bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Potential Spawning Areas: a novel framework for elasmobranch conservation and spatial management
Authors: Ruiz-García David , Barría Claudio , Colmenero Ana I. , Raga Juan A. , March David 
Published: February 2025

AbstractDefining and protecting critical habitats for elasmobranchs (sharks and rays), such as spawning areas, is essential for mitigating anthropogenic pressures that threaten their populations, primarily driven by fisheries and habitat degradation. This study presents a novel modelling-based framework to identify Potential Spawning Areas (PSAs) - habitats offering optimal conditions for oviposition. Using fisheries-dependent trawl bycatch data combined with environmental and anthropogenic predictors, we applied machine-learning models to delineate PSAs for the smallspotted catshark (Scyliorhinus canicula) and skates (Raja spp.) in the western Mediterranean. Static environmental predictors, including depth and slope, were primary drivers, while dynamic predictors, including sea bottom temperature and salinity played seasonally relevant roles. Trawl fishing pressure also influenced importantly the distribution of PSAs, revealing a concerning positive feedback loop between exploitation and habitat degradation. While PSAs experienced lower fishing effort than the rest of the study area, a substantial proportion of egg case bycatch still occurs within them. The current network of Marine Protected Areas in the region fails to adequately safeguard these habitats due to limited coverage and enforcement. Our findings underscore significant gaps in spatial management and the urgent need for targeted conservation measures. The PSA framework provides a robust, scalable tool for identifying critical habitats across regions and species, offering actionable insights for marine spatial planning and ecosystem-based management. This adaptable approach can support global conservation efforts for elasmobranchs and their ecosystems.SignificanceSharks and rays are vital to marine ecosystems but face alarming extinction risks due to overfishing and habitat loss. Identifying critical reproductive habitats, such as spawning areas, is essential for protection but remains a significant challenge. This study introduces a novel framework for identifying Potential Spawning Areas (PSAs) - habitats offering optimal conditions for oviposition - using machine-learning and fisheries bycatch data. Applied in the western Mediterranean for the smallspotted catshark and skates, it demonstrates how environmental factors and fishing pressures shape these habitats, highlighting significant management gaps. The PSAs framework offers a scalable approach to guide the establishment of marine protected areas and fisheries management plans, providing a novel approach for conserving vulnerable marine species and their habitats.
Genomic and functional adaptations in guanylate-binding protein 5 (GBP5) highlight specificities of bat antiviral innate immunity
Authors: Le Corf Amandine , Maesen Sarah , Loyer Clara , Vazquez Juan Manuel , Lauterbur M. Elise , Sareoua Lucas , Gray-Sandoval Genevieve , Cimarelli Andrea , Rey Carine , Sudmant Peter H , Enard David , Etienne Lucie 
Published: February 2025

AbstractBats are asymptomatic reservoirs of several zoonotic viruses. This may result from long-term coevolution between viruses and bats, that have led to host adaptations contributing to an effective balance between strong antiviral responses with innate immune tolerance. To better understand these virus-host interactions, we combined comparative transcriptomics, phylogenomics and functional assays to characterize the evolution of bat innate immune antiviral factors. First, we stimulated the type I interferon immune pathway inMyotis yumanensisprimary cells and identified guanylate-binding protein 5 (GBP5) as the most differentially expressed interferon-stimulated gene (ISG). Phylogenomic analyses showed that bat GBP5 has been under strong episodic positive selection, with numerous rapidly evolving sites and species-specific gene duplications, suggesting past evolutionary arms races. Functional tests on GBP5 orthologs from ten bat species covering the >60 million years of Chiroptera evolution revealed species- and virus-specific restrictions against RNA viruses (retrovirus HIV, and rhabdoviruses European bat lyssavirus and VSV), which are typical signatures of adaptations to past viral epidemics. Interestingly, we also observed a lineage-specific loss of the GBP5 prenylation motif in the common ancestor ofPipistrellusandEptesicusbats, associated with different GBP5 subcellular localization and loss of antiviral functions. Resurrection of the ancestral prenylation motif inEptesicus fuscusGBP5 rescued its subcellular localization, but not the complete antiviral activities, suggesting that additional determinants are necessary for the antiviral restriction. Altogether, our results highlight adaptations that contribute to bat specific immunity and provide insights into the functional evolution of antiviral effector GBP5.Key FindingsGBP5 is the most differentially expressed gene upon type I interferon stimulation ofMyotis yumanensisprimary cells.Bat GBP5 has evolved under strong episodic genomic and genetic diversification, including early stop codon leading to protein truncation and loss of prenylation motif.GBP5 diversification in bats impacts their subcellular localization and antiviral functions.Bat GBP5s exhibit species- and virus-specificity in their ability to inhibit infectivity of viral particles, bearing glycoproteins from retroviral HIV, vesicular stomatitis virus and European bat lyssavirus-1.Resurrection of the ancestral prenylation motif in a bat GBP5 rescues its subcellular localization but not its full antiviral activity
Investigating Gene Expression Noise Reduction by MicroRNAs and MiRISC Reinforcement by Self-Feedback Regulation of mRNA Degradation
Authors: Tian Shuangmei , Zhao Ziyu , Kassie Meharie G. , Zhang Fangyuan , Ren Beibei , Wang Degeng 
Published: February 2025

