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The systematic assessment of completeness of public metadata accompanying omics studies in the Gene Expression Omnibus. 基因表达综合数据库中伴随组学研究的公共元数据完整性的系统评估。
bioRxiv : the preprint server for biology Pub Date : 2025-07-07 DOI: 10.1101/2021.11.22.469640
Yu-Ning Huang, Pooja Vinod Jaiswal, Anushka Rajesh, Anushka Yadav, Dottie Yu, Fangyun Liu, Grace Scheg, Emma Shih, Grigore Boldirev, Irina Nakashidze, Aditya Sarkar, Jay Himanshu Mehta, Ke Wang, Khooshbu Kantibhai Patel, Mustafa Ali Baig Mirza, Kunali Chetan Hapani, Qiushi Peng, Ram Ayyala, Ruiwei Guo, Shaunak Kapur, Tejasvene Ramesh, Dumitru Ciorbă, Viorel Munteanu, Viorel Bostan, Mihai Dimian, Malak S Abedalthagafi, Serghei Mangul
{"title":"The systematic assessment of completeness of public metadata accompanying omics studies in the Gene Expression Omnibus.","authors":"Yu-Ning Huang, Pooja Vinod Jaiswal, Anushka Rajesh, Anushka Yadav, Dottie Yu, Fangyun Liu, Grace Scheg, Emma Shih, Grigore Boldirev, Irina Nakashidze, Aditya Sarkar, Jay Himanshu Mehta, Ke Wang, Khooshbu Kantibhai Patel, Mustafa Ali Baig Mirza, Kunali Chetan Hapani, Qiushi Peng, Ram Ayyala, Ruiwei Guo, Shaunak Kapur, Tejasvene Ramesh, Dumitru Ciorbă, Viorel Munteanu, Viorel Bostan, Mihai Dimian, Malak S Abedalthagafi, Serghei Mangul","doi":"10.1101/2021.11.22.469640","DOIUrl":"10.1101/2021.11.22.469640","url":null,"abstract":"<p><p>Recent advances in high-throughput sequencing technologies have made it possible to collect and share a massive amount of omics data, along with its associated metadata. Enhancing metadata availability is critical to ensure data reusability and reproducibility and to facilitate novel biomedical discoveries through effective data reuse. Yet, incomplete metadata accompanying public omics data may hinder reproducibility and reusability by reducing sample interpretability and limiting secondary analyses. In this study, we performed a comprehensive assessment of metadata completeness shared in both scientific publications and/or public repositories by analyzing over 253 studies encompassing over 164 thousands samples, including both human and non-human mammalian studies. We observed that studies often omit over a quarter of important phenotypes, with an average of only 74.8% of them shared either in the text of publication or the corresponding repository. Notably, public repositories alone contained 62% of the metadata, surpassing the textual content of publications by 3.5%. Only 11.5% of studies completely shared all phenotypes, while 37.9% shared less than 40% of the phenotypes. Studies involving non-human samples were more likely to share metadata than studies involving human samples. We observed similar results on the extended dataset spanning 2.1 million samples across over 61,000 studies from the Gene Expression Omnibus repository. The limited availability of metadata reported in our study emphasizes the necessity for improved metadata sharing practices and standardized reporting. Finally, we discuss the numerous benefits of improving the availability and quality of metadata to the scientific community and beyond, supporting data-driven decision-making and policy development in the field of biomedical research. This work provides a scalable framework for evaluating metadata availability and may help guide future policy and infrastructure development.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75449785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The transcription factor CLAMP is required for neurogenesis in Drosophila melanogaster. 转录因子CLAMP是黑腹果蝇神经发生所必需的。
bioRxiv : the preprint server for biology Pub Date : 2025-07-07 DOI: 10.1101/2020.10.09.333831
Maria A Tsiarli, James A Kentro, Ashley M Conard, Lucy Xu, Erica Nguyen, Kate O'Connor-Giles, Erica N Larschan
