bluuebunny/crossref_metadata_2025_split huggingface dataset:
The emergence and persistence of inequalities in adolescent mental health: the Resilience, Ethnicity and AdolesCent Mental Health (REACH) cohorts
Authors: Knowles Gemma , Gayer-Anderson Charlotte , Davis Samantha , Stanyon Daniel , Ofori Aisha , Blakey Rachel , Richards Thai-sha , Hashi Adna , Clement-Gbede Karima Shyan , Kitisu Jonas , Tettey Niiokani , Lowis Katie , Turner Alice , Dorn Lynsey , Putzgruber Esther , Pinfold Vanessa , Harding Seeromanie , Bhui Kamaldeep , Morgan Craig 
Published: January 2025

ABSTRACTBackgroundMental health problems are not distributed equally in society. Our understanding of when social inequalities in mental health emerge is limited. We sought to examine inequalities in trajectories of mental distress in diverse, representative cohorts of adolescents in inner-London.MethodsWe analysed longitudinal data from our cohort study of adolescent mental health, REACH (n=4663; 51% girls, 29% free school meals [FSM], 85% minoritised ethnic groups). We used latent growth curve models to estimate trajectories of mental distress (total, internalising, and externalising scores from the self-report Strengths and Difficulties Questionnaire) from age 11-16 years, overall and by gender, FSM, ethnic group, and their intersections.ResultsWe found strong evidence of differences in trajectories of mental distress by gender and FSM. Higher mean internalising scores in girls (vs. boys) were evident at age 11-12 and this inequality widened year-on-year (difference in mean intercepts: 0.74 [95% CI 0.52, 0.96]; slopes: 0.50 [0.39, 0.61]). Higher mean levels of distress among those receiving FSM (vs. not) were evident at age 11-12 years (e.g., difference in intercepts, general distress: 0.79 [0.19, 1.39]), and this difference, though modest, persisted through adolescence. By ethnic group and intersecting identities, the picture was more complex and mixed. Broadly, Black African youth generally reported better mental health trajectories vs. their peers; Black Caribbean and Mixed Black-and-White youth shared similar trajectories, differing somewhat from Black African; and by age 16, internalising distress was highest among lower-income White British girls.ConclusionsIn diverse inner-cities, adolescence is an important period in the emergence and persistence of some of the inequalities in mental health reported in adults; others are more nuanced.
Locally induced traveling waves generate globally observable traveling waves
Authors: Petras Kirsten , Grabot Laetitia , Dugué Laura 
Published: January 2025

AbstractCortical traveling waves have been proposed as a fundamental mechanism for neural communication and computation. Methodological uncertainties currently limit the interpretability of non-invasive, extracranial traveling wave data, sparking debates about their cortical origin. Studies using EEG or MEG typically report waves that cover large portions of the sensor array which are often interpreted as reflecting long range cortical waves. Meanwhile, invasive, intracranial recordings in humans and animals routinely find both local, mesoscopic waves and large scale, macroscopic waves in cortex. Whether the global sensor-array waves found with EEG/MEG necessarily correspond to macroscopic cortical waves or whether they are merely projections of local dynamics remains unclear. In this study, we made use of the well-established retinotopic organization of early visual cortex to generate traveling waves with known properties in human participants (N=19, m/f) via targeted visual stimulation, while simultaneously recording MEG and EEG. The inducer stimuli were designed to elicit waves whose traveling direction in mesoscopic retinotopic visual areas depends on stimulus direction, while leaving macroscopic activation patterns along the visual hierarchy largely unchanged. We observed that the preferred direction of traveling waves across the sensor array was influenced by that of the visual stimulus, but only at the stimulation frequency. Comparison between single-trial and trial-averaged responses further showed considerable temporal variation in traveling wave patterns across trials. Our results highlight that under tight experimental control, non-invasive, extracranial recordings can recover mesoscopic traveling wave activity, thus making them viable tools for the investigation of spatially constrained wave dynamics.Significant statementNon-invasively obtained time-resolved neuroimaging data is often thought to primarily reflect neural dynamics on the largest spatial scales. In the context of cortical traveling waves, this assumption can lead to a misinterpretation of spatio-temporal patterns observed in the sensor array. We here show that it is in principle possible that the global sensor array data is dominated by spatially constrained, local cortical traveling wave activity. Our findings crucially inform the ongoing discussion about the origin of traveling waves observed in surface recordings.
Intestinal stem cell renewal controlled by capillary morphogenesis gene 2 following injury
Authors: Bracq Lucie , Chuat Audrey , Kunz Béatrice , Burri Olivier , Guiet Romain , van der Goot F. Gisou 
Published: January 2025

