bluuebunny/crossref_metadata_2025_split huggingface dataset:
A maize near-isogenic line population designed for gene discovery and characterization of allelic effects
Authors: Zhong Tao , Mullens Alex , Morales Laura , Swarts Kelly L , Stafstrom William C , He Yijian , Sermons Shannon M , Yang Qin , Lopez-Zuniga Luis O , Rucker Elizabeth , Thomason Wade E , Nelson Rebecca J , Jamann Tiffany , Balint-Kurti Peter J , Holland James B 
Published: February 2025

AbstractIn this study we characterized a panel of 1,264 maize near-isogenic lines (NILs), developed from crosses between 18 diverse inbred lines and the recurrent parent B73, referred to as nested NILs (nNILs). 884 of the nNILs were genotyped using genotyping-by-sequencing (GBS). Subsequently, 24 of these nNILs, and all the parental lines, were re-genotyped using a high-density SNP chip. A novel pipeline for calling introgressions, which does not rely on knowing the donor parent of each nNIL, was developed based on a hidden Markov model (HMM) algorithm. By comparing the introgressions detected using GBS data with those identified using chip data, we optimized the HMM parameters for analyzing the entire nNIL population. A total of 2,972 introgressions were identified across the 884 nNILs. Individual introgression blocks ranged from 21 bp to 204 Mbp, with an average size of 17 Mbp. By comparing SNP genotypes within introgressed segments to the known genotypes of the donor lines we determined that in about one third of the lines, the identity of the donors did not match expectation based on their pedigrees.We characterized the entire nNIL population for three foliar diseases. Using these data, we mapped a number of quantitative trait loci (QTL) for disease resistance in the nNIL population and observed extensive variation in effects among the alleles from different donor parents at most QTL identified. This population will be of significant utility for dissecting complex agronomic traits and allelic series in maize.Significance StatementThe study reports the characterization of a publicly available population of 1,264 maize near-isogenic lines largely derived from a single recurrent parent and 18 donor lines. This population is likely to be of significant utility for the characterization of allelic series at loci of interest.
Microbial metabolite 4-ethylphenylsulfate (4EPS) interacts with AT1R, reduces blood pressure and outcome of AngII-induced aortic aneurysm
Authors: Harford Terri J. , Singh Dhanachandra Khuraijam , Pardhi Triveni R. , Desnoyer Russell , Ravi Tarun , Jara Zaira Palomino , Zalavadia Ajay , Stenson Kate , Prasad Sathyamangla V Naga , Karnik Sadashiva S. 
Published: February 2025

AbstractBACKGROUNDPlasma accumulation of the gut microbial metabolite, 4-ethylphenylsulfate (4EPS), produced from dietary protein aromatic amino acids has been observed in correlative and associative studies of cardiovascular, renal, metabolic and neurological diseases. 4EPS level increases upon AngII infusion in mice. How 4EPS alters host physiology to contribute to progression of any disease state is currently unknown.METHODSTo test the hypothesis that 4EPS interferes with angiotensin binding to AT1R, we used multiple approaches: AT1R pharmacology, cell-signaling, ex vivo vascular contraction and a mouse model of angiotensin-induced aortic aneurysm (AA) disease. ApoE-null mice were fed high-fat diet and infused with AngII, or co-infused with 4EPS and Olmesartan. BP was recorded. At the end of infusion, aortas were assessed for severity of AA, contractile response and histopathology. To evaluate signaling associated with different AA outcomes plasma proteomics analysis was done.RESULTSIn vitro, 4EPS reduced the binding of angiotensin and Candesartan to AT1R and calcium signaling. Ex vivo, 4EPS decreased vasomotor response of the aorta to AngII. In vivo, 4EPS inhibited AngII-mediated increase of BP and reduced mortality from AA. Abdominal aorta remodeling in 4EPS+AngII co-infused mice showed an increase of elastin area and reduced thickening of intimal/medial layers. Plasma proteome analysis indicated significant change in actin-cytoskeletal signaling associated with reduced ERK1/2 and Filamin-A activation, and cell motility.CONCLUSIONSBenign antagonism of AT1R by 4EPS involves direct interaction with AT1R. Molecular mechanisms of 4EPS responsible for reduced AA associated mortality in mice are distinct from those of AT1R blocker, Olmesartan.GRAPHIC ABSTRACT
Lytic IFNγ is stored in granzyme B-containing cytotoxic granules and co-secreted by effector CD8⁺ T cells
Authors: Li Xuemei , Schirra Claudia , Wirkner Marie-Louise , Tu Szu-Min , Lin Chin-Hsin , Hohmann Meltem , Alawar Nadia , Chouaib Abed , Becherer Ute , Pattu Varsha , Rettig Jens , Krause Elmar , Chang Hsin-Fang 
Published: February 2025

