bluuebunny/crossref_metadata_2025_split huggingface dataset:
FishCODE: a web-based information platform for comprehensive omics data exploration in fish research
Authors: Li Heng , Zhang Wanting , Ren Keyi , Yang Hong , Zhang Lei , Younas Waqar , Cheng Yingyin , Wang Yaping , Shi Mijuan , Xia Xiao-Qin 
Published: September 2024

AbstractIn terms of the utilization of omics data, the current fish database analysis functions are primarily relatively simple tools at the transcriptional level, aimed at obtaining the co-expression levels of specified genes or the data visualization of multiple genes, and do not enable users to perform comprehensive omics data analysis. Furthermore, the gene-level information currently provided by these multispecies fish genomics databases is incomplete, and there is a lack of a comprehensive portal that can offer multidimensional genetic information. To address these challenges, we collected extensive multi-omics information on 35 fishes and established the primary comprehensive multi-omics data information platform for fish, FishCODE (http://bioinfo.ihb.ac.cn/fishcode). We have collected experimental background of dataset which pertaining to the target fishes, selected a range of datasets that encompass a broad spectrum of research areas, and downloaded the corresponding raw omics data from public repositories such as the Sequence Read Archive (SRA). Through a unified pipeline analysis, FishCODE contains 11,216 samples from 540 sets of genomic, transcriptomic, and methylomic datasets. These data encompass transcript structure and expression, gene methylation levels, protein domains, protein subcellular localization, protein interactions, best matched protein (Swiss-Prot), associated SNP site information (47,111,018), orthologous genes, phylogenetic tree and GO/KEGG annotations. To facilitate comparison, we annotated the experimental background data sets of the FishCODE, FishGET, PhyloFish, FishSED and FishSCT databases using the Fish Experimental Condition Ontology. Currently, the FishCODE database omics dataset includes 146 unique experimental condition words, 654 cumulative experimental condition words, and 13 species with rich experimental background (more than 20 unique FECO words). These data are 3.5 times (42), 8.3 times (74), and 6.5 times (2) those of the second-ranked databases respectively. We generated word cloud maps for the experimental condition vocabularies of FishCODE and FishGET, illustrating the superior richness of FishCODE’s experimental background.
Betacoronaviruses Differentially Activate the Integrated Stress Response to Optimize Viral Replication in Lung Derived Cell Lines
Authors: Renner David M. , Parenti Nicholas A. , Weiss Susan R. 
Published: September 2024

ABSTRACTThe betacoronavirus genus contains five of the seven human viruses, making it a particularly critical area of research to prepare for future viral emergence. We utilized three human betacoronaviruses, one from each subgenus-HCoV-OC43 (embecovirus), SARS-CoV-2 (sarbecovirus) and MERS-CoV (merbecovirus)- to study betacoronavirus interaction with the PKR-like ER kinase (PERK) pathway of the integrated stress response (ISR)/unfolded protein response (UPR). The PERK pathway becomes activated by an abundance of unfolded proteins within the endoplasmic reticulum (ER), leading to phosphorylation of eIF2α and translational attenuation in lung derived cell lines. We demonstrate that MERS-CoV, HCoV-OC43, and SARS-CoV-2 all activate PERK and induce responses downstream of p-eIF2α, while only SARS-CoV-2 induces detectable p-eIF2α during infection. Using a small molecule inhibitor of eIF2α dephosphorylation, we provide evidence that MERS-CoV and HCoV-OC43 maximize replication through p-eIF2α dephosphorylation. Interestingly, genetic ablation of GADD34 expression, an inducible phosphatase 1 (PP1)-interacting partner targeting eIF2α for dephosphorylation, did not significantly alter HCoV-OC43 or SARS-CoV-2 replication, while siRNA knockdown of the constitutive PP1 partner, CReP, dramatically reduced HCoV-OC43 replication. Combining growth arrest and DNA damage-inducible protein (GADD34) knockout with peripheral ER membrane–targeted protein (CReP) knockdown had the maximum impact on HCoV-OC43 replication, while SARS-CoV-2 replication was unaffected. Overall, we conclude that eIF2α dephosphorylation is critical for efficient protein production and replication during MERS-CoV and HCoV-OC43 infection. SARS-CoV-2, however, appears to be insensitive to p-eIF2α and, during infection, may even downregulate dephosphorylation to limit host translation.IMPORTANCELethal human betacoronaviruses have emerged three times in the last two decades, causing two epidemics and a pandemic. Here, we demonstrate differences in how these viruses interact with cellular translational control mechanisms. Utilizing inhibitory compounds and genetic ablation, we demonstrate that MERS-CoV and HCoV-OC43 benefit from keeping p-eIF2α levels low to maintain high rates of virus translation while SARS-CoV-2 tolerates high levels of p-eIF2α. We utilized a PP1:GADD34/CReP inhibitor, GADD34 KO cells, and CReP-targeting siRNA to investigate the therapeutic potential of these pathways. While ineffective for SARS-CoV-2, we found that HCoV-OC43 seems to primarily utilize CReP to limit p-eIF2a accumulation. This work highlights the need to consider differences amongst these viruses, which may inform the development of host-directed pan-coronavirus therapeutics.
Rewilding alters mouse epigenetic aging
Authors: Zipple Matthew N , Zhao Ivan , Kuo Daniel Chang , Lee Sol Moe , Sheehan Michael J , Zhou Wanding 
Published: September 2024

