cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.22644303
title: Phylogenetic landscape of Monkeypox Virus (MPV) during the early outbreak in New York City, 2022

description: Monkeypox (MPOX) is a zoonotic disease endemic to regions of Central/Western Africa. The geographic endemicity of MPV has expanded, broadening the human-monkeypox virus interface and its potential for spillover. Since May 2022, a large multi-country MPV outbreak with no proven links to endemic countries has originated in Europe and has rapidly expanded around the globe, setting off genomic surveillance efforts. Here, we conducted a genomic analysis of 23 MPV-infected patients from New York City during the early outbreak, assessing the phylogenetic relationship of these strains against publicly available MPV genomes. Additionally, we compared the genomic sequences of clinical isolates versus culture-passaged samples from a subset of samples. Phylogenetic analysis revealed that MPV genomes included in this study cluster within the B.1 lineage (Clade IIb), with some of the samples displaying further differentiation into five different sub-lineages of B.1. Mutational analysis revealed 55 non-synonymous polymorphisms throughout the genome, with some of these mutations located in critical regions required for viral multiplication, structural and assembly functions, as well as the target region for antiviral treatment. In addition, we identified a large majority of polymorphisms associated with GA &gt; AA and TC &gt; TT nucleotide replacements, suggesting the action of human APOBEC3 enzyme. A comparison between clinical isolates and cell culture-passaged samples failed to reveal any difference. Our results provide a first glance at the mutational landscape of early MPV-2022 (B.1) circulating strains in NYC.
DOI: 10.6084/m9.figshare.22644303.v1
title: Phylogenetic landscape of Monkeypox Virus (MPV) during the early outbreak in New York City, 2022

description: Monkeypox (MPOX) is a zoonotic disease endemic to regions of Central/Western Africa. The geographic endemicity of MPV has expanded, broadening the human-monkeypox virus interface and its potential for spillover. Since May 2022, a large multi-country MPV outbreak with no proven links to endemic countries has originated in Europe and has rapidly expanded around the globe, setting off genomic surveillance efforts. Here, we conducted a genomic analysis of 23 MPV-infected patients from New York City during the early outbreak, assessing the phylogenetic relationship of these strains against publicly available MPV genomes. Additionally, we compared the genomic sequences of clinical isolates versus culture-passaged samples from a subset of samples. Phylogenetic analysis revealed that MPV genomes included in this study cluster within the B.1 lineage (Clade IIb), with some of the samples displaying further differentiation into five different sub-lineages of B.1. Mutational analysis revealed 55 non-synonymous polymorphisms throughout the genome, with some of these mutations located in critical regions required for viral multiplication, structural and assembly functions, as well as the target region for antiviral treatment. In addition, we identified a large majority of polymorphisms associated with GA &gt; AA and TC &gt; TT nucleotide replacements, suggesting the action of human APOBEC3 enzyme. A comparison between clinical isolates and cell culture-passaged samples failed to reveal any difference. Our results provide a first glance at the mutational landscape of early MPV-2022 (B.1) circulating strains in NYC.
DOI: 10.6084/m9.figshare.23501142
title: The ecology of viruses in urban rodents with a focus on SARS-CoV-2

description: Wild animals are naturally infected with a range of viruses, some of which may be zoonotic. During the human COVID pandemic there was also the possibility of rodents acquiring SARS-CoV-2 from people, so-called reverse zoonoses. To investigate this, we sampled rats (<i>Rattus norvegicus</i>) and mice (<i>Apodemus sylvaticus</i>) from urban environments in 2020 during the human COVID-19 pandemic. We metagenomically sequenced lung and gut tissue and faeces for viruses, PCR screened for SARS-CoV-2, and serologically surveyed for anti-SARS-CoV-2 Spike antibodies. We describe the range of viruses that we found in these two rodent species. We found no molecular evidence of SARS-CoV-2 infection, though in rats we found lung antibody responses and evidence of neutralization ability that are consistent with rats being exposed to SARS-CoV-2 and/or exposed to other viruses that result in cross-reactive antibodies.
DOI: 10.6084/m9.figshare.23501142.v1
title: The ecology of viruses in urban rodents with a focus on SARS-CoV-2

