bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guided assembly of multispecies positive biofilms targeting undesirable bacteria
Authors: Guéneau Virgile , Guillier Laurent , Berdous Cécile , Noirot-Gros Marie-Françoise , Jiménez Guillermo , Plateau-Gonthier Julia , Serror Pascale , Castex Mathieu , Briandet Romain 
Published: October 2024

AbstractThe use of synthetic microbial communities (SynComs) engineered to form positive biofilms that prevent the settlement of harmful bacteria is emerging as a promising strategy in biotechnology, particularly in reducing reliance on chemical antimicrobials. Despite this potential, the rationale for selecting specific strains in SynComs and the mechanisms underlying their antagonistic effects remains insufficiently understood. In this study, we present a bottom-up approach integrating live-cell imaging with high-throughput analysis of multi-strain biofilms across diverse scenarios. Through this method, we identified beneficial strains based on their superior ability to exclude undesirable bacteria and form mixed biofilms. Notably, our findings revealed that competitive strains against undesirable bacteria could also exclude other beneficial strains, emphasising the need for compatibility control in SynComs design. SynComs composed ofB. velezensisandPediococcusspp. demonstrated enhanced pathogen exclusion compared to single strains. Temporal analysis of biofilm interactions, supported by mathematical models, showed that pathogen exclusion was primarily driven by nutritional competition (Jameson effect) with additional specific interference mechanisms (prey-predator Lotka-Volterra model). Furthermore, pre-establishing SynComs to surfaces significantly increased pathogen inhibition, indicating a distinct biofilm-associated exclusion effect. These insights offer a framework for rational SynCom design and deepen our understanding of the mechanisms underpinning positive biofilm applications.Abstract Figure
Coarse-Grained Dynamic Simulation of Cytoskeletal Microtubule Twist
Authors: Zhu Renjie , Zhang Yuwei , Xia Fei 
Published: October 2024

AbstractMicrotubule, a key component of the cytoskeleton, plays a crucial role in cell mitosis. Modeling and dynamic simulation of microtubules at the micrometer scale remain a significant challenge. In this study, we developed the helix-based ultra-coarse-grained (HB-UCG) model for the dynamic simulation of microtubules, based on the helical characteristics obtained from electron microscopy density data. We constructed microtubules up to 35 μm in length and investigated the relationship between persistence length and contour length. By comparing our results with experimental data, we validated the potential of the HB-UCG model in simulating microtubule functions. We also simulated the twist process of microtubules driven by motor proteins, successfully demonstrating the model’s effectiveness in simulating biological processes. This study can provide the foundation for theoretical simulations of microtubule functions during mitosis.
Identification of Shared and Unique Key Biomarkers of Alcohol Liver Cirrhosis and Non-Alcoholic Steatohepatitis Through Machine Learning Network-Based Algorithms
Authors: Hajihosseini Morteza , Talarico Fernanda , Zhao Caroline , Campbell Scott , Udenze Daniel , Hajizadeh Bastani Nastaran , Ahmed Marawan , Ghasemi Erfan , Tonoyan Lusine , Guirguis Micheal , Mayo Patrick , Campanella Corinne 
Published: October 2024

AbstractIntroductionLiver fibrosis can progress to cirrhosis, liver failure, or hepatocellular carcinoma, which often requires transplantation and burdens healthcare systems around the world. Advances in single-cell RNA sequencing and machine learning have enhanced the understanding of immune responses in many liver diseases particularly alcohol liver cirrhosis (ALC) and non-alcoholic steatohepatitis (NASH). This study aims to identify key biomarkers involved in these conditions and assess their potential as non-invasive diagnostic tools.MethodsTwo gene expression profiles GSE136103 and GSE115469 were used to conduct differential gene expression (DEG) analysis. Using the results from DEG analysis, we then applied two machine learning network-based algorithms, master regulator analysis (MRA) and weighted key driver analysis (wKDA), to identify potential biomarker genes for NASH and ALC.ResultsA total of 1,435 and 5,074 DEGs were identified for ALC and NASH compared to healthy controls, including 1,077 shared DEGs between the two diseases. The MRA showed HLA-DPA1, HLA-DRB1, IFI44L, ISG15, and CD74 as the potential master regulators of ALC and HLA-DPB1, HLA-DQB1, HLA-DRB5, PFN1, and TMSB4X as the potential master regulators of NASH. In addition, wKDA analysis indicated CD300A, FCGR2A, RGS1, HLA-DMB, and C1QA as the key drivers of ALC and INPP5D, NCKAP1L, RAC2, PTPRC, and TYROBP as key drivers of NASH.ConclusionThis study presented a comprehensive framework for analyzing single-cell RNA-seq data, demonstrating the potential of combining advanced network-based machine-learning techniques with conventional DEG analysis to uncover actionable prognostic markers for ALC and NASH with potential use as target biomarkers in drug development.
The association between alcohol consumption and colorectal carcinogenesis is partially mediated by the gut microbiome
Authors: Kværner Ane Sørlie , Birkeland Einar , Avershina Ekaterina , Botteri Edoardo , Bucher-Johannessen Cecilie , Dines Knudsen Markus , Hjartåker Anette , Page Christian M. , Hov Johannes R. , Song Mingyang , Ranheim Randel Kristin , Hoff Geir , Rounge Trine B. , Berstad Paula 
Published: October 2024