SUMMARYThe aging of mammalian epigenomes fundamentally alters cellular functions, and such changes are the focus of many healthspan and lifespan studies. However, studies of this process typically use mouse models living under standardized laboratory conditions and neglect the impact of variation in social, physical, microbial, and other aspects of the living environment on age-related changes. We examined differences in age-associated methylation changes between traditionally lab-reared and “rewilded” C57BL6/J mice, which lived in an outdoor field environment with enhanced ecological realism. Systematic analysis of age-associated methylation dynamics in the liver indicates a genomic region-conditioned, faster epigenetic aging rate in mice living in the field than those living in the lab, implicating perturbed 3D genome conformation and liver function. Altered epigenetic aging rates were more pronounced in sites that gain methylation with age, including sites enriched for transcription factor binding related to DNA repair. These observations underscore the overlooked role of the social and physical environment in epigenetic aging with implications for both basic and applied aging research.
A genetically encoded fluorescent sensor enables sensitive and specific detection of IDH mutant associated oncometabolite D-2-hydroxyglutarate
Authors: Choate Kristian A. , Konickson Wren W.L. , Jennings Matthew J. , Mann Paul B. , Winn Robert J. , Kamson David O. , Pratt Evan P.S. 
Published: September 2024

AbstractD-2-hydroxyglutarate (D-2-HG) is an oncometabolite that accumulates due to mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2). D-2-HG may be used as a surrogate marker forIDH1/2mutant cancers, yet simple and specific methods for D-2-HG detection are limited. Here, we present the development and characterization of a genetically encoded fluorescent sensor of D-2-HG (D2HGlo). D2HGlo responds to clinically relevant concentrations of D-2-HG, demonstrates exceptional selectivity and can quantify D-2-HG in various body fluids and glioma tumor supernatants. Additionally, analysis of tumor lysates using D2HGlo accurately predicted the IDH mutational status of gliomas. Collectively, these results suggest that D2HGlo may be anin vitrodiagnostic device for the detection and monitoring of IDH mutant cancers through liquid biopsies. In addition to D2HGlo’s clinical utility, we also present preliminary findings for its adaptation to the cellular environment. To assess D-2-HG production in living immortalized glioma cells, we engineered D2HGlo sensors that localize to subcellular compartments, which yielded findings of elevated D-2-HG in the cytosol, mitochondria, and nucleus ofIDH1mutant cells.
Development of multi-species qPCR assays for a stress transcriptional profiling (STP) Chip to assess the resilience of salmonids to changing environments
Authors: Islam Shahinur S. , Heath Daniel D. , Dixon Brian , Karpowicz Phillip , Vuu Kelvin , LeBlanc Jonathon , Bernier Nicholas J. , Jeffries Kenneth M. 
Published: September 2024

