bluuebunny/crossref_metadata_2025_split huggingface dataset:
A specialized bacterial group II intron is a highly efficient retrotransposon
Authors: Gomes Lucie , Toffano-Nioche Claire , Gautheret Daniel , Costa Maria 
Published: December 2024

ABSTRACTMobile group II introns are site-specific retrotransposons composed of a large self-splicing ribozyme and an intron-encoded reverse transcriptase that are widespread in bacterial and organellar genomes. Sequence and structural variations of the ribozyme and the associated reverse transcriptase define several lineages of bacterial group II introns. Interestingly, some of these intron families evolved different mobility strategies while others colonize particular genetic contexts. Here, we have investigated the mobility activity of anEscherichia coligroup II intron that is inserted into the stop codon of the stress-response genegroEL. Using mobility assays based on over-expression from a donor plasmid, we demonstrate that this intron is a highly efficient and site-specific retrotransposon, capable of colonizing thegroELgene of anE. colihost strain according to the insertion pattern observed in natural genomes. Furthermore, we provide evidence that a chromosomal copy of the full-length retrotransposon can be expressed from its native genetic locus to yield mobile retroelement particles. This intron constitutes a novel model system that could help reveal original mobility strategies used by some group II intron retrotransposons to colonize bacterial genomes.
PAX2 is Transcriptionally Silenced by a Distinct Mechanism of Epigenetic Reprogramming to Initiate Endometrial Carcinogenesis
Authors: Sahoo Subhransu S. , Ramanand Susmita G. , Cuevas Ileana C. , Gao Yunpeng , Lee Sora , Abbas Ahmed , Zhang Xunzhi , Kumar Ashwani , Koduru Prasad , Roy Sambit , Broaddus Russell R. , Bae-Jump Victoria L. , Gladden Andrew B. , Lea Jayanthi , Lucas Elena , Xing Chao , Kobayashi Akio , Mani Ram S. , Castrillon Diego H. 
Published: December 2024

AbstractIn most cancers, including endometrial cancer, tumor suppressor genes harboring inactivating mutations have been systematically cataloged. However, locus-specific epigenetic alterations contributing to cancer initiation and progression remain only partly described, creating knowledge gaps about functionally significant tumor suppressors and underlying mechanisms associated with their inactivation. Here, we show that PAX2 is an endometrial tumor suppressor recurrently inactivated by a distinct epigenetic reprogramming event not associated with promoter hypermethylation. PAX2 is expressed throughout normal endometrial glands; however, microscopic clones with PAX2 protein loss arise spontaneously in adulthood and progress to endometrial precancers and cancers. Here we show that PAX2 protein loss occurs via transcriptional silencing in 80% of endometrial cancers. Mechanistically, transcriptomic, epigenomic, 3D genomic, and machine learning analyses showed that silencing is associated with replacement of open/active chromatin features (H3K27ac/H3K4me3) with inaccessible/repressive features (H3K27me3). The spread of the H3K27me3 signal is restrained by cohesin loops, preventing transcriptional dysregulation of neighboring genes. Functionally, PAX2 loss promoted endometrial carcinogenesis by rewiring the transcriptional landscape via global enhancer reprogramming. Genetically engineered mouse models together with organoid and human cell line studies establishedPax2as an in vivo endometrial tumor suppressor that cooperates withPtento produce lethal cancers. Our discovery of a specific and recurring epigenetic alteration that transcriptionally silencesPAX2to initiate most endometrial cancers opens new lines of investigation into the origins of endometrial cancer with diverse implications for its diagnosis and treatment.One Sentence SummaryWe demonstrate that PAX2 is silenced by a highly recurrent epigenetic mechanism to initiate most endometrial cancers, establishing a novel mechanism of tumor suppressor inactivation.
Flow rapidly replenishes scarce nutrients to promote bacterial growth
Authors: Padron Gilberto C. , Modi Zil , Koch Matthias D. , Sanfilippo Joseph E. 
Published: December 2024

