bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health, Disability, and Economic Inactivity Following a Diagnosis of a Severe Mental Illness: Cohort Study of Electronic Health Records Linked at the Individual-Level, to Census from England
Authors: Cybulski L , Dewey M E , Hildersley R , Morgan C , Stewart R , Wuerth M , Das-Munshi J 
Published: November 2024

Abstract

Background
The association of social and clinical indicators with employment, disability, and health outcomes among individuals with severe mental illnesses (SMI) remains unclear. Existing evidence primarily comes from smaller cohort studies limited by shorter follow-up and high attrition, or registry-based research, which lacks information on important social determinants.

Study Design
We utilized a novel data linkage consisting of clinical records of individuals diagnosed with schizophrenia-spectrum or bipolar disorders from the South London and Maudsley Mental Health Trust, linked at the individual-level to the 2011 UK Census, a rich source for sociodemographic information. Using logistic regression, we estimated adjusted odds ratios (aORs) and 95% confidence intervals to determine associations between socioeconomic and clinical indicators and economic inactivity, self-rated health, and disability outcomes.

Results
The sample comprised 8249 people with SMI diagnoses. Economic inactivity (77.3%), disability (68.3%) and poor health (61.1%) were highly prevalent. Longer duration of illness and comorbid substance misuse were associated with economic inactivity, poorer self-rated health, and disability, with associations noted between living alone and all outcomes (aORs and 95% CI: Economic inactivity: 1.72, 1.45-2.03; disability: 1.48, 1.31-1.68; poor health: 1.32, 1.18-1.49). Relative to the White British group, Black African, South Asian, and Other Black groups were more likely to be economically inactive. Black Caribbean and other groups were less likely to report poorer self-rated health or disability.

Conclusions
Our findings highlight considerable disability, poorer health, and economic inactivity experienced by people with SMI. Addressing comorbid substance misuse and social isolation could play a role in improving outcomes.
“My Whole Life Was the Two Suburbs That Surrounded the Church”: LGBTQ+ Participation in Australian Pentecostal-Charismatic Churches as “Greedy Institutions”
Authors: Jennings Mark A C 
Published: November 2024

Abstract
Over the course of interviews with Lesbian, Gay, Bisexual, Transgender, Queer/Questioning and other (LGBTQ+) participants (or former participants) in Australian Pentecostal-Charismatic Christian (PCC) churches, a question emerged: why do LGBTQ+ people remain in churches which do not affirm their sexuality and/or gender identity (or, in the case of those who leave, why did they stay as long as they did)? Understanding these churches as “Greedy Institutions,” which stake a claim for participants’ undivided commitment, offers one explanation. Greedy institutions ostensibly maximize loyalty and assent without coercion, and this fits well with the reports of respondents, whose churches became the center of their spiritual and social lives. However, recognising the presence of a “morality of extremes,” divergence from which is punished as disloyalty, requires an analysis which discloses the exercise of “symbolic violence.” This perspective reveals that assent is also ensured through the threat of loss of ministry opportunities and community, and even eternal consequences.
An Omics approach onMarchantia polymorphasingle FERONIA and MARIS homologs confirms links between cell wall integrity and abscisic acid
Authors: Jobe Timothy Owen , Litholdo Celso Gaspar , Stolze Sara Christina , Stephan Lisa , Westermann Jens , Harzen Anne , Hülskamp Martin , Nakagami Hirofumi , Boisson-Dernier Aurélien 
Published: November 2024

