cord-001270-l8aa9cl3	2011	In contrast to primates, feline species lack antiviral TRIM5α genes 11 but have potently restrictive APOBEC3 proteins 9, 10 , which sets up intriguing possibilities for testing such genes at the whole-animal level, for conferring gene-based immunity with them or engineered variants 12, 13 , and potentially for HIV-1 disease model development 10 . In experiments summarized in Supplementary Table 1 , we subjected 195 in vitro-matured grade I and II domestic cat oocytes to perivitelline space microinjection (PVSMI) with lentiviral vector TSinG 5 ; we performed injection 10-12 h before or 10-12 h after in vitro fertilization (IVF) (Supplementary Fig. 1 ). We consistently observed embryo-pervasive, abundant expression of both proteins encoded by dual gene vectors in cat blastocysts when we injected lentiviral vector before IVF ( Fig. 1b and Supplementary Table 2 ).
cord-003318-abs9rvjk	2018	Unexpectedly, in an effort to identify OsSGT1, we found the bacteria lacA gene in lac operon actually encoded an SGA, specifically catalyzing the acetylations of sugar moieties of steroid 17β-glucosides. The two-step process is characterized by EcSGA1-catalyzed regioselective acylations of all hydroxyl groups on the sugar unit of unprotected steroidal glycosides (SGs) in the late stage, thereby significantly streamlining the synthetic route towards ASGs and thus forming four monoacylates. We therefore inferred that testosterone (8) was first glycosylated at the 17β-hydroxyl group by OsSGT1 to form T-17β-G (8a), which was then selectively acetylated at C-6 0 of sugar moiety to yield the 6 0 -AT-17β-G (8b) by a soluble bacterial acetyltransferase ( Supplementary Information Fig. S52) . The optimal pH and temperature of OsSGT1-catalyzed reaction using the cell-free extract of BL21(DE3)[pET28a-OsSGT1þp-Gro7] as the biocatalyst were first determined to be alkaline pH value of 11 and 50 1C, respectively (Supplementary Information Fig. S62 ).
cord-004126-u6ts87ur	2020	Moreover, single vaccination induced cross-protective H5-specific antibodies and protected mice against lethal challenge with various H5 clade 2 viruses, highlighting the potential of the VSV-based HAfl as a pan-H5 influenza virus emergency vaccine. We found that a single vaccination with VSV-vectors expressing the full-length HA (HAfl) induced crossreactive H5-specific antibodies and conferred complete protection against lethal challenge with various H5 clade 2 viruses. In contrast to all the sHA-based vaccines, single doses of the VSV-EBOV-HAfl or VSV-HAfl vectors were sufficient to provide complete protection from lethal homologous H5N1 challenge in mice (Fig. 2) . However, this study did not provide any data supporting an advantage of including VSV-EBOV as part of the vector design over just expressing VSV-HAfl as both vectors performed similarly well with no statistically significant difference in efficacy following single-dose or prime/boost administration (Fig. 2 ) nor in antibody responses (Fig. 3, Table 1 ).
cord-006034-xfyavk3m	2016	Moreover, we found that the lack of innate immunological sensing in Myd88-cKO mice did not affect expression of the Ccl19-Cre transgene in CD31 − PDPN + stromal cells of PPs or mLNs (Fig. 1c,d) . Likewise, the expression of other canonical FRC markers was not altered by the absence of MyD88 in EYFP + cells of PPs or mLNs (Fig. 1g) MyD88 signaling in FRCs controls antiviral ILC1 responses To assess whether an invasive enteric pathogen would substantially alter the activity of FRCs, we infected MyD88-sufficient mice and mice with FRC-specific MyD88 deficiency with mouse hepatitis virus (MHV). The accelerated viral control in Myd88-cKO mice as early as on day 3 after infection suggested that innate antiviral immune cells had been activated by the FRC-specific MyD88 deficiency.
cord-007073-soov8q3q	2019	A similar pattern of PeV infection, but with lower incidence rates, was observed in 200 Finnish children enrolled between 1996 and 2007 where by age 12 months 22% had PeV detected in their stools on at least 1 occasion, which increased to 48% approaching their second birthday [15] . We therefore aimed to describe the epidemiology of PeV in the first 2 years of life by the means of an unselected communitybased birth cohort whose recruitment coincided with the first reported outbreak of severe PeV-A3 disease in Australia [5, 19] , and to investigate the risk factors and symptoms associated with acquiring PeV in these young children. The Observational Research in Childhood Infectious Diseases (ORChID) project (ClinicalTrials.gov identifier NCT01304914) is a community-based, longitudinal, birth cohort study of acute respiratory infections (ARIs) and acute gastroenteritis (AGE) in unselected, healthy Australian children in their first 2 years of life [20] [21] [22] [23] .
cord-013614-j6h338qa	2020	To identify potentially new NHEJ factors, we combined chemical perturbation screens on 36 compounds with focused CRISPRknockout screens on 414 genes in the CH12 B cell line ( Fig. 1a ; Supplementary information, Table S1 , see Materials and Methods for details). ERCC6L2 clusters with other NHEJ factors Next, we clustered all 414 DNA repair genes by their z-scores across the 36 chemicals used, which categorized genes into three major groups depending on their impact on cell growth (Supplementary information, Fig. S1a ). Furthermore, the helicase catalytic-dead (DEAH > AAAH) mutant did not promote CSR ( Fig. 3a ; Supplementary information, Fig. S4b ), indicating that ERCC6L2''s predicted catalytic activity is required for DNA end-joining. To bypass the B cell development defect of core-NHEJ factor deficiencies and quickly access the directional CSR, we deleted the non-productive IgH allele in CH12F3 cells as previous described 18 (Supplementary information, Fig. S8c , named CH12-NCDel cells) and perform HTGTS assay with endogenous AID Sμ baits.
