PLoS Biology最新文献

Personalised regional modelling predicts tau progression in the human brain. 个性化的区域模型预测了人脑中tau蛋白的发展。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-07-21 DOI: 10.1371/journal.pbio.3003241

Pavanjit Chaggar, Jacob Vogel, Alexa Pichet Binette, Travis B Thompson, Olof Strandberg, Niklas Mattsson-Carlgren, Linda Karlsson, Erik Stomrud, Saad Jbabdi, Stefano Magon, Gregory Klein, Oskar Hansson, Alain Goriely

{"title":"Personalised regional modelling predicts tau progression in the human brain.","authors":"Pavanjit Chaggar, Jacob Vogel, Alexa Pichet Binette, Travis B Thompson, Olof Strandberg, Niklas Mattsson-Carlgren, Linda Karlsson, Erik Stomrud, Saad Jbabdi, Stefano Magon, Gregory Klein, Oskar Hansson, Alain Goriely","doi":"10.1371/journal.pbio.3003241","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003241","url":null,"abstract":"Aggregation of the hyperphosphorylated tau protein is a central driver of Alzheimer's disease, and its accumulation exhibits a rich spatiotemporal pattern that unfolds during the course of the disease, sequentially progressing through the brain across axonal connections. It is unclear how this spatiotemporal process is orchestrated, namely, to what extent the spread of pathologic tau is governed by transport between brain regions, local production, or both. To address this, we develop a mechanistic model from tau PET data to describe tau dynamics along the Alzheimer's disease timeline. Our analysis reveals longitudinal changes in production and transport dynamics in two independent cohorts, with subjects in the early stage of the disease exhibiting transport-dominated spread, consistent with an initial spread of pathological tau seeds, and subjects in the late stage disease characterized primarily by local tau production. Further, we demonstrate that the model can predict accurately subject-specific longitudinal tau accumulation at the regional level, potentially providing a new clinical tool to monitor and classify patient disease progression.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 7","pages":"e3003241"},"PeriodicalIF":9.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683521","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

A protein-specific priority code in presequences determines the efficiency of mitochondrial protein import. 序列中的蛋白质特异性优先编码决定了线粒体蛋白质进口的效率。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-07-21 DOI: 10.1371/journal.pbio.3003298

Saskia Rödl, Yasmin Hoffman, Felix Jung, Annika Egeler, Annika Nutz, Oliver Šimončík, Martin Jung, Markus Räschle, Petr Muller, Zuzana Storchova, Timo Mühlhaus, Johannes M Herrmann

{"title":"A protein-specific priority code in presequences determines the efficiency of mitochondrial protein import.","authors":"Saskia Rödl, Yasmin Hoffman, Felix Jung, Annika Egeler, Annika Nutz, Oliver Šimončík, Martin Jung, Markus Räschle, Petr Muller, Zuzana Storchova, Timo Mühlhaus, Johannes M Herrmann","doi":"10.1371/journal.pbio.3003298","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003298","url":null,"abstract":"The biogenesis of mitochondria relies on the import of hundreds of different precursor proteins from the cytosol. Most of these proteins are synthesized with N-terminal presequences which serve as mitochondrial targeting signals. Presequences consistently form amphipathic helices, but they considerably differ with respect to their primary structure and length. Here we show that presequences can be classified into seven different groups based on their specific features. Using a test set of different presequences, we observed that group A presequences endow precursor proteins with improved in vitro import characteristics. We developed IQ-Compete (for Import and de-Quenching Competition assay), a novel assay based on fluorescence de-quenching, to monitor the import efficiencies of mitochondrial precursors in vivo. With this assay, we confirmed the increased import competence of group A presequences. Using mass spectrometry, we found that the presequence of the group A protein Oxa1 specifically recruits the tetratricopeptide repeat (TPR)-containing protein TOMM34 to the cytosolic precursor protein. TOMM34, and the structurally related yeast co-chaperone Cns1, apparently serve as a presequence-specific targeting factor which increases the import efficiency of a specific subset of mitochondrial precursor proteins. Our results suggest that presequences contain a protein-specific priority code that encrypts the targeting mechanism of individual mitochondrial precursor proteins.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 7","pages":"e3003298"},"PeriodicalIF":9.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683519","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

Can the tumor neural niche be targeted to re-program cancer? 肿瘤神经龛能否成为癌症重编程的靶点？

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-07-21 eCollection Date: 2025-07-01 DOI: 10.1371/journal.pbio.3003266