AbstractBackgroundAlcohol consumption is one of the major risk factors of colorectal cancer (CRC). However, the mechanisms underlying this relationship are not fully understood, particularly the potential role of gut microbes.ObjectiveTo study associations of alcohol intake with the gut microbiome and colorectal lesions among CRC screening participants. Of particular interest was the potential role of gut microbes in mediating the association between alcohol intake and colorectal lesions.MethodsParticipants included fecal immunochemical test-positive women and men enrolled in the CRCbiome study, aged 55-77 years at inclusion. Intake of alcohol was assessed using a validated, semi-quantitative food frequency questionnaire. Integrating with shotgun metagenome based taxonomic and functional profiles, we studied associations with screen-detected colorectal lesions. The potential role of alcohol-associated gut microbes in mediating the association between alcohol intake and colorectal lesions was examined using causal mediation analysis.ResultsOf 1,468 participants with dietary data, 414 were diagnosed with advanced lesions (advanced adenoma, advanced serrated lesions or CRC). Alcohol intake was positively associated with advanced lesions in a dose-dependent manner (ptrend= 0.008), with odds ratio of 1.09 (95% confidence interval, 1.00, 1.19) per 10 g/day increase. Compared to non-consumers, those consuming alcohol were characterized by a distinct microbial profile, manifested as modest, but consistent, shifts in α- and β-diversity, and differentially abundant bacteria (Log2 fold change (Log2FC) >0:B. finegoldiiandL. asaccharolyticus; Log2FC <0:S. mutans, B. dentinum,C. symbiosumandE. boltae). A causal mediation analysis showed that 12% of the association between alcohol intake and advanced lesions was mediated by alcohol-associated gut bacteria.ConclusionsAlcohol consumption was associated with a distinct microbial profile, which partly explained the association between alcohol intake and advanced colorectal lesions.Trial RegistrationThe BCSN is registered at clinicaltrials.gov (National clinical trial (NCT) no. 01538550).
Synaptic Vesicle Cycling Disorders: Cross-Sectional Phenotyping Study of a Gene Functional Network
Authors: Eck Josefine , Smith Tess , Kolesnik Anna , Al-jawahiri Reem , Baker Kate 
Published: October 2024

AbstractBackground and objectivesGenes associated with neurodevelopmental disorders (NDDs) can be grouped into networks according to their molecular and cellular functions. However, the links between gene functional networks and neurodevelopmental phenotypes are not well understood. Synaptic vesicle cycling (SVC) is one gene functional network in which rare, high penetrance variants are known to cause NDDs. SVC genes regulate neurotransmitter release and recycling, thus essential for synaptic transmission and plasticity. We investigated whether SVC disorders are associated with a different neurodevelopmental spectrum from other monogenic NDDs, and whether phenotypic variation within SVC disorders can be predicted.MethodsWe included 199 children, young people, and adults with a genetic NDD diagnosis (n=109 with SVC disorders, n=90 with non-SVC disorders). Families were recruited via clinical genetics and neurology services, and support organisations. Parents or carers completed quantitative questionnaire measures previously validated in populations with NDDs. We implemented a PCA-derived K-prototype clustering analysis to assess associations between gene functional network and neurodevelopmental variation.ResultsCohort-wide K-prototype clustering identified four phenotypic similarity clusters, each having membership from both SVC and non-SVC participants. The clusters differed in phenotype enrichments as follows: 1) behavioural difficulties and sleep problems, 2) less severe neurodevelopmental problems overall, 3) epilepsies, sleep problems, severe adaptive impairments and visual awareness difficulties, 4) sensory-motor problems. The SVC group was over-represented within cluster 3. Cluster memberships within the SVC group cannot be predicted by age, sex, variant type, gene or SVC sub-process.DiscussionThe K-prototype method can be used to describe multi-dimensional phenotypic structure within the heterogeneous genetic NDD population. We found that SVC functional network membership contributes to the likelihood of phenotype cluster memberships, but does not specify a distinct or homogeneous neurodevelopmental profile. Investigating convergent disease mechanisms arising from SVC dysfunction is central to understanding the observed neurodevelopmental spectrum, and may ultimately guide evidence-based prognostication and mechanism-informed management.
The complete blood count and cardiovascular disease: analyses across six cohorts of 23,370 adults
Authors: Goonewardena Sascha N. , Murthy Venkatesh L. 
Published: October 2024

