Nlrp3 −/− mice showed a similar pattern as that from Casp1/11 −/− mice (Fig. 5b) , indicating that deficiency of NLRP3 inflammasome genes reduced the secretion of several critical proinflammatory mediators in the lung of mice upon H7N9 IAV challenge. Pathology analysis showed that there were inflammatory responses in the infected lungs of all strains of mice, both at 3 d.p.i and at 7 d.p.i; and the pulmonary inflammations at 7 d.p.i. were more severe than that at 3 d.p.i.; moreover, the pulmonary inflammations of the WT mice were stronger than Casp1/11 −/− , Asc −/− and Nlrp3 −/− mice (Figs 3 and 7) . cord-002659-566uoozj 2017 Cytokine levels and virus titres in bronchoalveolar lavage fluid from mice with and without asthma after A(H1N1)pdm09 or seasonal H1N1 infection were examined. Virus titres in asthma/A(H1N1)pdm09 mice were highest at 3 days post-infection, and decreased by 7 days post-infection, although the levels at this time point were still higher than that in any other group. In the present study, we investigated the sequential changes in intra-tracheal cytokine production, viral loads, and pulmonary inflammation in a mouse model of bronchial asthma during the first 7 days after A(H1N1)pdm09 or seasonal H1N1 influenza infection. In contrast, the levels in control mice increased to 161.4 pg/mL by 3 days post-seasonal virus infection, which were similar to those in asthma/A(H1N1)pdm09 mice (p = 1.00), and these levels were maintained until 7 days post-infection. The notable findings in the present study were the early peak in both IL-6 and TNF-α levels, the high inflammatory cell infiltration in BAL fluids, and the severe pulmonary inflammation at 3 days post-infection in asthmatic/A(H1N1)pdm09 mice. cord-002673-5a1rfi6k 2017 This study uses statistical approaches and assessment of "characteristic attributes" (i.e. nucleotide positions that discriminate among strains) to assess whether published and new NNV RNA2 cds sequences show genetic differentiation over geography, host species and years. Within the red spotted grouper nervous necrosis virus (RGNNV) strain, to which all Asian grouper NNV belong, however, no one so far has reported evidence of genetic subgrouping by region, species or year in a formal statistical manner, especially when we restrict hosts just to Asian grouper. The goal of this report was to collate the most comprehensive data set to date on NNV RNA2 sequences for warm water Asian marine finfish, whether published and/or lodged in Genbank over the last 20 years, including some sequence data produced by our group for Vietnamese and Taiwanese grouper, to statistically test the data for evidence of NNV strain variation that associates with geography, host species and year and also to determine whether there are "characteristic attributes" that indicate regional (or host, year) specific differences among the strains. cord-002720-lrkscs71 2017 title: Development and evaluation of a rapid molecular diagnostic test for Zika virus infection by reverse transcription loop-mediated isothermal amplification The assay detected viral RNA at 14.5 TCID(50)/mL in virus-spiked serum or urine samples within 15 min, although it was slightly less sensitive than reference real time RT-PCR assay. We then evaluated the utility of this assay as a molecular diagnostic test using 90 plasma or serum samples and 99 urine samples collected from 120 suspected cases of arbovirus infection in the states of Paraíba and Pernambuco, Brazil in 2016. Therefore, it is difficult to detect ZIKV in blood samples from patients after the acute phase of infection, even with sensitive molecular diagnostic methods, such as reverse transcription-polymerase chain reaction (RT-PCR) 14, 18, 19 . These results suggested that the RT-LAMP assay could be used as a rapid, sensitive diagnostic test for ZIKV, the Tp value (i.e., less than 15 min) can be used as an indicator of the number of RNA copies in each reaction. cord-002758-d86hnox1 2017 We have examined the possibility to encode an arbitrary pair of protein domains as a dual gene, with the shorter coding sequence completely embedded in the longer one. An example of a designed overlapping gene was produced recently, where each DNA strand coded for a simplified but functional aminoacyl-tRNA synthetase "Urzyme" [13] [14] [15] [16] , with the two enzymes being homologous to the two modern synthetase classes. Considering all three reading frames, we found that over 16% of the (X, Y) pairs have homologous pairs (X′, Y′) that can be encoded in a fully overlapping manner, with a level of X/X′ and Y/Y′ homology corresponding to Blast E-values of 10 −10 or less and a match length of at least 85% of the total sequence length. Given the level of success and the generality of our algorithm, we also designed 200 triple genes, with three proteins encoded by the same DNA segment using both strands and three different reading frames. cord-002782-mena480g 2017 Our findings suggest that pulmonary function and imaging findings improved during the first 6 months especially for those with ARDS, however long-term lung disability and psychological impairment in H7N9 survivors persisted at 2 years after discharge from the hospital. In survivors of H5N1 virus infection, radiologic abnormalities including ground-glass opacities with a reticular pattern remained evident at the 12-month follow-up visit 10 . A study of the long-term outcomes of survivors with ARDS reported a mild restrictive pattern on lung-function testing, with a mild-to-moderate reduction in carbon monoxide diffusion capacity at 3 months; The median DLCO improved by 9% of the predicted value from 3 to 12 months 13 . A meta-analysis showed that recovery in the HRQoL of ARDS survivors occurred during the first 6 months after discharge 20 , but no significant improvement was evident at the 2-year follow-up in our study. Follow-up study on pulmonary function and lung radiographic changes in rehabilitating severe acute respiratory syndrome patients after discharge cord-002791-tqchfdmy 2017 cord-002802-594mmlk8 2017 Further, the recombinant TM-replaced H9N2-TM virus could provide better inter-clade protection in both mice and chickens against H9N2, suggesting that the H3-TM-replacement could be considered as a strategy to develop efficient subtype-specific H9N2 influenza vaccines. However, the biological characteristics, such as virus growth, ratio of trimer, thermal stability, acidic resistance and fusion activity were altered, suggesting an important role of the TM domain in viral replication and pathogenicity. Taken together, the increased thermal and acidic resistances of the recombinant H9N2-TM virus suggest that the substitution in the transmembrane (TM) domain can affect the stability of the HA, therefore alters viral biological characteristics. To explore whether the increased HA trimers and increased thermal and acidic resistances could result in better immune responses thus providing better protection in mice, we first vaccinated six-week-old mice with inactivated recombinant H9N2-WT and H9N2-TM viruses twice to check antibody responses. cord-002842-4evbeijx 2018 cord-002843-dvfmpm54 2018 We create a geometric analysis method (called GenomeLandscaper) to conduct landscape analysis of genome-fingerprints maps (GFM), trace large-scale repetitive regions, and assess their impacts on the global architectures of assembled chromosomes. Specifically, we delete a 1.30-Mbp (from 9,999,936 bp to 11,299,986 bp) target segment (Supplementary Dataset 1) from the prior-cleaned GRCh38p1.chrY, as guided by the turning-changed long sharp straight line on the 2D-trajectory map (X-Length) of the GGFM (Fig. 4a ). We conclude that the 1.30-Mbp target segment (Supplementary Dataset 1) does locate in the centromeric and pericentromeric region of GRCh38p1.chrY (and throughout GRCh38p10.chrY) (Figs 3, 4 and 5), which encourages us to trace its sub-constituents that contributed to the observed turning-changed long sharp straight line on the GGFM (Figs 3 and 4 ). cord-002844-jv42o789 2018 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. cord-002874-9rxv6fy9 2018 Here we applied this approach to test the efficacy of the 222-nm far-UVC light to inactivate influenza A virus (H1N1) carried by aerosols in a benchtop aerosol UV irradiation chamber, which generated aerosol droplets of sizes similar to those generated by human coughing and breathing. If these results are confirmed in other scenarios, it follows that the use of overhead low-level far-UVC light in public locations may represent a safe and efficient methodology for limiting the transmission and spread of airborne-mediated microbial diseases such as influenza and tuberculosis. In conclusion, we have shown for the first time that very low doses of far-UVC light efficiently inactivate airborne viruses carried by aerosols. If these results are confirmed in other scenarios, it follows that the use of overhead very low level far-UVC light in public locations may represent a safe and efficient methodology for limiting the transmission and spread of airborne-mediated microbial diseases. cord-002929-oqe3gjcs 2018 cord-002932-5e7xrd1y 2018 In the ferret model, these studies demonstrated that the inoculation of animals with highly pathogenic avian influenza H5N1 virus via the aerosol route led to higher nasal wash virus titers, earlier onset of clinical signs, and/or a broader spectrum of disease compared with infection via intranasal inoculation despite no difference in lethality [9] [10] [11] . On day 3 post-infection, VN3040 virus was recovered from nasal swabs of two and three animals in the conventional and aerosol method groups, respectively, and the mean virus titers were comparable between the two groups. Cynomolgus macaques were inoculated with 4 ml of a 10 7 PFU/ml solution of the highly pathogenic H5N1 avian influenza virus A/Vietnam/ UT3040/2004 strain (VN3040) through the aerosol route by using the ultrasonic nebulizer NE-U17 (defined as "the aerosol method group"). In contrast, VN3040 replicated well in the right-and left-lower lung lobes of the infected animals in the conventional method group [the virus mean titers were 3.51 and 4.75 log 10 (PFU/g), respectively]. cord-002956-e5ihpe4i 2018 title: Ventilator Dependence Risk Score for the Prediction of Prolonged Mechanical Ventilation in Patients Who Survive Sepsis/Septic Shock with Respiratory Failure A total of 379 patients with sepsis or septic shock and acute respiratory failure requiring mechanical ventilation were admitted to the medical intensive care unit in the Kaohsiung Chang Gung Memorial Hospital from August 2013 to October 2015. We also tested and found that SOFA PaO 2 /FiO 2 subscore and GCS subscore on admission day 7 could help predict ventilator dependence on sepsis and septic shock patients with significant difference in univariate analysis ( Table 5 ). Ventilator dependence risk score, including a history of stroke and data from day 7 (thrombocytopenia, acidosis, and the higher fraction of inspired oxygen), can be applied to predict prolonged mechanical ventilation in patients who survive sepsis and septic shock. cord-003004-iif2lnez 2018 The present study describes species-specific clinical presentation, the genetic variability and HPIV circulation in Viet Nam. The outcome of RSV infection in hospitalized children under 2 years of age presenting with acute lower respiratory infection (ALRI) in Ho Chi Minh City was described previously 17 . Samples were sourced from two previous acute respiratory infection (ARI) cohorts among in-and outpatients, that were conducted at Children''s Hospital 1 and 2 in Ho Chi Minh City, Viet Nam during years 2009 and 2010. For sequencing, HPIV-positive samples were further amplified in a hemi-nested PCR approach with newly designed species-specific primers targeting overlapping regions of the viral genome (Table S2) . In this study, the median age and gender distribution of infected children and frequency of clinical presentation (fever, cough, sore throat, runny nose and nasal congestion) as well as vital signs (pulse and respiratory rate) and duration of illness at presentation were similar between HPIV species (p > 0.05). cord-003011-vclnb0eh 2018 cord-003055-88q36g00 2018 The aim of the present study was to investigate long-term outcomes of the offspring in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) model and the effect of maternal molecular hydrogen (H(2)) administration. We have previously demonstrated in the MIA mouse model that maternal administration of H(2) attenuates oxidative damage and neuroinflammation, including induced pro-inflammatory cytokines and microglial activation, in the fetal brain. Since MIA has been considered to be a cause of behavioral abnormalities in offspring, including ASD/ Schizophrenia-like behavior, we subsequently evaluated the effect of LPS and maternal administration of HW on short-term memory, sociability, social novelty, and sensorimotor gating. Based on those findings, we subsequently performed Nissl staining and evaluated the number of neurons in the amygdala, cerebral cortex, and hippocampus to investigate the brain regions related to the results of the behavioral deficits induced by LPS exposure. cord-003148-o7y3wygc 2018 However, the results of the inoculation of the tracheal swab samples into 10-day-old embrynated chicken eggs showed that 14 out of 15 (93.3%) chickens vaccinated with rNDV expressing codon optimized S protein of IBV and 0 out of 5 (0%) of non-infected chickens were shedding virus in trachea, respectively, whereas 15 out of 15 (100%) of chickens of all other groups were shedding virus in the trachea (data not shown). To evaluate the effect of the route of inoculation of virulent IB challenge virus on the outcomes of the protective efficacy of rNDV expressing codon optimized S protein of IBV, SPF chicks were immunized at 1-day-old age. The protective efficacy of rNDV expressing codon optimized S gene of IBV was determined by challenging the immunized chickens with 10 4 EID 50 virulent IBV strain Mass-41 by the intraocular route at 3 week post-immunization. cord-003166-k3jxvzfi 2018 Even though the HN amino acids sequences were similar to those from viruses in the proposed genera Shaanvirus, it was also related to that of Sendai virus and human parainfluenza virus 1, which belong to a different genus, Respirovirus showing (Table 1) . In addition, among three pooled sera (two mouse sera each) against human parainfluenza virus 1 (KBPV-VR-44), one pooled serum was cross-reactive to the bat paramyxovirus B16-40 with 40 as the end-point titer for the fluorescent signal ( Table 2 , Fig. 4 ). Notably, even though the HN amino acids sequences were similar to those from viruses in the proposed genera Shaanvirus, it was also related to that of Sendai virus and human parainfluenza virus 1, which belong to a different genus, Respirovirus (Table 1) . In fact, in this study, when mouse antisera were made and tested against bat paramyxovirus B16-40 and human parainfluenza virus 1 (KBPV-VR-44), the two viruses were partially cross-reactive to each other in an indirect immunofluorescence assay. cord-003196-fdb6az0v 2018 title: Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells These changes in gene expression indicate the potential for hypercapnia to impact bronchial epithelial cell function in ways that may contribute to poor clinical outcomes in patients with severe acute or advanced chronic lung diseases. Major clusters from hypercapnia-downregulated genes are linked to immune response, nucleosome assembly, cell differentiation, oxidation reduction, and ion and lipid transport (Fig. 2) . In addition, the suppressive effect of elevated CO 2 on immune gene expression in the airway epithelium, along with similar effects on immune cells, suggest a reason why severe COPD and other lung disease associated