PLoS Biology最新文献_第2页

TiME for a change: The tumor microenvironment as the missing piece in cancer therapeutics. 是时候改变了：肿瘤微环境是癌症治疗中缺失的一块。

IF 7.2 1区生物学

PLoS Biology Pub Date : 2025-07-24 eCollection Date: 2025-07-01 DOI: 10.1371/journal.pbio.3003276

Jeremy Mo, Hanyun Zhang, Alexander Swarbrick

引用次数: 0

Phase separation of a PKA type I regulatory subunit regulates β-cell function through cAMP compartmentalization. PKA I型调控亚基的相分离通过cAMP区隔化调节β细胞功能。

IF 7.2 1区生物学

PLoS Biology Pub Date : 2025-07-24 eCollection Date: 2025-07-01 DOI: 10.1371/journal.pbio.3003262

Ha Neul Lee, Julia C Hardy, Emily H Pool, Jin-Fan Zhang, Su Hyun Kim, William F Buhl, Jessica G H Bruystens, Sohum Mehta, Susan S Taylor, Jin Zhang

{"title":"Phase separation of a PKA type I regulatory subunit regulates β-cell function through cAMP compartmentalization.","authors":"Ha Neul Lee, Julia C Hardy, Emily H Pool, Jin-Fan Zhang, Su Hyun Kim, William F Buhl, Jessica G H Bruystens, Sohum Mehta, Susan S Taylor, Jin Zhang","doi":"10.1371/journal.pbio.3003262","DOIUrl":"10.1371/journal.pbio.3003262","url":null,"abstract":"Cyclic adenosine monophosphate (cAMP), a ubiquitous second messenger, regulates a variety of cellular functions with high specificity. We previously showed that the type I regulatory subunit of cAMP-dependent protein kinase A (PKA), RIα, undergoes liquid-liquid phase separation (LLPS) to facilitate spatial compartmentalization of cAMP. However, how RIα LLPS regulates cellular function is largely unknown. Here, we identify the formation of RIα condensates in MIN6 β cells and reveal key roles for RIα LLPS in regulating β cell function. By combining CRISPR-based RIα knockout with an RIα mutant (Y122A) that exhibits defective cAMP-induced LLPS, we demonstrate that RIα LLPS drives cAMP compartmentalization to tune β cell Ca2+ and cAMP oscillation frequency, control insulin secretion, regulate CREB-mediated gene expression and prevent uncontrolled proliferation. Our data establish the Y122A mutant as a selective molecular tool for studying RIα LLPS and expand our understanding of the functional impact of LLPS-driven protein assemblies.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 7","pages":"e3003262"},"PeriodicalIF":7.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709622","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

Mediator complex subunit MED23 dampens antiviral innate immunity by restricting RIG-I expression. 中介复合物亚基MED23通过限制RIG-I表达抑制抗病毒先天免疫。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-07-24 DOI: 10.1371/journal.pbio.3003294

De-Fei Xiong, Yi-Yang Zhang, Zhi-Chao Wang, Yuan-Ming Zheng, Han-Qing Zhang, Gang Wang

{"title":"Mediator complex subunit MED23 dampens antiviral innate immunity by restricting RIG-I expression.","authors":"De-Fei Xiong, Yi-Yang Zhang, Zhi-Chao Wang, Yuan-Ming Zheng, Han-Qing Zhang, Gang Wang","doi":"10.1371/journal.pbio.3003294","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003294","url":null,"abstract":"The detection of cytosolic viral nucleic acids via pattern-recognition receptors (PRRs) activates multiple signaling pathways, leading to the production of interferons (IFNs), which are essential for host survival during viral infection. Precise control of PRR gene expression is crucial for maintaining immune homeostasis. Here, we showed that Mediator complex subunit 23 (Med23) is required for the precise production of the innate immune receptor RIG-I in response to RNA virus infection. Med23 deficiency markedly enhances the production of IFN-I, proinflammatory cytokines, and IFN-stimulated genes (ISGs) in both multiple cell lines (MEFs, RAW264.7 cells, and HeLa cells) and mouse primary macrophages (bone marrow-derived macrophages [BMDMs] and peritoneal macrophages [PEMs]) infected with RNA virus VSV or stimulated with poly(I:C). Myeloid-specific Med23 knockout mice were generated to test the critical role of Med23 in host resistance to VSV infection in vivo. Mechanistically, Med23 interacts with the transcription factor forkhead box O3 (Foxo3) to negatively regulate RIG-I, thereby modulating IFN-I signaling. Collectively, these findings elucidate a previously unrecognized role of Med23 as a gatekeeper of the RIG-I-mediated antiviral innate immune response and suggest a potential target for controlling viral infection.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 7","pages":"e3003294"},"PeriodicalIF":9.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709621","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

