cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.24925287.v2
title: Immunocompetent mouse models revealed that S100A4<sup>+</sup> monocytes/macrophages facilitate long-term Zika virus infection in the testes

description: During its global epidemic, Zika virus (ZIKV) attracted widespread attention due to its link with various severe neurological symptoms and potential harm to male fertility. However, the understanding of how ZIKV invades and persists in the male reproductive system is limited due to the lack of immunocompetent small animal models. In this study, immunocompetent murine models were generated by using anti-IFNAR antibody blocked C57BL/6 male mice and human STAT2 (hSTAT2) knock in (KI) male mice. After infection, viral RNA could persist in the testes even after the disappearance of viremia. We also found a population of ZIKV-susceptible S100A4<sup>+</sup> monocytes/macrophages that were recruited into testes from peripheral blood and played a crucial role for ZIKV infection in the testis. By using single-cell RNA sequencing, we also proved that S100A4<sup>+</sup> monocytes/macrophages had a great impact on the microenvironment of ZIKV-infected testes, thus promoting ZIKV-induced testicular lesions. In conclusion, this study proposed a novel mechanism of long-term ZIKV infection in the male reproductive system.
DOI: 10.6084/m9.figshare.26305048.v1
title: Genomic Characterization of Highly Pathogenic Avian Influenza A H5N1 Virus Newly Emerged in Dairy Cattle

description: In March 2024, the emergence of highly pathogenic avian influenza (HPAI) A (H5N1) infections in dairy cattle was detected in United States for the first time. We genetically characterize HPAI viruses from dairy cattle showing an abrupt drop in milk production, as well as from two cats, six wild birds, and one skunk. They share nearly identical genome sequences, forming a new genotype B3.13 within the 2.3.4.4b clade. B3.13 viruses underwent two reassortment events since 2023 and exhibit critical mutations in HA, M1, and NS genes but lack critical mutations in PB2 and PB1 genes, which enhance virulence or adaptation to mammals. The PB2 E627 K mutation in a human case associated with cattle underscores the potential for rapid evolution post-infection, highlighting the need for continued surveillance to monitor public health threats.
DOI: 10.6084/m9.figshare.25551974
title: Investigation of genomic and pathogenicity characteristics of <i>Streptococcus suis</i> ST1 human strains from Guangxi Zhuang Autonomous Region (GX) between 2005 and 2020 in China

description: <i>Streptococcus suis</i> is a significant and emerging zoonotic pathogen. ST1 and ST7 strains are the primary agents responsible for <i>S. suis</i> human infections in China, including the Guangxi Zhuang Autonomous Region (GX). To enhance our understanding of <i>S. suis</i> ST1 population characteristics, we conducted an investigation into the phylogenetic structure, genomic features, and virulence levels of 73 <i>S. suis</i> ST1 human strains from GX between 2005 and 2020. The ST1 GX strains were categorized into three lineages in phylogenetic analysis. Sub-lineage 3-1a exhibited a closer phylogenetic relationship with the ST7 epidemic strain SC84. The strains from lineage 3 predominantly harboured 89K-like pathogenicity islands (PAIs) which were categorized into four clades based on sequence alignment. The acquirement of 89K-like PAIs increased the antibiotic resistance and pathogenicity of corresponding transconjugants. We observed significant diversity in virulence levels among the 37 representative ST1 GX strains, that were classified as follows: epidemic (E)/highly virulent (HV) (32.4%, 12/37), virulent plus (V+) (29.7%, 11/37), virulent (V) (18.9%, 7/37), and lowly virulent (LV) (18.9%, 7/37) strains based on survival curves and mortality rates at different time points in C57BL/6 mice following infection. The E/HV strains were characterized by the overproduction of tumour necrosis factor (TNF)-α in serum and promptly established infection at the early phase of infection. Our research offers novel insights into the population structure, evolution, genomic features, and pathogenicity of ST1 strains. Our data also indicates the importance of establishing a scheme for characterizing and subtyping the virulence levels of <i>S. suis</i> strains.
DOI: 10.6084/m9.figshare.25551974.v2
title: Investigation of genomic and pathogenicity characteristics of <i>Streptococcus suis</i> ST1 human strains from Guangxi Zhuang Autonomous Region (GX) between 2005 and 2020 in China

