cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.5061/dryad.t2m14v1
title: Data from: Is it the song or the singers? Acoustic and social experiences shape adult reproductive tactics and condition

description: When sexual signals are perceived during growth and development they can
 provide information regarding the social conditions likely to be
 encountered as an adult. Perception of cues related to the presence and
 density of future mates and potential competitors can result in altered
 adult phenotypes. Previous studies have shown that adult male Teleogryllus
 oceanicus field crickets from a Kauai, Hawaii population reared alone and
 without hearing conspecific song are more phonotactic than those reared
 with song. These naïve males also reduce investment in body size and
 immunity. Here we examined whether another source of population density
 information, the presence of other males, affects behavior, size, and
 immunity. Specifically, we examined satellite behavior as evidenced by
 strength of phonotaxis, body condition, and immune response in males
 reared singly and in groups in the presence and absence of conspecific
 song. Body condition did not vary with rearing density, and immune
 response did not vary with either acoustic environment or rearing density.
 Interestingly, group-housed males were more phonotactic than singly-housed
 males. This pattern was largely driven by the low levels of phonotaxis
 exhibited by males that were singly-housed in the presence of conspecific
 song. These findings suggest that males respond to social cues in addition
 to conspecific song, but that these cues do not necessarily provide
 concordant information.
description: Balenger_cricket_density_dataForDataDryad.xlsx
DOI: 10.6084/m9.figshare.27959615
title: The E3 ligase RAD18-mediated ubiquitination of henipavirus matrix protein promotes its nuclear-cytoplasmic trafficking and viral egress

description: The nuclear-cytoplasmic trafficking of matrix proteins (M) is essential for henipavirus budding, with M protein ubiquitination playing a pivotal role in this dynamic process. Despite its importance, the intricacies of the M ubiquitination cascade have remained elusive. In this study, we elucidate a novel mechanism by which Nipah virus (NiV), a highly pathogenic henipavirus, utilizes a ubiquitination complex involving the E2 ubiquitin-conjugating enzyme RAD6A and the E3 ubiquitin ligase RAD18 to ubiquitinate the virus's M protein, thereby facilitating its nuclear-cytoplasmic trafficking. We demonstrate that RAD18 interacts with RAD6A, enabling the latter to supply ubiquitins for the RAD18-mediated transfer of ubiquitin to M through RAD18-M interactions. Specifically, M is ubiquitinated by the RAD6A-RAD18 complex at lysine (K) 258 through a K63-linked ubiquitination, a modification crucial for M's function. This ubiquitination drives M's relocation to the cytoplasm, directing it to plasma membranes for effective viral egress. Conversely, disrupting the RAD6A-RAD18-M axis, mutating RAD18′s E3 ligase activity, or inhibiting RAD6A activity with TZ9 (a RAD6-ubiquitin thioester formation inhibitor) impairs M ubiquitination, resulting in defective nuclear export and budding of NiV. Significantly, live NiV and Hendra virus infection is attenuated in RAD18 knockout cells or in cells treated with TZ9, highlighting the critical physiological role of RAD6A-RAD18-mediated M ubiquitination in the henipavirus life cycle. Our findings not only reveal how NiV manipulates a nucleus-localized ubiquitination complex to promote virus's M protein ubiquitination and nuclear export, but also suggest that the small molecule inhibitor TZ9 could serve as a potential therapeutic against henipavirus infection.
DOI: 10.6084/m9.figshare.27959615.v1
title: The E3 ligase RAD18-mediated ubiquitination of henipavirus matrix protein promotes its nuclear-cytoplasmic trafficking and viral egress