AbstractIn laboratory settings, bacteria grow in static culture with more nutrients than they require. However, bacteria in nature experience flowing environments that are nutrient limited. Using microfluidics and single cell imaging, we discover that flow promotes growth of the human pathogenPseudomonas aeruginosaat surprisingly low nutrient concentrations. In static environments, cells require high nutrient concentrations as they steadily consume non-renewable resources. In flowing environments, cells grow robustly at very low nutrient concentrations that are constantly replenished. Our simulation-guided experiments show how stopping flow halts growth within minutes and varying flow impacts growth gradients across bacterial populations. By precisely delivering nutrients using microfluidics, we learned that cells in flow can grow on glucose concentrations 1,000 times lower than those observed in typical laboratory experiments. The ultralow glucose concentrations sufficient for growth in flow closely align with the affinity of bacterial glucose transporters, suggesting that bacteria have evolved in flowing environments with scarce nutrients. Collectively, our results emphasize the limits of traditional culturing approaches and highlight how depleted environments can unexpectedly support bacterial growth.
Single-cell Organelle Extraction with Cellular Indexing
Authors: Lam Trinh , Su Alison , Gomez Martinez Ana E. , Fomitcheva-Khartchenko Anna , Herr Amy E. 
Published: December 2024

AbstractBulk methods to fractionate organelles lack the resolution to capture single-cell heterogeneity. While microfluidic approaches attempt to fractionate organelles at the cellular level, they fail to map each organelle back to its cell of origin—crucial for multiomics applications. To address this, we developed VacTrap, a high-throughput microfluidic device for isolating and spatially indexing single nuclei from mammalian cells. VacTrap consists of three aligned layers: (1) a Bis-gel microwells layer with a ‘trapdoors’ (BAC-gel) base, fabricated atop a through-hole glass slide; (2) a PDMS microwell layer to receive transferred nuclei; and (3) a vacuum manifold. VacTrap operation begins with cell lysis using DDF to release intact nuclei into the Bis-gel microwells, while cytoplasmic proteins are electrophoresed into the Bis-gel. Upon exposure to DTT and vacuum force, the trapdoors open, allowing nuclei to transfer to the PDMS microwells. VacTrap dissolves the trapdoors within 3-5 minutes and achieve synchronized nuclei transfer with 98% efficiency across 80% of trapdoors in a 256-microwell array, surpassing the <1% efficiency of passive transfer without vacuum. Morphology analysis confirmed preservation of organelle integrity throughout VacTrap operation. By enabling spatial indexing of nuclei back to their original cell, VacTrap provides a robust, high-throughput tool for single-cell multiomics applications.
Attention field as a cognitive-behavioral marker for demarcating internet- but not smoking-addiction from reward
Authors: Mao Mingxing , Cai Yaochun , Li Ye , Li Zhuoqun , Dong Wenshan , Wang Yuanyuan , Zhang Xilin 
Published: December 2024

AbstractAttentional effect (AE), attention profile (AP), and attention field (AF) have been studied extensively, however, their roles in addiction and demarcating addiction from rewards remain unclear. Using a modified Posner-paradigm with two types of pre-rewarded-cues (addiction-related and addiction-unrelated) and four groups (smoking-dependents, internet-dependents, and respective HCs), we found that both AEs and APs were independent of either cue type or group, while AFs were interactively modulated by the two. AFs of addiction-related cues were narrower than those of addiction-unrelated cues for internet-dependents, but not for either smoking-dependents or HCs; AFs of internet-dependents (not smoking-dependents) were narrower than those of HCs for addiction-related cues, but not for addiction-unrelated cues. Significantly, internet-dependents’ reduced AFs can be simulated by the divisive-normalization computation, both of which closely tracked their addictive severities. Our findings identify a cognitive-behavioral marker for demarcating internet-addiction from rewarding, arguing against the notion that internet-addiction, or, more generally, non-substance-addiction, is ill-posed.
Patches: A Representation Learning framework for Decoding Shared and Condition-Specific Transcriptional Programs in Wound Healing
Authors: Beker Ozgur , Amador Dreyton , Pomarino Nima Jose Francisco , Van Deursen Simon , Woappi Yvon , Dumitrascu Bianca 
Published: December 2024