description: Wild animals are naturally infected with a range of viruses, some of which may be zoonotic. During the human COVID pandemic there was also the possibility of rodents acquiring SARS-CoV-2 from people, so-called reverse zoonoses. To investigate this, we sampled rats (<i>Rattus norvegicus</i>) and mice (<i>Apodemus sylvaticus</i>) from urban environments in 2020 during the human COVID-19 pandemic. We metagenomically sequenced lung and gut tissue and faeces for viruses, PCR screened for SARS-CoV-2, and serologically surveyed for anti-SARS-CoV-2 Spike antibodies. We describe the range of viruses that we found in these two rodent species. We found no molecular evidence of SARS-CoV-2 infection, though in rats we found lung antibody responses and evidence of neutralization ability that are consistent with rats being exposed to SARS-CoV-2 and/or exposed to other viruses that result in cross-reactive antibodies.
DOI: 10.6084/m9.figshare.22793556
title: Reciprocal enhancement of SARS-CoV-2 and influenza virus replication in human pluripotent stem cell-derived lung organoids

description: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (FLUAV) coinfections were associated with severe respiratory failure and more deaths. Here, we developed a model for studying SARS-CoV-2 and FLUAV coinfection using human pluripotent stem cell-induced alveolar type II organoids (hiAT2). hiAT2 organoids were susceptible to infection by both viruses and had features of severe lung damage. A single virus markedly enhanced the susceptibility to other virus infections. SARS-CoV-2 delta variants upregulated α-2-3-linked sialic acid, while FLUAV upregulated angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Moreover, coinfection by SARS-CoV-2 and FLUAV caused hyperactivation of proinflammatory and immune-related signaling pathways and cellular damage compared to a respective single virus in hiAT2 organoids. This study provides insight into molecular mechanisms underlying enhanced infectivity and severity in patients with co-infection of SARS-CoV-2 and FLUAV, which may aid in the development of therapeutics for such co-infection cases.
DOI: 10.6084/m9.figshare.22793556.v3
title: Reciprocal enhancement of SARS-CoV-2 and influenza virus replication in human pluripotent stem cell-derived lung organoids

description: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (FLUAV) coinfections were associated with severe respiratory failure and more deaths. Here, we developed a model for studying SARS-CoV-2 and FLUAV coinfection using human pluripotent stem cell-induced alveolar type II organoids (hiAT2). hiAT2 organoids were susceptible to infection by both viruses and had features of severe lung damage. A single virus markedly enhanced the susceptibility to other virus infections. SARS-CoV-2 delta variants upregulated α-2-3-linked sialic acid, while FLUAV upregulated angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Moreover, coinfection by SARS-CoV-2 and FLUAV caused hyperactivation of proinflammatory and immune-related signaling pathways and cellular damage compared to a respective single virus in hiAT2 organoids. This study provides insight into molecular mechanisms underlying enhanced infectivity and severity in patients with co-infection of SARS-CoV-2 and FLUAV, which may aid in the development of therapeutics for such co-infection cases.
DOI: 10.6084/m9.figshare.22793556.v2
title: Reciprocal enhancement of SARS-CoV-2 and influenza virus replication in human pluripotent stem cell-derived lung organoids<sup>1</sup>

description: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (FLUAV) coinfections were associated with severe respiratory failure and more deaths. Here, we developed a model for studying SARS-CoV-2 and FLUAV coinfection using human pluripotent stem cell-induced alveolar type II organoids (hiAT2). hiAT2 organoids were susceptible to infection by both viruses and had features of severe lung damage. A single virus markedly enhanced the susceptibility to other virus infections. SARS-CoV-2 delta variants upregulated α-2-3-linked sialic acid, while FLUAV upregulated angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Moreover, coinfection by SARS-CoV-2 and FLUAV caused hyperactivation of proinflammatory and immune-related signaling pathways and cellular damage compared to a respective single virus in hiAT2 organoids. This study provides insight into molecular mechanisms underlying enhanced infectivity and severity in patients with co-infection of SARS-CoV-2 and FLUAV, which may aid in the development of therapeutics for such co-infection cases.
DOI: 10.6084/m9.figshare.22187218
title: HLA-Bw4 in association with KIR3DL1 favors natural killer cell-mediated protection against severe COVID-19