cord-013658-vygiate7	2020	Within saline lakes, a considerable amount of DOC is originated from terrestrially derived dissolved organic matter (tDOM) from surrounding soils [5] , and may undergo extensive transformations by lacustrine microbial communities [6] . To address these knowledge gaps, the linkage between aquatic microbial communities and the degradation potentials of tDOM in the QTP lakes of different salinity was investigated in this study by performing microcosm experiments and using a suite of analytical techniques. In the meanwhile, distinct microbial taxa appeared to be responsible for the transformation of tDOM among different lakes, as evidenced by abundance increases of lake-specific OTUs after microcosm incubations (Supplementary Table S2 ). In this study, the relative abundances of certain copiotrophic OTUs showed a dramatic increase (>10 times) in response to the addition of tDOM during microcosm incubations of two saline lake (TSL and XCDL) samples (Supplementary Table S2 ).
cord-013784-zhgjmt2j	2020	To move beyond serum-free sphere culture-based models, we utilized a DLP-based rapid 3D bioprinting system to generate 3D tri-culture or tetra-culture glioblastoma tissue models, with a background "normal brain" made up of NPCs and astrocytes and a tumor mass generated by GSCs, with or without macrophage, using brain-specific extracellular matrix (ECM) materials (Fig. 1a ). 35 While patient-derived glioblastoma cells grown under serum-free conditions enrich for stem-like tumor cells (GSCs) that form spheres and more closely replicate transcriptional profiles and invasive potential than standard culture conditions, we previously demonstrated that spheres display differential transcriptional profiles and cellular dependencies in an RNA interference screen compared to in vivo xenografts. [49] [50] [51] g Therapeutic efficacy prediction of drugs in all cancer cells in the CTRP dataset based on differentially expressed genes between the 3D tetra-culture model and GSCs grown in sphere culture as defined by RNA-seq.
cord-015527-ph576eji	2019	Although we performed mappings, read countings, and normalization for all samples, bat genome assemblies and all six data sets ( Table 2 ; overall 1568 mappings), we only selected one comparison per data set to exemplarily show novel and significantly differential expressed ncRNAs (Supplementary Files S2.1-S2.15; divided by data set and input annotation). To give a better estimation of transcribed and potentially functional ncRNAs, we used six Illumina short-read RNA-Seq data sets derived from four bat species (Table 2) to estimate the expression levels of our novel annotations. To this end, we used the RNA-Seq data sets Field-2015 , Field-2018 , Hölzer-2019 and Weber-2019 (Table 2 ) as a basis to identify DE ncRNAs that were newly discovered in this study and were not part of the current NCBI or Ensembl genome annotations for this bat species.
cord-024810-z323cl40	2020	Here, we have developed a tailored, electronic textile conformable suit (E-TeCS) to perform large-scale, multimodal physiological (temperature, heart rate, and respiration) sensing in vivo. Similar to a compression shirt, the soft and stretchable nature of the tailored E-TeCS allows intimate contact between electronics and the skin with a pressure value of around ~25 mmHg, allowing for physical comfort and improved precision of sensor readings on skin. Through this work, we have developed a technique of combining thin, customizable conformable electronic devices, including interconnect lines and off-the-shelf integrated circuits, with plastic substrates that can be woven into knitted textile using an accessible and high-throughput manufacturing approach. We demonstrate the capability of our electronic textile conformable suit (E-TeCS) for distributed, wireless physiological sensing, such as temperature, respiration and heart-rate detection, and physical activity monitoring around the human body during a physical exercise.
cord-102481-obig3mu1	2020	The validity of this prediction was tested by an independent biochemical method (ELISA), by measuring the Aβ-peptide concentrations within the isogenic T21:D21 organoid CM comparison, which showed an increase in absolute concentrations caused by T21 for each Aβ 1-38, 1-40 and 1-42, with no difference in the Aβ 1-42/1-40 ratio between T21 and isogenic D21 lines, mirroring the readout in the absolute levels of IP-MS peaks ( Supplementary Fig. 6 ). Pearson''s coefficient showed a high level of colocalisation (>0.55) of both the main substrate (Aβx-40) and its putative degradation product (Aβx-34) with BACE2 in neurons of cerebral organoids, in LAMP2+ compartment (known to be a subset of lyzosomes, therefore low pH vesicles) ( Fig. 3 & Supplementary Fig. 8 ). Our data in Figs.1 and Supplementary Fig. 7 suggest that anti-amyloidogenic activity of BACE2 is gene-dose dependent, and its level varies between individuals, with SNP allelic differences in BACE2 correlating with age of dementia onset.
cord-103081-k7ev5qkn	2020	Note that the expression of cluster-defining markers varied significantly during the injury and 63 recovery phases of sepsis ( Fig. S1b; Supplementary Table 1 ). One of the subclusters showed 112 increased expression of alternatively activated macrophages (M2) markers such as Arg1 113 (Arginase 1) and Mrc1 (Cd206) 27 at later time points (36 hours, Supplementary Fig. 4b) . Such 181 communication patterns among these four cell types may also explain macrophage clustering 182 around S1 tubules at later time points in sepsis as we previously reported 13 . To this end, we selected the differentially expressed genes from all cells combined (pseudo 203 bulk) for each time point across the mouse sepsis timeline (Supplementary Table 4) . Our data 215 cover nearly all renal cell types and are time-anchored, thus providing a detailed and precise 216 view of the evolution of sepsis in the kidney at the cellular and molecular level.
