PLoS Biology最新文献

Proteomic and phosphoproteomic analyses reveal that TORC1 is reactivated by pheromone signaling during sexual reproduction in fission yeast.

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-12-20 DOI: 10.1371/journal.pbio.3002963

Melvin Bérard, Laura Merlini, Sophie G Martin

{"title":"Proteomic and phosphoproteomic analyses reveal that TORC1 is reactivated by pheromone signaling during sexual reproduction in fission yeast.","authors":"Melvin Bérard, Laura Merlini, Sophie G Martin","doi":"10.1371/journal.pbio.3002963","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002963","url":null,"abstract":"Starvation, which is associated with inactivation of the growth-promoting TOR complex 1 (TORC1), is a strong environmental signal for cell differentiation. In the fission yeast Schizosaccharomyces pombe, nitrogen starvation has distinct physiological consequences depending on the presence of mating partners. In their absence, cells enter quiescence, and TORC1 inactivation prolongs their life. In presence of compatible mates, TORC1 inactivation is essential for sexual differentiation. Gametes engage in paracrine pheromone signaling, grow towards each other, fuse to form the diploid zygote, and form resistant, haploid spore progenies. To understand the signaling changes in the proteome and phospho-proteome during sexual reproduction, we developed cell synchronization strategies and present (phospho-)proteomic data sets that dissect pheromone from starvation signals over the sexual differentiation and cell-cell fusion processes. Unexpectedly, these data sets reveal phosphorylation of ribosomal protein S6 during sexual development, which we establish requires TORC1 activity. We demonstrate that TORC1 is re-activated by pheromone signaling, in a manner that does not require autophagy. Mutants with low TORC1 re-activation exhibit compromised mating and poorly viable spores. Thus, while inactivated to initiate the mating process, TORC1 is reactivated by pheromone signaling in starved cells to support sexual reproduction.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002963"},"PeriodicalIF":9.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869782","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

The representation of abstract goals in working memory is supported by task-congruent neural geometry.

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-12-19 DOI: 10.1371/journal.pbio.3002461

Mengya Zhang, Qing Yu

{"title":"The representation of abstract goals in working memory is supported by task-congruent neural geometry.","authors":"Mengya Zhang, Qing Yu","doi":"10.1371/journal.pbio.3002461","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002461","url":null,"abstract":"Successful goal-directed behavior requires the maintenance and implementation of abstract task goals on concrete stimulus information in working memory. Previous working memory research has revealed distributed neural representations of task information across cortex. However, how the distributed task representations emerge and communicate with stimulus-specific information to implement flexible goal-directed computations is still unclear. Here, leveraging electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) in human participants along with state space analyses, we provided converging evidence in support of a low-dimensional neural geometry of goal information congruent with a designed task space, which first emerged in frontal cortex during goal maintenance and then transferred to posterior cortex through frontomedial-to-posterior theta coherence for implementation on stimulus-specific representations. Importantly, the fidelity of the goal geometry was associated with memory performance. Collectively, our findings suggest that abstract goals in working memory are represented in an organized, task-congruent neural geometry for communications from frontal to posterior cortex to enable computations necessary for goal-directed behaviors.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002461"},"PeriodicalIF":9.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865932","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

Lessons about physiological relevance learned from large-scale meta-analysis of co-expression networks in brain organoids.

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-12-18 eCollection Date: 2024-12-01 DOI: 10.1371/journal.pbio.3002965

Yoshiaki Tanaka

引用次数: 0

PLOS Biology and the life sciences in 2024.

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-12-18 DOI: 10.1371/journal.pbio.3002985

Daniel Routledge

引用次数: 0

Maternal lipid mobilization is essential for embryonic development in the malaria vector Anopheles gambiae. 母体脂质动员对疟疾病媒冈比亚按蚊的胚胎发育至关重要。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-12-17 DOI: 10.1371/journal.pbio.3002960

Maurice A Itoe, W Robert Shaw, Iryna Stryapunina, Charles Vidoudez, Duo Peng, Esrah W Du, Tasneem A Rinvee, Naresh Singh, Yan Yan, Oleksandr Hulai, Kate E Thornburg, Flaminia Catteruccia