SUMMARYPatients with the rare genetic disorder Hyaline Fibromatosis Syndrome (HFS) often succumb before 18 months of age due to severe diarrhea and protein-losing enteropathy. As HFS is caused by loss-of-function mutations in the gene encoding capillary morphogenesis gene 2 (CMG2), also known as Anthrax Toxin Receptor 2, these symptoms highlight a critical yet unclear role for CMG2 in the gut. Here, we demonstrate that CMG2 knockout mice exhibit normal colon morphology and no signs of inflammation until the chemical induction of colitis. In these conditions, the colons of knockout mice do not regenerate despite previously experiencing similarly severe colitis, due to an inability to replenish their intestinal stem cell pool. Specifically, CMG2 knockout impairs the transition from fetal-like to Lgr5+ adult stem cells, which is associated with a defect in ß-catenin nuclear translocation. Our findings suggest that CMG2 functions as a context-specific modulator of Wnt signaling, essential for replenishing the pool of intestinal stem cells following injury. This study provides new insights into the molecular mechanisms underlying protein-losing enteropathy in HFS and offers a broader understanding of fetal-like regenerative responses.GRAPHICAL ABSTRACT
Pollen morphology, deep learning, phylogenetics, and the evolution of environmental adaptations inPodocarpus
Authors: Adaimé Marc-Élie , Urban Michael A. , Kong Shu , Jaramillo Carlos , Punyasena Surangi W. 
Published: January 2025

SummaryPodocarpuspollen morphology is shaped by both phylogenetic history and the environment. We analyzed the relationship between pollen traits quantified using deep learning and environmental factors within a comparative phylogenetic framework.We investigated the influence of mean annual temperature, annual precipitation, altitude, and solar radiation in driving morphological change. We used trait-environment regression models to infer the temperature tolerances of 31 NeotropicalPodocarpiditesfossils. Ancestral state reconstructions were applied to thePodocarpusphylogeny with and without the inclusion of fossils.Our results show that temperature and solar radiation influence pollen morphology, with thermal stress driving an increase in pollen size and higher UV-B radiation selecting for thicker corpus walls. Fossil temperature tolerances inferred from trait-environment models aligned with paleotemperature estimates from global paleoclimate models. Incorporating fossils into ancestral state reconstructions revealed that early ancestralPodocarpuslineages were likely adapted to warm climates, with cool-temperature tolerance evolving independently in high-latitude and high-altitude species.Our results highlight the importance of deep learning-derived features in advancing our understanding of plant environmental adaptations over evolutionary timescales. Deep learning allows us to quantify subtle interspecific differences in pollen morphology and link these traits to environmental preferences through statistical and phylogenetic analyses.
Mitigating Proinflammatory SASP and DAMP with Urolithin A: A Novel Senomorphic Strategy
Authors: Barkovskaya Anna , Brauning Ashley , Chamoli Manish , Rane Anand , Andersen Julie K , Sharma Amit 
Published: January 2025

AbstractSenescent cells are known to contribute to aging and age-related diseases. One key way they influence aging is by secreting senescence-associated secretory phenotype (SASP) factors along with several damage-associated molecular pattern (DAMP) molecules. Consequently, inhibiting SASP and DAMP signaling (senomorphics) has emerged as a therapeutic strategy. Urolithin A (UA), a gut-derived metabolite produced from ellagitannins and ellagic acid found in berries, nuts, and pomegranates, has demonstrated potent anti-inflammatory properties and protective effects against aging and age-related conditions in experimental models. Here we demonstrate that UA lowers the expression and release of pro-inflammatory SASP and DAMP factors at least in part, on the downregulation of cytosolic DNA release and subsequent decrease in cGAS-STING signaling.
β1 Integrin–FAK–Piezo1 signalling axis drivesin-situstiffening mediated ECM remodelling and invasion of 3D breast epithelium
Authors: Sakthivel Kabilan , Kotowska Anna , Portner Ellen Juel , Merry Catherine , Nordenfelt Pontus , Simonsen Adam Cohen , Wright Amanda J. , Swaminathan Vinay 
Published: January 2025

