bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood Pressure and Hypertension After Hypertensive Disorders of Pregnancy
Authors: Urrutia Rachel Peragallo , Loop Matthew Shane , Johnson Jasmine D , Wang Tracy Y , Price Thomas M , Daubert Melissa A 
Published: January 2025

AbstractIntroductionCardiovascular disease (CVD) is the leading cause of mortality for women. Timely diagnosis of hypertension after a hypertensive disorder of pregnancy (HDP) provides an opportunity for CVD prevention. We assessed the association between blood pressure (BP) 15-90 days postpartum and incident hypertension after an HDP.MethodsThis was a retrospective cohort study of women with an HDP between January 2014 and December 2017 at two health systems in the southeastern U.S. Cox proportional hazards models assessed the association of postpartum BP and incident hypertension 12 months postpartum. Covariates included type of HDP, gestational age at diagnosis, timing of measurement, comorbidities, and structural determinants of health. We excluded people with preexisting hypertension and without a BP measurement 15-90 days postpartum.ResultsOut of 5657 women, only 2514 (44%) met the inclusion criteria as almost 40% (2125) did not have a BP check at 15-90 days postpartum. The hazards of incident hypertension were significantly higher for those with elevated systolic postpartum BP (1.70, 95% CI: 1.37 - 2.12) and more severe HDPs. The estimated cumulative incidence of hypertension among participants with postpartum BP of 110/65 mmHg was 4.7% (CI, 2.0% - 7.4%) and for those with BP 140/90, it was 13.0% (CI 5.6% - 19.8%).ConclusionsThe risk of incident hypertension after an HDP is high in the first year postpartum. Despite this, for many participants, BP was not even measured within 15-90 days postpartum despite. Opportunities exist to improve care for individuals with HDPs.
Noncanonical PI(4,5)P2 coordinates lysosome positioning through cholesterol trafficking
Authors: Loughran Ryan M. , Arora Gurpreet K. , Sun Jiachen , Llorente Alicia , Crabtree Sophia , Ly Kyanh , Huynh Ren-Li , Cho Wonhwa , Emerling Brooke M. 
Published: January 2025

AbstractIn p53-deficient cancers, targeting cholesterol metabolism has emerged as a promising therapeutic approach, given that p53 loss dysregulates sterol regulatory element-binding protein 2 (SREBP-2) pathways, thereby enhancing cholesterol biosynthesis. While cholesterol synthesis inhibitors such as statins have shown initial success, their efficacy is often compromised by the development of acquired resistance. Consequently, new strategies are being explored to disrupt cholesterol homeostasis more comprehensively by inhibiting its synthesis and intracellular transport. In this study, we investigate a previously underexplored function of PI5P4Ks, which catalyzes the conversion of PI(5)P to PI(4,5)P2at intracellular membranes. Our findings reveal that PI5P4Ks play a key role in facilitating lysosomal cholesterol transport, regulating lysosome positioning, and sustaining growth signaling via the mTOR pathway. While PI5P4Ks have previously been implicated in mTOR signaling and tumor proliferation in p53-deficient contexts, this work elucidates an upstream mechanism that unifies these earlier observations.
Studying sleep orthologs in Epsilonproteobacteria through an evolutionary lens: Investigating sleep mysteries through phylogenomics
Authors: Pandi-Perumal Seithikurippu R , Saravanan Konda Mani , Paul Sayan , Warren Spence David , Chidambaram Saravana Babu 
Published: January 2025