description: The nuclear-cytoplasmic trafficking of matrix proteins (M) is essential for henipavirus budding, with M protein ubiquitination playing a pivotal role in this dynamic process. Despite its importance, the intricacies of the M ubiquitination cascade have remained elusive. In this study, we elucidate a novel mechanism by which Nipah virus (NiV), a highly pathogenic henipavirus, utilizes a ubiquitination complex involving the E2 ubiquitin-conjugating enzyme RAD6A and the E3 ubiquitin ligase RAD18 to ubiquitinate the virus's M protein, thereby facilitating its nuclear-cytoplasmic trafficking. We demonstrate that RAD18 interacts with RAD6A, enabling the latter to supply ubiquitins for the RAD18-mediated transfer of ubiquitin to M through RAD18-M interactions. Specifically, M is ubiquitinated by the RAD6A-RAD18 complex at lysine (K) 258 through a K63-linked ubiquitination, a modification crucial for M's function. This ubiquitination drives M's relocation to the cytoplasm, directing it to plasma membranes for effective viral egress. Conversely, disrupting the RAD6A-RAD18-M axis, mutating RAD18′s E3 ligase activity, or inhibiting RAD6A activity with TZ9 (a RAD6-ubiquitin thioester formation inhibitor) impairs M ubiquitination, resulting in defective nuclear export and budding of NiV. Significantly, live NiV and Hendra virus infection is attenuated in RAD18 knockout cells or in cells treated with TZ9, highlighting the critical physiological role of RAD6A-RAD18-mediated M ubiquitination in the henipavirus life cycle. Our findings not only reveal how NiV manipulates a nucleus-localized ubiquitination complex to promote virus's M protein ubiquitination and nuclear export, but also suggest that the small molecule inhibitor TZ9 could serve as a potential therapeutic against henipavirus infection.
DOI: 10.6084/m9.figshare.28624573
title: Genomic characterization of invasive <i>Neisseria meningitidis</i> in Spain (2011/12–2022/23): expansion of clonal complex 213 and the potential threat to 4CMenB vaccine strain coverage

description: Invasive meningococcal disease (IMD) is associated with significant global morbidity and mortality and is addressed by conjugated polysaccharide and subcapsular vaccines. In Spain, data on 4CMenB vaccine strain coverage and antimicrobial susceptibility are limited. This study aimed to describe the genomic epidemiology, predict 4CMenB vaccine strain coverage, and assess antimicrobial susceptibility of 323 <i>Neisseria meningitidis</i> isolates causing IMD, collected from 57 Clinical Microbiology Laboratories in Spain over 12 years (2011/12–2022/23). Whole genome sequencing was performed to identify serogroup, clonal complex (cc), and antimicrobial resistance determinants. Vaccine strain coverage for serogroup B (MenB) isolates was predicted using the genetic Meningococcal Antigen Typing System approach. The most prevalent serogroups were B (57.9%), W (21.4%), C (10.4%), and Y (8.4%). MenB predominated throughout most seasons, except during the 2019/20 season when serogroup W peaked. Post-COVID-19 pandemic, MenB remained the most frequent (70.2%). Thirteen cc were identified among MenB isolates, with cc213 being the most prevalent (40.1%). Only 28.9% of MenB isolates were predicted to be covered by 4CMenB, with cc213 showing an exceptionally low coverage rate (5.3%) due to antigenic variants poorly targeted by the vaccine. Notably, cc213 was responsible for twice the proportion of MenB cases in 4CMenB-vaccinated versus unvaccinated. All isolates were susceptible to third generation cephalosporins, and 13.5% showed penicillin resistance. This study highlights the alarming prevalence of cc213 among MenB IMD cases in Spain and the limited 4CMenB coverage against this cc. The disproportionate representation of cc213 in vaccinated individuals underscores its potential to compromise vaccine effectiveness.
DOI: 10.6084/m9.figshare.28624573.v4
title: Genomic characterization of invasive <i>Neisseria meningitidis</i> in Spain (2011/12–2022/23): expansion of clonal complex 213 and the potential threat to 4CMenB vaccine strain coverage