AbstractEcologically and socio-economically important salmonid fishes in Canada are threatened by diverse environmental stressors. However, predicting species’ responses to environmental change requires understanding the underlying molecular mechanisms governing environmental stress tolerance. Developing advanced molecular genetic tools will provide opportunities to predict how salmonid fishes will respond to environmental stressors and assess their adaptive potential and vulnerability into the future. Here, we developed a panel of Taqman quantitative PCR (qPCR) assays designed to measure mRNA transcript abundance at selected candidate loci for use across salmonids. We designed and applied those assays for use in a high-throughput nanofluidic OpenArray Stress Transcriptional Profiling Chip (STP-Chip) capable of 2688 simultaneous qPCR at multiple gene loci (112 targets for 12 samples in duplicate). Using the nanofluidic STP-Chip, we tested these 112 multi-species qPCR assays using gill, liver and muscle tissue from eight species of salmonids across four genera. Of the selected 112 assays, 69 assays showed amplification in gill, 64 in liver, and 67 in muscle across all eight salmonid species. The percentage of assays that showed amplification across three tissues varied between genera: In general,Salmo,Oncorhynchus, andSalvelinusspecies showed a higher success rate thanCoregonusspecies. Stress, circadian rhythm, apoptosis, growth-metabolism, and detoxification-relevant assays showed high success rates for amplification across all salmonid species for all three tissues. In contrast, neural plasticity, appetite regulation, osmoregulation, immune function, endocrine disruption, and hypoxia-relevant assays showed low success. Not surprisingly, we observed tissue-specific variation among qPCR amplification patterns. There were significant differences in mRNA transcript abundance among species across the four genera, but we did not see variation between species from the same genus. These qPCR assays can be used to design custom STP-Chips that can be used for quantifying stress in salmonid fish, improving health through more accurate diagnostic tests for disease, and monitoring adaptation to accelerated climate change regionally and globally.
Different signaling interpretations by PKC eta and theta control T cell function and exhaustion
Authors: Mann Thomas H. , Knox Hannah M. , Ma Shixin , Furgiuele Jesse , Globig Anna-Maria , LaPorta Michael , Chung Hokyung K. , McDonald Bryan , Ghassemian Majid , Zhao Steven , Tseng Hubert , Farsakoglu Yagmur , Tripple Victoria , Koo Johnny , Newton Alexandra C. , Kaech Susan M. 
Published: September 2024

SUMMARYChronic antigen signaling drives CD8+T cell exhaustion (TEX) in cancer and chronic infection. However, how the kinase cascades downstream of the T cell receptor drive exhaustion is not understood. We found that continuous agonism of protein kinase C (PKC) causes degradation of PKC theta, but not PKC eta, and induces terminal TEXcells. During chronic infection, PKC theta is necessary to maintain the progenitor exhausted (TEX-PROG) cells, and thus the antigen-specific T cell response, while agonism of PKC eta promotes terminal exhaustion (TEX-TERM)in vitroandin vivo. The cascades downstream of these kinases are distinct, with PKC theta promoting activity of canonical PKC targets in the MAPK and CDK families, while eta promotes activity of other targets, including casein kinase I G2 (CK1G2). Expression of an engineered, degradation-resistant PKC theta, or deletion of the gene encoding CK1G2, improves T cell function and tumor control. Our illustration of multiple therapeutic avenues arising from targeting PKC highlights its centrality in TEXdifferentiation and its clinical potential in cancer immunotherapy.HighlightsPKC theta sustains T cell function while PKC eta promotes terminal exhaustionPKC theta and eta drive distinct phospho-cascades to oppose each other’s differentiation instructionsAn engineered, degradation-resistant PKC theta improves T cell responses in chronic infection and cancerAblation of kinase CK1G2 downstream of PKC eta improves anti-tumor T cell responses
Increases in Arctic extreme climatic events are linked to negative fitness effects on the local biota
Authors: Lemaire M , Bokhorst S. , Witheford A. , Macias-Fauria M. , Salguero-Gomez R. 
Published: September 2024

1.AbstractThe Arctic harbours uniquely adapted biodiversity and plays an important role in climate regulation. Strong warming trends in the terrestrial Arctic have been linked to an increase in aboveground biomass (Arctic greening) and community-wide shifts such as the northwards-expansion of boreal species (borealisation). Whilst considerable efforts have been made to understand the effects of warming trends in average temperatures on Arctic biota, far fewer studies have focused on trends in extreme climate events and their biotic effects, which have been suggested to be particularly impactful during the Arctic winter months. Here, we present an analysis of trends in two ecologically-relevant winter extreme events –extreme winter warming and rain-on-snow, followed by a meta-analysis on the evidence base for their effects on Arctic biota. We show a strong increase in extreme winter warming across the entire Arctic and high variability in rain-on-snow trends, with some regions recently experiencing rain-on-snow for the first time whilst others seeing a decrease in these events. Ultimately, both extreme events show significant changes in their characteristics and patterns of emergence. Our meta-analysis –encompassing 178 effect sizes across 17 studies and 49 species– demonstrates that extreme winter warming and rain-on-snow induce negative impacts on Arctic biota, with certain taxonomic groups –notably angiosperms and chordates (mostly vertebrates)– exhibiting higher sensitivity than others. Our study provides evidence for both emerging trends in Arctic winter extreme climate events and significant negative biotic effects of such events –which calls for attention to winter weather variability under climate change in the conservation of Arctic biodiversity, whilst highlighting important knowledge gaps.
SEISMICgraph: a web-based tool for RNA structure data visualization
Authors: Fuchs Wightman Federico , Yang Grant , Martin des Taillades Yves J. , L’Esperance-Kerckhoff Casper , Grote Scott , Allan Matthew F. , Herschlag Daniel , Rouskin Silvi , Hagler Lauren D. 
Published: September 2024