AbstractCytotoxic CD8⁺ T cells form immunological synapses with target cells and release effector molecules, including IFNγ, to mediate antitumor immunity. However, the mechanisms by which IFNγ contributes to cytotoxicity remain incompletely understood. Here, we identify a subset of IFNγ stored within GzmB⁺ cytotoxic granules (CGs) in activated mouse and human CD8⁺ T cells, termed ’lytic IFNγ’. Lytic IFNγ is polarized to the synapse and co-secreted with GzmB in both soluble and supramolecular attack particle (SMAP)-associated forms. Mouse CD8⁺ T cells lacking the vesicle priming factor Munc13-4 exhibit impaired both CG and early IFNγ release at the immunological synapse, while prolonged synaptic engagement restores IFNγ secretion. Super-resolution imaging demonstrates that sustained synaptic interactions drive IFNγ secretion at distal membrane sites, suggesting the existence of distinct IFNγ populations with potentially diverse functions beyond lytic IFNγ. These findings uncover an unrecognized mechanism of IFNγ storage and release, underscoring its pivotal role in CD8⁺ T cell-mediated tumor elimination.
Metabolic remodeling of microorganisms by obligate intracellular parasites alters mutualistic community composition
Authors: Bisesi Ave T. , Carlson Ross P. , Cotner Lachlan , Harcombe William R. 
Published: February 2025

ABSTRACTBacteria carry many types of obligate intracellular parasites, including plasmids and bacteriophage. During infection, these parasites redirect intracellular resources away from bacterial processes toward parasite production. Because parasite-induced metabolic changes influence host traits such as growth rate, nutrient uptake, and waste excretion, parasitic infection should alter how microbes contribute to important community and ecosystem functions. Yet there are few empirical tests of how infection shapes metabolically-mediated interactions between host and non-host species. Here, we integrated a genome-scale metabolic modeling approach with anin vitroobligate cross-feeding system to investigate the metabolic consequences of two intracellular parasites ofEscherichia coli: the conjugative plasmid F128 and the filamentous phage M13. We examined the impact of these parasites on interactions between bacteria in a multispecies community composed ofE. coli,Salmonella enterica,andMethylobacterium extorquens. Modeling predicted that parasitic infection ofE. colishould have consequences for host growth rate and the secretion and reuptake of carbon byproducts. These theoretical results aligned broadly within vitroexperiments, where we found that parasitic infection changed the excretion profile ofE. coli, inducing the net externalization of lactate. We also found that parasite-driven changes to metabolism increased the density of cross-feeding species and changes to community composition were generalizable across community interactions and some host and parasite genotypes. Our work emphasizes that microbes infected by obligate intracellular parasites have different metabolisms than uninfected cells and demonstrates that these metabolic shifts can have significant consequences for microbial community structure and function.IMPORTANCEThe intracellular parasites of bacteria shape the structure and function of microbial communities in a variety of ways, including by killing their hosts or transferring genetic material. This study uses a combination of flux balance analysis and anin vitrosystem consisting ofEscherichia coli,Salmonella enterica,Methylobacterium extorquens, and two intracellular parasites ofE. coli, the F128 plasmid and the filamentous phage M13, to investigate how parasites change the community contributions of their hosts via metabolic remodeling. Flux balance analysis suggests that parasites change intracellular demand for different metabolic processes, leading to shifts in the identities and concentrations of compounds that infected hosts externalize into the environment. This finding is supported by experimental results, which additionally show that infection can induce the production of lactate. These findings extend our understanding of how bacteriophage and plasmids shape the structure and function of microbial communities.
FISHNET: A Network-based Tool for Analyzing Gene-level P-values to Identify Significant Genes Missed by Standard Methods
Authors: Acharya Sandeep , Moghaddam Vaha Akbary , Jung Wooseok J. , Kang Yu S. , Liao Shu , Province Michael A. , Brent Michael R. 
Published: February 2025

