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                  <text>Coronavirus</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>Mating of the stichotrichous ciliate Oxytricha trifallax induces production of a class of 27 nt small RNAs derived from the parental macronucleus.</text>
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                <text>Alan M Zahler, Zachary T Neeb, Athena Lin, Sol Katzman</text>
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                <text>Ciliated protozoans possess two types of nuclei; a transcriptionally silent micronucleus, which serves as the germ line nucleus, and a transcriptionally active macronucleus, which serves as the somatic nucleus. The macronucleus is derived from a new diploid micronucleus after mating, with epigenetic information contributed by the parental macronucleus serving to guide the formation of the new macronucleus. In the stichotrichous ciliate Oxytricha trifallax, the macronuclear DNA is highly processed to yield gene-sized nanochromosomes with telomeres at each end. Here we report that soon after mating of Oxytricha trifallax, abundant 27 nt small RNAs are produced that are not present prior to mating. We performed next generation sequencing of Oxytricha small RNAs from vegetative and mating cells. Using sequence comparisons between macronuclear and micronuclear versions of genes, we found that the 27 nt RNA class derives from the parental macronucleus, not the developing macronucleus. These small RNAs are produced equally from both strands of macronuclear nanochromosomes, but in a highly non-uniform distribution along the length of the nanochromosome, and with a particular depletion in the 30 nt telomere-proximal positions. This production of small RNAs from the parental macronucleus during macronuclear development stands in contrast to the mechanism of epigenetic control in the distantly related ciliate Tetrahymena. In that species, 28-29 nt scanRNAs are produced from the micronucleus and these micronuclear-derived RNAs serve as epigenetic controllers of macronuclear development. Unlike the Tetrahymena scanRNAs, the Oxytricha macronuclear-derived 27 mers are not modified by 2'O-methylation at their 3' ends. We propose models for the role of these 27macRNAs" in macronuclear development."</text>
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                <text>DOI: 10.1371/journal.pone.0042371</text>
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                <text>PLoS ONE</text>
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                <text>Public Library of Science (PLoS)</text>
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                <text>Science, Medicine</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>The Middle East respiratory syndrome coronavirus (MERS-CoV) does not replicate in Syrian hamsters.</text>
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                <text>Emmie de Wit, Joseph Prescott, Laura Baseler, Trenton Bushmaker, Tina Thomas, Matthew G. Lackemeyer, Cynthia Martellaro, Shauna Milne-Price, Elaine Haddock, Bart L. Haagmans, Heinz Feldmann, Vincent J. Munster</text>
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                <text>In 2012 a novel coronavirus, MERS-CoV, associated with severe respiratory disease emerged in the Arabian Peninsula. To date, 55 human cases have been reported, including 31 fatal cases. Several of the cases were likely a result of human-to-human transmission. The emergence of this novel coronavirus prompts the need for a small animal model to study the pathogenesis of this virus and to test the efficacy of potential intervention strategies. In this study we explored the use of Syrian hamsters as a small animal disease model, using intratracheal inoculation and inoculation via aerosol. Clinical signs of disease, virus replication, histological lesions, cytokine upregulation nor seroconversion were observed in any of the inoculated animals, indicating that MERS-CoV does not replicate in Syrian hamsters.</text>
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                <text>2013</text>
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                <text>DOI: 10.1371/journal.pone.0069127</text>
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                <text>PLoS ONE</text>
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                <text>Public Library of Science (PLoS)</text>
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            <description>The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant</description>
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                <text>Science, Medicine</text>
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              <description>A name given to the resource</description>
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                  <text>Coronavirus</text>
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              <name>Description</name>
              <description>An account of the resource</description>
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                  <text>Dominio científico: Coronavirus</text>
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      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
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        <description>The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.</description>
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            <name>Title</name>
            <description>A name given to the resource</description>
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                <text>Immune biomarkers predictive of respiratory viral infection in elderly nursing home residents.</text>
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            <description>An entity primarily responsible for making the resource</description>
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                <text>Jennie Johnstone, Robin Parsons, Fernando Botelho, Jamie Millar, Shelly McNeil, Tamàs Fülöp, Janet McElhaney, Melissa K Andrew, Stephen D. Walter, P J Devereaux, Mehrnoush Malekesmaeili, Ryan R. Brinkman, James Mahony, Jonathan Bramson, Mark Loeb</text>
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            <description>An account of the resource</description>
