bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrosteric, van der Waals and elastic interaction of polyelectrolyte hydrogels
Authors: Hill Reghan J. 
Published: December 2023

The electrosteric interaction energy for a charged hydrogel and hard plane, and between two charged hydrogels is derived in the Debye–Hückel approximation. This is combined with a van der Waals potential that explicitly addresses the Hamaker constant for the solvent-mediated hydrogel interactions. Then, in the Derjaguin approximation, DLVO-type interaction potentials are provided for hydrogel and hard/rigid spheres, accounting for elastic deformation that accompanies adhesion. As examples, this furnishes the energy for cohesion of soft polyelectrolyte microspheres, and provides a quantitative interpretation for the adhesion of rigid latex spheres to a soft deformable hydrogel, as reported by Sato
et al.
(Sato
et al.
2017
Sci. Rep.
7
, 1–10 (
doi:10.1038/s41598-017-06257-1
)). The theory demonstrates that weak van der Waals attraction of hydrogels is readily balanced by electrosteric interactions, e.g. making colloidal hydrogel dispersions less stable than their rigid-particulate counterparts.
Single cell discovery of m6A RNA modifications in the hippocampus
Authors: Feng Shuangshuang , Tellaetxe-Abete Maitena , Zhang Yujie , Peng Yan , Zhou Han , Larrea Erika , Xue Liang , Zhang Li , Koziol Magdalena J. 
Published: December 2023

ABSTRACTN6-methyladenosine (m6A) is a prevalent and highly regulated RNA modification essential for RNA metabolism and normal brain function. It is particularly important in the hippocampus, where m6A is implicated in neurogenesis and learning. Although extensively studied, its presence in specific cell types remain poorly understood. We investigated m6A in the hippocampus at the single cell level, revealing a comprehensive landscape of m6A modifications within individual cells. Our data also identifies transcripts which have high m6A density and are associated with brain diseases. Our data suggests that m6A containing transcripts might be of particular importance forCamk2aneurons. Overall, this work provides new insights into the molecular mechanisms underlying hippocampal physiology and lays the foundation for future studies investigating the dynamic nature of m6A RNA methylation in the healthy and diseased brain.
Ursodeoxycholic acid and severe COVID-19 outcomes in people with liver disease: a cohort study using the OpenSAFELY platform
Authors: Costello Ruth E , Jean Waller Karen Maree , Smith Rachel , Mells George F , Wong Angel YS , Schultze Anna , Mahalingasivam Viyaasan , Herrett Emily , Zheng Bang , Lin Liang-Yu , Mehrkar Amir , Bacon Sebastian CJ , Goldacre Ben , Tomlinson Laurie A , Tazare John , Rentsch Christopher T ,   the OpenSAFELY collaborative and the LH&W NCS (or CONVALESCENCE) Collaborative
Published: December 2023

AbstractBiological evidence suggests ursodeoxycholic acid (UDCA) - a common treatment of cholestatic liver disease - may prevent severe COVID-19 outcomes. With the approval of NHS England, we conducted a population-based cohort study using primary care records, linked to death registration data and hospital records through the OpenSAFELY-TPP platform. We estimated the hazard of COVID-19 hospitalisation or death between 1 March 2020 and 31 December 2022, comparing UDCA treatment to no UDCA treatment in a population with indication. Of 11,320 eligible individuals, 642 were hospitalised or died with COVID-19 during follow-up, 402 (63%) events among UDCA users. After confounder adjustment, UDCA was associated with a 21% (95% CI 7%-33%) relative reduction in the hazard of COVID-19 hospitalisation or death, consistent with an absolute risk reduction of 1.3% (95% CI 1.0%-1.6%). Our findings support calls for clinical trials investigating UDCA as a preventative measure for severe COVID-19 outcomes.
The complement pattern recognition molecule CL-11 promotes invasion and injury of respiratory epithelial cells by SARS-CoV-2
Authors: Polycarpou Anastasia , Wagner-Gamble Tara , Greenlaw Roseanna , O’ Neill Lauren A. , Khan Hataf , Malim Michael , Romano Marco , Smolarek Dorota , Doores Katie , Wallis Russell , Klavinskis Linda S. , Sacks Steven 
Published: December 2023