Erica K Sloan, Joo Sang Lee

引用次数: 0

Applying multilevel selection to understand cancer evolution and progression. 应用多层次选择来理解癌症的进化和进展。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-07-18 DOI: 10.1371/journal.pbio.3003290

Lucie Laplane, Anaïs Lamoureux, Harley I Richker, Gissel Marquez Alcaraz, Angelo Fortunato, Zachary Shaffer, Athena Aktipis, Paul S Mischel, Anya Plutynski, Jeffrey P Townsend, Carlo C Maley

引用次数: 0

Penguins exploit tidal currents for efficient navigation and opportunistic foraging. 企鹅利用潮流进行有效的导航和觅食。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-07-17 eCollection Date: 2025-07-01 DOI: 10.1371/journal.pbio.3002981

Richard M Gunner, Flavio Quintana, Mariano H Tonini, Mark D Holton, Ken Yoda, Margaret C Crofoot, Rory P Wilson

{"title":"Penguins exploit tidal currents for efficient navigation and opportunistic foraging.","authors":"Richard M Gunner, Flavio Quintana, Mariano H Tonini, Mark D Holton, Ken Yoda, Margaret C Crofoot, Rory P Wilson","doi":"10.1371/journal.pbio.3002981","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002981","url":null,"abstract":"Animals navigating in fluid environments often face forces from wind or water currents that challenge travel efficiency and route accuracy. We investigated how 27 Magellanic penguins (Spheniscus magellanicus) adapt their navigation strategies to return to their colony amid regional tidal ocean currents. Using GPS-enhanced dead-reckoning loggers and high-resolution ocean current data, we reconstructed penguin travel vectors during foraging trips to assess their responses to variable currents during their colony-bound movements. By integrating estimates of energy costs and prey pursuits, we found that birds balanced direct navigation with current-driven drift: in calm currents, they maintained precise line-of-sight headings to their colony. In stronger currents, they aligned their return with lateral flows, which increased travel distance, but at reduced energy costs, and provided them with increased foraging opportunities. Since the lateral tidal currents always reversed direction over the course of return paths, the penguins' return paths were consistently S-shaped but still resulted in the birds returning efficiently to their colonies. These findings suggest that Magellanic penguins can sense current drift and use it to enhance energy efficiency by maintaining overall directional accuracy while capitalizing on foraging opportunities.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 7","pages":"e3002981"},"PeriodicalIF":9.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144660805","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

Influenza A virus induces PI4P production at the endoplasmic reticulum in an ATG16L1-dependent manner to promote the egress of viral ribonucleoproteins. 甲型流感病毒以atg16l1依赖的方式诱导内质网产生PI4P，促进病毒核糖核蛋白的输出。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-07-16 DOI: 10.1371/journal.pbio.3002958

Carla Alemany, Juliane Da Graça, Quentin Giai Gianetto, Maud Dupont, Sylvain Paisant, Thibaut Douché, Catherine Isel, Cédric Delevoye, Lydia Danglot, Mariette Matondo, Etienne Morel, Jean-Baptiste Brault, Nadia Naffakh

{"title":"Influenza A virus induces PI4P production at the endoplasmic reticulum in an ATG16L1-dependent manner to promote the egress of viral ribonucleoproteins.","authors":"Carla Alemany, Juliane Da Graça, Quentin Giai Gianetto, Maud Dupont, Sylvain Paisant, Thibaut Douché, Catherine Isel, Cédric Delevoye, Lydia Danglot, Mariette Matondo, Etienne Morel, Jean-Baptiste Brault, Nadia Naffakh","doi":"10.1371/journal.pbio.3002958","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002958","url":null,"abstract":"The genomic RNAs of influenza A viruses (IAVs) are replicated in the nucleus of infected cells in the form of viral ribonucleoproteins (vRNPs) before being exported to the cytoplasm. The small GTPase RAB11A is involved in the transport of vRNPs to the sites of viral assembly at the plasma membrane, but the molecular mechanisms involved remain largely unknown. Here we show that IAV infection remodels the architecture of the endoplasmic reticulum (ER) sheets, where vRNPs tend to accumulate in the absence of RAB11A. To decipher the interplay between RAB11A, vRNPs, and the ER, we investigated viral-induced perturbations of RAB11A proximity interactome. To this end, we generated cells stably expressing a TurboID-RAB11A fusion protein and performed biotin-based proximity labeling upon viral infection. We found that cellular regulators of phophatidylinositol-4-phosphate (PI4P) homeostasis, including the autophagic and stress response protein ATG16L1, are significantly enriched at the vicinity of RAB11A in infected cells. Infection induces an increase in cellular PI4P levels in an ATG16L1-dependent manner, while ATG16L1 relocalizes to ER membranes upon infection. Depletion of ATG16L1 decreases the co-distribution of vRNPs with PI4P punctae on ER membranes, and reduces the accumulation of vRNPs at the plasma membrane as well as the production of IAV infectious particles. Our data extend to IAVs the notion that viruses can modulate the metabolism and localization of phosphoinositides to control host membrane dynamics and point to the ER as an essential platform for vRNP transport. They provide evidence for a pivotal role of ATG16L1 in regulating the identity of endomembranes and coordinating RAB11A and PI4P-enriched membranes to ensure delivery of vRNPs to the plasma membrane.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 7","pages":"e3002958"},"PeriodicalIF":9.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651004","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