cord-103638-n5kpvsvg	2020	By extending the 3''or 5''-ends of the crRNA with different lengths of ssDNA, ssRNA, and phosphorothioate ssDNA, we discovered a new self-catalytic behavior and an augmented rate of LbCas12a-mediated collateral cleavage activity as high as 3.5-fold compared to the wild-type crRNA. With isothermal amplification of SARS-CoV-2 RNA using RT-LAMP, the modified crRNAs were incorporated in a paper-based lateral flow assay that could detect the target with up to 23-fold higher sensitivity within 40-60 minutes. However, the ENHANCE showed 5.4-fold and 3.4-fold and higher trans-cleavage activity compared to the wild-type crRNA for targeting the methylated dsDNA and ssDNA, respectively (Fig. 3e, Supplementary Fig. 20a) . While no clinical samples were tested, the results indicated the 3''DNA7-modified crRNA consistently demonstrated higher sensitivity for detecting CoV-2 dsDNA within 30 minutes as compared to the wild-type crCoV-2 ( Supplementary Figs.
cord-103683-xcsal8vk	2020	The structure also provides new insights into conserved aspects of HAdV architecture such as a proposed location of protein V, which links the viral DNA to the capsid, and assembly-induced conformational changes in the penton base protein. Compared to the two other reported structures of human adenoviruses, HAdV-C5 (PDB: 6B1T (20) ) and HAdV-D26 (PDB: 5TX1(21)), the sequence identity of the capsid proteins ranges from 30-80% (Supplementary Table 3 ). The HAdV-F41 penton base undergoes assembly-induced conformational changes Located on the five-fold symmetry axes of adenovirus capsids, the penton base (PB) protein forms a homopentamer that contains integrin-binding motifs and serves as an assembly hub connecting the icosahedral capsid to the fibers (Fig. 1A) . The DNA-binding protein V is located at a conserved position at the inner face of the capsid After initial model building of the virion at pH=7.4, the asymmetric unit contained five peptide chains that still had not been assigned an identity.
cord-103892-v6gkubd4	2020	Overall, these data demonstrated that the enhanced or diminished capabilities of the variant RNAPs to utilize 2''dGTP in the SNA assays reflected, in qualitative terms, their capabilities to utilize all four 2''dNTPs. The role of the β''Arg425 in selectively promoting the binding of NTPs was easy to explain because the β''Arg425 interacts with the 2''OH of the NTP analogues in several RNAP structures (Supplementary Table 5 , Fig. 1c, 4a, b) . We further hypothesized and demonstrated by in silico docking experiments that the 3''OH could move to within the hydrogen bond distance of the β''Arg425 if the deoxyribose moiety adopted a 2''-endo conformation (Supplementary Fig. 8 To test this hypothesis in crystallo, we solved the X-ray crystal structure of the initially transcribing complexes containing T. Overall, the comparative analysis of RNAP structures with CMPCPP, 2''dCTP and 3''dCTP suggested that the β''Arg425 inhibited the incorporation of 2''dNTPs by interacting with their 3''OH group and favoring the 2''-endo conformation of the deoxyribose moiety.
cord-103915-rzy7mejb	2018	We have previously shown that gene therapy delivery of human NT3 into the affected triceps brachii forelimb muscle improves sensorimotor recovery after ischemic stroke in adult and elderly rats. We also recently showed that injection of an adeno-associated viral vector (AAV) encoding full-length human NT3 (preproNT3, 30kDa) into forelimb muscles 24 hours after stroke in adult or elderly rats improved sensorimotor recovery 19 . We examined anatomical neuroplasticity in the C7 cervical spinal cord because we knew from experiments using adult and elderly rats that the less-affected corticospinal tract sprouts at this level (as well as other levels) after injection of AAV-NT3 into muscles including triceps brachii 19 . fMRI performed one week after stroke confirmed that somatosensory cortex was not active when the affected paw was stimulated in either vehicle or NT3 treated rats (p>0.05, Supplementary Fig. 6b ). Treatment of disabled arm muscles with NT3 protein, initiated 24 hours after stroke, caused changes in multiple locomotor circuits, and promoted a progressive recovery of sensory and motor function in rats.
cord-198395-v15queyh	2020	Fraction of shared ride requests from different origins (red) served by the four major for-hire vehicle transportation service providers in New York City by destination zone (January -December 2019) [27] . To understand how these incentives determine the adoption of ride-sharing, we study sharing decisions in a stylized city network [30] with a common origin o (e.g., from a central downtown location) in the center and multiple destinations d (illustrated in Fig. 3 ). a,b Sharing decisions for New York City and Chicago (blue dots) accumulate on two branches corresponding to the predicted high-and low-sharing regime as a function of request rate (compare Fig. 4) . The data is provided by New York City''s Taxi & Limousine Commission (TLC) [27] and consists of origin and destination zone per request, pickup and dropoff times, as well as a shared request tag, denoting a request for a single or shared ride.
cord-252597-ea78sjcs	2020	Moreover, the in-depth analysis of the mutational landscape of SARS-CoV-2 confirms a statistically significant increase of genomic diversity in time and allows us to identify a number of variants that are transiting from minor to clonal state in the population, as well as several homoplasies, some of which might indicate ongoing positive selection processes. The outbreak of coronavirus disease 2019 (COVID19) , which started in late 2019 in Wuhan (China) [1, 2] and was declared pandemic by the World Health Organization, is fueling the publication of an increasing number of studies aimed at exploiting the information provided by the viral genome of SARS-CoV-2 virus to identify its proximal origin, characterize the mode and timing of its evolution, as well as to define descriptive and predictive models of geographical spread and evaluate the related clinical impact [3, 4, 5] .