Regulation of working memory switches from striatal dopamine D2-receptor to D1-receptor neurons under high cognitive load. 高认知负荷下工作记忆的调节从纹状体多巴胺d2受体神经元切换到d1受体神经元。

IF 7.2 1区生物学

PLoS Biology Pub Date : 2025-07-24 eCollection Date: 2025-07-01 DOI: 10.1371/journal.pbio.3003289

Xing-Jun Chen, Fei Li, Xinyue Zhao, Long Chen, Jin Xue, Zhimo Yao, Zuobin Gan, Xiaoyue Lian, Zhenghao Liu, Luyao Tong, Qingshan Yan, Linan Qiu, Qin Wang, Jiang-Fan Chen, Zhihui Li

{"title":"Regulation of working memory switches from striatal dopamine D2-receptor to D1-receptor neurons under high cognitive load.","authors":"Xing-Jun Chen, Fei Li, Xinyue Zhao, Long Chen, Jin Xue, Zhimo Yao, Zuobin Gan, Xiaoyue Lian, Zhenghao Liu, Luyao Tong, Qingshan Yan, Linan Qiu, Qin Wang, Jiang-Fan Chen, Zhihui Li","doi":"10.1371/journal.pbio.3003289","DOIUrl":"10.1371/journal.pbio.3003289","url":null,"abstract":"Working memory (WM) is a fundamental cognitive function crucial adaptive behavior. The intricate interplay between the frontal cortex and striatum in governing WM maintenance and updating remains a central question. In this study, we employed optogenetics to demonstrate that inhibiting both dorsomedial striatum (DMS) D1R- and D2R-neurons enhances WM, while their activation impairs it across T-maze and operant-based delayed-non-match-to-place (DNMTP) paradigms in mice. Notably, these neurons selectively modulate WM maintenance and retrieval, with no impact on encoding. Analysis through signal detection theory (SDT) revealed specific regulation of WM signal detection sensitivity, with no alterations in motivational or motor states during the operant DNMTP task. Interestingly, DMS D2R-neurons govern WM regulation under low cognitive load, switching to D1R-neurons as cognitive load increases. Activation of DMS D1R-neurons during the delay phase severely impairs WM under high cognitive load, a deficit rescued by optogenetic inhibition of dopaminergic neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), or dopaminergic terminals in DMS. Additionally, treatment with the D1R antagonist SCH39166, but not the D2R antagonist Sulpiride mitigates these impairments. Collectively, our findings propose a \"relay\" model wherein cognitive load-dependent WM control switches from DMS D2R- to D1R-neurons, offering nuanced, complementary, and inhibitory regulation of WM maintenance and retrieval. This study suggests potential strategies to enhance WM by promoting a suppressive state in DMS and to increase WM capacity through specific modulation of DMS D1R-neurons.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 7","pages":"e3003289"},"PeriodicalIF":7.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709623","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

Challenges and opportunities for the next generation of computational tumor models. 下一代计算肿瘤模型的挑战与机遇。

IF 7.2 1区生物学

PLoS Biology Pub Date : 2025-07-23 eCollection Date: 2025-07-01 DOI: 10.1371/journal.pbio.3003269

Lance L Munn, Rakesh K Jain

引用次数: 0

Legionella effector LpPIP recruits protein phosphatase 1 to the mitochondria to induce dephosphorylation of outer membrane proteins. 军团菌效应物LpPIP向线粒体招募蛋白磷酸酶1，诱导外膜蛋白去磷酸化。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-07-23 DOI: 10.1371/journal.pbio.3003261

Kai-Qi Yek, Evie Hodgson, Ching-Seng Ang, Catherine S Palmer, Ann E Frazier, Hayley J Newton, Diana Stojanovski