description: <i>Streptococcus suis</i> is a significant and emerging zoonotic pathogen. ST1 and ST7 strains are the primary agents responsible for <i>S. suis</i> human infections in China, including the Guangxi Zhuang Autonomous Region (GX). To enhance our understanding of <i>S. suis</i> ST1 population characteristics, we conducted an investigation into the phylogenetic structure, genomic features, and virulence levels of 73 <i>S. suis</i> ST1 human strains from GX between 2005 and 2020. The ST1 GX strains were categorized into three lineages in phylogenetic analysis. Sub-lineage 3-1a exhibited a closer phylogenetic relationship with the ST7 epidemic strain SC84. The strains from lineage 3 predominantly harboured 89K-like pathogenicity islands (PAIs) which were categorized into four clades based on sequence alignment. The acquirement of 89K-like PAIs increased the antibiotic resistance and pathogenicity of corresponding transconjugants. We observed significant diversity in virulence levels among the 37 representative ST1 GX strains, that were classified as follows: epidemic (E)/highly virulent (HV) (32.4%, 12/37), virulent plus (V+) (29.7%, 11/37), virulent (V) (18.9%, 7/37), and lowly virulent (LV) (18.9%, 7/37) strains based on survival curves and mortality rates at different time points in C57BL/6 mice following infection. The E/HV strains were characterized by the overproduction of tumour necrosis factor (TNF)-α in serum and promptly established infection at the early phase of infection. Our research offers novel insights into the population structure, evolution, genomic features, and pathogenicity of ST1 strains. Our data also indicates the importance of establishing a scheme for characterizing and subtyping the virulence levels of <i>S. suis</i> strains.
DOI: 10.6084/m9.figshare.27158335
title: Impaired mucosal IgA response in patients with severe COVID-19

description: Several studies have investigated the antibody response to SARS-CoV-2, focusing particularly on the systemic humoral immune response and the production of immunoglobulin G (IgG) antibodies. IgA antibodies play a crucial role in protecting against respiratory viral infections but have also been associated with the pathophysiology of COVID-19. We performed a prospective study of 169 COVID-19 patients – 50 with critical/severe (ICU), 47 with moderate (Non-ICU), and 72 with asymptomatic COVID-19 – to explore the humoral immune response to SARS-CoV-2 infection. We found that the early systemic IgA response strongly induced in patients with severe disease did not block IgG neutralization functions and activated FcRs more effectively than IgG. However, even if SIgA levels were high, mucosal IgA antibodies could not control the infection effectively in patients with severe disease. Our findings highlight the complexity of the immune response to SARS-CoV-2 exhibiting high systemic levels of IgA with strong neutralizing capacity in severe cases, together with higher levels of IgA-FcR activation than in asymptomatic patients. They also suggest the need for further research to fully understand the role of IgA and its structural alterations in mucosal tissues in cases of severe disease and the impact of these antibodies on disease progression.
DOI: 10.6084/m9.figshare.27158335.v1
title: Impaired mucosal IgA response in patients with severe COVID-19

description: Several studies have investigated the antibody response to SARS-CoV-2, focusing particularly on the systemic humoral immune response and the production of immunoglobulin G (IgG) antibodies. IgA antibodies play a crucial role in protecting against respiratory viral infections but have also been associated with the pathophysiology of COVID-19. We performed a prospective study of 169 COVID-19 patients – 50 with critical/severe (ICU), 47 with moderate (Non-ICU), and 72 with asymptomatic COVID-19 – to explore the humoral immune response to SARS-CoV-2 infection. We found that the early systemic IgA response strongly induced in patients with severe disease did not block IgG neutralization functions and activated FcRs more effectively than IgG. However, even if SIgA levels were high, mucosal IgA antibodies could not control the infection effectively in patients with severe disease. Our findings highlight the complexity of the immune response to SARS-CoV-2 exhibiting high systemic levels of IgA with strong neutralizing capacity in severe cases, together with higher levels of IgA-FcR activation than in asymptomatic patients. They also suggest the need for further research to fully understand the role of IgA and its structural alterations in mucosal tissues in cases of severe disease and the impact of these antibodies on disease progression.
DOI: 10.6084/m9.figshare.26245432
title: Evolutionary accumulation of <i>FKS</i>1 mutations from clinical echinocandin-resistant <i>Candida auris</i>