ABSTRACTThe current study employed phylogenomic methods to examine the evolutionary role and significance of sleep-related genes inSulfurimonas paralvinellaeof the Epsilonproteobacteria class. This has facilitated the identification of conserved sleep orthologs, including DnaK, serine hydroxymethyltransferase, and potassium channel family proteins, exhibiting sequence similarities ranging from 39.13% to 61.45%. These findings align with prior research indicating that chaperones and ion channels are conserved during sleep. This was demonstrated by the observation that proteins with fewer domains exhibited more significant conservation than others, such as adenylate kinase, which is substantial under selective pressure. Distinct adaptations in bifunctional protein - serine/threonine kinases and phosphatases were linked toS. paralvinellae, an extremophilic organism adapted to high-pressure and/or high-temperature conditions, indicating functional divergence influenced by the organism’s environment. The Gene Ontology study results indicated catalytic activity, potassium channel function, and cellular processes, underscoring the significance of ion channels in regulating the sleep-wake cycle. Furthermore, the categories not recognized as particularly significant for the over-represented genes encompassed metabolic and signal transduction categories, suggesting enhanced functional flexibility within this protein subfamily. The findings emphasize that orthologous interactions are complex and influenced by subfunctionalization and neofunctionalization of ecology and evolution. These findings enhance the existing understanding of the evolution of sleep-related genes and their association with metabolic and environmental changes, providing a foundation for subsequent experimental investigations and cross-taxonomic comparisons.
From Nets to Molecules: A Comparative Study of Stream Fish Diversity Recovery Using Different Sampling Methods in Eastern Amazonia
Authors: Rosa Fabricio dos Anjos Santa , Carvalho Cintia Oliveira , Queiroz Anna Karolina Oliveira de , Silva Derlan José Ferreira , Barreto Silvia Britto , Thorbek Birgitte Lisbeth Graae , Sales João Bráullio de Luna , Mauvisseau Quentin , de Boer Hugo , Ready Jonathan Stuart 
Published: January 2025

ABSTRACTThe Neotropical freshwaters of South America host an exceptional level of ichthyofaunal diversity with over 5,160 species, making it the richest continental fauna worldwide. Despite their richness, these freshwater ecosystems face severe threats from human activities, leading to significant declines in fish populations. Traditional fish sampling techniques, such as netting, have been fundamental to ichthyology, offering insights into species richness and abundance. However, the complexity of stream environments limits the effectiveness of conventional sampling tools. As a result, more elusive or niche species are often missed. In recent years, water environmental DNA (eDNA) has emerged as a complementary method to traditional sampling. It allows for detection of aquatic organisms from water samples, expanding the scope of biodiversity assessments. Nevertheless, eDNA filtration faces challenges, especially in turbid waters, including the likelihood of co-extracting inhibitors that can affect amplification and detection processes, as well as the downstream flow of eDNA signals, which means that samples predominantly detect upstream fauna. To address these limitations, the use of bulk samples, such as stomach contents, provides a robust alternative by directly analyzing biological tissues and leveraging the bidirectional mobility of organisms within the stream, enabling the detection of taxa from both upstream and downstream regions. Given these issues, this study combines traditional netting, water eDNA analysis, and dietary metabarcoding to assess the fish biodiversity in three Neotropical streams in the Capim River basin, Pará, Brazil. The integration of multiple sampling techniques offers a more accurate picture of biodiversity, helping to overcome the limitations of each individual method and providing essential insights for conservation efforts.
Brain-Guided Convolutional Neural Networks Reveal Task-Specific Representations in Scene Processing
Authors: Hansen Bruce C. , Greene Michelle R. , Lewinsohn Henry A.S. , Kris Audrey E. , Smyth Sophie , Tang Binghui 
Published: January 2025

AbstractScene categorization is the dominant proxy for visual understanding, yet humans can perform a large number of visual tasks within any scene. Consequently, we know little about how different tasks change how the scene is processed, represented, and its features ultimately used. Here, we developed a novel brain-guided convolutional neural network (CNN) where each convolutional layer was separately guided by neural responses taken at different time points while observers performed two different tasks on the same set of images. We then reconstructed each layer’s activation maps via deconvolution to spatially assess how different features were used as a function of task. The brain-guided CNN made use of image features that human observers identified as being crucial to complete each task starting around 244 ms and persisted to 402 ms. Critically, because the same images were used across the two tasks, the CNN could only succeed if the neural data captured task-relevant differences. Our analyses of the activation maps across layers revealed that the brain’s spatiotemporal representation of local image features evolves systematically over time. This underscores how distinct image features emerge at different stages of processing, shaped by the observer’s goals and behavioral context.
Genome-wide analysis of DtxR and HrrA regulons reveals novel targets and a high level of interconnectivity between iron and heme regulatory networks inCorynebacterium glutamicum
Authors: Krüger Aileen , Weber Ulrike , Frunzke Julia 
Published: January 2025

