bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences between Scaly-sided Merganser (Mergus squamatus) and Common Merganser (M. merganser) feather microstructure
Authors: Li Donghong , Zhang Shiyu , Tian Ran , Zhao Yongbin , Yi Guodong 
Published: February 2025

AbstractThe microstructures of breast feathers, flank feathers, rectrices, and down feathers of both Scaly-sided Merganser (Mergus squamatus) and Common Merganser (M. merganser) were meticulously examined using scanning electron microscope. The observed data were subjected to the Mann-WhitneyUtest, followed by hierarchical clustering and Fisher’s discriminant analysis of indicators with significant differences in morphological structure. The findings revealed statistically significant differences between Scaly-sided Merganser and Common Merganser in terms of the length of the base handle from distal barbules in the breast feathers, the length of the base handle, the number of hooked barbules, the number of cilia from distal barbules, and the number of ventral teeth from proximal barbules in rectrices. Additionally, variations in the distance between nodules, the nodular diameter, and the length of the base nodular of the down feathers were noted. Hierarchical clustering successfully categorized Scaly-sided Merganser and Common Merganser into distinct groups, achieving a 100% accuracy rate. Moreover, Fisher’s discriminant analysis demonstrated a 100% correctness rate when the back-substitution method was used to test the discriminant equation. Consequently, the length of the base handle of distal barbules in breast feathers, along with all selected indicators from rectrices and down feathers, may provide references to identify Scaly-sided Merganser and Common Merganser.
Polygenic scores for disease risk are not associated with clinical outcomes in Parkinson’s disease
Authors: Tan Manuela MX , Iwaki Hirotaka , Bandres-Ciga Sara , Sosero Yuri , Shoai Maryam , Brockmann Kathrin , Williams Nigel M , Alcalay Roy N , Maple-Grødem Jodi , Alves Guido , Tysnes Ole-Bjørn , Auinger Peggy , Eberly Shirley , Heutink Peter , Simon David K. , Kieburtz Karl , Hardy John , Williams-Gray Caroline H , Grosset Donald G , Corvol Jean-Christophe , Gan-Or Ziv , Toft Mathias , Pihlstrøm Lasse 
Published: February 2025

AbstractPolygenic risk scores (PRS) in Parkinson’s disease (PD) are associated with disease risk. Recently, pathway-specific PRS have been created to take advantage of annotations inking variants to biological pathways or cell types. Here, we investigated 8 biological pathways or regions of open chromatin using pathway-specific PRS: alpha-synuclein pathway, adaptive immunity, innate immunity, lysosomal pathway1, endocytic membrane-trafficking pathway, mitochondrial pathway, microglial open chromatin single nucleotide polymorphisms (SNPs), and monocyte open chromatin SNPs. We analysed 7,402 PD patients across 18 ‘in-person’ PD cohorts, and 6,717 patients from the online Fox Insight study. We did not find any significant associations between the 8 pathway-specific PRSs and 8 clinical outcomes in PD. Though this may be due to a lack of statistical power and limited sample size, it may also suggest that the genetic architecture of sporadic PD risk is different from the genetics of PD progression and clinical outcomes.
Discovery of Epigenetically Silenced Tumour Suppressor Genes in Aggressive Breast Cancer Through a Computational Approach
Authors: Vitte Anne-Laure , Chuffart Florent , Jacquet Emmanuelle , Nika Eleni , Mousseau Mireille , Jung Ina , Tabone-Eglinger Séverine , Bachelot Thomas , Rousseaux Sophie , Khochbin Saadi , Bourova-Flin Ekaterina 
Published: February 2025