Long-term musical training can protect against age-related upregulation of neural activity in speech-in-noise perception. 长期的音乐训练可以防止与年龄相关的噪音中言语感知的神经活动上调。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-07-15 eCollection Date: 2025-07-01 DOI: 10.1371/journal.pbio.3003247

Lei Zhang, Bernhard Ross, Yi Du, Claude Alain

{"title":"Long-term musical training can protect against age-related upregulation of neural activity in speech-in-noise perception.","authors":"Lei Zhang, Bernhard Ross, Yi Du, Claude Alain","doi":"10.1371/journal.pbio.3003247","DOIUrl":"10.1371/journal.pbio.3003247","url":null,"abstract":"During cognitive tasks, older adults often show increased frontoparietal neural activity and functional connectivity. Cognitive reserve accrued from positive life choices like long-term musical training can provide additional neural resources to help cope with the effect of aging. However, the relationship between cognitive reserve and upregulated neural activity in older adults remains poorly understood. In this study, we measured brain activity using functional magnetic resonance imaging during a speech-in-noise task and assessed whether cognitive reserve accumulated from long-term musical training bolsters or holds back age-related increase in neural activity. Older musicians exhibited less upregulation of task-induced functional connectivity than older non-musicians in auditory dorsal regions, which predicted better behavioral performance in older musicians. Furthermore, older musicians demonstrated more youth-like spatial patterns of functional connectivity, as compared to older non-musicians. Our findings show that cognitive reserve accrued through long-term music training holds back age-related neural recruitment during speech-in-noise perception and enlighten the intricate interplay between cognitive reserve and age-related upregulated activity during cognitive tasks.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 7","pages":"e3003247"},"PeriodicalIF":9.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12262870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643944","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

Loss of Pol III repressor Maf1 in neurons promotes longevity by preventing the age-related decline in 5S rRNA and translation. 神经元中Pol III抑制因子Maf1的缺失通过阻止5S rRNA和翻译的年龄相关下降来促进寿命。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-07-15 eCollection Date: 2025-07-01 DOI: 10.1371/journal.pbio.3003250

Bowen Xu, Alexander Hull, Olivia N M Hill, Naja Kobal, Enric Ureña, Linda Partridge, Nazif Alic

{"title":"Loss of Pol III repressor Maf1 in neurons promotes longevity by preventing the age-related decline in 5S rRNA and translation.","authors":"Bowen Xu, Alexander Hull, Olivia N M Hill, Naja Kobal, Enric Ureña, Linda Partridge, Nazif Alic","doi":"10.1371/journal.pbio.3003250","DOIUrl":"10.1371/journal.pbio.3003250","url":null,"abstract":"Attenuating protein synthesis promotes longevity in multiple species. However, numerous studies indicate that aging drives a decrease in protein synthetic capacity. These observations hint at potential, unexplored benefits of stimulating protein synthesis in old age. In this work, we focus on Maf1, a repressor of protein synthesis genes transcribed by RNA Polymerase (Pol) III, such as the 5S rRNA and tRNAs, and its role in aging. We show that the knockdown of Maf1 extends lifespan in Drosophila. Maf1 limits longevity specifically from adult neurons in both female and male fruit flies. In older females, adult neuron-specific knockdown of Maf1 improves neuromuscular function as well as the function of a distal organ, the gut. We find that the extension of female lifespan upon Maf1 knockdown requires Pol III initiation on the 5S rRNA. Indeed, reducing neuronal Maf1 activity rescues the age-related decline in 5S expression and protein synthesis in the brain of female flies. Hence, our findings show that stimulating neuronal protein synthesis can promote healthy aging.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 7","pages":"e3003250"},"PeriodicalIF":9.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12262857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643945","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

A toolkit for mapping cell identities in relation to neighbors reveals conserved patterning of neuromesodermal progenitor populations. 一个用于绘制细胞身份与邻居关系的工具包揭示了神经中胚层祖细胞群体的保守模式。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-07-15 DOI: 10.1371/journal.pbio.3003244