with hypercapnia all carry a high risk of pulmonary infection. Thus, CO 2 -induced alterations in airway epithelial gene expression may underlie the increase in mortality associated with hypercapnia in advanced COPD, as well as community-acquired pneumonia 9 , adenoviral lung infections 10 and cystic fibrosis 11 . cord-003387-82573enr 2018 title: Gene expression profiles alteration after infection of virus, bacteria, and parasite in the Olive flounder (Paralichthys olivaceus) In this study, we carried out transcriptome analysis using the olive flounder gill tissues after infection of three types of pathogens (Virus; Viral hemorrhagic septicemia virus, Bacteria; Streptococcus parauberis, and Parasite; Miamiensis avidus), respectively. Our goals are to provide plenty of genomic knowledge about olive flounder transcripts for further research and report genes, which were changed in their expression after specific pathogen infection. To profile gene expression after infection of three pathogens (VHSV, Streptococcus parauberis, and Miamiensis avidus), transcriptome analysis was conducted using gill tissues of olive flounders, respectively. In this study, we understood the relation between three types of pathogen infection and differential gene expression in the olive flounder genome through transcriptome analysis, respectively. cDNA microarray analysis of viral hemorrhagic septicemia infected olive flounder, Paralichthys olivaceus: immune gene expression at different water temperature cord-003444-dmpoy0b1 2019 cord-003490-swlkjtyo 2019 The current investigation applied a Bayesian modeling approach to a unique experimental transmission study to estimate the occurrence of transmission of foot-and-mouth disease (FMD) during the incubation phase amongst group-housed pigs. This current study focused on investigating the concept of θ and ω for direct contact transmission of a virulent strain of foot-and-mouth disease virus (FMDV) amongst juvenile domestic pigs, and examining the impact of pre-clinical transmission on simulated outbreak size and severity within a US swine production system assuming either optimal or suboptimal response conditions. The most noteworthy findings from this approach were the substantial changes in the modeled estimates of the duration of latency and subclinical infectiousness (ω) when defining the onset of infectiousness by either the occurrence of clinical signs of FMD in donor pigs or by any detection of FMDV RNA in OPF. cord-003504-wjab4y0g 2019 Finally, an in vivo immunisation model showed that BCG vaccination under PD-L1 blockade could enhance antigen-specific memory CD4 T-cell responses. Here, we show for the first time that BCG can induce the up-regulation of PD-L1 on both macrophages and dendritic cells (DCs) via autocrine/paracrine secretion of STAT3-activating cytokines, chiefly IL-6 and IL-10. Upon infection with BCG, both APC types expressed high levels of PD-L1 compared to the unstimulated control at 24 h and 48 h (p < 0.0001), and a dose trend was observed for increasing MOI in macrophages at 48 h. To confirm that STAT3 was mediating the up-regulation of PD-L1 expression by BCG, cells were then pre-treated with Stattic or a vehicle control for 2 hours before infection with a low dose of bacteria (Fig. 5C) . BCG vaccine mediated reduction in the MHC-II expression of macrophages and dendritic cells is reversed by activation of Toll-like receptors 7 and 9 cord-003505-qr6ukfti 2019 In this work, we have developed a novel colorimetric molecular assay that integrates nucleic acid analysis by dynamic chemistry (ChemNAT) with reverse dot-blot hybridization in an array format for a rapid and easy discrimination of Leishmania major and Trypanosoma cruzi. Once the abasic PNA probes hybridize with target sequences, the SMART-C-Biotin dynamic incorporation takes place, enabling the unequivocal identification of the parasite present in the amplicon sample, because of the unique colorimetric pattern that each Trypanosomatid amplicon generates. DNA amplicon products were denatured and then together with the dynamic chemistry reaction reagents added directly into the internal column of the Spin-Tube that supports the nylon membrane for the color-development assay (Fig. 4) . 20 ng of human gDNA were used as PCR template for its amplification with the set of primers described in our study and neither colorimetric signals nor bands were detected using the Spin-Tube and capillary electrophoresis analysis respectively (Fig. 5 , column 2: 2A and 2B), hence probing the specificity when human gDNA is present. cord-003558-7lvqpz21 2019 We present the clinical use of EIT in six conditions: Asthma, Ventilation weaning and expansion recoil, Sequential Lobar Collapse, Targeted Physiotherapy, Pleural Effusion assessment, and PEEP optimisation. Electrical Impedance Tomography (EIT) is a radiation-free functional modality that enables bedside imaging and monitoring of lung function and expansion. It has been used in various clinical settings including acute respiratory distress syndrome (ARDS), establishing the best positive end expiratory pressure (PEEP) [8] [9] [10] [11] [12] , the response of the lungs to recruitment manoeuvres [12] [13] [14] [15] [16] and trying to minimize areas of collapse and hyperinflation 6, 17 . Clinical interest in this method has been driven by the need for bedside monitoring of the dynamics of the lungs and the effects of ventilatory manoeuvres, including changes in ventilator settings, suctioning, chest drains, positioning and physiotherapy. Clinical interest in this method has been driven by the need for bedside monitoring of the dynamics of the lungs and the effects of ventilatory manoeuvres, including changes in ventilator settings, suctioning, chest drains, positioning and physiotherapy. cord-003623-n01rgqyv 2019 To evaluate the ability of our system comprising seven filovirus-specific indirect ELISAs to predict the filovirus species most antigenically similar to the species responsible for past infection, we tested seven Marburg virus convalescent serum 35 or whole blood 36 samples collected from experimentally inoculated ERBs. Five of these samples www.nature.com/scientificreports www.nature.com/scientificreports/ were collected four weeks post primary Marburg virus inoculation 35, 36 , while two of the samples were collected at 23 and 27 weeks post primary inoculation following a "natural" boost (i.e., Marburg virus-specific antibody levels waned in these bats and then increased following contact with infectious cagemates) 36 . Although significant levels of serological IgG cross-reactivity were observed between the prime-boost filovirus-specific antisera and some of the filovirus antigens, when the overall covariance of the seven-individual indirect ELISAs in the system were considered, we were able to predict the filovirus species responsible for past infection 100% of the time using as little as 25 μL of sera (each serum was tested against each antigen in duplicate). cord-003667-u1xa44nw 2019 cord-004006-tfp2idq2 2019 cord-004016-iaktm72a 2019 The Ag@cur-P(MEO 2 MA) core-doped shell hybrid NPs were prepared by free radical precipitation polymerization (FRPP) of the stimuli-responsive MEO 2 MA monomer in the presence of TEGDMA (crosslinking agent), using curcumin-decorated Ag@cur NPs as seeds (Fig. 1) . However, the dual key-role of curcumin, as reducing agent and growth-polymerization promoter in this specific synthesis, required additional investigation to understand and optimize the chemical variables (solubility, concentration and reaction temperature) in order to achieve homogeneous, monodisperse and mononuclear Ag@cur-P(MEO 2 MA) core-shell nanohybrids. The presence of hydrophobic curcumin nearby the metallic surface led to precipitation-polymerization of P(MEO 2 MA) around the AgNPs previously formed (Fig. 1B,C) ; and the resulting Ag@cur-P(MEO 2 MA) nanoparticles were born negatively charged due to the persulfate groups from the APS initiator, which promotes their colloidal stability. cord-004060-nxw5k9y1 2019 After adjusting for other covariates, a spatially unstructured random effect term (v i ), a spatially structured conditional autoregression term (υ i ), a first-order random walk-correlated time variable (γ 1j ), and an interaction term for time and place (δ ij ) in the multivariate adjusted spatiotemporal model, the flu vaccines (per million doses), flu surveillance protocols, rate of influenza A (H1N1)pdm09, latitude and longitude still remain statistically significant. Based on the incidence data of influenza gained from the Chinese Notifiable Infectious Disease Reporting System, we used the Bayesian spatiotemporal model in this study to assess the space-time patterns of the influenza epidemic at the prefecture level in mainland China from 2005 to 2018 and explored several factors that may be associated with the changing spatial and temporal patterns in the influenza incidence risk. cord-004062-yxx3xxio 2019 We performed an in vitro study to evaluate the sequential immunological reactions and viral load in dengue virus type 2-infected mononuclear cells of patients with ESRD (n = 34) and in healthy controls (n = 30). The concentrations of interleukins (IL)-1 receptor antagonist (Ra), IL-2, IL-6, IL-8, IL-10, IL-12p40, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1b (MIP-1b), vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α and viral load cycle threshold (Ct) were measured in the dengue virus type 2-infected mononuclear cells at 6 h, 24 h, 48 h, and 72 h post-infection. In the present study, eleven immune mediators and viral load Ct values were measured in DENV2-infected mononuclear cells of adults with ESRD, and in healthy participants. Our results have been somewhat inconsistent with the reported overwhelming immune activation that is associated with dengue disease severity 5, 7 ; however, our findings clearly reflect the impairment of immune responses in vitro study of DENV2-infected mononuclear cells in ESRD patients. cord-004069-nuep8nim 2019 A pharmacokinetic (PK) study in rhesus macaques (2 groups of 2 males and 2 females) was performed to monitor plasma concentrations of AQ (Fig. 1a ) and the active metabolite DEAQ (Fig. 1b) . samples from infected animals collected on days 0, 3, 5, and 7 postexposure and on day of necropsy (days 6, 7 or 8) were analyzed for determination of plasma levels of AQ and its metabolite DEAQ. Animals that were treated on days 0, 1 and 2 (Group 2, Fig. 7a ), had plasma DEAQ levels ranging from 0 to 205 ng/ml on days 3, 5, 7 and 8 postexposure. www.nature.com/scientificreports www.nature.com/scientificreports/ The goal of the study was to treat animals with AQ using a similar dosing strategy as for human patients, with a target blood concentration range of the parent compound AQ of 29.2 ± 10.9 ng/mL 12 . cord-004140-ujzrqzv3 2020 cord-004150-ybikajhh 2020 The genes with most markedly increased expression included members of the erythrocyte binding antigens (EBA), reticulocyte binding homologues (RH), surface associated interspersed proteins (SURFIN), exported protein family 1 (EPF1) and Plasmodium Helical Interspersed Sub-Telomeric (PHIST) gene families. The data indicate changes in expression of a repertoire of genes not previously associated with erythrocyte invasion phenotypes, suggesting the possibility that moving suspension culture may also select for other traits. Additionally, a large number of virulence associated genes, including members of the surface-associated interspersed protein (SURFIN) family, exported protein family 1 (EPF1), ring exported protein 1 (REX1) and interspersed repeat antigen (FIRA); all of which are exported into host erythrocytes, were significantly expressed at higher levels in SP parasites relative to BL (Fig. 2) . A comparison of the levels of differential expression of the eba and rh gene between ST and SP parasites in the current RNA sequencing study and our previous RT-qPCR analysis shows a strong positive correlation of results from the two studies ( Supplementary Fig. 12 ). cord-004156-79peyzc9 2020 cord-004170-ri5qsarz 2020 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. cord-004181-exbs3tz7 2020 The efficacy of the chimeric multiepitope construct as a recombinant protein vaccine and DNA vaccine was evaluated in Nile tilapia, followed by S. The epitopes of immunogenic proteins were predicted by the BCPREDS server based on B cell epitopes to be used in chimeric multiepitope vaccine construction. In this study, not only immunogenic proteins from the immunoproteomics analysis were used but also other subunit vaccine candidates were subjected to epitope prediction and combined to produce a chimeric multiepitope vaccine. The recombinant chimeric multiepitope protein vaccination showed that 45F2 and 42E2 produced cumulative mortality rates of 30.00 ± 10.00% and 26.67 ± 5.77%, respectively, which were significantly lower than those of the negative control group, at 70% (P < 0.05) (Fig. 6A) . agalactiae serotype Ia and III demonstrated that fish vaccinated with recombinant protein vaccine 42E2 and 45F2 showed cross-reactivity to whole cell lysate of S. cord-004222-z4butywi 2020 We characterized the heavy chain and kappa light chain antibody repertoires of a model animal, the OmniRat, by high throughput antibody sequencing and made use of two novel datasets for comparison to human repertoires. Multiple differences were found in both the heavy and kappa chain repertoires between OmniRats and humans including gene segment usage, CDR3 length distributions, class switch recombination, somatic hypermutation levels and in features of V(D)J recombination. We individually separated total RNA from spleens and lymph nodes of three unimmunized OmniRats and PCR amplified the heavy and kappa chain antibody V gene segments. We started by making intra-animal comparisons, intra-species comparisons and inter-species comparisons of the immunoglobulin gene segment usage frequencies for each antibody repertoire by performing hierarchical clustering ( Fig. 1 ) and linear regression analysis (Figs. cord-004280-c470nlie 2020 In this study, we evaluated the use of a bioaerosol sampling method to noninvasively detect and quantify airborne influenza A virus (IAV) densities in a public elementary school. Significantly different (p = 0.049) airborne IAV densities were detected between all three indoor locations (i.e., gymnasium, classroom, and corridor) and all positive samples were collected during the last two weeks of 66 , and a 20-30% relative humidity level; Descriptive of an average elementary school student in the USA weighing ~23-32 kg with an assumed tidal volume (V T ) of 7 mL per kg of body mass. Given the high airborne IAV densities detected in the school corridor, along with elevated student contact rates, it is plausible to conclude that the school corridor is a "hotspot" for influenza virus transmission. cord-004292-6lnxb0px 2020 With their flexible form factors, two pacemakers were implanted epicardially on the right and left ventricles of a porcine model and were inductively powered at 13.56 MHz and 40.68 MHz industrial, scientific, and medical (ISM) bands, respectively. The closed-chest pacing only requires the external source power of 0.3 W and 0.8 W at 13.56 MHz and 40.68 MHz, respectively, which leads to specific absorption rates (SARs) 2–3 orders of magnitude lower than the safety regulation limit. Not only is the need for intravascular leads eliminated, but synchronized and leadless pacing across different chambers becomes feasible, which offers the flexibility in customizing patient-specific CRTs. Prior studies have investigated wirelessly powered single-site cardiac pacing on rodent, rabbit and open-chest porcine models 4, 5, 21 . To demonstrate wireless CRT, two such pacemakers were epicardially implanted on the right ventricle (RV) and left ventricle (LV) in a porcine model for synchronized biventricular (BiV) pacing with controllable interventricular offsets. cord-004310-hl7fa4af 2020 We recorded patient information, including age, sex, surgical procedure, and daily severity data (including severity of organ dysfunction and sedative/muscle relaxant dosages) during PICU stays for five days after the end of muscle relaxant usage. We found that, overall, the amount of MDZ administered was increased in DS versus controls after ending muscle relaxants and observed the reduced sedative effect of MDZ for DS patients while DEX was not different as estimated by Bayesian inference modeling. To adjust these biases, we used multivariate www.nature.com/scientificreports www.nature.com/scientificreports/ analysis with respect to these factors but we also "double checked" our results by using the demographic data propensity score for DS patients as a covariate in Bayesian inference modeling. To conclude, we conducted a retrospective study based on validated evaluative tools that indicated a need for higher doses of MDZ with higher doses of compensating sedatives for the 5-day period immediately after muscle relaxant usage following pediatric heart surgery. cord-004342-9uok77wb 2020 cord-004378-g1rxygef 2020 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. 