{"title":"Maternal lipid mobilization is essential for embryonic development in the malaria vector Anopheles gambiae.","authors":"Maurice A Itoe, W Robert Shaw, Iryna Stryapunina, Charles Vidoudez, Duo Peng, Esrah W Du, Tasneem A Rinvee, Naresh Singh, Yan Yan, Oleksandr Hulai, Kate E Thornburg, Flaminia Catteruccia","doi":"10.1371/journal.pbio.3002960","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002960","url":null,"abstract":"Lipid metabolism is an essential component in reproductive physiology. While lipid mobilization has been implicated in the growth of Plasmodium falciparum malaria parasites in their Anopheles vectors, the role of this process in the reproductive biology of these mosquitoes remains elusive. Here, we show that impairing lipolysis in Anopheles gambiae, the major malaria vectors, leads to embryonic lethality. Embryos derived from females in which we silenced the triglyceride lipase AgTL2 or the lipid storage droplet AgLSD1 develop normally during early embryogenesis but fail to hatch due to severely impaired metabolism. Embryonic lethality is efficiently recapitulated by exposing adult females to broad-spectrum lipase inhibitors prior to blood feeding, unveiling lipolysis as a potential target for inducing mosquito sterility. Our findings provide mechanistic insights into the importance of maternal lipid mobilization in embryonic health that may inform studies on human reproduction.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002960"},"PeriodicalIF":9.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847982","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

Postingestive reward acts through behavioral reinforcement and is conserved in obesity and after bariatric surgery.

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-12-17 eCollection Date: 2024-12-01 DOI: 10.1371/journal.pbio.3002936

Gabriela Ribeiro, Ana B Fernandes, Francisco P M Oliveira, João S Duarte, Manuela Oliveira, Clotilde Limbert, Rui M Costa, Durval C Costa, Albino J Oliveira-Maia

{"title":"Postingestive reward acts through behavioral reinforcement and is conserved in obesity and after bariatric surgery.","authors":"Gabriela Ribeiro, Ana B Fernandes, Francisco P M Oliveira, João S Duarte, Manuela Oliveira, Clotilde Limbert, Rui M Costa, Durval C Costa, Albino J Oliveira-Maia","doi":"10.1371/journal.pbio.3002936","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002936","url":null,"abstract":"Postingestive nutrient stimulation conditions food preferences through striatal dopamine and may be associated with blunted brain responses in obesity. In a cross-sectional study, we tested flavor-nutrient conditioning (FNC) with maltodextrin-enriched yogurt, with maltodextrin previously optimized for concentration and dextrose equivalents (n = 57), and to mask texture cues (n = 102). After conditioning, healthy volunteers (n = 52) increased preference for maltodextrin-paired (+102 kcal, CS+), relative to control (+1.8 kcal, CS-) flavors, as assessed according to intake, but not pleasantness. In a clinical study (n = 61), behavioral conditioning without effects on pleasantness was confirmed across pre-bariatric candidates with obesity, weight-stable post-surgery patients, and healthy controls, without significant differences between groups. Striatal dopamine D2-like receptor (DD2lR) availability, assessed with [123I]IBZM SPECT, was reduced in the obesity group and strongly correlated with conditioning strength and a measure of restrained eating in patients with gastric bypass. These results show that postingestive nutrient stimulation influences human food choices through behavioral reinforcement, and is conserved in obesity and after bariatric surgery. Trial Registration: ISRCTN17965026: Dopaminergic neurotransmission in dietary learning and obesity.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002936"},"PeriodicalIF":9.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848091","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

Comprehensive analysis of the C. elegans connectome reveals novel circuits and functions of previously unstudied neurons. 对 elegans 连接组的全面分析揭示了以前未研究过的神经元的新电路和功能。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-12-17 eCollection Date: 2024-12-01 DOI: 10.1371/journal.pbio.3002939

Scott W Emmons

{"title":"Comprehensive analysis of the C. elegans connectome reveals novel circuits and functions of previously unstudied neurons.","authors":"Scott W Emmons","doi":"10.1371/journal.pbio.3002939","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002939","url":null,"abstract":"Despite decades of research on the Caenorhabditis elegans nervous system based on an anatomical description of synaptic connectivity, the circuits underlying behavior remain incompletely described and the functions of many neurons are still unknown. Updated and more complete chemical and gap junction connectomes of both adult sexes covering the entire animal including the muscle end organ have become available recently. Here, these are analyzed to gain insight into the overall structure of the connectivity network and to suggest functions of individual neuron classes. Modularity analysis divides the connectome graph into 10 communities that can be correlated with broad categories of behavior. A significant role of the body wall musculature end organ is emphasized as both a site of significant information convergence and as a source of sensory input in a feedback loop. Convergence of pathways for multisensory integration occurs throughout the network-most interneurons have similar indegrees and outdegrees and hence disperse information as much as they aggregate it. New insights include description of a set of high degree interneurons connected by many gap junctions running through the ventral cord that may represent a previously unrecognized locus of information processing. There is an apparent mechanosensory and proprioceptive field covering the entire body formed by connectivity of the many mechanosensory neurons of multiple types to 2 interneurons with output connections across the nervous system. Several additional significant, previously unrecognized circuits and pathways are uncovered, some involving unstudied neurons. The insights are valuable for guiding theoretical investigation of network properties as well as experimental studies of the functions of individual neurons, groups of neurons, and circuits.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002939"},"PeriodicalIF":9.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847980","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