AbstractCollectin-11 is a soluble C-type lectin produced at epithelial surfaces to initiate pathogen elimination by complement. Given the respiratory epithelium is a source of CL-11 and downstream complement-pathway components, we investigated the potential of CL-11 to impact the pathogenicity of SARS-CoV-2. While the SARS-CoV-2 spike trimer could bind CL-11 and trigger complement activation followed by MAC formation, the virus was resistant to lysis. Surprisingly, virus production by infected respiratory epithelial cells was enhanced by CL-11 opsonisation of virus but this effect was fully inhibited by sugar-blockade of CL-11. Moreover, SARS-CoV-2 spike protein expressed at the bronchial epithelial cell surface was associated with increased CL-11 binding and MAC formation. We propose that SARS-CoV-2 pathogenicity is exacerbated both by resistance to complement and CL-11 driven respiratory cell invasion and injury at the portal of entry. Contrary to expectation, CL-11 blockade could offer a novel approach to limit the pathogenicity of SARS-CoV-2.
“Mesenchymal Osr1+ cells regulate embryonic lymphatic vessel formation”
Authors: Vallecillo-García Pedro , Kühnlein Mira Nicola , Orgeur Mickael , Hansmeier Nils Rouven , Kotsaris Georgios , Timmermann Bernd , Giesecke-Thiel Claudia , Hägerling René , Stricker Sigmar 
Published: December 2023

AbstractThe lymphatic system is formed during embryonic development by the commitment of specialized lymphatic endothelial cells (LECs) and their subsequent assembly in primary lymphatic vessels. While lymphatic cells are in continuous contact with mesenchymal cells during development and in adult tissues, the role of mesenchymal cells in lymphatic vasculature development remains poorly characterized. Here, we show that a subpopulation of mesenchymal cells expressing the transcription factorOsr1are in close association with migrating LECs and established lymphatic vessels in mice. Lineage tracing experiments revealed that Osr1+ cells precede LEC arrival during lymphatic vasculature assembly in the back of the embryo. Using Osr1-deficient embryos and functionalin vitroassays, we show thatOsr1acts in a non-cell autonomous manner controlling proliferation and early migration of LECs to peripheral tissues. Thereby, mesenchymal Osr1+ cells control in a bimodal manner the production of extracellular matrix scaffold components and signal ligands critical for lymphatic vessels formation.
Increased blood–brain barrier leakage in schizophrenia spectrum disorders compared to healthy controls in dynamic contrast-enhanced magnetic resonance imaging
Authors: Moussiopoulou Joanna , Yakimov Vladislav , Rauchmann Boris-Stephan , Toth Hannah , Melcher Julian , Jäger Iris , Lutz Isabel , Kallweit Marcel , Papazov Boris , Seelos Klaus , Dehsarvi Amir , Röll Lukas , Campana Mattia , Raabe Florian , Maurus Isabel , Falkai Peter , Hasan Alkomiet , Franzmeier Nicolai , Keeser Daniel , Wagner Elias 
Published: December 2023

AbstractBackgroundThere is growing evidence for inflammatory mechanisms in schizophrenia spectrum disorders (SSD) that have been associated with blood-brain barrier (BBB) disruption. Previous studies investigating the BBB in SSD focused on cerebrospinal fluid (CSF) markers, that cannot adequately assess BBB integrity. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) represents a sensitive method for investigating subtle barrier breakdown in vivo. So far, only one pilot study has investigated BBB breakdown in SSD with DCE-MRI, in a relatively small cohort. We hypothesized higher leakage in SSD compared to HC, indicative of a clinical sub-phenotype of SSD.MethodsForty-one people with SSD and 40 age- and sex-matched healthy controls (HC) were included in the final analyses of the cross-sectional study. DCE-MRI, clinical characterization, cognitive assessments, blood and CSF analyses were conducted. The volume transfer constant Ktranswas calculated with pharmacokinetic modelling (Patlak method), to estimate the rate of contrast agent transfer between blood and the brain’s extravascular space. Ktransmaps were compared between the groups to detect group differences in BBB leakage. Within the SSD cohort, the association between leakage and clinical characteristics was investigated with linear regression analyses.ResultsGroup comparisons of Ktransmaps showed higher leakage in SSD compared to HC on a whole brain level. The effect was more pronounced in first episode compared to multiple episode psychosis. No association was detected between leakage and measures of cognition, psychopathology, peripheral inflammation and albumin CSF/serum ratio.DiscussionThis is the largest study to date investigating the BBB in SSD with DCE-MRI in a multimodal approach, allowing direct exploration of the BBB, compared to a HC group. The integrity of the BBB is crucial for maintaining the brain’s microenvironment, and its disruption could be associated with potential immune system abnormalities. The results of this study provide the first in vivo evidence of higher BBB leakage on a whole brain level compared to HC. The disruption of the BBB in SSD, as detected through DCE-MRI, may provide insights into the disease’s mechanisms and potential for targeted treatments. Further research in this area may clarify specific biological disease mechanisms and identify new therapeutic targets.
Single-cell RNAseq reveals the pro-regenerative role of senescent FAPs in muscle regeneration
Authors: Chen Cheng , Saclier Marielle , Chantrel Jérémy , Mella Sébastian , Chiche Aurélie , Li Han 
Published: December 2023

