bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of bronchiolitis and vaccine-induced enhanced respiratory disease in Syrian hamsters caused by respiratory syncytial virus infection
Authors: Zhao Binbin , Zhang Gengxin , Wu Jing , Ding Xiaoyue , Wei Xiaohui , Peng Wanjun , Rong Na , Yang Hekai , Liu Jiangning 
Published: July 2024

AbstractRespiratory syncytial virus (RSV) presents a significant health risk to pediatric and old populations. The quest for developing effective RSV vaccines and immunoprophylactic measures remains highly active, while the catastrophic enhanced respiratory disease (ERD) reaction triggered by RSV vaccines poses lingering concerns. Meanwhile, as the basis of vaccine research, the development of animal models of RSV infection has shown less substantial progress, with considerable disparities in immunological and pathological responses compared to humans. The Syrian hamster, which is reported to be susceptible to RSV infection, seems promising, but the lack of in-depth studies has hampered its application. Consequently, we have refined the RSV-infected hamster model by establishing infection models at different ages, reanalyzing virological and pathological data, and applying vaccination with heat-inactivated RSV virus for ERD reaction. In general, neonatal hamsters exhibited the highest level of viral amplification, while old hamsters displayed the most severe pathological manifestations, with adult hamsters in between. Although Syrian hamsters were moderately susceptible to RSV infection, they showed typical pathological changes of bronchitis in all age groups, with adult and old animals even showing clinical signs of coughing. In addition, hamsters demonstrated the typical ERD response to heat-inactivated virus, characterized by the exacerbation of lung injury with extensive neutrophil and eosinophil infiltration, as well as TH2 polarization. Collectively, these characteristics suggest that the Syrian hamster model has significant potential for investigating the pathogenesis of RSV infection, elucidating the mechanism of ERD, and evaluating vaccine efficacy and safety.ImportanceThe Syrian hamster has been shown in our study to be a potential model for respiratory syncytial virus (RSV) infection, according to the following characteristics:Hamsters of three different age groups all developed typical pulmonary bronchiolitis following RSV infection, whereas adult and old hamsters showed typical cough symptoms, comparable to those observed in clinical patients.Hamsters of different ages showed considerable variability. Neonatal hamsters tolerated more viral replication, while old hamsters suffered the most severe pulmonary pathology.Hamsters exhibited typical ERD responses after inoculation with heat-inactivated RSV virus, including enhanced lung pathology, pulmonary eosinophilic and neutrophil infiltration, and Th2 polarization, which was remarkable and more similar to the typical characteristics of the ERD response in humans.
Logan: Planetary-Scale Genome Assembly Surveys Life’s Diversity
Authors: Chikhi Rayan , Raffestin Brice , Korobeynikov Anton , Edgar Robert , Babaian Artem 
Published: July 2024

AbstractThe NCBI Sequence Read Archive (SRA) is the largest public repository of DNA sequencing data, containing the most comprehensive snapshot of Earth’s genetic diversity to date. As its size exceeds 50.0 petabases across >27 million sequencing datasets, the entirety of these data cannot be searched for genetic sequences of interest in a reasonable time. To drastically increase the accessibility of this data we perform genome assembly over each SRA dataset using massively parallel cloud computing. The resulting Logan assemblage is the largest dataset of assembled sequencing data to date, and we believe will enable a new-era of accessible petabase-scale computational biology inquiry. We provide free and unrestricted access to the Logan assemblage and disseminate these datasets to foster early adoption. To illustrate the usefulness of Logan we align a diverse set of sequence queries across all of the SRA, completing queries in as little as 11 hours.
Transcriptome profiling of maize transcription factor mutants to probe gene regulatory network predictions
Authors: Ellison Erika L. , Zhou Peng , Chu Yi-Hsuan , Hermanson Peter , Gomez-Cano Lina , Myers Zachary A. , Abnave Ankita , Gray John , Hirsch Candice N. , Grotewold Erich , Springer Nathan M. 
Published: July 2024