Multiomic profiling of chronically activated CD4+ T cells identifies drivers of exhaustion and metabolic reprogramming. 对慢性活化的 CD4+ T 细胞进行多组学分析，确定衰竭和代谢重编程的驱动因素。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-12-17 DOI: 10.1371/journal.pbio.3002943

Matthew L Lawton, Melissa M Inge, Benjamin C Blum, Erika L Smith-Mahoney, Dante Bolzan, Weiwei Lin, Christina McConney, Jacob Porter, Jarrod Moore, Ahmed Youssef, Yashasvi Tharani, Xaralabos Varelas, Gerald V Denis, Wilson W Wong, Dzmitry Padhorny, Dima Kozakov, Trevor Siggers, Stefan Wuchty, Jennifer Snyder-Cappione, Andrew Emili

{"title":"Multiomic profiling of chronically activated CD4+ T cells identifies drivers of exhaustion and metabolic reprogramming.","authors":"Matthew L Lawton, Melissa M Inge, Benjamin C Blum, Erika L Smith-Mahoney, Dante Bolzan, Weiwei Lin, Christina McConney, Jacob Porter, Jarrod Moore, Ahmed Youssef, Yashasvi Tharani, Xaralabos Varelas, Gerald V Denis, Wilson W Wong, Dzmitry Padhorny, Dima Kozakov, Trevor Siggers, Stefan Wuchty, Jennifer Snyder-Cappione, Andrew Emili","doi":"10.1371/journal.pbio.3002943","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002943","url":null,"abstract":"Repeated antigen exposure leads to T-cell exhaustion, a transcriptionally and epigenetically distinct cellular state marked by loss of effector functions (e.g., cytotoxicity, cytokine production/release), up-regulation of inhibitory receptors (e.g., PD-1), and reduced proliferative capacity. Molecular pathways underlying T-cell exhaustion have been defined for CD8+ cytotoxic T cells, but which factors drive exhaustion in CD4+ T cells, that are also required for an effective immune response against a tumor or infection, remains unclear. Here, we utilize quantitative proteomic, phosphoproteomic, and metabolomic analyses to characterize the molecular basis of the dysfunctional cell state induced by chronic stimulation of CD4+ memory T cells. We identified a dynamic response encompassing both known and novel up-regulated cell surface receptors, as well as dozens of unexpected transcriptional regulators. Integrated causal network analysis of our combined data predicts the histone acetyltransferase p300 as a driver of aspects of this phenotype following chronic stimulation, which we confirmed via targeted small molecule inhibition. While our integrative analysis also revealed large-scale metabolic reprogramming, our independent investigation confirmed a global remodeling away from glycolysis to a dysfunctional fatty acid oxidation-based metabolism coincident with oxidative stress. Overall, these data provide both insights into the mechanistic basis of CD4+ T-cell exhaustion and serve as a valuable resource for future interventional studies aimed at modulating T-cell dysfunction.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002943"},"PeriodicalIF":9.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848087","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

SLMO transfers phosphatidylserine between the outer and inner mitochondrial membrane in Drosophila.

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-12-16 eCollection Date: 2024-12-01 DOI: 10.1371/journal.pbio.3002941

Siwen Zhao, Xuguang Jiang, Ning Li, Tao Wang

{"title":"SLMO transfers phosphatidylserine between the outer and inner mitochondrial membrane in Drosophila.","authors":"Siwen Zhao, Xuguang Jiang, Ning Li, Tao Wang","doi":"10.1371/journal.pbio.3002941","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002941","url":null,"abstract":"Phospholipids are critical building blocks of mitochondria, and proper mitochondrial function and architecture rely on phospholipids that are primarily transported from the endoplasmic reticulum (ER). Here, we show that mitochondrial form and function rely on synthesis of phosphatidylserine (PS) in the ER through phosphatidylserine synthase (PSS), trafficking of PS from ER to mitochondria (and within mitochondria), and the conversion of PS to phosphatidylethanolamine (PE) by phosphatidylserine decarboxylase (PISD) in the inner mitochondrial membrane (IMM). Using a forward genetic screen in Drosophila, we found that Slowmo (SLMO) specifically transfers PS from the outer mitochondrial membrane (OMM) to the IMM within the inner boundary membrane (IBM) domain. Thus, SLMO is required for shaping mitochondrial morphology, but its putative conserved binding partner, dTRIAP, is not. Importantly, SLMO's role in maintaining mitochondrial morphology is conserved in humans via the SLMO2 protein and is independent of mitochondrial dynamics. Our results highlight the importance of a conserved PSS-SLMO-PISD pathway in maintaining the structure and function of mitochondria.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"22 12","pages":"e3002941"},"PeriodicalIF":9.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840184","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

Compressing human brain activity for studying brain function.

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-12-16 eCollection Date: 2024-12-01 DOI: 10.1371/journal.pbio.3002966

Bratislav Misic

引用次数: 0