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                <text>To determine if immune phenotypes associated with immunosenescence predict risk of respiratory viral infection in elderly nursing home residents.Residents ≥ 65 years from 32 nursing homes in 4 Canadian cities were enrolled in Fall 2009, 2010 and 2011, and followed for one influenza season. Following influenza vaccination, peripheral blood mononuclear cells (PBMCs) were obtained and analysed by flow cytometry for T-regs, CD4+ and CD8+ T-cell subsets (CCR7+CD45RA+, CCR7-CD45RA+ and CD28-CD57+) and CMV-reactive CD4+ and CD8+ T-cells. Nasopharyngeal swabs were obtained and tested for viruses in symptomatic residents. A Cox proportional hazards model adjusted for age, sex and frailty, determined the relationship between immune phenotypes and time to viral infection.1072 residents were enrolled; median age 86 years and 72% female. 269 swabs were obtained, 87 were positive for virus: influenza (24%), RSV (14%), coronavirus (32%), rhinovirus (17%), human metapneumovirus (9%) and parainfluenza (5%). In multivariable analysis, high T-reg% (HR 0.41, 95% CI 0.20-0.81) and high CMV-reactive CD4+ T-cell% (HR 1.69, 95% CI 1.03-2.78) were predictive of respiratory viral infection.In elderly nursing home residents, high CMV-reactive CD4+ T-cells were associated with an increased risk and high T-regs were associated with a reduced risk of respiratory viral infection.</text>
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                <text>2014</text>
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                <text>DOI: 10.1371/journal.pone.0108481</text>
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            <description>A related resource from which the described resource is derived</description>
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              <elementText elementTextId="1143">
                <text>PLoS ONE</text>
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            <name>Publisher</name>
            <description>An entity responsible for making the resource available</description>
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                <text>Public Library of Science (PLoS)</text>
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                <text>Science, Medicine</text>
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              <name>Title</name>
              <description>A name given to the resource</description>
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                  <text>Coronavirus</text>
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              <name>Description</name>
              <description>An account of the resource</description>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>The Inhibitory Effect of Non-Substrate and Substrate DNA on the Ligation and Self-Adenylylation Reactions Catalyzed by T4 DNA Ligase.</text>
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            <description>An entity primarily responsible for making the resource</description>
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                <text>Robert J. Bauer, Thomas C Evans, Gregory J S Lohman</text>
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            <description>An account of the resource</description>
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                <text>DNA ligases are essential both to in vivo replication, repair and recombination processes, and in vitro molecular biology protocols. Prior characterization of DNA ligases through gel shift assays has shown the presence of a nick site to be essential for tight binding between the enzyme and its dsDNA substrate, with no interaction evident on dsDNA lacking a nick. In the current study, we observed a significant substrate inhibition effect, as well as the inhibition of both the self-adenylylation and nick-sealing steps of T4 DNA ligase by non-nicked, non-substrate dsDNA. Inhibition by non-substrate DNA was dependent only on the total DNA concentration rather than the structure; with 1 μg/mL of 40-mers, 75-mers, or circular plasmid DNA all inhibiting ligation equally. A &gt;15-fold reduction in T4 DNA ligase self-adenylylation rate when in the presence of high non-nicked dsDNA concentrations was observed. Finally, EMSAs were utilized to demonstrate that non-substrate dsDNA can compete with nicked dsDNA substrates for enzyme binding. Based upon these data, we hypothesize the inhibition of T4 DNA ligase by non-nicked dsDNA is direct evidence for a two-step nick-binding mechanism, with an initial, nick-independent, transient dsDNA-binding event preceding a transition to a stable binding complex in the presence of a nick site.</text>
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                <text>2016</text>
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                <text>DOI: 10.1371/journal.pone.0150802</text>
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              <elementText elementTextId="1152">
                <text>PLoS ONE</text>
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                <text>Public Library of Science (PLoS)</text>
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                <text>Selective inhibitors of protozoan protein N-myristoyltransferases as starting points for tropical disease medicinal chemistry programs.</text>
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                <text>Andrew S. Bell, James E Mills, Gareth P Williams, James A. Brannigan, Anthony J. Wilkinson, Tanya Parkinson, Robin J. Leatherbarrow, Edward W. Tate, Anthony A. Holder, Deborah F. Smith</text>
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                <text>Inhibition of N-myristoyltransferase has been validated pre-clinically as a target for the treatment of fungal and trypanosome infections, using species-specific inhibitors. In order to identify inhibitors of protozoan NMTs, we chose to screen a diverse subset of the Pfizer corporate collection against Plasmodium falciparum and Leishmania donovani NMTs. Primary screening hits against either enzyme were tested for selectivity over both human NMT isoforms (Hs1 and Hs2) and for broad-spectrum anti-protozoan activity against the NMT from Trypanosoma brucei. Analysis of the screening results has shown that structure-activity relationships (SAR) for Leishmania NMT are divergent from all other NMTs tested, a finding not predicted by sequence similarity calculations, resulting in the identification of four novel series of Leishmania-selective NMT inhibitors. We found a strong overlap between the SARs for Plasmodium NMT and both human NMTs, suggesting that achieving an appropriate selectivity profile will be more challenging. However, we did discover two novel series with selectivity for Plasmodium NMT over the other NMT orthologues in this study, and an additional two structurally distinct series with selectivity over Leishmania NMT. We believe that release of results from this study into the public domain will accelerate the discovery of NMT inhibitors to treat malaria and leishmaniasis. Our screening initiative is another example of how a tripartite partnership involving pharmaceutical industries, academic institutions and governmental/non-governmental organisations such as Medical Research Council and Wellcome Trust can stimulate research for neglected diseases.</text>