description: Invasive meningococcal disease (IMD) is associated with significant global morbidity and mortality and is addressed by conjugated polysaccharide and subcapsular vaccines. In Spain, data on 4CMenB vaccine strain coverage and antimicrobial susceptibility are limited. This study aimed to describe the genomic epidemiology, predict 4CMenB vaccine strain coverage, and assess antimicrobial susceptibility of 323 <i>Neisseria meningitidis</i> isolates causing IMD, collected from 57 Clinical Microbiology Laboratories in Spain over 12 years (2011/12–2022/23). Whole genome sequencing was performed to identify serogroup, clonal complex (cc), and antimicrobial resistance determinants. Vaccine strain coverage for serogroup B (MenB) isolates was predicted using the genetic Meningococcal Antigen Typing System approach. The most prevalent serogroups were B (57.9%), W (21.4%), C (10.4%), and Y (8.4%). MenB predominated throughout most seasons, except during the 2019/20 season when serogroup W peaked. Post-COVID-19 pandemic, MenB remained the most frequent (70.2%). Thirteen cc were identified among MenB isolates, with cc213 being the most prevalent (40.1%). Only 28.9% of MenB isolates were predicted to be covered by 4CMenB, with cc213 showing an exceptionally low coverage rate (5.3%) due to antigenic variants poorly targeted by the vaccine. Notably, cc213 was responsible for twice the proportion of MenB cases in 4CMenB-vaccinated versus unvaccinated. All isolates were susceptible to third generation cephalosporins, and 13.5% showed penicillin resistance. This study highlights the alarming prevalence of cc213 among MenB IMD cases in Spain and the limited 4CMenB coverage against this cc. The disproportionate representation of cc213 in vaccinated individuals underscores its potential to compromise vaccine effectiveness.
DOI: 10.6084/m9.figshare.28624573.v3
title: Genomic characterisation of invasive <i>Neisseria meningitidis</i> in Spain (2011/12-2022/23): Expansion of clonal complex 213 and the potential threat to 4CMenB vaccine strain coverage.

description: Invasive meningococcal disease (IMD) is associated with significant global morbidity and mortality and is addressed by conjugated polysaccharide and subcapsular vaccines. In Spain, data on 4CMenB vaccine strain coverage and antimicrobial susceptibility are limited. This study aimed to describe the genomic epidemiology, predict 4CMenB vaccine strain coverage, and assess antimicrobial susceptibility of 323 <i>Neisseria meningitidis</i> isolates causing IMD, collected from 57 Clinical Microbiology Laboratories in Spain over 12 years (2011/12-2022/23). Whole genome sequencing was performed to identify serogroup, clonal complex (cc), and antimicrobial resistance determinants. Vaccine strain coverage for serogroup B (MenB) isolates was predicted using the genetic Meningococcal Antigen Typing System approach. The most prevalent serogroups were B (57.9%), W (21.4%), C (10.4%), and Y (8.4%). MenB predominated throughout most seasons, except during the 2019/20 season when serogroup W peaked. Post-COVID-19 pandemic, MenB remained the most frequent (70.2%). Thirteen cc were identified among MenB isolates, with cc213 being the most prevalent (40.1%). Only 28.9% of MenB isolates were predicted to be covered by 4CMenB, with cc213 showing an exceptionally low coverage rate (5.3%) due to antigenic variants poorly targeted by the vaccine. Notably, cc213 was responsible for twice the proportion of MenB cases in 4CMenB-vaccinated versus unvaccinated. All isolates were susceptible to third generation cephalosporins, and 13.5% showed penicillin resistance. This study highlights the alarming prevalence of cc213 among MenB IMD cases in Spain and the limited 4CMenB coverage against this cc. The disproportionate representation of cc213 in vaccinated individuals underscores its potential to compromise vaccine effectiveness.
DOI: 10.6084/m9.figshare.29869116
title: Two-threshold defined immune non-responders are associated with long-term morbidity in people with HIV: a prospective cohort study