AbstractBackgroundThe complete blood count (CBC) is one of the most performed laboratory studies. However, the CBC and its components are not commonly used to understand and quantify cardiovascular disease (CVD) risk.ObjectiveWe sought to define the relationships between the CBC, traditional CVD risk factors, and common CVD biomarkers and their joint association with all-cause mortality and CVD.MethodsWe examined the relationships between the CBC, traditional CVD risk factors, and mortality in NHANES (n=7843). We validated and extended these findings to more refined CVD endpoints in five additional cohorts (n=15,527).ResultsWe first examined the variance accounted for by common laboratory studies (lipid panel, HbA1c, hs-CRP, and basic metabolic panel) by traditional risk factors in NHANES. Except for hemoglobin (Hb) components, we found that traditional risk factors accounted for less than 20% of the variance in the CBC, suggesting that the CBC provides unique information beyond traditional risk factors and CVD biomarkers. Additionally, the CBC was strongly associated with all-cause mortality (p<0.0001), even more than traditional CVD biomarkers (lipid panel, HbA1c, and CRP). We validated and extended these findings across five additional cohorts with a mean follow-up of 16 years and more refined CVD endpoints. In the fully adjusted analyses, several CBC components, including the white blood cell (WBC) count, neutrophil (PMN) count, Hb level, and an integrated immune cell score, were associated with individual CVD endpoints (incident stroke, MI, or revascularization) and a composite CV endpoint (MACE3) with standardized hazard ratios of 1.13 (p=0.002), 1.15 (p=0.0006), 0.82 (p<0.0001), and 2.16 (p<0.0001) respectively.ConclusionThis study represents the first systematic examination of the relationship between the CBC, all-cause mortality, and CVD in a diverse cohort of 23,370 adults. These findings underscore the added value of the CBC over traditional risk factors and common CVD biomarkers for CVD risk assessment. Future studies should explore the integration of CBC parameters into predictive models to enhance our understanding, early identification, and prevention strategies for CVD.
Thermal Proteome Profiling reveals rapid proteomic responses to redox changes in specific cellular compartments
Authors: Revazian Aram , Nesterenko Alexey , Ezeriņa Daria , Luo Ting , Vertommen Didier , Gibhardt Christine S. , Bogeski Ivan , Messens Joris , Belousov Vsevolod V. 
Published: October 2024

AbstractHydrogen peroxide (H2O2) functions as a secondary messenger in cellular redox signaling, acting mainly via oxidation of protein thiols. Its spatially and temporally regulated activity within cells is essential for maintaining proper redox balance, and disruptions in these patterns can lead to oxidative stress and various related pathologies. Redox proteomics, which examines the impact of H2O2at the proteome level, typically focuses only on thiol oxidation, overlooking broader proteomic alterations and the significance of subcellular localization in these redox processes. In this study, we address these open questions by combining chemogenetics with Thermal Proteome Profiling (TPP) to map global proteome response to compartmentalized H2O2production. We identified hundreds of proteins with altered thermostability and/or abundance upon localized H2O2generation in the cytosol, nucleus, and the ER lumen, highlighting their roles in cellular responses to localized H2O2. We identified proteins such as MAP2K1, PARK7, TRAP1, and UBA2 to be highly sensitive to localized H2O2production. Furthermore, we validated their altered thermostability and found that these changes are controlled via dysregulated protein-protein interactions. This study provides a valuable resource for researchers exploring redox-mediated signal transduction and offers novel insights that could be harnessed in treating oxidative stress-induced pathologies.
Force-dependent Reorganization and Mechanostability of the Izumo1:Juno Complex Involved in Human Fertilization
Authors: Boult Sean , Pacak Paulina , Yang Byeongseon , Liu Haipei , Vogel Viola , Nash Michael A. 
Published: October 2024

