bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-invasive eDNA reveals the ecological and genetic status of the Western Capercaillie (Tetrao urogallus aquitanicus) in the Eastern Pyrenees
Authors: Buso Pauline , Paris Céleste , Canal Manon , Tassaint Morgane , Daniello Sylvain , Gibert Anaïs , Palme Rupert , Macho-Maschler Sabine , Llauro Christel , Jacob Gwenaël , Delorme-Hinoux Valérie , Bertrand Joris A. M. , Rey Olivier 
Published: January 2025

ABSTRACTThe Anthropocene era is expected to bring about significant biodiversity and habitat loss for many species. These geographical changes, whether driven by climatic or anthropogenic factors, are likely to lead to considerable alterations in population size, structure, and genetic diversity. Monitoring natural populations is therefore essential to assess these impacts and enable informed conservation strategies for threatened species. The Western Capercaillie (Tetrao urogallus, L. 1758) has a widespread distribution in Boreal forests but fragmented in mountainous regions of the Palearctic, and is locally threatened by climate change, habitat destruction, and human disturbance. Our study focused on the eastern population of the subspeciesT. u. aquitanicus,which is endemic to the Pyrenees mountains. The monitoring of this population has relied on direct methods and no genetic information had been generated so far. Here, we conducted a molecular study based on 229 non-invasive samples (faeces) to assess the ecological and genetic status of local population in the Catalan Nature Reserves of the Pyrénées-Orientales (Occitanie region, France). At the individual level, we assessed multi-locus genotypes, sexing, levels of inbreeding, stress level (Fecal Corticosterone Metabolites; FCMs) and diet. At the population level, we assessed sex ratio, genetic diversity and structure. We identified 62 individuals with a balanced sex ratio and estimated a census size of 79 individuals [95%CI = 68–92] in the study area. Genetic diversity was low and suggested significant inbreeding levels. FCM levels were lower in birds of areas considered as disturbed by humans and metabarcoding approach indicated a geographical structuring of diet composition at the reserve scale, with individuals exhibiting feeding behavior upon only one or few plant species. Our estimate of population census size was higher with figures assessed from lek counts, and the genetic approach provided additional insights on this population, establishing a baseline that will support conservation management plans.
Periodic Obstacles Regulate Membrane Tension Propagation to Enable Localized Mechanotransduction
Authors: Català-Castro Frederic , Bonilla-Quintana Mayte , Sanfeliu-Cerdán Neus , Rangamani Padmini , Krieg Michael 
Published: January 2025

AbstractForces applied to cellular membranes lead to transient membrane tension gradients. The manner in which membrane tension propagates away from the stimulus into the membrane reservoir has emerged as a key property in cellular adaptation, mechanotransduction, and thus organismal physiology. However, it remains unclear whether tension propagation in membranes is actively regulated or is a passive property and how it depends on the cell type. Here, we combined membrane nanorheology with time-shared optical traps and mathematical modeling to investigate plasma membrane tension propagation in culturedCaenorhabditis elegansmechanosensory neurons using a dual tether extrusion assay. Our results showed that, surprisingly, the propagation of tension was restricted to 30 μm in the neurites and traveled quickly, at speeds exceeding 120 μm/s. Although membrane lipid properties had minimal impact, tension propagation strongly relied on the intact actin and microtubule cytoskeleton. In particular, the organization of theα/β-spectrin network and the MEC-2 stomatin condensates acted as barriers, limiting the spread of tension. A biophysical model for tension propagation suggests that obstacle density and arrangement play a key role in controlling the propagation of mechanical information. Our findings suggest that restricting membrane tension propagation in space and time enables precise localized signaling. This localization may facilitate the recruitment of mechanosensitive ion channels and allow a single neuron to process mechanical signals in multiple distinct domains, thus expanding its computational capacity.
New insights into thecis-regulation of theCFTRgene in pancreatic cells
Authors: Blotas Clara , Le Nabec Anaïs , Collobert Mégane , Bulcaen Mattijs , Carlon Marianne S. , Férec Claude , Moisan Stéphanie 
Published: January 2025