ABSTRACTIn recent years, RNA has been increasingly recognized for its essential roles in biology, functioning not only as a carrier of genetic information but also as a dynamic regulator of gene expression through its interactions with other RNAs, proteins, and itself. Advances in chemical probing techniques have significantly enhanced our ability to identify RNA secondary structures and understand their regulatory roles. These developments, alongside improvements in experimental design and data processing, have greatly increased the resolution and throughput of structural analyses. Here, we introduce SEISMICgraph, a web-based tool designed to support RNA structure research by offering data visualization and analysis capabilities for a variety of chemical probing modalities. SEISMICgraph enables simultaneous comparison of data across different sequences and experimental conditions through a user-friendly interface that requires no programming expertise. We demonstrate its utility by investigating known and putative riboswitches and exploring how RNA modifications influence their structure and binding. SEISMICgraph’s ability to rapidly visualize adenine-dependent structural changes and assess the impact of pseudouridylation on these transitions provides novel insights and establishes a roadmap for numerous future applications.GRAPHICAL ABSTRACT
LRRC8 complexes are adenosine nucleotide release channels regulating platelet activation and arterial thrombosis
Authors: Tranter John D. , Mikami Ryan T. , Kumar Ashutosh , Brown Gavriel , Abd El-Aziz Tarek M. , Zhao Yonghui , Abraham Nihil , Meyer Chloe , Ajanel Abigail , Xie Litao , Ashworth Katrina , Hong Juan , Zhang Haixia , Kumari Tripti , Balutowski Adam , Liu Alice , Bark David , Nair Vinayak K. , Lasky Nina M. , Feng Yongmei , Stitziel Nathan O. , Lerner Daniel J. , Campbell Robert A. , Paola Jorge Di , Cho Jaehyung , Sah Rajan 
Published: September 2024

AbstractPlatelet shape and volume changes are early mechanical events contributing to platelet activation and thrombosis. Here, we identify single-nucleotide polymorphisms in Leucine-Rich Repeat Containing 8 (LRRC8) protein subunits that form the Volume-Regulated Anion Channel (VRAC) which are independently associated with altered mean platelet volume. LRRC8A is required for functional VRAC in megakaryocytes (MKs) and regulates platelet volume, adhesion, and agonist-stimulated activation, aggregation, ATP secretion and calcium mobilization. MK-specific LRRC8A cKO mice have reduced arteriolar thrombus formation and prolonged arterial thrombosis without affecting bleeding times. Mechanistically, platelet LRRC8A mediates swell-induced ATP/ADP release to amplify agonist-stimulated calcium and PI3K-AKT signaling via P2X1, P2Y1and P2Y12receptors. Small-molecule LRRC8 channel inhibitors recapitulate defects observed in LRRC8A-null plateletsin vitroandin vivo. These studies identify the mechanoresponsive LRRC8 channel complex as an ATP/ADP release channel in platelets which regulates platelet function and thrombosis, providing a proof-of-concept for a novel anti-thrombotic drug target.
Pancreatic cancer cells overexpressing interleukin 6 induce T-cell-mediated tumor clearance and durable anti-tumor immune response
Authors: Arneson-Wissink Paige C. , Bartlett Alexandra Q. , Mendez Heike , Zhu Xinxia , Dickie Jessica , McWhorter Matthew , Levasseur Peter R. , Diba Parham , Byrne Katelyn T. , Scott Gregory D. , Eil Robert , Grossberg Aaron J. 
Published: September 2024

