PLoS Biology最新文献

LXR-dependent enhancer activation regulates the temporal organization of the liver's response to refeeding leading to lipogenic gene overshoot. 依赖于 LXR 的增强子激活调节了肝脏对再进食反应的时间组织，导致致脂基因超调。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-09-06 eCollection Date: 2024-09-01 DOI: 10.1371/journal.pbio.3002735

Noga Korenfeld, Tali Gorbonos, Maria C Romero Florian, Dan Rotaro, Dana Goldberg, Talia Radushkevitz-Frishman, Meital Charni-Natan, Meirav Bar-Shimon, Carolyn L Cummins, Ido Goldstein

{"title":"LXR-dependent enhancer activation regulates the temporal organization of the liver's response to refeeding leading to lipogenic gene overshoot.","authors":"Noga Korenfeld, Tali Gorbonos, Maria C Romero Florian, Dan Rotaro, Dana Goldberg, Talia Radushkevitz-Frishman, Meital Charni-Natan, Meirav Bar-Shimon, Carolyn L Cummins, Ido Goldstein","doi":"10.1371/journal.pbio.3002735","DOIUrl":"10.1371/journal.pbio.3002735","url":null,"abstract":"Transitions between the fed and fasted state are common in mammals. The liver orchestrates adaptive responses to feeding/fasting by transcriptionally regulating metabolic pathways of energy usage and storage. Transcriptional and enhancer dynamics following cessation of fasting (refeeding) have not been explored. We examined the transcriptional and chromatin events occurring upon refeeding in mice, including kinetic behavior and molecular drivers. We found that the refeeding response is temporally organized with the early response focused on ramping up protein translation while the later stages of refeeding drive a bifurcated lipid synthesis program. While both the cholesterol biosynthesis and lipogenesis pathways were inhibited during fasting, most cholesterol biosynthesis genes returned to their basal levels upon refeeding while most lipogenesis genes markedly overshoot above pre-fasting levels. Gene knockout, enhancer dynamics, and ChIP-seq analyses revealed that lipogenic gene overshoot is dictated by LXRα. These findings from unbiased analyses unravel the mechanism behind the long-known phenomenon of refeeding fat overshoot.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11379474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143435","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

Syllable processing is organized in discrete subregions of the human superior temporal gyrus. 人类颞上回的离散亚区组织了音节处理。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-09-06 DOI: 10.1371/journal.pbio.3002774

Daniel R Cleary, Youngbin Tchoe, Andrew Bourhis, Charles W Dickey, Brittany Stedelin, Mehran Ganji, Sang Heon Lee, Jihweean Lee, Dominic A Siler, Erik C Brown, Burke Q Rosen, Erik Kaestner, Jimmy C Yang, Daniel J Soper, Seunggu Jude Han, Angelique C Paulk, Sydney S Cash, Ahmed M Raslan, Shadi A Dayeh, Eric Halgren

{"title":"Syllable processing is organized in discrete subregions of the human superior temporal gyrus.","authors":"Daniel R Cleary, Youngbin Tchoe, Andrew Bourhis, Charles W Dickey, Brittany Stedelin, Mehran Ganji, Sang Heon Lee, Jihweean Lee, Dominic A Siler, Erik C Brown, Burke Q Rosen, Erik Kaestner, Jimmy C Yang, Daniel J Soper, Seunggu Jude Han, Angelique C Paulk, Sydney S Cash, Ahmed M Raslan, Shadi A Dayeh, Eric Halgren","doi":"10.1371/journal.pbio.3002774","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002774","url":null,"abstract":"Modular organization at approximately 1 mm scale could be fundamental to cortical processing, but its presence in human association cortex is unknown. Using custom-built, high-density electrode arrays placed on the cortical surface of 7 patients undergoing awake craniotomy for tumor excision, we investigated receptive speech processing in the left (dominant) human posterior superior temporal gyrus. Responses to consonant-vowel syllables and noise-vocoded controls recorded with 1,024 channel micro-grids at 200 μm pitch demonstrated roughly circular domains approximately 1.7 mm in diameter, with sharp boundaries observed in 128 channel linear arrays at 50 μm pitch, possibly consistent with a columnar organization. Peak latencies to syllables in different modules were bimodally distributed centered at 252 and 386 ms. Adjacent modules were sharply delineated from each other by their distinct time courses and stimulus selectivity. We suggest that receptive language cortex may be organized in discrete processing modules.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143436","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

Centrosome amplification primes ovarian cancer cells for apoptosis and potentiates the response to chemotherapy. 中心体扩增可使卵巢癌细胞凋亡并增强对化疗的反应。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-09-05 DOI: 10.1371/journal.pbio.3002759