AbstractSingle-cell genomics enables the study of cell states and cell state transitions across biological conditions like aging, drug treatment, or injury. However, existing computational methods often struggle to simultaneously disentangle shared and condition-specific transcriptional patterns, particularly in experimental designs with missing data, unmatched cell populations, or complex attribute combinations. To address these challenges,Patchesidentifies universal transcriptomic features alongside condition-dependent variations in scRNA-seq data. Using conditional subspace learning, Patches enables robust integration, cross-condition prediction, and biologically interpretable representations of gene expression. Unlike prior methods, Patches excels in experimental designs with multiple attributes, such as age, treatment, and temporal dynamics, distinguishing general cellular mechanisms from condition-dependent changes. We appliedPatchesto both simulated data and real transcriptomic datasets from skin injury models, focusing on the effects of aging and drug treatment.Patchesrevealed shared wound healing patterns and condition-specific changes in cell behavior and extracellular matrix remodeling. These insights deepen our understanding of tissue repair and can identify potential biomarkers for therapeutic interventions, particularly in contexts where the experimental design is complicated by missing or difficult-to-collect data.
Unveiling theranostic potential: Insights into cell-free microRNA-protein interactions
Authors: Sahu Vishal Kumar , Sur Subhayan , Agarwal Sanjana , Madhyastha Harish , Ranjan Amit , Basu Soumya 
Published: December 2024

AbstractMicroRNAs (miRNAs) belong to a short endogenous class of non-coding RNAs which have been well studied for their crucial role in regulating cellular homeostasis. Their role in modulation of diverse biological pathways by intracellular or extracellular communication and interaction with DNA, RNA or protein, projects them or their targets as promising biomarkers and therapeutic agents. However, studying specific interactions in the extracellular or cell-free environment for drug discovery or biomarker establishment is resource-intensive. In this study, we derive a computational approach based on available experimental data to decipher patterns in miRNA-protein interactions in the cell-free milieu. We characterized the miRNA-protein interactome (miRPin,https://www.mirna.in/miRPin) and identified consensus sequences governing these interactions. The study establishes the role of multiple miRNAs and protein interactions present in cell-free environments leading to pathological conditions, viz., role of proteins like METTL3 and AGO2 etc. and miRNAs like hsa-miR-484 and hsa-miR-30 families, hsa-mir-126-5p etc. in association with multiple miRNAs in different cancer types, cardiovascular diseases, and neurological disorders. The findings outlined in the study may facilitate new avenues of therapeutic discovery leading to the understanding of cellular mechanisms underlying therapy relapse and drug resistance. By addressing these interactions in an extracellular environment may further gain insight into regulating disease initiation and progression, overcoming challenges related to drug efficacy and drug delivery in the presence of bilayer membranes with drug efflux pumps.
Laser Speckle Contrast Imaging of Hepatic Microcirculation
Authors: Zhukov Oleg , Postnov Dmitry D. , Hejn Kamilla H. , Ravnskjær Kim , Sosnovtseva Olga 
Published: December 2024

AbstractThe liver controls blood homeostasis and depends critically on adequate blood supply. While the global regulation of liver blood flow via the hepatic arterial buffer response is well established, the mechanisms governing hepatic sinusoidal hemodynamics remain elusive. We use laser speckle contrast imaging to investigate the hepatic microvascular blood flow in anesthetized rats. Laser speckle contrast imaging offers a spatial resolution of a few micrometers, enabling visualization of individual microvessels, and a temporal resolution sufficient to track flow dynamics. This allowed us to resolve individual sinusoids and venules on the liver surface and to detect a reduction of the blood flow following local Angiotensin-II injections. We show that the blood flow oscillates with frequencies within the range of 0.05–0.4 Hz, which may be linked to rhythmic contraction of upstream blood vessels. Our findings provide insights into vessel-specific liver microcirculationin vivo, offering new opportunities to explore vascular dysfunction mechanisms in metabolic liver diseases.
Atypical Visual Selective Attention in Children with Dyslexia: Evidence from N2pc and PD
Authors: Liu Hongyu , Sun Yulu , Wang Zimo , Guo Jialiang , Song Yan , Meng Xiangzhi 
Published: December 2024