cord-256652-ent4vu3z	2018	investigate this response at high resolution, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized by repeated injection of irradiated PfSPZ and who were found to be protected from controlled human malaria infection (CHMI) with infectious homologous PfSPZ. investigate this response at high resolution, we isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized by repeated injection of irradiated PfSPZ and who were found to be protected from controlled human malaria infection (CHMI) with infectious homologous PfSPZ. These findings, combined with data from peptide array experiments ( Supplementary Fig. 7) , identify the N-terminal junction binding site of the most potent neutralizing antibodies as including the first unit of the NANP repeat region and flanking non-repeat sequences, providing a molecular basis for the dual specificity of these antibodies.
cord-262470-nkql7h9x	2020	title: Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. To assess the association of age, sex, and smoking status with the expression of ACE2, TMPRSS2, and CTSL, we aggregated 22 scRNA-seq datasets of healthy human nasal and lung cells, as well as fetal samples.
cord-263868-ewnf96cz	2020	ZIKV was labeled on its surface with a chemical probe, which carries a photocrosslinker to covalently link virus-interacting proteins in living cells on UV exposure at different time points, and a biotin tag for subsequent enrichment and mass spectrometric identification of the receptor or other host proteins critical for virus internalization. We used the labeled ZIKV to infect Vero cells and interacting proteins were crosslinked at fixed time points to identify the virus-host factors and elucidate the virus entry mechanism (Fig. 1c) . To further investigate whether the strategy was also capable of correlating spatial information with the virus crosslinked proteins, we performed the STRING analysis to determine whether there is statistical overrepresentation of specific genes or proteins in the sample at specific time points and identify proteins specific at the attachment or cellular entry stages ( Supplementary Fig. 6 ).
cord-265418-yqe9vdj1	2020	Integrated interactome-transcriptome analysis to generate Calu-3-specific humanIt is likely that the outcome of SARS-CoV-2 infection can largely be determined by the interaction patterns of host proteins and viral factors. By integrating this Calu-3 co-expression network with SIPs-derived PPI subnetwork, we generated Calu-3-specific human-SARS-CoV-2 Interactome (CSI) that contains 214 SIPs interacting with their first and second neighbors make a network of 4,123 nodes and 14,650 edges (Fig. 1c, Supplementary Data 1) . We showed that CSI follows a power law degree distribution with a few nodes harboring increased connectivity, and thus exhibits properties of a scale-free network (r 2 = 0.91; (Fig. 1d , Supplementary Data 1), similar to the previously generated other human-viral interactomes 12, 13, 14, 15, 16, 17, 18, 19, 20, 24, 25, 26, 27, 28 . In conclusion, we generated a human-SARS-CoV-2 interactome, integrated virusrelated transcriptome to interactome, discover COVID-19 pertinent structural and functional modules, identify high-value viral targets, and perform dynamic transcriptional modeling.
cord-268645-5op2m7pu	2015	However, the understanding of the viral population and the ecological diversity residing in bat populations is unclear, which complicates the determination of the origins of certain EIDs. Here, using bats as a typical wildlife reservoir model, virome analysis was conducted based on pharyngeal and anal swab samples of 4440 bat individuals of 40 major bat species throughout China. Based on the partial genomic sequences of the viruses obtained by the assembly, we designed specific nested primers for PCR or reverse trancriptase-PCR to screen for each virus in individual samples from each bat species (the primer sequences for each virus are available in Supplementary Table S2 ). The diverse BtCoVs were grouped into several novel evolutionary clades that significantly differed from those of all known αand β-CoVs, providing additional evidence to support investigations of the evolution of bat-originated CoVs. With regard to BtParaVs, a previous study has revealed that bats host major mammalian ParaVs in the genera Rubulavirus, Morbillivirus, Henipavirus and the subfamily Pneumovirinae (Drexler et al., 2012) .
cord-271693-7tg21up3	2020	Many different approaches have been devised or applied to detect structures in biological data, including standard clustering, network community detection, and low-dimensional data projection [5] [6] [7] , some of which can be tuned for sensitivity to objects of a certain size or scale (so-called ''resolution parameters'') [8, 9] . We first explored the idea of measuring community persistence via analysis of synthetic datasets [15] in which communities were simulated and embedded in the similarity network at two different scales (Supplementary Fig. 1a; Methods) . Application to protein-protein interaction networks from budding yeast and human found that HiDeF captured knowledge in GO more significantly than previous pipelines proposed for this task, including the NeXO approach to hierarchical community detection [23] and standard hierarchical clustering of pairwise protein distances calculated by three recent network embedding approaches [24] [25] [26] (Fig. 3a, Fig. 7) .
cord-282566-rgo5sj5i	2014	However, β 2 -AR-depleted endothelial cells, although unable to promote signaling events, still support pilus-mediated bacterial adhesion, thus indicating that the primary meningococcal attachment requires another, yet unidentified, host receptor for type IV pili. Here, we report that CD147, a member of the immunoglobulin (Ig) superfamily, is a receptor for type IV pilus-mediated adhesion of pathogenic meningococci to human brain or peripheral endothelial cells through interaction with both major and minor pilins-PilE and PilV-and we establish the central role of CD147 for vascular colonization by meningococci in vivo. This study demonstrates that the specific interaction between the meningococcal ligands PilE and PilV and the cellular host receptor CD147 is essential for meningococcal adhesion to human endothelial cells and colonization of human blood vessels, a prerequisite to the major vascular alterations that are the hallmark of invasive meningococcal infections.