AbstractMuscle regeneration is associated with transient induction of cellular senescence. However, the role of senescence in muscle regeneration of young mice remains unclear. Using a mouse model deficient in both Cdkn1a and Cdkn2a, we find that a marked reduction in senescent cells correlates with delayed muscle regeneration. Single-cell RNA sequencing reveals a heterogeneous senescence program composing of multiple cell types. Notably, senescent fibro-adipogenic progenitors (FAPs) upregulate Mcl-1 to acquire apoptosis resistance. Moreover, removing senescent FAPs using a Mcl-1 inhibitor S63845 impairs muscle regeneration. Furthermore, we find that senescent FAPs promotes myogenic differentiation in a paracrine manner. Hence, these results highlight the beneficial role of senescent stromal cells in supporting muscle regeneration.
Membrane-embedded polar residues target membrane proteins for degradation by the quality control protease FtsH
Authors: Chai-Danino Michal , Ravensary Noy , Onyshchuk Tetiana , Plöhn Martin , Barshap Alon B.D. , Bsoul Aseel , Peled-Zehavi Hadas , Fluman Nir 
Published: December 2023

AbstractMembrane proteins (MPs) navigate challenging biogenesis. Errors in this process are rigorously surveilled by cellular quality control to eliminate faulty MPs. The first critical challenge of this surveillance is the accurate recognition of misfolded proteins. However, how this recognition is achieved for MPs remains poorly defined. Here we reveal the specificity mechanism of FtsH, the major quality control protease clearing faulty MPs inEscherichia coli. Analyzing the in vivo degradation of two substrates, we show that lipid-facing polar residues direct substrates to FtsH-mediated degradation. Such polar residues are typically buried in the structural cores of folded MPs, and their exposure to the membrane may thus signify misfolding and flag proteins for degradation. Remarkably, lipid-facing polar residues are sufficient for recognition and can target even folded MPs for degradation. The recognition depends on the FtsH transmembrane domain. Thus, MP misfolding is sensed within the membrane to maintain a healthy membrane proteome.
High-resolution bulked segregant analysis enables candidate gene identification for bacterial wilt resistance in Italian ryegrass
Authors: Florian Goettelmann , Yutang Chen , Verena Knorst , Steven Yates , Dario Copetti , Bruno Studer , Roland Kölliker 
Published: December 2023

AbstractBacterial wilt, caused byXanthomonas translucenspv.graminis(Xtg), is a serious disease of economically important forage grasses, including Italian ryegrass (Lolium multiflorumLam.). A major QTL for resistance toXtgwas previously identified, but the precise location as well as the genetic factors underlying the resistance are yet to be determined. To this end, we applied a bulked segregant analysis (BSA) approach, using whole-genome deep sequencing of pools of the most resistant and most susceptible individuals of a large (n = 7,484) biparental F2population segregating for resistance toXtg. Using chromosome-level genome sequences as references, we were able to define a ∼300 kb region highly associated to resistance on pseudo-chromosome 4. Further investigation of this region revealed multiple genes with a known role in disease resistance, including genes encoding for Pik2-like disease resistance proteins, cysteine-rich kinases, and RGA4- and RGA5-like disease resistance proteins. Investigation of allele frequencies in the pools and comparative genome analysis in the grandparents of the F2population revealed that some of these genes contain variants with allele frequencies that correspond to the expected heterozygosity in the resistant grandparent. This study emphasizes the efficacy combining BSA studies in very large populations with whole genome deep sequencing and high-quality genome sequences to pinpoint regions associated with a binary trait of interest and accurately define a small set of candidate genes. Furthermore, markers identified in this region hold significant potential for marker-assisted breeding strategies to breed resistance toXtgin Italian ryegrass cultivars more efficiently.
Neurophysiological mechanisms underlying post-stroke deficits in contralesional perceptual processing
Authors: Pearce Daniel J. , Loughnane Ger M. , Chong Trevor T.-J. , Demeyere Nele , Mattingley Jason B. , Moore Margaret J. , New Peter W. , O’Connell Redmond G. , O’Neill Megan H. , Rangelov Dragan , Stolwyk Renerus J. , Webb Sam S. , Zhou Shou-Han , Brosnan Méadhbh B. , Bellgrove Mark A. 
Published: December 2023