AbstractEfficient visual attention is fundamental to the development of reading abilities. Previous studies have identified visual attention impairments in individuals with dyslexia, particularly in visual attention span and sluggish attention shifting. However, findings regarding basic visual selective attention remain controversial. To address this issue, the present study provides event-related potential (ERP) evidence to verify whether children with developmental dyslexia (DD) suffered from deficits in visual selective attention. A pop-out visual search task was used to examine visual attentional patterns to a lateral target in 66 children (33 children with DD and 33 typically developing (TD) children) using electroencephalography. Compared to TD children, children with DD showed a larger and prolonged P1 component, as well as a larger target-evoked N2pc component. The larger P1 amplitude was associated with lower reading fluency while the larger N2pc amplitude was associated with poor reading comprehension performance. Interestingly, the target-elicited N2pc was followed by positivity (PDcomponent) in TD children but not in children with DD; however, the N2pc amplitude was correlated with the PDamplitude in children with DD. Children with DD show immature early attentional processing and may have an imbalance in the regulation of visual selective attention between attentional selection and suppression. Our findings provide ERP evidence for interpreting the underlying neural mechanism of visual selective attention in children with DD and may offer a new perspective for exploring the mechanism of visual attention deficits in dyslexia.Research HighlightsIn a pop-out visual search task, children with dyslexia exhibited a larger N2pc and an absent PDcomponent.The absence of the PDcomponent in children with dyslexia may be associated with their larger N2pc amplitudes.N2pc amplitude is associated with reading ability in children with dyslexia.Children with dyslexia need to allocate more resources towards the target but also struggle to disengage from the attended location.
Genomic characterization of novel bat kobuviruses in Madagascar: implications for viral evolution and zoonotic risk
Authors: Gonzalez Freddy L. , Ranaivoson Hafaliana Christian , Andrianiaina Angelo , Andry Santino , Raharinosy Vololoniaina , Randriambolamanantsoa Tsiry Hasina , Lacoste Vincent , Dussart Philippe , Héraud Jean-Michel , Brook Cara E. 
Published: December 2024

AbstractKobuviruses (familyPicornaviridae, genusKobuvirus) are enteric viruses that infect a wide range of both human and animal hosts. Much of the evolutionary history of kobuviruses remains elusive, largely due to limited screening in wildlife. Bats have been implicated as major sources of virulent zoonoses, including coronaviruses, henipaviruses, and filoviruses, though much of the bat virome still remains uncharacterized. While most bat virus research has historically focused on immediately recognizable zoonotic clades (e.g. SARS-related coronaviruses), a handful of prior reports catalog kobuvirus infection in bats and posit the role of bats as potential progenitors of downstream kobuvirus evolution. As part of a multi-year study, we carried out metagenomic Next Generation Sequencing (mNGS) on fecal samples obtained from endemic, wild-caught Madagascar fruit bats to characterize potentially zoonotic viruses circulating within these populations. The wild bats of Madagascar represent diverse Asian and African phylogeographic histories, presenting a unique opportunity for viruses from disparate origins to mix, posing significant public health threats. Here, we report detection of kobuvirus RNA in Malagasy fruit bat (Eidolon dupreanum) feces and undertake phylogenetic characterization of one full genome kobuvirus sequence, which nests within the Aichivirus A clade - a kobuvirus clade known to infect a wide range of hosts including humans, rodents, canids, felids, birds, and bats. Given the propensity of kobuviruses for recombination and cross-species infection, further characterization of this clade is critical to accurate evaluation of future zoonotic threats.
Polaris: a universal tool for chromatin loop annotation in bulk and single-cell Hi-C data
Authors: Hou Yusen , Baguette Audrey , Blanchette Mathieu , Zhang Yanlin 
Published: December 2024

AbstractAnnotating chromatin loops is essential for understanding the 3D genome’s role in gene regulation, but current methods struggle with low coverage, particularly in single-cell datasets. Chromatin loops are kilo-to mega-range structures that exhibit broader features, such as co-occurring loops, stripes, and domain boundaries along axial directions of Hi-C contact maps. However, existing tools primarily focus on detecting localized, highly-concentrated, interactions. Furthermore, the wide variety of available chromatin conformation datasets is rarely utilized in developing effective loop callers. Here, we present Polaris, a universal tool that integrates axial attention with a U-shaped backbone to accurately detect loops across different 3D genome assays. By leveraging extensive Hi-C contact maps in a pretrain-finetune paradigm, Polaris achieves consistent performance across various datasets. We compare Polaris against existing tools in loop annotation from both bulk and single-cell data and find that Polaris outperforms other programs across different cell types, species, sequencing depths, and assays.
Sex-specific transcriptome dynamics ofAnopheles gambiaeduring embryonic development
Authors: Kalita Agata Izabela , Marois Eric , Rühle Frank , Keller Valsecchi Claudia Isabelle 
Published: December 2024

