cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.27060509.v2
title: Copper sensing transcription factor ArsR2 regulates VjbR to sustain virulence in <i>Brucella abortus</i>

description: Brucellosis, caused by the intracellular pathogen <i>Brucella</i>, is a major zoonotic infection that promotes reproductive disease in domestic animals and chronic debilitating conditions in humans. The ArsR family of transcriptional regulators plays key roles in diverse cellular processes, including metal ion homeostasis, responding to adverse conditions, and virulence. However, little is known about the function of ArsR family members in <i>Brucella</i>. Here, we identified ArsR2 as a nonclassical member of the family that lacks autoregulatory function, but which nevertheless plays a vital role in maintaining copper homeostasis in <i>B. abortus</i>. ArsR2 is a global regulator of 241 genes, including those involved in the VirB type IV secretion system (T4SS). Significantly, ArsR2 regulates T4SS production in <i>B. abortus</i> by targeting VjbR which encodes a LuxR-type family transcriptional regulator. Moreover, copper modulates transcriptional activity of ArsR2, but not of VjbR. Furthermore, deletion of <i>arsR2</i> attenuated virulence in a mouse model. Collectively, these findings enhance understanding of the mechanism by which ArsR proteins regulate virulence gene expression in pathogenic <i>Brucella</i> species.
DOI: 10.25549/webster-c100-77372
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.
DOI: 10.6084/m9.figshare.27060509.v1
title: Copper Sensing Transcription Factor ArsR2 Regulates VjbR to Sustain Virulence in <i>Brucella abortus</i>

description: Brucellosis, caused by the intracellular pathogen <i>Brucella</i>, is a major zoonotic infection that promotes reproductive disease in domestic animals and chronic debilitating conditions in humans. The ArsR family of transcriptional regulators plays key roles in diverse cellular processes, including metal ion homeostasis, responding to adverse conditions, and virulence. However, little is known about the function of ArsR family members in <i>Brucella</i>. Here, we identified ArsR2 as a nonclassical member of the family that lacks autoregulatory function, but which nevertheless plays a vital role in maintaining copper homeostasis in <i>B. abortus</i>. ArsR2 is a global regulator of 241 genes, including those involved in the VirB type IV secretion system (T4SS). Significantly, ArsR2 regulates T4SS production in <i>B. abortus</i> by targeting VjbR which encodes a LuxR-type family transcriptional regulator. Moreover, copper modulates transcriptional activity of ArsR2, but not of VjbR. Furthermore, deletion of <i>arsR2</i> attenuated virulence in a mouse model. Collectively, these findings enhance understanding of the mechanism by which ArsR proteins regulate virulence gene expression in pathogenic <i>Brucella</i> species.
DOI: 10.25549/webster-c100-77355
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.
DOI: 10.6084/m9.figshare.25347879
title: Effective and targeted latency reversal in CD4<sup>+</sup> T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection

description: To date, an affordable, effective treatment for an HIV-1 cure remains only a concept with most “latency reversal” agents (LRAs) lacking specificity for the latent HIV-1 reservoir and failing in early clinical trials. We assessed HIV-1 latency reversal using a multivalent HIV-1-derived virus-like particle (HLP) to treat samples from 32 people living with HIV-1 (PLWH) in Uganda, US and Canada who initiated combined antiretroviral therapy (cART) during chronic infection. Even after 5–20 years on stable cART, HLP could target CD4<sup>+</sup> T cells harbouring latent HIV-1 reservoir resulting in 100-fold more HIV-1 release into culture supernatant than by common recall antigens, and 1000-fold more than by chemotherapeutic LRAs. HLP induced release of a divergent and replication-competent HIV-1 population from PLWH on cART. These findings suggest HLP provides a targeted approach to reactivate the majority of latent HIV-1 proviruses among individuals infected with HIV-1.
DOI: 10.6084/m9.figshare.25347879.v2
title: Effective and targeted latency reversal in CD4<sup>+</sup> T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection

description: To date, an affordable, effective treatment for an HIV-1 cure remains only a concept with most “latency reversal” agents (LRAs) lacking specificity for the latent HIV-1 reservoir and failing in early clinical trials. We assessed HIV-1 latency reversal using a multivalent HIV-1-derived virus-like particle (HLP) to treat samples from 32 people living with HIV-1 (PLWH) in Uganda, US and Canada who initiated combined antiretroviral therapy (cART) during chronic infection. Even after 5–20 years on stable cART, HLP could target CD4<sup>+</sup> T cells harbouring latent HIV-1 reservoir resulting in 100-fold more HIV-1 release into culture supernatant than by common recall antigens, and 1000-fold more than by chemotherapeutic LRAs. HLP induced release of a divergent and replication-competent HIV-1 population from PLWH on cART. These findings suggest HLP provides a targeted approach to reactivate the majority of latent HIV-1 proviruses among individuals infected with HIV-1.
DOI: 10.6084/m9.figshare.25404101
title: Genomic epidemiology and ceftazidime-avibactam high-level resistance mechanisms of <i>Pseudomonas aeruginosa</i> in China from 2010 to 2022

description: Ceftazidime-avibactam (CZA) resistance is a huge threat in the clinic; however, the underlying mechanism responsible for high-level CZA resistance in <i>Pseudomonas aeruginosa</i> (PA) isolates remains unknown. In this study, a total of 5,763 <i>P. aeruginosa</i> isolates were collected from 2010 to 2022 to investigate the ceftazidime-avibactam (CZA) high-level resistance mechanisms of <i>Pseudomonas aeruginosa</i> (PA) isolates in China. Fifty-six PER-producing isolates were identified, including 50 isolates carrying <i>bla</i><sub>PER-1</sub> in PA, and 6 isolates carrying <i>bla</i><sub>PER-4</sub>. Of these, 82.1% (46/56) were classified as DTR-PA isolates, and 76.79% (43/56) were resistant to CZA. Importantly, <i>bla</i><sub>PER-1</sub> and <i>bla</i><sub>PER-4</sub> overexpression led to 16-fold and &gt;1024-fold increases in the MICs of CZA, respectively. WGS revealed that the <i>bla</i><sub>PER-1</sub> gene was located in two different transferable IncP-2-type plasmids and chromosomes, whereas <i>bla</i><sub>PER-4</sub> was found only on chromosomes and was carried by a class 1 integron embedded in a Tn<i>6485</i>-like transposon. Overexpression of efflux pumps may be associated with high-level CZA resistance in <i>bla</i><sub>PER-1</sub>-positive strains. Kinetic parameter analysis revealed that PER-4 exhibited a similar <i>kcat</i>/<i>Km</i> with ceftazidime and a high (∼3359-fold) IC50 value with avibactam compared to PER-1. Our study found that overexpression of PER-1 combined with enhanced efflux pump expression and the low affinity of PER-4 for avibactam contributes to high-level resistance to CZA. Additionally, the Tn<i>6485</i>-like transposon plays a significant role in disseminating <i>bla</i><sub>PER</sub>. Urgent active surveillance is required to prevent the further spread of high-level CZA resistance in DTR-PA isolates.
DOI: 10.6084/m9.figshare.25404101.v1
title: Genomic epidemiology and ceftazidime-avibactam high-level resistance mechanisms of <i>Pseudomonas aeruginosa</i> in China from 2010 to 2022