AbstractPlant cells are surrounded by an extracellular cell wall that shields them from their abiotic and biotic environment. To coordinate their growth with their cell wall status, plant cells have developed cell wall integrity (CWI) mechanisms, at the center of which lies the transmembrane Malectin-like receptor kinase FERONIA (FER). FER controls a myriad of plant developmental processes including sexual reproduction, cell growth and morphogenesis, often intersecting with phytohormones-dependent pathways such as abscisic acid (ABA) signaling or plant immunity. Interestingly, FER together with its downstream receptor-like cytoplasmic kinase MARIS (MRI) was shown to similarly control root hair and rhizoid integrity in the vascular angiosperm Arabidopsis and the early diverging bryophyteMarchantia polymorpha, respectively.Here, we performed comparative transcriptomics and proteomics on theM. polymorphamutant plants, Mpfer-1and Mpmri-1,and their corresponding wild-type accessions Tak-1 and Tak-2. Large and significant overlaps were observed between differentially expressed genes and differentially abundant proteins in both mutants. Our multi-omics approach revealed that MpFER and MpMRI largely cooperate to negatively regulate transcriptional and translational networks, particularly those related to plant defense and ABA responses. Moreover, our phenotypic analyses showed that Mpfer-1plants are hypersensitive to ABA-dependent growth inhibition, indicating that FER’s function of negatively regulating ABA-related growth responses is conserved between bryophytes and vascular plants.
The effects of early-life ambient temperature on the gut microbiome of a wild bird? an experimental approach
Authors: Ruuskanen Suvi , Hollmen Lotta , Stier Antoine , Hsu Bin-Yan , Cossin-Sevrin Nina , Marciau Coline , Hukkanen Mikaela , Vesterinen Eero 
Published: November 2024

AbstractVertebrate gut microbiome has significant effects on host development, health, and fitness. Multiple external factors contribute to gut microbiome variation, and the role of ambient temperature has gained increasing attention. Yet, temperature effects are often tested in extremes and in captive systems. We experimentally studied the effect of subtle temperature decreases during post-natal development on gut microbiome diversity and composition in wild pied flycatchers (Ficedula hypoleuca). We also performed partial cross-fostering to study the relative contribution of genetic and rearing environment on microbiome. Nest-box cold treatment did not influence gut microbiome diversity or composition, which may be due to the small temperature change, ontogenetic stage, or other factors, such as diet, causing large variation in the data. Rearing environment explained more of the variation in gut microbiome than genetic background, but the variance explained was relatively small. Future studies need to further address the drivers of the large intraspecific variation in microbiome in natural populations.
Systemic exposure to COVID-19 virus-like particles modulates firing patterns of cortical neurons in the living mouse brain
Authors: Das Aniruddha , Icardi Jacob , Borovicka Julie , Holden Sarah , Harrison Henry F. , Hirsch Alec J. , Raber Jacob , Dana Hod 
Published: November 2024

AbstractSevere Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) causes a systemic infection that affects the central nervous system. We used virus-like particles (VLPs) to explore how exposure to the SARS-CoV-2 proteins affects brain activity patterns in wild-type (WT) mice and in mice that express the wild-type human tau protein (htau mice). VLP exposure elicited dose-dependent changes in corticosterone and distinct chemokine levels. Longitudinal two-photon microscopy recordings of primary somatosensory and motor cortex neurons that express the jGCaMP7s calcium sensor tracked modifications of neuronal activity patterns following exposure to VLPs. There was a substantial short-term increase in stimulus-evoked activity metrics in both WT and htau VLP-injected mice, while htau mice showed also increased spontaneous activity metrics and increase activity in the vehicle-injected group. Over the following weeks, activity metrics in WT mice subsided, but remained above baseline levels. For htau mice, activity metrics either remain elevated or decreased to lower levels than baseline. Overall, our data suggest that exposure to the SARS-CoV-2 VLPs leads to strong short-term disruption of cortical activity patterns in mice with long-term residual effects. The htau mice, which have a more vulnerable genetic background, exhibited more severe pathobiology that may lead to more adverse outcomes.
A widely-occurring family of pore-forming effectors broadens the impact of theSerratiaType VI secretion system
Authors: Reglinski Mark , Hurst Quenton W. , Williams David J. , Gierlinski Marek , Şahin Alp Tegin , Mathers Katharine , Ostrowski Adam , Bergkessel Megan , Zachariae Ulrich , Pitt Samantha J. , Coulthurst Sarah J. 
Published: November 2024

