bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional and causal neural mechanisms of human voice perception in noisy situations
Authors: Ceravolo Leonardo , Jaussi Elisa Scariati , Frühholz Sascha , Van De Ville Dimitri , Grandjean Didier 
Published: October 2024

AbstractHuman communication entails an efficient way of simultaneously processing voice and reducing the impact of environmental noise. By manipulating background noise, we aimed at clarifying the neural mechanisms allowing voice comprehension in noisy situations. Our results point to spatial and temporal coexistence of lateral and medial temporal cortex networks when voice is easily detected in highly noisy conditions, revealing the necessary neural underpinnings of human communication in realistic situations.
Connectome-based Predictive Models of General and Specific Executive Functions
Authors: Qu Shijie , Qu Yueyue Lydia , Yoo Kwangsun , Chun Marvin M. 
Published: October 2024

AbstractExecutive functions, the set of cognitive control processes that facilitate adaptive thoughts and actions, are composed primarily of three distinct yet interrelated cognitive components: Inhibition, Shifting, and Updating. While prior research has examined the nature of different components as well as their inter-relationships, fewer studies examined whole-brain connectivity to predict individual differences for the three cognitive components and associated tasks. Here, using the Connectome-based Predictive Modelling (CPM) approach and open-access data from the Human Connectome Project, we built brain network models to successfully predict individual performance differences on the Flanker task, the Dimensional Change Card Sort task, and the 2-back task, each putatively corresponding to Inhibition, Shifting, and Updating. We focused on grayordinate fMRI data collected during the 2-back tasks after confirming superior predictive performance over resting-state and volumetric data. High cross-task prediction accuracy as well as joint recruitment of canonical networks, such as the frontoparietal and default-mode networks, suggest the existence of a common executive function factor. To investigate the relationships among the three executive function components, we developed new measures to disentangle their shared and unique aspects. Our analysis confirmed that a shared executive function component can be predicted from functional connectivity patterns densely located around the frontoparietal, default-mode and dorsal attention networks. The Updating-specific component showed significant cross-prediction with the general executive function factor, suggesting a relatively stronger role than the other components. In contrast, the Shifting-specific and Inhibition-specific components exhibited lower cross-prediction performance, indicating more distinct and specialized roles. Given the limitation that individual behavioral measures do not purely reflect the intended cognitive constructs, our study demonstrates a novel approach to infer common and specific components of executive function.
Deletion of Zyxin Reduces Endothelial Inflammation and Mitigates Atherosclerosis
Authors: Huang Haozhong , Wang Yingzi , Gao Zhenyu , Feng Yi , Yang Tan , Liu Zihao , Li Lei , Weng Huimin , Tang Yuquan , Liu Linlu , Li Yuhao , Li Zhixin , Xie Yucheng , Liao Bin , Yu Fengxu , Nie Yongmei 
Published: October 2024

ABSTRACTBACKGROUNDOscillatory shear stress (OSS)-induced endothelial inflammation plays a critical role in the pathogenesis of atherosclerosis. However, the involvement of endothelial zyxin, a mechanosensor, in OSS-associated atherosclerosis and its underlying mechanisms remains unclear.METHODSTo investigate the role of zyxin in vivo, ZyxiniECKOApoE−/−mice were utilized in atherosclerosis model induced by carotid artery ligation; in vitro, endothelial cells were subjected to disturbed flow in Ibidi systerm.RESULTSZyxin was significantly upregulated in the OSS regions of both human and mouse arteries. The specific deletion of zyxin in endothelial cells (ECs) in ApoE−/−(ZyxiniECKOApoE−/−) mice reversed the ECs activation and atherosclerosis induced by OSS. In vitro studies indicated that the absence of zyxin reduced the induction of adhesion molecules and pro-inflammatory cytokines stimulated by OSS. Mechanistic investigations demonstrated that 14-3-3β facilitated yes-associated protein (YAP) phosphorylation at Serine 127, which played a critical role in retaining YAP within the cytoplasm. Under OSS stimulation, zyxin inhibited the phosphorylation of YAP at Serine 127 through its interaction with 14-3-3β, rather than direct regulation of YAP. This inhibition enhanced YAP’s nuclear translocation and promoted endothelial inflammation. Furthermore, it was shown that rosuvastatin inhibited zyxin expression in human umbilical vein endothelial cells and the vascular endothelium of ApoE−/−mice. This inhibition led to decreased levels of inflammatory markers and adhesion molecules associated with atherosclerotic lesions observed in the partially ligated left common carotid arteries of ApoE−/−mice.CONCLUSIONSThis study further confirms that zyxin is a mechanoreceptor in endothelial cells and elucidates the indispensable role of the zyxin-14-3-3β-YAP axis in endothelial inflammation and atherogenesis. This indicates that Zyxin plays a crucial role in protecting against atherosclerosis.
Transcriptional Signatures of the Right Ventricle in End-Stage Heart Failure
Authors: Garry Jonah D. , Davogustto Giovanni E. , Agrawal Vineet , Ye Fei , Tomasek Kelsey , Su Yan Ru , Absi Tarek , West James D. , Hemnes Anna , Brittain Evan L. 
Published: October 2024

