bluuebunny/crossref_metadata_2025_split huggingface dataset:
EEG-based Assessment of Long-Term Vigilance and Lapses of Attention using a User- Centered Frequency-Tagging Approach
Authors: Ladouce S , Tresols J. J. Torre , Goff K. Le , Dehais F 
Published: January 2025

ABSTRACTSustaining vigilance over extended periods is crucial for many critical operations but remains challenging due to the cognitive resources required. Fatigue and other factors contribute to fluctuations in vigilance, causing attentional focus to drift from task-relevant information. Such lapses of attention, common in prolonged tasks, lead to decreased performance and missed critical information, with potentially serious consequences. Identifying physiological markers that predict inattention is key to developing preventive strategies. Previous research has established electroencephalography (EEG) responses to periodic visual stimuli, known as steady-state visual evoked potentials (SSVEP), as sensitive markers of attention. In this study, we evaluated a minimally intrusive SSVEP-based approach for tracking vigilance in healthy participants (N = 16) during two sessions of a 45-minute sustained visual attention task (Mackworth’s clock task). A 14 Hz frequency-tagging flicker was either superimposed on the task or absent. Results revealed that SSVEP responses were lower prior to lapses of attention, while other spectral EEG markers, such as frontal theta and parietal alpha activity, did not reliably distinguish between detected and missed attention probes. Importantly, the flicker did not affect task performance or participant experience. This non-intrusive frequency-tagging method provides a continuous measure of vigilance, effectively detecting attention lapses in prolonged tasks. It holds promise for integration into passive brain-computer interfaces, offering a practical solution for real-time vigilance monitoring in high-stakes settings like air traffic control or driving.Highlights-Fluctuations in the SSVEP response to a continuous frequency-tagging flicker presented throughout a 45-minutes long vigilance task was used to characterize lapses of attention-The frequency-tagging flicker superimposed to the task was designed to be minimally intrusive thanks to its low luminance and low contrast-Neither the user experience nor the task performance were altered by the presence of the frequency-tagging flicker-The SSVEP response outperformed measures of individual alpha peak and theta band activity in the distinction of attentional lapses (missed events) from successful target event identification-The present findings have implications for the design of Human-Computer Interfaces aimed at monitoring (in)attention during the performance of monotonous routines (e.g., surveillance, driving,…)
Deep functional profiling of gene sets using Large Language Models: A blueprint for tailored, context-aware functional annotation
Authors: Khan Taushif , Yurieva Marina , Kabeer Basirudeen Syed Ahamed , Toufiq Mohammed , Rinchai Darawan , Palucka Karolina , Chaussabel Damien 
Published: January 2025

ABSTRACTIn this study, we present a proof-of-concept approach leveraging Large Language Models (LLMs) for the deep functional profiling of gene sets, addressing the limitations of traditional functional annotation tools. By employing a stepwise prompting strategy with OpenAI’s GPT-4, we systematically retrieve, consolidate, and score immune functions associated with each gene in a module, generating ranked lists of functions with detailed justifications and supporting literature evidence. As a blueprint for this approach, we demonstrate how this in-depth, context-aware analysis can characterize Module M10.4 from the BloodGen3 transcriptional module repertoire, confirming its central role in neutrophil-mediated innate immunity and antimicrobial defense while uncovering a nuanced network of immune functions overlooked by conventional methods. The LLM-based workflow identifies cell types and transcriptional programs driving these functions, offering a more granular and quantitative assessment of the gene set’s functional associations compared to direct LLM prompting or pathway enrichment analysis. Our results showcase the potential of LLMs in providing biologically meaningful interpretations of gene expression signatures, accounting for cellular composition changes and transcriptional regulation. This initial proof-of-concept study establishes a foundation for the automated, high-throughput functional profiling of transcriptional signatures. By integrating advanced language models with traditional literature-based validation, we present a powerful strategy for unraveling the complex biology of gene sets and transcriptional modules, ultimately facilitating the translation of systems-level molecular data into actionable knowledge.
Effects of Environmental Salinity on Global and Endocrine-Specific Transcriptomic Profiles in the Caudal Neurosecretory System of Salmonid Fishes
Authors: Culbert Brett M. , McCormick Stephen D. , Bernier Nicholas J. 
Published: January 2025