AbstractBreast cancer is characterized by genetic and epigenetic deregulations, leading to aberrant expression of tissue-specific genes that are normally silent in healthy breast tissue. Our previous work identified the embryonic stem cell-specific geneDNMT3B, ade novoDNA methyltransferase, as aberrantly activated in breast cancer, correlating with aggressive tumour behaviour and high relapse risk, regardless of molecular subtype. Through integrative bioinformatic analyses of DNA methylation and transcriptomic data, we identified 154 genes downregulated viaDNMT3B-driven promoter hypermethylation, many of which are associated with high relapse risk. Notably, the tumour suppressor geneGATA3emerged as a primary target of functional inactivation through either loss-of-function mutations orDNMT3B-controlled hypermethylation, in a mutually exclusive manner.Both mechanisms ofGATA3inactivation were associated with similar molecular signatures linked to tumour progression, increased malignancy, and poorer prognosis. However, distinct differences were observed, with immune- and inflammation-related genes enriched inGATA3hypermethylation cases but depleted in mutation-driven silencing. Additionally, our analysis uncovered other potential tumour suppressor genes epigenetically repressed in aggressive breast cancers. These findings underscore a broader role ofGATA3inactivation beyond genetic alterations and suggest therapeutic opportunities to target epigenetically silenced tumour suppressors in aggressive breast tumours.
The WIPI homolog Atg18 binds to and tethers membranes containing phosphatidylinositol-3,4,5-triphosphate
Authors: Noguera-Cañas Fernando L. , Díaz-Agustín Aitor , Gavira Jose A. , Paredes Jose M. , Salto Rafael , Orte Angel , Conejero-Lara Francisco , Martín-Martínez Mercedes , Pérez-Lara Ángel 
Published: February 2025

AbstractAtg18 —for Autophagy-related gene 18— is a member of the PROPPIN (β-propellers that bindpolyphosphoinositides) family, which is known for its binding to phosphorylated phosphoinositides through two conserved binding sites. Although Atg18 binding to polyphosphoinositides is crucial for its roles in both autophagic and non-autophagic functions within cells, the precise molecular mechanism by which Atg18 selectively binds to specific phosphatidylinositols remains unresolved. Here, we combined molecular dynamic simulations and biophysical methods —including isothermal titration calorimetry (ITC), cosedimentation, fluorescence resonance energy transfer (FRET), and dynamic light scattering (DLS)— to characterize the interaction between Atg18 and polyphosphoinositides. In contrast to previous findings, we demonstrate that Atg18 binds to and clusters liposomes containing phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3), suggesting that Atg18 oligomerizes and tethers opposing membranes containing this physiological phosphatidylinositol. Hence, our results provide new insights into how Atg18 and its mammalian homologs, WIPI —for WD-repeat domain phosphoinositide-interacting— proteins, may regulate organelle membrane organization and vesicle trafficking required for both autophagic and non-autophagic functions.
Branched chain amino acid metabolism and microbiome in adolescents with obesity during weight loss therapy
Authors: McCann Jessica R. , Yang Chengxin , Bihlmeyer Nathan , Tang Runshi , Truong Tracy , An Jie , Jawahar Jayanth , Ilkayeva Olga , Muehlbauer Michael , Hu Zheng Zheng , Dressman Holly , Poppe Lisa , Granek Joshua , David Lawrence A. , Shi Pixu , Balikcioglu Pinar Gumus , Shah Svati , Armstrong Sarah C. , Newgard Christopher B. , Seed Patrick C. , Rawls John F. 
Published: February 2025

ABSTRACTBACKGROUNDTowards improving outcomes for adolescents with obesity, we aimed to define metabolic and microbiome phenotypes at baseline and post-weight loss intervention.METHODSThe Pediatric Obesity Microbiome and Metabolism Study enrolled 220 adolescents aged 10-18 with severe obesity (OB) and 67 healthy weight controls (HWC). Blood, stool, and clinical measures were collected at baseline and after a 6-month intervention for the OB group. Serum metabolomic and fecal microbiome data were analyzed for associations with BMI, insulin resistance, and inflammation. Fecal microbiome transplants were performed on germ-free mice using samples from both groups to assess weight gain and metabolomic changes.RESULTSAdolescents with OB exhibited elevated serum branched-chain amino acids (BCAA) but reduced ketoacid metabolites (BCKA) compared to HWC. This pattern was sex- and age-dependent, unlike adults with OB, who showed elevated levels of both. The fecal microbiomes of adolescents with OB and HWC had similar diversity but differed in membership and functional potential. FMT from OB and HWC donors had similar effects on mouse body weight, with specific taxa linked to weight gain in FMT recipients. Longitudinal analysis identified metabolic and microbial features correlated with changes in health measures during the intervention.CONCLUSIONAdolescents with OB have unique metabolomic adaptations and microbiome signatures compared to their HWC counterparts and adults with OB.TRIAL REGISTRATIONClinicalTrials.govIdentifier:NCT03139877(Observational Study) andNCT02959034(Repository)FUNDING SOURCESAmerican Heart Association Grants: 17SFRN33670990, 20PRE35180195National Institute of Diabetes and Digestive and Kidney Diseases Grant: R24-DK110492
Large language models improve transferability of electronic health record-based predictions across countries and coding systems
Authors: Kirchler Matthias , Ferro Matteo , Lorenzini Veronica ,   FinnGen, Lippert Christoph , Ganna Andrea 
Published: February 2025

