cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.25549/webster-c100-39791
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.24720302
title: Characterization of highly pathogenic avian influenza A (H5N1) viruses isolated from cats in South Korea, 2023

description: Characterization of highly pathogenic avian influenza A (H5N1) viruses isolated from cats in South Korea, 2023
DOI: 10.6084/m9.figshare.24720302.v2
title: Characterization of highly pathogenic avian influenza A (H5N1) viruses isolated from cats in South Korea, 2023

description: Characterization of highly pathogenic avian influenza A (H5N1) viruses isolated from cats in South Korea, 2023
DOI: 10.6084/m9.figshare.25332001
title: Lansoprazole interferes with fungal respiration and acts synergistically with amphotericin B against multidrug-resistant <i>Candida auris</i>

description: <i>Candida auris</i> has emerged as a problematic fungal pathogen associated with high morbidity and mortality. Amphotericin B (AmB) is the most effective antifungal used to treat invasive fungal candidiasis, with resistance rarely observed among clinical isolates. However, <i>C. auris</i> possesses extraordinary resistant profiles against all available antifungal drugs, including AmB. In our pursuit of potential solutions, we screened a panel of 727 FDA-approved drugs. We identified the proton pump inhibitor lansoprazole (LNP) as a potent enhancer of AmB’s activity against <i>C. auris.</i> LNP also potentiates the antifungal activity of AmB against other medically important species of <i>Candida</i> and <i>Cryptococcus.</i> Our investigations into the mechanism of action unveiled that LNP metabolite(s) interact with a crucial target in the mitochondrial respiratory chain (complex III, known as cytochrome <i>bc<sub>1</sub></i>). This interaction increases oxidative stress within fungal cells. Our results demonstrated the critical role of an active respiratory function in the antifungal activity of LNP. Most importantly, LNP restored the efficacy of AmB in an immunocompromised mouse model, resulting in a 1.7-log (∼98%) CFU reduction in the burden of <i>C. auris</i> in the kidneys. Our findings strongly advocate for a comprehensive evaluation of LNP as a cytochrome <i>bc<sub>1</sub></i> inhibitor for combating drug-resistant <i>C. auris</i> infections.
DOI: 10.6084/m9.figshare.25332001.v1
title: Lansoprazole interferes with fungal respiration and acts synergistically with amphotericin B against multidrug-resistant <i>Candida auris</i>

description: <i>Candida auris</i> has emerged as a problematic fungal pathogen associated with high morbidity and mortality. Amphotericin B (AmB) is the most effective antifungal used to treat invasive fungal candidiasis, with resistance rarely observed among clinical isolates. However, <i>C. auris</i> possesses extraordinary resistant profiles against all available antifungal drugs, including AmB. In our pursuit of potential solutions, we screened a panel of 727 FDA-approved drugs. We identified the proton pump inhibitor lansoprazole (LNP) as a potent enhancer of AmB’s activity against <i>C. auris.</i> LNP also potentiates the antifungal activity of AmB against other medically important species of <i>Candida</i> and <i>Cryptococcus.</i> Our investigations into the mechanism of action unveiled that LNP metabolite(s) interact with a crucial target in the mitochondrial respiratory chain (complex III, known as cytochrome <i>bc<sub>1</sub></i>). This interaction increases oxidative stress within fungal cells. Our results demonstrated the critical role of an active respiratory function in the antifungal activity of LNP. Most importantly, LNP restored the efficacy of AmB in an immunocompromised mouse model, resulting in a 1.7-log (∼98%) CFU reduction in the burden of <i>C. auris</i> in the kidneys. Our findings strongly advocate for a comprehensive evaluation of LNP as a cytochrome <i>bc<sub>1</sub></i> inhibitor for combating drug-resistant <i>C. auris</i> infections.
DOI: 10.6084/m9.figshare.25412374
title: Differential susceptibility of geographically distinct <i>Ixodes ricinus</i> populations to tick-borne encephalitis virus and louping ill virus