{"title":"The transcription factor CLAMP is required for neurogenesis in <i>Drosophila melanogaster</i>.","authors":"Maria A Tsiarli, James A Kentro, Ashley M Conard, Lucy Xu, Erica Nguyen, Kate O'Connor-Giles, Erica N Larschan","doi":"10.1101/2020.10.09.333831","DOIUrl":"10.1101/2020.10.09.333831","url":null,"abstract":"<p><p>Neural stem cell (NSC) differentiation is controlled by cell-intrinsic and external signals from the stem cell niche including niche surface glia (SG). However, the mechanisms by which transcription factors drive NSC differentiation within the niche remain largely unknown. Here, we show that the <i>Drosophila</i> melanogaster transcription factor, Chromatin-linked adaptor for MSL proteins (CLAMP) is required for regulation of stemness and proliferation of NSCs, especially of the optic lobe (OL). CLAMP promotes transcription of genes involved in stemness, proliferation, and glial development and represses transcription of genes involved in neurogenesis and niche survival. Consistent with transcriptional changes, CLAMP promotes NSC proliferation and niche SG production, while lack of CLAMP severely and specifically impacts OL development. Το identify potential mechanisms by which CLAMP may regulate brain development, we examined CLAMP motifs and available CLAMP ChIP-seq data to determine which genes may be direct versus indirect targets. CLAMP motifs are present at many target genes including the glial-determining gene, <i>glial cells missing,</i> while <i>Tailless,</i> the master regulator of OL-development is directly bound by CLAMP. In accordance to these results, in larval OL NSCs lacking CLAMP, Tailless levels are decreased dramatically, suggesting that CLAMP controls OL neurogenesis <i>via</i> Tailless. Overall, our results suggest that CLAMP regulates a transcriptional program which drives NSC proliferation and differentiation <i>via</i> cell-intrinsic and niche-dependent mechanisms that involve transcriptional regulation of <i>Tailless</i> and niche glia.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"120 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87768591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lithium Restores Inhibitory Function and Neuronal Excitability through GSK-3β Inhibition in a Bipolar Disorder-Associated Ank3 Variant Mouse Model. 慢性锂治疗对Ank3突变小鼠模型神经元兴奋性和gaba能传递的影响。
bioRxiv : the preprint server for biology Pub Date : 2025-07-02 DOI: 10.1101/2023.10.26.564203
René N Caballero-Florán, Kendall P Dean, Andrew D Nelson, Lia Min, Paul M Jenkins
{"title":"Lithium Restores Inhibitory Function and Neuronal Excitability through GSK-3β Inhibition in a Bipolar Disorder-Associated <i>Ank3</i> Variant Mouse Model.","authors":"René N Caballero-Florán, Kendall P Dean, Andrew D Nelson, Lia Min, Paul M Jenkins","doi":"10.1101/2023.10.26.564203","DOIUrl":"10.1101/2023.10.26.564203","url":null,"abstract":"<p><p>Bipolar disorder (BD) is a prevalent psychiatric condition characterized by mood dysregulation, psychosocial impairment, and an increased risk of suicide. The gene <i>ANK3</i> has been identified as a risk locus for BD through multiple genome-wide association studies (GWAS). However, the mechanisms by which <i>ANK3</i> variants influence BD pathophysiology and treatment response remain unclear. <i>ANK3</i> encodes ankyrin-G, a protein that organizes the axon initial segment (AIS) and nodes of Ranvier by scaffolding ion channels and cell adhesion molecules to the cytoskeleton. Recent studies show that ankyrin-G interacts with the GABA <sub>A</sub> receptor-associated protein (GABARAP) to stabilize inhibitory synapses, potentially linking <i>ANK3</i> variants to inhibitory (GABAergic) signaling deficits associated with BD. We previously demonstrated that the BD-associated variant, <i>ANK3</i> p.W1989R, disrupts the ankyrin-G/ GABARAP interaction, resulting in inhibitory deficits and cortical pyramidal neuron hyperexcitability in mice. In this study, we investigate how lithium, a common BD therapeutic, modulates neuronal excitability in this model. Our findings show that chronic lithium treatment selectively enhances presynaptic GABAergic neurotransmission, reduces neuronal