AbstractVariation in medical practices and reporting standards across healthcare systems limits the transferability of prediction models based on structured electronic health record (EHR) data. We introduce GRASP, a novel transformer-based architecture that enhances the generalizability of EHR-based prediction by embedding medical codes into a unified semantic space using a large language model. We applied GRASP to predict the onset of 21 diseases and all-cause mortality in over one million individuals from UK Biobank (UK), FinnGen (Finland) and Mount Sinai (USA), all harmonized to OMOP common data model. Trained on the UK Biobank and evaluated in FinnGen and Mount Sinai, GRASP achieved an average ΔC-index that was 83% and 35% higher than language-unaware models, respectively. GRASP also showed significantly higher correlations with polygenic risk scores for 62% of diseases. Notably, GRASP mantained robust performance even when datasets were not harmonized to the same data model, accurately predicting disease risk from ICD-10-CM codes without direct mappings to OMOP. GRASP enables accurate and transferable disease predictions across heterogeneous healthcare systems with minimal resource requirements.
Monocyte-derived macrophage recruitment mediated by TRPV1 is required for eardrum wound healing
Authors: Zhang Yunpei , Wang Pingting , Neng Lingling , Sharma Kushal , Kachelmeier Allan , Shi Xiaorui 
Published: February 2025

AbstractThe tympanic membrane (TM), or eardrum, is a thin, sensitive tissue critical for hearing by vibrating and transmitting sound waves to the inner ear. TM perforation and development of otitis media and conductive hearing loss are commonly seen in the clinic. In this study, we demonstrate the role of TRPV1 signaling mediated macrophage recruitment and angiogenesis in TM repair. By creating a wounded TM mouse model with a perforation in the anteroinferior region of the pars tensa — a region in humans often damaged in traumatic injury, we observed a massive accumulation of macrophages in the vicinity of the acutely wounded TM. Using 5-Ethynyl-2’-deoxyuridine pause labeling and a chimeric bone marrow transplant model, we found that most of the recruited macrophages did not originate from local tissue-resident macrophages but rather from blood-circulating monocytes. Parallel to macrophage recruitment, angiogenesis was observed near the wound on day 3 after perforation and further progressed by day 7. The angiogenic process was strongly associated with the recruited macrophages, as macrophage depletion resulted in a notable reduction in angiogenesis. At the transcriptional level, we found that macrophages facilitate angiogenesis through several signaling pathways. Additionally, we identified direct intercellular communication between macrophages and endothelial cells mediated by phosphoprotein 1 signaling. Furthermore, Gene Ontology analysis of bulk RNA sequencing data from TMs revealed that the macrophage recruitment is associated with neuroinflammatory responses. Using a fluorescence reporter mouse driven by TRPV1, we discovered that the TM contains rich sensory nerve fibers expressing TRPV1. A genetic mutation in theTrpv1gene resulted in a marked decrease in the expression of neuroinflammatory genes, such asTac1. This decrease subsequently resulted in reduced macrophage recruitment, impaired angiogenesis, and delayed wound healing. Together, these findings highlight the crucial role of TRPV1 signaling in monocyte migration and macrophage-related angiogenesis, both of which are crucial for facilitating healing of the TM. These results also open new opportunities for clinical interventions. Targeting TRPV1 signaling could enhance TM immunity, improve blood circulation, promote the repair of damaged TM, and ultimately prevent middle ear infections.
A novel deep optimal transport framework reveals prostate cancer risk heterogeneity, Alzheimer’s disease risk heterogeneity, and myeloma cells associated with a short-term sham bortezomib response and progressive disease
Authors: Liu Ziyu , Li Sihong , Couetil Justin , Zhang Jie , Huang Kun , Johnson Travis S. 
Published: February 2025