description: Introduction: Drug resistance to echinocandins, first-line drugs used to treat <i>Candida auris</i> infection, is rapidly emerging. However, the accumulation of mutations in genes other than <i>FKS</i>1 (before an isolate develops to resistance via <i>FKS</i>1 mutations), remains poorly understood. <i>Methods:</i> Four clinical cases and 29 isolates associated with the incremental process of echinocandin resistance were collected and analyzed using antifungal drug susceptibility testing and genome sequencing to assess the evolution of echinocandin resistance. Findings: Six echinocandin minimum inhibitory concentration (MIC)-elevated <i>C. auris</i> strains and seven resistant strains were isolated from the urinary system of patients receiving echinocandin treatment. Meanwhile, phylogenetic analyses illustrated that the echinocandin-resistant strains were closely related to other strains in the same patient. Genomic data revealed that the echinocandin-resistant strains had <i>FKS</i>1 mutations. Furthermore, three categories (ECN-S/E/R) of non-synonymous mutant SNP genes (such as <i>RBR</i>3, <i>IFF</i>6, <i>MKC</i>1, <i>MPH</i>1, <i>RAD</i>2, and <i>MYO</i>1) in <i>C. auris</i> appeared to be associated with the three-stage-evolutionary model of echinocandin resistance in <i>C. glabrata</i>: cell wall stress, drug adaptation, and genetic escape (<i>FKS</i> mutation). Interpretation: Echinocandin-resistant <i>C. auris</i> undergoes spatial and temporal phase changes closely related to echinocandin exposure, particularly in the urinary system. These findings suggest that <i>FKS1</i> mutations mediate an evolutionary accumulation of echinocandin resistance followed by modulation of chromosome remodelling and DNA repair processes that ultimately lead to <i>FKS</i>1 hot spot mutations and the development of drug resistance. This study provides an in-depth exploration of the molecular pathways involved in the evolution of <i>Candida auris</i> echinocandin resistance.
DOI: 10.6084/m9.figshare.26245432.v1
title: Evolutionary accumulation of <i>FKS</i>1 mutations from clinical echinocandin-resistant <i>Candida auris</i>

description: Introduction: Drug resistance to echinocandins, first-line drugs used to treat <i>Candida auris</i> infection, is rapidly emerging. However, the accumulation of mutations in genes other than <i>FKS</i>1 (before an isolate develops to resistance via <i>FKS</i>1 mutations), remains poorly understood. <i>Methods:</i> Four clinical cases and 29 isolates associated with the incremental process of echinocandin resistance were collected and analyzed using antifungal drug susceptibility testing and genome sequencing to assess the evolution of echinocandin resistance. Findings: Six echinocandin minimum inhibitory concentration (MIC)-elevated <i>C. auris</i> strains and seven resistant strains were isolated from the urinary system of patients receiving echinocandin treatment. Meanwhile, phylogenetic analyses illustrated that the echinocandin-resistant strains were closely related to other strains in the same patient. Genomic data revealed that the echinocandin-resistant strains had <i>FKS</i>1 mutations. Furthermore, three categories (ECN-S/E/R) of non-synonymous mutant SNP genes (such as <i>RBR</i>3, <i>IFF</i>6, <i>MKC</i>1, <i>MPH</i>1, <i>RAD</i>2, and <i>MYO</i>1) in <i>C. auris</i> appeared to be associated with the three-stage-evolutionary model of echinocandin resistance in <i>C. glabrata</i>: cell wall stress, drug adaptation, and genetic escape (<i>FKS</i> mutation). Interpretation: Echinocandin-resistant <i>C. auris</i> undergoes spatial and temporal phase changes closely related to echinocandin exposure, particularly in the urinary system. These findings suggest that <i>FKS1</i> mutations mediate an evolutionary accumulation of echinocandin resistance followed by modulation of chromosome remodelling and DNA repair processes that ultimately lead to <i>FKS</i>1 hot spot mutations and the development of drug resistance. This study provides an in-depth exploration of the molecular pathways involved in the evolution of <i>Candida auris</i> echinocandin resistance.
DOI: 10.25549/webster-c100-39752
title: Interviews of city of Los Angeles, Emergency Operations Organization, 1992-08/1992-09