AbstractSlowed responding to sensory inputs presented in contralesional space is pervasive following unilateral cerebral stroke, but the causal neurophysiological pathway by which this occurs remains unclear. To this end, here we leverage a perceptual decision-making framework to disambiguate information processing stages between sensation and action in 30 unilateral stroke patients (18 right hemisphere, 12 left hemisphere) and 27 neurologically healthy adults. By recording neural activity using electroencephalography (EEG) during task performance, we show that the relationship between strokes in either hemisphere and slowed contralesional response times is sequentially mediated by weaker target selection signals in the contralateral hemisphere (the N2c ERP), and subsequently delayed evidence accumulation signals (the centroparietal positivity). Notably, asymmetries in CPP and response times across hemispheres are associated with everyday functioning. Together, these data suggest a plausible neurophysiological pathway by which post-stroke contralesional slowing arises and highlight the utility of neurophysiological assessments for tracking clinically relevant behaviour.
Distributed representations for cognitive control in frontal medial cortex
Authors: Colin Thomas R. , Ikink Iris , Holroyd Clay B. 
Published: December 2023

AbstractIn natural and artificial neural networks, modularity and distributed structure afford complementary but competing benefits. The former allows for hierarchical representations that can flexibly recombine modules to address novel problems, whereas the latter affords better generalization. Here we investigate these competing demands in the context of sequential behavior. First, we explore this by comparing the properties of several recurrent neural network models. We find that explicit hierarchical structure fails to provide an advantage for generalization above a “flat” model that does not incorporate hierarchical structure. However, hierarchy appears to facilitate cognitive control processes that support non-routine behaviors and behaviors that are carried out under computational stress. Second, we compare these models against functional magnetic resonance imaging (fMRI) data using representational similarity analysis. We find that a model that incorporates so-called wiring costs in the cost function, which produces a hierarchically-organized gradient of representational structure across the hidden layer of the neural network, best accounts for fMRI data collected from human participants in a previous study (Holroyd et al., 2018). The results reveal that the anterior cingulate cortex (ACC) encodes distributed representations of sequential task context along a rostro-caudal gradient of abstraction: rostral ACC encodes relatively abstract and temporally extended patterns of activity compared to those encoded by caudal ACC. These results provide insight into the role of ACC in motivation and cognitive control.
A collection of Predicted No-Effect Concentrations of human pharmaceuticals and their metabolites
Authors: Giunchi Valentina , Poluzzi Elisabetta 
Published: December 2023

AbstractThe environmental impact of pharmaceuticals is a growing concern, necessitating methodologies for risk assessment. Current evaluation methods rely on comparing pharmaceutical concentrations in exposed environments with relevant animal or plant tolerance thresholds, often represented by Predicted No-Effect Concentration (PNEC) values. However, challenges arise from the limited accessibility and standardization of PNEC data. This study addresses these challenges by consolidating PNEC values from diverse sources into a unified and accessible tool. Investigated data sources were the NORMAN Ecotoxicology Database, the Swedish National Formulary of Drugs (FASS) website, the EU Watch List working documents, the European Public Assessment Reports (EPAR), the US EPA ECOTOX database, the UBA ETOX database, the WikiPharma database, the AstraZeneca documents, the European Chemical Agency registration dossiers, and the AMR Industry Alliance database. We retrieved 93,287 PNEC values associated with 92,850 substances, primarily medicines or their metabolites. Notably, 352 substances had more than one PNEC value, with the highest discrepancies often attributed to in-silico predicted values. The resulting database, available in the related OSF repository as a spreadsheet file, includes source information and processing scripts and is freely available for risk assessment analyses. While acknowledging limitations, future efforts should prioritize integrating additional data sources, addressing misspellings, and enhancing information on PNEC derivation. Collaboration in PNEC data collection is crucial for advancing collective knowledge in pharmaceutical risk assessment.
EasyCircR: Detection and reconstruction of circular RNAs post-transcriptional regulatory interaction networks
Authors: Aparo Antonino , Avesani Simone , Parmigiani Luca , Napoli Sara , Bertoni Francesco , Bonnici Vincenzo , Cascione Luciano , Giugno Rosalba 
Published: December 2023