AbstractTranscription factors (TFs) play important roles in regulation of gene expression and phenotype. A variety of approaches have been utilized to develop gene-regulatory networks (GRNs) to predict the regulatory targets for each TF, such as yeast-one-hybrid (Y1H) screens and gene co-expression network (GCN) analysis. Here we identified potential TF targets and used a reverse genetics approach to test the predictions of several GRNs in maize. Loss-of-function mutant alleles were isolated for 22 maize TFs. These mutants did not exhibit obvious morphological phenotypes. However, transcriptomic profiling identified differentially expressed genes in each of the mutant genotypes, and targeted metabolic profiling indicated variable phenolic accumulation in some mutants. An analysis of expression levels for predicted target genes based on Y1H screens identified a small subset of predicted targets that exhibit altered expression levels. The analysis of predicted targets from GCN-based methods found significant enrichments for prediction sets of some TFs, but most predicted targets did not exhibit altered expression. This could result from false-positive GCN predictions, a TF with a secondary regulatory role resulting in minor effects on gene regulation, or redundant gene regulation by other TFs. Collectively, these findings suggest that loss-of-function for single uncharacterized TFs might have limited phenotypic impacts but can reveal subsets of GRN predicted targets with altered expression.
Disrupted Nitric Oxide Homeostasis Impacts Fertility Through Multiple Processes Including Protein Quality Control
Authors: Treffon Patrick , Vierling Elizabeth 
Published: July 2024

AbstractPlant fertility is fundamental to plant survival and requires the coordinated interaction of developmental pathways and signaling molecules. Nitric oxide (NO) is a small gaseous signaling molecule that plays crucial roles in plant fertility as well as other developmental processes and stress responses. NO influences biological processes through S-nitrosation, the posttranslational modification of protein cysteines to S-nitrosocysteine (R-SNO). NO homeostasis is controlled by S-nitrosoglutathione reductase (GSNOR), which reduces S-nitrosoglutathione (GSNO), the major form of NO in cells. GSNOR mutants (hot5-2/gsnor1) have defects in female gametophyte development along with elevated levels of reactive nitrogen species and R-SNOs. To better understand the fertility defects inhot5-2we investigated thein vivonitrosoproteome of floral tissues coupled with quantitative proteomics of pistils. To identify protein-SNOs we employed, for the first time in plants, an organomercury-based method that involves direct reaction with S-nitrosocysteine, enabling specific identification of S-nitrosocysteine–containing peptides and S-nitrosated proteins. We identified 1102 endogenously S-nitrosated proteins in floral tissues, of which 1049 were unique tohot5-2.Among the identified proteins, 728 were novel S-nitrosation targets. Notably, specific UGT-glycosyltransferases and argonaute proteins are S-nitrosated in floral tissues and differentially regulated in pistils. We also discovered S-nitrosation of proteins of the 26S proteasome together with increased abundance of proteasomal components and enhanced trypsin-like proteasomal activity inhot5-2pistils. Our data establish a new method for nitrosoprotein detection in plants, expand knowledge of the plant S-nitrosoproteome, and suggest that nitro-oxidative modification and NO homeostasis are critical to protein quality control in reproductive tissues.
Identification of Glyoxalase A in Group BStreptococcusand its contribution to methylglyoxal tolerance and virulence
Authors: Akbari Madeline S. , Joyce Luke R. , Spencer Brady L. , Brady Amanda , McIver Kevin S. , Doran Kelly S. 
Published: July 2024

AbstractGroup BStreptococcus(GBS) is a Gram-positive pathobiont that commonly colonizes the gastrointestinal and lower female genital tracts but can cause sepsis and pneumonia in newborns and is a leading cause of neonatal meningitis. Despite the resulting disease severity, the pathogenesis of GBS is not completely understood, especially during the early phases of infection. To investigate GBS factors necessary for blood stream survival, we performed a transposon (Tn) mutant screen in our bacteremia infection model using a GBSmarinertransposon mutant library previously developed by our group. We identified significantly underrepresented mutations in 623 genes that contribute to survival in the blood, including those encoding known virulence factors such as capsule, the β-hemolysin, and inorganic metal ion transport systems. Most of the underrepresented genes have not been previously characterized or studied in GBS, includinggloAandgloB,which are homologs for genes involved in methylglyoxal (MG) detoxification. MG is a byproduct of glycolysis and a highly reactive toxic aldehyde that is elevated in immune cells during infection. Here, we observed MG sensitivity across multiple GBS isolates and confirm thatgloAcontributes to MG tolerance and invasive GBS infection. We show specifically thatgloAcontributes to GBS survival in the presence of neutrophils and depleting neutrophils in mice abrogates the decreased survival and infection of thegloAmutant. The requirement of the glyoxalase pathway during GBS infection suggests that MG detoxification is important for bacterial survival during host-pathogen interactions.
MLCK/MLCP regulates mammalian axon regeneration and redistributes the growth cone F-actin
Authors: Saijilafu  , Wang Wei-Hua , Ma Jin-Jin , Yin Yin , Ma Yan-Xia 
Published: July 2024