description: A substantial proportion of people with HIV (PWH) fail to achieve full immune recovery despite long-term antiretroviral therapy (ART), potentially increasing their risk of serious comorbidities. This study investigated the association between immune non-responder (INR) and the incidence of AIDS-defining diseases (ADs) and non-AIDS-defining diseases (NADs) in a prospective cohort at the Third People's Hospital of Shenzhen, China. The low – and high-threshold cohorts included 7,874 and 8,077 individuals with baseline CD4<sup>+</sup> T-cell counts &lt; 350 and &lt; 500cells/μL, respectively. INR was defined as failure to reach CD4<sup>+</sup> T-cell thresholds (350 or 500 cells/μL) in two consecutive measurements during follow-up. Kaplan-Meier curves and Cox proportional hazards models were used to assess associations. Median follow-up after immune classification was 49.4 and 42.2 months in the low – and high-threshold cohorts, respectively. In the low-threshold cohort, INR was independently associated with significantly increased risks of ADs, including pneumocystis pneumonia (adjusted hazard ratio [aHR], 10.10; 95% confidence interval [CI]: 4.94–20.70), talaromycosis marneffei (aHR, 7.38; 95% CI: 3.51–15.50), and AIDs-defining cancers (aHR, 3.67; 95% CI: 1.20–11.20); and NADs, including end-stage liver disease (aHR, 15.00; 95% CI: 5.59–40.00), cardiovascular disease (aHR, 3.83; 95% CI: 2.14–6.87), chronic kidney disease (aHR, 1.78; 95% CI: 1.23–2.58), and non-AIDS-defining cancers (aHR, 4.75; 95% CI: 2.31–9.74). Similar associations were observed in the high-threshold cohort. INR is strongly associated with long-term morbidity in PWH. These findings highlight the need for improved risk assessment beyond CD4<sup>+</sup> T-cell monitoring to reduce disease burden in PWH.
DOI: 10.6084/m9.figshare.29869116.v1
title: Two-threshold defined immune non-responders are associated with long-term morbidity in people with HIV: a prospective cohort study

description: A substantial proportion of people with HIV (PWH) fail to achieve full immune recovery despite long-term antiretroviral therapy (ART), potentially increasing their risk of serious comorbidities. This study investigated the association between immune non-responder (INR) and the incidence of AIDS-defining diseases (ADs) and non-AIDS-defining diseases (NADs) in a prospective cohort at the Third People's Hospital of Shenzhen, China. The low – and high-threshold cohorts included 7,874 and 8,077 individuals with baseline CD4<sup>+</sup> T-cell counts &lt; 350 and &lt; 500cells/μL, respectively. INR was defined as failure to reach CD4<sup>+</sup> T-cell thresholds (350 or 500 cells/μL) in two consecutive measurements during follow-up. Kaplan-Meier curves and Cox proportional hazards models were used to assess associations. Median follow-up after immune classification was 49.4 and 42.2 months in the low – and high-threshold cohorts, respectively. In the low-threshold cohort, INR was independently associated with significantly increased risks of ADs, including pneumocystis pneumonia (adjusted hazard ratio [aHR], 10.10; 95% confidence interval [CI]: 4.94–20.70), talaromycosis marneffei (aHR, 7.38; 95% CI: 3.51–15.50), and AIDs-defining cancers (aHR, 3.67; 95% CI: 1.20–11.20); and NADs, including end-stage liver disease (aHR, 15.00; 95% CI: 5.59–40.00), cardiovascular disease (aHR, 3.83; 95% CI: 2.14–6.87), chronic kidney disease (aHR, 1.78; 95% CI: 1.23–2.58), and non-AIDS-defining cancers (aHR, 4.75; 95% CI: 2.31–9.74). Similar associations were observed in the high-threshold cohort. INR is strongly associated with long-term morbidity in PWH. These findings highlight the need for improved risk assessment beyond CD4<sup>+</sup> T-cell monitoring to reduce disease burden in PWH.
DOI: 10.6084/m9.figshare.28615131
title: Hypermutability of <i>Mycolicibacterium smegmatis</i> due to ribonucleotide reductase-mediated oxidative homeostasis and imbalanced dNTP pools

