cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.27015796
title: Genome-wide CRISPR/Cas9 library screen identifies C16orf62 as a host dependency factor for porcine deltacoronavirus infection

description: Porcine deltacoronavirus (PDCoV) is an emerging pathogen that can cause severe diarrhoea and high mortality in suckling piglets. Moreover, evidence of PDCoV infection in humans has raised concerns regarding potential public health risks. To identify potential therapeutic targets for PDCoV, we performed a genome-wide CRISPR/Cas9 library screening to find key host factors important to PDCoV infection. Several host genes in this screen were enriched, including ANPEP, which encodes the PDCoV receptor aminopeptidase N (APN). Furthermore, we discovered C16orf62, also known as the VPS35 endosomal protein sorting factor like (VPS35L), as an important host factor required for PDCoV infection. C16orf62 is an important component of the multiprotein retriever complex involved in protein recycling in the endosomal compartment and its gene knockout led to a remarkable decrease in the binding and internalization of PDCoV into host cells. While we did not find evidence for direct interaction between C16orf62 and the viral s (spike) protein, C16orf62 gene knockout was shown to downregulate APN expression at the cell surface. This study marks the first instance of a genome-wide CRISPR/Cas9-based screen tailored for PDCoV, revealing C16orf62 as a host factor required for PDCoV replication. These insights may provide promising avenues for the development of antiviral drugs against PDCoV infection.
DOI: 10.6084/m9.figshare.27015796.v1
title: Genome-wide CRISPR/Cas9 library screen identifies C16orf62 as a host dependency factor for porcine deltacoronavirus infection

description: Porcine deltacoronavirus (PDCoV) is an emerging pathogen that can cause severe diarrhoea and high mortality in suckling piglets. Moreover, evidence of PDCoV infection in humans has raised concerns regarding potential public health risks. To identify potential therapeutic targets for PDCoV, we performed a genome-wide CRISPR/Cas9 library screening to find key host factors important to PDCoV infection. Several host genes in this screen were enriched, including ANPEP, which encodes the PDCoV receptor aminopeptidase N (APN). Furthermore, we discovered C16orf62, also known as the VPS35 endosomal protein sorting factor like (VPS35L), as an important host factor required for PDCoV infection. C16orf62 is an important component of the multiprotein retriever complex involved in protein recycling in the endosomal compartment and its gene knockout led to a remarkable decrease in the binding and internalization of PDCoV into host cells. While we did not find evidence for direct interaction between C16orf62 and the viral s (spike) protein, C16orf62 gene knockout was shown to downregulate APN expression at the cell surface. This study marks the first instance of a genome-wide CRISPR/Cas9-based screen tailored for PDCoV, revealing C16orf62 as a host factor required for PDCoV replication. These insights may provide promising avenues for the development of antiviral drugs against PDCoV infection.
DOI: 10.25549/webster-c100-76645
title: After-action reporting for April/May riots, 1992

description: After-action reporting for April/May riots, Operations - Bureau of Special Investigation, 1992. PART OF SERIES: Included in the series are internal documents produced by the LAPD, which aided the Webster Commission in its assessment of the Department's operations. Materials include copies of the Watch Commander's Daily Reports between October, 1991 and May, 1992; critiques and after-action reports on the riots issued by each LAPD bureau; and correspondence regarding personnel and budget matters, crime statistics, and several Department-initiated programs. Also included are several documents, including schedules, press releases, and memoranda, that were issued by the office of Los Angeles Mayor Tom Bradley regarding the verdicts in the Rodney King case.
DOI: 10.6084/m9.figshare.25957687.v2
title: Genetic variation and evolutionary characteristics of Echovirus 11: new variant within genotype D5 associated with neonatal death found in China