AbstractThe caudal neurosecretory system (CNSS) is a fish-specific neuroendocrine complex whose function(s) remain uncertain despite 60+ years of research. Osmoregulatory roles for the CNSS have been hypothesized, but molecular regulation of the CNSS following changes in environmental salinity remains poorly characterized. Therefore, we performed transcriptomics on the CNSS of rainbow trout (Oncorhynchus mykiss) to establish: 1) how the CNSS responds following seawater (SW) transfer, and 2) which endocrine systems contribute to osmoregulatory responses in the CNSS. Responses following SW transfer varied at 24 h versus 168 h, with changes primarily affecting membrane transport and transcriptional processes at 24 h and neuronal processes at 168 h. Components of several osmoregulation-associated endocrine systems were affected (e.g., corticosteroid receptors), including some which have not previously been identified in the CNSS (e.g., calcitonin). Additionally, transcript levels of corticotropin-releasing factor (CRF) peptides—which have osmoregulatory functions and were highly abundant in the CNSS—were ∼2-fold higher after 24 h in SW. Therefore, we performed additional experiments investigating CRF peptides in a more euryhaline salmonid, Atlantic salmon (Salmo salar). Smolts had up to 12-fold higher levels of CRF peptide transcripts than parr, but abundance declined following SW transfer. Additionally, CRF transcripts were lower 24 h following freshwater transfer of SW-acclimated salmon. These results suggest that CRF peptides acutely aid in coordinating physiological responses following fluctuations in environmental salinity via anticipatory and/or responsive mechanisms. Collectively, our data indicate that CNSS-mediated production of CRF peptides has osmoregulatory functions and provide a resource for investigations of novel CNSS functions.
Integrated multi-omics highlights alterations of gut microbiome functions in prodromal and idiopathic Parkinson’s disease
Authors: Villette Remy , Ortís Sunyer Júlia , Novikova Polina V. , Aho Velma T. E. , Petrov Viacheslav A. , Hickl Oskar , Busi Susheel Bhanu , De Rudder Charlotte , Kunath Benoit , Heintz-Buschart Anna , Trezzi Jean-Pierre , Halder Rashi , Jäger Christian , Lebrun Laura A. , Daujeumont Annegrät , Schade Sebastian , Janzen Annette , Jehmlich Nico , von Bergen Martin , Laczny Cédric C. , May Patrick , Trenkwalder Claudia , Oertel Wolfgang , Mollenhauer Brit , Wilmes Paul 
Published: January 2025

SummaryParkinson’s disease (PD) is associated with gut microbiome shifts, but the functional consequences remain unclear. Here, we use an integrated multi-omics approach to compare the gut microbiomes of individuals with PD and prodromal PD as well as healthy individuals. After analyzing each omics, meta-metabolomic was selected to inform the analysis as it represents the most discriminatory and robust ome. We identified 11 metabolites that were differentially abundant between the groups, amongst which β-glutamate was increased in PD and prodromal PD, and correlated with the transcriptional activities ofMethanobrevibacter smithiiandClostridiumspp. We identified decreases in transcripts, but not in gene abundances, related to glutamate metabolism, bile acids, chemotaxis and flagellar assembly in PD, particularly in keystone genera such asRoseburia, AgathobacterandBlautia. Our findings, integrated into the Expobiome map, reveal multifactorial microbiome alterations which converge with PD pathways. Our study highlights the importance of investigating the gut microbiome’s functional dimensions to better resolve microbiome-host interactions in health and disease.
Sex Differences in Auditory Brainstem Responses in the Hispid Pocket Mouse (Chaetodipus hispidus)
Authors: Joseph Luberson , Joseph Desi M. , Hobbs Sarah , Rivera Naleyshka Colon , McCullagh Elizabeth A. 
Published: January 2025

