PLoS Biology最新文献

The m5C reader Ybx1 regulates embryonic cortical neurogenesis by promoting progenitor cell cycle progression. m5C阅读器Ybx1通过促进祖细胞周期进展调节胚胎皮质神经发生。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-28 DOI: 10.1371/journal.pbio.3003175

Jian Zhang, Pengfei Che, Zhuoxuan Yang, Pingrui Zhang, Yuxuan Shui, Xibin Lu, Jiuzhou Xu, Yuanchu She, Yanbo Zhang, Jun Yu, Sheng-Jian Ji

{"title":"The m5C reader Ybx1 regulates embryonic cortical neurogenesis by promoting progenitor cell cycle progression.","authors":"Jian Zhang, Pengfei Che, Zhuoxuan Yang, Pingrui Zhang, Yuxuan Shui, Xibin Lu, Jiuzhou Xu, Yuanchu She, Yanbo Zhang, Jun Yu, Sheng-Jian Ji","doi":"10.1371/journal.pbio.3003175","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003175","url":null,"abstract":"The reversible epitranscriptomic mark, 5-methylcytosine (m5C) modification, is implicated in numerous cellular processes, but its role in neural development remains largely unexplored. In this study, we discovered high expression of the m5C reader Ybx1 in the developing mouse cortex. To elucidate its role in cortical development, Ybx1 was ablated in embryonic cortical neural stem cells (NSCs). Interestingly, conditional knockout (cKO) of Ybx1 led to perinatal mortality in mice, along with abnormal cortical development. Cortical progenitor cells lacking Ybx1 exhibited impaired proliferation and differentiation. Multi-omics analysis identified the target mRNAs of Ybx1, which encode the key cell cycle regulatory proteins converging on cyclin D2 (Ccnd2). Ybx1 was found to regulate the stability of its target transcripts. Both knockdown and overexpression of Ybx1 targets via in utero electroporation confirmed that they mediated Ybx1 regulation of proliferation and differentiation of neural precursor cells. Further analysis showed that the G1 to S phase transition in cortical progenitor cells is delayed in the Ybx1 cKO. This study highlights the crucial function of the m5C reader protein Ybx1 in promoting cell cycle progression of the embryonic cortical progenitors, essential for proper cortical development.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003175"},"PeriodicalIF":9.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

qByte: An open-source isothermal fluorimeter for democratizing analysis of nucleic acids, proteins and cells. qByte：一个开源的等温荧光仪，用于大众化的核酸、蛋白质和细胞分析。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-28 DOI: 10.1371/journal.pbio.3003199

Francisco J Quero, Guy Aidelberg, Hortense Vielfaure, Yann Huon de Kermadec, Severine Cazaux, Amir Pandi, Ana Pascual-Garrigos, Anibal Arce, Samuel Sakyi, Urs Gaudenz, Fernan Federici, Jennifer C Molloy, Ariel B Lindner

{"title":"qByte: An open-source isothermal fluorimeter for democratizing analysis of nucleic acids, proteins and cells.","authors":"Francisco J Quero, Guy Aidelberg, Hortense Vielfaure, Yann Huon de Kermadec, Severine Cazaux, Amir Pandi, Ana Pascual-Garrigos, Anibal Arce, Samuel Sakyi, Urs Gaudenz, Fernan Federici, Jennifer C Molloy, Ariel B Lindner","doi":"10.1371/journal.pbio.3003199","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003199","url":null,"abstract":"Access to affordable and reliable scientific instrumentation remains a significant barrier to the democratization of healthcare and scientific research. In the field of biotechnology, in particular, the complexity, cost, and infrastructure requirements of many instruments continue to limit their accessibility, especially in resource-limited environments. Despite the recent increase in the development of open-source tools, driven by advances in digital fabrication and electronic prototyping, few of these projects have reached large-scale implementation or validation in real-world settings. Here, we present qByte, an open-source, 8-tube isothermal fluorimeter designed to overcome these barriers by offering a cost-effective ($60) yet production-ready solution. qByte leverages standard digital manufacturing and Printed Circuit Board (PCB) assembly techniques and is designed to be portable, making it ideal for both laboratory and field use. The device has been benchmarked against commercial real-time thermocyclers and spectrophotometers, showing comparable results across four key applications: nucleic acid amplification and detection, including the on-site diagnosis of human parasites in Ghana, analysis of protein activity and stability, genetic construct characterization, and bacterial viability tests. Taken together, our results proved qByte as flexible and reliable equipment for a variety of biological tests and applications, while its affordability and open-source design simplify further development and allow adaptation to the needs of future users.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003199"},"PeriodicalIF":9.8,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rhythm profiling using COFE reveals multi-omic circadian rhythms in human cancers in vivo. 使用COFE的节律分析揭示了体内人类癌症的多组昼夜节律。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-27 DOI: 10.1371/journal.pbio.3003196