description: Tick-borne encephalitis virus (TBEV) is an emerging pathogen in the Netherlands. Multiple divergent viral strains are circulating and the focal distribution of TBEV remains poorly understood. This may, however, be explained by differences in the susceptibility of tick populations for specific viruses and viral strains, and by viral strains having higher infection success in their local tick population. We investigated this hypothesis by exposing Dutch <i>Ixodes ricinus</i> ticks to two different TBEV strains: TBEV-NL from the Netherlands and TBEV-Neudoerfl from Austria. In addition, we exposed ticks to louping Ill virus (LIV), which is endemic to large parts of the United Kingdom and Ireland, but has not been reported in the Netherlands. Ticks were collected from two locations in the Netherlands: one location without evidence of TBEV circulation and one location endemic for the TBEV-NL strain. Ticks were infected in a biosafety level 3 laboratory using an artificial membrane feeding system. Ticks collected from the region without evidence of TBEV circulation had lower infection rates for TBEV-NL as compared to TBEV-Neudoerfl. <i>Vice versa</i>, ticks collected from the TBEV-NL endemic region had higher infection rates for TBEV-NL compared to TBEV-Neudoerfl. In addition, LIV infection rates were much lower in Dutch ticks compared to TBEV, which may explain why LIV is not present in the Netherlands. Our findings show that ticks from two distinct geographical populations differ in their susceptibility to TBEV strains, which could be the result of differences in the genetic background of the tick populations.
DOI: 10.6084/m9.figshare.25412374.v1
title: Differential susceptibility of geographically distinct <i>Ixodes ricinus</i> populations to tick-borne encephalitis virus and louping ill virus

description: Tick-borne encephalitis virus (TBEV) is an emerging pathogen in the Netherlands. Multiple divergent viral strains are circulating and the focal distribution of TBEV remains poorly understood. This may, however, be explained by differences in the susceptibility of tick populations for specific viruses and viral strains, and by viral strains having higher infection success in their local tick population. We investigated this hypothesis by exposing Dutch <i>Ixodes ricinus</i> ticks to two different TBEV strains: TBEV-NL from the Netherlands and TBEV-Neudoerfl from Austria. In addition, we exposed ticks to louping Ill virus (LIV), which is endemic to large parts of the United Kingdom and Ireland, but has not been reported in the Netherlands. Ticks were collected from two locations in the Netherlands: one location without evidence of TBEV circulation and one location endemic for the TBEV-NL strain. Ticks were infected in a biosafety level 3 laboratory using an artificial membrane feeding system. Ticks collected from the region without evidence of TBEV circulation had lower infection rates for TBEV-NL as compared to TBEV-Neudoerfl. <i>Vice versa</i>, ticks collected from the TBEV-NL endemic region had higher infection rates for TBEV-NL compared to TBEV-Neudoerfl. In addition, LIV infection rates were much lower in Dutch ticks compared to TBEV, which may explain why LIV is not present in the Netherlands. Our findings show that ticks from two distinct geographical populations differ in their susceptibility to TBEV strains, which could be the result of differences in the genetic background of the tick populations.
DOI: 10.6084/m9.figshare.24925322
title: Monoclonal antibody therapy demonstrates increased virulence of a lineage VII strain of Lassa virus in nonhuman primates

description: Lassa virus (LASV) is a World Health Organization (WHO) priority pathogen that causes high morbidity and mortality. Recently, we showed that a combination of three broadly neutralizing human monoclonal antibodies known as Arevirumab-3 (8.9F, 12.1F, 37.2D) based on the lineage IV Josiah strain protected 100% of cynomolgus macaques against heterologous challenge with lineage II and III strains of LASV when therapy was initiated beginning at day 8 after challenge. LASV strains from Benin and Togo represent a new lineage VII that are more genetically diverse from lineage IV than strains from lineages II and III. Here, we tested the ability of Arevirumab-3 to protect macaques against a LASV lineage VII Togo isolate when treatment was administered beginning 8 days after exposure. Unexpectedly, only 40% of treated animals survived challenge. In a subsequent study we showed that Arevirumab-3 protected 100% of macaques from lethal challenge when treatment was initiated 7 days after LASV Togo exposure. Based on our transcriptomics data, successful Arevirumab-3 treatment correlated with diminished neutrophil signatures and the predicted development of T cell responses. As the <i>in vitro</i> antiviral activity of Arevirumab-3 against LASV Togo was equivalent to lineage II and III strains, the reduced protection in macaques against Togo likely reflects the faster disease course of LASV Togo in macaques than other strains. This data causes concern regarding the ability of heterologous vaccines and treatments to provide cross protection against lineage VII LASV isolates.
DOI: 10.6084/m9.figshare.24925322.v2
title: Monoclonal antibody therapy demonstrates increased virulence of a lineage VII strain of Lassa virus in nonhuman primates