AbstractStiffening of tissue is a hallmark of cancer progression, driving invasive phenotypes through complex interactions between cells and their extracellular matrix (ECM). However, the mechanisms linking mechanical cues to ECM remodelling and invasion remain incompletely understood. Here, using anin-situstiffening model that allows for modulation of ECM stiffness around fully formed normal mammary acini embedded in their native ECM microenvironment, we identify critical steps in basement membrane (BM) and stromal ECM remodelling during invasion and discover the molecular mechanisms driving this process. We find that stiffening of the ECM around normal mammary acini results in rapid loss and degradation of laminin (LN) and upregulation of the fibronectin (FN) secretion around the acini. This priming phase is followed by the onset of invasion which requires localized upregulation of LN production and ECM remodelling. Mechanistically, ECM production and remodelling as well as invasion is mediated by β1 integrin–FAK signalling, which activates mechanosensitive ion channels (MSCs). Further, we identify Piezo1 as the MSC downstream of β1 integrin–FAK that drives BM disruption and stromal ECM remodelling. Taken together, our results identify the mechanisms by which stiffness can trigger invasive phenotypes from normal tissues.
SDS-22 stabilizes the PP1 catalytic subunits GSP-1/-2 contributing to polarity establishment inC. elegansembryos
Authors: Li Yi , Calvi Ida , Gotta Monica 
Published: January 2025

AbstractIn many cells, cell polarity depends on the asymmetric distribution of the conserved PAR proteins, maintained by a balanced activity between kinases and phosphatases. TheC. elegansone-cell embryo is polarized along the anterior-posterior axis, with the atypical protein kinase C PKC-3 enriched in the anterior, and the ring finger protein PAR-2 in the posterior. PAR-2 localization is regulated by PKC-3 and the PP1 phosphatases GSP-1/-2. Here, we find that, like GSP-2 depletion, depletion of the conserved PP1 interactor SDS-22 results in the rescue of the polarity defects of apkc-3temperature-sensitive mutant. Consistent with the rescue, SDS-22 depletion or mutation results in reduced GSP-1/-2 protein levels and activity. The decreased levels of GSP-1/-2 can be rescued by reducing proteasomal activity. Our data suggest that SDS-22 regulates polarity not by directly regulating the localization or activity of GSP-1/-2, but by protecting these PP1 catalytic subunits from proteasome-mediated degradation, supporting recent data in human cells showing the SDS22 is required to stabilize nascent PP1.
Disentangling the evolutionary history of terrestrial planarians through phylogenomics
Authors: Benítez-Álvarez Lisandra , Escudero Nuria , Salces-Ortiz Judit , Rojo Iñaki , Fernández-Álvarez Fernando Ángel , Mateos Eduardo , Carbayo Fernando , Fernández Rosa 
Published: January 2025

ABSTRACTTriclads (Platyhelminthes, Tricladida) are found in marine, freshwater, and terrestrial habitats worldwide except Antarctica. Terrestrial planarians are grouped into the family Geoplanidae, which is subdivided into the subfamilies Geoplaninae, Bipaliinae, Rhynchodeminae, and Microplaninae. Some of these subfamilies result from taxonomic rearrangements based on molecular phylogenies inferred from a few molecular markers. However, the diagnosis of Rhynchodeminae was not aligned with the morphology of all its representatives. While the subfamilies are recovered as monophyletic in recent molecular phylogenies, robust hypotheses regarding the relationships between them remain unknown. In this study, we employ for the first time a phylogenomic framework to investigate the evolutionary relationships among the subfamilies, starting by obtaining the first transcriptomes for 15 species of terrestrial planarians. A total of 16 different datasets, comprising nearly two thousand single-copy genes inferred from transcriptomic data, were analyzed using various phylogenetic inference methods. We recovered, for the first time, a well-supported topology of phylogenetic relationships among Geoplanidae subfamilies, positioning Bipaliinae and Microplaninae as a clade sister to Rhynchodeminae + Geoplaninae. Internal relationships within the genusMicroplanawere not supported in our analyses. The subfamily Rhynchodeminae, represented in our phylogeny by species from the tribes Rhynchodemini and Caenoplanini, is re-diagnosed to align with previous taxonomic rearrangements. This study not only represents a significant step forward in the phylogenetic resolution of Geoplanidae but also provides important insights into the broader evolutionary dynamics shaping land planarian diversity.HighlightsFirst transcriptomes of multiple terrestrial planarians sequenced.First molecular phylogeny of terrestrial planarians at subfamily level based on transcriptomic data.Highly supported topology for phylogenetic interrelationship among terrestrial planarians subfamilies.Unclear interrelationships between species from the genusMicroplana.The subfamily Rhynchodeminae is re-diagnosed at the morphological level.
Metabolic tagging reveals surface-associated lipoproteins in mycobacteria
Authors: Parkin Lia A. , Maceren Julian P. , Palande Aseem , Previti Mary L. , Seeliger Jessica C. 
Published: January 2025