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. Panel B: Material balance for Trp and Tyr residues determined by UPLC analysis with direct fluorescence detection on acid-hydrolysed UV-exposed CRP-cAMP complex. UPLC analysis of native and oxidized CRP showed that UV exposure of CRP resulted in significant modification (relative to controls) to Trp, Tyr, Ser, Met and Arg residues (Fig. 3A) . Q-TOF MS analysis of cAMP-CRP-DNA complexes exposed to UV light showed a similar pattern of damage, but higher extents of Met modification (7.6%; Fig. 3C ). cord-004379-91a7sgir 2020 The aim of this study was to evaluate age-related clinical manifestations of adverse events (AEs) related to NAIs. FAERS and WebMD data were downloaded. A disproportionality analysis showed that signals for vomiting and hallucinations were detected in younger patients given oseltamivir, while an abnormal hepatic function, cardiac failure, shock, and cardio-respiratory arrest were detected in older patients given peramivir. However, there is still concern regarding the adverse effects of NAIs. This study analyzed the age-related AEs associated with NAIs using data from FAERS and WebMD. Oseltamivir was the NAI most commonly showing AEs in the FAERS data, and the most common AEs for this drug were psychiatric and gastrointestinal disorders, similar to the findings of previous studies 8, [13] [14] [15] [16] . However, in the WebMD data, we could not detect signals by these disproportionality analyses due to the small number of AE cases, although psychiatric and gastrointestinal disorders were the most common AEs reported. cord-004385-xna32qve 2020 title: Use of corticosteroids in influenza-associated acute respiratory distress syndrome and severe pneumonia: a systemic review and meta-analysis We obtained the following data: (a) characteristics of studies (design, setting, country, period, methodological details for quality assessment); (b) characteristics of participants (demographics, co-morbid illnesses, disease severity, numbers in each group, influenza virus type); (c) characteristics of interventions (type, dose, timing and duration of corticosteroid use); and (d) outcomes. Another study reporting the result of 62 patients with acute respiratory failure due to influenza showed no statistically significant difference between low dose and high dose corticosteroid therapy (8/19 versus 7/19, p > 0.05) 16 . The overall findings of this meta-analysis indicated that patients with pneumonia or acute respiratory distress syndrome who were administered corticosteroids had significantly higher mortality and incidence of nosocomial infection but the use of corticosteroids did not influence the length of hospital stay. cord-004416-qw6tusd2 2020 cord-004418-08dljap3 2020 In this study we evaluated the antibody responses and efficacy of an aluminum hydroxide adjuvanted purified inactivated Zika vaccine (PIZV) against challenge with Zika virus (ZIKV) strain PRVABC59. As with neutralizing antibodies, all PIZV doses were immunogenic and no anti-Zika IgG was detected in the control group prior to ZIKV challenge. PIZV elicited a dose dependent neutralizing antibody immune response and an anti-Zika IgG response which correlated with a reduction in ZIKV vRNA post-challenge (Table 2 ). Vaccinating with a broad range of PIZV dose levels enabled us to correlate both neutralizing and anti-Zika IgG antibody titers to protection against ZIKV infection. A Zika RVP assay (Sonnberg et al., manuscript in preparation) was used to determine neutralizing antibody titers in serum following the administration of PIZV (study days 1, 29, 57, and 71), and 30 days post-ZIKV challenge (day 101). cord-004419-81w7apdk 2020 Little variation was seen between level two and three units, although gestational age was a significant independent variable for several practices, including delayed cord clamping, stabilisation with intubation, early enteral feeding and caffeine administration. Prospective, anonymised audits of the management of RDS in all preterm infants born at <34 weeks gestational age and cared for in a participating neonatal unit in Wales were undertaken. This represented the best-practice document for the management of RDS in infants born at <34 weeks gestational age, concentrating on areas which were supported by Grade A evidence (http://www.gradeworkinggroup.org/). The audit proforma was based upon the recommendations in the European Consensus Guideline on the Management of RDS in Preterm Infants 2013, and concentrated on management areas which were supported by Grade A evidence 9 . The 2013 edition of the European consensus guideline recommended a change in practice towards stabilising preterm infants on non-invasive respiratory support at delivery rather than elective intubation 9 . cord-005507-equnyib7 2020 Given this, we developed serum epitope repertoire analysis (SERA), a method to rapidly discover conserved, pathogen-specific antigens and their epitopes, and applied it to develop an assay for Chagas disease caused by the protozoan parasite Trypanosoma cruzi. We applied serum epitope repertoire analysis (SERA) to discover shared, but highly specific immunogenic epitope motifs associated with Chagas disease caused by the protozoan parasite Trypanosoma cruzi, and thereby develop a serological assay. To identify antibody epitope motifs specific to Chagas disease, we applied the IMUNE motif discovery algorithm 15 (see Methods for parameters) to epitope repertoires from 28 Chagas specimens and 30 non-Chagas sera, yielding 331 candidate motifs (Supplementary Table S2 ). Using Chagas disease seropositive specimens, a panel of 31 peptide motifs was identified that exhibited 100% sensitivity (60/60) and 100% specificity (120/120) in independent validation sets. cord-007851-v6h1yro7 2020 We used a combined application of this method involving immune-specific signature analysis and HLA-associated peptidomics using samples from six patients with triple-negative breast cancer (TNBC) in order to select immunogenic HLA epitopes for in vitro testing. Integrated WTS data revealed a higher priority to select promising HLA-peptides via high-resolution bioinformatics analysis, showing immune-cell-specific signatures and TCR-repertoire diversity in tumors. We then found a positive correlation between TCR diversity, reflecting clonal composition, and the expression of MHC-class І molecules, suggesting that active tumor-antigen presentation promotes the generation of antigen-specific TILs. Additionally, immune-specific signature analysis can discriminate specific immune-cell types in each patient and thus enhance the efficiency of selective HLA-peptidomic approaches. In this study, the HLA-peptidomics approach combined with comprehensive analysis of immune-specific signatures and TCR repertories showed high selectivity to determine the immunogenic T-cell epitopes. Identification of potential vaccine epitopes coupled with immune-specific signature analysis, HLA-peptidomics, and single-cell-based immunogenicity testing offers a discriminative and powerful tool for cancer-vaccine development. cord-009690-kbwz7xop 2020 title: Development of a Nanoparticle-based Lateral Flow Strip Biosensor for Visual Detection of Whole Nervous Necrosis Virus Particles The principle of viral particles detection based on lateral flow biosensor with functionalized nanoparticles is presented in Fig. 1 . Nodavirus intact particles (virions), obtained either from SSN-1 cell culture supernatants or homogenized tissue samples, are directly applied on the LFB. The sample contains the nodavirus particles (virions) and is applied on the conjugation pad next to functionalized gold nanoparticles (Au) with polyclonal anti-nodavirus antibody. Application of that conjugate on the LFB resulted in a strong signal in the control zone, confirming the successful conjugation of anti-nodavirus antibody to Au nanoparticles (Fig. 2e) . To enable on site analysis of nodavirus, we developed and optimized a paper LFB based on gold nanoparticles for easy, specific and sensitive visual detection of nodavirus viral particles (virions) in biological samples. cord-009691-gkynxdz3 2020 The present study revealed that several cagPAI genes from Latin American Western HP strains contains a number of non-synonymous variants in relatively high frequencies which could influence on the clinical outcome. When comparing the frequency of the 520 selected alleles between the isolates from subjects with gastritis and isolates from subjects with IM or GC we found statistically significant differences in allele distribution for three polymorphisms in cagA gene (Q/K427R, N467G and V1041T), three in cagC gene (V22I, V37I, I45V), one in the cagE gene (K981E), one in cagL gene (S10F), one in cagX gene (G11N), one in cagS (G146D), one in cagζ (S35A), three in cagδ (V353I, P406L, N407E) and one in cagβ (N125A) ( Table 2) . In a previous study conducted with amplicon sequencing by 454 for 84 Mexican and 11 Venezuelan samples we reported 10 non-synonymous SNPs with differential allelic distribution between gastritis and gastric cancer at conventional P-values between 0.01-0.05 28 . cord-010140-nl1j2s56 2020 cord-010328-uxpedpz8 2020 cord-010640-s1oqphvn 2020 In an effort to discover new LASV vaccines, we employ several sequence-based computational prediction tools to identify LASV GP major histocompatibility complex (MHC) class I and II T-cell epitopes. In this study, we have identified and characterized T and B-cell epitopes for the LASV GP using different sequence and structure-based computational epitope prediction methods. MHC-I T-cell epitope prediction with the LASV GP sequence was performed using three different methods separately: ProPred-1, CTLPred, and NetCTL1.2, and the results are shown in Supplementary Table S1. MHC-II T-cell epitope prediction with the LASV GP sequence was performed using three different methods separately: ProPred, NetMHCII 2.3, and EpiTOP 3.0, and the results are shown in Supplementary Table S2 . Docking of the four consensus MHC-I epitopes (Table 1 ) was performed using Autodock Vina, which enabled the docking of epitopes obtained from the sequence-based MHC-1 T-cell prediction into the promising allele structures. cord-010675-acdfvjm5 2020 The aims of the present work were to determine the prevalence and titer of serum antibodies against several rotavirus VP8* proteins from different P genotypes in children and adults in Valencia, Spain; and to determine the role of the secretor status (FUT2(G428A) polymorphism) in the antibody response. Significant differences in the antibody titers between secretors and non-secretors were found when the whole viral particles from the Wa rotavirus strain (G1P[8]) were used as the antigen. Sero-epidemiological studies are of importance to elucidate the different viral agents and genotypes that are circulating in a particular area, for this reason the main aim of this work was to determine the serum antibody prevalence and titer to a panel of VP8* proteins from different rotavirus genotypes (P [4] , P [6] , P [8] , P [9] , P [11] , P [14] and P [25] ) in children and adults. cord-011892-b9zlig0r 2020 In this work, two different network construction algorithms, Weighted correlation network analysis (WGCNA) and Multiscale Clustering of Geometric Network (MEGENA), were applied on publicly available glioma, control brain and stem cell gene expression RNA-seq datasets, to identify gene network regulatory modules associated with GBM. Characterization of HuAgeGBsplit_18 (WGCNA) and c1_HuAgeGBsplit_32/193 (MEGENA) modules showed significant enrichment of rodent quiescent stem cell marker genes (GSE70696_QNPbyTAP). Enrichment of proliferative and quiescent stem cell marker genes identified by differential gene expression analysis above, in WGCNA and MEGENA modules was determined using useListEnrichment R function 22, 23, 46 . showed that HuAgeGBsplit_18 WGCNA GBM module and its equivalent c1_HuAgeGBsplit_193/32 MEGENA GBM modules, were the only GBM modules significantly enriched with proliferative and quiescent stem cell marker genes (Fig. 4A,B) . A meta-analysis was performed on publicly available high-throughput gene expression datasets from human glioma samples, control human brains, normal stem cells and GBM cells in quiescent and proliferative states 18, [26] [27] [28] [29] [30] [31] [32] [33] [34] . cord-012742-lpk6r54i 2020 Soaking experi-Scientific RepoRtS | (2020) 10:14422 | https://doi.org/10.1038/s41598-020-70870-w www.nature.com/scientificreports/ ments were performed with crystals of GETV macro domain co-crystallized with ADP-ribose by adding mother liquor supplemented with aspartic acid to the crystallization droplet followed by 2-3 h or overnight incubation at 20 °C. Finally, we obtained a last GETV macro domain/ADP-ribose complex by co-crystallizing the protein with 3 mM ADP-ribose and 3 mM aspartic acid and diffraction data were collected to 1.45 Å resolution. Lastly, co-crystallization of GETV macro domain with low concentrations of ADP-ribose and aspartic acid (3 mM each) led to a structure where the distal ribose is covalently attached to Cys34. In addition to the pose of ADP-ribose found in other structures of alphavirus macro domain, this work reveals original features such as the opening of the distal Scientific RepoRtS | (2020) 10:14422 | https://doi.org/10.1038/s41598-020-70870-w www.nature.com/scientificreports/ ribose, and its stabilization by Ser30, representing a peculiar GETV specific substitution in the catalytic loop. cord-013977-xb0r2axf 2020 cord-030295-jlhht2l9 2020 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. cord-031937-qhlatg84 2020 In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. The contributions of the microorganisms in the co-evolved IBD and ReA as part of the disease network was created through the interactive maps of the essential host interaction proteins (verified using literature survey) and the information processed through gene expression data analysis 64 . The pathways of the above host interacting proteins were found out using KEGG database that provides ontologies for proteins related to biological processes 67 www.nature.com/scientificreports/ Subsequently, the role of drugs or inhibitors used to suppress the effect of IBD and ReA such as indomethacin, prednisone, ciprofloxacin, sulfasalazine, azathioprine, methotrexate and hydroxychloroquine was scored in the disease network through their docking studies against the potential targets (both host as well microbial targets) as