Bharath Ananthasubramaniam, Ramji Venkataramanan

{"title":"Rhythm profiling using COFE reveals multi-omic circadian rhythms in human cancers in vivo.","authors":"Bharath Ananthasubramaniam, Ramji Venkataramanan","doi":"10.1371/journal.pbio.3003196","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003196","url":null,"abstract":"The study of ubiquitous circadian rhythms in human physiology requires regular measurements across time. Repeated sampling of the different internal tissues that house circadian clocks is both practically and ethically infeasible. Here, we present a novel unsupervised machine learning approach (COFE) that can use single high-throughput omics samples (without time labels) from individuals to reconstruct circadian rhythms across cohorts. COFE can simultaneously assign time labels to samples and identify rhythmic data features used for temporal reconstruction, while also detecting invalid orderings. With COFE, we discovered widespread de novo circadian gene expression rhythms in 11 different human adenocarcinomas using data from The Cancer Genome Atlas (TCGA) database. The arrangement of peak times of core clock gene expression was conserved across cancers and resembled a healthy functional clock except for the mistiming of a few key genes. Moreover, rhythms in the transcriptome were strongly associated with the cancer-relevant proteome. The rhythmic genes and proteins common to all cancers were involved in metabolism and the cell cycle. Although these rhythms were synchronized with the cell cycle in many cancers, they were uncoupled with clocks in healthy matched tissue. The targets of most of FDA-approved and potential anti-cancer drugs were rhythmic in tumor tissue with different amplitudes and peak times. These findings emphasize the utility of considering \"time\" in cancer therapy, and suggest a focus on clocks in healthy tissue rather than free-running clocks in cancer tissue. Our approach thus creates new opportunities to repurpose data without time labels to study circadian rhythms.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003196"},"PeriodicalIF":9.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An interbacterial cysteine protease toxin inhibits cell growth by targeting type II DNA topoisomerases GyrB and ParE. 细菌间半胱氨酸蛋白酶毒素通过靶向II型DNA拓扑异构酶GyrB和ParE抑制细胞生长。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-27 DOI: 10.1371/journal.pbio.3003208

Pin-Yi Song, Chia-En Tsai, Yung-Chih Chen, Yu-Wen Huang, Po-Pang Chen, Tzu-Haw Wang, Chao-Yuan Hu, Po-Yin Chen, Chuan Ku, Kuo-Chiang Hsia, See-Yeun Ting

{"title":"An interbacterial cysteine protease toxin inhibits cell growth by targeting type II DNA topoisomerases GyrB and ParE.","authors":"Pin-Yi Song, Chia-En Tsai, Yung-Chih Chen, Yu-Wen Huang, Po-Pang Chen, Tzu-Haw Wang, Chao-Yuan Hu, Po-Yin Chen, Chuan Ku, Kuo-Chiang Hsia, See-Yeun Ting","doi":"10.1371/journal.pbio.3003208","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003208","url":null,"abstract":"Bacteria deploy a diverse arsenal of toxic effectors to antagonize competitors, profoundly influencing the composition of microbial communities. Previous studies have identified an interbacterial toxin predicted to exhibit proteolytic activity that is broadly distributed among gram-negative bacteria. However, the precise mechanism of intoxication remains unresolved. Here, we demonstrate that one such protease toxin from Escherichia coli, Cpe1, disrupts DNA replication and chromosome segregation by cleaving conserved sequences within the ATPase domain of type II DNA topoisomerases GyrB and ParE. This cleavage effectively inhibits topoisomerase-mediated relaxation of supercoiled DNA, resulting in impaired bacterial growth. Cpe1 belongs to the papain-like cysteine protease family and is associated with toxin delivery pathways, including the type VI secretion system and contact-dependent growth inhibition. The structure of Cpe1 in complex with its immunity protein reveals a neutralization mechanism involving competitive substrate binding rather than active site occlusion, distinguishing it from previously characterized effector-immunity pairs. Our findings unveil a unique mode of interbacterial intoxication and provide insights into how bacteria protect themselves from self-poisoning by protease toxins.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003208"},"PeriodicalIF":9.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An animal toxin-antidote system kills cells by creating a novel cation channel. 动物毒素解毒剂系统通过创造新的阳离子通道杀死细胞。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-27 DOI: 10.1371/journal.pbio.3003182