description: Ribonucleotide reductase (RNR) catalyzes the synthesis of four deoxyribonucleoside triphosphates (dNTPs), which are essential for DNA replication. Although dNTP imbalances reduce replication fidelity and elevate mutation rates, the impact of RNR dysfunction on Mycobacterium tuberculosis (Mtb) physiology and drug resistance remains unknown. Here, we constructed inducible knockdown strains for the RNR R1 subunit NrdE in Mtb and Mycolicibacterium smegmatis (Msm). NrdE knockdown significantly impaired growth and metabolic imbalances, indirectly disrupting oxidative homeostasis and mycolic acid synthesis, while increasing levels of intracellular ROS accumulation and enhancing cell wall permeability. Additionally, we developed genomic mutant strains, Msm-Y252A and Msm-Q255A, featuring targeted point mutations in the substrate-specific site (S-site) of the RNR loop domain, which determines NDP reduction specificity. The Msm-Y252A displayed a 1.9-fold decrease in dATP and increases in dGTP (1.6-fold), dTTP (9.0-fold), and dCTP (1.3-fold). In contrast, Msm-Q255A exhibited elevated intracellular levels of dGTP (1.6-fold), dTTP (6.1-fold), and dATP (1.5-fold), while dCTP levels remained unchanged. Neither the NrdE knockdown strain nor the S-site mutants exhibited direct resistance development; however, they both showed genomic instability, enhancing the emergence of rifampicin-resistant mutants, even with a 70-fold and a 25-fold increase in mutation frequency for Msm-Y252A and Msm-Q255A, respectively. This study demonstrates that NrdE is integral to Mycobacterium survival and genomic stability and that its RNR dysfunction creates a mutagenic environment under selective pressure, indirectly contributes to the development of drug resistance, positioning NrdE as an effective target for therapeutic strategies and a valuable molecular marker for early detection of drug-resistant Mtb.
DOI: 10.6084/m9.figshare.28563717
title: Evidence of Mpox clade IIb infection in primary human alveolar epithelium

description: Monkeypox virus (Mpox) has been recognized for causing distinct skin lesions and is primarily transmitted through skin and sexual contact. To date, the transmissibility and pathogenesis of the Mpox virus in distal human lung has never been completely explored. Here the transmission pathways and Mpox tropism on patient-derived air-liquid epithelium (ALE) model fabricated using isolated primary human alveolar epithelial cells (hAECs) were investigated. hAECs were cultured and exposed to the Mpox virus clade IIb isolated from the patient. DNA, proteins, and the tropism were elucidated using polymerase chain reaction (PCR), Western blot, and high-content fluorescent imaging. Transmission electron microscopy (TEM) was employed to systematically observe the cellular distribution of viral particles. Viral titres were determined by TCID<sub>50</sub> assay. Innate immune response and inflammatory mediators were measured using Milliplex® multiplex and ELISA analysis. Pathology at alveolar barrier integrity was determined using transepithelial electrical resistance (TEER) analysis. The study included mock-infected cells as control. Mpox virus significantly infected 42.82% of total hAEC populations. The prominent observed pathology included a significant reduction in TEER values, loss of tight junction protein, presence of tunnelling nanotubes (TNTs), and syncytium morphology. Four stages of Mpox biogenesis were clearly observed without significant activation of IL-6, MIP1alpha, TNF-α, and Galectin-9, although IL-1β were subtly promoted. The developed patient-derived ALE is a versatile model for Mpox virus clade IIb infection reflecting respiratory transmission competence of the Mpox. Postinfection lung pathogenesis demonstrated alveolar barrier damage without significant inflammation, raising concerns about possible immune evasion by the virus.
DOI: 10.6084/m9.figshare.28563717.v3
title: Evidence of Mpox clade IIb infection in primary human alveolar epithelium