AbstractThe ability to compete with diverse competitors is essential for bacteria to succeed in microbial communities. A widespread strategy for inter-bacterial competition is the delivery of antibacterial toxins, or effector proteins, directly into rival cells using the Type VI secretion system (T6SS). Whilst a large number of broad-spectrum enzymatic T6SS effectors have been described, relatively few which form pores in target cell membranes have been reported. Here, we describe a widely-occurring new family of T6SS-dependent pore-forming effectors, exemplified by Ssp4 ofSerratia marcescensDb10. We showin vitrothat Ssp4 forms regulated pores that have higher selectivity for cations and use molecular dynamics simulations to support a high resolution structural model of a tetrameric membrane pore formed by Ssp4. Notably, Ssp4 displays a distinct ion selectivity, phylogenetic distribution and impact on intoxicated cells compared with Ssp6, the other cation-selective pore-forming toxin delivered by the same T6SS. Ssp4 is also active against a wider range of target species than Ssp6, highlighting that T6SS effectors are not always broad-spectrum. Finally, use of Tn-seq to identify Ssp4-resistant mutants reveals that amucAmutant ofPseudomonas fluorescens, which overproduces extracellular polysaccharide, provides resistance to T6SS attacks. We conclude that possession of two distinct T6SS-dependent pore-forming toxins may be a common strategy to ensure effective de-energisation of closely- and distantly-related competitors.
HelD is a Global Transcription Factor Enhancing Gene Expression in Rapidly Growing Mycobacteria
Authors: Vaňková Hausnerová Viola , Kumar Dilip , Shoman Mahmoud , Schwarz Marek , Modrák Martin , Jirát Matějčková Jitka , Neva Silvia , Havelková Jarmila , Šiková Michaela , Pospíšilová Debora , Halada Petr , Šanderová Hana , Holubová Jana , Dohál Matúš , Převorovský Martin , Staněk Ondřej , Knejzlík Zdeněk , Dvořáková Věra , Hnilicová Jarmila 
Published: November 2024

ABSTRACTHelD protein, also named HelR (encoded byMSMEG_2174inMycobacterium smegmatis), interacts with mycobacterial RNA polymerase (RNAP) and affects rifampicin resistance inMycobacterium abscessus. Here, we provide data on rifampicin resistance andhelDpresence in the genomes of other clinically relevant nontuberculous mycobacteria.We show thathelDis primarily found in rapidly growing mycobacteria, such asM. smegmatis, where we detected HelD at a subset of promoters that can also associate with CarD and RbpA. Transcriptome analysis of ahelDdeletion strain using RNA-seq revealed that HelD enhances gene expression during exponential growth and decreases it in stationary phase, during which we observed reduced levels of CarD, RbpA, and GTP, the initiation nucleotide for the majority ofM. smegmatistranscripts. We propose a model in which HelD releases abortive RNAP complexes and confirm that HelD dissociates RNAP from the promoterin vitro.HelD not only helps mycobacteria overcome rifampicin treatment but also supports efficient transcription during rapid growth, which indicates a dual role of this transcription regulator.
Comparative genomic analysis of a metagenome-assembled genome reveals distinctive symbiotic traits in a Mucoromycotina fine root endophyte arbuscular mycorrhizal fungus
Authors: Cole Joshua , Raguideau Sébastien , Abbaszadeh-Dahaji Payman , Hilton Sally , Muscatt George , Mushinski Ryan M. , Nilsson R. Henrik , Ryan Megan H. , Quince Christopher , Bending Gary D. 
Published: November 2024

SummaryRecent evidence shows that arbuscular mycorrhizal (AM) symbiosis is established by two distinct fungal groups, with the distinctive ‘fine root endophyte’ morphotype formed by fungi from the sub-phylum Mucoromycotina rather than the sub-phylum Glomeromycotina. While Mucoromycotina AM fungi are globally distributed, their genomic basis for the symbiosis or how this compares to other mycorrhizal symbionts is unknown.We used culture-independent metagenome sequencing to assemble and characterise the metagenome-assembled genome (MAG) of a putative fine root endophyte, which we show belonged to the family Planticonsortiaceae within the order Densosporales.The MAG shares key traits with Glomeromycotina fungi, which indicate obligate biotrophy, including absence of fatty acid and thiamine biosynthesis pathways, limited enzymatic abilities to degrade plant cell walls, and a high abundance of calcium transporters. In contrast to Glomeromycotina fungi, it exhibited a higher capacity for degradation of microbial cell walls, a complete cellulose degradation pathway, low abundances of copper, nitrate and ammonium transporters, and a complete pathway for vitamin B6 biosynthesis.These differences highlight the potential for contrasting interactions between Mucoromycotina and Glomeromycotina AM fungi with their host plant and the environment which could support niche differentiation and complementary ecological functions.
Rac1 inhibition prevents axonal cytoskeleton dysfunction in Transthyretin Amyloid Polyneuropathy
Authors: Magalhães Joana , Dias Vítor , Eira Jessica , Nóvoa Guilherme , Oliveira da Silva Marina I. , Kan Yu Yu , Dias Andreia , Carvalho Estefânia , Santos Mariana , Seixas Ana I , Coelho Teresa , Taipa Ricardo , Paes de Faria Joana , Lemos Carolina , Hsieh Sung-Tsang , Liz Márcia A. 
Published: November 2024

AbstractHereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is characterized by the deposition of amyloidogenic TTR, particularly in dorsal root ganglia (DRG) and peripheral nerve axons, resulting in sensorimotor axonopathy with autonomic dysfunction. Here, we investigated cytoskeleton alterations in peripheral axons from an ATTRv-PN mouse model, the hTTRA97S knock-in mice. Proteomics of hTTRA97S sural nerves revealed dysregulation of actin-related proteins. hTTRA97S DRG neurons presented a defective actin distribution in growth cones along with a reduction in axonal actin trails, and an associated impairment in the pool of pre-synaptic vesicles. Microtubule dynamics and axonal transport abnormalities were also observed in mutant axons. Importantly, cytoskeletal defects in hTTRA97S neurons preceded axonal degeneration and were mediated by Rac1 hyperactivation in DRG neurites and sciatic nerves of pre-symptomatic mice. Rac1 inhibition rescued cytoskeleton alterations, preventing degeneration. Remarkably, in ATTRv-PN patients with late-onset disease, a variant in RACGAP1, encoding a Rac1 inactivator, supported the neuroprotective role of Rac1 inhibition. Our findings demonstrate that cytoskeletal defects precede axonal degeneration in ATTRv-PN and highlight Rac1 as a promising therapeutic target.
In vivoregulation of an endogenously-tagged protein by a light-regulated kinase
Authors: Bao Mengjing , Lepeta Katarzyna , Aguilar Gustavo , Schnider Sophie , Affolter Markus , Vigano Maria Alessandra 
Published: November 2024

AbstractPost-translational modifications (PTMs) are indispensable modulators of protein activity. Most cellular behaviours, from cell division to cytoskeletal organization, are controlled by PTMs, their miss-regulation being associated with a plethora of human diseases. Traditionally, the role of PTMs has been studied employing biochemical techniques. However, these approaches fall short when studying PTM dynamicsin vivo. In recent years, functionalized protein binders have allowed the post-translational modification of endogenous proteins by bringing an enzymatic domain in close proximity to the protein they recognize. To date, most of these methods lack the temporal control necessary to understand the complex effects triggered by PTMs. In this study, we have developed a method to phosphorylate endogenous Myosin in a light-inducible manner. The method relies both on nanobody-targeting and light-inducible activation in order to achieve both tight specificity and temporal control. We demonstrate that this technology is able to disrupt cytoskeletal dynamics duringDrosophilaembryonic development. Together, our results highlight the potential of combining optogenetics and protein binders for the study of the proteome in multicellular systems.
Inflammatory Mesenchymal Stromal Cells and IFN-responsive T cells are key mediators of human bone marrow niche remodeling in CHIP and MDS
Authors: Prummel Karin D. , Woods Kevin , Kholmatov Maksim , Schmitt Eric C. , Vlachou Evi P. , Poschmann Gereon , Stühler Kai , Wehner Rebekka , Schmitz Marc , Winter Susann , Oelschlaegel Uta , Schwartz Logan S. , Moura Pedro L. , Hellström-Lindberg Eva , Theobald Matthias , Trowbridge Jennifer J. , Platzbecker Uwe , Zaugg Judith B. , Guezguez Borhane 
Published: November 2024