Lews Caro, Aguan D Wei, Christopher A Thomas, Galen Posch, Ahmet Uremis, Michaela C Franzi, Sarah J Abell, Andrew H Laszlo, Jens H Gundlach, Jan-Marino Ramirez, Michael Ailion

引用次数: 0

Predictable motion is progressively extrapolated across temporally distinct processing stages in the human visual cortex. 可预测的运动是在人类视觉皮层的时间上不同的处理阶段逐步外推的。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-23 DOI: 10.1371/journal.pbio.3003189

William Turner, Charlie Sexton, Philippa A Johnson, Ella Wilson, Hinze Hogendoorn

{"title":"Predictable motion is progressively extrapolated across temporally distinct processing stages in the human visual cortex.","authors":"William Turner, Charlie Sexton, Philippa A Johnson, Ella Wilson, Hinze Hogendoorn","doi":"10.1371/journal.pbio.3003189","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003189","url":null,"abstract":"Neural processing of sensory information takes time. Consequently, to estimate the current state of the world, the brain must rely on predictive processes-for example, extrapolating the motion of a ball to determine its probable present position. Some evidence implicates early (pre-cortical) processing in extrapolation, but it remains unclear whether extrapolation continues during later-stage (cortical) processing, where further delays accumulate. Moreover, the majority of such evidence relies on invasive neurophysiological techniques in animals, with accurate characterization of extrapolation effects in the human brain currently lacking. Here, we address these issues by demonstrating how precise probabilistic maps can be constructed from human EEG recordings. Participants (N = 18, two sessions) viewed a stimulus moving along a circular trajectory while EEG was recorded. Using linear discriminant analysis (LDA) classification, we extracted maps of stimulus location over time and found evidence of a forwards temporal shift occurring across temporally distinct processing stages. This accelerated emergence of position representations indicates extrapolation occurring at multiple stages of processing, with representations progressively shifted closer to real-time. We further show evidence of representational overshoot during early-stage processing following unexpected changes to an object's trajectory, and demonstrate that the observed dynamics can emerge without supervision in a simulated neural network via spike-timing-dependent plasticity.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003189"},"PeriodicalIF":9.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Landscape of essential growth and fluconazole-resistance genes in the human fungal pathogen Cryptococcus neoformans. 人类真菌病原体新型隐球菌的基本生长景观和氟康唑耐药基因。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-22 DOI: 10.1371/journal.pbio.3003184

R Blake Billmyre, Caroline J Craig, Joshua W Lyon, Claire Reichardt, Amy M Kuhn, Michael T Eickbush, Sarah E Zanders