{"title":"Legionella effector LpPIP recruits protein phosphatase 1 to the mitochondria to induce dephosphorylation of outer membrane proteins.","authors":"Kai-Qi Yek, Evie Hodgson, Ching-Seng Ang, Catherine S Palmer, Ann E Frazier, Hayley J Newton, Diana Stojanovski","doi":"10.1371/journal.pbio.3003261","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003261","url":null,"abstract":"Legionella pneumophila utilizes a type IVB secretion system (T4SS) to translocate over 300 effector proteins into host cells, hijacking cellular processes, including those within the mitochondrion. Currently, no Legionella effectors have been identified at the mitochondrial outer membrane, a critical interface between the organelle and the rest of the cell. We screened the Legionella effector repertoire for features of mitochondrial tail-anchored (TA) proteins and identified four putative TA effectors. Among them, LpPIP (Lpg1625) localizes to the mitochondrial outer membrane and interacts with all three isoforms of protein phosphatase 1 (PP1) via an RVxF motif. LpPIP functions as a PP1-interacting protein (PIP) as PP1 remains catalytically active upon interaction with LpPIP to the dephosphorylate mitochondrial outer membrane proteins. Altering the TA signature to direct LpPIP to the ER induces ER-recruitment of PP1 and dephosphorylation of ER-resident proteins, indicating that LpPIP controls PP1 localization and not substrate specificity. This study uncovers a novel pathogen-mediated strategy to modulate PP1 and manipulate the host cell phosphoproteome.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 7","pages":"e3003261"},"PeriodicalIF":9.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700184","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

Natural sounds can be reconstructed from human neuroimaging data using deep neural network representation. 利用深度神经网络表征，可以从人类神经成像数据重构自然声音。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-07-23 DOI: 10.1371/journal.pbio.3003293

Jong-Yun Park, Mitsuaki Tsukamoto, Misato Tanaka, Yukiyasu Kamitani

{"title":"Natural sounds can be reconstructed from human neuroimaging data using deep neural network representation.","authors":"Jong-Yun Park, Mitsuaki Tsukamoto, Misato Tanaka, Yukiyasu Kamitani","doi":"10.1371/journal.pbio.3003293","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003293","url":null,"abstract":"Reconstruction of perceptual experiences from brain activity offers a unique window into how population neural responses represent sensory information. Although decoding visual content from functional MRI (fMRI) has seen significant success, reconstructing arbitrary sounds remains challenging due to the fine temporal structure of auditory signals and the coarse temporal resolution of fMRI. Drawing on the hierarchical auditory features of deep neural networks (DNNs) with progressively larger time windows and their neural activity correspondence, we introduce a method for sound reconstruction that integrates brain decoding of DNN features and an audio-generative model. DNN features decoded from auditory cortical activity outperformed spectrotemporal and modulation-based features, enabling perceptually plausible reconstructions across diverse sound categories. Behavioral evaluations and objective measures confirmed that these reconstructions preserved short-term spectral and perceptual properties, capturing the characteristic timbre of speech, animal calls, and musical instruments, while the reconstructed sounds did not reproduce longer temporal sequences with fidelity. Leave-category-out analyses indicated that the method generalizes across sound categories. Reconstructions at higher DNN layers and from early auditory regions revealed distinct contributions to decoding performance. Applying the model to a selective auditory attention (\"cocktail party\") task further showed that reconstructions reflected the attended sound more strongly than the unattended one in some of the subjects. Despite its inability to reconstruct exact temporal sequences, which may reflect the limited temporal resolution of fMRI, our framework demonstrates the feasibility of mapping brain activity to auditory experiences-a step toward more comprehensive understanding and reconstruction of internal auditory representations.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 7","pages":"e3003293"},"PeriodicalIF":9.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700185","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

Arthropod biodiversity loss from nitrogen deposition is buffered by natural and semi-natural habitats. 自然和半自然生境对氮沉降造成的节肢动物生物多样性损失有缓冲作用。

IF 7.2 1区生物学

PLoS Biology Pub Date : 2025-07-22 eCollection Date: 2025-07-01 DOI: 10.1371/journal.pbio.3003285