AbstractIzumo1:Juno-mediated adhesion between sperm and egg cells is essential for mammalian sexual reproduction. However, conventional biophysical and structural approaches have provided only limited functional insights. Using atomic force microscopy-based single- molecule force spectroscopy and all-atom steered molecular dynamic simulations, we explored the role of mechanical forces in regulating the human Izumo1:Juno complex. Our findings reveal a multi-state catch bond capable of withstanding forces up to 600 pN- mechanostability rarely observed among eukaryotic protein complexes. We further found that this mechanostability was impaired in the infertility-associated mutant, JunoH177Q. Detailed steered molecular dynamics simulations show how force-dependent reorganization of the Izumo1:Juno complex engages new binding conformations to achieve this state of high mechanostability. Overall, this study significantly enhances our understanding of the mechanical underpinnings that regulate human fertilization.
Multi-omics investigation of spontaneous T2DM macaque reveals gut microbiota promote T2DM by up-regulating the absorption of excess palmitic acid
Authors: Liu Xu , Yang Shengzhi , Xie Yuchen , Jiang Cong , Shang Ke , Luo Jinxia , Zhang Lin , Hu Gang , Liu Qinghua , Yue Bisong , Fan Zhenxin , He Zhanlong , Li Jing 
Published: October 2024

AbstractAlthough gut microbiota and lipid metabolites have been suggested to be closely associated with type 2 diabetes mellitus (T2DM), the interactions between gut microbiota, lipid metabolites and the host in T2DM development remains unclear. Rhesus macaques may be the best animal model to investigate these relationships given their spontaneous development of T2DM. We identified eight spontaneous T2DM macaques and conducted a comprehensive study investigating the relationships using multi-omics sequencing technology. Our results from 16S rRNA, metagenome, metabolome and transcriptome analyses identified that gut microbiota imbalance, tryptophan metabolism and fatty acid β oxidation disorders, long-chain fatty acid (LCFA) accumulation, and inflammation occurred in T2DM macaques. We verified the accumulation of palmitic acid (PA) and activation of inflammation in T2DM macaques. Importantly, mice transplanted with spontaneous T2DM macaque fecal microbiota and fed a high PA diet developed prediabetes within 120 days. We determined that gut microbiota mediated the absorption of excess PA in the ileum, resulting in the accumulation of PA in the serum consequently leading to T2DM in mice. In particular, we demonstrated that the specific microbiota composition was probably involved in the process. This study provides new insight into interactions between microbiota and metabolites and confirms causative effect of gut microbiota on T2DM development.
Spectrin coordinates cortical actomyosin organization and differentiation essential for a functional epithelial barrier
Authors: Soffer Arad , Bhosale Aishwarya , Matsui Takeshi , Niessen Carien M. , Luxenburg Chen , Rübsam Matthias 
Published: October 2024

AbstractCell shape and cell fate are tightly linked. However, how cortical cytoskeletal organization that controls cell shape connects to signaling and drives cell fate changes is still poorly understood. Here we used the skin epidermis as paradigm for spatiotemporally coordinated cell shape and fate changes. Upon induction of differentiation, epidermal stem cells stratify and increasingly flatten to form a functional barrier. Here, we identify spectrin, an actin-binding membrane cytoskeleton protein, as a major regulator of epidermal cell shape, signaling and differentiation to control the formation of a functional epithelial barrier. Loss of αII-spectrin (encoded bySptan1) in the developing mouse epidermis inhibited suprabasal cell flattening, differentiation, and epidermal barrier function. Spectrin cortical localization required E-cadherin and actomyosin, while spectrin itself controls cortical actomyosin organization. In detail, using high resolution imaging and laser ablation revealed that spectrin was essential to form actin-based honeycomb-like cortical lattices that are essential to maintain cortical tension and structural integrity. We found that spectrin-dependent actomyosin organization controlled the activity and localization of the growth factor receptor EGFR, and the cation channel TRPV3, known to activate the enzyme transglutaminase essential for barrier function. Indeed, loss of spectrin, E-cadherin or actomyosin inhibition reduce TGM1 activity. Together, our results provide novel insights into how cortical organization and mechanics regulate cell shape and spatially activate signals necessary for differentiation and epithelial tissue function.
Exploring the Antifibrotic Potential of the heparan sulfate mimetic OTR4120: Insights from Preclinical Models
Authors: Marega Manuela , Mejdoubi-Charef Najet , Wiegard David , Khan Muzamil Majid , Bartkuhn Marek , Gambs Laura , Procida-Kowalski Tara , Wilhelm Jochem , Vasquez-Pacheco Esmeralda , Noori Afshin , Dong Ying , Zheng Yi , Chu Xuran , Lingampally Arun , Zukowska Joanna , Charef Said , Chiappini Franck , Choppin Agnes , Papy Garcia Dulce , Pepperkok Rainer , Muley Thomas , Winter Hauke , Ruppert Clemens , Seeger Werner , Gunther Andreas , Barritault Denis , Chen Chengshui , Chao Cho-Ming , Rivetti Stefano , Bellusci Saverio 
Published: October 2024