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                <text>DOI: 10.1371/journal.pntd.0001625</text>
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                <text>PLoS Neglected Tropical Diseases</text>
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            <description>An entity responsible for making the resource available</description>
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                <text>Public Library of Science (PLoS)</text>
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            <description>The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant</description>
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                <text>Arctic medicine. Tropical medicine, Public aspects of medicine</text>
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            <description>A language of the resource</description>
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                <text>EN</text>
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              <name>Title</name>
              <description>A name given to the resource</description>
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                  <text>Coronavirus</text>
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              <description>An account of the resource</description>
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                  <text>Dominio científico: Coronavirus</text>
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          <element elementId="50">
            <name>Title</name>
            <description>A name given to the resource</description>
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              <elementText elementTextId="1165">
                <text>SARS coronavirus 3b accessory protein modulates transcriptional activity of RUNX1b.</text>
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            <description>An entity primarily responsible for making the resource</description>
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              <elementText elementTextId="1166">
                <text>Bhavna Varshney, Sudhakar Agnihothram, Yee-Joo Tan, Ralph Baric, Sunil K. Lal</text>
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                <text>BACKGROUND: The causative agent of severe acute respiratory syndrome, SARS coronavirus (SARS-CoV) genome encodes several unique group specific accessory proteins with unknown functions. Among them, accessory protein 3b (also known as ORF4) was lately identified as one of the viral interferon antagonist. Recently our lab uncovered a new role for 3b in upregulation of AP-1 transcriptional activity and its downstream genes. Thus, we believe that 3b might play an important role in SARS-CoV pathogenesis and therefore is of considerable interest. The current study aims at identifying novel host cellular interactors of the 3b protein. METHODOLOGY/PRINCIPAL FINDINGS: In this study, using yeast two-hybrid and co-immunoprecipitation techniques, we have identified a host transcription factor RUNX1b (Runt related transcription factor, isoform b) as a novel interacting partner for SARS-CoV 3b protein. Chromatin immunoprecipitaion (ChIP) and reporter gene assays in 3b expressing jurkat cells showed recruitment of 3b on the RUNX1 binding element that led to an increase in RUNX1b transactivation potential on the IL2 promoter. Kinase assay and pharmacological inhibitor treatment implied that 3b also affect RUNX1b transcriptional activity by regulating its ERK dependent phosphorylation levels. Additionally, mRNA levels of MIP-1α, a RUNX1b target gene upregulated in SARS-CoV infected monocyte-derived dendritic cells, were found to be elevated in 3b expressing U937 monocyte cells. CONCLUSIONS/SIGNIFICANCE: These results unveil a novel interaction of SARS-CoV 3b with the host factor, RUNX1b, and speculate its physiological relevance in upregulating cytokines and chemokine levels in state of SARS virus infection.</text>
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                <text>2012</text>
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                <text>DOI: 10.1371/journal.pone.0029542</text>
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              <elementText elementTextId="1170">
                <text>PLoS ONE</text>
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              <elementText elementTextId="1171">
                <text>Public Library of Science (PLoS)</text>
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                <text>Science, Medicine</text>
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            <description>A language of the resource</description>
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              <elementText elementTextId="1173">
                <text>EN</text>
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              <name>Title</name>
              <description>A name given to the resource</description>
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                  <text>Coronavirus</text>
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              <description>An account of the resource</description>
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                  <text>Dominio científico: Coronavirus</text>
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      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
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          <element elementId="50">
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            <description>A name given to the resource</description>