description: Ceftazidime-avibactam (CZA) resistance is a huge threat in the clinic; however, the underlying mechanism responsible for high-level CZA resistance in <i>Pseudomonas aeruginosa</i> (PA) isolates remains unknown. In this study, a total of 5,763 <i>P. aeruginosa</i> isolates were collected from 2010 to 2022 to investigate the ceftazidime-avibactam (CZA) high-level resistance mechanisms of <i>Pseudomonas aeruginosa</i> (PA) isolates in China. Fifty-six PER-producing isolates were identified, including 50 isolates carrying <i>bla</i><sub>PER-1</sub> in PA, and 6 isolates carrying <i>bla</i><sub>PER-4</sub>. Of these, 82.1% (46/56) were classified as DTR-PA isolates, and 76.79% (43/56) were resistant to CZA. Importantly, <i>bla</i><sub>PER-1</sub> and <i>bla</i><sub>PER-4</sub> overexpression led to 16-fold and &gt;1024-fold increases in the MICs of CZA, respectively. WGS revealed that the <i>bla</i><sub>PER-1</sub> gene was located in two different transferable IncP-2-type plasmids and chromosomes, whereas <i>bla</i><sub>PER-4</sub> was found only on chromosomes and was carried by a class 1 integron embedded in a Tn<i>6485</i>-like transposon. Overexpression of efflux pumps may be associated with high-level CZA resistance in <i>bla</i><sub>PER-1</sub>-positive strains. Kinetic parameter analysis revealed that PER-4 exhibited a similar <i>kcat</i>/<i>Km</i> with ceftazidime and a high (∼3359-fold) IC50 value with avibactam compared to PER-1. Our study found that overexpression of PER-1 combined with enhanced efflux pump expression and the low affinity of PER-4 for avibactam contributes to high-level resistance to CZA. Additionally, the Tn<i>6485</i>-like transposon plays a significant role in disseminating <i>bla</i><sub>PER</sub>. Urgent active surveillance is required to prevent the further spread of high-level CZA resistance in DTR-PA isolates.
DOI: 10.6084/m9.figshare.25905072.v1
title: Emergence of multidrug-resistant <i>Staphylococcus haemolyticus</i> in neonatal intensive care unit in Southern France, a genomic study

description: An emergence of multidrug-resistant (MDR) <i>Staphylococcus haemolyticus</i> has been observed in the neonatal intensive care unit (NICU) of Nîmes University Hospital in southern France. A case–control analysis was conducted on 96 neonates, to identify risk factors associated with <i>S. haemolyticus</i> infection, focusing on clinical outcomes. Forty-eight MDR <i>S. haemolyticus</i> strains, isolated from neonates between October 2019 and July 2022, were investigated using routine <i>in vitro</i> procedures and whole-genome sequencing. Additionally, five <i>S. haemolyticus</i> isolates from adult patients were sequenced to identify clusters circulating within the hospital environment. The incidence of neonatal <i>S. haemolyticus</i> was significantly associated with low birth weight, lower gestational age, and central catheter use (<i>p </i>&lt; 0.001). Sepsis was the most frequent clinical manifestation in this series (20/46, 43.5%) and was associated with five deaths. Based on whole-genome analysis, three <i>S. haemolyticus</i> genotypes were predicted: ST1 (6/53, 11%), ST25 (3/53, 5.7%), and ST29 (44/53, 83%), which included the subcluster II-A, predominantly emerging in the neonatal department. All strains were profiled <i>in silico</i> to be resistant to methicillin, erythromycin, aminoglycosides, and fluoroquinolones, consistent with <i>in vitro</i> antibiotic susceptibility tests. Moreover, <i>in silico</i> prediction of biofilm formation and virulence-encoding genes supported the association of ST29 with severe clinical outcomes, while the persistence in the NICU could be explained by the presence of antiseptic and heavy metal resistance-encoding genes. The clonality of <i>S. haemolyticus</i> ST29 subcluster II-A isolates confirms healthcare transmission causing severe infections. Based on these results, reinforced hygiene measures are necessary to eradicate the nosocomial transmission of MDR strains.
DOI: 10.6084/m9.figshare.25905072
title: Emergence of multidrug-resistant <i>Staphylococcus haemolyticus</i> in neonatal intensive care unit in Southern France, a genomic study