AbstractBackgroundSpatial organization of the genome is fundamental for ensuring accurate gene expression. This process depends on the communication between gene promoters and distalcis-regulatory elements (CREs), which together make up 8% of the human genome and are supported by the chromatin structure. It is estimated that over 90% of disease-associated variants are located in the non-coding region of the genome and may affect CRE. For thecystic fibrosis transmembrane conductance regulator(CFTR)gene, a complete understanding of tissue-specificCFTRexpression and regulation is missing, in particular in the pancreas. Mechanistic insights into tissue-specific expression may provide clarity on the clinical heterogeneity observed in Cystic Fibrosis and CFTR-related disorders.MethodsTo understand the role of 3D chromatin architecture in establishing tissue-specific expression of theCFTRgene, we mapped chromatin interactions via circular chromosome conformation capture (4C) and epigenomic regulation through H3K27ac and DNase Hypersensitive site I (DHS) in Capan-1 pancreatic cells. Candidate regulatory regions are validated by luciferase reporter assay and CRISPR-knock out.ResultsWe identified active regulatory regions not only around theCFTRgene but also outside the topologically associating domain (TAD). By performing functional assays, we validated our targets and revealed a cooperative effect of the −44 kb, −35 kb, +15.6 kb and 37.7 kb regions, which share common predicted transcription factor (TF) motifs. Comparative 3D genomic analysis and functional assays using the Caco-2 intestinal cell line revealed the presence of tissue-specific CREs.ConclusionBy studying the chromatin architecture of theCFTRlocus in Capan-1 cells, we demonstrated the involvement of multiple CREs upstream and downstream of theCFTRgene. We also extend our analysis to compare intestinal and pancreatic cells and provide information on the tissue-specificity of CRE. These findings highlight the importance of expanding the search for causative variants beyond the gene coding sequence but also by considering the tissue-specific 3D genome.
Atomic Force Microscopy reveals differences in mechanical properties linked to cortical structure in mouse and human oocytes
Authors: Bulteau Rose , Barbier Lucie , Lamour Guillaume , Lemseffer Yassir , Verlhac Marie-Hélène , Tessandier Nicolas , Labrune Elsa , Lenz Martin , Terret Marie-Emilie , Campillo Clément 
Published: January 2025

ABSTRACTCell mechanical properties regulate biological processes such as oocyte development. Cortical tension is regulated via actomyosin cortex remodeling to ensure optimal oocyte quality. However, the evolution of other mechanical parameters and their relationship with cortex structure remain poorly understood in mammalian oocytes. In this work, we propose a methodology combining multiple mechanical parameters measured through Atomic Force Microscopy to investigate the relationship between oocyte mechanical properties and cortex organization. By studying mouse oocytes at various stages of development, along with engineered ones with specific cortex organization, we demonstrate that a thin actin cortex corresponds to stiff oocytes while a thick one is associated with softer oocytes. We further reveal that maternal age, a critical factor for fertility, affects mouse oocytes mechanics correlating with alterations in their cortex structure. Finally, we show that the evolution of mechanical properties differs between human and mouse oocyte development, highlighting species-specific differences in cortex organization.
The Lipocone Superfamily: A Unifying Theme In Metabolism Of Lipids, Peptidoglycan And Exopolysaccharides, Inter-Organismal Conflicts And Immunity
Authors: Burroughs A. Maxwell , Nicastro Gianlucca G. , Aravind L 
Published: January 2025

ABSTRACTWnt proteins are critical signaling molecules in developmental processes across animals. Despite intense study, their evolutionary roots have remained enigmatic. Using sensitive sequence analysis and structure modeling, we establish that the Wnts are part of a vast assemblage of domains, the Lipocone superfamily, defined here for the first time. It includes previously studied enzymatic domains like the phosphatidylserine synthases (PTDSS1/2) and the TelC toxin domain fromStreptococcus intermedius, the enigmatic VanZ proteins, the animal Serum Amyloid A (SAA) and a further host of uncharacterized proteins in a total of 30 families. Though the metazoan Wnts are catalytically inactive, we present evidence for a conserved active site across this superfamily, versions of which are consistently predicted to operate on head groups of either phospholipids or polyisoprenoid lipids, catalyzing transesterification and phosphate-containing head group severance reactions. We argue that this superfamily originated as membrane proteins, with one branch (including Wnt and SAA) evolving into soluble versions. By comprehensively analyzing contextual information networks derived from comparative genomics, we establish that they act in varied functional contexts, including regulation of membrane lipid composition, extracellular polysaccharide biosynthesis, and biogenesis of bacterial outer-membrane components, like lipopolysaccharides. On multiple occasions, members of this superfamily, including the bacterial progenitors of Wnt and SAA, have been recruited as effectors in biological conflicts spanning inter-organismal interactions and anti-viral immunity in both prokaryotes and eukaryotes. These findings establish a unifying theme in lipid biochemistry, explain the origins of Wnt signaling and provide new leads regarding immunity across the tree of life.
Decoding MASLD Progression: A Molecular Trajectory-Based Framework for Modelling Disease Dynamics
Authors: Kamzolas Ioannis , Koutsandreas Thodoris , Barker Charlie George , Vathrakokoili Pournara Anna , Weston Harry , Vacca Michele , Papatheodorou Irene , Vidal-Puig Antonio , Petsalaki Evangelia 
Published: January 2025

AbstractMetabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has emerged as a silent pandemic, affecting nearly one-third of the global population. This condition encompasses a spectrum of liver disorders, ranging from simple steatosis to Metabolic Dysfunction-Associated Steatohepatitis (MASH), which is characterised by liver steatosis, lipotoxicity, hepatocellular damage, inflammation, and fibrosis. Left unchecked, MASLD/MASH can progress to cirrhosis and hepatocellular carcinoma. Despite the progressive nature of MASLD/MASH, current research primarily relies on static, histopathologically defined stages, which fail to capture the dynamic disease continuum.In this study, we present an integrative stratification approach that combines patient pseudo-temporal ordering, network analysis, and cell-type deconvolution to map the continuous disease trajectory. By analyzing transcriptomic profiles, we predict patients’ positions along this trajectory, moving beyond conventional stage-based classifications. This approach reveals the sequence of critical molecular events driving MASLD/MASH progression, providing new insights into the disease’s pathophysiology. Furthermore, we identify novel trajectory-specific biomarkers that support a more refined, personalised strategy for managing MASLD. This work highlights the potential of trajectory-based frameworks in advancing our understanding and treatment of complex metabolic diseases.
Cell Type-Specific and Diabetic Kidney Disease-Associated Expression of Long Non-Coding RNAs in Human Kidneys
Authors: de Klerk Juliette A , Slieker Roderick C , Parker Wilson C , Wu Haojia , Muto Yoshiharu , Postma Rudmer J , ’t Hart Leen M , Peerlings Janneke HD , Herrewijnen Floris , Song Heein , Spijker H Siebe , Dumas Sébastien J , Koning Marije , van der Pluijm Loïs AK , Baelde Hans J , Gerrits Tessa , Rotmans Joris I , van Zonneveld Anton Jan , van Solingen Coen , Humphreys Benjamin D , Bijkerk R 
Published: January 2025

AbstractBackgroundLong non-coding RNAs (lncRNAs) play essential roles in cellular processes, often exhibiting cell type-specific expression and influencing kidney function. While single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cellular specificity, past studies focus solely on protein-coding genes. We hypothesize that lncRNAs, due to their cell-specific nature, have crucial functions within particular renal cells and thereby play essential roles in renal cell function and disease.MethodsUsing single-nucleus RNA sequencing (snRNA-seq) data from kidney samples of five healthy individuals and six DKD patients, we explored the non-coding transcriptome. Cell type-specific lncRNAs were identified, and their differential expression in DKD was assessed. Integrative analyses included expression quantitative trait loci (eQTL), genome-wide association studies (GWAS) for estimated glomerular filtration rate (eGFR), and gene regulatory networks. Functional studies focused onTARID, a lncRNA with podocyte-specific expression, to elucidate its role in podocyte health.Resultswe identified 349 lncRNAs with cell type-specific expression across kidney cell types. Of these, 104 lncRNAs were differentially expressed in DKD. Integrative analyses, including eQTL data, GWAS results for eGFR and gene regulatory networks, pinpointedTARID, a podocyte-specific lncRNA, as a key candidate upregulated in DKD. Functional studies confirmedTARID’s podocyte-specific expression and revealed its central role in actin cytoskeleton reorganization, a critical process in podocyte health.ConclusionsOur study provides a comprehensive resource of single-cell lncRNA expression in the human kidney and highlights the importance of cell type-specific lncRNAs in kidney function and disease. Specifically, we demonstrate the functional relevance ofTARIDin podocyte health. This work underscores the utility of integrating scRNA-seq with functional genomics to uncover novel regulatory mechanisms in kidney biology.Key pointsThis provides a resource for kidney (cell type-specific) lncRNA expression and demonstrates the importance of lncRNAs in renal health.We identified 349 cell type-specific lncRNAs in the human kidney, with 104 showing altered expression in diabetic kidney disease (DKD).TARID, a podocyte-specific lncRNA upregulated in DKD, is crucial for actin cytoskeleton reorganization in podocytes.
Spatial map of native duct cell populations in human pancreas and their representation in pancreatic cancers
Authors: Van den Bossche JL , Van der Vliet M , Michiels E , Senar O Azurmendi , Madran Z , Coolens K , Van Lint S , Nacher M , Arsenijevic T , Messaoudi N , Lefesvre P , Montanya E , Rovira M , Van Laethem J , Baldan J , Houbracken I , Rooman I 
Published: January 2025

