PLoS Biology最新文献_第10页

Are oligodendrocytes bystanders or drivers of Parkinson's disease pathology? 少突胶质细胞是帕金森病病理的旁观者还是驱动者？

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-01-08 eCollection Date: 2025-01-01 DOI: 10.1371/journal.pbio.3002977

José María Salazar Campos, Lena F Burbulla, Sarah Jäkel

{"title":"Are oligodendrocytes bystanders or drivers of Parkinson's disease pathology?","authors":"José María Salazar Campos, Lena F Burbulla, Sarah Jäkel","doi":"10.1371/journal.pbio.3002977","DOIUrl":"10.1371/journal.pbio.3002977","url":null,"abstract":"The major pathological feature of Parkinson 's disease (PD), the second most common neurodegenerative disease and most common movement disorder, is the predominant degeneration of dopaminergic neurons in the substantia nigra, a part of the midbrain. Despite decades of research, the molecular mechanisms of the origin of the disease remain unknown. While the disease was initially viewed as a purely neuronal disorder, results from single-cell transcriptomics have suggested that oligodendrocytes may play an important role in the early stages of Parkinson's. Although these findings are of high relevance, particularly to the search for effective disease-modifying therapies, the actual functional role of oligodendrocytes in Parkinson's disease remains highly speculative and requires a concerted scientific effort to be better understood. This Unsolved Mystery discusses the limited understanding of oligodendrocytes in PD, highlighting unresolved questions regarding functional changes in oligodendroglia, the role of myelin in nigral dopaminergic neurons, the impact of the toxic environment, and the aggregation of alpha-synuclein within oligodendrocytes.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002977"},"PeriodicalIF":9.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957292","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

Cortical direction selectivity increases from the input to the output layers of visual cortex. 从视觉皮层的输入层到输出层，皮层的方向选择性增加。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-01-08 eCollection Date: 2025-01-01 DOI: 10.1371/journal.pbio.3002947

Weifeng Dai, Tian Wang, Yang Li, Yi Yang, Yange Zhang, Yujie Wu, Tingting Zhou, Hongbo Yu, Liang Li, Yizheng Wang, Gang Wang, Dajun Xing

{"title":"Cortical direction selectivity increases from the input to the output layers of visual cortex.","authors":"Weifeng Dai, Tian Wang, Yang Li, Yi Yang, Yange Zhang, Yujie Wu, Tingting Zhou, Hongbo Yu, Liang Li, Yizheng Wang, Gang Wang, Dajun Xing","doi":"10.1371/journal.pbio.3002947","DOIUrl":"10.1371/journal.pbio.3002947","url":null,"abstract":"Sensitivity to motion direction is a feature of visual neurons that is essential for motion perception. Recent studies have suggested that direction selectivity is re-established at multiple stages throughout the visual hierarchy, which contradicts the traditional assumption that direction selectivity in later stages largely derives from that in earlier stages. By recording laminar responses in areas 17 and 18 of anesthetized cats of both sexes, we aimed to understand how direction selectivity is processed and relayed across 2 successive stages: the input layers and the output layers within the early visual cortices. We found a strong relationship between the strength of direction selectivity in the output layers and the input layers, as well as the preservation of preferred directions across the input and output layers. Moreover, direction selectivity was enhanced in the output layers compared to the input layers, with the response strength maintained in the preferred direction but reduced in other directions and under blank stimuli. We identified a direction-tuned gain mechanism for interlaminar signal transmission, which likely originated from both feedforward connections across the input and output layers and recurrent connections within the output layers. This direction-tuned gain, coupled with nonlinearity, contributed to the enhanced direction selectivity in the output layers. Our findings suggest that direction selectivity in later cortical stages partially inherits characteristics from earlier cortical stages and is further refined by intracortical connections.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002947"},"PeriodicalIF":9.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957295","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

Dynamic collateral sensitivity profiles highlight opportunities and challenges for optimizing antibiotic treatments. 动态侧枝敏感性概况突出了优化抗生素治疗的机遇和挑战。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-01-08 eCollection Date: 2025-01-01 DOI: 10.1371/journal.pbio.3002970

Jeff Maltas, Anh Huynh, Kevin B Wood

{"title":"Dynamic collateral sensitivity profiles highlight opportunities and challenges for optimizing antibiotic treatments.","authors":"Jeff Maltas, Anh Huynh, Kevin B Wood","doi":"10.1371/journal.pbio.3002970","DOIUrl":"10.1371/journal.pbio.3002970","url":null,"abstract":"As failure rates for traditional antimicrobial therapies escalate, recent focus has shifted to evolution-based therapies to slow resistance. Collateral sensitivity-the increased susceptibility to one drug associated with evolved resistance to a different drug-offers a potentially exploitable evolutionary constraint, but the manner in which collateral effects emerge over time is not well understood. Here, we use laboratory evolution in the opportunistic pathogen Enterococcus faecalis to phenotypically characterize collateral profiles through evolutionary time. Specifically, we measure collateral profiles for 400 strain-antibiotic combinations over the course of 4 evolutionary time points as strains are selected in increasing concentrations of antibiotic. We find that at a global level-when results from all drugs are combined-collateral resistance dominates during early phases of adaptation, when resistance to the selecting drug is lower, while collateral sensitivity becomes increasingly likely with further selection. At the level of individual populations; however, the trends are idiosyncratic; for example, the frequency of collateral sensitivity to ceftriaxone increases over time in isolates selected by linezolid but decreases in isolates selected by ciprofloxacin. We then show experimentally how dynamic collateral sensitivity relationships can lead to time-dependent dosing windows that depend on finely timed switching between drugs. Finally, we develop a stochastic mathematical model based on a Markov decision process consistent with observed dynamic collateral profiles to show measurements across time are required to optimally constrain antibiotic resistance.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002970"},"PeriodicalIF":9.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11709278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957297","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