hyperexcitability, and partially rescues AIS length, without altering the density of GABAergic synapses. We also show that the selective glycogen synthase kinase-3 beta (GSK-3β) inhibitor Tideglusib recapitulates the enhancement of presynaptic GABAergic signaling. These findings shed new light on how <i>ANK3</i> variants may contribute to inhibitory deficits in BD and demonstrate that lithium treatment is able to restore these deficits, likely through GSK-3β inhibition. Furthermore, these findings highlight GSK-3β inhibition as a promising therapeutic strategy for treating BD and other neurological disorders affected by GABAergic dysfunction.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92157709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multi-omic identification of key transcriptional regulatory programs during endurance exercise training in rats. 耐力运动训练过程中关键转录调控程序的多组鉴定。
bioRxiv : the preprint server for biology Pub Date : 2025-07-02 DOI: 10.1101/2023.01.10.523450
Gregory R Smith, Bingqing Zhao, Malene E Lindholm, Archana Raja, Mark Viggars, Hanna Pincas, Nicole R Gay, Yifei Sun, Yongchao Ge, Venugopalan D Nair, James A Sanford, Mary Anne S Amper, Mital Vasoya, Kevin S Smith, Stephen Montgomery, Elena Zaslavsky, Sue C Bodine, Karyn A Esser, Martin J Walsh, Michael P Snyder, Stuart C Sealfon
{"title":"Multi-omic identification of key transcriptional regulatory programs during endurance exercise training in rats.","authors":"Gregory R Smith, Bingqing Zhao, Malene E Lindholm, Archana Raja, Mark Viggars, Hanna Pincas, Nicole R Gay, Yifei Sun, Yongchao Ge, Venugopalan D Nair, James A Sanford, Mary Anne S Amper, Mital Vasoya, Kevin S Smith, Stephen Montgomery, Elena Zaslavsky, Sue C Bodine, Karyn A Esser, Martin J Walsh, Michael P Snyder, Stuart C Sealfon","doi":"10.1101/2023.01.10.523450","DOIUrl":"10.1101/2023.01.10.523450","url":null,"abstract":"<p><p>Transcription factors (TFs) play a key role in regulating gene expression. We conducted an integrated analysis of chromatin accessibility, DNA methylation, mRNA expression, protein abundance and phosphorylation across eight tissues in fifty rats of equally represented sexes following endurance exercise training (EET) to identify coordinated epigenomic and transcriptional changes and determine key TFs involved. We uncovered tissue-specific EET associated changes and TF motif enrichment across differentially expressed genes (DEGs), accessible regions (DARs), and methylated regions (DMRs). We discovered distinct routes of EET-induced regulation through either epigenomic alterations providing better access for TFs to affect target genes, or via changes in TF expression or activity enabling target gene responses. We identified TF motifs enriched among correlated epigenomic and transcriptomic alterations, DEGs correlated with exercise-related phenotypic and cell type composition changes, and EET-induced activity changes of TFs whose target genes are enriched for DEGs. This analysis elucidates the unique gene regulatory mechanisms mediating diverse transcriptional responses to EET across tissues.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/79/bf/nihpp-2023.01.10.523450v1.PMC9882056.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10698707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spatiotemporal mapping of the contractile and adhesive forces sculpting early C. elegans embryos. 早期秀丽隐杆线虫胚胎的收缩力和粘附力的时空映射。
bioRxiv : the preprint server for biology Pub Date : 2025-07-01 DOI: 10.1101/2023.03.07.531437
Kazunori Yamamoto, Sacha Ichbiah, Matthieu Perez, Joana Borrego-Pinto, Fabrice Delbary, Nate Goehring, Hervé Turlier, Guillaume Charras