SummaryThe molecular mechanisms of right ventricular (RV) adaptation to stress and failure in end stage heart failure (HF) are largely unknown. In this study, we performed transcriptomic analysis on paired RV and left ventricular (LV) myocardial samples from 33 subjects with AHA stage D HF referred for transplantation, and 8 controls who provided donor hearts not ultimately used for transplantation. We categorized patients by RV function - defining failure by Pulmonary Artery Pulsatility Index <1.85 - into control (n=8), compensated (n=25), and failing groupings (n=8). Our analysis found dysregulation of extracellular matrix remodeling, fatty acid metabolism, mitochondrial function, and inflammation in the stressed RV (comparing compensated and failing RVs to controls), implicating similar molecular mechanisms to those identified from studies of pre-capillary pulmonary hypertension (PH) associated RV dysfunction. The compensated and failing RVs were differentiated by protein production/processing and inflammation. PPAR signaling and fatty acid metabolism were consistently enriched in the RV compared to the LV. We also examined 16 previously proposed transcriptional biomarkers of RV failure, finding that none effectively differentiated between RV compensation and failure, and only 4 were RV-specific (changing in RV-failure but not LV-failure). Our findings suggest that the molecular mechanisms of pre-capillary PH and HF-associated RV dysfunction exhibit significant overlap. Furthermore, fatty acid metabolism and related signaling may be constitutively different between the RV and LV in both normal function and failure.
Age-Dependent Maturation and Rejuvenation of the Neural 3D Chromatin Interactome in Enriched Environments
Authors: Gancedo-Verdejo Javier , Urdinguio Rocío G. , Tejedor Juan Ramón , Pérez Raúl F. , Peñarroya Alfonso , Santamarina-Ojeda Pablo , Roberti Annalisa , Kefauver Jennifer M. , Álvarez-Díaz Carlota , Rodríguez-Santamaría Mar , Trejo José Luis , Tomás-Daza Laureano , Rovirosa Llorenç , Javierre Biola M. , Fernández Agustín F. , Fraga Mario F. 
Published: October 2024

ABSTRACTAging is a multifactorial biological process resulting in physiological and cellular decline. However, our understanding of age-related changes in 3D genome organization and the effect of external interventions on this process, remains limited. Here we describe alterations in the landscape of the 3D chromatin interactome upon aging, utilizing the low input Promoter Capture Hi-C (liCHi-C) technique with hippocampal neurons. We integrated liCHi-C data with RNA-seq data to identify functional implications. Furthermore, we assessed the effect of exposure to environmental enrichment (EE). Remarkably, our results demonstrated an age- dependent modulation of promoter interactions and expression with EE, with aging-like changes induced in young mice upon EE, likely associated with early brain maturation; while age-related alterations were reverted in old mice, leading to a partial rejuvenation of aged mouse hippocampi. These findings revealed a dynamic behaviour of the neuronal 3D chromatin structure over time, which can be modulated by external interventions.
Novel bacteriophages targeting wheat phyllosphere bacteria carry DNA modifications and single-strand breaks
Authors: Dougherty Peter Erdmann , Pedersen Maja Schmidt , Forero-Junco Laura Milena , Carstens Alexander Byth , Raaijmakers Jos M. , Riber Leise , Hansen Lars Hestbjerg 
Published: October 2024