Frances Edwards, Giulia Fantozzi, Anthony Y Simon, Jean-Philippe Morretton, Aurelie Herbette, Andrea E Tijhuis, Rene Wardenaar, Stacy Foulane, Simon Gemble, Diana C J Spierings, Floris Foijer, Odette Mariani, Anne Vincent-Salomon, Sergio Roman-Roman, Xavier Sastre-Garau, Oumou Goundiam, Renata Basto

{"title":"Centrosome amplification primes ovarian cancer cells for apoptosis and potentiates the response to chemotherapy.","authors":"Frances Edwards, Giulia Fantozzi, Anthony Y Simon, Jean-Philippe Morretton, Aurelie Herbette, Andrea E Tijhuis, Rene Wardenaar, Stacy Foulane, Simon Gemble, Diana C J Spierings, Floris Foijer, Odette Mariani, Anne Vincent-Salomon, Sergio Roman-Roman, Xavier Sastre-Garau, Oumou Goundiam, Renata Basto","doi":"10.1371/journal.pbio.3002759","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002759","url":null,"abstract":"Centrosome amplification is a feature of cancer cells associated with chromosome instability and invasiveness. Enhancing chromosome instability and subsequent cancer cell death via centrosome unclustering and multipolar divisions is an aimed-for therapeutic approach. Here, we show that centrosome amplification potentiates responses to conventional chemotherapy in addition to its effect on multipolar divisions and chromosome instability. We perform single-cell live imaging of chemotherapy responses in epithelial ovarian cancer cell lines and observe increased cell death when centrosome amplification is induced. By correlating cell fate with mitotic behaviors, we show that enhanced cell death can occur independently of chromosome instability. We identify that cells with centrosome amplification are primed for apoptosis. We show they are dependent on the apoptotic inhibitor BCL-XL and that this is not a consequence of mitotic stresses associated with centrosome amplification. Given the multiple mechanisms that promote chemotherapy responses in cells with centrosome amplification, we assess such a relationship in an epithelial ovarian cancer patient cohort. We show that high centrosome numbers associate with improved treatment responses and longer overall survival. Our work identifies apoptotic priming as a clinically relevant consequence of centrosome amplification, expanding our understanding of this pleiotropic cancer cell feature.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141488","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

Keeping time: How musical training may boost cognition. 保持时间音乐训练如何提高认知能力

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-09-05 DOI: 10.1371/journal.pbio.3002810

M Florencia Assaneo, Fernando Lizcano-Cortés, Pablo Ripolles

引用次数: 0

A flexible loop in the paxillin LIM3 domain mediates its direct binding to integrin β subunits. paxillin LIM3 结构域中的柔性环介导其与整合素 β 亚基的直接结合。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-09-04 eCollection Date: 2024-09-01 DOI: 10.1371/journal.pbio.3002757

Timo Baade, Marcus Michaelis, Andreas Prestel, Christoph Paone, Nikolai Klishin, Marleen Herbinger, Laura Scheinost, Ruslan Nedielkov, Christof R Hauck, Heiko M Möller

{"title":"A flexible loop in the paxillin LIM3 domain mediates its direct binding to integrin β subunits.","authors":"Timo Baade, Marcus Michaelis, Andreas Prestel, Christoph Paone, Nikolai Klishin, Marleen Herbinger, Laura Scheinost, Ruslan Nedielkov, Christof R Hauck, Heiko M Möller","doi":"10.1371/journal.pbio.3002757","DOIUrl":"10.1371/journal.pbio.3002757","url":null,"abstract":"Integrins are fundamental for cell adhesion and the formation of focal adhesions (FA). Accordingly, these receptors guide embryonic development, tissue maintenance, and haemostasis but are also involved in cancer invasion and metastasis. A detailed understanding of the molecular interactions that drive integrin activation, FA assembly, and downstream signalling cascades is critical. Here, we reveal a direct association of paxillin, a marker protein of FA sites, with the cytoplasmic tails of the integrin β1 and β3 subunits. The binding interface resides in paxillin's LIM3 domain, where based on the NMR structure and functional analyses, a flexible, 7-amino acid loop engages the unstructured part of the integrin cytoplasmic tail. Genetic manipulation of the involved residues in either paxillin or integrin β3 compromises cell adhesion and motility of murine fibroblasts. This direct interaction between paxillin and the integrin cytoplasmic domain identifies an alternative, kindlin-independent mode of integrin outside-in signalling particularly important for integrin β3 function.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134183","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