ABSTRACTLeveraging single-cell gene expression profiles can significantly enhance our understanding of diseases by associating single cells with traits such as disease subtypes, prognosis, and drug response. Although previous efforts have linked single cell clusters and groups with these attributes, they have primarily focused on changes in cell proportions while overlooking transcriptional changes at the single cell level. To further unravel cell heterogeneity with clusters and reveal the nuanced behaviors of cellular subtypes, it is essential to assess the disease associations of individual cells. Previous methods often fail to capture complex patterns that are only discernible through summarizing non-linear relationships across multiple genes. The Diagnostic Evidence GAuge of Single-cells/Spatial-transcriptomics (DEGAS) framework advances these efforts by aligning single cells and/or spatial transcriptomics regions with patients through a unified latent space using non-linear transformations learned from deep neural networks (DNNs). DEGAS achieves superior performance in analyzing single cell and spatial transcriptomics datasets, including Alzheimer’s disease (AD), multiple myeloma (MM), and prostate cancer (PDAC). Here we present DEGAS version 2, which has been updated with optimial transport based transfer learning and improved time-to-event loss functions, more advanced model architecture, and improved model baseline evaluations. DEGASv2 outperformed other methods in both single cell and spatial transcriptomic baseline comparisons. On the multiple myeloma discovery dataset, DEGASv2 enabled us to discover cell types that exhibited distinct drug response patterns over various time frames and were validated with time series single cell multiomic data that we generated, demonstrating a dangerous subtype of cell and novel therapeutic target.
Duration discrimination in the bumblebeeBombus terrestris
Authors: Davidson Alexander , Nanda Ishani , Ong Lay Mun Anita , Chittka Lars , Versace Elisabetta 
Published: February 2025

AbstractThe ability to process temporal information is crucial for animal activities like foraging, mating, and predator avoidance. While circadian rhythms have been extensively studied, there is limited knowledge regarding how insects process durations in the range of seconds and sub-seconds. This study aimed to assess bumblebees’ (Bombus terrestris) ability to differentiate the durations of flashing lights, and use this information in a free-foraging task. Bees were trained to associate either the long or short-duration stimulus with a sugar reward versus an unpalatable solution until reaching a criterion, and then tested without sucrose solution with the same stimuli. In Experiment 1, we tested the ability to discriminate between a long stimulus (2.5 or 5 seconds) vs a short stimulus (0.5 or 1 second). The bees learned to discriminate between the two stimuli. To check whether bees solve the task without using the absolute difference in proximal stimulation as a cue, we ran a second experiment. In Experiment 2, the flashing stimuli were presented for the same total amount of time in a cycle. Bees could discriminate between durations even when the overall amount of stimulation in each presentation cycle was the same. This shows general learning abilities in bumblebees, that can discriminate seconds/subseconds intervals in visual flashing stimuli. This reveals an insect’s ability to use non-naturalistic stimuli and temporal cues in free foraging.
Endoderm differentiates into a transient epidermis in the mouse perineum
Authors: Larkins Christine E. , Grunberg Daniel M. , Daniels Gabriel M. , Feldtmann Erik J. , Cohn Martin J. 
Published: February 2025

AbstractIn eutherian mammals, the embryonic cloaca is partitioned into genitourinary and anorectal canals by the urorectal septum. At the caudal end of the mouse embryo, the urorectal septum contributes to the perineum, which separates the anus from the external genitalia. Growth of the urorectal septum displaces cloacal endoderm to the surface of the perineum, where it is incorporated into epidermis, an enigmatic fate for endodermal cells. Here we show that endodermal cells differentiate into true epidermis in the perineum, expressing basal, spinous, and granular cell markers. Endodermal epidermis is lost through terminal differentiation and desquamation postnatally, when it is replaced by ectoderm. Live imaging and single-cell tracking reveal that ectodermal cells move at a faster velocity in a lateral-to-medial direction, converging towards the narrow band of endoderm between the anus and external genitalia. Although the perineum is sexually dimorphic, similar spatiotemporal patterns of cell movement were observed in males and females. These results demonstrate that cloacal endoderm differentiates into a non-renewing, transient epidermis at the midline of the perineum. Differential movement of endodermal and ectodermal cells suggests that perineum epidermis develops by convergent extension. These findings provide a foundation for further studies of perineum development and of sex-specific epidermal phenotypes.
Cross-Species Communication via Fungal Extracellular Vesicles
Authors: Piraine Renan E. A. , Oliveira Henrique T. , Santos Patrick W. , Froldi Julia L. , Oliveira Bianca T. M. , Rezende Caroline P. , Trentin Gabriel E. S. , Nogueira Lucas F. B. , Colombo Arnaldo L. , Casadevall Arturo , Rodrigues Marcio L. , Almeida Fausto 
Published: February 2025