description: Lassa virus (LASV) is a World Health Organization (WHO) priority pathogen that causes high morbidity and mortality. Recently, we showed that a combination of three broadly neutralizing human monoclonal antibodies known as Arevirumab-3 (8.9F, 12.1F, 37.2D) based on the lineage IV Josiah strain protected 100% of cynomolgus macaques against heterologous challenge with lineage II and III strains of LASV when therapy was initiated beginning at day 8 after challenge. LASV strains from Benin and Togo represent a new lineage VII that are more genetically diverse from lineage IV than strains from lineages II and III. Here, we tested the ability of Arevirumab-3 to protect macaques against a LASV lineage VII Togo isolate when treatment was administered beginning 8 days after exposure. Unexpectedly, only 40% of treated animals survived challenge. In a subsequent study we showed that Arevirumab-3 protected 100% of macaques from lethal challenge when treatment was initiated 7 days after LASV Togo exposure. Based on our transcriptomics data, successful Arevirumab-3 treatment correlated with diminished neutrophil signatures and the predicted development of T cell responses. As the <i>in vitro</i> antiviral activity of Arevirumab-3 against LASV Togo was equivalent to lineage II and III strains, the reduced protection in macaques against Togo likely reflects the faster disease course of LASV Togo in macaques than other strains. This data causes concern regarding the ability of heterologous vaccines and treatments to provide cross protection against lineage VII LASV isolates.
DOI: 10.6084/m9.figshare.25574381
title: Small regulatory RNA RSaX28 promotes virulence by reinforcing the stability of RNAIII in community-associated ST398 clonotype <i>Staphylococcus aureus</i>

description: <i>Staphylococcus aureus</i> (<i>S. aureus</i>) is a notorious pathogen that cause metastatic or complicated infections. Hypervirulent ST398 clonotype strains, remarkably increased in recent years, dominated Community-associated <i>S. aureus</i> (CA-SA) infections in the past decade in China. Small RNAs like RNAIII have been demonstrated to play important roles in regulating the virulence of <i>S. aureus</i>, however, the regulatory roles played by many of these sRNAs in the ST398 clonotype strains are still unclear. Through transcriptome screening and combined with knockout phenotype analysis, we have identified a highly transcribed sRNA, RSaX28, in the ST398 clonotype strains. Sequence analysis revealed that RSaX28 is highly conserved in the most epidemic clonotypes of <i>S. aureus</i>, but its high transcription level is particularly prominent in the ST398 clonotype strains. Characterization of RSaX28 through RACE and Northern blot revealed its length to be 533nt. RSaX28 is capable of promoting the hemolytic ability, reducing biofilm formation capacity, and enhancing virulence of <i>S. aureus</i> in the <i>in vivo</i> murine infection model. Through IntaRNA prediction and EMSA validation, we found that RSaX28 can specifically interact with RNAIII, promoting its stability and positively regulating the translation of downstream alpha-toxin while inhibiting the translation of Sbi, thereby regulating the virulence and biofilm formation capacity of the ST398 clonotype strains. RSaX28 is an important virulence regulatory factor in the ST398 clonotype <i>S. aureus</i> and represents a potential important target for future treatment and immune intervention against <i>S. aureus</i> infections.
DOI: 10.6084/m9.figshare.25574381.v2
title: Small regulatory RNA RSaX28 promotes virulence by reinforcing the stability of RNAIII in community-associated ST398 clonotype <i>Staphylococcus aureus</i>