cord-284015-vvtv492b	2020	We identified that megabat genomes are distinct in that they have extremely low activity of SINE retrotranspositions, expansion of two chemosensory gene families, including the trace amine receptor (TAAR) and olfactory receptor (OR), and elevation of the dN/dS ratio in genes for immunity and protein catabolism. The protein-coding genes in the genomes of Egyptian fruit bat and Leschenault''s rousette were identified based on the alignment with annotated gene sequences of 14 mammals (cat, dog, horse, cow, hedgehog, human, macaque, mouse, rat, Black flying fox, Little brown bat, Brandt''s bat, David''s myotis, and Large flying fox; Supplementary Table S2 ) that are available in the database. 71 Suggesting that FPR-mediated chemodetection is not directly linked with the difference in their habitats, mega-and microbats both possess two to eight FPRs. However, a previous study, by comparing the orthologous sequences among a broad range of mammals, found the signatures for the operation of positive selection in FPRs. 72 Therefore, to examine the possible contribution of FPRs to the adaptive evolution of megabats, more detailed investigation is necessary by focussing on the dN/dS values among orthologous FPR sequences of many bat species, which are lacking at present.
cord-286217-3uklf2u2	2020	Here we construct a SARS-CoV-2 proteome microarray containing 18 out of the 28 predicted proteins and apply it to the characterization of the IgG and IgM antibodies responses in the sera from 29 convalescent patients. We detected the SARS-CoV-2-specific IgG and IgM proteins bound to the array using fluorescent-labeled anti-human antibodies, thereby generating a global assessment of each patient''s humoral antibody response. All of the samples and the controls were probed on the proteome microarray, and after data filtering and normalization, we constructed the IgG and IgM profile for each serum and performed clustering analysis to generate heatmaps (Figs. To statistically analyze the IgG responses against SARS-CoV-2 proteins, we calculated the p-values followed by multiple testing correction (or q-values), and applied significant analysis of microarray (SAM) to identify significant positive proteins (Supplementary Fig. 7 and Data 2).
cord-288824-sygnmiun	2020	To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We correlated changes in the energy of the complex with changes in the structure of ACE2, chemical properties of residues in the binding interface, and experimental COVID-19 infection phenotypes from in vivo and in vitro animal studies. We used multiple methods to assess the relative change in binding energy (ΔΔG) of the SARS-CoV-2 S-protein:ACE2 complex following mutations in DC residues and DCEX residues that are likely to influence binding. Irrespective of host, the SARS-CoV-2 spike receptor binding domain is conserved (Fig. 4b) across tested human and animal associated SARS-CoV-2, suggesting mutations in the RBD are not required for infections observed in non-human species to date.
cord-288916-i8ukefp8	2019	A pulse SILAC methodology identified IRF1, HLA-B, and ISG15 as the most dominating IFNγ inducible proteins whose synthesis was attenuated in the IFITM1/IFITM3 double-null cells. SWATH-MS proteomic screens in cells treated with IFITM1-targeted siRNA cells resulted in the attenuation of an interferon regulated protein subpopulation including MHC Class I molecules as well as IFITM3, STAT1, B2M, and ISG15. These data have implications for the function of IFITM1/3 in mediating IFNγ stimulated protein synthesis including ISG15ylation and MHC Class I production in cancer cells. The HPV16+ and IFITM1/3 positive cervical cancer cell line SiHa [38] [39] exhibit IFNγ inducible STAT1, IRF1, and IFITM1/3 proteins (Fig. 1G ). Also of note is attenuation of HLA-A, HLA-B, HLA-C, and ISG15 protein synthesis 24 h post-IFNγ treatment in the IFITM1/IFITM3 double null cells compared to parental SiHa (Fig. 5F vs 5B). By contrast, basal HLA-B protein expression was attenuated in the IFITM1/IFITM3 double null cells after IFNγ treatment (Fig. 6F vs 6E) .
cord-292862-ezrkg0dc	2020	We show that polystyrene nanoparticles and five liposome formulations do not accumulate in injured lungs, indicating that nanostructures that are not based on protein are not intrinsically drawn to marginated neutrophils in acute inflammation. 6, 10, 14, 18 Single cell suspensions prepared from mouse lungs were probed by flow cytometry to further characterize pulmonary neutrophils in naïve mice and in mice following LPS-induced inflammation. The protein component of each particle was labeled with 125 I for tracing in biodistributions, and assessed 30 minutes after IV administration of NPs. Both absolute LDNG lung uptake and ratio of lung uptake to liver uptake registered a ~25-fold increase between naïve control and LPS-injured animals (Figure 2A , Supplementary Table 1) . As with LDNGs and albumin NPs in Figure 2C -H, single cell suspensions were prepared from LPS-inflamed and naïve control lungs after circulation of fluorescent DBCO-IgG liposomes.
cord-295482-qffg6r91	2017	Here we report the X-ray crystal structure of the receptor-binding domain (RBD) of the human coronavirus, HCoV-229E, in complex with the ectodomain of its receptor, aminopeptidase N (APN). Phylogenetic analysis shows that the natural HCoV-229E receptor-binding loop variation observed defines six RBD classes whose viruses have successively replaced each other in the human population over the past 50 years. The structure shows that receptor binding is mediated solely by three extended loops, a feature shared by HCoV-NL63 and the closely related porcine respiratory coronavirus, PRCoV. The six RBDs differ in their receptor-binding affinity and their ability to be bound by a neutralizing antibody (9.8E12) and taken together, our findings suggest that the HCoV-229E sequence variation observed arose through adaptation and selection. HCoV-229E infection in humans does not provide protection against different isolates 37 , and viruses that contain a new RBD class that cannot be bound by the existing repertoire of loop-binding neutralizing antibodies provide an explanation for this observation.