description: Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. From 2018 to 2023, a surge in severe neonatal cases and fatalities linked to a novel variant of genotype D5 was documented in China, France, and Italy. However, the prevention and control of E11 variants have been hampered by limited background data on the virus circulation and genetic variance. Therefore, the present study investigated the circulating dynamics of E11 and the genetic variation and molecular evolution of genotype D5 through the collection of strains from the national acute flaccid paralysis (AFP) and hand, foot, and mouth disease (HFMD) surveillance system in China during 2000–2022 and genetic sequences published in the GenBank database. The results of this study revealed a prevalent dynamic of E11 circulation, with D5 being the predominant genotype worldwide. Further phylogenetic analysis of genotype D5 indicated that it could be subdivided into three important geographic clusters (D5-CHN1: 2014–2019, D5-CHN2: 2016–2022, and D5-EUR: 2022–2023). Additionally, variant-specific (144) amino acid mutation sites and positive-selection pressure sites (132, 262) were identified in the <i>VP1</i> region. Cluster-specific recombination patterns were also identified, with CVB5, E6, and CVB4 as the major recombinant viruses. These findings provide a preliminary landscape of E11 circulation worldwide and basic scientific data for further study of the pathogenicity of E11 variants.
DOI: 10.6084/m9.figshare.26196889
title: The nuclear localization signal of monkeypox virus protein P2 orthologue is critical for inhibition of IRF3-mediated innate immunity

description: The <i>Orthopoxvirus</i> (OPXV) genus of the <i>Poxviridae</i> includes human pathogens variola virus (VARV), monkeypox virus (MPXV), vaccinia virus (VACV), and a number of zoonotic viruses. A number of Bcl-2-like proteins of VACV are involved in escaping the host innate immunity. However, little work has been devoted to the evolution and function of their orthologues in other OPXVs. Here, we found that MPXV protein P2, encoded by the <i>P2L</i> gene, and P2 orthologues from other OPXVs, such as VACV protein N2, localize to the nucleus and antagonize interferon (IFN) production. Exceptions to this were the truncated P2 orthologues in camelpox virus (CMLV) and taterapox virus (TATV) that lacked the nuclear localization signal (NLS). Mechanistically, the NLS of MPXV P2 interacted with karyopherin α-2 (KPNA2) to facilitate P2 nuclear translocation, and competitively inhibited KPNA2-mediated IRF3 nuclear translocation and downstream IFN production. Deletion of the NLS in P2 or orthologues significantly enhanced IRF3 nuclear translocation and innate immune responses, thereby reducing viral replication. Moreover, deletion of NLS from N2 in VACV attenuated viral replication and virulence in mice. These data demonstrate that the NLS-mediated translocation of P2 is critical for P2-induced inhibition of innate immunity. Our findings contribute to an in-depth understanding of the mechanisms of OPXV P2 orthologue in innate immune evasion.
DOI: 10.6084/m9.figshare.26196889.v1
title: The nuclear localization signal of monkeypox virus protein P2 orthologue is critical for inhibition of IRF3-mediated innate immunity

description: The <i>Orthopoxvirus</i> (OPXV) genus of the <i>Poxviridae</i> includes human pathogens variola virus (VARV), monkeypox virus (MPXV), vaccinia virus (VACV), and a number of zoonotic viruses. A number of Bcl-2-like proteins of VACV are involved in escaping the host innate immunity. However, little work has been devoted to the evolution and function of their orthologues in other OPXVs. Here, we found that MPXV protein P2, encoded by the <i>P2L</i> gene, and P2 orthologues from other OPXVs, such as VACV protein N2, localize to the nucleus and antagonize interferon (IFN) production. Exceptions to this were the truncated P2 orthologues in camelpox virus (CMLV) and taterapox virus (TATV) that lacked the nuclear localization signal (NLS). Mechanistically, the NLS of MPXV P2 interacted with karyopherin α-2 (KPNA2) to facilitate P2 nuclear translocation, and competitively inhibited KPNA2-mediated IRF3 nuclear translocation and downstream IFN production. Deletion of the NLS in P2 or orthologues significantly enhanced IRF3 nuclear translocation and innate immune responses, thereby reducing viral replication. Moreover, deletion of NLS from N2 in VACV attenuated viral replication and virulence in mice. These data demonstrate that the NLS-mediated translocation of P2 is critical for P2-induced inhibition of innate immunity. Our findings contribute to an in-depth understanding of the mechanisms of OPXV P2 orthologue in innate immune evasion.
DOI: 10.6084/m9.figshare.27160566
title: Ad5-nCoV boosted vaccine and reinfection-induced memory T/B cell responses and humoral immunity to SARS-CoV-2: based on two prospective cohorts