description: Monkeypox virus (Mpox) has been recognized for causing distinct skin lesions and is primarily transmitted through skin and sexual contact. To date, the transmissibility and pathogenesis of the Mpox virus in distal human lung has never been completely explored. Here the transmission pathways and Mpox tropism on patient-derived air-liquid epithelium (ALE) model fabricated using isolated primary human alveolar epithelial cells (hAECs) were investigated. hAECs were cultured and exposed to the Mpox virus clade IIb isolated from the patient. DNA, proteins, and the tropism were elucidated using polymerase chain reaction (PCR), Western blot, and high-content fluorescent imaging. Transmission electron microscopy (TEM) was employed to systematically observe the cellular distribution of viral particles. Viral titres were determined by TCID<sub>50</sub> assay. Innate immune response and inflammatory mediators were measured using Milliplex® multiplex and ELISA analysis. Pathology at alveolar barrier integrity was determined using transepithelial electrical resistance (TEER) analysis. The study included mock-infected cells as control. Mpox virus significantly infected 42.82% of total hAEC populations. The prominent observed pathology included a significant reduction in TEER values, loss of tight junction protein, presence of tunnelling nanotubes (TNTs), and syncytium morphology. Four stages of Mpox biogenesis were clearly observed without significant activation of IL-6, MIP1alpha, TNF-α, and Galectin-9, although IL-1β were subtly promoted. The developed patient-derived ALE is a versatile model for Mpox virus clade IIb infection reflecting respiratory transmission competence of the Mpox. Postinfection lung pathogenesis demonstrated alveolar barrier damage without significant inflammation, raising concerns about possible immune evasion by the virus.
DOI: 10.6084/m9.figshare.28615131.v1
title: Hypermutability of <i>Mycolicibacterium smegmatis</i> due to ribonucleotide reductase-mediated oxidative homeostasis and imbalanced dNTP pools

description: Ribonucleotide reductase (RNR) catalyzes the synthesis of four deoxyribonucleoside triphosphates (dNTPs), which are essential for DNA replication. Although dNTP imbalances reduce replication fidelity and elevate mutation rates, the impact of RNR dysfunction on Mycobacterium tuberculosis (Mtb) physiology and drug resistance remains unknown. Here, we constructed inducible knockdown strains for the RNR R1 subunit NrdE in Mtb and Mycolicibacterium smegmatis (Msm). NrdE knockdown significantly impaired growth and metabolic imbalances, indirectly disrupting oxidative homeostasis and mycolic acid synthesis, while increasing levels of intracellular ROS accumulation and enhancing cell wall permeability. Additionally, we developed genomic mutant strains, Msm-Y252A and Msm-Q255A, featuring targeted point mutations in the substrate-specific site (S-site) of the RNR loop domain, which determines NDP reduction specificity. The Msm-Y252A displayed a 1.9-fold decrease in dATP and increases in dGTP (1.6-fold), dTTP (9.0-fold), and dCTP (1.3-fold). In contrast, Msm-Q255A exhibited elevated intracellular levels of dGTP (1.6-fold), dTTP (6.1-fold), and dATP (1.5-fold), while dCTP levels remained unchanged. Neither the NrdE knockdown strain nor the S-site mutants exhibited direct resistance development; however, they both showed genomic instability, enhancing the emergence of rifampicin-resistant mutants, even with a 70-fold and a 25-fold increase in mutation frequency for Msm-Y252A and Msm-Q255A, respectively. This study demonstrates that NrdE is integral to Mycobacterium survival and genomic stability and that its RNR dysfunction creates a mutagenic environment under selective pressure, indirectly contributes to the development of drug resistance, positioning NrdE as an effective target for therapeutic strategies and a valuable molecular marker for early detection of drug-resistant Mtb.