AbstractMalaria-transmitting mosquitoes are extremely sexually dimorphic in their anatomy and behaviour. Sex-specific gene expression inAnopheles gambiaeis well-studied in adult stages, but its onset during embryogenesis, apart from sex-determination factors likeYob, remains largely unknown. Here, we report a comprehensive single-embryo transcriptome atlas ofA. gambiaemales and females to understand the earliest stages of establishing the sex-specific expression networks. Our dataset reveals embryonic RNA isoform diversity including a global shift towards distal alternative polyadenylation (APA) sites during the maternal-to-zygotic genome transition. Sex-biased gene expression and alternative splicing are limited during embryogenesis, with most sex-specific patterns emerging post- embryonically. X chromosome dosage compensation is established shortly after zygotic genome activation concomitant with direct binding of the master regulator protein SOA to X- linked promoters. Unlike the dosage compensation regulators inDrosophilaor mammals, SOA operates in a one-step fashion, directly binding CA-rich promoter motifs without prioritizing certain gene groups over others. We propose that theAnophelesdosage compensation system represents an evolutionary endpoint of a gene-by-gene regulatory mechanism that evolved to a chromosome-wide scale.
Chicken shank color determined byInhibition of dermal melanin(ID) is mediated by a structural variation regulatingCDKN2Aexpression
Authors: Li Jingyi , Wang Lei , Yang Sendong , Zhou Xin , Gou Qinli , Cai Jinping , Yang Hongrui , Wang Qiaohua , Li Shijun 
Published: December 2024

AbstractIt is well established that the color of a chicken’s shank is primarily determined by four genetic loci. Among these, theInhibition of dermal melanin(ID) locus, which suppresses black pigmentation in the dermal layer of the shank, is the sole sex-linked mutation and its molecular mechanisms remained elusive. In this study, a resource family with segregating shank colors was constructed. A genome-wide association study utilizing FarmCPU software identified a top-associated SNP located on the Z chromosome. Subsequent linkage mapping further refined the candidate region, enabling the screening of the candidate structural variation. The candidate structural variation is associated with the yellow shank and characterized by a 143 bp deletion accompanied by a 2 bp insertion. Within the same Topologically Associating Domain, only theCDKN2Agene showed differential expression. Functional studies, including CRISPR/Cas9-edited cells, provided evidence that this mutation regulatesCDKN2Atranscription and is responsible for theIDshank color in chickens. The absence of melanocytes is likely due to their apoptosis. This study completes the puzzle of chicken shank color genetics and paves the way for the application of theIDmutation in the auto-sexing of chicks which is intensively needed in layer and broiler industries.
How large could the
CP
violation in neutral
B
-meson mixing be? Implications for baryogenesis and upcoming searches
Authors: Miró Carlos , Escudero Miguel , Nebot Miguel 
Published: December 2024

CP violation in neutral B meson oscillations is an experimental observable that could be directly related to the baryon asymmetry of the Universe through the B-mesogenesis mechanism. As this phenomenon is highly suppressed in the Standard Model, it could also be a sensitive probe for many new physics scenarios that modify neutral meson mixing. Motivated by these facts, and the timely B physics program at the LHC and Belle II, we analyze how large CP violation in the mixing of neutral Bd and Bs meson systems could be. We answer this question, in light of current experimental data, within three different scenarios, namely: (i) generic heavy new physics only affecting the mass mixing M12q, (ii) vectorlike quark extensions that introduce deviations of 3×3 CKM unitarity, and (iii) light new physics modifying the decay mixing Γ12q. We find that enhancements of the semileptonic asymmetries, that measure the amount of CP violation in mixing, at the level of 10−3 for the Bd system and 10−4 for the Bs system can be achieved within scenarios (i) and (ii), while they are much more suppressed in realistic UV completions triggering scenario (iii). With respect to cosmology, the difficulty of finding large CP asymmetries in our analysis puts the B-mesogenesis mechanism in tension. Finally, we conclude that upcoming experimental searches for CP violation in B meson mixing at LHCb and Belle II are unlikely to detect a new physics signal for the most generic models.

Published by the American Physical Society
2024