description: Replicating SARS-CoV-2 has been shown to degrade HLA class I on target cells to evade the cytotoxic T-cell (CTL) response. HLA-I downregulation can be sensed by NK cells to unleash killer cell immunoglobulin-like receptor (KIR)-mediated self-inhibition by the cognate HLA-I ligands. Here, we investigated the impact of HLA and KIR genotypes and HLA-KIR combinations on COVID-19 outcome. We found that the peptide affinities of HLA alleles were not correlated with COVID-19 severity. The predicted poor binders for SARS-CoV-2 peptides belong to HLA-B subtypes that encode KIR ligands, including Bw4 and C1 (introduced by B*46:01), which have a small F pocket and cannot accommodate SARS-CoV-2 CTL epitopes. However, HLA-Bw4 weak binders were beneficial for COVID-19 outcome, and individuals lacking the HLA-Bw4 motif were at higher risk for serious illness from COVID-19. The presence of the HLA-Bw4 and KIR3DL1 combination had a 58.8% lower risk of developing severe COVID-19 (OR = 0.412, 95% CI = 0.187-0.904, <i>p </i>= 0.02). This suggests that HLA-Bw4 alleles that impair their ability to load SARS-CoV-2 peptides will become targets for NK-mediated destruction. Thus, we proposed that the synergistic responsiveness of CTLs and NK cells can efficiently control SARS-CoV-2 infection and replication, and NK-cell-mediated anti-SARS-CoV-2 immune responses being mostly involved in severe infection when the level of ORF8 is high enough to degrade HLA-I. The HLA-Bw4/KIR3DL1 genotype may be particularly important for East Asians undergoing COVID-19 who are enriched in HLA-Bw4-inhibitory KIR interactions and carry a high frequency of HLA-Bw4 alleles that bind poorly to coronavirus peptides.
DOI: 10.6084/m9.figshare.22187218.v2
title: HLA-Bw4 in association with KIR3DL1 favors natural killer cell-mediated protection against severe COVID-19

description: Replicating SARS-CoV-2 has been shown to degrade HLA class I on target cells to evade the cytotoxic T-cell (CTL) response. HLA-I downregulation can be sensed by NK cells to unleash killer cell immunoglobulin-like receptor (KIR)-mediated self-inhibition by the cognate HLA-I ligands. Here, we investigated the impact of HLA and KIR genotypes and HLA-KIR combinations on COVID-19 outcome. We found that the peptide affinities of HLA alleles were not correlated with COVID-19 severity. The predicted poor binders for SARS-CoV-2 peptides belong to HLA-B subtypes that encode KIR ligands, including Bw4 and C1 (introduced by B*46:01), which have a small F pocket and cannot accommodate SARS-CoV-2 CTL epitopes. However, HLA-Bw4 weak binders were beneficial for COVID-19 outcome, and individuals lacking the HLA-Bw4 motif were at higher risk for serious illness from COVID-19. The presence of the HLA-Bw4 and KIR3DL1 combination had a 58.8% lower risk of developing severe COVID-19 (OR = 0.412, 95% CI = 0.187-0.904, <i>p </i>= 0.02). This suggests that HLA-Bw4 alleles that impair their ability to load SARS-CoV-2 peptides will become targets for NK-mediated destruction. Thus, we proposed that the synergistic responsiveness of CTLs and NK cells can efficiently control SARS-CoV-2 infection and replication, and NK-cell-mediated anti-SARS-CoV-2 immune responses being mostly involved in severe infection when the level of ORF8 is high enough to degrade HLA-I. The HLA-Bw4/KIR3DL1 genotype may be particularly important for East Asians undergoing COVID-19 who are enriched in HLA-Bw4-inhibitory KIR interactions and carry a high frequency of HLA-Bw4 alleles that bind poorly to coronavirus peptides.
DOI: 10.6084/m9.figshare.22736988
title: Respiratory microbiota imbalance in children with Mycoplasma pneumoniae pneumonia

description: Although previous studies have reported the dysregulation of respiratory tract microbiota in infectious diseases, insufficient data exist regarding respiratory microbiota imbalances in the lower respiratory tracts (LRTs) of children with <i>Mycoplasma pneumoniae</i> pneumonia (MPP). Here, we analysed the microbial community using 16S rRNA gene sequencing. Finally, bronchoalveolar lavage fluid (BALF) samples from 158 children with MPP and 29 with bacterial or viral pneumonia (control group) were collected. The diversity of the microbial community was significantly different between the two groups. A significantly increased abundance of Tenericutes and <i>Mycoplasma</i> was detected in the MPP group, exceeding 67% and 65% of the total bacterial population, respectively. Using <i>Mycoplasma</i> abundance as the diagnostic method, the sensitivity and specificity of the model was 97.5% and 96.6%, respectively. Compared to the mild MPP group, lower alpha diversity and significantly increased <i>Mycoplasma</i> abundance were found in the severe MPP group (<i>P </i>&lt; 0.01). The abundance of <i>Mycoplasma</i> was positively correlated with complications and clinical indices in children with severe MPP compared with children with mild MPP. Our study describes the features of the LRT microbiota of children with MPP and uncovered its association with disease severity. This finding may offer insights into the pathogenesis of MPP in children.
DOI: 10.6084/m9.figshare.22736988.v2
title: Respiratory microbiota imbalance in children with Mycoplasma pneumoniae pneumonia