AbstractMicroRNA (miRNA) induced silencing complex (miRISC) is the targeting apparatus and arguably rate-limiting step of the miRNA-mediated regulatory subsystem – the major noise reducing though metabolically wasteful mechanism. Recently, we reported that miRISC channels miRNA-mediated regulatory activity back onto their own mRNAs to form negative self-feedback loops, a noise-reduction technique in engineering and synthetic/systems biology. Here, we describe mathematical modeling that predicts mRNA expression noise to correlate negatively with degradation rate (Kdeg) and noise reduction by self-feedback control of Kdeg. We also calculated Kdegand expression noise of mRNAs detected in a cutting-edge total-RNA single-cell RNA-seq (scRNA-seq) dataset. As predicted, miRNA-targeted mRNAs exhibited higher Kdegvalues in conjunction with lower inter-cell expression noise. Moreover, as predicted by our self-feedback loop model, miRISC mRNAs (AGO1/2/3 and TNRC6A/B/C) exhibited further reduced expression noise. In short, mathematical-modeling and total-RNA scRNA-seq data-analysis shed insight into operational trade-off between noise reduction and metabolic/energetic expenditure in producing miRNA-targeted mRNAs destined for enhanced degradation and translational inhibition, as well as negative self-feedback loop reinforcement of miRISC – the core of miRNA-mediated noise-reduction subsystem. To our knowledge, this is the first report of concurrent mRNA degradation and expression noise analyses and of noise reduction by self-feedback control of mRNA degradation.
CycleMix: Gaussian Mixture Modeling of the Cell Cycle
Authors: Peplinski Jack Edward , Andrews Tallulah 
Published: February 2025

AbstractThe cell cycle is a crucial component of many biological processes, including cancer, tissue repair, and inflammation. However, due to the heterogeneity of this cycle it has been difficult to assess the extent of proliferation in clinical tissues. Single-cell RNAseq (scRNAseq) and spatial transcriptomics enables high resolution measurement of gene expression enabling the classification of individual cells into their cycling state. The most widely used method for cell-cycle assignment is Seurat, however their approach is limited to classifying cells into only 3 states: G1, S, G2M and frequently incorrectly labels fully mature non-cycling cells (e.g. neurons) as S/G2M. Here we propose CycleMix, an alternative cell-cycle assignment algorithm that can flexibly assign cells into any number of states provided sufficient marker genes as well as being capable of identifying when cells are not cycling.
CyclicBoltz1, fast and accurately predicting structures of cyclic peptides and complexes containing non-canonical amino acids using AlphaFold 3 Framework
Authors: Xie Xuezhi , Li Christina Z , Lee Jin Sub , Kim Philip M 
Published: February 2025

AbstractCyclic peptides exhibit favourable properties making them promising candidates as therapeutics. While the design and modeling of peptides in general has seen rapid advances since the advent of modern machine learning methods, existing deep learning models cannot effectively predict cyclic peptide structures containing non-canonical amino acids (ncAAs), which are often crucial for peptide therapeutics. To address this limitation, we here extend the recent AF3-style model Boltz to cyclic peptides with ncAAs. In addition to the positional encoding offset, we used a simple yet effective extension of the cyclic offset encoding based on AlphaFold3’s tokenization scheme that allows the modeling of cyclic peptides with modified residues. On a test set of peptides with ncAAs, our approach outperforms HighFold2 on 13/17 cases, with an average CαRMSD of 1.877Å and an average all-atom RMSD of 3.361Å. Our results show that the cyclic offset encoding shown for AlphaFold2 generalizes to AlphaFold3-based models and can be extended to incorporate ncAAs, showing potential in the design of novel cyclic peptides with ncAAs for therapeutic applications.
p21-activated kinase regulates Rab3a vesicles to repair plasma membrane damage caused by Amyloid-β oligomers
Authors: Valappil Deepak Kunhi , Veerabhadraswamy Priyadarshini , Sarathi Shylaja Partha , Hegde Prakhyath , Gowda Jeevan M , Kumar Anujith , Gandasi Nikhil R , Nath Sangeeta 
Published: February 2025