description: Here, we regularly followed two SARS-CoV-2 infected cohorts to investigate the combined effects of neutralizing antibodies (NAbs) and B and T cell profiles during the convalescent period. Ten infected participants in December 2022 were selected to assess the effects of an inhaled adenovirus type 5 vectored COVID-19 vaccine (Ad5-nCoV) booster on B cells and humoral immunity in the first cohort. To evaluate T cell responses, eight primary and 20 reinfection participants were included in the second cohort. Blood samples from all 38 participants were collected at 1-, 2-, and 6-months post-infection. In the first cohort, eighteen monoclonal antibodies (mAbs) with neutralizing activity from memory B cells (MBC) against SARS-CoV-2 mutants were obtained by high throughput single-B-cell cloning method, which lasted from 1- month to 6- month post infection. The overall number of mAbs from MBC in the boosted immunization group was higher than that in the nonboosted immunization group at 2-, and 6-months post-infection. In the second cohort, circulating T follicular helper cells (cTfh) and AIM <sup>+ </sup>CD4 <sup>+ </sup>T cells increased over time in the reinfection group (<i>P</i> &lt; 0.05). In both cohorts, serum NAb titers showed significant immune escape, while cTfh and AIM <sup>+ </sup>CD4 <sup>+ </sup>T cells in the second cohort essentially showed no immune escape to new strains (including XBB, EG.5). AIM <sup>+ </sup>CD4 <sup>+ </sup>T cells against BA.5 and EG.5 were strongly negatively correlated with the time to viral clearance in the reinfected group at 6-months post-infection. We comprehensively assessed the ability of the SARS-CoV-2 boosted immunization and reinfection-induced generation of T/B cell immune memories in preventing reinfection.
DOI: 10.6084/m9.figshare.27160566.v1
title: Ad5-nCoV boosted vaccine and reinfection-induced memory T/B cell responses and humoral immunity to SARS-CoV-2: based on two prospective cohorts

description: Here, we regularly followed two SARS-CoV-2 infected cohorts to investigate the combined effects of neutralizing antibodies (NAbs) and B and T cell profiles during the convalescent period. Ten infected participants in December 2022 were selected to assess the effects of an inhaled adenovirus type 5 vectored COVID-19 vaccine (Ad5-nCoV) booster on B cells and humoral immunity in the first cohort. To evaluate T cell responses, eight primary and 20 reinfection participants were included in the second cohort. Blood samples from all 38 participants were collected at 1-, 2-, and 6-months post-infection. In the first cohort, eighteen monoclonal antibodies (mAbs) with neutralizing activity from memory B cells (MBC) against SARS-CoV-2 mutants were obtained by high throughput single-B-cell cloning method, which lasted from 1- month to 6- month post infection. The overall number of mAbs from MBC in the boosted immunization group was higher than that in the nonboosted immunization group at 2-, and 6-months post-infection. In the second cohort, circulating T follicular helper cells (cTfh) and AIM <sup>+ </sup>CD4 <sup>+ </sup>T cells increased over time in the reinfection group (<i>P</i> &lt; 0.05). In both cohorts, serum NAb titers showed significant immune escape, while cTfh and AIM <sup>+ </sup>CD4 <sup>+ </sup>T cells in the second cohort essentially showed no immune escape to new strains (including XBB, EG.5). AIM <sup>+ </sup>CD4 <sup>+ </sup>T cells against BA.5 and EG.5 were strongly negatively correlated with the time to viral clearance in the reinfected group at 6-months post-infection. We comprehensively assessed the ability of the SARS-CoV-2 boosted immunization and reinfection-induced generation of T/B cell immune memories in preventing reinfection.
DOI: 10.6084/m9.figshare.27628910.v2
title: Dissecting immunological mechanisms underlying influenza viral nucleoprotein-induced mucosal immunity against diverse viral strains