per published methodologies 68, 69 . cord-034746-uxhpufnv 2020 We therefore analyzed standard markers of glomerular proteinuria (e.g. immunoglobulin G [IgG]), urinary nephrin excretion (podocyte injury) and serum levels of the soluble urokinase plasminogen activator receptor (suPAR), a proposed pathomechanically involved molecule in INS, in PUUV-infected patients. On admission, patients suffering from hantavirus infection showed significantly increased urinary nephrin, IgG, α1-MG and serum suPAR levels compared to healthy controls (Fig. 3A ). Though, urinary biomarker levels decreased in both groups over time, patients with severe PCR showed significantly higher levels of nephrin, IgG, ACR and PCR during the first 48 h after admission ( Table 2 ). Our data show a strong association between urinary nephrin levels and the extent of (non-selective) glomerular proteinuria, suggesting that hantavirus infection causes a pronounced podocyte damage and subsequent impairment of the GFB. To date, one other study showed significantly elevated blood suPAR levels and their association with hantavirus disease severity but did not include nephrinuria and the extent of proteinuria in their analysis 19 . cord-254090-x8tnweih 2015 It is interesting to notice that the required threshold electric field magnitudes at the resonant frequency (86.9 V/m) to fracture H3N2 viruses as shown in Fig. 3 (c) are within the IEEE Microwave Safety Standard (106 V/m), indicating high SRET efficiency, even though the quality factor of the H3N2 virus is low. To further investigate the efficiency of this SRET effect from microwave to virus and the threshold effect, we further measured the inactivation ratio of H3N2 virus with different power densities at the resonant frequency ~8 GHz of the confined acoustic dipolar mode. Second, at the resonant frequency, we do observe H3N2 virus inactivation by illuminating 82 W/m 2 (lower than the IEEE safety standard in public space) 8 GHz microwaves on our viral solution, corresponding to an average 87 V/m electric field intensity inside the solution, confirming that our proposed simple model to estimate the field threshold (86.9 V/m) to structurally fracture the virus is quantitatively correct, especially combining the observed threshold effect as discussed above. cord-254653-4ffuivil 2020 We address the diffusion of information about the COVID-19 with a massive data analysis on Twitter, Instagram, YouTube, Reddit and Gab. We analyze engagement and interest in the COVID-19 topic and provide a differential assessment on the evolution of the discourse on a global scale for each platform and their users. We fit information spreading with epidemic models characterizing the basic reproduction number [Formula: see text] for each social media platform. Unlike previous works, we do not only focus on models that imply specific growth mechanisms, but also on phenomenological models that emphasize the reproducibility of empirical data 41 www.nature.com/scientificreports/ Most of the epidemiological models focus on the basic reproduction number R 0 , representing the expected number of new infectors directly generated by an infected individual for a given time period 42 . Furthermore, we model the spread of information using epidemic models and provide basic growth parameters for each social media platform. cord-255511-nk3iyg07 2020 Here, we propose a quantitative and systematic framework to identify spatial super-spreaders and the novel concept of super-susceptibles, i.e. respectively, places most likely to contribute to disease spread or to people contracting it. We applied this analysis framework to the Singapore public transport flow network, and identified the SSP and SSS using the SUI and SPI indexes. This study uses a community detection method (MapEquation algorithm 60 ) to identify the zones from the flow network, instead of using the administrative spatial boundaries (i.e. the boundaries of planning areas and regions as defined by the Singapore Government in its Master Plan 2014 59 ) that were designed and selected for governance and political purposes. Figure 7 shows the local out-and in-degree (left column), the outgoing and incoming neighborhood zone-entropy (central column) and coreness-entropy (right column) of the weekday (first two rows) and weekend (bottom two rows) flow networks. cord-255586-wshvvgxg 2020 The demographic features, clinical symptoms, laboratory results, comorbidities, co-infections, treatments, illness severities and chest CT scan results of 267 patients were collected from 1st January to 15th February 2020. | (2020) 10:17365 | https://doi.org/10.1038/s41598-020-74284-6 www.nature.com/scientificreports/ disease progression, no differences were found, suggesting this group of COVID-19 patients could be difficult to detect by using standard clinical data. All raw clinical and laboratory results were collected from electronic medical records system of the Central Hospital of Wuhan, followed by a follow up visit up to 14 days (also known as the discharge quarantine) to test for a re-positive nucleic acid assay. Definition of "re-positive": when a confirmed COVID-19 patient is detected SARS-CoV-2 RNA positive during the 14 days post-discharge quarantine (random test timing). Since understanding of the mechanisms of SARS-CoV-2 infection is still lacking, a careful discharge protocol should be applied (e.g. negative results of the nucleic acid tests of respiratory pathogens for 3 consecutive times), and post-discharge quarantine should be strictly observed, especially for severe and critical COVID-19 patients. cord-258678-0atfsivf 2013 Here, we report the development of a small and simple protein tag that complements the therapeutic and targeting functionalities of chimera with two functional domains: a dsRNA binding domain (dsRBD) for siRNA docking and a pH-dependent polyhistidine to disrupt endosomal membrane. Therefore, it is of critical importance to design a delivery system that is simple for potential regulatory approval and mass production, universal for all siRNAaptamer chimera, neutral and siRNA-binding specific to ensure aptamer targeting, and small to avoid major alteration of chimera''s biodistribution profile. To assess their dsRNA binding activity, siRNA-aptamer chimera labeled with fluorophore FAM were incubated with the protein tags and probed with gel electrophoresis (1% agarose). To evaluate the targeting specificity of the aptamer block, PSMA-positive LNCaP cells and PSMA-negative PC3 cells were treated with complex of chimera and dsRBD-His 18 (chimera/protein tag molar ratio at 152, 100 nM chimera) in serum free medium for 2 hours, followed by incubation in complete medium for another 12 h. cord-259378-5g2y68i2 2020 With recent technological advances in multiple research fields-such as materials science, micro-/nano-technology, cellular and molecular biology, and bioengineering-attention is shifting toward the development of new diagnostic tools that not only address needs for high sensitivity and specificity, but that fulfill economic, environmental, and rapid point-of-care (POC) needs, for groups and individuals with constrained resources and, possibly, limited training. This pump accepted commonly available silicone rubber tubing in a range of sizes, from 1.5 to 3 mm, and was capable of producing flow rates up to 1.6 mL/min 6 www.nature.com/scientificreports/ microfluidic technologies may be used for a variety of POC diagnostic applications (e.g., infectious diseases, COVID-19 diagnosis) because they are disposable, inexpensive, portable, and easy to use, especially when they are manufactured using low-cost materials such as paper (and other materials such as cotton or bamboo 7, 8 ). cord-259416-gvzp2h5g 2016 Systematic site-directed spin labeling (SDSL) and electron paramagnetic resonance (EPR) studies of IFITM3 in detergent micelles identified a single, long transmembrane helix in the C-terminus and an intramembrane segment in the N-terminal hydrophobic region. Systematic site scanning of spin labeling, EPR dynamic and accessibility analysis identified a C-terminal transmembrane α -helix and an N-terminal IFITM3 segment (composed of two short α -helices) lying on the surface of micelles. Collectively, the analysis of the accessibility parameter (Π O2 and Π NiEDDA ) and the immersion depth parameter (Φ ) derived from the power saturation experiments demonstrated that the IFITM3 protein contains a long transmembrane α -helix covering the residue sequence from A96 to A131 in the putative hydrophobic region. Therefore, the combined EPR and solution NMR studies clearly supported the type II transmembrane protein topology model for IFITM3, which is consistent with the previously proposed mechanism of its antiviral function. cord-259794-6qoksn00 2017 Porcine epidemic diarrhea virus (PEDV) replicates in the cytoplasm of infected cells, but its nucleocapsid (N) protein localizes specifically to the nucleolus. The results suggest potential linkages among viral strategies for the regulation of cell survival activities, possibly through an interaction of N protein with NPM1 which prevents its proteolytic cleavage and enhances cell survival, thus ultimately promoting the replication of PEDV. In this study, to determine the intracellular distribution of N protein at the protein level, PEDV-infected Vero E6 cells were lysed, separated into nuclear and cytoplasmic fractions, and analyzed by western blotting. This study was based on different lines of evidence, reflecting both in vivo and in vitro situations, and demonstrated that PEDV N protein is able to associate with the major nucleolar protein NPM1 of Vero E6 cells (Fig. 2) ; we failed to detect an interaction with the fibrillarin or nucleolin (See Supplementary Fig. S2 ). cord-260834-v254de8k 2019 The phage ELISA was conducted to measure the performances and effects of different blocking agents on the binding of αUbi phages against crude rUbi. Out of the four samples, the combination of PTM buffer and lysate showed the highest signal (1.226) detected with anti-c-myc-HRP as shown in Fig. 4c . Lysate preblocking and phage preincubation effects towards αUbi and M13KO7 phages against rUbi. To further optimize the biopanning conditions against crude antigens, the ''Yin-Yang'' (capture and eliminate) approach was designed to reduce non-specific binding by background phages. coli proteins in the crude fraction of rUbi with the actual concentration of rUbi being expected to be lower than the purified rUbi, the binding capability of αUbi is still unaffected as shown in phage ELISA assay upon affinity selection against crude rUbi. The blocking effect of PTM and E. cord-263088-zj14ro5j 2020 All trials across the ''olfactory'' , ''visual'' , and ''acoustic'' conditions of phase I were pseudo-randomised within a session so that each session consisted of an equal number of trials of left and right correct choices (based on the side of the chamber in which a container was placed), no one side was baited with food more than three consecutive times in a row, and the first three trials for each session across all conditions were always tests rather than controls to avoid a frustration effect. Phase I control containers (i.e., opaque with solid lids) were used as the stimulus containers in the test trials for this condition as we wanted the subject to make olfactory decisions based on the trail scent without being influenced by the odor of the food inside the container. cord-263627-8ufjh70o 2020 Covid-19 mortality rate was negatively associated with Covid-19 test number per 100 people (RR = 0.92, P = 0.001), government effectiveness score (RR = 0.96, P = 0.017), and number of hospital beds (RR = 0.85, P < 0.001). Furthermore, the negative association between Covid-19 mortality and test number was stronger among low-income countries and countries with lower government effectiveness scores, younger populations and fewer hospital beds. In the multiple regression analysis, Covid-19 mortality rate was regressed on Covid-19 test number, case number, critical case rate, government effectiveness score, proportion of population aged 65 or older, number of beds, deaths attributable to communicable diseases, and transport infrastructure quality score. Figure 1e and 1f exhibits that the negative correlation between Covid-19 mortality rate and test number was significant for countries with moderate (r = -0.33, P = 0.021) and low (r = − 0.42, P = 0.002) government effectiveness scores, respectively. cord-265211-a7whyds8 2017 title: miRNA-36 inhibits KSHV, EBV, HSV-2 infection of cells via stifling expression of interferon induced transmembrane protein 1 (IFITM1) In this study, we show the ability of host cell novel miR-36 to specifically inhibit KSHV-induced expression of interferon induced transmembrane protein 1 (IFITM1) to limit virus infection of cells. Transfecting cells with miR-36 mimic specifically lowered IFITM1 expression and thereby significantly dampening KSHV infection. The doses of the mimic In panels ''C and D'' , Student t test was performed to study the effect of HS and compare infection of cells with KSHV versus UV.KSHV on miR-36 expression at 5, 10, 15, and 30 min PI. Transfection of BJAB (Fig. 2C ) and HMVEC-d (Fig. 2D ) cells with miR-36 mimic significantly reduced KSHV infection of cells as monitored by the expression of ORF50 gene as early as 30 min PI. Interestingly, the effect of miR-36 mimic on KSHV infection of BJAB and HMVEC-d cells could be significantly reversed by co-transfecting cells with 10 nM of miR-36 inhibitor (Fig. 2E ). cord-265891-jmpterrj 2020 Therefore, we will here implement a crude form of contact tracing where we (1) close the workplaces of people who are tested positive for the disease, (2) isolate their regular social contacts for a limited period, and (3) keep symptomatic individuals in quarantine until they recover. If 10% efficiency is possible, corresponding to detecting about a third of infectious cases, then peak height could be reduced by a factor of almost three with to a 60% drop, if the probability of infected people being tested is only 10% per day of illness. In Fig. 4 , we show two possible scenarios where testing and contact tracing is implemented after a 30-day lockdown with a 75% reduction of the work and social spheres. Using reasonable COVID-19 infection parameters we find that the 1STQ strategy can contribute to epidemic mitigation, in the sense that it can reduce the peak number of infected individuals by about a factor of two even with a realistic testing rate of 10% per day of illness. cord-268414-7fcc5i7i 2020 The formulated nanoparticles (GANPs) were characterized for physicochemical properties and size and were then evaluated for antioxidant and antihypertensive effects using various established in vitro assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide scavenging (NO), β-carotene bleaching and angiotensin-converting enzyme (ACE) inhibitory assays. This study is the first to confirm the synergistic effects of gum arabic in the encapsulation of gallic acid by increasing the selectivity towards cancer cells and enhancing the antioxidant properties. According to the results, significant cytotoxicity was elicited among the HepG2, MCF7, MDA-MB231, and HT29 cell lines after treatment with IC 50 concentrations of free and nano encapsulated gallic acid as shown in Fig. 12 . The MDA-MB231 and HT29 cells had a lower fluorescence intensity of PI attributed to the lower toxicity of GA/C6NPs. www.nature.com/scientificreports/ The migration assay was carried out to assess the effect of GANPS and free GA with the IC 50 value of concentrations on MCF7, MDA-MB-231, HepG2, and HT29. cord-269270-i2odcsx7 2020 cord-269756-tid8a464 2016 Although membrane fusion promoted by class I viral glycoproteins, such as SARS-CoV Spike, human immunodeficiency virus (HIV) gp160 