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                <text>Inhibition of SARS pseudovirus cell entry by lactoferrin binding to heparan sulfate proteoglycans.</text>
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            <description>An entity primarily responsible for making the resource</description>
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              <elementText elementTextId="1175">
                <text>Jianshe Lang, Ning Yang, Jiejie Deng, Kangtai Liu, Peng Yang, Guigen Zhang, Chengyu Jiang</text>
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            <description>An account of the resource</description>
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              <elementText elementTextId="1176">
                <text>It has been reported that lactoferrin (LF) participates in the host immune response against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) invasion by enhancing NK cell activity and stimulating neutrophil aggregation and adhesion. We further investigated the role of LF in the entry of SARS pseudovirus into HEK293E/ACE2-Myc cells. Our results reveal that LF inhibits SARS pseudovirus infection in a dose-dependent manner. Further analysis suggested that LF was able to block the binding of spike protein to host cells at 4°C, indicating that LF exerted its inhibitory function at the viral attachment stage. However, LF did not disrupt the interaction of spike protein with angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV. Previous studies have shown that LF colocalizes with the widely distributed cell-surface heparan sulfate proteoglycans (HSPGs). Our experiments have also confirmed this conclusion. Treatment of the cells with heparinase or exogenous heparin prevented binding of spike protein to host cells and inhibited SARS pseudovirus infection, demonstrating that HSPGs provide the binding sites for SARS-CoV invasion at the early attachment phase. Taken together, our results suggest that, in addition to ACE2, HSPGs are essential cell-surface molecules involved in SARS-CoV cell entry. LF may play a protective role in host defense against SARS-CoV infection through binding to HSPGs and blocking the preliminary interaction between SARS-CoV and host cells. Our findings may provide further understanding of SARS-CoV pathogenesis and aid in treatment of this deadly disease.</text>
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            <name>Date</name>
            <description>A point or period of time associated with an event in the lifecycle of the resource</description>
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              <elementText elementTextId="1177">
                <text>2011</text>
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              <elementText elementTextId="1178">
                <text>DOI: 10.1371/journal.pone.0023710</text>
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            <description>A related resource from which the described resource is derived</description>
            <elementTextContainer>
              <elementText elementTextId="1179">
                <text>PLoS ONE</text>
              </elementText>
            </elementTextContainer>
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            <name>Publisher</name>
            <description>An entity responsible for making the resource available</description>
            <elementTextContainer>
              <elementText elementTextId="1180">
                <text>Public Library of Science (PLoS)</text>
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            <description>The spatial or temporal topic of the resource, the spatial applicability of the resource, or the jurisdiction under which the resource is relevant</description>
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                <text>Science, Medicine</text>
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            <description>A language of the resource</description>
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            <element elementId="50">
              <name>Title</name>
              <description>A name given to the resource</description>
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                  <text>Coronavirus</text>
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              <name>Description</name>
              <description>An account of the resource</description>
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                  <text>Dominio científico: Coronavirus</text>
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      <name>Text</name>
      <description>A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.</description>
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          <element elementId="50">
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            <description>A name given to the resource</description>
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                <text>Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review.</text>
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              <elementText elementTextId="1184">
                <text>Khai Tran, Karen Cimon, Melissa Severn, Carmem L Pessoa-Silva, John Conly</text>
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                <text>Aerosol generating procedures (AGPs) may expose health care workers (HCWs) to pathogens causing acute respiratory infections (ARIs), but the risk of transmission of ARIs from AGPs is not fully known. We sought to determine the clinical evidence for the risk of transmission of ARIs to HCWs caring for patients undergoing AGPs compared with the risk of transmission to HCWs caring for patients not undergoing AGPs. We searched PubMed, EMBASE, MEDLINE, CINAHL, the Cochrane Library, University of York CRD databases, EuroScan, LILACS, Indian Medlars, Index Medicus for SE Asia, international health technology agencies and the Internet in all languages for articles from 01/01/1990 to 22/10/2010. Independent reviewers screened abstracts using pre-defined criteria, obtained full-text articles, selected relevant studies, and abstracted data. Disagreements were resolved by consensus. The outcome of interest was risk of ARI transmission. The quality of evidence was rated using the GRADE system. We identified 5 case-control and 5 retrospective cohort studies which evaluated transmission of SARS to HCWs. Procedures reported to present an increased risk of transmission included [n; pooled OR(95%CI)] tracheal intubation [n = 4 cohort; 6.6 (2.3, 18.9), and n = 4 case-control; 6.6 (4.1, 10.6)], non-invasive ventilation [n = 2 cohort; OR 3.1(1.4, 6.8)], tracheotomy [n = 1 case-control; 4.2 (1.5, 11.5)] and manual ventilation before intubation [n = 1 cohort; OR 2.8 (1.3, 6.4)]. Other intubation associated procedures, endotracheal aspiration, suction of body fluids, bronchoscopy, nebulizer treatment, administration of O2, high flow O2, manipulation of O2 mask or BiPAP mask, defibrillation, chest compressions, insertion of nasogastric tube, and collection of sputum were not significant. Our findings suggest that some procedures potentially capable of generating aerosols have been associated with increased risk of SARS transmission to HCWs or were a risk factor for transmission, with the most consistent association across multiple studies identified with tracheal intubation.</text>