ABSTRACTThe hispid pocket mouse (C. hispidus) is a solitary semi-fossorial rodent that has been the subject of various ecological and genetic studies. However, no previous studies have characterized its hearing ability, which is important for its survival and fitness. We collected auditory brainstem responses (ABRs) fromC. hispidusand measured craniofacial and pinna morphological features to assess hearing ability and test differences in hearing thresholds, monaural and binaural ABR amplitudes and latencies between the sexes. ABR recordings revealed that similar to other small mammals,C. hispidusdisplayed the lowest threshold to sounds between 8-16 kHz, indicating best hearing across those frequencies. We found significant differences in auditory thresholds of the ABRs between the sexes, with females showing lower frequency hearing compared to males. However, no significant differences were detected in monaural and binaural ABR amplitudes and latencies between the sexes. We also found no significant differences in craniofacial and pinna dimensions between the sexes. These findings shed novel insights into the auditory systems across species and highlighted for the first time sex differences in auditory thresholds for this rodent species.
Maizerough endosperm6is a predicted RNA helicase required for miRNA processing and endosperm cell patterning
Authors: Yang Tianxiao , Suzuki Masaharu , Hannah L. Curtis , Settles A. Mark 
Published: January 2025

AbstractMaizerough endospermmutants have defective kernels with a rough, etched, or pitted endosperm surface. Molecular genetic analysis of this mutant class has identified multiple RNA processing proteins critical to endosperm development. Here, we report thatrough endosperm6(rgh6) encodes a predicted DEAD-box RNA helicase required for miRNA processing. Mutantrgh6kernels reduce grain fill and increase relative transcript levels of markers specific to epidermal endosperm cell types. B-A translocation crosses revealed thatrgh6mutant endosperm inhibits normal embryo development. We mapped thergh6locus to a three gene interval and confirmed it encodes a predicted DEAD-box RNA helicase with two independent transposon-tagged alleles. Transient expression of a RGH6-green fluorescent protein (GFP) fusion is localized to nucleolus and nuclear speckles consistent with a function in nuclear RNA processing. Mutantrgh6endosperms have increased precursor miRNA and decreased mature miRNA levels indicating thatrgh6impacts miRNA processing. Our study demonstrates that precursor miRNA processing and miRNA target regulation are required for normal endosperm development.
Origins and Implications of Intron Retention Quantitative Trait Loci in Human Tissues
Authors: Park Eddie , Xing Yi 
Published: January 2025

AbstractIntron retention is a type of alternative splicing in which introns remain unspliced in mature RNA transcripts. In order to explore the landscape and consequences of genetically regulated intron retention, we perform an intron retention quantitative trait loci (irQTL) analysis in 49 human tissues across 838 individuals. We identify 8,624 unique intron retention events associated with genetic polymorphisms. 1,369 irQTLs (16%) are also associated with genome-wide association study (GWAS) traits, suggesting that genetically regulated intron retention may play a causal role in the regulation of these GWAS traits. 1,999 irQTLs (23%) colocalize with eQTLs to their respective gene, suggesting that intron retention and steady-state gene expression levels are regulated by shared sets of genetic variants. Through a colocalization analysis of irQTL:eQTL events, we demonstrate that irQTLs are sufficient to generate eQTLs when one of the alternatively spliced transcripts is preferentially targeted by the nonsense mediated decay (NMD) pathway. Surprisingly, for intron retention events whose potential NMD effects can be confidently predicted based on their positions within known gene annotations, we find that 58.8% (923/1570) of the colocalized irQTL and eQTL pairs show effect size directions that are discordant with the NMD model. Moreover, we find that irQTLs are significantly more likely to occur in the same gene with the same effect size direction as compared to exon skipping QTLs. Through mathematical modeling and analysis of experimental perturbation data, we provide evidence that eQTLs are able to generate irQTLs by altering the steady state ratios of spliced and unspliced transcripts, and we postulate that this mechanism may partially underlie the widespread intron retention observed previously in various biological conditions. Taken together, these results show that intron retention and steady state gene expression levels are closely intertwined to regulate phenotypic traits.
Landscape and regulation of new protein translation in the earlyC. elegansembryo
Authors: Shukla Yash , Ghatpande Vighnesh , Hu Cindy F. , Dickinson Daniel J. , Cenik Can 
Published: January 2025