AbstractThe phyllosphere microbiome can positively or negatively impact plant health and growth, but we currently lack the tools to control microbiome composition. Contributing to a growing collection of bacteriophages (phages) targeting bacteria living in the wheat phyllosphere, we here isolate and sequence eight novel phages targeting common phyllosphereErwiniaandPseudomonasstrains, including two jumbo phages. We characterize genomic, phylogenetic, and morphological traits from these phages and argue for establishing four novel viral genera. We also search the genomes for anti-defense systems and investigate DNA modifications using Nanopore sequencing. In Pseudomonas phage Rembedalsseter we find evidence of 13 motif-associated single-stranded DNA breaks. A bioinformatics search revealed that 60 relatedPseudomonasphages are enriched in the same motif, suggesting these single-stranded nicks may be widely distributed in this family of phages. Finally, we also search the Sequence Read Archive for similar phages in public metagenomes. We find close hits to theErwiniajumbo-phage Kaldavass in a wide variety of plant, food, and wastewater metagenomes including a near-perfect hit from a Spanish spinach sample, illustrating how interconnected geographically distant phages can be.
The transfer of antibiotic resistance genes between evolutionary distant bacteria
Authors: Parras-Moltó Marcos , Lund David , Ebmeyer Stefan , Larsson DG Joakim , Johnning Anna , Kristiansson Erik 
Published: October 2024

AbstractInfections from antibiotic-resistant bacteria threaten human health globally. Resistance is often caused by mobile antibiotic resistance genes (ARGs) shared horizontally between bacterial genomes. Many ARGs originate from environmental and commensal bacteria and are transferred between divergent bacterial hosts before they reach pathogens. This process remains, however, poorly understood, which complicates the development of countermeasures that reduce the spread of ARGs. In this study, we aimed to systematically analyze the ARGs transferred between the most evolutionary distant bacteria, here defined based on their phylum. We implemented an algorithm that identified inter-phyla transfers (IPTs) by combining ARG-specific phylogenetic trees with the taxonomy of the bacterial hosts. From the analysis of almost 1 million resistance genes identified in >400,000 bacterial genomes, we identified 661 IPTs, which included transfers between all major bacterial phyla. The frequency of IPTs varies substantially between ARG classes and was highest for the aminoglycoside resistance gene AAC(3) while the levels for beta-lactamases were, generally, lower. ARGs involved in IPTs also differed between phyla where, for example, tetracycline resistance genes were commonly transferred between Firmicutes and Proteobacteria, but rarely between Actinobacteria and Proteobacteria. The results, furthermore, show that conjugative systems are seldom shared between bacterial phyla, suggesting that other mechanisms drive the dissemination of ARGs between divergent hosts. We also show that bacterial genomes involved in IPTs of ARGs are either over- or under-represented in specific environments. These IPTs were also found to be more recent compared to transfers associated with bacteria isolated from water, soil, and sediment. While macrolide and tetracycline resistance genes involved in ITPs almost always were +95% identical between phyla, corresponding β-lactamases showed a median identity of < 60%. We conclude that inter-phyla transfer is recurrent and our results offer new insights into how resistance genes are disseminated between evolutionary distant bacteria.
NIPBL and STAG1 enable loop extrusion by providing differential DNA-cohesin affinity
Authors: van Wee Raman , Asor Roi , Li Yiwen , Drechsel David , Popova Maria , Litos Gabriele , Davidson Iain , Peters Jan-Michael , Kukura Philipp 
Published: October 2024

AbstractDNA loop extrusion by cohesin has emerged as a critical pathway for chromosome organization. In vitro single-molecule experiments indicate that loop extrusion requires the assembly of an heteropentameric complex consisting of the SMC1/SMC3 heterodimer, STAG1, NIPBL and the kleisin SCC1. The multimeric nature of this complex and regulatoin of its dynamic DNA interactions that are modulated by ATP binding-hydrolysis cycles make it challenging to reveal the molecular mechanism of loop extrusion. Here, we use mass photometry to quantify the key interactions responsible for cohesin assembly, DNA binding, and their modulation by ATP binding and hydrolysis. We find that STAG1 binds tightly to the trimeric complex formed by the SMC1/SMC3 heterodimer and SCC1, creating a DNA binding site whose strength is modulated by the presence of ATP. NIPBL binds strongly to both DNA and the STAG1-tetramer, enabling assembly of the holoenzyme in the absence of DNA or ATP. Taken together, these results suggest that NIPBL acts as a DNA anchor, while a dynamic STAG1-Trimer binding site drives DNA loop formation.
Rejuvenating aged osteoprogenitors for bone repair
Authors: Reeves Joshua , Tournier Pierre , Becquart Pierre , Carton Robert , Tang Yin , Vigilante Alessandra , Fang Dong , Habib Shukry J 
Published: October 2024