AbstractFISHNET uses prior biological knowledge, represented as gene interaction networks and gene function annotations, to identify genes that do not meet the genome-wide significance threshold but replicate nonetheless. Its input is gene-level P-values from any source, including omicsWAS, aggregation of GWAS P-values, CRISPR screens, or differential expression analysis. It is based on the idea that genes whose P-values are low due to sampling error are distributed randomly across networks and functions, so genes with suggestive P-values that cluster in densely connected subnetworks and share common functions are less likely to reflect sampling error and more likely to replicate. FISHNET combines network and function analysis with permutation-based P-value thresholds to identify a small set of exceptional genes that we call FISHNET genes.Applied to 11 cardiovascular risk traits, FISHNET identified 19 gene-trait relationships that missed genome-wide significance thresholds but, nonetheless, replicated in an independent cohort. The replication rate of FISHNET genes matched or exceeded that of other genes with similar P-values. FISHNET identified a novel association betweenRUNX1expression and HDL that is supported by experimental evidence thatRUNX1promotes white fat browning, which increases HDL cholesterol levels. FISHNET also identified an association betweenLTBexpression and BMI that is supported by experimental evidence that higher LTB expression increases BMI via activation of the LTβR pathway. Both associations failed genome-wide significance thresholds, highlighting FISHNET’s ability to uncover meaningful relationships missed by traditional methods. FISHNET software is freely available athttps://doi.org/10.5281/zenodo.14765850.
Rhizosphere Bacteria and Fungi are Differentially Structured by Host Plants, Soil Mineralogy and Ectomycorrhizal Communities in the Alaskan Tundra
Authors: Schaefer Sean Robert , Montaño-López Fernando , Holland-Moritz Hannah , Hicks Pries Caitlin , Ernakovich Jessica Gilman 
Published: February 2025

AbstractThe rhizosphere contains a diverse group of bacteria and fungi living near plant roots whose composition and function are key drivers of ecosystem and biogeochemical processes. Despite rich literature on rhizosphere communities, surprisingly few studies have examined the drivers of rhizosphere community structures in natural settings. We collected 513 root samples from 141 individual plants representing six plant species and three mycorrhizal association types across four glacial drifts in the North Slope of Alaska. Glacial drifts ranged from 11,000 to 4.5 million years since deglaciation representing a gradient in glacial history and mineralogical weathering. We found that glacial history, a strong proxy for soil mineralogy, explained most of the captured variation in rhizosphere bacterial communities (13.3%) and ectomycorrhizal fungal communities (10.2%) while interactions between glacial history and host plants explained the most variation in fungal rhizosphere communities (11.6%). We analyzed ectomycorrhizal fungal communities from the shrubBetula nanaacross spatial scales and sites and found a large correlation between ectomycorrhizal and rhizosphere communities, and that ectomycorrhizal composition was most similar among root fragments belonging to the same plant, followed by plants at the same site, and were most dissimilar for plants at different sites.
TSC1mRNA processing alterations in tuberous sclerosis complex (TSC) patients with negative or inconclusive genetic testing results
Authors: de Mello Garcia Arthur Bandeira , da Silveira Fischer Taís , de Freitas Pinho Maria Clara , Jataí Lucas Fernandesw , da Silva Patrícia Santos , Andreis Tiago Finger , Reis Larissa Brussa , Oliveira Netto Cristina Brinckmann , Ashton-Prolla Patricia , Rosset Clévia 
Published: February 2025

AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by the presence of pathogenic germline variants inTSC1orTSC2genes. However, mostTSC1andTSC2genetic testing strategies are limited and about 20% of patients have inconclusive or negative results. In this study, we standardized a low-cost technique based on RT-PCR followed by Sanger sequencing, aimed to complement genetic testing strategies. Patients with clinical suspicion of TSC andTSC1andTSC2inconclusive (n=3) or negative (n=1) genetic testing results were recruited. Exon 5 skipping inTSC1gene was identified in one patient with a previous negative genetic testing result. In addition, a 9-base-pair intronic inclusion was found in theTSC1of an individual with a previously identified variant of uncertain significance, c.664-10A>C. No alterations were found in the other two patients. The present study was successful in identifying errors in mRNA processing in two TSC patients with previously negative or inconclusive genetic testing results. Furthermore, this strategy was useful to reclassify a VUS to pathogenic. Finally, the validated technique could be used to complement coding region genetic tests and to investigate causality of VUS in TSC and other monogenic diseases.Highlights-A novel cDNA analysis method revealed the presence of exon 5 skipping in the-TSC1gene-A nine-base-pair retention in TSC1 mRNA is caused by the intronic variant c.664-10A>C-The variant of uncertain significance c.664-10A>C inTSC1was reclassified as pathogenic-A strategy using cDNA could be a good complement to conventional molecular diagnosis protocols
Association of ICH Score with Withdrawal of Life-Sustaining Treatment: A Decade from the Florida Stroke Registry
Authors: Massad Nina , Zhou Lili , Manolovitz Brian , Asdaghi Negar , Gardener Hannah , Ying Hao , Gutierrez Carolina M , Jameson Angus , Rose David , Kottapally Mohan , Merenda Amedeo , O’Phelan Kristine , Koch Sebastian , Romano Jose G. , Rundek Tatjana , Alkhachroum Ayham 
Published: February 2025