AbstractIron is an essential trace element required by nearly all organisms as a cofactor in enzymes, regulatory proteins, and cytochromes of the respiratory chain. Maintaining iron homeostasis is crucial, since elevated levels cause oxidative stress through the formation of reactive oxygen species. InCorynebacterium glutamicum, iron and heme homeostasis are tightly interconnected and controlled by the global regulators DtxR and HrrA. While DtxR senses intracellular Fe2+, the two-component system HrrSA is activated by heme, functioning as a global regulator of heme homeostasis. This study provides the first genome-wide analysis of DtxR and HrrA binding dynamics under varying iron and heme conditions using chromatin affinity purification sequencing (ChAP-seq). Our conditional ChAP- Seq approach revealed 25 novel DtxR targets and 210 previously unrecognized HrrA targets. Among these,metH,encoding homocysteine methyltransferase, andxerC,encoding a tyrosine recombinase, were bound by DtxR exclusively under heme conditions, underscoring condition-dependent variation in DtxR binding. Activation ofmetHby DtxR links iron metabolism to methionine synthesis, potentially relevant for the mitigation of oxidative stress. Beyond novel targets, this study highlights the interconnected nature of the DtxR and HrrA regulons, identifying 16 shared targets with in some cases overlapping operator sequences. Strikingly, we provide several examples for weak ChAP-Seq peaks, often disregarded in global approaches, that feature a significant impact of the regulator on differential gene expression. These findings emphasize the importance of genome-wide profiling under different conditions to uncover novel targets and shed light on the complexity and dynamic nature of bacterial regulatory networks.ImportanceThe trace element iron is essential for life, but elevated levels can rapidly cause cellular damage through oxidative stress. Bacteria, likeCorynebacterium glutamicum, tightly regulate iron and heme homeostasis via the global regulators DtxR and HrrA. This study provides the first analysis of the genome-wide binding patterns of these two regulators demonstrating significant differences in binding dependent on the tested iron regimes. Overall, we identified 25 new DtxR targets and 210 previously unknown HrrA targets, including genes with crucial roles in central metabolism and DNA repair. Notably, DtxR was shown to link iron metabolism to methionine synthesis, which might be important to protect the cell from oxidative stress. Our findings highlight the interconnected nature of DtxR and HrrA networks and underscore the value of condition-specific analysis to deepen the understanding of how bacteria adapt to environmental changes.
Estimating the distribution of fitness effects in aye-ayes (Daubentonia madagascariensis), accounting for population history as well as mutation and recombination rate heterogeneity
Authors: Soni Vivak , Versoza Cyril J. , Pfeifer Susanne P. , Jensen Jeffrey D. 
Published: January 2025

ABSTRACTThe distribution of fitness effects (DFE) characterizes the range of selection coefficients from which new mutations are sampled, and thus holds a fundamentally important role in evolutionary genomics. To date, DFE inference in primates has been largely restricted to haplorrhines, with limited data availability leaving the other suborder of primates, strepsirrhines, largely under-explored. To advance our understanding of the population genetics of this important taxonomic group, we here map exonic divergence in aye-ayes (Daubentonia madagascariensis) – the only extant member of the Daubentoniidae family of the Strepsirrhini suborder. We further infer the DFE in this highly-endangered species, utilizing a recently published high-quality annotated reference genome, a well-supported model of demographic history, as well as both direct and indirect estimates of underlying mutation and recombination rates. The inferred distribution is generally characterized by a greater proportion of deleterious mutations relative to humans, providing evidence of a larger long-term effective population size. In addition however, both immune-related and sensory-related genes were found to be amongst the most rapidly evolving in the aye-aye genome.
Endothelial Sensitivity to Pro-Fibrotic Signals Links Systemic exposure to Pulmonary Fibrosis
Authors: Möbus Lena , Ylä-Outinen Laura , Mannino Luca , Migliaccio Giorgia , Kosunen Karoliina , D’Alessandro Nicoletta , Serra Angela , Greco Dario 
Published: January 2025