description: An emergence of multidrug-resistant (MDR) <i>Staphylococcus haemolyticus</i> has been observed in the neonatal intensive care unit (NICU) of Nîmes University Hospital in southern France. A case–control analysis was conducted on 96 neonates, to identify risk factors associated with <i>S. haemolyticus</i> infection, focusing on clinical outcomes. Forty-eight MDR <i>S. haemolyticus</i> strains, isolated from neonates between October 2019 and July 2022, were investigated using routine <i>in vitro</i> procedures and whole-genome sequencing. Additionally, five <i>S. haemolyticus</i> isolates from adult patients were sequenced to identify clusters circulating within the hospital environment. The incidence of neonatal <i>S. haemolyticus</i> was significantly associated with low birth weight, lower gestational age, and central catheter use (<i>p </i>&lt; 0.001). Sepsis was the most frequent clinical manifestation in this series (20/46, 43.5%) and was associated with five deaths. Based on whole-genome analysis, three <i>S. haemolyticus</i> genotypes were predicted: ST1 (6/53, 11%), ST25 (3/53, 5.7%), and ST29 (44/53, 83%), which included the subcluster II-A, predominantly emerging in the neonatal department. All strains were profiled <i>in silico</i> to be resistant to methicillin, erythromycin, aminoglycosides, and fluoroquinolones, consistent with <i>in vitro</i> antibiotic susceptibility tests. Moreover, <i>in silico</i> prediction of biofilm formation and virulence-encoding genes supported the association of ST29 with severe clinical outcomes, while the persistence in the NICU could be explained by the presence of antiseptic and heavy metal resistance-encoding genes. The clonality of <i>S. haemolyticus</i> ST29 subcluster II-A isolates confirms healthcare transmission causing severe infections. Based on these results, reinforced hygiene measures are necessary to eradicate the nosocomial transmission of MDR strains.
DOI: 10.6084/m9.figshare.26936455
title: African swine fever virus modulates the endoplasmic reticulum stress-ATF6-calcium axis to facilitate viral replication

description: African swine fever (ASF), caused by African swine fever virus (ASFV), is a devastating infectious disease of domestic pigs and wild boar, which threatens the global pig industry. Endoplasmic reticulum (ER) is a multifunctional signaling organelle in eukaryotic cells that is involved in protein synthesis, processing, posttranslational modification and quality control. As intracellular parasitic organisms, viruses have evolved several strategies to modulate ER functions to favor their life cycles. We have previously demonstrated that the differentially expressed genes associated with unfolded protein response (UPR), which represents a response to ER stress, are significantly enriched upon ASFV infection. However, the correlation between the ER stress or UPR and ASFV replication has not been illuminated yet. Here, we demonstrated that ASFV infection induces ER stress both in target cells and <i>in vivo</i>, and subsequently activates the activating transcription factor 6 (ATF6) branch of the UPR to facilitate viral replication. Mechanistically, ASFV infection disrupts intracellular calcium (Ca<sup>2+</sup>) homeostasis, while the ATF6 pathway facilitates ASFV replication by increasing the cytoplasmic Ca<sup>2+</sup> level. More specifically, we demonstrated that ASFV infection triggers ER-dependent Ca<sup>2+</sup> release <i>via</i> the inositol triphosphate receptor (IP3R) channel. Notably, we showed that the ASFV B117L protein plays crucial roles in ER stress and the downstream activation of the ATF6 branch, as well as the disruption of Ca<sup>2+</sup> homeostasis. Taken together, our findings reveal for the first time that ASFV modulates the ER stress-ATF6-Ca<sup>2+</sup> axis to facilitate viral replication, which provides novel insights into the development of antiviral strategies for ASFV.
DOI: 10.6084/m9.figshare.26936455.v2
title: African swine fever virus modulates the endoplasmic reticulum stress-ATF6-calcium axis to facilitate viral replication