ABSTRACTBackground and PurposeThe intracerebral hemorrhage (ICH) score was created as a tool improve communication and consistency among providers, and authors initially cautioned against its use as a predictor of outcomes. We aimed to investigate the association of ICH score with mortality and withdrawal of life-sustaining treatment (WLST).MethodsPatients with a diagnosis of ICH were identified using data from Florida Stroke Registry (FSR) hospitals participating in the American Heart Association (AHA) Get with the Guidelines-Stroke (GWTG-S) from 2013-2022. Outcomes of WLST and in-hospital mortality were collected. ICH score was stratified into three groups: ICH score 0-2; 3-4; 5-6. Importance plots were generated to identify the most predictive factors associated with WLST. AUC-ROC curves were generated for logistic regression (LR) and random forest (RF) models, adjusted for relevant confounders. Secondary outcome analyses were performed using stratified univariate logistic regression to assess changes between 2015-2018 and 2019-2022.ResultsA total of 12,426 (26%) patients had documented ICH scores (mean age 69, 55% male, 56% white). The most predictive factors associated with WLST were ICH score, age, state region, presenting level of consciousness, insurance status and race (RF AUC=.94, LR AUC=.82). Mortality was 6.6%, 41.5% and 66% for ICH score 0-2, 3-4 and 5-6. Decision to WLST occurred more for ICH scores 3-4 (OR 9.35, 95% CI: 8.5-10.3) and ICH scores 5-6 (15.43, 95% CI: 15.28-22.74). Early WLST (< 2 days) was more likely for ICH score 3-4 (OR 2.97, 95% CI: 2.48-3.55) and score 5-6 groups (OR 9.51, 95% CI: 7.33-12.35).ConclusionAmong ICH patients admitted across Florida, we noted a significant association between ICH score and likelihood of mortality, decision to WLST, and specifically WLST within two days of presentation. We identified the most predictive variable associated with WLST to be the ICH score. These findings suggest a continued influence of the self-fulfilling prophecy in ICH.
Repurposing Regulatory Toxicology Safety Data to Identify Potential Pro-Longevity Substances
Authors: Miwa Satomi , Kucheryavenko Olena , Herrmann Kristin , Saunter Christopher , Raimundo Adelaide , Weinkove David , Niemann Lars , von Zglinicki Thomas 
Published: February 2025

AbstractThe repurposing of existing biosafety datasets offers unique opportunities in biomedical research. Here, we demonstrate how pesticide toxicity data, which include long-term survival studies in mammalian models, can be harnessed to uncover potential drug candidates or drug targets that can improve survival. We show that these substances frequently affect mitochondrial bioenergetics and that they can improve animal healthspan.
Cardiac diffusion kurtosis imaging in the human heart in vivo using 300mT/m gradients
Authors: Afzali Maryam , Coveney Sam , Mueller Lars , Jones Sarah , Fasano Fabrizio , Evans C John , Teh Irvin , Dall’Armellina Erica , Szczepankiewicz Filip , Jones Derek K , Schneider Jürgen E 
Published: February 2025