AbstractAxon regrowth is a key determinant of the restoration of the biological function of the nervous system after trauma. However, mature mammalian neurons have limited capacity for axon regeneration. We have previously demonstrated that neuronal axon growth both in the central and the peripheral nervous systems is markedly enhanced when non-muscle myosin II (NMII) is inhibited with blebbistatin. The activity of NMII is primarily regulated by MLCK and MLCPviathe phosphorylation and dephosphorylation of its light chain, respectively; however, the functional roles of MLCK and MLCP in mammalian axonal regeneration remain unknown. In the present study, we provide strong evidence that the inhibition of MLCK activity significantly blocks axon regeneration in mice. Conversely, the inhibition of MLCP promotes axon regrowth of both the peripheral and central nervous system. Our findings further indicate that the MLCK/MLCP regulates axon regeneration and redistributes the growth cone F-actin, and this result suggests that direct regulation of the growth cone machinery is a potential strategy to promote axon regeneration.
Receptor Binding Specificity of a Bovine A(H5N1) Influenza Virus
Authors: Chopra Pradeep , Page Caroline K. , Shepard Justin D. , Ray Sean D. , Kandeil Ahmed , Jeevan Trushar , Bowman Andrew S. , Ellebedy Ali H. , Webby Richard J. , de Vries Robert P. , Tompkins S. Mark , Boons Geert-Jan 
Published: July 2024

AbstractOutbreaks in the US of highly pathogenic avian influenza virus (H5N1) in dairy cows have been occurring for months creating new possibilities for direct contact between the virus and humans. Eisfeldet al. examined the pathogenicity and transmissibility of a bovine HPAI H5N1 virus isolated from New Mexico in a series ofin vitroandin vivoassays. They found the virus has a dual human- and avian virus-like receptor-binding specificity as measured in a solid phase glycan binding assay. Here, we examined the receptor specificity of a bovine HPAI H5N1 virus (A/bovine/OH/B24OSU-432/2024, H5N1, clade 2.3.4.4b) employing four different assays including glycan array technology, bio-layer interferometry (BLI), a solid phase capture assay and hemagglutination of glycan remodeled erythrocytes. As controls, well characterized avian (A/Vietnam/1203/2004, H5N1, clade 1) and human (A/CA/04/2009, H1N1) IAVs were included that bind α2,3- and α2,6-sialosides, respectively. We found that A/bovine/OH/B24OSU-432/2024 preferentially binds to “avian type” receptors (α2,3-sialosides). Furthermore, sequence alignments showed that A/bovine has maintained amino acids in its HA associated with α2,3-sialoside (avian) receptor specificity. We conclude that while we find no evidence that A/bovine has acquired human virus receptor binding specificity, ongoing efforts must be placed on monitoring for this trait.
Closing the genome ofTeredinibacter turneraeT7902 by long-read nanopore sequencing
Authors: Gasser Mark T. , Liu Annie , Flatau Ron , Altamia Marvin , Filone Claire Marie , Distel Dan 
Published: July 2024

AbstractWe present the complete closed circular genome sequence derived from Oxford Nanopore sequencing of the shipworm endosymbiontTeredinibacter turneraeT7902 (DSM 15152, ATCC 39867), originally isolated from the shipwormLyrodus pedicellatus(1). This sequence will aid in the comparative genomics of shipworm endosymbionts and the understanding of host-symbiont evolution.
Effect of assortative mating and sexual selection on polygenic barriers to gene flow
Authors: Surendranadh Parvathy , Sachdeva Himani 
Published: July 2024