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              <elementText elementTextId="1186">
                <text>2012</text>
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              <elementText elementTextId="1187">
                <text>DOI: 10.1371/journal.pone.0035797</text>
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            <description>A related resource from which the described resource is derived</description>
            <elementTextContainer>
              <elementText elementTextId="1188">
                <text>PLoS ONE</text>
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            <name>Publisher</name>
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              <elementText elementTextId="1189">
                <text>Public Library of Science (PLoS)</text>
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                <text>Science, Medicine</text>
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            <description>A language of the resource</description>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>Design, synthesis and biological evaluation of novel piperazine derivatives as CCR5 antagonists.</text>
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              <elementText elementTextId="1193">
                <text>Tao Liu, Zhiyong Weng, Xiaowu Dong, Linjie Chen, Ling MA, Shan Cen, Naiming Zhou, Yongzhou Hu</text>
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                <text>By using a fragment-assembly strategy and bioisosteric-replacement principle, a series of novel piperazine derivatives were designed, synthesized, and evaluated for their cellular target-effector fusion activities and in vitro antiviral activities against HIV-1. Preliminary structure-activity relationships (SARs) of target compounds were concluded in this study, and five compounds were found to exhibited medium to potent CCR5 fusion activities with IC(50) values in low micromolar level. Among evaluated compounds, 23 h was found to be a CCR5 antagonist with an IC(50) value of 6.29 µM and an anti-HIV-1 inhibitor with an IC(50) value of 0.44 µM.</text>
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                <text>DOI: 10.1371/journal.pone.0053636</text>
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                  <text>Coronavirus</text>
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                  <text>Dominio científico: Coronavirus</text>
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                <text>Using common spatial distributions of atoms to relate functionally divergent influenza virus N10 and N11 protein structures to functionally characterized neuraminidase structures, toxin cell entry domains, and non-influenza virus cell entry domains.</text>
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                <text>Arthur Weininger, Susan Weininger</text>
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                <text>The ability to identify the functional correlates of structural and sequence variation in proteins is a critical capability. We related structures of influenza A N10 and N11 proteins that have no established function to structures of proteins with known function by identifying spatially conserved atoms. We identified atoms with common distributed spatial occupancy in PDB structures of N10 protein, N11 protein, an influenza A neuraminidase, an influenza B neuraminidase, and a bacterial neuraminidase. By superposing these spatially conserved atoms, we aligned the structures and associated molecules. We report spatially and sequence invariant residues in the aligned structures. Spatially invariant residues in the N6 and influenza B neuraminidase active sites were found in previously unidentified spatially equivalent sites in the N10 and N11 proteins. We found the corresponding secondary and tertiary structures of the aligned proteins to be largely identical despite significant sequence divergence. We found structural precedent in known non-neuraminidase structures for residues exhibiting structural and sequence divergence in the aligned structures. In N10 protein, we identified staphylococcal enterotoxin I-like domains. In N11 protein, we identified hepatitis E E2S-like domains, SARS spike protein-like domains, and toxin components shared by alpha-bungarotoxin, staphylococcal enterotoxin I, anthrax lethal factor, clostridium botulinum neurotoxin, and clostridium tetanus toxin. The presence of active site components common to the N6, influenza B, and S. pneumoniae neuraminidases in the N10 and N11 proteins, combined with the absence of apparent neuraminidase function, suggests that the role of neuraminidases in H17N10 and H18N11 emerging influenza A viruses may have changed. The presentation of E2S-like, SARS spike protein-like, or toxin-like domains by the N10 and N11 proteins in these emerging viruses may indicate that H17N10 and H18N11 sialidase-facilitated cell entry has been supplemented or replaced by sialidase-independent receptor binding to an expanded cell population that may include neurons and T-cells.</text>
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                <text>DOI: 10.1371/journal.pone.0117499</text>
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                <text>PLoS ONE</text>
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            <name>Publisher</name>
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                <text>Public Library of Science (PLoS)</text>
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                <text>Science, Medicine</text>
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