or influenza virus hemagglutinin (HA), has been broadly studied in recent years [16] [17] [18] [19] , many aspects of the molecular mechanism behind the virus-host cell membrane fusion remain unknown, including conformational changes of the lipid bilayers during peptide-membrane interactions. In the present study, we investigated the effects of two putative fusion peptides from SARS-CoV S glycoprotein, corresponding to residues 770-788 (SARS FP ) and 873-888 (SARS IFP ) 13, 15, 22, 23 , on the structural dynamics, physicochemical properties, and thermotropic phase behavior of lipid model membranes by differential scanning calorimetry (DSC), continuous wave (CW) and pulsed electron spin resonance (ESR) along with nonlinear least-squares (NLLS) spectral fitting 24 . cord-271328-zdf5ji4k 2016 In this paper, we report that angiotensin-converting enzyme-2 (ACE2) protected against severe lung injury induced by RSV infection in an experimental mouse model and in pediatric patients. To determine the role of ACE2 in RSV-induced lung injury, we first measured the levels of Ang II in the plasma of RSV-infected patients. Importantly, ACE2 protein levels were dramatically decreased in lung homogenates from mice infected with RSV BJ016 virus at 3 days post-infection (p < 0.01; Fig. 1d ). Our data suggest that RSV infection causes severe lung injury in an experimental mouse model and in patients, at least in part by modulating the RAS system via down-regulation of the ACE2-AT1R axis. Importantly, the levels of Ang II were elevated following down-regulation of ACE2, causing severe lung injury via AT1R during the process of RSV infection (Fig. 5d) . cord-271602-f14wccj3 2017 A 12-year (2004–2015) regional air quality simulation was conducted over East Asia (27-km) and over South Korea (9-km) to assess the impact of meteorology under constant anthropogenic emissions. Simulated PM concentrations show a strong negative correlation (i.e. R = −0.86) with regional wind speed, implying that reduced regional ventilation is likely associated with more stagnant conditions that cause severe pollutant episodes in South Korea. We conclude that the current PM concentration trend in South Korea is a combination of long-term decline by emission control efforts and short-term fluctuation of regional wind speed interannual variability. Three factors, long-term trend by emission control, short-term variation by meteorology, and sporadic offsets by unexpected social or economic episodes, seem to be affecting PM concentrations in South Korea. In order to investigate the interannual variation of surface PM concentration in the SMA, we conducted a 12-year simulation using a regional air quality modeling system. cord-272092-ko9y5m2s 2017 title: The cellular protein hnRNP A2/B1 enhances HIV-1 transcription by unfolding LTR promoter G-quadruplexes Surface plasmon resonance confirmed G-quadruplex specificity over linear sequences and fluorescence resonance energy transfer analysis indicated that hnRNP A2/B1 is able to efficiently unfold the LTR G-quadruplexes. Our data highlight a tightly regulated control of transcription based on G-quadruplex folding/unfolding, which depends on interacting cellular proteins. Silencing of the LTR G4 folding/stabilizing protein nucleolin significantly increased promoter activity, indicating the inhibitory effect of nucleolin on LTR-driven transcription 22 . Our results showing decreased transcriptional activity upon depletion of hnRNP A2/B1 indicate a possible additional mechanism of inhibition of virus production mediated by increased G4 folding in the HIV-1 LTR promoter in the absence of hnRNP A2/B1. Nucleolin stabilizes G-quadruplex structures folded by the LTR promoter and silences HIV-1 viral transcription Protein hnRNP A1 and its derivative Up1 unfold quadruplex DNA in the human KRAS promoter: implications for transcription cord-272576-ez731lif 2016 cord-272623-j5gpww9q 2016 cord-273283-gb0m6fue 2020 cord-276185-ysspkbj7 2018 In experiments in vitro, three human APOBEC3 proteins (A3C, A3F and A3H) inhibited HCoV-NL63 infection and limited production of progeny virus, but did not cause hypermutation of the coronaviral genome. Although the precise molecular mechanism of deaminase-dependent inhibition of coronavirus replication remains elusive, our results further our understanding of APOBEC-mediated restriction of RNA virus infections. HCoV-NL63 infection resulted in upregulation of expression of A3A, A3C, A3D and A3F and A3C, A3F and A3H all inhibited HCoV-NL63 replication, we tested whether this inhibition was the result of the catalytic activity of the APOBECs. Plasmids encoding variants of A3C, A3F and A3H with Glu → Gln substitutions in the catalytic site were prepared 31 and mRNAs encoding active or inactive proteins were transfected into LLC-Mk2 cells, which were infected with HCoV-NL63 and cultured prior to visualisation of viral proteins with specific antibodies. cord-276444-jidvkij5 2017 cord-276997-hbovh7s9 2020 However, the infectivity of airborne human noroviruses has not been possible to assess in real-world environments, nor in laboratory experiments, since there is no well-established cell culturing system for these viruses working at the low concentrations obtained in air samples 6 . SLAG: Sparging liquid aerosol generator; HEPA filter: high efficiency particulate air filter; nsRNA: negative sense RNA; psRNA: positive sense RNA; MNV: murine norovirus; qRT-PCR: quantitative reverse transcriptase polymerase chain reaction. Taken together, as compared to the atomizer, a smaller amount of SLAG aerosol is collected by the BioSampler (i.e., higher physical dilution), but these particles contain more MNV psRNA copies (lower viral dilution relative the physical dilution). The experimental setup described here highlights some difficulties in studies on aerosolized viruses: (1) the lack of standards in how to generate bioaerosol that results in significant differences in aerosol particle size and concentration, (2) the necessity to determine both physical and viral dilution factors, and (3) www.nature.com/scientificreports/ during airborne transport due to the low-solute solution and dilution in the setup. cord-277816-ncdy9qgb 2020 title: Gastrointestinal symptoms and fecal nucleic acid testing of children with 2019 coronavirus disease: a systematic review and meta-analysis In order to understand the clinical manifestations and incidence of gastrointestinal symptoms of coronavirus disease (COVID-19) in children and discuss the importance of fecal nucleic acid testing.We retrospectively analyzed studies on gastrointestinal symptoms and fecal nucleic acid detection in pediatric COVID-19 patients from January 1, 2020 to August 10, 2020, including prospective clinical studies and case reports. Stata12.0 software was used for meta-analysis.The results showed that the most common gastrointestinal symptoms in children with COVID-19 were vomiting and diarrhea, with a total incidence of 17.7% (95% Cl 13.9–21.5%). At present, there is no relevant study on whether there is a difference in the positive rate of fecal nucleic acid testing in COVID-19 children with and without diarrhea. Clinical features of 33 cases in children infected with SARS-CoV-2 in Anhui Province, China: a multi-center retrospective cohort study. cord-279598-xzionafe 2019 cord-280334-7b7rvr25 2020 cord-281536-8y7yxcp4 2020 title: Hot spot profiles of SARS-CoV-2 and human ACE2 receptor protein protein interaction obtained by density functional tight binding fragment molecular orbital method In this work, to find common hot spot amino acids on the interfaces between the RBD domain and hACE2 of the three complexes, RBD-SARS-CoV-2/hACE2 (twelve experimental structural data), RBD-SARS-CoV-1/ hACE2 (four experimental structural data), and RBD-HCoV-NL63/hACE2 (one experimental structural data), we performed FMO-DFTB3/D/PCM calculations. Consequently, we summarized the FMO-DFTB3/D/PCM/3D-SPIEs results as interaction maps and found the hot spot regions in RBD-SARS-CoV-2 and hACE2 at a QM level. In order to narrow down the hot spot regions between hACE2 and RBD-SARS-CoV-1, we performed FMO calculations on four RBD-SARS-CoV-1/antibody complexes (Supplementary Table S14-S19). In order to find common hot spot amino acids in RBD-SARS-CoV-1 against hACE2 and SARS-CoV-1 antibodies, we illustrated the FMO results with a 3D-SPIEs-based map. cord-283583-pwlbrxn3 2015 A higher frequency of severe clinical outcome and nervous system manifestation were also observed in the SAFV-positive HFMD patients. A patient was considered to be infected with SAFV when positive detection was obtained in any type of the samples. Genetic characterization of SAFVs. A phylogenetic tree was constructed based on the VP1 nucleotide sequences of Saffold cardiovirus detected in clinical samples of 82 patients in the current study, and sequences downloaded from GenBank by maximum likelihood method using MEGA 6.0 (Figure 1) . Detection of SAFV in sera and CSFs. Additional 171 CSFs were collected from patients with HFMD-associated encephalitis, and six (3.5%) were found to be SAFV-positive using real-time RT-PCR, and five were further confirmed by nested RT-PCR targeting the 59-UTR. In our study, SAFVs were co-detected with other viruses in 14 (82.4%), 9 (75.0%), and 28 (32.6) specimens in ARTI, diarrhea and HFMD patients respectively. cord-284374-sqxlnk9e 2020 title: Infection Prevention Measures for Surgical Procedures during a Middle East Respiratory Syndrome Outbreak in a Tertiary Care Hospital in South Korea Our experience with setting up a temporary negative-pressure operation room and our conservative approach for managing MERS-related patients can be referred in cases of future unexpected MERS outbreaks in non-endemic countries. Anesthesiologists were recommended to apply enhanced PPE (including PAPR from the middle of the outbreak) when managing all MERS-related patients because they were most directly exposed to the aerosol-producing high-risk procedures, such as endotracheal intubation and extubation. Almost all hospitals generally have positive-pressure operating rooms and they may experience an outbreak without facilities that are prepared for perioperative management of MERS patients, as our hospital did in 2015. First, although the previous guidelines recommended that asymptomatic MERS-exposed patients be managed as general patients undergoing surgery, we applied standard PPE to HCWs and we performed MERS-CoV PCR screening twice. cord-284429-d7qxfo6d 2020 cord-284582-xwedgllw 2020 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. cord-286413-a7wue2e3 2020 title: Cardiac adverse events associated with chloroquine and hydroxychloroquine exposure in 20 years of drug safety surveillance reports The cardiac AEs of these therapeutics are of increased concern since a subset of patients infected with COVID-19 present with cardiac injury, suggesting a relevant cardiovascular involvement in the pathophysiology of the disease 22 . The goal of this study is to reanalyze the extensive clinical data of CQ and HCQ cardiac AEs collected during the last 20 years to derive the strength of the associations and, more importantly, contributing risk factors. In our study we analyzed 702,274 FDA adverse event reports divided into CQ, HCQ and control cohorts to determine their association with cardiac AEs when taking into account other factors. The regression model was instrumental to exclude this aspirin association from the quantification of the direct cardiac side effects of CQ and HCQ, which remained significant after adjustment ( Generalizability of results to COVID-19 treatment with CQ and HCQ. cord-286559-y8z0pwgn 2017 cord-287708-0qvwjejv 2020 cord-288451-npefpo3t 2016 cord-288721-3bv3aak6 2019 Thus, single-organelle and multi-parameter resolution allows to explore altered energy metabolism and antiviral defence by tagged mitochondria selectively in virus-infected cells and will be instrumental to identify viral immune escape and to develop and monitor novel mitochondrial-targeted therapies. When challenged with high concentrations of calcium (100 µM), mitochondria isolated from virus-infected livers are much more fragile shown by time-dependent loss of membrane potential and change of their morphology indicated by decrease in side-scatter (Fig. 2F ). Number of viable mitochondria detected per second by flow-cytometry declined after calcium challenge, consistent with loss of mitochondrial integrity, and did so much faster in samples from virus-infected livers (Fig. 2F ). In order to further evaluate mitochondrial functionality, we challenged mitochondria with Ca 2+ as stress test and performed time kinetic measurements of DilC 1 (5) fluorescence and side-scatter of mito-DsRed + and mito-DsRed − mitochondria isolated from Ad-CMV-mitoRL infected livers. cord-288731-x2cwyvb7 2020 cord-288761-fyvr0tc1 2017 These structures identified three distinct APN conformations, based on active site accessibility, which we termed closed, intermediate and open forms (Fig. 1a) . The phenylalanine was located in the loop that connects α 26 and α 27 in the single domain IV ARM repeat of human and pig APN (Fig. 2a) ; it penetrated the active site groove in the closed conformation and locked the peptide, ready for hydrolysis. CoV binding to APN would lock the protein in its open conformation (Fig. 2b) , preventing the ectodomain movement probably necessary for peptide hydrolysis (Fig. 2a) . In flow cytometry, we determined the binding of an RBD-Fc fusion protein to cells that expressed pAPN or an active site mutant (pAPN-HH/AA), alone or with various drugs (Fig. 4a,b) . Disulfide bonds that lock the APN closed conformation or drugs that prevent opening of the ectodomain inhibited CoV protein binding and cell infection, whereas porcine CoV S proteins probably hinder APN transition to the closed form and peptide hydrolysis. cord-289932-dsysiefx 2018 cord-293372-saqoft9p 2020 Quantitative proteomics data were obtained from two CHO cell lines (CHO-S and CHO DG44) and compared with seven Chinese hamster (Cricetulus griseus) tissues (brain, heart, kidney, liver, lung, ovary and spleen) by tandem mass tag (TMT) labeling followed by mass spectrometry, providing a comprehensive hamster tissue and cell line proteomics atlas. This study was undertaken to compare protein expression of various CHO cell lines and hamster tissues, resulting in the most comprehensive multi-tissue analysis of the Cricetulus griseus proteome (Fig. 1A) . Similar to the ovary and lung comparison, there are a greater number of proteins with higher expression in the heart tissue when compared to cell lines. These differences highlight the role of tissues in executing key organ functions which require a specific metabolic processes, such as transport and communication, in comparison to CHO cells, which are focused on replication and gene expression, characteristics useful for rapid growth and the production of biologics. cord-293505-1t3hg4wi 2019 cord-293747-ds8rhbkv 2015 cord-294220-ewp1m8jp 2020 cord-296562-3h2oqb9k 2020 In contrast to other respiratory viral infections like influenza, a major pathogenic mechanism implicated in severe clinical manifestations of COVID-19 is an aberrant host immune response resulting in an excessive cytokine and chemokine release known as "cytokine storm" or "cytokine release syndrome" 2,3 . In a sensitivity analysis including only the 55 patients with confirmed SARS-CoV-2 infection by RT-PCR, the significant variables in the adjusted multivariate model were a NLR > 2.55 (OR 5.26; 95% CI 1.02-25), higher Charlson comorbidity index (OR 1.56; 95% CI 1.04-2.34) per unit, and higher SOFA score (OR 5.05; 95% CI 1.10-23.24) (Supplementary Table 2 ). This biomarker reflects excessive inflammation and dysregulation of immune cells that play a central role in severity of disease in