AbstractExtracellular vesicles (EVs) play crucial roles in fungal communication and host immune modulation, representing potential therapeutic targets for fungal infections. This study investigated the role of fungal EVs in both intra- and interspecies communication, focusing on their effects on virulence and immune responses. Co-incubation experiments were performed using EVs derived fromCandida albicansandCandida auristo assess interactions withC. albicansplanktonic cells and biofilms, as well asCryptococcus neoformansandCryptococcus gattiiEVs interacting withC. neoformanscultures. EVs were observed associating with recipient cell surfaces, suggesting subsequent internalization. Functional assays revealed that EV exposure led to increased expression ofCap59, Lac1, Ure1,andErg11genes, correlating with reduced antifungal susceptibility in both planktonic and biofilm forms. Additionally, EVs facilitated cross-species communication, enhancing biofilm adhesion and dispersion, which underscores their role in phenotypic modulation. Macrophages stimulated with fungal EVs exhibited receptor-specific gene expression changes, notably the upregulation ofgalectin-3, along with a pro-inflammatory phenotype marked by increasediNOSexpression and elevated cytokine levels (IL-1β, IL-6, and IL-8). Collectively, these findings underscore a critical role for fungal EVs in interspecies communication, biofilm regulation, and immune modulation, offering valuable insights into fungal pathogenicity mechanisms.ImportanceCurrently, no vaccines exist to prevent fungal infections, underscoring the need for new therapies. As fungal diseases increase globally, understanding fungal biology is essential to identifying treatment targets. Fungi use EVs to communicate and evade immune responses. EVs mediate cell-cell communication, transporting proteins, polysaccharides, lipids, and nucleic acids – serving as “messages” exchanged within a fungal network. Understanding how these vesicles facilitate communication not only within a single species but also across different fungal species can shed light on their contribution to infection persistence and cross-species adaptability. Moreover, EVs may have a broader role in inter-kingdom communication, influencing how fungi interact with host immune cells. The impact of fungal EVs on human innate immune responses remains a largely underexplored area, with significant gaps in our knowledge. This study aims to examine how fungal EVs affect immune responses and whether their signaling varies across species, potentially revealing new therapeutic targets.
Manipulating PARK7/DJ-1 Levels by Genotoxic Stress Alters Noncoding RNAs and Cellular Homeostasis
Authors: Zohar Keren , Zoubi Haya Obied , Goldberg Michal , Eliyahu Tsiona , Linial Michal 
Published: February 2025

AbstractDJ-1/PARK7 is a multifunctional protein that plays a vital role in sensing oxidative stress and maintaining redox homeostasis. As an oncogene, DJ-1 influences p53-mediated stress responses and contributes to cancer progression. This study investigates the impact of X-ray-induced DNA breaks on cellular responses post-irradiation under varying DJ-1 expression levels. Using siRNA knockdown and overexpression to modulate DJ-1 levels, transcriptional changes were analyzed through RNA-seq. Naïve cells exhibited only a moderate transcriptional response to X-ray exposure, including suppression of the cell cycle and activation of stress pathways. Overexpression of DJ-1 led to pronounced gene expression suppression, particularly suppression of most ribosomal and mitochondrial genes. Conversely, DJ-1 knockdown caused extensive, non-specific transcriptional changes, indicating disrupted cellular homeostasis. Notably, around 25% of non-coding RNAs were differentially expressed under these conditions. DJ-1 overexpression suppressed lncRNA of the host genes for snoRNAs, thus altering the miRNA sponging capacity after X-ray exposure. These findings underscore DJ-1’s critical role in modulating cellular responses to genotoxic stress, reshaping transcriptional landscapes, and regulating non-coding RNA profiles. DJ-1 emerges as essential for maintaining genomic stability.