description: Summaries of interviews conducted with personnel from the City of Los Angeles's Emergency Operations Organization, 1992 August - September. PART OF SERIES: In addition to analyzing the 1992 riots as a whole, the Webster Commission also divided into several smaller task forces and study groups, each of which addressed one specific aspect of the civil disturbance. The series consists of reports and appendices produced by five of these groups: the Chronology Team, the Public Officials and Community Team, the LAPD Team, the Comparisons Study Group, and the Inter-Agency Team. Also included are two copies of Webster Scope, a report that interprets the riots and their cumulative effects primarily through graphs, charts, statistics, and figures, and several research memoranda that discuss the legality of several riot-response tactics. PART OF SUBSERIES: Materials related to a final report issued by the Webster Commission's Inter-Agency Team. which evaluated the collaboration between the LAPD and other law enforcement agencies in the advent of the 1992 riots. Included is a copy of the final report and the report's appendices, which are comprised of interviews, memoranda, statistical analyses, handbooks, and other miscellaneous documents.
DOI: 10.6084/m9.figshare.27275252
title: SARS-CoV-2 hijacks host CD55, CD59 and factor H to impair antibody-dependent complement-mediated lysis

description: The complement system is a vital anti-microbial defence mechanism against circulating pathogens. Excessive complement activation can have deleterious outcomes for the host and is consequently tightly modulated by a set of membrane-associated and fluid-phase regulators of complement activation (RCAs). Here, we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks host cellular RCA members CD55 and CD59 and serum-derived Factor H (FH) to resist antibody-dependent complement-mediated lysis triggered by immunized human sera. Blockage of the biological functions of virion-associated CD55 and CD59 and competition of FH recruitment with functionally inactive recombinant FH-derived short consensus repeats SCR18-20 restore SARS-CoV-2 complement sensitivity in a synergistic manner. Moreover, complement-mediated virolysis is dependent on classical pathway activation and does not occur in the absence of virus-specific antibodies. Altogether, our findings present an intriguing immune escape mechanism that provides novel insights into the immunopathology observed in severe coronavirus disease 2019 (COVID-19).
DOI: 10.6084/m9.figshare.25624754
title: Transmission of <i>bla</i><sub>NDM</sub> in Enterobacteriaceae among animals, food and human

description: Despite carbapenems not being used in animals, carbapenem-resistant Enterobacterales (CRE), particularly New Delhi metallo-β-lactamase-producing CRE (NDM-CRE), are prevalent in livestock. Concurrently, the incidence of human infections caused by NDM-CRE is rising, particularly in children. Although a positive association between livestock production and human NDM-CRE infections at the national level was identified, the evidence of direct transmission of NDM originating from livestock to humans remains largely unknown. Here, we conducted a cross-sectional study in Chengdu, Sichuan Province, to examine the prevalence of NDM-CRE in chickens and pigs along the breeding–slaughtering–retail chains, in pork in cafeterias of schools, and in colonizations and infections from children's hospital and examined the correlation of NDM-CRE among animals, foods and humans. Overall, the <i>bla</i><sub>NDM</sub> increases gradually along the chicken and pig breeding (4.70%/2.0%) –slaughtering (7.60%/22.40%) –retail (65.56%/34.26%) chains. The slaughterhouse has become a hotspot for cross-contamination and amplifier of <i>bla</i><sub>NDM</sub>. Notably, 63.11% of pork from the school cafeteria was positive for <i>bla</i><sub>NDM</sub>. The prevalence of <i>bla</i><sub>NDM</sub> in intestinal and infection samples from children's hospitals was 21.68% and 19.80%, respectively. whole genome sequencing (WGS) analysis revealed the sporadic, not large-scale, clonal spread of NDM-CRE along the chicken and pig breeding–slaughtering–retail chain, with further spreading via IncX3-<i>bla</i><sub>NDM</sub> plasmid within each stage of whole chains. Clonal transmission of NDM-CRE is predominant in children's hospitals. The IncX3-<i>bla</i><sub>NDM</sub> plasmid was highly prevalent among animals and humans and accounted for 57.7% of <i>Escherichia coli</i> and 91.3% of <i>Klebsiella pneumoniae</i>. Attention should be directed towards the IncX3 plasmid to control the transmission of <i>bla</i><sub>NDM</sub> between animals and humans.
DOI: 10.6084/m9.figshare.25624754.v2
title: Transmission of <i>bla</i><sub>NDM</sub> in Enterobacteriaceae among animals, food and human