viral infections 23 , and has been associated with mortality in patients hospitalized with COVID-19 24 . www.nature.com/scientificreports/ four comorbidities are included in the Charlson index, and have been associated with higher disease severity in patients with COVID-19 31 . cord-296867-6o4scan1 2020 title: Surveillance of early stage COVID-19 clusters using search query logs and mobile device-based location information In contrast, we utilized web search query logs per user to detect WSSCI and gather their location histories to identify locations they visited or passed through, resulting in COVID-19 cluster detection. In the Kitami area (Fig. 3a) , the WSSCI has a maximum cross-correlation of 0.766, determined 2 days after the change in the number of new patients. This study attempted to detect early clusters by identifying people who suspected their own COVID-19 infection using web search query logs and by extracting their location information. We utilized web search query log data and location information provided by Yahoo Japan Corporation 17 as signals for syndromic surveillance. Syndromic surveillance using search query logs and user location information from smartphones against COVID-19 clusters in Japan cord-299605-j1ewxk4q 2017 c. chabaudi, AS and CB, that differ in virulence in C57BL/6 mice, we performed high-resolution comparative whole-blood transcriptomic analysis throughout the acute phase of the blood-stage infection, and identified several transcriptomic signatures associated with severe malarial pathology before the onset of pathology or disease. Spearman''s rank correlation coefficient (r s ) analysis of unfiltered transcripts normalised across the median of all samples, revealed high levels of similarity amongst naïve and 2, 4 dpi samples in both AS and CB infections (Fig. 2ai ,ii, r s ranging from 0.73 to 0.88), while from 6 dpi onwards the whole blood transcriptomes diverge significantly from the earlier time points (r s ranging from 0.08 to − 0.59 compared to naïve controls). Importantly, in 4 of the CB infected mice that had reached humane end points at 9 dpi, these 5 genes showed an even higher level of up-regulation compared to naïve controls (Fig. 3c) , indicating possible lung pathology in these 4 CB infected mice. cord-301016-9t7v7ipt 2015 cord-302080-fegcf1fu 2020 cord-302459-grs2x26l 2018 In this study we profiled 372 cancer-associated miRNAs in plasma collected before (~60% patients) and after/during commencement of treatment (~40% patients), from age-matched prostate cancer patients and healthy controls, and observed elevated levels of 4 miRNAs miR-4289, miR-326, miR-152-3p and miR-98-5p, which were validated in an independent cohort. Analysis of published miRNA transcriptomic data from clinical samples in the TCGA dataset demonstrated low expression of miR-152-3p in tumour compared to adjacent non-malignant tissues (p = 0.001) (Wilcoxon test, p ≤ 0.05) (Fig. 4) Figure S3) . Similarly, other groups have assessed the diagnostic performance of plasma or serum miRNAs in patients with localised or metastatic prostate cancer, BPH and healthy controls, and in most instances the specificity and sensitivity of the miRNA biomarkers have outperformed the accuracy of the PSA test 23, 28, 29 . cord-303601-o8uk6if2 2020 This includes modeling the dynamics of affected populations, estimating the model parameters and hidden states from data, and an optimal control strategy for sequencing social distancing and testing events such that the number of infections is minimized. Figure 2 shows the predicted values obtained by solving the parameter estimation problem and the historical data by country, retrieved by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (https ://githu b.com/CSSEG ISand Data/COVID -19; accessed April 16, 2020). For the estimated parameter values as described previously, we simulate the results of implementing two different simplistic control policies: (i) continuing with strict social distancing, quarantining, and testing, policies that result from continuing to lower the asymptomatic ( α a ) and infected ( α i ) exposures shown in Fig. 2 ; and (ii) a relaxed policy with more lenient measures and reduced testing, in this case the values of α a and α i are increased to 0.2 and 0.02, respectively, while κ is decreased to 0.2. cord-304040-64obh7i3 2018 cord-305031-9ze0097w 2020 We cannot consider delay changes for freight traffic, as its volume was strongly affected by the Rastatt disruption; and more generally, freight traffic does not stop at stations thus having a ill-defined delay; and Scientific Reports | (2020) 10:18584 | https://doi.org/10.1038/s41598-020-75538-z www.nature.com/scientificreports/ despite its buffer times are typically large, its performance is often erratic. We now discuss how a state-of-the-art simulation model, OnTime, based on typical delay propagation theory 39 (the Methods section describes its assumptions and functioning, and its calibration for the test case) can partially replicate the degree by which the delay performance of passenger trains improved in the area of Basel, and decreased in the area of Schaffhausen. Newly designed statistical tests were applied to delay analysis in railway networks, performed at different percentile levels, over multiple time scales, and two specific factors (reduced entrance delay for passenger trains and rerouted freight trains). cord-305132-jspxlk1a 2014 In this study, we analyzed murine IRF-3 promoter activity in detail and its relationship to prion infection, and have shown that the octamer-binding transcription factor-1 (Oct-1) positively regulates murine IRF-3, and the expression levels of Oct-1 decreased in prion-infected cells. Furthermore, in the persistently other prion strain-infected cells by the mouse-adapted Gerstmann-Sträussler-Schenker syndrome (GSS) Fukuoka-1 strain (FK-N2a58), IRF-3 mRNA and the promoter activity were also significantly decreased (Supplementary Fig. S6a and S6b). PCR analysis revealed that the Oct-1 antibody precipitated the promoter region (nt -119 to -1) from N2a58 cells (Fig. 4a) , while the negative control (anti-rabbit IgG) did not exhibit the DNA binding activity. These results demonstrate that reduced IRF-3 promoter activity in prion-infected cells is accompanied by decreased levels of Oct-1. In summary, our results demonstrated that Oct-1 binds to the murine IRF-3 promoter region and increases the transcription level and IRF-3 expression is reduced by prion infection. cord-305473-w30hsr4m 2017 cord-306517-tls0849i 2017 cord-308302-5yns1hg9 2020 We used machine learning for processing laboratory findings of 110 patients with SARS-CoV-2 pneumonia (including 51 non-survivors and 59 discharged patients). Thus it is feasible to establish an accurate prediction model of outcome of SARS-CoV-2 pneumonia based on laboratory findings. Laboratory tests for SARS-CoV-2 pneumonia included: blood routine test, serum biochemical (including glucose, renal and liver function, creatine kinase, lactate dehydrogenase, and electrolytes), coagulation profile, cytokine test, markers of myocardial injury, infection-related makers, and other enzymes. 68 discharged patients with SARS-CoV-2 pneumonia whose age and gender matched the non-survivors were selected (46 male, median age 66 years). A number of laboratory features were compared between non-survivors and discharged patients with SARS-CoV-2 pneumonia. With machine learning methods previously used in radiomics, a prediction model combining seven out of thirty-eight laboratory features was built for predicting the outcome of SARS-CoV-2 pneumonia. cord-308687-wrzzb9cy 2020 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. cord-309127-kxivgxbg 2018 title: Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4 In line with these observations, high amounts of MERS-CoV antigen were detected within the respiratory epithelium of the nasal turbinates of mock-vaccinated dromedaries at 4 dpi by immunohistochemistry in areas SciEntiFic REpORTS | (2018) 8:9778 | DOI:10.1038/s41598-018-28109-2 with most severe lesions ( Fig. 2A) . To finally elucidate the histogenesis of cells staining positive for MERS-CoV nucleocapsid antigen within the lamina propria of the nasal turbinates of mock-vaccinated dromedaries, additional double immunofluorescence labeling was performed. Since DPP4 was only detectable within the apical brush border of the surface epithelium and submucosal glands, but not on the surface of inflammatory cells within lamina propria and submucosa of the nasal turbinates by immunofluorescence, dromedary and human lymphoid tissue were stained for comparison and control. cord-312777-5925lvue 2020 cord-313126-7hrjzapj 2019 Nineteen complete TGEV genomes and a single strain of porcine respiratory coronavirus (PRCV) from the US were generated and compared to historical strains to investigate the evolution of these endemic coronaviruses. The "variant" genotype shared similar unique deletions and amino acid changes with the recent PRCV strain identified in this study, suggesting a recombination event occurred between the ''''variant'''' TGEV and PRCV. Complete genomic sequences, a key residue in the spike protein and deletions in nonstructural protein 3b of US strains of the virulent and attenuated coronaviruses, transmissible gastroenteritis virus and porcine respiratory coronavirus cord-314753-xflhxb13 2017 The percentage of reads mapping to RNA virus genomes in the rRNA-depleted BBV Panel samples was between 40 and 150-fold higher than in corresponding untreated controls. The depth plots in Fig. 3 again show unbiased and even coverages across both genomes, and the percentages of reads mapping to viral targets was again much higher in the rRNA-depleted sample than in the untreated comparator (61-fold and 85-fold for HCV and HPgV respectively). By depleting host-derived nucleic acids and making modifications to an existing library preparation protocol to account for ultra-low RNA input quantities, we have been able to reconstruct effectively full-length genomes of HCV, HEV and HIV from plasma samples with viral loads of 10 4 IU/ml (copies/ml for HIV) and substantial fractions of complete genomes at 10 3 IU/ml. Additionally, our system was able to recover viral sequences from a panel of diverse RNA viruses diluted in human plasma, with a broad correlation between the genomic coverage and depth metrics and approximate concentration. cord-315415-3aotsb2g 2020 In this study we used computer-aided design to construct multi-specific VHH antibodies fused to human IgG1 Fc domains based on the epitope predictions for leading VHHs. The resulting tri-specific VHH-Fc antibodies show more potent S1 binding, S1/ACE2 blocking, and SARS-CoV-2 pseudovirus neutralization than the bi-specific VHH-Fcs or combination of individual monoclonal VHH-Fcs. Furthermore, protein stability analysis of the VHH-Fcs shows favorable developability features, which enable them to be quickly and successfully developed into therapeutics against COVID-19. (c) The binding of VHH-Fcs and ACE2 to Expi293 cells expressing SARS-CoV-2 S1 wild type (WT) or mutant proteins (del1-del5) were assessed by flow cytometry following FITC-conjugated secondary antibody treatment. Based on the binding and epitope binning data, we constructed 3D docking models that predicted the interactions between SARS-CoV-2 S1 RBD, ACE2 and lead VHH-Fcs (Fig. 2e) . Next, we tested whether the combination of individual VHHs binding to different S1 RBD epitopes into bi-specific antibody molecules would yield synergistic effects in SARS-CoV-2 binding and S/ACE2 blocking. cord-315483-l6dm82pp 2018 cord-315781-dejh8q22 2019 It should be noted that avian viruses showed lower PC values and appeared around the centre of the PCA, while swine and human viruses exhibited extreme values (Figs. Thus, avian viruses had sequences that were similar to the average among samples at amino acids that were characteristic to the three groups of human and swine viruses: R, M, and U. Avian samples also showed characteristic motifs at other positions, which may appear in lower PCs. The relationships observed among the strains presented here are different from the classic ones 4, [8] [9] [10] [11] [12] in several elements. www.nature.com/scientificreports www.nature.com/scientificreports/ One of the major differences observed was the direct shift from avian to swine or human viruses. Drifts and spreading: the genomes of the R group of human viruses have been changing yearly (Figs. cord-316930-0s7k9guq 2020 cord-316983-h4mtpcyc 2016 cord-317579-ige2h4pd 2020 The results confirmed that the SeO(3)(2−) was doped at the PO(4)(3−) position and silver nanoparticles were deposited on the surface of SeB-NPs. Next, Transmission Electron Microscopy (TEM) analysis displayed that the prepared (Ag)SeB-NPs had a needle-cluster-like morphology. At the same time, biphasic calcium phosphate nanoparticles (BCP-NPs) and selenium-doped hydroxyapatite nanoparticles (SeHA-NPs) were prepared for comparison (Electronic Supplementary Material). Compared with the control group, the doping selenium into BCP-NPs had slight influence on the antibacterial activity, and it had a slight inhibitory effect against bacteria of SeB-NPs after 12 h of culture. The stated objective of this study was to synthesis new-style biphasic calcium phosphate nanoparticles (BCP-NPs) with excellent cytocompatibility and antibacterial activity for further hard-tissue engineering applications. After the deposition of silver, cells cultured with all Ag SeB-NPs samples had similar proliferation profiles compared with SeB-NPs. Not only can the addition of selenium and silver improve the growth of the cells with BCP-NPs, but the antibacterial activity was acquired, which has potential for infection-resistant replacement materials 61, 62 . cord-317813-sisfxdso 2016 Applying in-depth bacterial community analysis using high-throughput 16 S rRNA gene sequencing, a high inter-individual variation was observed among the studied guano samples. Additionally, 16 S rRNA gene sequencing was performed using Ion Torrent PGM to identify the bacterial communities and screened for the presence of putative human pathogens. Sequence analysis of the cytochrome B (cytB) gene amplified from total extracted DNA of the guano pellets revealed that the collected fecal pellets were from a single bat species i.e. Rousettus leschenaultii, a predominant bat species reported from the Robber''s cave 23 . Further, computation of core microbiome from Ion Torrent sequences of fresh guano revealed the presence of five bacterial phyla i.e. Proteobacteria, Tenericutes, Candidate division TM7, Firmicutes and Actinobacteria but in different proportions (Fig. 5, Supplementary Figure S7 ). Additionally, Ion Torrent sequencing of 16 S rRNA gene provided information about the general bacterial communities with specific emphasis on pathogens among the total communities present in bat guano. cord-318187-c59c9vi3 2020 The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Of interest are nasal spray simulation studies on in silico models, re-constructed from medical imaging, to measure drug delivery along the nasal passages 9 , in the sinuses 10, 11 , and on the effects of surgical alterations of the anatomy on nasal airflow [12] [13] [14] [15] as well as on topical transport of drugs [16] [17] [18] [19] . The computational fluid dynamics (CFD) models of droplet transport and the in silico prediction of their deposition sites along the nasal airway walls have been compared with in vitro spray experiments in 3D-printed solid replicas of the same anatomic reconstructions. cord-318314-oxlv847d 2020 Comparison of single representative pathogenic and non-pathogenic ovine isolates over ten time-points by enumeration of tissue-associated bacteria, histology, immunofluorescence microscopy and scanning electron