AbstractBackground & AimsEpithelial tumors generally resemble the cellular architecture of their tissue of origin. However, this link remains largely unexplored in the pancreas.MethodsUsing Nanostring GeoMx DSP®, Resolve Molecular Cartography® and Nanostring CosMx®, and integration with single cell RNAseq datasets, we mapped the human pancreatic ductal epithelium in non-neoplastic pancreas, and compared it to pancreatic cancer subtypes.ResultsGroups of Keratin-5+cells among the Pan-Cytokeratin+cells in the duct have a gene signature reminiscent of stem cells and (supra)basal cells from other tissues. In spatial analysis at single cell resolution, the pancreatic duct manifests as a stratified epithelium comprising a basal and four luminal populations; In large ducts, KRT5+basal (BAS) cells express ΔNp63 while KRT5+luminal (LUM)-B cells reside supra-basally and are distinct from the common KRT5-LUM-A cells. LUM-C and LUM-D cells pertain to intercalated ducts and ductal glands, respectively. LUM-A and -C cells express gel-forming mucins while LUM-B cells have membrane-bound MUC4 and MUC16. In cancer, BAS and LUM-B signatures associate with the basal-like pancreatic ductal adenocarcinoma (PDAC) and correlate with lower survival but exhibit a mixed spatial pattern with a diffracted gene signature. In contrast, adenosquamous cancers of the pancreas (ASCP) preserve the normal spatially unmixed identity of LUM-B cells and BAS cells that is regulated by ΔNp63. Next to ΔNp63, conserved drug targets were identified for both populations.ConclusionThis study offers a refined pancreatic tumor classification based on the native ductal architecture, with better preservation of the LUM-B and BAS cell population identity in ASCP than in PDAC, including the conserved drug targets.
The Single-Cell Landscape of Peripheral and Tumor-infiltrating Immune Cells in HPV- HNSCC
Authors: Galvani Rômulo Gonçalves Agostinho , Rojas Adolfo , Matuck Bruno F. , Rupp Brittany T. , Kumar Nikhil , Huynh Khoa , de Biagi Junior Carlos Alberto Oliveira , Liu Jinze , Sheth Siddharth , Maria Krol Jelte Martinus , Maracaja-Coutinho Vinicius , Byrd Kevin Matthew , Severino Patricia 
Published: January 2025

AbstractHead and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. HPV-negative HNSCC, which arises in the upper airway mucosa, is particularly aggressive, with nearly half of patients succumbing to the disease within five years and limited response to immune checkpoint inhibitors compared to other cancers. There is a need to further explore the complex immune landscape in HPV-negative HNSCC to identify potential therapeutic targets. Here, we integrated two single-cell RNA sequencing datasets from 29 samples and nearly 300,000 immune cells to investigate immune cell dynamics across tumor progression and lymph node metastasis. Notable shifts toward adaptative immune cell populations were observed in the 14 distinct HNSCC-associated peripheral blood mononuclear (PBMCs) and 21 tumor-infiltrating immune cells (TICs) considering disease stages. All PBMCs and TICs revealed unique molecular signatures correlating with lymph node involvement; however, broadly, TICs increased ligand expression among effector cytokines, growth factors, and interferon-related genes. Pathway analysis comparing PBMCs and TICs further confirmed active cell signaling among Monocyte-Macrophage, Dendritic cell, Natural Killer (NK), and T cell populations. Receptor-ligand analysis revealed significant communication patterns shifts among TICs, between CD8+ T cells and NK cells, showing heightened immunosuppressive signaling that correlated with disease progression. In locally invasive HPV-negative HNSCC samples, highly multiplexed immunofluorescence assays highlighted peri-tumoral clustering of exhausted CD8+ T and NK cells, alongside their exclusion from intra-tumoral niches. These findings emphasize cytotoxic immune cells as valuable biomarkers and therapeutic targets, shedding light on the mechanisms by which the HNSCC sustainably evades immune responses.
Age-Associated Decline in Autophagy Pathways in Retinal Pigment Epithelium and Protective Effects of Topical Trehalose in Light-induced Outer Retinal Degeneration in Mice
Authors: Cox Katherine , Shi Gongyu , Read Neve , Ou Kepeng , Liu Zijia , Wu Jiahui , Cendanawati Suci , Powell Jenna Le Brun , Nicholson Lindsay B. , Dick Andrew D. , Liu Jian 
Published: January 2025