{"title":"Spatiotemporal mapping of the contractile and adhesive forces sculpting early <i>C. elegans</i> embryos.","authors":"Kazunori Yamamoto, Sacha Ichbiah, Matthieu Perez, Joana Borrego-Pinto, Fabrice Delbary, Nate Goehring, Hervé Turlier, Guillaume Charras","doi":"10.1101/2023.03.07.531437","DOIUrl":"10.1101/2023.03.07.531437","url":null,"abstract":"<p><p>Embryo shape is determined by individual cell mechanics, intercellular interaction strength, and geometrical constraints. Models based on surface tensions at cell interfaces can predict 3D static cellular arrangements within aggregates. However, predicting the dynamics of such arrangements is challenging due to difficulties in measuring temporal changes in tensions. Here, we characterise the spatiotemporal changes in cellular tensions shaping the early nematode embryo using AFM, live microscopy, and tension inference. Using excoriated embryos, we validate a hybrid inference pipeline that calibrates relative inferred tensions temporally using cortical myosin enrichment and absolute tensions using AFM measurements. Applied to embryos within their native shell, we infer a spatiotemporal map of absolute tensions, revealing that ABa, ABp, and EMS compaction is driven by increased tension at free surfaces, while P<sub>2</sub>'s initial exclusion is due to high tension at intercellular contacts. We uncover a direct and non-affine contribution of cadherins to cell-cell contact tension, comparable to cadherins' indirect contribution via actomyosin regulation.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89062248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Developmentally Conserved CDX2 Cells from Human Term Placenta Drive Cardiovascular Regeneration. 从人胎盘中发现一种多能细胞。
bioRxiv : the preprint server for biology Pub Date : 2025-06-30 DOI: 10.1101/2023.08.02.551028
Sangeetha Vadakke-Madathil, Esmaa Bouhamida, Bingyan J Wang, Prabhu Mathiyalagan, Parichitran Ayyamperumal, Amir Khan, Micayla Oniskey, Carlos Santos-Gallegos, Michael Hadley, Lori Croft, Fumiko Dekio, Rachel Brody, Shari Gelber, Rhoda Sperling, Hina W Chaudhry
{"title":"Developmentally Conserved CDX2 Cells from Human Term Placenta Drive Cardiovascular Regeneration.","authors":"Sangeetha Vadakke-Madathil, Esmaa Bouhamida, Bingyan J Wang, Prabhu Mathiyalagan, Parichitran Ayyamperumal, Amir Khan, Micayla Oniskey, Carlos Santos-Gallegos, Michael Hadley, Lori Croft, Fumiko Dekio, Rachel Brody, Shari Gelber, Rhoda Sperling, Hina W Chaudhry","doi":"10.1101/2023.08.02.551028","DOIUrl":"10.1101/2023.08.02.551028","url":null,"abstract":"<p><p>We report a population of multipotent cells isolated from term human placentas that exhibit clonal expansion and migratory capacity, along with a gene expression profile that indicates immune privilege. Previously known largely for its role in early placentation, the developmental regulator CDX2 marks cells capable of differentiating into cardiomyocytes and vascular lineages. Building on our prior findings that murine Cdx2 cells improved cardiac function in mice after myocardial infarction (MI), we isolated CDX2⁺ cells from placentas of 180 healthy pregnancies. These human CDX2 cells spontaneously generate cardiac and vascular lineages <i>in vitro, in vivo,</i> and express transcriptomic signatures associated with cardiogenesis, vasculogenesis, immune modulation, and chemotaxis. When administered to NOD/SCID mice after MI, the cells restore cardiac function. Additionally, CDX2 cells can be clonally propagated while retaining cardiovascular differentiation potential. Our findings support the therapeutic potential of placental CDX2 cells as an ethically accessible and regenerative strategy for cardiovascular disease.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9991211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Computation-guided redesign of promoter specificity of a bacterial RNA polymerase. 一种细菌RNA聚合酶启动子特异性的计算引导重新设计。
bioRxiv : the preprint server for biology Pub Date : 2025-06-27 DOI: 10.1101/2022.11.29.518332
Xiangyang Liu, Anthony T Meger, Thomas Gillis, Jonah O'Mara Schwartz, Balendra Sah, Robert Landick, Srivatsan Raman