{"title":"Landscape of essential growth and fluconazole-resistance genes in the human fungal pathogen Cryptococcus neoformans.","authors":"R Blake Billmyre, Caroline J Craig, Joshua W Lyon, Claire Reichardt, Amy M Kuhn, Michael T Eickbush, Sarah E Zanders","doi":"10.1371/journal.pbio.3003184","DOIUrl":"10.1371/journal.pbio.3003184","url":null,"abstract":"Fungi can cause devastating invasive infections, typically in immunocompromised patients. Treatment is complicated both by the evolutionary similarity between humans and fungi and by the frequent emergence of drug resistance. Studies in fungal pathogens have long been slowed by a lack of high-throughput tools and community resources that are common in model organisms. Here we demonstrate a high-throughput transposon mutagenesis and sequencing (TN-seq) system in Cryptococcus neoformans that enables genome-wide determination of gene essentiality. We employed a random forest machine learning approach to classify the C. neoformans genome as essential or nonessential, predicting 1,465 essential genes, including 302 that lack human orthologs. These genes are ideal targets for new antifungal drug development. TN-seq also enables genome-wide measurement of the fitness contribution of genes to phenotypes of interest. As proof of principle, we demonstrate the genome-wide contribution of genes to growth in fluconazole, a clinically used antifungal. We show a novel role for the well-studied RIM101 pathway in fluconazole susceptibility. We also show that insertions of transposons into the 5' upstream region can drive sensitization of essential genes, enabling screenlike assays of both essential and nonessential components of the genome. Using this approach, we demonstrate a role for mitochondrial function in fluconazole sensitivity, such that tuning down many essential mitochondrial genes via 5' insertions can drive resistance to fluconazole. Our assay system will be valuable in future studies of C. neoformans, particularly in examining the consequences of genotypic diversity.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003184"},"PeriodicalIF":9.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Horizontal gene transfer of molecular weapons can reshape bacterial competition. 分子武器的水平基因转移可以重塑细菌竞争。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-21 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003095

Elisa T Granato, Jacob D Palmer, Christian Kirk, Connor Sharp, George Shillcock, Kevin R Foster

{"title":"Horizontal gene transfer of molecular weapons can reshape bacterial competition.","authors":"Elisa T Granato, Jacob D Palmer, Christian Kirk, Connor Sharp, George Shillcock, Kevin R Foster","doi":"10.1371/journal.pbio.3003095","DOIUrl":"10.1371/journal.pbio.3003095","url":null,"abstract":"Bacteria commonly use molecular weaponry to kill or inhibit competitors. Genes encoding many weapons and their associated immunity mechanisms can be transmitted horizontally. These transfer events are striking because they appear to undermine bacterial weapons when given to competing strains. Here, we develop an ecological model of bacterial warfare to understand the impacts of horizontal gene transfer. Our model predicts that weapon gene transfer from an attacker to a target strain is possible, but will typically occur at a low rate such that transfer has a negligible impact on competition outcomes. We tested the model empirically using a transmissible plasmid encoding colicin E2, a potent antibacterial toxin produced by Escherichia coli. As predicted by the model, we find that toxin plasmid transfer is feasible during warfare, but the resulting transconjugants remain rare. However, exploring the model further reveals realistic conditions where transfer is predicted to have major impacts. Specifically, the model predicts that whenever competing strains have access to unique nutrients, transconjugants can proliferate and reach high abundances. In support of these predictions, short- and long-term experiments show that transconjugants can thrive when nutrient competition is relaxed. Our work shows how horizontal gene transfer can reshape bacterial warfare in a way that benefits a weapon gene and strains that receive it. Interestingly, we also find that there is little cost to a strain that transfers a weapon gene, which is expected to further enable the horizontal gene transfer of molecular weapons.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003095"},"PeriodicalIF":9.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of the nucleolar RNA exosome facilitates adaptation to starvation. 抑制核仁RNA外泌体有助于适应饥饿。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-21 DOI: 10.1371/journal.pbio.3003190

Xi Feng, Xiaoman Wang, Shouhong Guang, Shanshan Pang, Haiqing Tang

引用次数: 0

Correction: Genome size influences plant growth and biodiversity responses to nutrient fertilization in diverse grassland communities. 更正：基因组大小影响不同草地群落植物生长和生物多样性对养分施肥的响应。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-20 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003195

Joseph A Morton, Carlos Alberto Arnillas, Lori Biedermann, Elizabeth T Borer, Lars A Brudvig, Yvonne M Buckley, Marc W Cadotte, Kendi Davies, Ian Donohue, Anne Ebeling, Nico Eisenhauer, Catalina Estrada, Sylvia Haider, Yann Hautier, Anke Jentsch, Holly Martinson, Rebecca L McCulley, Xavier Raynaud, Christiane Roscher, Eric W Seabloom, Carly J Stevens, Katerina Vesela, Alison Wallace, Ilia J Leitch, Andrew R Leitch, Erika I Hersch-Green

引用次数: 0