description: The nucleoprotein (NP) of type A influenza virus (IAV) is highly conserved across all virus strains, making it an attractive candidate antigen for universal vaccines. While various studies have explored NP-induced mucosal immunity, here we interrogated the mechanistic differences between intramuscular (IM) and intranasal (IN) delivery of a recombinant adenovirus carrying NP fused with a bifunctional CD40 ligand. Despite being less effective than IM delivery in inducing systemic cellular immune responses and antibody-dependent cellular cytotoxicity (ADCC), IN immunization elicited superior antigen-specific recall humoral and cellular response in the nasal associated lymphoid tissue (NALT) of the upper respiratory tract, the initial site of immune recognition and elimination of inhaled pathogens. IN vaccination also induced significantly stronger pulmonary T cell responses in the lower respiratory tract than IM vaccination, in particular the CD8 T cells. Moreover, blocking lymphocyte circulation abrogated IM but not IN immunization induced protection, illustrating the critical role of local memory immune response upon viral infection. Notably, the CD40-targeted nasal delivery not only improved the magnitude but also the breadth of protection, including against lethal challenge with a newly isolated highly pathogenic avian H5N1 strain. These findings are informative for the design of universal mucosal vaccines, where the predominant mode of protection is independent of neutralizing antibodies.
DOI: 10.6084/m9.figshare.27628910
title: Dissecting immunological mechanisms underlying influenza viral nucleoprotein-induced mucosal immunity against diverse viral strains

description: The nucleoprotein (NP) of type A influenza virus (IAV) is highly conserved across all virus strains, making it an attractive candidate antigen for universal vaccines. While various studies have explored NP-induced mucosal immunity, here we interrogated the mechanistic differences between intramuscular (IM) and intranasal (IN) delivery of a recombinant adenovirus carrying NP fused with a bifunctional CD40 ligand. Despite being less effective than IM delivery in inducing systemic cellular immune responses and antibody-dependent cellular cytotoxicity (ADCC), IN immunization elicited superior antigen-specific recall humoral and cellular response in the nasal associated lymphoid tissue (NALT) of the upper respiratory tract, the initial site of immune recognition and elimination of inhaled pathogens. IN vaccination also induced significantly stronger pulmonary T cell responses in the lower respiratory tract than IM vaccination, in particular the CD8 T cells. Moreover, blocking lymphocyte circulation abrogated IM but not IN immunization induced protection, illustrating the critical role of local memory immune response upon viral infection. Notably, the CD40-targeted nasal delivery not only improved the magnitude but also the breadth of protection, including against lethal challenge with a newly isolated highly pathogenic avian H5N1 strain. These findings are informative for the design of universal mucosal vaccines, where the predominant mode of protection is independent of neutralizing antibodies.
DOI: 10.6084/m9.figshare.27628910.v1
title: Dissecting Immunological Mechanisms Underlying Influenza Viral Nucleoprotein-induced Mucosal Immunity Against Diverse Viral Strains

description: The nucleoprotein (NP) of type A influenza virus (IAV) is highly conserved across all virus strains, making it an attractive candidate antigen for universal vaccines. While various studies have explored NP-induced mucosal immunity, here we interrogated the mechanistic differences between intramuscular (IM) and intranasal (IN) delivery of a recombinant adenovirus carrying NP fused with a bifunctional CD40 ligand. Despite being less effective than IM delivery in inducing systemic cellular immune responses and antibody-dependent cellular cytotoxicity (ADCC), IN immunization elicited superior antigen-specific recall humoral and cellular response in the nasal associated lymphoid tissue (NALT) of the upper respiratory tract, the initial site of immune recognition and elimination of inhaled pathogens. IN vaccination also induced significantly stronger pulmonary T cell responses in the lower respiratory tract than IM vaccination, in particular the CD8 T cells. Moreover, blocking lymphocyte circulation abrogated IM but not IN immunization induced protection, illustrating the critical role of local memory immune response upon viral infection. Notably, the CD40-targeted nasal delivery not only improved the magnitude but also the breadth of protection, including against lethal challenge with a newly isolated highly pathogenic avian H5N1 strain. These findings are informative for the design of universal mucosal vaccines, where the predominant mode of protection is independent of neutralizing antibodies.
DOI: 10.25549/webster-c100-38298
title: Inter-Agency Team Final Report, Los Angeles County Sheriff's Department, 1992