AbstractAge is a primary risk factor for chronic conditions, including age-related macular degeneration (AMD). Impairments in autophagy processes are implicated in AMD progression, but the extent of autophagy’s contribution and its therapeutic potential remain ambiguous. This study investigated age-associated transcriptomic changes in autophagy pathways in the retinal pigment epithelium (RPE) and evaluated the protective effects of topical trehalose, an autophagy-enhancing small molecule, against light-induced outer retinal degeneration in mice. Transcriptomic analysis of human RPE/choroid and mouse RPE revealed consistent downregulation of autophagy pathways with age, alongside variable changes as AMD severity progressed. Given the age- and AMD-associated perturbation of autophagy pathways, we examined trehalose treatmentin vitro, which enhanced autophagic flux and restored mitochondrial respiratory function in primary murine RPE cells exposed to oxidative stress.In vivo, topical trehalose improved autophagy-lysosome activity in mouse RPE, demonstrated by elevated LC3B turnover and SQSTM1/p62 degradation. Furthermore, trehalose eyedrops protected mice from light-induced damage to the RPE and photoreceptors, preserving outer nuclear layer thickness, RPE morphology, and junctional F-actin organization. Taken together, the data support that age-related decline and severe dysregulation in autophagy contributed to AMD progression. By restoring autophagic flux, topical trehalose demonstrates therapeutic potential to address early autophagy-related pathological changes in AMD.
Investigating antiviral pathways in Atlantic salmon cells through interferon receptor knockouts via CRISPR-Cas9
Authors: Reza Mohammad Ali Noman , Harvey Thomas Nelson , Ahmed Abdelrahim Gamil Amr , Evensen Øystein , Gillard Gareth Benjamin , Sandvik Guro Katrine 
Published: January 2025

AbstractIn Atlantic salmon (Salmo salar), infectious salmon anemia virus (ISAV) and infectious pancreatic necrosis virus (IPNV) evade host immune response through complex antagonistic mechanisms. Type I interferons (IFNs) play a pivotal role in antiviral defense by signaling through heterodimeric receptors to activate the JAK-STAT pathway and drives the expression of interferon-stimulated genes (ISGs). In this study, CRISPR-Cas9 was used to knock out (KO) interferon receptor genes (crfb1a,crfb5a,il10rb,ifngr2a) and a combined group of candidate receptors (crfb1a,crfb5a,il10rb,ifngr2a,il10r2) to investigate their roles and their impact on downstream signaling cascades with RNA sequencing. Recombinant IFNa was used to induce an antiviral state before challenging cells with ISAV and IPNV.The knockouts significantly disrupt downstream antiviral signaling, with two knockouts,crfb1aandcrfb5a, showing pronounced effects. During ISAV infection, thecrfb1aKO group exhibited a marked reduction in the expression of critical signaling genes such asstat1b, stat2, stat6,andirf3during ISAV infection, whileirf7was upregulated during IPNV infection. Thecrfb5aKO group exhibited reducedstat2expression in ISAV infection and upregulatedirf7during IPNV infection. Despite these disruptions, ISGs such asMxandisg15maintained their expression levels across all knockout groups, suggesting potential alternative signaling pathways. Pathway analysis further revealed upregulation of cellular processes like actin regulation and phagosome activity, which may compensate for impaired immune signaling. These findings highlight the distinct roles of IFN receptor genes in mediating antiviral responses and underscore the complexity of IFN signaling in Atlantic salmon.