AbstractRationaleIdiopathic pulmonary fibrosis (IPF) is a debilitating lung disease characterized by excessive deposition of extracellular matrix (ECM), resulting in lung function impairment. Heparan sulfate mimetics (HSm) have been suggested to have potential antifibrotic effects by regulating ECM. This study aims to investigate the impact of a specific HSm named OTR4120 on fibrotic processes inex vivo,in vitroandin vivomodels.MethodsHuman Precision Cut Lung Slices (hPCLS) treated with a fibrotic cocktail alone or with OTR4120 were evaluated using second-harmonic imaging microscopy (SHIM) to assess collagen deposition. Human embryonic fibroblast WI-38 cell line and primary fibroblasts obtained from human donors were differentiated into myofibroblasts (MYF) using TGF-β1 and treated with OTR4120 or a control vehicle. Gene expression analysis for MYF markers was performed using quantitative PCR (qPCR). Protein expression of MYF markers was evaluated using immunofluorescence techniques. Bulk-RNA sequencing analysis on WI-38 cells cultured under different experimental conditions was conducted. Finally, the therapeutic effects of OTR4120 on a bleomycin-induced fibrosis mouse model were investigated.ResultsSHIM analysis on OTR4120-treated hPCLS showed a decrease in collagen deposition. OTR4120 treatment of primary fibroblasts and WI-38 cells exposed to TGF-β1 significantly reduced the expression of MYF markers. Bulk-RNA sequencing analysis on OTR4120-treated WI-38 cells showed significant impacts on fibrosis-related processes. Therapeutic application of OTR4120in vivoto bleomycin-induced fibrosis mice resulted in enhanced fibrosis resolution.ConclusionOTR4120 has potential therapeutic benefits as an antifibrotic agent in the context of lung fibrosis. Further investigations are necessary to understand the precise mechanism through which OTR4120 exerts its antifibrotic effects.
Development and validation of an open-source Hand Laterality Judgement Task for in-person and online studies
Authors: Moreno-Verdú Marcos , McAteer Siobhán M , Waltzing Baptiste M , Van Caenegem Elise , Hardwick Robert M 
Published: October 2024

ABSTRACTThe Hand Laterality Judgement Task (HLJT) is considered a measure of the ability to manipulate motor images. The ‘biomechanical constraints’ effect (longer reaction times for hand rotations towards anatomically difficult versus biomechanically easier movements) is considered the behavioural hallmark indicating motor imagery is being used. Previous work has used diverse HLJT paradigms, and there is no standardized procedure for the task. We developed an open-source, freely available version of the HLJT in PsychoPy2, which needs no programming skills and is highly customisable. Some studies suggest responding to the HLJT with the hands may interfere with performance, which would limit practical application of the task. We examined this potential issue using in-person and online versions. For the in-person version, 40 right-footed/handed individuals performed the HLJT with their feet or bimanually (N=20 each). For the online version, 60 right-handed individuals performed the task bimanually or unimanually (N=20 each). Bayesian mixed-effect analyses quantified the evidence for and against equivalence within and between the in-person and online versions. Both versions replicated previously described behavioural phenomena, including effects of angle, hand view, and the ‘biomechanical constraints’ effect. While responding with different effectors modified overall reaction times, it did not interact with other factors analysed, and did not affect accuracy or the ‘biomechanical constraints’ effect. There was also evidence for equivalence between in-person and online bimanual groups for all measures. We conclude that this open-source, standardized HLJT protocol (available athttps://osf.io/8h7ec/) can reliably detect previously identified effects and works equally well in-person or online.