AbstractAssortative mating and sexual selection are widespread in nature and can play an important role in speciation, through the buildup and maintenance of reproductive isolation (RI). However, their contribution to genome-wide suppression of gene flow during RI is rarely quantified. Here, we consider a polygenic ‘magic’ trait that is divergently selected across two populations connected by migration, while also serving as the basis of assortative mating, thus generating sexual selection on one or both sexes. We obtain theoretical predictions for divergence at individual trait loci by assuming that the effect of all other loci on any locus can be encapsulated via an effective migration rate, which bears a simple relationship to measurable fitness components of migrants and various early generation hybrids. Our analysis clarifies how ‘tipping points’ (characterised by an abrupt collapse of adaptive divergence) arise, and when assortative mating can shift the critical level of migration beyond which divergence collapses. We quantify the relative contributions of viability and sexual selection to genome-wide barriers to gene flow and discuss how these depend on existing divergence levels. Our results suggest that effective migration rates provide a useful way of understanding genomic divergence, even in scenarios involving multiple, interacting mechanisms of RI.
Quorum sensing employs a dual regulatory mechanism to repress T3SS gene expression
Authors: Paul Payel , Podicheti Ram , Geyman Logan J. , Papenfort Kai , van Kessel Julia C. 
Published: July 2024

AbstractThe type III secretion system (T3SS) is a needle-like complex used by numerous bacterial pathogens in host infection by directly injecting exotoxins into the host cell cytoplasm, leading to cell death. The T3SS is a known virulence factor in the shrimp pathogenVibrio campbellii. The ∼40 genes comprising theV. campbelliiT3SS are regulated by a network of transcription factors in response to changes in the cell’s environment: cell density (quorum sensing; QS), temperature, calcium, and host cell contact. Under positive environmental stimuli, the master T3SS transcription factor ExsA activates expression of the four structural T3SS operons required for needle formation. Previous studies identified a key role of the master QS transcription factor LuxR: repression ofexsAtranscription via DNA binding at theexsBApromoter. Here we uncovered a new regulatory role of LuxR: indirect post-translational repression of ExsA activity via direct transcriptional repression of the gene encoding the anti-anti-activator ExsC. InV. campbellii, ExsC is a positive regulator of T3SS transcription: high ExsC expression leads to full ExsA transcription activation of the T3SS structural promoters. LuxR binding at theexsCpromoter represses transcription ofexsCthrough disruption of ExsA binding. Our findings collectively show thatV. campbelliiresponds to high cell density signals to shut down the expression of the T3SS. We postulate that this dual regulatory mechanism by LuxR enables both the rapid inactivation of existing ExsA protein and blocks its further synthesis, leading to a rapid shutdown of T3SS activity at high cell density.ImportanceVibrio campbelliiutilizes the type III secretion system (T3SS) as a mechanism of pathogenesis, which is a highly studied ‘injectisome’ complex that delivers exotoxins into host cells during infection. The T3SS pathogenicity island inV. campbelliicomprises ∼40 genes that are organized into four structural operons. In this study, we determined that quorum sensing – a method of bacterial communication – regulates T3SS genes both at the transcriptional and post-translational levels to shut down T3SS gene expression at high population densities.
Phosphorylation of Zearalenone retains its toxicity
Authors: Asaduzzaman Muhammad , Pavlov Ivan , St-Jean Guillaume , Zhu Yan , Castex Mathieu , Chorfi Younes , del Castillo Jerome R E , Zhou Ting , Alassane-Kpembi Imourana 
Published: July 2024

ABSTRACTMicrobial biotransformation of Zearalenone (ZEN) is a promising deactivation approach. The residual toxicity and stability of Zearalenone-14-phosphate (ZEN-14-P) and Zearalenone-16-phosphate (ZEN-16-P), two novel microbial phosphorylation products of ZEN, remain unknown.We investigated the cytotoxicity, oxidative stress, pro-inflammatory, and estrogenic activity of phosphorylated ZENs using porcine intestinal cells and uterine explants, and human endometrial cells, and traced their metabolic fate by LC-MS/MS analysis.The phosphorylated ZENs significantly decreased the viability of IPEC-J2 and Ishikawa cells. Similar to ZEN, phosphorylation products induced significant oxidative stress, activated the expression of pro-inflammatory cytokines, and demonstrated estrogenic activity through upregulation of estrogen-responsive genes, activation of alkaline phosphatase and proliferation of endometrial glands. LC-MS/MS analysis pointed that although phosphorylated ZENs are partially hydrolyzed to ZEN, their respective metabolic pathways differ. We conclude that phosphorylation might not be sufficient to detoxify ZEN, leaving its cytotoxic, pro-inflammatory and estrogenic properties intact.Graphical abstract
Cryo-EM Structure ofSalmonella typhimuriumArnC; the Key Enzyme in Lipid-A Modification Conferring Polymyxin Resistance
Authors: Patel Dhruvin H. , Karimullina Elina , Guo Yirui , Semper Cameron , Patel Deepak T. , Emde Tabitha , Borek Dominika , Savchenko Alexei 
Published: July 2024