Shunxiang Fan, Tim Newbold, Jan C Axmacher, Charlotte L Outhwaite, Yi Zou, Zhenrong Yu, Yunhui Liu

{"title":"Arthropod biodiversity loss from nitrogen deposition is buffered by natural and semi-natural habitats.","authors":"Shunxiang Fan, Tim Newbold, Jan C Axmacher, Charlotte L Outhwaite, Yi Zou, Zhenrong Yu, Yunhui Liu","doi":"10.1371/journal.pbio.3003285","DOIUrl":"10.1371/journal.pbio.3003285","url":null,"abstract":"Nitrogen (N) deposition is known to strongly modify biogeochemical cycles and trophic interactions, in turn altering ecosystem functioning and plant diversity around the globe. However, our understanding of N deposition effects on arthropod diversity remains limited. Here, we investigate how N deposition impacts the diversity of arthropods by combining biodiversity data from the PREDICTS database with data on global N deposition and land cover using mixed-effects models. We then explore the potential for semi-natural and natural habitats ('SNH') to buffer against potential N deposition-linked biodiversity losses. N deposition has a negative effect on arthropod biodiversity. Both, species richness and abundance are significantly reduced in areas of high levels of N deposition when compared to areas of low N deposition, with responses varying across different land-use types. The strongest negative effects of N deposition on arthropod diversity were observed in locations where the local land use entails the least anthropogenic modification. At the same time, with the exception of cropland-dominated landscapes, increases in the amount of SNH in the surrounding landscape reduced arthropod biodiversity losses associated with N deposition. We conclude that SNH can play an important role in mitigating the negative effects of N deposition on arthropod diversity, with the conservation and creation of these habitats promoting arthropod diversity even under high levels of N deposition.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 7","pages":"e3003285"},"PeriodicalIF":7.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12282910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692183","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

Systematic screen uncovers regulator contributions to chemical cues in Escherichia coli. 系统筛选揭示了调节剂对大肠杆菌化学线索的贡献。

IF 7.2 1区生物学

PLoS Biology Pub Date : 2025-07-22 eCollection Date: 2025-07-01 DOI: 10.1371/journal.pbio.3003260

Christoph Binsfeld, Roberto Olayo-Alarcon, Lucía Pérez Jiménez, Morgane Wartel, Mara Stadler, André Mateus, Christian Müller, Ana Rita Brochado

{"title":"Systematic screen uncovers regulator contributions to chemical cues in Escherichia coli.","authors":"Christoph Binsfeld, Roberto Olayo-Alarcon, Lucía Pérez Jiménez, Morgane Wartel, Mara Stadler, André Mateus, Christian Müller, Ana Rita Brochado","doi":"10.1371/journal.pbio.3003260","DOIUrl":"10.1371/journal.pbio.3003260","url":null,"abstract":"In Gram-negative bacteria, the uptake and export of a wide range of molecules, including antibiotics, is facilitated by porins and efflux pumps. Because of their role in regulating small molecule permeability of the outer and inner membrane, these transport machineries are tightly regulated at the transcriptional and post-transcriptional levels. However, regulation of transport by external chemical cues remains poorly understood. Here we investigated transcriptional regulation of three prominent transporter genes in Escherichia coli across 94 defined chemical cues, and simultaneously mapped the contributions of the key regulators MarA, SoxS and Rob to promoter activity. One third of all tested compounds triggered transcriptional changes, the majority of which were previously unknown. Importantly, we exposed main drivers of transport control in E. coli, e.g., bacteriostatic but not bactericidal antibiotics trigger the expression of efflux pumps, and Rob contributes to ~1/3 of all measured transcriptional changes, thereby emerging as a more prominent regulator of transport than previously thought. We showcase the potential of our resource by elucidating the molecular mechanism of antibiotic antagonisms with widely consumed caffeine in E. coli. Altogether, our analysis provides a quantitative overview of how different regulators orchestrate the transcriptional response of major transport determinants to environmental chemical cues.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 7","pages":"e3003260"},"PeriodicalIF":7.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12282887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692184","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

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 7.2 1区生物学

PLoS Biology Pub Date : 2025-07-21 eCollection Date: 2025-07-01 DOI: 10.1371/journal.pbio.3003241

Pavanjit Chaggar, Jacob W 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 W 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":"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":7.2,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303394/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0