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-315483-l6dm82pp	2018	To confirm the sequence of the cDNA and to identify the genomic structure of the identified IFIT gene, the transcript was amplified from RNA extracted from NDV-infected CEFs. Complete sequence analysis of the gene revealed an open reading frame (ORF) of 1440 bps (479 amino acids excluding stop codon) with high sequence identity (48% and 67%) with the human and duck IFIT5 proteins, respectively ( Supplementary Fig. 1B) . The levels of chIFN-β gene induction was proportional to the NDV replication (Fig. 2D) , therefore, it can be inferred that the virus-induced expression of chicken IFIT5 is IFN-dependent and that chIFIT5 is an early-ISG with capacity to modulate initial steps of virus life cycle. To compare anti-viral effects of chIFIT5 (only IFIT gene identified in chickens so far) with its orthologous and homologous human proteins, huIFIT1, huIFIT2, huIFIT3 and huIFIT5 were expressed in chicken cells and antiviral affect was monitored (Fig. 5A ).
cord-318079-jvx1rh7g	2020	The ABM was developed to simulate different non-pharmaceutical interventions including lockdown, physical distancing, self-isolation on symptoms, testing and contact tracing. A previous study of social contacts for infectious disease modelling, based on participants being asked to recall their interactions over the past day, has estimated the mean number of interactions that individuals have by age group [12] . We present OpenABM-Covid19, a COVID-19-specific agent-based model suitable for simulating the epidemic in different settings and assessing non-pharmaceutical interventions, including contact tracing using a mobile phone app. Further, on developing symptoms or during interventions such as contact tracing, the interaction pattern of individuals change to only include those in the household. One of the key aims of OpenABM-Covid19 was to model non-pharmaceutical interventions and, in particular, different forms of contact tracing. OpenABM-Covid19 is a versatile tool to model the COVID-19 epidemic in different settings and simulate different non-pharmaceutical interventions including contact tracing.
cord-320325-sjab8zsk	2018	Using purified KSHV SOX protein, we reconstituted the cleavage reaction in vitro and reveal that SOX displays robust, sequence-specific RNA binding to residues proximal to the cleavage site, which must be presented in a particular structural context. Using an RNA substrate that is efficiently cleaved by SOX in cells, we revealed that specific RNA sequences within and outside of the cleavage site significantly contribute to SOX binding efficiency and target processing. Given that both substrates contain the requisite unpaired bulge at the predicted cleavage site (see Figure 2A and Supplementary Figure S2 ), these observations suggest that additional sequence or structural features impact SOX targeting efficiency on individual RNAs. Two SOX point mutants, P176S and F179A, located in an unstructured region of the protein that bridges domains I and II have been shown to be selectively required for its endonucleolytic processing of RNA substrates (Supplementary Figure S3A and S3B) (8, 21) .
cord-322129-uyswj4ow	2020	Infection studies of rhesus monkeys, long-tailed macaques, and vervets as biomedical models have made it clear that at least some nonhuman primate species are permissive to SARS-CoV-2 infection and develop symptoms in response to infection that resemble those of humans following the development of COVID-19, including similar age-related effects [11] [12] [13] [14] [15] [16] . We assessed the variation at amino acid residues identified as critical for ACE2 recognition by the SARS-CoV-2 RBD and undertook an analysis of positive selection and protein modeling to gauge the potential for adaptive differences and the likely effects of protein variation. In particular, the twelve sites in the ACE2 protein that are critical for binding of the SARS-CoV-2 virus are invariant across the Catarrhini, which includes great apes, gibbons, and monkeys of Africa and Asia (Fig. 1) .
cord-322286-2de6r1h6	2020	title: Positive Selection and Gene Expression Analyses from Salivary Glands Reveal Discrete Adaptations within the Ecologically Diverse Bat Family Phyllostomidae We sequenced expressed transcripts from phyllostomid salivary glands and found strong signals of selection among immune-related genes. We sequenced the SMG transcriptomes of nine phyllostomid bats representing different subfamilies and different diets, and through analysis of orthologs characterized how selection on coding sequence and expression differences have shaped SMGs. Nine species from seven out of the 11 recognized subfamilies were chosen to maximize representation of the phylogenetic and dietary diversity of Phyllostomidae ( fig. After correcting for FDR, we found 53 genes where models of evolution allowing positive selection were significantly better fit to the data than neutrality in both M2a and M8 tests (supplementary table S2, Supplementary Material online). Moreover, given that some Golgi body-related genes appeared under selection in all branch-site tests, this organelle played some role in the adaptive radiation of phyllostomids.
cord-323307-nu9ib62h	2016	For homology-based gene prediction, the protein sequences of human, mouse, dog, cow, little brown bat and large flying fox were downloaded from Ensembl Release 72 and mapped onto the repeat-masked genome using GenBlastA (She, et al. Moreover, we identified 577, 453 and 182 positively selected genes in the great leaf-nosed bat, the Chinese rufous horseshoe bat and the large flying fox, (Supplementary Tables S10, 11, 12), respectively. Clade model C implemented in PAML was employed (Weadick and Chang 2012) , and the result also persisted that more positively selected genes were detected in the branches leading to echolocating bats (Supplementary Table S20 ). The genome re-sequencing analysis has been performed based generally on the following considerations: 1) to characterize the genetic diversity and patterns of evolution; 2) to understand the genetic bases of adaptation to high altitude in the great leaf-nosed bats.