ABSTRACTMycobacteria such as the causative agent of tuberculosis,Mycobacterium tuberculosis, encode over 100 bioinformatically predicted lipoproteins. Despite the importance of these post-translationally modified proteins for mycobacterial survival, many remain experimentally unconfirmed. Here we characterized metabolic incorporation of diverse fatty acid analogues as a facile method of adding chemical groups that enable downstream applications such as detection, crosslinking and enrichment, of not only lipid-modified proteins, but also their protein interactors. Having shown that incorporation is an active process dependent on the lipoprotein biosynthesis pathway, we discovered that lipid-modified proteins are also located at the mycobacterial cell surface. These data counter the commonly held assumption that mycobacteria do not move lipoproteins across the cell envelope and thus have implications for uncovering a novel transport pathway and the roles of lipoproteins at the interface with the host environment. Our findings and the tools we developed will enable the further study of pathways related to lipoprotein function and metabolism in mycobacteria and other bacteria in which lipoproteins remain poorly understood.
Specificity Protein 1 is essential for the limb trajectory of ephrin-mediated spinal motor axons
Authors: Liao Pinwen , Chang Ming-Yuan , Yang Wen-Bin , Lin Keefer , Li Yi-Chao , Chuang Jian-Ying , Wu Yi-Hsin , Kania Artur , Chang Wen-Chang , Hsu Tsung-I , Kao Tzu-Jen 
Published: January 2025

AbstractThe precise organization of neural circuits requires highly specific axon guidance, facilitated by cell-surface guidance receptors on axonal growth cones that help neurons reach their target destinations. Despite a limited repertoire of known guidance receptors and ligands, neural systems achieve complex axonal networks, suggesting that additional regulatory mechanisms exist. One proposed strategy is the co-expression of ligands and their receptors on the same axons, allowing modulation of receptor responsiveness to guidance cues. To investigate this mechanism, we studied the spinal lateral motor column (LMC) motor neurons, which make a binary axon pathfinding decision toward limb targets. We hypothesized that specificity protein 1 (Sp1), a transcription factor, regulates ephrin expression in LMC neurons, thereby modulating receptor functions viacis-attenuation to ensure accurate axonal pathfinding. Our results show that Sp1 is indeed expressed in LMC neurons during critical axonal extension periods. Manipulating Sp1 activity disrupted LMC axon trajectory selection, and RNA-Seq analysis indicated that Sp1 regulates genes associated with axon guidance, including ephrins. We found that Sp1 knockdown affected ephrin/Ephcis-binding andtrans-signaling, highlighting Sp1’s role in controlling axonal projections through ephrin gene regulation. Additionally, coactivators p300 and CBP are essential for Sp1’s regulatory function. These findings identify Sp1 as a key transcription factor in LMC neurons, essential for ephrin expression and ephrin/Eph-mediated axon guidance, providing insights into the molecular mechanisms of neural circuit formation.
The zinc-finger protein POGZ associates with Polycomb repressive complex 1 to regulate bone morphogenetic protein signaling during neuronal differentiation
Authors: Chavez Jessenia , Wolf Trevor , Geng Zhuangzhuang , Tai Yen Teng , Bright Kathleen , Stafford James , Gao Zhonghua 
Published: January 2025