Conserved features of recombination control in vertebrates. 脊椎动物重组控制的保守特征。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-01-07 eCollection Date: 2025-01-01 DOI: 10.1371/journal.pbio.3002959

Linda Odenthal-Hesse

引用次数: 0

FLCCR is a fluorescent reporter system that quantifies the duration of different cell cycle phases at the single-cell level in fission yeast. FLCCR是一种荧光报告系统，在单细胞水平上量化分裂酵母不同细胞周期阶段的持续时间。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-01-07 eCollection Date: 2025-01-01 DOI: 10.1371/journal.pbio.3002969

Guillem Murciano-Julià, Marina Francos-Cárdenas, Clàudia Salat-Canela, Elena Hidalgo, José Ayté

{"title":"FLCCR is a fluorescent reporter system that quantifies the duration of different cell cycle phases at the single-cell level in fission yeast.","authors":"Guillem Murciano-Julià, Marina Francos-Cárdenas, Clàudia Salat-Canela, Elena Hidalgo, José Ayté","doi":"10.1371/journal.pbio.3002969","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002969","url":null,"abstract":"Fission yeast is an excellent model system that has been widely used to study the mechanism that control cell cycle progression. However, there is a lack of tools that allow to measure with high precision the duration of the different phases of the cell cycle in individual cells. To circumvent this problem, we have developed a fluorescent reporter that allows the quantification of the different phases of the cell cycle at the single-cell level in most genetic backgrounds. To prove the accuracy of this fluorescent reporter, we have tested the reporter in strains known to have a delay in the G1/S or G2/M transitions, confirming the strength and versatility of the system. An advantage of this reporter is that it eliminates the need for culture synchronization, avoiding stressing the cells. Using this reporter, we show that unperturbed cells lacking Sty1 have a standard cell cycle length and distribution and that the extended length of these cells is due to their increased cell growth rate but not to alterations in their cell cycle progression.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002969"},"PeriodicalIF":9.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11706491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142957299","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

Functional analysis of conserved C. elegans bHLH family members uncovers lifespan control by a peptidergic hub neuron. 保守的秀丽隐杆线虫bHLH家族成员的功能分析揭示了肽能中枢神经元对寿命的控制。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-01-06 eCollection Date: 2025-01-01 DOI: 10.1371/journal.pbio.3002979

G Robert Aguilar, Berta Vidal, Hongzhu Ji, Joke Evenblij, Chien-Po Liao, Hongfei Ji, Giulio Valperga, Christopher Fang-Yen, Oliver Hobert

{"title":"Functional analysis of conserved C. elegans bHLH family members uncovers lifespan control by a peptidergic hub neuron.","authors":"G Robert Aguilar, Berta Vidal, Hongzhu Ji, Joke Evenblij, Chien-Po Liao, Hongfei Ji, Giulio Valperga, Christopher Fang-Yen, Oliver Hobert","doi":"10.1371/journal.pbio.3002979","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002979","url":null,"abstract":"Throughout the animal kingdom, several members of the basic helix-loop-helix (bHLH) family act as proneural genes during early steps of nervous system development. Roles of bHLH genes in specifying terminal differentiation of postmitotic neurons have been less extensively studied. We analyze here the function of 5 Caenorhabditis elegans bHLH genes, falling into 3 phylogenetically conserved subfamilies, which are continuously expressed in a very small number of postmitotic neurons in the central nervous system. We show (a) that 2 orthologs of the vertebrate bHLHe22/e23 genes, called hlh-17 and hlh-32, function redundantly to specify the identity of a single head interneuron class (AUA), as well as an individual motor neuron (VB2); (b) that the PTF1a ortholog hlh-13 acts as a terminal selector to control terminal differentiation and function of the sole octopaminergic neuron class in C. elegans, RIC; and (c) that the NHLH1/2 ortholog hlh-15 controls terminal differentiation and function of the peptidergic AVK head interneuron class, a known neuropeptidergic signaling hub in the animal. Strikingly, through null mutant analysis and cell-specific rescue experiments, we find that loss of hlh-15/NHLH in the peptidergic AVK neurons and the resulting abrogation of neuropeptide secretion from these neurons causes a substantially extended lifespan of the animal, which we propose to be akin to hypothalamic control of lifespan in vertebrates. Our functional analysis reveals themes of bHLH gene function during terminal differentiation that are complementary to the earlier lineage specification roles of other bHLH family members. However, such late functions are much more sparsely employed by members of the bHLH transcription factor family, compared to the function of the much more broadly employed homeodomain transcription factor family.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 1","pages":"e3002979"},"PeriodicalIF":9.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980352","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

Correction: Thalamic spindles and Up states coordinate cortical and hippocampal co-ripples in humans. 更正：丘脑纺锤波和向上状态协调人类皮层和海马体的共同波纹。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-12-23 eCollection Date: 2024-12-01 DOI: 10.1371/journal.pbio.3002971

引用次数: 0

Proteomic and phosphoproteomic analyses reveal that TORC1 is reactivated by pheromone signaling during sexual reproduction in fission yeast. 蛋白质组学和磷酸化蛋白质组学分析表明，TORC1在裂变酵母有性生殖过程中被信息素信号重新激活。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-12-20 eCollection Date: 2024-12-01 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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750111/pdf/","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":"OA","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. 抽象目标在工作记忆中的表征得到任务一致神经几何的支持。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2024-12-19 eCollection Date: 2024-12-01 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":"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. 从脑类器官共表达网络的大规模荟萃分析中获得的生理相关性经验教训。

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