description: Despite carbapenems not being used in animals, carbapenem-resistant Enterobacterales (CRE), particularly New Delhi metallo-β-lactamase-producing CRE (NDM-CRE), are prevalent in livestock. Concurrently, the incidence of human infections caused by NDM-CRE is rising, particularly in children. Although a positive association between livestock production and human NDM-CRE infections at the national level was identified, the evidence of direct transmission of NDM originating from livestock to humans remains largely unknown. Here, we conducted a cross-sectional study in Chengdu, Sichuan Province, to examine the prevalence of NDM-CRE in chickens and pigs along the breeding–slaughtering–retail chains, in pork in cafeterias of schools, and in colonizations and infections from children's hospital and examined the correlation of NDM-CRE among animals, foods and humans. Overall, the <i>bla</i><sub>NDM</sub> increases gradually along the chicken and pig breeding (4.70%/2.0%) –slaughtering (7.60%/22.40%) –retail (65.56%/34.26%) chains. The slaughterhouse has become a hotspot for cross-contamination and amplifier of <i>bla</i><sub>NDM</sub>. Notably, 63.11% of pork from the school cafeteria was positive for <i>bla</i><sub>NDM</sub>. The prevalence of <i>bla</i><sub>NDM</sub> in intestinal and infection samples from children's hospitals was 21.68% and 19.80%, respectively. whole genome sequencing (WGS) analysis revealed the sporadic, not large-scale, clonal spread of NDM-CRE along the chicken and pig breeding–slaughtering–retail chain, with further spreading via IncX3-<i>bla</i><sub>NDM</sub> plasmid within each stage of whole chains. Clonal transmission of NDM-CRE is predominant in children's hospitals. The IncX3-<i>bla</i><sub>NDM</sub> plasmid was highly prevalent among animals and humans and accounted for 57.7% of <i>Escherichia coli</i> and 91.3% of <i>Klebsiella pneumoniae</i>. Attention should be directed towards the IncX3 plasmid to control the transmission of <i>bla</i><sub>NDM</sub> between animals and humans.
DOI: 10.6084/m9.figshare.27275252.v1
title: SARS-CoV-2 hijacks host CD55, CD59 and Factor H to impair antibody-dependent complement-mediated lysis

description: The complement system is a vital anti-microbial defence mechanism against circulating pathogens. Excessive complement activation can have deleterious outcomes for the host and is consequently tightly modulated by a set of membrane-associated and fluid-phase regulators of complement activation (RCAs). Here, we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks host cellular RCA members CD55 and CD59 and serum-derived Factor H (FH) to resist antibody-dependent complement-mediated lysis triggered by immunised human sera. Blockage of the biological functions of virion-associated CD55 and CD59 and competition of FH recruitment with functionally inactive recombinant FH-derived short consensus repeats SCR18-20 restore SARS-CoV-2 complement sensitivity in a synergistic manner. Moreover, complement-mediated virolysis is dependent on classical pathway activation and does not occur in the absence of virus-specific antibodies. Altogether, our findings present an intriguing immune escape mechanism that provides novel insights into the immunopathology observed in severe coronavirus disease 2019 (COVID-19).
DOI: 10.6084/m9.figshare.27275252.v2
title: SARS-CoV-2 hijacks host CD55, CD59 and factor H to impair antibody-dependent complement-mediated lysis

description: The complement system is a vital anti-microbial defence mechanism against circulating pathogens. Excessive complement activation can have deleterious outcomes for the host and is consequently tightly modulated by a set of membrane-associated and fluid-phase regulators of complement activation (RCAs). Here, we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks host cellular RCA members CD55 and CD59 and serum-derived Factor H (FH) to resist antibody-dependent complement-mediated lysis triggered by immunized human sera. Blockage of the biological functions of virion-associated CD55 and CD59 and competition of FH recruitment with functionally inactive recombinant FH-derived short consensus repeats SCR18-20 restore SARS-CoV-2 complement sensitivity in a synergistic manner. Moreover, complement-mediated virolysis is dependent on classical pathway activation and does not occur in the absence of virus-specific antibodies. Altogether, our findings present an intriguing immune escape mechanism that provides novel insights into the immunopathology observed in severe coronavirus disease 2019 (COVID-19).