SummaryTranslation of maternal mRNAs is crucial for early embryonic development. InC. elegans,cell fates become determined from the first division without new transcription, making this organism ideal for studying post-transcriptional regulation of lineage specification. Using low-input ribosome profiling combined with RNA sequencing on precisely staged embryos, we measured protein translation during the first four cell cycles ofC. elegansdevelopment. We uncovered stage-specific patterns of developmentally coordinated translational regulation. We found that mRNA localization correlates with translational efficiency, though initial translational repression in germline precursors occurs prior to P-granule association. The RNA-binding protein OMA-1 emerged as a key regulator of translational efficiency in a stage-specific manner. These findings illuminate how post-transcriptional mechanisms shape the embryonic proteome to direct cell differentiation, with implications for understanding similar regulation across species where maternal factors guide early development.
Study protocol for the EYEdentify project: An examination of gaze behaviour in autistic adults using a virtual reality-based paradigm
Authors: Jeppesen Alberte C. E. , Andresen Johannes , Parvaiz Rizwan , Clemmensen Lars , Møllegaard Jepsen Jens Richardt , Hansen Dan Witzner , Glenthøj Louise Birkedal 
Published: January 2025

AbstractIntroductionAutism Spectrum Condition (ASC) is characterised by difficulties in social communication and interaction, which may pose significant challenges to daily functioning throughout life. While current diagnostic methods for ASC often rely on measures based on subjective reports, there is a growing need for objective, quantifiable measures to support current clinical assessment of ASC. Eye-tracking technology records eye and gaze movements in real time and provides a direct and objective method for assessing social attention. Integrating eye-tracking within virtual reality (VR) environments presents a novel approach for capturing gaze behaviour in dynamic, ecologically valid social scenarios. This study aims to investigate whether VR-based eye information can reveal group differences in gaze behaviour between autistic adults and neurotypical controls in simulated social interactions.MethodsThis case-control study will include 140 adults diagnosed with ASC and 50 neurotypical controls, matched by age and gender. Participants will engage in six VR-based social scenarios, which vary in social complexity and the presence of non-social distractors. Eye information will be measured using eye-tracking technology integrated into a head-mounted display. Gaze behaviour will be analysed through fixation-based metrics on parameters including number of fixations, mean fixation time, and dwell time, on predetermined Areas of Interest.AnalysisStatistical analyses will assess between-group differences in gaze behaviour as well as correlations between gaze metrics and clinical measures of social functioning, social cognition and symptom severity.DiscussionThis study utilises VR-based eye-tracking to investigate novel paradigms for assessing gaze behaviour in ASC in immersive, interactive environments and aims to advance the current understanding of visual social attention in ASC. Positive outcomes from this study may support further research into VR- based eye-tracking to supplement existing clinical assessment methods.
Quantitative Detection of Amyloid Fibrils using Fluorescence Resonance Energy Transfer (FRET) Between Engineered Yellow and Cyan Proteins
Authors: Moustouka Caitlyn , Makhatadze George I. 
Published: January 2025

AbstractOver 20 human diseases are caused by or associated with amyloid formation. Developing diagnostic tools to understand the process of amyloid fibril formation is essential for creating therapeutic agents to combat these widespread and growing health problems. Here, we capitalize on our recent striking discovery that green fluorescent protein (GFP), one of the most used proteins in molecular and cell biology, has a high intrinsic binding affinity to various structural intermediates along the fibrillation pathway, independent of amyloid sequence. Using engineered GFP with the fluorescence properties of Aquamarine and mCitrine, we developed a FRET-based sensor to quantitatively monitor amyloid fibrils. The proof-of-principle characterization was performed on a test system consisting of PAPf39 fibrils.
Insight into the Thermo-responsive Phase Behavior of P1 Domain ofα-synuclein using Atomistic Simulations
Authors: Chakraborty Sanchari , Biswas Mithun 
Published: January 2025