cord-325155-lqzgz6p3	2020	Two adjacent haplotype blocks characterize the 9p21.3 cardiovascular risk locus: left, the block or island containing the first part of the p15 gene and its wellcharacterized promoter, in which we observed clearly elevated associations (red) with blood pressure (DBP, SBP) and/or hypertension in a Colombian and a European study sample, and right, the block hypertension and BP association ''Hypertension island'' * (haplotype block < 60 kb) Lead CVD risk SNPs (haplotype block < 60 kb) Furthermore, in the European blood pressure studies [15, 16] genome-wide significance of DBP associations was attained, outside of the classic 9p21.3 CVD risk locus and its flanking regions, in the next gene MTAP (see Figure 2 and Theory), with a lowest p-value of 1.3 × 10 −10 for the sentinel SNP rs4364717 (red asterisk and red horizontal bar at left in Figure 2 ; see also the LocusZoom plot in Supplementary Material S3.2) .
cord-333145-a20dlaxn	2020	In a meta-analysis of three GWAS for susceptibility to Kawasaki disease (KD) conducted in Japan, Korea, and Taiwan and follow-up studies with a total of 11,265 subjects (3428 cases and 7837 controls), a significantly associated SNV in the immunoglobulin heavy variable gene (IGHV) cluster in 14q33.32 was identified (rs4774175; OR = 1.20, P = 6.0 × 10(−9)). Considering that significant association of SNVs in the IGHV region with disease susceptibility was previously known only for rheumatic heart disease (RHD), a complication of acute rheumatic fever (ARF), these observations suggest that common B-cell related mechanisms may mediate the symptomology of KD and ARF as well as RHD. Instead, 7 out of 12 groups of SNVs in the 6p21 region examined in the Stage 2 analyses showed significant association in the metaanalyses of the data sets in the three GWAS as well as in the follow-up studies ( Table 1 and Supplementary Fig. 3A ).
cord-336209-grpi7gnc	2020	Finally, an effective science policy interface includes the establishment of a scientifically sound monitoring system and data infrastructure, technical capacities and tools to support assessment of land degradation as well as progress in LDN implementation, the evaluation of economic, social and environmental benefits and trade-offs associated with achieving LDN, and the effective collation and translation of scientific knowledge to policy-makers, planners and other relevant stakeholders (Akhtar-Schuster et al., 2011; Chasek et al., 2019; Cowie et al., 2018; Orr et al., 2017) . Enablers lagging furthest behind in terms of individual country progress correspond to the financial dimension (2.1 and 2.2), some elements of the policy/regulatory environment (3.1 land tenure, 3.2 integrated land-use planning, and 3.3 neutrality mechanism), as well as national technical capacities for LDN assessments and implementation (4.2).
cord-340907-j9i1wlak	2020	Here, based on a novel statistical framework and a large-scale genomic analysis of 2,625 viruses from all classes infecting 439 host organisms from all kingdoms of life, we identify short nucleotide sequences that are under-represented in the coding regions of viruses and their hosts. Figure 3A and B depicts the average number of under-represented sequences of size m ¼ 3, 4, and 5 nucleotides, identified in few subsets of viruses in both the original and random variants of the virus. A sampling analysis that we performed (see Supplementary document, Section 2.8) suggests that the number of under-represented sequences identified in dsDNA viruses matches their genomic size, when compared with RNA viruses. To show that the correspondence between selection against short palindromic sequences in viruses and restriction sites cannot be explained by basic coding region features such as amino-acid content and order, codon usage bias and dinucleotide distribution, we also evaluated the overlap between restriction sites and common under-represented sequences of random variants of viruses.
cord-342012-1w3x0g42	2020	For a completely novel pathogen, especially one with a high (say, >2) basic reproductive number (the expected number of secondary cases generated by a primary case in a completely susceptible population) relative to other recently emergent and seasonal directly transmissible respiratory pathogens 4 , assuming homogeneous mixing and mass action dynamics, the majority of the population will be infected eventually unless drastic public health interventions are applied over prolonged periods and/or vaccines become available sufficiently quickly. We therefore extended our previously published transmission dynamics model 4 , updated with real-time input data and enriched with additional new data sources, to infer a preliminary set of clinical severity estimates that could guide clinical and public health decision-making as the epidemic continues to spread globally. Given that we have parameterized the model using death rates inferred from projected case numbers (from traveler data) and observed death numbers in Wuhan, the precise fatality risk estimates may not be generalizable to those outside the original epicenter, especially during subsequent phases of the epidemic.
cord-342047-pm3i54mb	2020	Interestingly, combining the two distinct stress paradigms did not have an additive effect on behavioural and biological outcomes, but resulted in yet a different phenotype, characterized by increased anxiety-like behaviour, decreased plasma levels of IL1β, IL4 and VEGF, and decreased hippocampal neuronal differentiation, without altered neuroinflammation or corticosterone reactivity. Each treatment comprised one or two distinct stressors that was either in the form of repeated injection, which has been previously shown to differentially alter stress responses in BALB/C mice 20 and affective outcomes in outbred rats with high and low emotional reactivity 21 , or permanent social isolation, which has consistently been associated with depressivelike phenotypes 8, 9, 11 . Based on our data, we believe that the neurogenic profiles observed are a functional consequence of the neuroinflammatory changes associated with each stress exposure, given that microglia and astrocytes play an important role b Representative photomicrographs of the ventral (i) and dorsal (ii) dentate gyrus stained for Iba1 for repeatedly injected and socially isolated mice, respectively, all relative to controls.