description: Although previous studies have reported the dysregulation of respiratory tract microbiota in infectious diseases, insufficient data exist regarding respiratory microbiota imbalances in the lower respiratory tracts (LRTs) of children with <i>Mycoplasma pneumoniae</i> pneumonia (MPP). Here, we analysed the microbial community using 16S rRNA gene sequencing. Finally, bronchoalveolar lavage fluid (BALF) samples from 158 children with MPP and 29 with bacterial or viral pneumonia (control group) were collected. The diversity of the microbial community was significantly different between the two groups. A significantly increased abundance of Tenericutes and <i>Mycoplasma</i> was detected in the MPP group, exceeding 67% and 65% of the total bacterial population, respectively. Using <i>Mycoplasma</i> abundance as the diagnostic method, the sensitivity and specificity of the model was 97.5% and 96.6%, respectively. Compared to the mild MPP group, lower alpha diversity and significantly increased <i>Mycoplasma</i> abundance were found in the severe MPP group (<i>P </i>&lt; 0.01). The abundance of <i>Mycoplasma</i> was positively correlated with complications and clinical indices in children with severe MPP compared with children with mild MPP. Our study describes the features of the LRT microbiota of children with MPP and uncovered its association with disease severity. This finding may offer insights into the pathogenesis of MPP in children.
DOI: 10.6084/m9.figshare.22808049
title: Discovery of a new chemical scaffold for the treatment of superbug <i>Candida auris</i> infections

description: <i>Candida auris</i> has emerged as a serious threat of public health and caused global epidemic due to multi-drug resistance, remarkable transmissibility and high mortality. To tackle the challenging super fungus, novel benzoanilide antifungal agents were discovered by an integrated strategy of phenotypic screen, hit optimization, antifungal assays and mechanism exploration. The most promising compound <b>A1</b> showed potent <i>in vitro</i> and <i>in vivo</i> efficacy against <i>Candida auris</i> infection. Mechanism investigation revealed that compound <b>A1</b> blocked the biosynthesis of virulence factors and fungal cell walls through the inhibition of glycosylphosphatidylinositol (GPI) and GPI-anchored proteins. Thus, compound <b>A1</b> represents a promising lead compound to combat drug-resistant candidiasis.
DOI: 10.6084/m9.figshare.22808049.v1
title: Discovery of a new chemical scaffold for the treatment of superbug <i>Candida auris</i> infections

description: <i>Candida auris</i> has emerged as a serious threat of public health and caused global epidemic due to multi-drug resistance, remarkable transmissibility and high mortality. To tackle the challenging super fungus, novel benzoanilide antifungal agents were discovered by an integrated strategy of phenotypic screen, hit optimization, antifungal assays and mechanism exploration. The most promising compound <b>A1</b> showed potent <i>in vitro</i> and <i>in vivo</i> efficacy against <i>Candida auris</i> infection. Mechanism investigation revealed that compound <b>A1</b> blocked the biosynthesis of virulence factors and fungal cell walls through the inhibition of glycosylphosphatidylinositol (GPI) and GPI-anchored proteins. Thus, compound <b>A1</b> represents a promising lead compound to combat drug-resistant candidiasis.
DOI: 10.5061/dryad.v2890
title: Data from: Stressful colors: corticosterone concentrations in a free-living songbird vary with the spectral composition of experimental illumination