PurposeDiffusion tensor imaging (DTI) is commonly used in cardiac diffusion magnetic resonance imaging (dMRI). However, the tissue’s microstructure (cells, membranes, etc.) restricts the movement of the water molecules, making the spin displacements deviate from Gaussian behaviour. This effect may be observed with diffusion kurtosis imaging (DKI) using sufficiently high b-values (b>450 s/mm2), which are presently outside the realm of routine cardiac dMRI due to the limited gradient strength of clinical scanners. The Connectom scanner with Gmax= 300 mT/m enables high b-values at echo times (TE) similar to DTI on standard clinical scanners, therefore facilitating cardiac DKI in humans.MethodsCardiac-gated, second-order motion-compensated dMRI was performed with bmax= 1350 s/mm2in 10 healthy volunteers on a 3T MRI scanner with Gmax= 300 mT/m. The signal was fitted to a cumulant expansion up to and including the kurtosis term and diffusion metrics such as fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) were calculated.ResultsWe demonstrate deviation of the signal from monoexponential decay for b-values>450 s/mm2(MK = 0.32±0.03). Radial kurtosis (RK = 0.35±0.04) was observed slightly larger than axial kurtosis (AK = 0.27±0.02), and the difference is statistically significant (RK−AK = 0.08±0.04, p = 2e−4).ConclusionThis work demonstrates the feasibility of quantifying kurtosis effect in the human heart in vivo (at an echo time shorter than typical TEs reported for cardiac DTI), using high-performance gradient systems (which are 4-8 times stronger than on standard clinical scanners). Our work lays the foundation for exploring new biomarkers in cardiac dMRI beyond DTI.
Arabidopsisseed stored mRNAs and translation regulation during post-harvest ripening and imbibition
Authors: Balarynová J. , Klčová B. , Čegan R. , Raabe K. , Krejčí P. , Bednář P. , Potěšil D. , Pustka V. , Tarkowská D. , Turečková V. , Zdráhal Z. , Honys D. , Smýkal P. 
Published: February 2025

AbstractSeed germination marks the critical transition from dormancy to active growth, driven by environmental cues and water availability. This study explores translational regulation during germination by comparing twoArabidopsis thalianaaccessions with contrasting dormancy phenotypes: Columbia (Col), which germinates readily, and Cape Verde Islands (Cvi), which exhibits deep dormancy. Using sucrose gradient centrifugation, we isolated monosomal and polysomal fractions from freshly harvested (FH), after-ripened (AR), and imbibed (IM) seeds. RNA-seq analysis revealed stage- and genotype-specific gene expression, with Col IM seeds displaying the highest number of expressed genes. We identified ∼14,000 mRNAs in FH seeds, increasing to 19,000 in Col and 17,000 in Cvi upon imbibition. Of these, 9,000 were shared, while 3,000 were accession-specific in monosomes. Enrichment analysis highlighted molecular pathways associated with translation and dormancy release. Analysis of RNA modifications identified N1-methyladenosine (m1A) as the predominant modification, with Col seeds exhibiting higher m1A levels than Cvi, peaking at three months post-harvest. m6A sequencing revealed distinct modification patterns between accessions, with the highest abundance of m6A-modified transcripts in IM seeds. Positional analysis of m6A peaks suggested a link to differential gene expression between Col and Cvi. Proteomic analysis identified ∼15,000 proteins, with translation-related proteins enriched in IM seeds. Notable differences between Col and Cvi were observed in both monosomal and polysomal fractions. RNA-binding proteins exhibited similar profiles in FH and AR stages but diverged significantly in IM seeds. Col-specific proteins were enriched in 40S ribosomes, processing bodies, and RNA-binding complexes.These findings provide new insights into the molecular and translational dynamics underlying seed germination, advancing our understanding of dormancy release and early seedling establishment.
Sociodemographic Inequalities in Heat-Related Mortality across Summer Seasons from 2022 to 2024 in Peru
Authors: Intimayta-Escalante Claudio 
Published: February 2025

ABSTRACTAimTo assess sociodemographic inequalities in Heat-Related Mortality (HRM) across Peruvian departments during the summer seasons from 2022 to 2024.MethodsAn ecological study was conducted to analyze excess mortality during the summers of 2022–2023 and 2023–2024 in relation to maximum temperature records across 24 Peruvian departments. Sociodemographic factors, including sex, age group (<60 years or≥60 years), and educational level (elementary or lower vs. higher education), were considered. HRM was estimated for the overall population and stratified by sociodemographic characteristics using Poisson regression models. Inequality in HRM was quantified using the GINI index, where values near 1 indicate absolute inequality, while values closer to 0 suggest greater equality.ResultsA total of 70,832 deaths were analyzed, with 35,268 occurring in the summer of 2022–2023 and 35,564 in 2023–2024. The mean HRM was 29.24%, ranging from 2.26% to 166.67% across 10 departments. Higher HRM values were observed among females (HRM=51.90%), individuals<60 years (HRM=68.63%), and those with higher educational attainment (HRM=62.20%). The overall GINI index for HRM was 0.64, with greater inequality observed among females (GINI=0.38), individuals<60 years (GINI=0.51), and those with higher education levels (GINI=0.47).ConclusionSignificant sociodemographic inequalities in HRM were observed across Peruvian departments during the summer seasons from 2022 to 2024. The highest inequalities were found among females, individuals<60 years, and those with higher educational attainment.