SummaryPulmonary fibrosis (PF) is a life-threatening condition characterised by excessive extracellular matrix deposition and tissue scarring. While much of PF research has focused on alveolar epithelial cells and fibroblasts, endothelial cells have emerged as active contributors to the disease initiation, especially in the context of systemic exposure to pro-fibrotic substances. Here, we investigate early transcriptomic and secretory responses of human umbilical vein endothelial cells (HUVEC) to subtoxic doses of bleomycin, a known pro-fibrotic agent, and TGF-beta, a key cytokine in fibrosis. Bleomycin exposure induced a rapid and extensive shift in the endothelial transcriptional programme, including signatures of endothelial to mesenchymal transition, cellular senescence, and immune cell recruitment. These findings suggest endothelial cells as early initiators of pro-fibrotic signals, independent of contributions from other cell types. In contrast, TGF-beta effects were limited and transient, indicating its pro-fibrotic action may require another initial stimulus and interplay with other cells like fibroblasts. This study highlights the sensitivity of endothelial cells to systemic pro-fibrotic exposure and provides a blueprint of early pro-fibrotic mechanisms, emphasising their pivotal role in PF pathogenesis.
Iron retention coupled with trade-offs in localized symbiotic effects confers tolerance to combined iron deficiency and drought in soybean
Authors: Hasan Md Rokibul , Thapa Asha , Kabir Ahmad H. 
Published: January 2025

ABSTRACTIron (Fe) and water availability are closely interlinked, with deficiencies in both adversely affecting soybean growth. However, the strategies employed by soybean to tolerate such conditions remain poorly understood. This study elucidates the interactions of physiological adjustments, host factors, and microbial associations in soybean using multi-omics approaches in Clark (tolerant) and Arisoy (sensitive) genotypes exposed to Fe deficiency and drought. Clark demonstrated stress resilience by maintaining osmotic balance, nutritional status, and photosynthetic efficiency, whereas these were severely affected in Arisoy. Furthermore, Fe retention in Clark, accompanied by the upregulation of ferritin-like proteins, may mitigate oxidative stress by reducing Fenton reactions. Interestingly, the elevated jasmonic acid and salicylic acid in the roots of Clark, compared to the lower levels in Arisoy, may contribute to differential physiological adjustments for stress adaptations. RNA-seq analysis revealed 818 and 500 upregulated, along with 931 and 361 downregulated genes, in roots of Clark and Arisoy, respectively, under stress. We observed the upregulation of symbiotic genes, such asChalcone-flavonone isomerase1 andSWEET10, accompanied by increased rhizosphere siderophore and root flavonoid in Clark. This indicates a significant microbial role in driving differential stress tolerance. Amplicon sequencing revealed distinct root and nodule microbiome dynamics, with Clark recruiting beneficial microbes such asVariovoraxandPaecilomyces, known for promoting plant growth, whereas Arisoy displayed an opposite pattern. In addition, Clark maintainedBradyrhizobiumand tissue nitrogen status, supported by ammonium retention and induction ofAmmonium transporter1 in the roots. Furthermore,in vitrocompatibility betweenV. paradoxusand P. lilacinussuggests a synergistic interaction, with their localized signals benefiting Clark. Remarkably, enriched microbiomes significantly improved growth parameters, accompanied by elevated rhizosphere siderophore in sensitive genotypes under stress. This study is the first to uncover mechanisms of dual stress tolerance in soybean that may advance breeding and biofertilizer strategies for climate resilience.
The microtubule-severing enzyme spastin regulates spindle dynamics to promote chromosome segregation inTrypanosoma brucei
Authors: Souza Onofre Thiago , Zhou Qing , Li Ziyin 
Published: January 2025