AbstractSomatic mutations in hematopoietic stem/progenitor cells (HSPCs) can lead to clonal hematopoiesis of indeterminate potential (CHIP), potentially progressing to myelodysplastic syndromes (MDS). Here, we investigated how CHIP and MDS remodel the human bone marrow (BM) niche relative to healthy elderly donors, using single cell and anatomical analyses in a large BM cohort. We found distinct inflammatory remodeling of the BM in CHIP and MDS. Furthermore, the stromal compartment progressively lost its HSPC-supportive adipogenic CXCL12-abundant reticular cells while an inflammatory mesenchymal stroma cell (iMSCs) population emerged in CHIP, which expanded in MDS. iMSCs exhibited distinct functional signatures in CHIP and MDS, retaining residual HSPC-support and angiogenic activity in MDS, corresponding with an increase in microvasculature in the MDS niche. Additionally, an IFN-responsive T cell population was linked to fueling inflammation in the stroma. Overall, these findings open new avenues for early intervention in hematological malignancies.
Notch Signaling Drives Pro-Regenerative and Migratory Traits in Glandular Stem/Progenitor cells
Authors: Cinat Davide , Maturi Rufina , Gunawan Jeremy P. , Bruin Anne L Jellema-de , Kracht Laura , Martinez Paola Serrano , Wu Yi , Soto-Gamez Abel , van Goethem Marc-Jan , Holtman Inge R. , Pringle Sarah , Barazzuol Lara , Coppes Rob P. 
Published: November 2024

AbstractOrganoid models have advanced our understanding of adult stem/progenitor cell dynamics and function. However, uncovering the regulatory mechanisms of scarce and often quiescent stem cells in organs like the salivary glands remains challenging. Using single-cell RNA sequencing and bulk ATAC and RNA-sequencing analysis, we conducted in-depth profiling of the cellular populations and key signaling pathways characterizing a mouse submandibular salivary gland organoid (mSGO) model at different temporal stages and in response to radiation damage. We identifiedSox9-andItgb1-expressing cells as the most primitive adult stem/progenitor populations and uncover novel stemness and migratory roles forCd44-expressing cells. Moreover, we revealed that Notch signaling is essential for maintaining self-renewal and migration potential of these stem/progenitor cells post-irradiation. Extending these findings to patient-derived mSGOs, as well as murine and patient-derived mammary and thyroid gland organoids, we confirmed Notch signaling as a conserved regulator of stem/progenitor cell function under migrative and regenerative conditions.
Paired CRISPR screens to map gene regulation incisandtrans
Authors: Xue Xinhe , Gajic Zoran Z. , Caragine Christina M. , Legut Mateusz , Walker Conor , Kim James Y.S. , Wang Xiao , Yan Rachel E. , Wessels Hans-Hermann , Lu Congyi , Bapodra Neil , Gürsoy Gamze , Sanjana Neville E. 
Published: November 2024

SummaryRecent massively-parallel approaches to decipher gene regulatory circuits have focused on the discovery of eithercis-regulatory elements (CREs) ortrans-acting factors. Here, we develop a scalable approach that pairscis- andtrans-regulatory CRISPR screens to systematically dissect how the key immune checkpointPD-L1is regulated. In human pancreatic ductal adenocarcinoma (PDAC) cells, we tile thePD-L1locus using ∼25,000 CRISPR perturbations in constitutive and IFNγ-stimulated conditions. We discover 67 enhancer- or repressor-like CREs and show that distal CREs tend to contact the promoter ofPD-L1and related genes. Next, we measure how loss of all ∼2,000 transcription factors (TFs) in the human genome impacts PD-L1 expression and, using this, we link specific TFs to individual CREs and reveal novel PD-L1 regulatory circuits. For one of these regulatory circuits, we confirm the binding of predictedtrans-factors (SRF and BPTF) using CUT&RUN and show that loss of either the CRE or TFs potentiates the anti-cancer activity of primary T cells engineered with a chimeric antigen receptor. Finally, we show that expression of these TFs correlates withPD-L1expressionin vivoin primary PDAC tumors and that somatic mutations in TFs can alter response and overall survival in immune checkpoint blockade-treated patients. Taken together, our approach establishes a generalizable toolkit for decoding the regulatory landscape of any gene or locus in the human genome, yielding insights into gene regulation and clinical impact.