AbstractCircular RNAs (circRNAs) are regulatory RNAs that play a crucial role in various biological activities and have been identified as potential biomarkers for the development of neurological disorders and cancer. CircRNAs have emerged as significant regulators of gene expression through different mechanisms, including regulation of transcription and splicing, modulation of translation, and post-translational modification. Additionally, some circRNAs function as microRNA (miRNA) sponges in the cytoplasm, enhancing the expression of target genes by suppressing miRNA activity. Although existing pipelines reconstruct circRNAs, identify miRNAs sponged by them, retrieve cascade-regulated mRNAs, and represent the regulatory interactions as complex circRNA-miRNA-mRNA networks, none of the state-of-the-art approaches can discriminate the biological level at which the mRNAs involved in the interactions are regulated.EasyCircR is a novel R package that combines circRNA detection and reconstruction with post-transcriptional gene expression analysis (exon-intron split analysis) and miRNA response element prediction. The package enables estimation and visualization of circRNA-miRNA-mRNA interactions through an intuitive Shiny application, taking advantage of the post-transcriptional regulatory nature of circRNAs and excluding unrealistic regulatory outcomes. EasyCircR source code, Docker container and user guide are available at:https://github.com/InfOmics/EasyCircR
PvdL Orchestrates the Assembly of the Nonribosomal Peptide Synthetases Involved in Pyoverdine Biosynthesis inPseudomonas aeruginosa
Authors: Manko Hanna , Steffan Tania , Gasser Véronique , Mély Yves , Schalk Isabelle J , Godet Julien 
Published: December 2023

The pyoverdine siderophore is produced byPseudomonas aeruginosato access iron. Its synthesis involves the complex co-ordination of four nonribosomal peptide synthetases (NRPSs), responsible for assembling the pyoverdine peptide backbone. The precise cellular organization of these NRPSs and their mechanisms of interaction remain unclear.Here, we used a combination of several single-molecule microscopy techniques to to elucidate the spatial arrangement of NRPSs within pyoverdine-producing cells. Our findings revealed that PvdL differs from the three other NRPS in term of localization and mobility patterns. PvdL is predominantly located at the inner membrane, while the other also explore the cytoplasmic compartment. Leveraging the power of multicolor single-molecule localization, we further reveal co-localization between PvdL and the other NRPSs, suggesting a pivotal role for PvdL in orchestrating the intricate biosynthetic pathway.Our observations strongly indicates that PvdL serves as a central orchestrator in the assembly of NRPSs involved in pyoverdine biosynthesis, assuming a critical regulatory function.
cancercelllines.org - a Novel Resource for Genomic Variants in Cancer Cell Lines
Authors: Paloots Rahel , Baudis Michael 
Published: December 2023

AbstractCancer cell lines are an important component in biological and medical research, enabling studies of cellular mechanisms as well as the development and testing of pharmaceuticals. Genomic alterations in cancer cell lines are widely studied as models for oncogenetic events and are represented in a wide range of primary resources. We have created a comprehensive, curated knowledge resource -cancercelllines.org- with the aim to enable easy access to genomic profiling data in cancer cell lines, curated from a variety of resources and integrating both copy number and single nucleotide variants (SNVs) data. We have gathered over 5,600 copy number profiles as well as SNV annotations for 16,000 cell lines and provide this data with mappings to the GRCh38 reference genome. Both genomic variations and associated curated metadata can be queried through the GA4GH Beacon v2 API and a graphical user interface with extensive data retrieval enabled using GA4GH data schemas under a permissive licensing scheme.