AbstractPolycomb Repressive Complex 1 (PRC1) is a family of epigenetic regulators critical for mammalian development. Elucidating PRC1 composition and function across cell types and developmental stages is key to understanding the epigenetic regulation of cell fate determination. In this study, we discovered POGZ, a prominent Autism Spectrum Disorder (ASD) risk factor, as a novel component of PRC1.6, forming the PRC1.6-POGZ complex. Functional assays revealed that POGZ elicits transcriptional repression that is dependent on RING1B expression. Analysis of publicly available ChIP-Seq data showed that POGZ highly colocalizes with RING1B and HP1γ, two PRC1.6 components, at genes involved in multiple aspects of transcriptional regulation in the embryonic mouse cortex. AlthoughPogzknockout (KO) does not compromise stem cell pluripotency,Pogzablation in neuronal progenitor cells (NPCs) led to widespread transcriptomic dysregulation with failed activation of key neuronal genes. Finally, we demonstrated that PRC1.6-POGZ regulates neuronal differentiation by repressing the bone morphogenetic protein (BMP) signaling pathway. These findings reveal a mechanism by which PRC1 and POGZ coordinate transcriptional regulation during neuronal differentiation, which offers insights into how disruptions in this pathway may contribute to neurodevelopmental disorders such as ASD.
Nucleotide-resolution Mapping of RNA N6-Methyladenosine (m6A) modifications and comprehensive analysis of global polyadenylation events in mRNA 3’ end processing in malaria pathogenPlasmodium falciparum
Authors: Catacalos-Goad Cassandra , Chakrabarti Manohar , Salem Doaa Hassan , Camporeale Carli , Somalraju Sahiti , Tegowski Matthew , Singh Ruchi , Reid Robert W. , Janies Daniel A. , Meyer Kate D. , Janga Sarath Chandra , Hunt Arthur G. , Chakrabarti Kausik 
Published: January 2025

ABSTRACTPlasmodium falciparumis an obligate human parasite of the phylum Apicomplexa and is the causative agent of the most lethal form of human malaria. Although N6-methyladenosine modification is thought to be one of the major post-transcriptional regulatory mechanisms for stage-specific gene expression in apicomplexan parasites, the precise base position of m6A in mRNAs or noncoding RNAs in these parasites remains unknown. Here, we report global nucleotide-resolution mapping of m6A residues inP. falciparumusing DART-seq technology, which quantitatively displayed a stage-specific, dynamic distribution pattern with enrichment near mRNA 3’ ends. In this process we identified 894, 788, and 1,762 m6A-modified genes in Ring, Trophozoite and Schizont stages respectively, with an average of 5-7 m6A sites per-transcript at the individual gene level. Notably, several genes involved in malaria pathophysiology, such as KAHRP, ETRAMPs, SERA and stress response genes, such as members of Heat Shock Protein (HSP) family are highly enriched in m6A and therefore could be regulated by this RNA modification. Since we observed preferential methylation at the 3’ ends ofP. falciparumtranscripts and because malaria polyadenylation specificity factor PfCPSF30 harbors an m6A reader ‘YTH’ domain, we reasoned that m6A might play an important role in 3’-end processing of malaria mRNAs. To investigate this, we used two complementary high-throughput RNA 3’-end mapping approaches, which provided an initial framework to explore potential roles of m6A in the regulation of alternative polyadenylation (APA) during malaria development in human hosts.
Rapid clinical diagnosis and treatment of common, undetected, and uncultivable bloodstream infections using metagenomic sequencing from routine blood cultures with Oxford Nanopore
Authors: Govender Kumeren N. , Eyre David W. 
Published: January 2025

AbstractMetagenomic sequencing could potentially revolutionise clinical microbiology, including identifying pathogens and predicting antimicrobial resistance (AMR) in seriously unwell patients with bloodstream infections. We present a direct-from-blood culture sequencing method that delivers results rapidly and accurately. In 273 randomly-selected blood cultures (211 positive, 62 negative), we achieved 97% sensitivity and 94% specificity (improving to 100% accounting for plausible additional infections) for species identification compared to established diagnostic methods. We detected 18 additional infections—13 polymicrobial and 5 previously unidentifiable—and delivered findings in 3.5 hours, nearly a third of time taken by routine methods. For the top ten pathogens, our method produced AMR results 20 hours quicker, with 88% sensitivity and 93% specificity. ForStaphylococcus aureusandEscherichia coli, AMR prediction sensitivity was 100% and 91%, and specificity 99% and 94% respectively. These findings suggest the potential of integrating clinical metagenomics into standard diagnostics for faster and more comprehensive pathogen detection.