microscopy revealed temporal differences in adhesion, proliferation, bacterial cell physiology and host cell responses. Comparison of eight isolates of bovine and ovine origin at three key time-points (2 h, 48 h and 72 h), revealed that colonisation was not strictly pathogen or serotype specific, with isolates of serotype A1, A2, A6 and A12 being capable of colonising the cell layer regardless of host species or disease status of the host. haemolytica 11, 38 , coupled with a suggested role for the polysaccharide capsule (on which the serotyping classification is based) in cell adhesion 17 , indicates that isolates may be specifically adapted to colonising the airway tissues of discrete hosts. We assessed whether interactions with differentiated OTECs could reflect this species-specificity by analysing colonisation of pathogenic and non-pathogenic isolates of both bovine and ovine origin. cord-318587-ewvnkdr2 2020 We evaluated the suitability of EBOV GP pseudotyped human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV) to measure the neutralising ability of plasma from EVD survivors, when compared to results from a live EBOV neutralisation assay. The aim of this study was to assess the suitability of EBOV GP pseudotyped HIV-1 and VSV systems to measure neutralisation by EVD survivor plasma, in comparison with results from a live EBOV neutralisation assay. To determine the optimal pseudotyped virus input to use in the HIV-and VSV-based assays, neutralisation of different amounts of the EBOV GP pseudotyped viruses by plasma from a Guinean EVD survivor donor or human anti-EBOV GP mAb KZ52 was assessed. When IC 50 values of EBOV GP pseudotyped HIV-1 neutralisation of the 30 EVD survivor and 10 negative plasma samples were compared with GMT values for the live EBOV neutralisation assay, a positive correlation (r s = 0.54) was determined using the nonparametric Spearman correlation coefficient (Fig. 5a) and this was statistically significant (p = 0.0004). cord-319118-47ovbto5 2015 We previously reported two human monoclonal antibodies that target the receptor binding domain (RBD) of the spike and exhibit strong neutralization activity against live and pesudotyped MERS-CoV infection. We found Trp535 as an anchor residue in the RBD for MERS-27 recognition, and its interaction with N-linked carbohydrates of DPP4 is important for the binding to DPP4 and for viral entry of MERS-CoV. In sum, results of viral entry, neutralization, and binding assays consistently indicated that Trp535 and Asp539 are critical for both MERS-CoV spike glycoprotein recognition by MERS-27 and binding with receptor DPP4. The interaction between Trp535 of RBD and the DPP4 carbohydrate is also important for receptor binding and viral entry of MERS-CoV. The receptor binding domain of the new Middle East respiratory syndrome coronavirus maps to a 231-residue region in the spike protein that efficiently elicits neutralizing antibodies A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein cord-320709-2pnqpljt 2016 cord-321667-jkzxjk54 2019 cord-322486-qwl7nzkr 2020 We estimated the parameter which describes the age-dependency of susceptibility by fitting the model to reported data, including the effect of change in contact patterns during the epidemics of COVID-19, and the fraction of symptomatic infections. Our study revealed that if the mortality rate or the fraction of symptomatic infections among all COVID-19 cases does not depend on age, then unrealistically different age-dependencies of susceptibilities against COVID-19 infections between Italy, Japan, and Spain are required to explain the similar age distribution of mortality but different basic reproduction numbers (R(0)). Assuming that the age-dependency of mortality by COVID-19 is determined by only age-dependent susceptibility (model 1), i.e., the mortality rate does not depend on age, the exponent parameter, φ, describing the variation of susceptibility among age groups for each country, Italy, Japan, and Spain, was estimated as shown in Fig. 4 . cord-323087-3cxyogor 2017 cord-324696-htx0ul4o 2017 This first ever study of IAV receptors in a bat species suggest that LBBs, a widely-distributed bat species in North America, could potentially be co-infected with avian and human IAVs, facilitating the emergence of zoonotic strains. To resolve this enigma, we investigated for the first time the distribution of SA receptors in little brown bats (LBBs) (Myotis lucifugus), a widely-distributed bat species in North America and their compatibility to support avian and human IAV binding. H5N2 virus binding pattern was in accordance with the relative abundance of SA α2,3-Gal receptors in tissues such that greater virus binding to the tracheal ( In addition to the virus binding assay using antibody-based detection, we also visualized virus binding using scanning electron microscopy (SEM) which also confirmed abundant binding of avian H5N2 virus (Fig. 5A ) and human H1N1 virus (Fig. 5B ) to LBB trachea (Fig. 5) . time, this study demonstrated that little brown bats (LBBs), a widely-distributed bat species in North America, co-express both avian and human type influenza receptors in their respiratory and gastrointestinal systems. cord-325405-cu4nx891 2019 Logistic regression analyses with sex stratification showed that abdominal pain, fever and ingestion of unsafe food at restaurants were independent factors more frequently associated with bacterial gastroenteritis irrespective of sex; red cell-positive fecal matter was associated with bacterial gastroenteritis with an odds ratio (OR) of 3.28 only in males; and white blood cell count was associated with bacterial gastroenteritis with an OR of 1.02 only in females. No significant differences in the age, percentage of local residents, frequency of vomiting, frequency of watery stools, frequency of diarrhea, duration of diarrhea, rate dehydration, heart rate, blood pressure, or rate of ingesting possible unsafe food variables was observed between the viral and bacterial gastroenteritis groups ( Independent factors differentially associated with pathogen by sex. Among males, univariate analyses showed that nausea, vomiting frequency, watery stools, abdominal pain, fever, ingesting unsafe food at restaurants, fecal leukocyte-positive, fecal red cell-positive and white blood cell count were potential independent factors that were differentially associated with viral and bacterial gastroenteritis. cord-325657-s2vdazq0 2020 cord-326868-3az13h1h 2020 The present study takes a neural trait approach, examining whether the temporal dynamics of resting EEG networks are associated with inter-individual differences in prosociality. In two experimental sessions, we collected 55 healthy males'' resting EEG, their self-reported prosocial concern and values, and their incentivized prosocial behavior across different reward domains (money, time) and social contexts (collective, individual). On the basis of resting EEG networks'' significance for non-social behavior, personality, and psychiatric conditions 20,31 , we expected that revealing an individual''s tendency to engage these networks at rest would help explain inter-individual differences in prosociality and illuminate the potential psychological processes that underlie these differences. Correlative analyses revealed that participants with more transitions from microstate C to A were more prosocial [R(53) = 0.414, P = 0.002, Scientific RepoRtS | (2020) 10:13066 | https://doi.org/10.1038/s41598-020-69999-5 www.nature.com/scientificreports/ significant after Bonferroni-correction for multiple testing; prosocial concern: R s (53) = 0.261, P = 0.054; prosocial values: R s (53) = 0.366, P = 0.006; collective prosocial behavior: R s (53) = 0.081, P > 0.20; individual prosocial behavior: R s (53) = 0.261, P = 0.054, see Fig. 4 ]. cord-327405-xgtqfwyn 2020 37 non-severe patients with persistent SARS-CoV-2 presence that were transferred to Zhongnan hospital of Wuhan University were retrospectively recruited to the PP (persistently positive) group, which was further allocated to PPP group (n = 19) and PPN group (n = 18), according to their testing results after 7 days (N = negative). Finally, paired results of these lymphocyte subpopulations from 10 PPN patients demonstrated that the number of T cells and B cells significantly increased when the SARS-CoV-2 tests turned negative. These results indicated that non-severe COVID-19 patients (PA group) have already dysregulated immune system at disease onset, and those with persistent SARS-CoV-2 shedding could restore this abnormality to certain level. Together, these results indicated that the abnormalities in adaptive immune cells, but not symptoms and laboratory indicators, were associated with SARS-CoV-2 viral RNA detection in non-severe COVID-19 patients. cord-329155-ddpfox68 2020 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 ). cord-329424-hmsidrc7 2020 title: Differential type I interferon response and primary airway neutrophil extracellular trap release in children with acute respiratory distress syndrome Since viral lower respiratory tract infections are a primary trigger for PARDS, we questioned whether differential ISG expression was associated with neutrophil responses in intubated children at risk or with PARDS. We hypothesized that children with PARDS would have a greater type I IFN response resulting in more neutrophil extracellular trap (NET) release. Our study assessed neutrophil activation, the differential expression of ISGs and activation of the STAT1 signaling pathway, and NETosis in the airways of intubated children with acute respiratory failure due to lower respiratory tract infections. While we detected higher type I IFN signaling and NET production in the airways of children with versus without PARDS, due to the clinical nature of our study, we are not able to attribute causation of neutrophil dysfunction to high ISG expression in study participants. cord-329766-9bwdb6o2 2020 cord-330057-3vucm0s1 2020 In the present study, 361 IBV QX (the most relevant field genotype in Italy) sequences were obtained between 2012 and 2016 from the two main Italian integrated poultry companies. Finally, the different viral population pattern observed in the two companies over the same time period supports the pivotal role of management and control strategies on IBV epidemiology. Almost identical results were obtained including a third "ghost" deme (i.e. an estimated deme for which no sequences were available, representative of other unsampled companies and farms) in the analysis or using the "traditional" coalescent approach. In the particular Italian QX scenario, the serially sampled (i.e. with known collection date) strains were used to infer the migration rate and history between the two integrated poultry companies (i.e. considered as different demes) over time. cord-330562-dabjcvno 2020 cord-331148-40gvay7i 2018 Independently, a retrospective cohort study (which enrolled 639 infected patients during the five seasons) was conducted at Chang Gung Memorial Hospital to explore the risk factors associated with influenza A(H1N1)pdm09-related complications. The results of the logistic regression analysis on the risk factors associated with influenza A(H1N1)pdm09-related complications and pneumonia are shown in Table 4 , and respiratory failure with mechanical ventilation and ARDS are also presented in Table 5 . In the univariate analysis, 6B/6B.1/6B.2 season, age (50-64 years), onset to presentation, underlying conditions, obesity, smoking, alcoholism, and antiviral therapy were significant risk factors of complications, pneumonia, mechanical ventilation, and ARDS (Tables 4 and 5 ). In the multivariate logistic regression analysis, 6B/6B.1/6B.2 season, age (50-64 years and ≥65 years), underlying conditions, and antiviral therapy were significant independent risk factors of complications, pneumonia, and mechanical ventilation (Tables 4 and 5). cord-331475-mmcu18c8 2018 title: Selection and validation of suitable reference genes for qPCR gene expression analysis in goats and sheep under Peste des petits ruminants virus (PPRV), lineage IV infection In this study, we evaluated the expression stability of ten most commonly used reference genes (GAPDH, ACTB, HSP90, HMBS, 18S rRNA, B2M, POLR2A, HPRT1, ACAC, YWHAZ) in fourteen different Peste des petits ruminants virus (PPRV) infected tissues of goats and sheep. GAPDH (Glyceraldehyde-3-phosphate dehydrogenase), 18S rRNA (18S ribosomal RNA), B2M (β 2 microglobulin), HSP 90 (heat shock protein 90), ACAC-alpha (Acetyl coenzyme carboxylase alpha), HMBS (Hydroxymethylbilane synthase), YWHAZ (Tyrosine 3-monooxygenase activation protein zeta polypeptide), POLR2A (Polymerase 32 II (DNA directed) polypeptide A), ACTB (beta actin) and HPRT1 (Hypoxanthin Phosphoribosyl transferase 1) in fourteen different tissues obtained from healthy and PPRV infected goats and sheep to identify the best possible reference gene(s) for qRT-PCR normalization. cord-331775-iaxkfszq 2020 cord-333067-3zan82yf 2017 cord-334228-n69iewmx 2016 Like other known CoV-3CLpro structures, such as TGEV, hCoV-229E, hCoV-HKU1, and IBV 2-5 , SARS-3CLpro has a highly conserved three-dimensional structure, dimer interface, catalysis dyad, and substrate binding site, but an extremely low homology with cellular proteases. Ser139 and Phe140 are two key residues that not only contribute to interactions between the two protomers in the parent dimer but also maintain the correct conformation of the S1 subsite in the substrate-binding pocket. Other residue mutations, which are neither on the dimer interface nor key to catalysis, can also influence enzyme activity and dimer association-dissociation of SARS-3CLpro via long-range interactions 15, 16 . Our molecular dynamics simulations showed that Ser139-Leu141 maintains a stable 3 10 -helix conformation in the inactive monomer structure and a well-defined loop conformation in the active protomer of the dimer structure. Although SARS-3CLpro uses the dimer structure to maintain its enzyme activity, our study shows that the monomer can also be evolved into an active enzyme via mutations. cord-335055-gzuug3p5 2020 title: Patterns of viral pathogens causing upper respiratory tract infections among symptomatic children in Mwanza, Tanzania Therefore, there is a paramount need to establish information on the common etiologies of RTIs in Tanzania, the information that can stimulate further studies and possible control interventions including introduction of cheap and reliable methods to detect these pathogens in clinical settings. In addition due to increased use of antibiotic without a support of a diagnostic test in the treatment of URTI as observed in number of previous studies [11] [12] [13] , make the availability of epidemiological data on the patterns of etiology of URTI of paramount important. A cross sectional hospital based study involving 339 children aged 1-59 months presenting with RTI symptoms was conducted from October 2017 to February 2018 in the city of Mwanza, Tanzania. A previous study 33 , documented Rhinovirus to cause up to 25-85% of the upper respiratory tract infections. cord-335576-b34nc3ay 2020 Patients were stratified according to the receipt of tocilizumab for cytokine storm and matched to controls using propensity scores. The current analysis does not support the use of tocilizumab for the management of cytokine storm in patients with COVID-19. The objective of this analysis was to evaluate the clinical outcome of in-hospital mortality in patients with COVID-19 treated with tocilizumab in a single medical center. Subsequently, propensity score matching was performed to account for treatment strategy influenced by confounding by indication (the tendency of clinicians to prescribe tocilizumab in patients perceived to have cytokine storm and worsening trajectory). Currently