AbstractAging is marked by a decline in tissue regeneration, posing significant challenges to an increasingly older population. Here, we investigate age-related impairments in calvarial bone healing and introduce a novel two-part rejuvenation strategy to restore youthful repair. We demonstrate that aging negatively impacts the calvarial bone structure and its osteogenic tissues, diminishing osteoprogenitor number and function and severely impairing bone formation. Notably, increasing osteogenic cell numbers locally fails to rescue repair in aged mice, identifying the presence of intrinsic cellular deficits. Our strategy combines Wnt-mediated osteoprogenitor expansion with intermittent fasting, which leads to a striking restoration of youthful levels of bone healing. We find that intermittent fasting improves osteoprogenitor function, benefits that can be recapitulated by modulating NAD+dependent pathways or the gut microbiota, underscoring the multifaceted nature of this intervention. Mechanistically, we identify mitochondrial dysfunction as a key component in age-related decline in osteoprogenitor function and show that both cyclical nutrient deprivation and Nicotinamide mononucleotide rejuvenate mitochondrial health, enhancing osteogenesis. These findings offer a promising therapeutic avenue for restoring youthful bone repair in aged individuals, with potential implications for rejuvenating other tissues.
A rational approach for the targeted discovery and characterisation of microbiome-derived therapeutics
Authors: Krause Lutz , Boyd Joel , Vivian Charlotte , Krueger Annika , Jimenez Loayza Jeimy , Ljungberg Johanna K. , Zhou Joyce , Rabellino Andrea , Nyeverecz Bozica , Nissen Michael , Tousignant Kaylyn , Bongers Mareike , Cooper Martha M. , Parks Donovan H. , Alsheikh Areej , Vera-Wolf Patricia , Sullivan Mitchell , Newell Rhys , Masterman Kelly-Anne , Evans Peter , Fang Liang , MacDonald Samantha , Chuvochina Maria , Bessette Darrell , Zimmermann Kate , Pribyl Alena , Chipperfield Hiram , Caban Shandelle , McCarthy Huw , Soh Joanne , Reid Luke , Frazer Ian H. , Angel Nicola , Kenna Tony , Wood David L.A. , Wills Blake , Begun Jakob , Keely Simon , Munro Trent , Tyson Gene W. , Hugenholtz Philip , Cuív Páraic Ó 
Published: October 2024

AbstractThe human gut microbiome is intrinsically involved in health and disease, representing a wealth of untapped therapeutic potential. Here, we demonstrate the utility and potential of a metagenome guided, large cohort-based approach for the rational selection of live biotherapeutics from the human gut. We applied this approach to Inflammatory Bowel Disease (IBD), identifying several lead candidates that were significantly depleted in individuals with IBD compared to healthy controls. Their therapeutic potential was assessed in preclinical models of IBD where they improved markers of disease pathology by reducing inflammation and promoting mucosal healing and wound repair. All leads had excellent safety profilesin silicoandin vitro, and several additionally presented favourable manufacturing properties, supporting their progression into clinical trials. We believe that this rational approach will be generalisable to any disease state with underlying microbiome aetiology and will expedite the development of novel microbiome-derived therapeutics to improve human health.
An end-to-end model of active electrosensation
Authors: Turcu Denis , Zadina Abigail , Abbott L.F. , Sawtell Nathaniel B. 
Published: October 2024