cord-343107-oj1re34k	2019	Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. The 7D10 antibody recognizes the NTD of MERS-CoV S glycoprotein and neutralizes the infectivity of pseudotyped and live virus with a potency comparable to those of the most active RBD-targeting antibodies. The NTD N222Q mutation also dramatically reduced the binding and neutralization by 7D10, but did not dramatically affect the cell infection of pseudotyped MERS-CoV ( Supplementary Fig. 11) . A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein A humanized neutralizing antibody against MERS-CoV targeting the receptor-binding domain of the spike protein
cord-346054-k84rcpav	2018	Here, we develop a chip containing 130 different micro-arrayed RV proteins and peptides and demonstrate in a cohort of 120 pre-school children, most of whom had been hospitalized due to acute wheeze, that it is possible to determine the culprit RV species with a minute blood sample by serology. The analysis of IgG reactivity to structural and non-structural proteins and to recombinant fragments and synthetic peptides spanning VP1, VP2, and VP3 from RV89 is shown in Supplementary Fig. 2a for all 120 children and in Supplementary Fig. 2b for those children (n = 41) who had shown increases of RV89-specific antibody responses in follow-up serum samples taken after recovery. Based on our previous observations that antibody increases specific for the N-terminal portion of VP1 can be detected in serum samples obtained from subjects after RV infection 36 , the PreDicta chip was equipped with a VP1 peptide set which should allow detecting species-specific immune responses at high resolution ( Fig. 1 ).
cord-348972-r94fhpe0	2020	The most striking and obvious common feature of the Acrs is their small size (weighted mean Acr length: 104 aa, Table 1 ), and the tendency to form sets of small proteins that are encoded by co-directional and closely spaced genes in (pro)virus genomes (hereafter directons; Fig. 1 , Table 1 ). As genes encoding Acrs tend to form small directons, we sought to estimate a heuristic maximum threshold for the mean directon size in a candidate family that would enrich our protein set for true Acrs. The initial set consisted of 232,616 clusters and was first filtered for clusters that included at least one member with an HTH-domain-containing protein encoded downstream, and at least one member from a self-targeting genome, two hallmark Acr characteristics 20 .
cord-350286-n7ylgqfu	2020	The results of this analysis are summarized in Table 2 , which clearly shows that most of the SARS-CoV-2 proteins contain at least one MoRF, indicating that disorder does play an important role in the functionality of these viral proteins. As it follows from Figure 3 , these cleavage sites are located within the IDPRs. In Human SARS CoV S protein, fusion peptide (residues 770-788) is located within a flexible region, is characterized by the mean disorder score of 0.232±0.053. Global analysis of intrinsic disorder in the replicase polyprotein 1ab Table 3 represents the PPID mean scores of 15 non-structural proteins (Nsps) derived from the Replicase polyprotein 1ab in SARS-CoV-2, Human SARS CoV, and Bat CoV. Similar to many other non-structural proteins of coronaviruses, Nsp15s from SARS-CoV-2, Human SARS, and Bat CoV are predicted to possess multiple flexible regions but contain virtually no IDPRs (see Figures 32A, 32B, and 32C) .
cord-351837-vasuu70k	2020	title: Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis It possesses both unusually high nucleotide incorporation rates and high-error rates allowing facile insertion of Favipiravir into viral RNA, provoking C-to-U and G-to-A transitions in the already low cytosine content SARS-CoV-2 genome. This enzyme readily incorporates T-705-ribose-5′-phosphate into viral RNA in vitro, and cell culture based infectious virus studies show an increase in mutations in the presence of Favipiravir. To determine the efficacy and MoA of T-705 against SARS-CoV we first characterised nsp12 primerdependent activity using traditional annealed primer-template (PT) and self-priming hairpin (HP) RNAs that may confer additional stability on the elongation complex ( Supplementary Fig. 1c) . These data reveal that the SARS-CoV nsp12 is the fastest viral RdRp known, with rates significantly faster than the 5-20 s −1 observed for picornaviral polymerases at room temperature [33] [34] [35] and 4-18 s −1 for hepatitis C and dengue virus polymerases at 30 and 37°C 36, 37 .
cord-354003-ko45l1qv	2020	Pioneering efforts to identify the mechanisms regulating translation of 5 0 TOP mRNAs, however, did show that wheat germ extracts contain a repressor that specifically limits translation of 5 0 TOP mRNAs in cell-free translation assays (Biberman and Meyuhas, 1999; Shama and Meyuhas, 1996) , suggesting that plants also discriminately regulate translation of 5 0 TOP mRNAs. Here, we show that the TOR-LARP1-5 0 TOP signaling axis regulates translation in Arabidopsis, impacting expression of a set of deeply conserved 5 0 TOP genes, including translation elongation factors, polyA-binding proteins, karyopherins/importins, and the translationally-controlled tumor protein. TOR-LARP1-5 0 TOP signaling in Arabidopsis seedlings regulates translation of mRNAs that encode deeply conserved eukaryotic proteins, plant lineage-specific proteins, and diverse proteins involved in ribosome biogenesis.
cord-354743-mjaqt6wk	2016	Intriguingly, unlike for non-immune VIPs or all VIPs considered together (top of Figure 4B ), immune VIPs, including antiviral VIPs (Supplementary file 1D), do not show any increase of adaptation compared to immune non-VIPs. The lack of a signal is unlikely to be due to reduced statistical power of the comparison in a smaller set of immune proteins, given that 1000 random samples of non-immune VIPs with the same size as the immune VIPs sample (241) always exhibited a significantly (p<0.05) increased rate of adaptation compared to non-immune non-VIPs. The classic MK test is known to be biased downward by the presence of slightly deleterious non-synonymous variants (Charlesworth and Eyre-Walker, 2008b) and this bias is difficult to eliminate fully even by excluding low frequency variants (Messer and Petrov, 2013) .