description: Organisms have evolved under natural daily light/dark cycles for millions
 of years. These cycles have been disturbed as night-time darkness is
 increasingly replaced by artificial illumination. Investigating the
 physiological consequences of free-living organisms in artificially lit
 environments is crucial to determine whether nocturnal lighting disrupts
 circadian rhythms, changes behaviour, reduces fitness and ultimately
 affects population numbers. We make use of a unique, large-scale network
 of replicated field sites which were experimentally illuminated at night
 using lampposts emanating either red, green, white or no light to test
 effect on stress hormone concentrations (corticosterone) in a songbird,
 the great tit (Parus major). Adults nesting in white-light transects had
 higher corticosterone concentrations than in the other treatments. We also
 found a significant interaction between distance to the closest lamppost
 and treatment type: individuals in red light had higher corticosterone
 levels when they nested closer to the lamppost than individuals nesting
 farther away, a decline not observed in the green or dark treatment.
 Individuals with high corticosterone levels had fewer fledglings,
 irrespective of treatment. These results show that artificial light can
 induce changes in individual hormonal phenotype. As these effects vary
 considerably with light spectrum, it opens the possibility to mitigate
 these effects by selecting street lighting of specific spectra.
description: 2014adultslon -
 dryadraw data on fitness and
 cort
DOI: 10.6084/m9.figshare.22353104
title: Characterizing the cellular and molecular variabilities of peripheral immune cells in healthy recipients of BBIBP-CorV inactivated SARS-CoV-2 vaccine by single-cell RNA sequencing

description: Over 3 billion doses of inactivated vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been administered globally. However, our understanding of the immune cell functional transcription and T cell receptor (TCR)/B cell receptor (BCR) repertoire dynamics following inactivated SARS-CoV-2 vaccination remains poorly understood. Here, we performed single-cell RNA and TCR/BCR sequencing on peripheral blood mononuclear cells at four time points after immunization with the inactivated SARS-CoV-2 vaccine BBIBP-CorV. Our analysis revealed an enrichment of monocytes, central memory CD4<sup>+</sup> T cells, type 2 helper T cells and memory B cells following vaccination. Single-cell TCR-seq and RNA-seq comminating analysis identified a clonal expansion of CD4<sup>+</sup> T cells (but not CD8<sup>+</sup> T cells) following a booster vaccination that corresponded to a decrease in the TCR diversity of central memory CD4<sup>+</sup> T cells and type 2 helper T cells. Importantly, these TCR repertoire changes and CD4<sup>+</sup> T cell differentiation were correlated with the biased VJ gene usage of BCR and the antibody-producing function of B cells post-vaccination. Finally, we compared the functional transcription and repertoire dynamics in immune cells elicited by vaccination and SARS-CoV-2 infection to explore the immune responses under different stimuli. Our data provide novel molecular and cellular evidence for the CD4<sup>+</sup> T cell-dependent antibody response induced by inactivated vaccine BBIBP-CorV. This information is urgently needed to develop new prevention and control strategies for SARS-CoV-2 infection. (ClinicalTrials.gov Identifier: NCT04871932).
DOI: 10.6084/m9.figshare.22353104.v2
title: Characterizing the cellular and molecular variabilities of peripheral immune cells in healthy recipients of BBIBP-CorV inactivated SARS-CoV-2 vaccine by single-cell RNA sequencing

description: Over 3 billion doses of inactivated vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been administered globally. However, our understanding of the immune cell functional transcription and T cell receptor (TCR)/B cell receptor (BCR) repertoire dynamics following inactivated SARS-CoV-2 vaccination remains poorly understood. Here, we performed single-cell RNA and TCR/BCR sequencing on peripheral blood mononuclear cells at four time points after immunization with the inactivated SARS-CoV-2 vaccine BBIBP-CorV. Our analysis revealed an enrichment of monocytes, central memory CD4<sup>+</sup> T cells, type 2 helper T cells and memory B cells following vaccination. Single-cell TCR-seq and RNA-seq comminating analysis identified a clonal expansion of CD4<sup>+</sup> T cells (but not CD8<sup>+</sup> T cells) following a booster vaccination that corresponded to a decrease in the TCR diversity of central memory CD4<sup>+</sup> T cells and type 2 helper T cells. Importantly, these TCR repertoire changes and CD4<sup>+</sup> T cell differentiation were correlated with the biased VJ gene usage of BCR and the antibody-producing function of B cells post-vaccination. Finally, we compared the functional transcription and repertoire dynamics in immune cells elicited by vaccination and SARS-CoV-2 infection to explore the immune responses under different stimuli. Our data provide novel molecular and cellular evidence for the CD4<sup>+</sup> T cell-dependent antibody response induced by inactivated vaccine BBIBP-CorV. This information is urgently needed to develop new prevention and control strategies for SARS-CoV-2 infection. (ClinicalTrials.gov Identifier: NCT04871932).