1AbstractWeakly electric fish localize and identify objects by sensing distortions in a self-generated electric field. Fish can determine the resistance and capacitance of an object, for example, even though the field distortions being sensed are small and highly-dependent on object distance and size. Here we construct a model of the responses of the fish’s electroreceptors on the basis of experimental data, and we develop a model of the electric fields generated by the fish and the distortions due to objects of different resistances and capacitances. This provides us with an accurate and efficient method for generating large artificial data sets simulating fish interacting with a wide variety of objects. Using these sets, we train an artificial neural network (ANN), representing brain areas downstream of electroreceptors, to extract the 3D location, size, and electrical properties of objects. The model performs best if the ANN operates in two stages: first estimating object distance and size and then using this information to extract electrical properties. This suggests a specific form of modularity in the electrosensory system that can be tested experimentally and highlights the potential of end-to-end modeling for studies of sensory processing.
Sociodemographic, clinical, and genetic factors associated with self-reported antidepressant response outcomes in the UK Biobank
Authors: Kamp Michelle , Lo Chris Wai Hang , Kokkinidis Grigorios , Chauhan Mimansa , Gillett Alexandra C. ,   AMBER Research Team, McIntosh Andrew M. , Pain Oliver , Lewis Cathryn M. 
Published: October 2024

ABSTRACTBackgroundIn major depressive disorder (MDD), only ∼35% achieve remission after first-line antidepressant therapy. Using UK Biobank data, we identify sociodemographic, clinical, and genetic predictors of antidepressant response through self-reported outcomes, aiming to inform personalized treatment strategies.MethodsIn UK Biobank Mental Health Questionnaire 2, participants with MDD reported whether specific antidepressants helped them. We tested whether retrospective lifetime response to four selective serotonin reuptake inhibitors (SSRIs) (N=19,516)-citalopram (N=8,335), fluoxetine (N=8,476), paroxetine (N=2,297) and sertraline (N=5,883)-was associated with sociodemographic (e.g., age, gender) and clinical factors (e.g., episode duration). Genetic analyses evaluated the association between CYP2C19 variation and self-reported response, while polygenic score (PGS) analysis assessed whether genetic predisposition to psychiatric disorders and antidepressant response predicted self-reported SSRI outcomes.Results71%-77% of participants reported positive responses to an SSRI. Non-response was significantly associated with self-medication (OR=1.56, p=2.08×10−19), younger age (OR=0.87, p=2.49×10−11), male gender (OR=1.26, p=3.18×10−08), and lower income (OR=1.34, p=6.17×10−07). A worst episode lasting over two years (OR=1.97, p=1.25×10−16) and no mood improvement from positive events (OR=1.33, p=1.35×10−06) were also associated with non-response. CYP2C19 poor metabolizers had higher non-response rates (OR=1.31, p=1.77×10−02). Additionally, higher PGS for depression (OR=1.08, p=3.37×10−05), ADHD (OR=1.06, p=1.06×10−03), and schizophrenia (OR =1.06, p=1.53×10−03) predicted negative SSRI outcomes.ConclusionSelf-reported antidepressant response in the UK Biobank is influenced by sociodemographic, clinical, and genetic factors, mirroring clinical response measures. While positive outcomes are more frequent than remission reported in clinical trials, these self-reports replicate known treatment associations, suggesting they capture meaningful aspects of antidepressant effectiveness from the patient’s perspective.
Analysis of crystallographic phase retrieval using iterative projection algorithms
Authors: Barnett Michael J. , Millane Rick P. , Kingston Richard L. 
Published: October 2024

For protein crystals in which more than two thirds of the volume is occupied by solvent, the featureless nature of the solvent region often generates a constraint that is powerful enough to allow direct phasing of X-ray diffraction data. Practical implementation relies on the use of iterative projection algorithms with good global convergence properties to solve the difficult nonconvex phase-retrieval problem. In this paper, some aspects of phase retrieval using iterative projection algorithms are systematically explored, where the diffraction data and density-value distributions in the protein and solvent regions provide the sole constraints. The analysis is based on the addition of random error to the phases of previously determined protein crystal structures, followed by evaluation of the ability to recover the correct phase set as the distance from the solution increases. The properties of the difference-map (DM), relaxed–reflect–reflect (RRR) and relaxed averaged alternating reflectors (RAAR) algorithms are compared. All of these algorithms prove to be effective for crystallographic phase retrieval, and the useful ranges of the adjustable parameter which controls their behavior are established. When these algorithms converge to the solution, the algorithm trajectory becomes stationary; however, the density function continues to fluctuate significantly around its mean position. It is shown that averaging over the algorithm trajectory in the stationary region, following convergence, improves the density estimate, with this procedure outperforming previous approaches for phase or density refinement.