ABSTRACTTumor immune resistance is recognized as a contributor to low survivorship in pancreatic ductal adenocarcinoma (PDAC). We developed a novel murine model of spontaneous PDAC clearance, generated by overexpressing interleukin-6 (IL-6) in orthotopically implanted PDAC cancer cells (OT-PDACIL6). Circulating IL-6 was 100-fold higher in OT-PDACIL6than in OT-PDACparentalmice. OT-PDACIL6tumors were present at 5 days post-implantation, and undetectable by 10 days post implantation. Flow cytometry revealed increased T cells and NK cells, and decreased T regulatory cells in OT-PDACIL6as compared to OT-PDACparentaltumors. Increased lymphoid aggregates were apparent by histological assessment and may account for elevated T cell content. Antibody-based depletion of CD4+and CD8+T cells prevented tumor clearance and significantly reduced survival of OT-PDACIL6mice. The anti-tumor immune response to OT-PDACIL6rendered mice immune to re-challenge with OT-PDACparentaltumors. In high concentrations, IL-6 acts in opposition to previously described pro-tumorigenic effects by enhancing the T cell-mediated anti-tumor response to PDAC.Statement of SignificanceInterleukin 6 overexpression in pancreatic ductal adenocarcinoma cells induces T cell-driven tumor clearance that is rapid and durable. Supraphysiologic levels of interleukin 6 are sufficient to drive an anti-tumor immune microenvironment hallmarked by increased lymphoid aggregate formation, increased CD4 T cell abundance, and decreased Treg abundance.
Screen Cauchy–Riemann (SCR)-lightlike submanifolds of metallic semi-Riemannian manifolds
Authors: Shanker Gauree , Yadav Ankit , Kaur Ramandeep 
Published: September 2024

PurposeThe screen Cauchy–Riemann (SCR)-lightlike submanifold is an important class of submanifolds of semi-Riemannian manifolds. It contains various other classes of submanifolds as its sub-cases. It has been studied under various ambient space. The purpose of this research is to study the geometry of SCR-lightlike submanifolds of metallic semi-Riemannian manifolds.Design/methodology/approachThe article is divided into five sections. The first section is introductory section which represents brief overview of the conducted research of this article. The second section outlines the key results that are utilized throughout the paper. In section three, the definition of SCR-lightlike submanifold is constructed with one non-trivial example. In section four and five, the important results on integrability, totally geodesic foliations and warped product are given.FindingsThe SCR-lightlike submanifold is introduced. One non-trivial example is constructed which helps to understand the given structure. The necessary and sufficient conditions for the integrability and to be totally geodesic for various distributions are obtained. The necessary and sufficient conditions for induced connection on totally umbilical SCR-lightlike submanifolds to be a metric connection are discussed. Various results are found on totally umbilical SCR-lightlike submanifolds. Finally, the existence of the warped product lightlike submanifold of the type N⊥×λNT is studied.Originality/valueSCR-lightlike submanifolds have been explored within ambient manifolds possessing various structures, such as Kaehler, Sasakian and Kenmotsu structures. In this article, we investigate this structure on submanifolds of metallic semi-Riemannian manifolds. This original and authentic research will aid researchers in advancing the study of semi-Riemannian manifolds.
Supply chain resilience during COVID-19 pandemic: role of market orientation, knowledge management orientation and innovative capability
Authors: Tukamuhabwa Benjamin , Makepu Ngobi Joel , Mutebi Henry , Tumukunde Ivan 
Published: September 2024

PurposeThis paper explores the direct relationships between market orientation (MO), knowledge management orientation (KMO), innovative capability (IC) and supply chain resilience (SCRES). Moreover, the indirect effects of both MO and KMO on SCRES through IC are also examined.Design/methodology/approachA theoretical model developed from the extant literature was empirically validated through a cross-sectional survey of 195 manufacturing firms in Uganda during the COVID-19 pandemic. The data were analysed using partial least squares structural equation modelling (PLS-SEM).FindingsThe study found that there are positive and significant direct effects of MO and KMO on IC. KMO and IC have positive and significant effects on SCRES, while the positive relationship between MO and SCRES is non-significant. Furthermore, the results indicate that the effects of both MO and KMO on SCRES are partially mediated by IC.Originality/valueEmpirical evidence is provided on the antecedents of SCRES in a developing economy in the context of COVID-19. Moreover, a multidisciplinary model incorporating marketing, knowledge management and innovation literature to explain the SCRES phenomenon is validated. Further, the partial mediating role of IC is examined and confirmed.