High temperatures increase the virulence of Vibrio bacteria towards their coral host and competing bacteria via type VI secretion systems. 高温会增加弧菌通过 VI 型分泌系统对珊瑚宿主和竞争细菌的毒力。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-09-04 eCollection Date: 2024-09-01 DOI: 10.1371/journal.pbio.3002788

Weiquan Wang, Kaihao Tang, Xiaoxue Wang

引用次数: 0

The coral pathogen Vibrio coralliilyticus uses a T6SS to secrete a group of novel anti-eukaryotic effectors that contribute to virulence. 珊瑚病原体珊瑚弧菌（Vibrio coralliilyticus）利用 T6SS 分泌出一组新型抗真核生物效应物，这些效应物有助于增强其毒性。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-09-03 eCollection Date: 2024-09-01 DOI: 10.1371/journal.pbio.3002734

Shir Mass, Hadar Cohen, Ram Podicheti, Douglas B Rusch, Motti Gerlic, Blake Ushijima, Julia C van Kessel, Eran Bosis, Dor Salomon

{"title":"The coral pathogen Vibrio coralliilyticus uses a T6SS to secrete a group of novel anti-eukaryotic effectors that contribute to virulence.","authors":"Shir Mass, Hadar Cohen, Ram Podicheti, Douglas B Rusch, Motti Gerlic, Blake Ushijima, Julia C van Kessel, Eran Bosis, Dor Salomon","doi":"10.1371/journal.pbio.3002734","DOIUrl":"10.1371/journal.pbio.3002734","url":null,"abstract":"Vibrio coralliilyticus is a pathogen of coral and shellfish, leading to devastating economic and ecological consequences worldwide. Although rising ocean temperatures correlate with increased V. coralliilyticus pathogenicity, the specific molecular mechanisms and determinants contributing to virulence remain poorly understood. Here, we systematically analyzed the type VI secretion system (T6SS), a contact-dependent toxin delivery apparatus, in V. coralliilyticus. We identified 2 omnipresent T6SSs that are activated at temperatures in which V. coralliilyticus becomes virulent; T6SS1 is an antibacterial system mediating interbacterial competition, whereas T6SS2 mediates anti-eukaryotic toxicity and contributes to mortality during infection of an aquatic model organism, Artemia salina. Using comparative proteomics, we identified the T6SS1 and T6SS2 toxin arsenals of 3 V. coralliilyticus strains with distinct disease etiologies. Remarkably, T6SS2 secretes at least 9 novel anti-eukaryotic toxins comprising core and accessory repertoires. We propose that T6SSs differently contribute to V. coralliilyticus's virulence: T6SS2 plays a direct role by targeting the host, while T6SS1 plays an indirect role by eliminating competitors.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127113","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 dystroglycan-laminin-integrin axis coordinates cell shape remodeling in the developing Drosophila retina. 发育中果蝇视网膜中的肌冻蛋白-层粘连蛋白-整合素轴协调细胞形状重塑。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-09-03 DOI: 10.1371/journal.pbio.3002783

Rhian F Walther, Courtney Lancaster, Jemima J Burden, Franck Pichaud

{"title":"A dystroglycan-laminin-integrin axis coordinates cell shape remodeling in the developing Drosophila retina.","authors":"Rhian F Walther, Courtney Lancaster, Jemima J Burden, Franck Pichaud","doi":"10.1371/journal.pbio.3002783","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002783","url":null,"abstract":"Cell shape remodeling is a principal driver of epithelial tissue morphogenesis. While progress continues to be made in our understanding of the pathways that control the apical (top) geometry of epithelial cells, we know comparatively little about those that control cell basal (bottom) geometry. To examine this, we used the Drosophila ommatidium, which is the basic visual unit of the compound eye. The ommatidium is shaped as a hexagonal prism, and generating this 3D structure requires ommatidial cells to adopt specific apical and basal polygonal geometries. Using this model system, we find that generating cell type-specific basal geometries starts with patterning of the basal extracellular matrix, whereby Laminin accumulates at discrete locations across the basal surface of the retina. We find the Dystroglycan receptor complex (DGC) is required for this patterning by promoting localized Laminin accumulation at the basal surface of cells. Moreover, our results reveal that localized accumulation of Laminin and the DGC are required for directing Integrin adhesion. This induces cell basal geometry remodeling by anchoring the basal surface of cells to the extracellular matrix at specific, Laminin-rich locations. We propose that patterning of a basal extracellular matrix by generating discrete Laminin domains can direct Integrin adhesion to induce cell shape remodeling in epithelial morphogenesis.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127096","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