AbstractMicrotubule-severing enzymes play essential roles in regulating diverse cellular processes, including mitosis and cytokinesis, by modulating microtubule dynamics. In the early branching protozoan parasiteTrypanosoma brucei, microtubule-severing enzymes are involved in cytokinesis and flagellum length control during different life cycle stages, but none of them have been found to regulate mitosis in any life cycle form. Here, we report the biochemical and functional characterization of the microtubule-severing enzyme spastin in the procyclic form ofT. brucei. We demonstrate that spastin catalyzes microtubule severingin vitroand ectopic overexpression of spastin disrupts spindle microtubulesin vivoin trypanosome cells, leading to defective chromosome segregation. Knockdown of spastin impairs spindle integrity and disrupts chromosome alignment in metaphase and chromosome segregation in anaphase. We further show that the function of spastin requires the catalytic AAA-ATPase domain, the microtubule-binding domain, and the microtubule interacting and trafficking domain, and that the association of spastin with spindle depends on the microtubule-binding domain. Together, these results uncover an essential role for spastin in chromosome segregation by regulating spindle dynamics in this unicellular eukaryote.
Maternal type 2 immunity promotes a microchimeric transfer of systemic type 2 immunity to offspring
Authors: Gabier Malika , Darby Matthew , Chetty Alisha , Taliep Aisha , Cook Peter , Ryffel Bernhard , Dewals Benjamin , Oudhoff Menno , Cunningham Adam , Hickey Emer , Horsnell William 
Published: January 2025

AbstractDuring maternity mothers undergo an immune pivot to a type 2 immune phenotype which is independent of any antigen experience. In this study we present this maternal Type 2 immunity as a key enabler of optimal maternally-driven microchimeric transfer of immunity to helminth infection in offspring.To demonstrate that maternal type 2 immunity dictates offspring immunity we nursed wildtype (WT) offspring on WT or IL-4Rα-/-foster mothers. WT offspring nursed on IL-4Ra-/-mothers acquired a reduced type 2 immune signature compared to WT offspring nursed on WT mothers. This demonstrated maternal IL-4Rα imprints type 2 immunity in offspring. This increased type 2 immunity in offspring related to a maternal IL-4Rα dependent increased frequency of maternal microchimeric cells (MMc) being detected in offspring. Higher worm burdens were detected in offspring nursed on IL-4Rα-/-mothers, demonstrating that an antigen independent promotion of maternal type 2 immunity provides offspring with protective immunity against a helminth infection. To establish the contribution of increased MMc in offspring nursed on WT mothers in the control of infection, we undertook an antibody mediated depletion of MMc cells in WT offspring. This MMc depletion impaired the control of infection and reduced the magnitude of offspring type 2 immune response against a helminth infection. These findings present antigen independent maternal IL-4Rα driven type 2 immunity during pregnancy as critical for imparting a profound immune influence via MMc on offspring immunity to infection.
Extracellular vesicles from diverse fungal pathogens induce species-specific and endocytosis-dependent immunomodulation
Authors: Kwaku Geneva N. , Jensen Kirstine Nolling , Simaku Patricia , Floyd Daniel J. , Saelens Joseph W. , Reardon Christopher M. , Ward Rebecca A. , Basham Kyle J. , Hepworth Olivia W. , Vyas Tammy D. , Zamith-Miranda Daniel , Nosanchuk Joshua D. , Vyas Jatin M. , Brown Harding Hannah 
Published: January 2025

ABSTRACTMicrobial pathogens generate extracellular vesicles (EVs) for intercellular communication and quorum sensing. Microbial EVs also induce inflammatory pathways within host innate immune cells. We previously demonstrated that EVs secreted byCandida albicanstrigger type I interferon signaling in host cells specifically via the cGAS-STING innate immune signaling pathway. Here, we show that despite sharing similar properties of morphology and internal DNA content, the interactions between EVs and the innate immune system differ according to the parental fungal species. EVs secreted byC. albicans,Saccharomyces cerevisiae, Cryptococcus neoformans,andAspergillus fumigatusare endocytosed at different rates by murine macrophages triggering varied cytokine responses, innate immune signaling, and subsequent immune cell recruitment. Notably, cell wall constituents that decorateC. neoformansandA. fumigatusEVs inhibit efficient internalization by macrophages and dampen innate immune activation. Our data uncover the transcriptional and functional consequences of the internalization of diverse fungal EVs by immune cells and reveal novel insights into the early innate immune response to distinct clinically significant fungal pathogens.