Food and Drug Administration approved for use in the management of rheumatoid conditions and cytokine release storm-related to chimeric antigen receptor (CAR)-T cell therapy, tocilizumab has gained momentum as a potentially effective option in reducing IL-6 associated fevers and preventing clinical deterioration in COVID-19. cord-336493-ggo9wsrm 2013 cord-336901-q6kgzuob 2015 cord-338041-gl65i3s0 2015 cord-338142-acqiyqwz 2020 cord-338588-rc1h4drd 2020 cord-339973-kj56zi59 2018 Although baseline metagenomic maps created from these studies are said to be useful for mitigating bioterrorism and infectious disease outbreaks, most of them focus largely on mapping surface-borne bacterial DNA 17 and neglect to address the threat of weaponized or global catastrophic biological risk-level (GCBR-level) agents, both of which would likely be aerosolized or respiratory-borne RNA viruses 19 . Bioaerosol sampling in the field provides a noninvasive way to monitor and characterize the community of aerosolized respiratory viruses that regularly infect the public, as well as potentially detect or discover novel pathogens with pandemic potential, such as the influenza A(H7N9) virus. Although the air pump flow rate and sample collection times used in our study have been demonstrated to efficiently capture aerosolized influenza virus and RSV RNA [33] [34] [35] , it is possible that these parameters are not optimal for capturing the other respiratory virus DNA/RNA targeted in our study. cord-340105-471x03f9 2016 First, to determine the minimum concentration of niclosamide that would block bacterial blight, we examined the niclosamide dosage effect on disease responses to the representative Xoo strain PXO99. These results clearly indicate that niclosamide blocks the development of rice leaf blight by directly inhibiting Xoo bacterial growth (Figs 2c and 3c) and/or by inducing defense-related gene expression (Fig. 6) . In conclusion, the results presented herein indicate that niclosamide protects rice plants from bacterial leaf blight by inhibiting Xoo growth, inducing SA accumulation, and/or by inducing the expression of defense-related gene pathways. To examine the systemic effect of niclosamide on Xoo-mediated leaf blight development, the fully expanded uppermost leaves of 80-day-old rice plants were inoculated with PXO99 by the leaf-clipping as described above. Plant growth-promoting rhizobacteria mediate induced systemic resistance in rice against bacterial leaf blight caused by Xanthomonas oryzae pv cord-340781-z348xbn0 2019 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 . cord-342122-certy2v8 2020 In this work, we tested (1) FeH and FeL in bone marrow (BM) and sera in patients with macrophage activation syndrome (MAS); (2) pro-inflammatory effects of ferritin, FeL, and FeH on macrophages; (3) ability of FeH-stimulated macrophages to stimulate the proliferation of peripheral blood mononuclear cells (PBMCs); (4) production of mature IL-1β and IL-12p70 in extracellular compartments of FeH-stimulated macrophages. Finally, www.nature.com/scientificreports/ FeH-treated macrophages enhanced the proliferation of co-cultured PBMCs. Taking together all these results and considering that AOSD and MAS could be included in the so-called "hyperferritinaemic syndrome" 14 , our data could reinforce the hypothesis that higher levels of ferritin may not only be considered a consequence or an epiphenomenon of the inflammation, but it may actively play a role in pathogenic mechanisms of those diseases, thus enhancing the inflammatory burden. cord-342289-zpstb7h9 2018 As subepithelial myofibroblasts secrete extracellular matrix and growth factors contributing to the attachment, proliferation and differentiation of epithelial cells, co-cultures of primary porcine enterocytes (ileocytes and colonocytes) with myofibroblasts were developed and evaluated for their susceptibility to enteric viruses. The differentiation status of porcine intestinal epithelial cells of 3 days old piglets and the co-cultured enterocytes were analyzed by scanning electron microscopy. To determine the percentage of rotavirus infected cells in primary porcine enterocytes, cells were fixed at different time points (0, 3, 6, 9, 12, 24 h) post inoculation with a low-passage archival RVA strain. Therefore, the susceptibility of primary porcine enterocytes co-cultured with myofibroblasts to four different genotypes of rotavirus A contained in fecal suspensions was tested by RT-qPCR (Fig. 7) . Although rotavirus was reported to have an exclusive tropism for small intestinal enterocytes 41 , rotavirus RVA/Pig-tc/BEL/RV277/1977/G1P [7] strain could infect both primary ileum and colon epithelial cells with a trypsin treatment. cord-342676-ykog278j 2016 To identify the regions of the viral genome involved in this process, we used SELEX (systematic evolution of ligands by exponential enrichment) to identify RNA aptamers which bind specifically to Core in vitro. Comparison of these aptamers to multiple HCV genomes revealed the presence of a conserved terminal loop motif within short RNA stem-loop structures. We wished to investigate the possibility that similar specific secondary structures are present within HCV RNAs destined for packaging, and whether their interactions with Core cooperatively drive the RNA encapsidation and nucleocapsid assembly processes. A mutant genome unable to form such structures displays impaired viral infectivity whilst RNA replication is unaffected, indicating these motifs may interact specifically with Core. Role of RNA structures in genome terminal sequences of the hepatitis C virus for replication and assembly cord-342782-xty16m8w 2019 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. cord-343302-g9vcchrh 2016 cord-343528-5283jsnu 2016 cord-344344-q32b742a 2020 cord-344421-rmnck42f 2018 cord-344871-486sk4wc 2016 We have previously shown that a non-structural protein 1 (NS1)-binding monoclonal antibody, termed as 2H6, can significantly reduce influenza A virus (IAV) replication when expressed intracellularly. As comparative ELISA in this and previous studies 29 showed that residues N48 and T49 in NS1(RBD) are important for the interaction with mAb 2H6, they were defined as active residues involved in the binding interaction to generate a series of models of the NS1(RBD) and 2H6-Fab complex. Overall, the predicted model from cluster 2 is consistent with our comparative ELISA data and suggests that residues N48 and T49 are important for the binding between NS1(RBD) and 2H6-Fab because their side-chains could make hydrogen bonds with residues in the VH-CDR2 of the Fab. In addition, R44 of NS1(RBD) was distal from the antibody-antigen interface, which is consistent with the results from comparative ELISA ( Figure S1 ) showing that substitution of R44 of NS1(RBD) with K did not affect its interaction with mAb 2H6. cord-344953-gtg12hiu 2017 title: Knockout of maternal CD163 protects fetuses from infection with porcine reproductive and respiratory syndrome virus (PRRSV) After infection of the porcine dam at about 90 days of gestation, porcine reproductive and respiratory syndrome virus (PRRSV) crosses the placenta and begins to infect fetuses. In this study, CD163-positive fetuses, recovered between 109 days of gestation or 20 days after maternal infection, were completely protected from PRRSV in dams possessing a complete knockout of the CD163 receptor. The hypothesis to be tested was that the presence of the CD163 KO genotype of the dam would be sufficient to protect fetuses following maternal infection with PRRSV. PRRSV nucleic acid, measured at 7 dpi, showed a viremia level for Dam No. 139 of 5.5 log 10 templates per reaction, demonstrating the presence of a productive PRRSV infection. Gene-edited pigs are protected from porcine reproductive and respiratory syndrome virus cord-345359-okmkgsbr 2020 After infecting mice with intranasal applications of 500 plaque-forming units of A/Puerto Rico/8/34 (H1N1; PR8) virus, the serum levels of most intermediates in the tricarboxylic acid (TCA) cycle and related metabolic pathways were significantly reduced. www.nature.com/scientificreports/ investigated metabolic changes by determining the serum levels of metabolites, insulin sensitivity in the liver, glucose availability, and hepatic gene expressions in the early stages of symptom onset as well as the lethal phase of influenza in a mouse model. The results of this study indicate that influenza virus infection dysregulates glucose and fatty acid metabolism and decreases tricarboxylic acid (TCA) cycle activity, leading to enhanced degradation of adenosine triphosphate (ATP) and guanosine triphosphate (GTP). Metabolites that were present at reduced levels in the sera of PR8 virus-infected mice were mainly related to the TCA cycle, urea cycle, and amino acid metabolism, as indicated by the serum levels of metabolite in these pathways at 1, 3, and 6 dpi (Fig. 2) . cord-346483-jc0xklzk 2020 cord-348515-bqqyly23 2014 Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. Thorough characterization of these pathogens is evidenced by the availability of two genome sequences (JF800905 and JX625134), both of which are further identified as the HAdV-7d genome type in this report, and shown to be nearly identical to this report of an isolate from a 2011 ARD outbreak in Guangdong Province (strain DG01_2011) by comparative genomics and, in particular, in silico REA pattern analysis, as presented in Figure 2 . cord-350255-tthttyl3 2020 To disentangle if our reproductive number estimates could be explained by importation of cases from Wuhan, Hubei, alone; and if they could be interpreted as indicators of local transmission, we formulated a linear model with the local R proxy as the response variable, and human mobility as a predictor at the province level. In all steps of filtering at the province-level, and for both time periods, τ 1 and τ 2 , absolute humidity was not associated to R proxy , with P values ranging between 0.161 and 0.922 (Tables 9, 10 , 11, 12, 13, 14, 15) . For cities, for time-period τ 1 , and after the first step of filtering, absolute humidity appeared to be associate with R proxy with a p value equal to 0.004 (Supplementary Table S5 ). cord-350468-32qin4ak 2020 Multivariate logistic regression analysis showed that CD4(+) cell count, neutrophil-to-lymphocyte ratio (NLR) and D-dimer were risk factors for severe cases. Afterward, the CD4 + cell count (P = 0.015), NLR (P = 0.032) and D-dimer (P = 0.016) were considered the independent risk factors of the severe COVID-19 cases (Table 3) www.nature.com/scientificreports/ To evaluate the predictive value of CT score, CPIS, and three independent risk factors, the ROC curve analysis was performed (Fig. 7) . In our study, we compared clinical characteristics between healthy people and COVID-19 patients, and then compared these features between severe and mild cases. Parameters including CD4 + T cell count, NLR, and D-dimer, CT score, and CPIS had quite great value for predicting disease severity, which could be considered in early warning of severe patients. Several studies have shown that severe SARS-CoV-2-infected patients have a higher NLR 11, 12 , an independent risk factor for mortality in COVID-19 patients 13 . cord-350957-10wcqgaq 2016 Recently, based on our model of immune signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) model, we suggested specific molecular mechanisms used by different viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) to modulate the host immune response mediated by members of the family of multichain immune recognition receptors (MIRRs). Previously, we reported that incorporation of another immunomodulatory peptide, GF9, that employs the SCHOOL mechanisms of action and targets triggering receptor expressed on myeloid cells 1 (TREM-1), into synthetic HDL-like nanoparticles of spherical shape (sHDL) significantly reduces the effective therapeutic dosage of GF9 in animal models of sepsis, lung cancer, and RA 33, 34 . As expected from the anti-arthritic activities demonstrated in animal models of autoimmune arthritis for TCR CP 20,21,23 and HIV gp41 FP 18 , the SARS-CoV FP-derived peptide sequence MG11 significantly suppresses CIA in mice: the peptide at 25 mg/kg/day inhibits inflammation in CIA as assessed by clinical evaluation and scoring of the disease (Fig. 2) . cord-351295-4toxlskr 2019 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). cord-351659-ujbxsus4 2020 We propose a time-varying sparse vector autoregressive (VAR) model to retrospectively analyze and visualize the dynamic transmission routes of this outbreak in mainland China over January 31–February 19, 2020. Our results demonstrate that the influential inter-location routes from Hubei have become unidentifiable since February 4, 2020, whereas the self-transmission in each provincial-level administrative region (location, hereafter) was accelerating over February 4–15, 2020. Implications of our results suggest that in addition to the origin of the outbreak, virus preventions are of crucial importance in locations with the largest migrant workers percentages (e.g., Jiangxi, Henan and Anhui) to controlling the spread of COVID-19. This enables the detection and visualization of time-varying inter-location and self-transmission routes of the COVID-19 on the daily basis. On the fifth day (February 4, 2020), no influential transmission routes were found from Hubei to directly affect other locations, and there were only three influential routes identified nationally, including Zhejiang-Shaanxi, www.nature.com/scientificreports/ Zhejiang-Jiangxi and Jiangxi-Shanghai. cord-352020-9wxwktck 2020 To alleviate this issue, we developed a plug-and-play platform using the spontaneous isopeptide-bond formation of the SpyTag:SpyCatcher system to display trimeric antigens on self-assembling nanoparticles, including the 60-subunit Aquifex aeolicus lumazine synthase (LuS) and the 24-subunit Helicobacter pylori ferritin. The versatile platform described here thus allows for multivalent plug-and-play presentation on self-assembling nanoparticles of trimeric viral antigens, with SARS-CoV-2 spike-LuS nanoparticles inducing particularly potent neutralizing responses. To improve protein solubility and expression, we added glycans to the surface of the nanoparticles, designing a panel of LuS and ferritin constructs with SpyTag and SpyCatcher (Table 1 and Supplementary Table S1 ). To demonstrate the versatility of our SpyTag-displaying nanoparticles in immunogen development, we conjugated them to three viral antigens of vaccine interest, the DS2-preF stabilized RSV F 33 , a DS2-stabilized version of PIV3 F 34 , and the 2P-stabilized version of SARS-CoV-2 spike 24 . cord-352061-x6tt9kx5 2020 cord-355179-wmfwl2bh 2019 cord-356027-ckdx56j1 2016 Compared with the normal group, the detection rates of respiratory syncytial virus (RSV) and human rhinovirus (HRV) were significantly higher in the thrombocytosis group (P = 0.017 and 0.042, respectively). Multiplex nested polymerase chain reaction (PCR) was used to detect the following common respiratory viruses, as described previously [11] [12] [13] [14] [15] : RSV subtypes A and B (RSVA, RSVB); influenza virus (IFV) subtypes A, B and C (IFVA, IFVB, IFVC); human coronaviruses (HCoV); metapneumovirus (MPV); parainfluenza virus type 1 to 4 (PIV1-4); adenovirus (ADV); human bocavirus type 1 (HBoV1) and human rhinovirus (HRV) subtypes A and C (HRVA, HRVC). Compared with the normal group, the total detection rates of RSV and HRV were both significantly higher (P = 0.001 and 0.033, respectively) in the thrombocytosis group, and ADV and IFV were lower (P = 0.001 and 0.007, respectively). ST was especially common in patients with lower respiratory tract infections and occurred most frequently in the mild thrombocytosis group (500-699 × 10 9 /L).