description: African swine fever (ASF), caused by African swine fever virus (ASFV), is a devastating infectious disease of domestic pigs and wild boar, which threatens the global pig industry. Endoplasmic reticulum (ER) is a multifunctional signaling organelle in eukaryotic cells that is involved in protein synthesis, processing, posttranslational modification and quality control. As intracellular parasitic organisms, viruses have evolved several strategies to modulate ER functions to favor their life cycles. We have previously demonstrated that the differentially expressed genes associated with unfolded protein response (UPR), which represents a response to ER stress, are significantly enriched upon ASFV infection. However, the correlation between the ER stress or UPR and ASFV replication has not been illuminated yet. Here, we demonstrated that ASFV infection induces ER stress both in target cells and <i>in vivo</i>, and subsequently activates the activating transcription factor 6 (ATF6) branch of the UPR to facilitate viral replication. Mechanistically, ASFV infection disrupts intracellular calcium (Ca<sup>2+</sup>) homeostasis, while the ATF6 pathway facilitates ASFV replication by increasing the cytoplasmic Ca<sup>2+</sup> level. More specifically, we demonstrated that ASFV infection triggers ER-dependent Ca<sup>2+</sup> release <i>via</i> the inositol triphosphate receptor (IP3R) channel. Notably, we showed that the ASFV B117L protein plays crucial roles in ER stress and the downstream activation of the ATF6 branch, as well as the disruption of Ca<sup>2+</sup> homeostasis. Taken together, our findings reveal for the first time that ASFV modulates the ER stress-ATF6-Ca<sup>2+</sup> axis to facilitate viral replication, which provides novel insights into the development of antiviral strategies for ASFV.
DOI: 10.25549/webster-c100-45734
title: Daily worksheets, Hollenbeck, 1992-04-29

description: Daily worksheets maintained by the Los Angeles Police Department's Hollenbeck area, 1992 April 29 - May 3, 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
DOI: 10.6084/m9.figshare.26936455.v1
title: African Swine Fever Virus Modulates the Endoplasmic Reticulum Stress-ATF6-Calcium Axis to Facilitate Viral Replication

description: African swine fever (ASF), caused by African swine fever virus (ASFV), is a devastating infectious disease of domestic pigs and wild boar, which threatens the global pig industry. The endoplasmic reticulum (ER) is a multifunctional signaling organelle in eukaryotic cells that is involved in protein synthesis, processing, posttranslational modification and quality control. As intracellular parasitic organisms, viruses have evolved several strategies to modulate ER functions to favor their life cycles. We have previously demonstrated that the differentially expressed genes associated with the unfolded protein response (UPR) (downstream the ER stress) are significantly enriched upon ASFV infection. However, the correlation between the ER stress or UPR and ASFV replication has not been illuminated yet. Here, we demonstrated that ASFV infection induces ER stress both in target cells and <i>in vivo</i>, and subsequently activates the activating transcription factor 6 (ATF6) branch of the UPR to facilitate viral replication. Mechanistically, ASFV infection disrupts intracellular calcium (Ca<sup>2+</sup>) homeostasis, while the ATF6 pathway facilitates ASFV replication by increasing the cytoplasmic Ca<sup>2+</sup> level. More specifically, we demonstrated that ASFV infection triggers ER-dependent Ca<sup>2+</sup> release via the inositol triphosphate receptor (IP3R) channel. Notably, we showed that the ASFV B117L protein plays crucial roles in ER stress and the downstream activation of the ATF6 branch, as well as the disruption of Ca<sup>2+</sup> homeostasis. Taken together, our findings reveal for the first time that ASFV modulates the ER stress-ATF6-Ca<sup>2+</sup> axis to facilitate viral replication, which provides novel insights into the development of antiviral strategies for ASFV.
DOI: 10.6084/m9.figshare.25957687
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.