{"title":"Computation-guided redesign of promoter specificity of a bacterial RNA polymerase.","authors":"Xiangyang Liu, Anthony T Meger, Thomas Gillis, Jonah O'Mara Schwartz, Balendra Sah, Robert Landick, Srivatsan Raman","doi":"10.1101/2022.11.29.518332","DOIUrl":"10.1101/2022.11.29.518332","url":null,"abstract":"<p><p>The ability to regulate genetic circuits and metabolic pathways is central to cellular control. The existing toolkit is predominantly comprised of local transcription regulators that are unsuitable for exerting control at a global genome-wide scale. Bacterial sigma factors are ideal global regulators as together they direct the RNA polymerase to thousands of transcription sites. Here, we redesigned the promoter specificity of the <i>E. coli</i> housekeeping sigma factor, sigma-70, toward five orthogonal promoter targets not recognized by the native sigma-70. These orthogonal sigma-70 factors were developed by screening a pooled library of computationally designed variants of the -35 DNA recognition helix, each tailored to a specific target promoter. In the redesigned sigma factors new target-specific interactions facilitate new promoter recognition. Activity of the top performing redesigned sigma-70s varied across the promoter targets and ranged from 17% to 77% of native sigma-70 on its canonical active promoter. These orthogonal sigma factors represent a new suite of regulators for global transcriptional control.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12262734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84622366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Incorporation of collagen into Pseudomonas aeruginosa, Staphylococcus aureus , and Burkholderia pseudomallei biofilms enhances their elasticity and resistance against phagocytic clearance. 铜绿假单胞菌和金黄色葡萄球菌生物膜中胶原蛋白的掺入阻碍了中性粒细胞的吞噬作用。
bioRxiv : the preprint server for biology Pub Date : 2025-06-27 DOI: 10.1101/2023.10.25.564018
Xuening Zhou, Ashlee McGovern, Marilyn J Wells, Deepesh B Verma, Hailey Currie, Afsana Mimi Raka, Jiachun Shen, Katherine A Brown, Rae Robertson-Anderson, Vernita D Gordon
{"title":"Incorporation of collagen into <i>Pseudomonas aeruginosa, Staphylococcus aureus</i> , and <i>Burkholderia pseudomallei</i> biofilms enhances their elasticity and resistance against phagocytic clearance.","authors":"Xuening Zhou, Ashlee McGovern, Marilyn J Wells, Deepesh B Verma, Hailey Currie, Afsana Mimi Raka, Jiachun Shen, Katherine A Brown, Rae Robertson-Anderson, Vernita D Gordon","doi":"10.1101/2023.10.25.564018","DOIUrl":"10.1101/2023.10.25.564018","url":null,"abstract":"<p><p>Biofilms are communities of microbes embedded in a matrix of extracellular polymeric substances (EPS) and other components such as proteins. Matrix components can be produced by the microorganisms themselves but can also originate from the environment and then be incorporated into the biofilm. For example, we and our collaborators have recently shown that collagen, a host-produced protein that is abundant in many different infection sites, can be taken up into the matrices of <i>Pseudomonas aeruginosa</i> biofilms, altering biofilm mechanics. In an infection, the biofilm matrix protects bacteria from clearance by the immune system, and some of that protection likely arises from the mechanical properties of the biofilm. <i>P. aeruginosa, Staphylococcus aureus</i> , and <i>Burkholderia pseudomallei</i> are human pathogens notable for forming biofilms <i>in vitro</i> and <i>in vivo</i> in tissues rich in collagen such as lung and skin. Here, we show that the incorporation of Type I collagen into <i>P. aeruginosa, S. aureus</i> , and <i>B. pseudomallei</i> biofilms significantly enhances biofilm elasticity and hinders phagocytosis of biofilm bacteria by human neutrophils. Additionally, enzymatic degradation of collagen using collagenase reverses these effects, increasing biofilm susceptibility to neutrophils. Our findings suggest that host materials play significant roles in stabilizing biofilms and may present promising targets for therapeutic interventions.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92157703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Widespread epistasis shapes RNA Polymerase II active site function and evolution. 广泛的上位性塑造了RNA聚合酶II活性位点的功能和进化。