1AbstractPolymyxins are last-resort antimicrobial peptides administered clinically against multi-drug resistant bacteria, including Gram-negative ESKAPE pathogens. However, an increasing number of pathogens employ a defense strategy involving a relay of enzymes encoded by thepmrE(ugd)loci and thearnBCDTEFoperon. As a result, an Ara-4N headgroup is added to the lipid-A component of outer membrane (OM) lipopolysaccharides (LPS) rendering polymyxins ineffective. Here, we report the cryo-EM structures of glycosyltransferase ArnC fromSalmonella typhimuriumresolved in both apo and UDP-bound forms at resolutions 2.75 Å and 3.8 Å, respectively. The structure of the ArnC protomer comprises of three distinct regions: an N-terminal glycosyltransferase domain, transmembrane region, and the interface helices (IHs). ArnC forms a stable tetramer with C2 symmetry through interactions in the C-terminal region, which is expected to protrude into the cytosol, where the β8 strand inserts into the adjacent protomer. ArnC protomers have two distinct types of interfaces involving multiple hydrogen bonds and salt bridges. The binding of UDP induces conformational changes that stabilizes structurally labile A-loop, spanning residues 201 to 213, and part of the putative catalytic pocket formed by IH1 and IH2. The comparative analysis of ArnC structures with homologs GtrB and DPMS suggests the key residues involved in ArnC catalytic activity.
Personality assessment of synanthropic rhesus macaques: implications and challenges
Authors: Gill Taniya , Gautam Anshul , Massen Jorg J.M. , Bhattacharjee Debottam 
Published: July 2024

Abstract“What makes animals thrive in human-dominated environments?” is a question that has been extensively researched transcending disciplines, but findings remain inconclusive. Consistent inter-individual differences or personalities can potentially explain the functional significance of habitat-specific traits and their variations that help animals successfully coexist with humans. Rhesus macaques (Macaca mulatta) are the most successful non-human primate in the Anthropocene, living in diverse climatic and environmental conditions. Studying the personalities of synanthropic rhesus macaques can provide insights into the biological traits that facilitate their success in human-dominated environments. We employed a multi-method ‘bottom-up’ approach of behavioral observations and novelty experiments, standardized for assessing captive non-human primates, to evaluate the personalities of synanthropic adult rhesus macaques (N=52). To our surprise, novelty experiments encountered significant challenges, limiting their effectiveness. However, behavioral observations in the form of focal sampling revealed two repeatable traits:sociabilityandcautiousness. We found an effect of sex on sociability, where males were more sociable than females. In an additional analysis, we found that individuals who obtained food through contact provisioning had higher cautiousness scores than individuals who obtained food through non-contact provisioning. We discuss how the observed personality traits and their variations potentially offer adaptive advantages in human-dominated environments, where rhesus macaques face both benefits, such as anthropogenic subsidies and reduced predation, and costs, like exposure to anthropogenic stressors. We also emphasize that protocols designed for captive conditions may not be directly applicable to free-living animals. Thus, the study underscores the need to reconsider experimental designs to obtain comparable empirical evidence between captive and non-captive populations to enhance the ecological validity of personality assessments. Nevertheless, empirically identifying traits using observations in synanthropic species like rhesus macaques can still provide valuable insights into the mechanisms that enable certain animals to thrive amidst a rapid expansion of anthropogenic activities.Research highlightsStudying personalities of synanthropic animals can shed light on the biological traits that help them thrive in human-dominated environments.A ‘bottom-up’ multi-method approach, standardized for assessing captive NHP personalities, was employed to study a population of synanthropic rhesus macaques.Behavioral observations captured two repeatable traits, namelysociabilityandcautiousness, where comparatively more cautious individuals obtained food through contact provisioning. Novelty experiments faced significant challenges.