AbstractBiomolecular condensate formation driven by intrinsically disordered proteins (IDPs) is regulated by interaction between various domains of the protein. Such condensates are implicated in various neurodegenerative diseases. The presynaptic intrinsically disordered protein,α-Syn is involved in the pathogenesis of Parkinson’s disease. The central non-amyloidβ-component (NAC) domain in the protein is considered to be a major driver of pathogenic aggregation, although recent studies have suggested that the P1 domain from the flanking N-terminal region, can act as a ‘master controller’ forα-Syn function and aggregation. To gain molecular insight into the phase behavior of the P1 domain itself, we investigate how assemblies of P1 (residues 36-42) chains phase separate with varying temperatures using all-atom molecular dynamics simulations. The simulations reveal that P1 is able to phase separate above a lower critical solution temperature. Formation of the condensed phase is driven by exclusion of water molecules by the hydrophobic chains. P1 chain density in the condensate is determined by weak multi-chain interactions between the residues. Moreover, Tyrosine (Y39) is involved in the formation of strongest contacts between residue pairs in the dense phase. These results provide a detailed picture of condensate formation by a key segment of theα-Syn molecule, which may help deciphering the phase behavior of the full-length protein.
Prosit-XL: enhanced cross-linked peptide identification by accurate fragment intensity prediction to study protein-protein interactions and protein structures
Authors: Kalhor Mostafa , Saylan Cemil Can , Picciani Mario , Fischer Lutz , Schimweg Falk , Lapin Joel , Rappsilber Juri , Wilhelm Mathias 
Published: January 2025

AbstractIt has been shown that integrating peptide property predictions such as fragment intensity into the scoring process of peptide spectrum match can greatly increase the number of confidently identified peptides compared to using traditional scoring methods. Here, we introduce Prosit-XL, a robust and accurate fragment intensity predictor covering the cleavable (DSSO/DSBU) and non-cleavable cross-linkers (DSS/BS3), achieving high accuracy on various holdout sets with consistent performance on external datasets without fine-tuning. Due to the complex nature of false positives in XL-MS, a novel approach to data-driven rescoring was developed that benefits from Prosit-XL’s predictions while limiting the overestimation of the false discovery rate (FDR). We first evaluated this approach using two ground truth datasets that demonstrate the accurate and precise FDR estimation. Second, we applied Prosit-XL on a proteome-scale dataset, demonstrating an up to ∼3.4-fold improvement in PPI discovery compared to classic approaches. Finally, Prosit-XL was used to increase the coverage and depth of a spatially resolved interactome map of intact human cytomegalovirus virions, leading to the discovery of previously unobserved interactions between human and cytomegalovirus proteins.
Echidna: A Bayesian framework for quantifying gene dosage effect impacting phenotypic plasticity
Authors: Fan Joy Linyue , Zhang Mingxuan , O’Brien William , Myers Joshua D. , Melms Johannes C. , Biermann Jana , D’Souza Edridge , Tagore Somnath , Beltran-Velez Nicolas , Hoffer-Hawlik Kevin , Preau Alexander , Arora Isha , Chatterjee Sharanya , Izar Benjamin , Azizi Elham 
Published: January 2025

AbstractPhenotypic plasticity, the ability of cells to adapt their behavior in response to genetic or environmental changes, is a fundamental biological process that drives cellular diversity in both normal and pathological contexts, including in tumor evolution. While chromosomal instability and somatic copy number alterations (CNAs) are known to influence cellular states, it remains difficult to separate genetic from cell non-autonomous mechanisms that govern transcriptional variability. Here, we presentEchidna, a Bayesian hierarchical model that integrates single-cell RNA sequencing (scRNA-seq) and bulk whole-genome sequencing (WGS) data to quantify the impact of CNAs on gene expression dynamics. By jointly inferring clone-specific CNA profiles and uncovering clonal dependencies, Echidna bridges genomic and transcriptomic landscapes within and across multiple time points, enabling the decoupling of gene dosage effects from cell-extrinsic factors on phenotypic plasticity. Applying Echidna to patient tumor specimens, we demonstrate its superior performance in clonal reconstruction and derive insights into resistance mechanisms.