description: <i>Staphylococcus aureus</i> (<i>S. aureus</i>) is a notorious pathogen that cause metastatic or complicated infections. Hypervirulent ST398 clonotype strains, remarkably increased in recent years, dominated Community-associated <i>S. aureus</i> (CA-SA) infections in the past decade in China. Small RNAs like RNAIII have been demonstrated to play important roles in regulating the virulence of <i>S. aureus</i>, however, the regulatory roles played by many of these sRNAs in the ST398 clonotype strains are still unclear. Through transcriptome screening and combined with knockout phenotype analysis, we have identified a highly transcribed sRNA, RSaX28, in the ST398 clonotype strains. Sequence analysis revealed that RSaX28 is highly conserved in the most epidemic clonotypes of <i>S. aureus</i>, but its high transcription level is particularly prominent in the ST398 clonotype strains. Characterization of RSaX28 through RACE and Northern blot revealed its length to be 533nt. RSaX28 is capable of promoting the hemolytic ability, reducing biofilm formation capacity, and enhancing virulence of <i>S. aureus</i> in the <i>in vivo</i> murine infection model. Through IntaRNA prediction and EMSA validation, we found that RSaX28 can specifically interact with RNAIII, promoting its stability and positively regulating the translation of downstream alpha-toxin while inhibiting the translation of Sbi, thereby regulating the virulence and biofilm formation capacity of the ST398 clonotype strains. RSaX28 is an important virulence regulatory factor in the ST398 clonotype <i>S. aureus</i> and represents a potential important target for future treatment and immune intervention against <i>S. aureus</i> infections.
DOI: 10.25549/webster-c100-39807
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.24925287
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
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 the United Sates 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.26305048.v2
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 the United Sates 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.26509458
title: TCR-like bispecific antibodies toward eliminating infected hepatocytes in HBV mouse models

description: Therapeutics for eradicating hepatitis B virus (HBV) infection are still limited and current nucleos(t)ide analogs (NAs) and interferon are effective in controlling viral replication and improving liver health, but they cannot completely eradicate the hepatitis B virus and only a very small number of patients are cured of it. The TCR-like antibodies recognizing viral peptides presented on human leukocyte antigens (HLA) provide possible tools for targeting and eliminating HBV-infected hepatocytes. Here, we generated three TCR-like antibodies targeting three different HLA-A2.1-presented peptides derived from HBV core and surface proteins. Bispecific antibodies (BsAbs) were developed by fuzing variable fragments of these TCR-like mAbs with an anti-CD3ϵ antibody. Our data demonstrate that the BsAbs could act as T cell engagers, effectively redirecting and activating T cells to target HBV-infected hepatocytes <i>in vitro</i> and <i>in vivo</i>. In HBV-persistent mice expressing human HLA-A2.1, two infusions of BsAbs induced marked and sustained suppression in serum HBsAg levels and also reduced the numbers of HBV-positive hepatocytes. These findings highlighted the therapeutic potential of TCR-like BsAbs as a new strategy to cure hepatitis B.
DOI: 10.6084/m9.figshare.26509458.v1
title: TCR-like bispecific antibodies toward eliminating infected hepatocytes in HBV mouse models

description: Therapeutics for eradicating hepatitis B virus (HBV) infection are still limited and current nucleos(t)ide analogs (NAs) and interferon are effective in controlling viral replication and improving liver health, but they cannot completely eradicate the hepatitis B virus and only a very small number of patients are cured of it. The TCR-like antibodies recognizing viral peptides presented on human leukocyte antigens (HLA) provide possible tools for targeting and eliminating HBV-infected hepatocytes. Here, we generated three TCR-like antibodies targeting three different HLA-A2.1-presented peptides derived from HBV core and surface proteins. Bispecific antibodies (BsAbs) were developed by fuzing variable fragments of these TCR-like mAbs with an anti-CD3ϵ antibody. Our data demonstrate that the BsAbs could act as T cell engagers, effectively redirecting and activating T cells to target HBV-infected hepatocytes <i>in vitro</i> and <i>in vivo</i>. In HBV-persistent mice expressing human HLA-A2.1, two infusions of BsAbs induced marked and sustained suppression in serum HBsAg levels and also reduced the numbers of HBV-positive hepatocytes. These findings highlighted the therapeutic potential of TCR-like BsAbs as a new strategy to cure hepatitis B.
DOI: 10.25549/webster-c100-44450
title: Manual of the Los Angeles Police Department, 1992

description: The Los Angeles Police Department's departmental manual, 1992. PART OF SERIES: The series includes materials related to the performance of the LAPD prior to and during the 1992 Los Angeles riots. Included are reports and documents pertaining to the department's tactical planning measures for unusual occurrences and emergencies; riot-related statistics and figures; and arrest logs, incident logs, and activities reports maintained during the riots.