bioRxiv : the preprint server for biology Pub Date : 2025-06-27 DOI: 10.1101/2023.02.27.530048
Bingbing Duan, Chenxi Qiu, Sing-Hoi Sze, Craig Kaplan
{"title":"Widespread epistasis shapes RNA Polymerase II active site function and evolution.","authors":"Bingbing Duan, Chenxi Qiu, Sing-Hoi Sze, Craig Kaplan","doi":"10.1101/2023.02.27.530048","DOIUrl":"10.1101/2023.02.27.530048","url":null,"abstract":"<p><p>Multi-subunit RNA Polymerases (msRNAPs) are responsible for transcription in all kingdoms of life. These enzymes rely on dynamic, highly conserved active site domains such as the so-called \"trigger loop\" (TL) to accomplish steps in the transcription cycle. Mutations in the RNA polymerase II (Pol II) TL confer a spectrum of biochemical and genetic phenotypes that suggest two main classes, which decrease or increase catalysis or other nucleotide addition cycle (NAC) events. The Pol II active site relies on networks of residue interactions to function, and mutations likely perturb these networks in ways that may alter mechanisms. We have undertaken a structural genetics approach to reveal residue interactions within and surrounding the Pol II TL - determining its \"interaction landscape\" - by deep mutational scanning in <i>Saccharomyces cerevisiae</i> Pol II. This analysis reveals connections between TL residues and surrounding domains, demonstrating that TL function is tightly coupled to its specific enzyme context.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5e/78/nihpp-2023.02.27.530048v2.PMC10002619.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9307975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Brain-wide arousal signals are segregated from movement planning in the superior colliculus. 上丘的全脑唤醒信号与运动规划信号是分离的。
bioRxiv : the preprint server for biology Pub Date : 2025-06-27 DOI: 10.1101/2024.04.26.591284
Richard Johnston, Matthew A Smith
{"title":"Brain-wide arousal signals are segregated from movement planning in the superior colliculus.","authors":"Richard Johnston, Matthew A Smith","doi":"10.1101/2024.04.26.591284","DOIUrl":"10.1101/2024.04.26.591284","url":null,"abstract":"<p><p>The superior colliculus (SC) is traditionally considered a brain region that functions as an interface between processing visual inputs and generating eye movement outputs. Although its role as a primary reflex center is thought to be conserved across vertebrate species, evidence suggests that the SC has evolved to support higher-order cognitive functions including spatial attention. When it comes to oculomotor areas such as the SC, it is critical that high precision fixation and eye movements are maintained even in the presence of signals related to ongoing changes in cognition and brain state, both of which have the potential to interfere with eye position encoding and movement generation. In this study, we recorded spiking responses of neuronal populations in the SC while monkeys performed a memory-guided saccade task and found that the activity of some of the neurons fluctuated over tens of minutes. By leveraging the statistical power afforded by high-dimensional neuronal recordings, we were able to identify a low-dimensional pattern of activity that was correlated with the subjects' arousal levels. Importantly, we found that the spiking responses of deep-layer SC neurons were less correlated with this brain-wide arousal signal, and that neural activity associated with changes in pupil size and saccade tuning did not overlap in population activity space with movement initiation signals. Taken together, these findings provide a framework for understanding how signals related to cognition and arousal can be embedded in the population activity of oculomotor structures without compromising the fidelity of the motor output.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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