Matthew French, Rosa P Migueles, Alexandra Neaverson, Aishani Chakraborty, Tom Pettini, Benjamin Steventon, Erik Clark, J Kim Dale, Guillaume Blin, Valerie Wilson, Sally Lowell

{"title":"A toolkit for mapping cell identities in relation to neighbors reveals conserved patterning of neuromesodermal progenitor populations.","authors":"Matthew French, Rosa P Migueles, Alexandra Neaverson, Aishani Chakraborty, Tom Pettini, Benjamin Steventon, Erik Clark, J Kim Dale, Guillaume Blin, Valerie Wilson, Sally Lowell","doi":"10.1371/journal.pbio.3003244","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003244","url":null,"abstract":"Patterning of cell fates is central to embryonic development, tissue homeostasis, and disease. Quantitative analysis of patterning reveals the logic by which cell-cell interactions orchestrate changes in cell fate. However, it is challenging to quantify patterning when graded changes in identity occur over complex 4D trajectories, or where different cell states are intermingled. Furthermore, comparing patterns across multiple individual embryos, tissues, or organoids is difficult because these often vary in shape and size. This problem is further exacerbated when comparing patterning between species. Here we present a toolkit of computational approaches to tackle these problems. These strategies are based on measuring properties of each cell in relation to the properties of its neighbors to quantify patterning, and on using embryonic landmarks in order to compare these patterns between embryos. We perform detailed neighbor-analysis of the caudal lateral epiblast of E8.5 mouse embryos, revealing local patterning in emergence of early mesoderm cells that is sensitive to inhibition of Notch activity. We extend this toolkit to compare mouse and chick embryos, revealing conserved 3D patterning of the caudal-lateral epiblast that scales across an order of magnitude difference in size between these two species. We also examine 3D patterning of gene expression boundaries across the length of Drosophila embryos. We present a flexible approach to examine the reproducibility of patterning between individuals, to measure phenotypic changes in patterning after experimental manipulation, and to compare of patterning across different scales and tissue architectures.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 7","pages":"e3003244"},"PeriodicalIF":9.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643942","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

A comprehensive atlas of full-length Arabidopsis eccDNA populations identifies their genomic origins and epigenetic regulation. 一个完整的全长拟南芥eccDNA种群图谱确定了它们的基因组起源和表观遗传调控。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-07-15 eCollection Date: 2025-07-01 DOI: 10.1371/journal.pbio.3003275

Syed Shan-E-Ali Zaidi, Sara Shakir, Hanne De Kort, Devang Mehta, Vu Nguyen, Ruben Gutzat, Hervé Vanderschuren

{"title":"A comprehensive atlas of full-length Arabidopsis eccDNA populations identifies their genomic origins and epigenetic regulation.","authors":"Syed Shan-E-Ali Zaidi, Sara Shakir, Hanne De Kort, Devang Mehta, Vu Nguyen, Ruben Gutzat, Hervé Vanderschuren","doi":"10.1371/journal.pbio.3003275","DOIUrl":"10.1371/journal.pbio.3003275","url":null,"abstract":"Extrachromosomal circular DNA (eccDNA) has been described in several eukaryotic species and has been shown to impact phenomena as diverse as cancer and herbicide tolerance. EccDNA is thought to arise mainly through transposable element (TE) mobilization. Because studies based on short-read sequencing cannot efficiently identify full-length eccDNA forms generated from TEs, we employed the CIDER-Seq pipeline based on long-read sequencing, to obtain full-length eccDNAs from Arabidopsis. The generated eccDNA datasets identified centromeric/pericentromeric regions as hotspots of eccDNAs with several eccDNA molecules originating from Helitron and LTR TEs. To investigate the role of epigenetic marks on TE-derived eccDNA biogenesis, we studied Arabidopsis methylation mutants dcl3, rdr6, ros1, and ddm1. Contrasting the TE-suppression previously reported in the hypermethylated ros1 mutants, we identified activation of TEs in ros1, specifically of LTR/Gypsy TEs. An enrichment of LTR/Copia elements was identified in actively dividing calli and the shoot apical meristem (SAM). Uncharacterized \"variable TEs\" with high eccDNA and expression were identified in the SAM, including ATCOPIA58. Together, our study reveals the genomic origins of eccDNAs and delineates the link between epigenetic regulation, transposon mobilization, and eccDNA biogenesis.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 7","pages":"e3003275"},"PeriodicalIF":9.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643941","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