AbstractThe interaction of amyloid-β (Aβ) peptides with the plasma membrane (PM) is a potential trigger that initiates the formation of higher-order aggregates, membrane alterations/damage, and progressive neurotoxicity in Alzheimer’s disease (AD). In a previous study, we showed that oligomers of Aβ1-42(oAβ1-42) induced PM damage, resulting in PM repair cascade via lysosomal exocytosis coupled with endocytosis, and facilitation of tunneling nanotubes (TNTs)-like membrane protrusions to promote direct cell-to-cell transfer of aggregates. In this study, we demonstrated that PM damage induced by oligomers of the aggregation-prone peptide Aβ1-42significantly facilitates PM repair by enhancing phosphorylated p21-activated kinase 1 (pPAK1)-dependent endocytosis and Rab3a-dependent exocytosis in SH-SY5Y and SK-N-SH neuronal cells compared to control and oAβ1-40treated cells. We studied the kinetics of pPAK1-dependent endocytosis and the fusion of EGFP-Rab3a vesicles near the PM using total internal reflection fluorescence (TIRF) microscopy. IPA-3, a selective non-ATP competitive inhibitor of PAK1, inhibits endocytosis of oAβ peptides and Rab3a-dependent PM repair. Further, shRNA-mediated knockdown of the Rab3a gene inhibits pPAK1 and disrupts PM repair. Repair of damaged PM is a vital protective mechanism for non-proliferative cells like neurons, as disruption in PM repair leads to gradual neuronal cell death. However, there was no explicit understanding of PM repair in response to Aβ oligomers. This study revealed the interconnected action of Rab3a and pPAK1 in PM repair in response to oAβ-mediated damage, and its potential correlation in AD pathogenesis.
A Novel TRPC6 Mutation Causes Autosomal Dominant FSGS
Authors: Bhattacharya Rohan , Mou Xingrui , Leeman Sophia M. , Mishra Alekshyander , Kalejaiye Titilola D. , Stangl Megan , Silas Daniel , Soldano Karen , Sperati C. John , Olabisi Opeyemi , Hall Gentzon , Musah Samira 
Published: February 2025

SUMMARYFSGS is the most common primary glomerular lesion that causes kidney failure in the US. FSGS results from injury or loss of glomerular visceral epithelial cells (i.e. podocytes). Pathogenic variants inTRPC6can cause FSGS through dysregulated calcium conductance and associated disturbances in podocyte physiology. Here, we describe a 5-generation kindred with FSGS caused by a novel compound C-terminal TRPC6 mutation. Analysis of patient-specific iPSC-derived podocytes and glomerular capillary wall-on-a-chip systems revealed that the compound variants disrupt TRPC6 protein structure, intermolecular interactions, and membrane localization. Combined therapy with Sildenafil and Losartan ameliorated these disturbances compared to conventional immunosuppressive treatment.
Intermittent Fasting Reprograms Chromatin Accessibility to Modulate Gene Expression in Brain and Muscle
Authors: Fan Yibo , Peng Xiangyuan , Ebrahimi Mansour , Tabassum Nishat I. , Cheng Xiangru , Kumar Yatendra , Liu Yong U. , Chen Guobing , Okun Eitan , Johns Terrance G. , Sobey Christopher G. , Lai Mitchell K. P. , Gunaratne Jayantha , Mattson Mark P. , Jo Dong-Gyu , Arumugam Thiruma V. 
Published: February 2025