Phosphorylation of the DNA damage repair factor 53BP1 by ATM kinase controls neurodevelopmental programs in cortical brain organoids. ATM激酶对DNA损伤修复因子53BP1的磷酸化控制着大脑皮层器官组织的神经发育程序。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-09-03 DOI: 10.1371/journal.pbio.3002760

Bitna Lim, Yurika Matsui, Seunghyun Jung, Mohamed Nadhir Djekidel, Wenjie Qi, Zuo-Fei Yuan, Xusheng Wang, Xiaoyang Yang, Nina Connolly, Abbas Shirinifard Pilehroud, Haitao Pan, Fang Wang, Shondra M Pruett-Miller, Kanisha Kavdia, Vishwajeeth Pagala, Yiping Fan, Junmin Peng, Beisi Xu, Jamy C Peng

{"title":"Phosphorylation of the DNA damage repair factor 53BP1 by ATM kinase controls neurodevelopmental programs in cortical brain organoids.","authors":"Bitna Lim, Yurika Matsui, Seunghyun Jung, Mohamed Nadhir Djekidel, Wenjie Qi, Zuo-Fei Yuan, Xusheng Wang, Xiaoyang Yang, Nina Connolly, Abbas Shirinifard Pilehroud, Haitao Pan, Fang Wang, Shondra M Pruett-Miller, Kanisha Kavdia, Vishwajeeth Pagala, Yiping Fan, Junmin Peng, Beisi Xu, Jamy C Peng","doi":"10.1371/journal.pbio.3002760","DOIUrl":"10.1371/journal.pbio.3002760","url":null,"abstract":"53BP1 is a well-established DNA damage repair factor that has recently emerged to critically regulate gene expression for tumor suppression and neural development. However, its precise function and regulatory mechanisms remain unclear. Here, we showed that phosphorylation of 53BP1 at serine 25 by ATM is required for neural progenitor cell proliferation and neuronal differentiation in cortical brain organoids. Dynamic phosphorylation of 53BP1-serine 25 controls 53BP1 target genes governing neuronal differentiation and function, cellular response to stress, and apoptosis. Mechanistically, ATM and RNF168 govern 53BP1's binding to gene loci to directly affect gene regulation, especially at genes for neuronal differentiation and maturation. 53BP1 serine 25 phosphorylation effectively impedes its binding to bivalent or H3K27me3-occupied promoters, especially at genes regulating H3K4 methylation, neuronal functions, and cell proliferation. Beyond 53BP1, ATM-dependent phosphorylation displays wide-ranging effects, regulating factors in neuronal differentiation, cytoskeleton, p53 regulation, as well as key signaling pathways such as ATM, BDNF, and WNT during cortical organoid differentiation. Together, our data suggest that the interplay between 53BP1 and ATM orchestrates essential genetic programs for cell morphogenesis, tissue organization, and developmental pathways crucial for human cortical development.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127112","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

Hijackers, hitchhikers, or co-drivers? The mysteries of mobilizable genetic elements. 劫持者、搭便车者还是共同驾驶者？可移动遗传因子的奥秘。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-08-29 DOI: 10.1371/journal.pbio.3002796

Manuel Ares-Arroyo, Charles Coluzzi, Jorge A Moura de Sousa, Eduardo P C Rocha

{"title":"Hijackers, hitchhikers, or co-drivers? The mysteries of mobilizable genetic elements.","authors":"Manuel Ares-Arroyo, Charles Coluzzi, Jorge A Moura de Sousa, Eduardo P C Rocha","doi":"10.1371/journal.pbio.3002796","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002796","url":null,"abstract":"Mobile genetic elements shape microbial gene repertoires and populations. Recent results reveal that many, possibly most, microbial mobile genetic elements require helpers to transfer between genomes, which we refer to as Hitcher Genetic Elements (hitchers or HGEs). They may be a large fraction of pathogenicity and resistance genomic islands, whose mechanisms of transfer have remained enigmatic for decades. Together with their helper elements and their bacterial hosts, hitchers form tripartite networks of interactions that evolve rapidly within a parasitism-mutualism continuum. In this emerging view of microbial genomes as communities of mobile genetic elements many questions arise. Which elements are being moved, by whom, and how? How often are hitchers costly hyper-parasites or beneficial mutualists? What is the evolutionary origin of hitchers? Are there key advantages associated with hitchers' lifestyle that justify their unexpected abundance? And why are hitchers systematically smaller than their helpers? In this essay, we start answering these questions and point ways ahead for understanding the principles, origin, mechanisms, and impact of hitchers in bacterial ecology and evolution.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113911","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