description: Inter-Agency Team Final Report, Appendix: Los Angeles County Sheriff's Department Miscellaneous materials collected by the Inter-Agency team regarding the role of the Los Angeles County Sheriff's Department in the response to the 1992 riots, 1992. 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.26180723
title: Plasma immune profiling combined with machine learning contributes to diagnosis and prognosis of active pulmonary tuberculosis

description: Tuberculosis (TB) remains one of the deadliest chronic infectious diseases globally. Early diagnosis not only prevents the spread of TB but also ensures effective treatment. However, the absence of non-sputum-based diagnostic tests often leads to delayed TB diagnoses. Inflammation is a hallmark of TB, we aimed to identify biomarkers associated with TB based on immune profiling. We collected 222 plasma samples from healthy controls (HCs), disease controls (non-TB pneumonia; PN), patients with TB (TB), and cured TB cases (RxTB). A high-throughput protein detection technology, multiplex proximity extension assays (PEA), was applied to measure the levels of 92 immune proteins. Based on differential analysis and the correlation with TB severity, we selected 9 biomarkers (CXCL9, PDL1, CDCP1, CCL28, CCL23, CCL19, MMP1, IFNγ and TRANCE) and explored their diagnostic capabilities through 7 machine learning methods. We identified combination of these 9 biomarkers that distinguish TB cases from controls with an area under the receiver operating characteristic curve (AUROC) of 0.89–0.99, with a sensitivity of 82–93% at a specificity of 88–92%. Moreover, the model excels in distinguishing severe TB cases, achieving AUROC exceeding 0.95, sensitivities and specificities exceeding 93.3%. In summary, utilizing targeted proteomics and machine learning, we identified a 9 plasma proteins signature that demonstrates significant potential for accurate TB diagnosis and clinical outcome prediction.
DOI: 10.6084/m9.figshare.26180723.v1
title: Plasma immune profiling combined with machine learning contributes to diagnosis and prognosis of active pulmonary tuberculosis

description: Tuberculosis (TB) remains one of the deadliest chronic infectious diseases globally. Early diagnosis not only prevents the spread of TB but also ensures effective treatment. However, the absence of non-sputum-based diagnostic tests often leads to delayed TB diagnoses. Inflammation is a hallmark of TB, we aimed to identify biomarkers associated with TB based on immune profiling. We collected 222 plasma samples from healthy controls (HCs), disease controls (non-TB pneumonia; PN), patients with TB (TB), and cured TB cases (RxTB). A high-throughput protein detection technology, multiplex proximity extension assays (PEA), was applied to measure the levels of 92 immune proteins. Based on differential analysis and the correlation with TB severity, we selected 9 biomarkers (CXCL9, PDL1, CDCP1, CCL28, CCL23, CCL19, MMP1, IFNγ and TRANCE) and explored their diagnostic capabilities through 7 machine learning methods. We identified combination of these 9 biomarkers that distinguish TB cases from controls with an area under the receiver operating characteristic curve (AUROC) of 0.89–0.99, with a sensitivity of 82–93% at a specificity of 88–92%. Moreover, the model excels in distinguishing severe TB cases, achieving AUROC exceeding 0.95, sensitivities and specificities exceeding 93.3%. In summary, utilizing targeted proteomics and machine learning, we identified a 9 plasma proteins signature that demonstrates significant potential for accurate TB diagnosis and clinical outcome prediction.
DOI: 10.25549/webster-c100-77361
title: After-action reporting for April/May riots, 1992-06-24

description: After-action reporting for April/May riots, Operations - Valley Bureau, 1992 June 24. PART OF SERIES: Included in the series are internal documents produced by the LAPD, which aided the Webster Commission in its assessment of the Department's operations. Materials include copies of the Watch Commander's Daily Reports between October, 1991 and May, 1992; critiques and after-action reports on the riots issued by each LAPD bureau; and correspondence regarding personnel and budget matters, crime statistics, and several Department-initiated programs. Also included are several documents, including schedules, press releases, and memoranda, that were issued by the office of Los Angeles Mayor Tom Bradley regarding the verdicts in the Rodney King case.