AbstractIntermittent fasting (IF), a dietary regimen that mimics the natural feeding patterns observed across diverse organisms—from single-celled life to mammals—is thought to activate systemic survival responses and confer health benefits. However, the molecular mechanisms underlying these effects remain poorly understood. In this study, we utilized ATAC-Seq and RNA-Seq to investigate how IF influences chromatin accessibility and gene expression in brain and muscle tissues of mice, compared to ad libitum feeding. Our results reveal that IF induces significant changes in chromatin accessibility, modulating pathways related to metabolism, ribosome function, HIF-1 signaling, and glycolysis. Motif analysis identified tissue-specific transcription factors enriched in IF-regulated regions, including Sp1, Mef2a, NeuroD2, Banp, and NFIA in the brain, and SMAD4, TCF4, STAT5B, NKX3-1, and ZEB2 in muscle. Integrative analysis of ATAC-Seq and RNA-Seq data demonstrated that IF upregulates 50 genes and downregulates 15 in the cortex, while upregulating 31 genes and downregulating 10 in muscle. These gene expression changes are linked to pathways associated with neuroprotection and enhanced muscle function, offering mechanistic insights into the health benefits of IF. Our findings underscore the role of IF-induced chromatin remodeling in driving adaptive gene regulation.
SMCLMDA: statistical meta-paths contrastive learning for predicting miRNA-disease multidimensional relationships
Authors: Zhu Yangfeng , Fan Yongxian , Sun Guicong , Li Xueping 
Published: February 2025

AbstractThe accurate identification of miRNA-disease associations plays a crucial role in biomedical research and clinical applications. However, most research focuses on the existence of the association, without conducting further exploration. In this study, we propose a novel statistical meta-path contrastive learning-based approach (SMCLMDA), which aims to accurately identify the multidimensional relationships(up/down-regulation and causal/non-causal) between miRNAs and diseases. SMCLMDA first obtains the local structural information of miRNAs and diseases based on Node2Vec and uses it as the initial node input of the graph convolutional neural network (GCN). Then, the meta-path view constructed by the statistical method further enhances the representation of the similarity view via a contrastive learning strategy. Finally, SMCLMDA calculates the predicted probability of the multidimensional relationships of miRNA-disease via a multilayer perceptron(MLP). The experimental results demonstrate that SMCLMDA surpasses current state-of-the-art computational methods in predicting traditional associations, as well as up/down-regulation and causality/non-causality relationships. The case study additionally validates the effectiveness of SMCLMDA in identifying potential miRNA-disease associations.
Immune response to co-administration of bovine tuberculosis and contraceptive vaccines in badgers (Meles meles)
Authors: Palphramand Kate L. , Anderson Paul , Bellamy Fiona , Birch Colin , Davé Dipesh , Eckery Doug , Gomm Matt , Jinks Rachel , Massei Giovanna , Pinkham Rebecca , Rahou Sabah , Simmons Hugh , Vial Flavie , Williams Gareth A. , Smith Graham C. 
Published: February 2025

AbstractControlling bovine tuberculosis (bTB) in livestock is often hindered by the presence of a wildlife reservoir, such as the Eurasian badger in the UK and Ireland. Vaccinating badgers against bTB can reduce the severity ofMycobacterium bovisinfection and potential onwards transmission to cattle, badgers and other species, thus combined with population control might provide additional benefits (and reference models). To evaluate the effects of co-administration of a bTB vaccine (BCG) and a contraceptive vaccine (GonaCon), captive badgers were injected intramuscularly with either BCG only, GonaCon only or BCG+GonaCon (phase 1). The duration of immune response to BCG vaccination and booster vaccination was also evaluated in the BCG only group over a 24-month period (phase 2). The cellular immune responses to purified protein derivatives PPDA and PPDB, used to measure the effects of BCG, did not differ significantly between the BCG only and BCG+GonaCon badgers but were significantly different between the BCG only and GonaCon only badgers. Anti-GnRH antibody titres, quantified to measure the effect of GonaCon, peaked at the first sampling point for the majority of badgers in the GonaCon only and BCG+GonaCon groups. Throughout phase 1, lasting three months post-vaccination, badgers in both GonaCon treatment groups maintained high anti-GnRH antibody titres (1:128,000 or above) that are associated with infertility in this species, with no significant difference between the two GonaCon groups. The immune responses to BCG vaccination in the BCG only badgers (phase 2) were elevated at the first sampling point, approximately three weeks after initial vaccination and booster vaccination, generally declining thereafter. The results from the current study suggest that co-administration of BCG and GonaCon do not have notable deleterious effects on either of the vaccines and that the protective effect of BCG is enhanced by booster vaccination. The protective effects afforded by both vaccines when given together, in terms of reduced disease burden or fecundity, should be determined by further studies.
Over half of the phylogenetic diversity accumulated on the African plant tree of life may be eroded under current biodiversity crisis even though threatened species are not evolutionarily unique
Authors: Tiawoun Makuete A.P. , Phogole Bopaki , Kandolo Bahati Samuel , Yessoufou Kowiyou 
Published: February 2025

AbstractAlthough Africa contributes tremendously to global biodiversity, we have a poor understanding of how the African tree of life might be pruned owing to the ongoing biodiversity crisis. Here, we investigated this question integrating statistics and phylogenetics of ∼24000 African vascular plants. We found that 54% of African plant families are hot nodes of threatened species, thus heightening the risk of losing entire clades. We also found that, if all threatened species go extinction, 59% of the evolutionary history of the African plant tree of life would be eroded, and this loss is more than expected at random, although threatened species are not evolutionarily unique. Unfortunately, ∼72% of threatened species and ∼79% of the top-1000-EDGE species are not found in any form of protected areas. Overall, our analysis reveals the extent of biodiversity crisis in Africa and the need for steadfast commitments to i) increased data collection efforts particularly in central African regions and ii) implementation of existing policy for an accelerated recovery.
Cholesterol depletion activates trafficking-coupled sphingolipid synthesis
Authors: Kim Yeongho , Parolek Jan , Burd Christopher G. 
Published: February 2025

AbstractWithin cellular membranes, sphingomyelin is associated with cholesterol and this complex facilitates homeostatic regulation of membrane viscosity. Acute cholesterol depletion increases the synthesis of very-long-chain (VLC) sphingomyelin, but a link between lipid sensing and sphingolipid synthesis is lacking. Using sphingolipid metabolic flux analysis, we observed that VLC-ceramide, the precursor to VLC complex sphingolipids that are produced in the Golgi apparatus, was rapidly consumed after cholesterol depletion, while synthesis of long-chain sphingolipids was unaffected. Sphingolipid trafficking assays showed that cholesterol depletion enhances VLC-Ceramide trafficking from the endoplasmic reticulum to the Golgi apparatus. Changes in the sizes of coatomer II ER exit sites were correlated with increased VLC-Ceramide trafficking and concomitant increase in sphingomyelin. Depletion of Sec16A, a component of the COPII network, abolished VLC-SM synthesis. This study reveals ER-to-Golgi trafficking of VLC-Ceramide as a key regulatory node in organelle membrane homeostasis pathways.SummaryIn cellular membranes, sphingomyelin is associated with cholesterol. Metabolic flux analysis of sphingolipid metabolism showed that synthesis rate of sphingomyelin, but not ceramide, was increased after depletion of cholesterol due increased rate of COPII-dependent ER-to-Golgi transport of ceramide.
A functional map of phosphoprotein phosphatase regulation identifies an evolutionary conserved reductase for the catalytic metal ions
Authors: Meeusen Bob , Ambjørn Sara M. , Veis Jiri , Riley Rachel C. , Vit Gianmatteo , Brauer Brooke L. , Møller Mads H. , Greiner Elora C. , Chan Camilla B. , Weisser Melanie B. , Garvanska Dimitriya H. , Zhu Hao , Davey Norman E. , Kettenbach Arminja N. , Ogris Egon , Nilsson Jakob 
Published: February 2025

AbstractSerine/Threonine phosphoprotein phosphatases (PPPs, PP1-PP7) are conserved metalloenzymes and central to intracellular signaling in eukaryotes, but the details of their regulation is poorly understood. To address this, we performed genome-wide CRISPR knockout and focused base editor screens in PPP perturbed conditions to establish a high-resolution functional map of PPP regulation that pinpoints novel regulatory mechanisms. Through this, we identify the orphan reductase CYB5R4 as an evolutionarily conserved activator of PP4 and PP6, but not the closely related PP2A. Heme binding is essential for CYB5R4 function and mechanistically involves the reduction of the metal ions in the active site. Importantly, CYB5R4-mediated activation of PP4 is critical for cell viability when cells are treated with DNA damage-inducing agents known to cause oxidative stress. The discovery of a dedicated PPP reductase points to shared regulatory principles with protein tyrosine phosphatases, where specific enzymes dictate activity by regulating the active site redox state. In sum, our work provides a resource for understanding PPP function and the regulation of intracellular signaling.