PLoS Biology最新文献

{"title":"The multiscale brain structural re-organization that occurs from childhood to adolescence correlates with cortical morphology maturation and functional specialization.","authors":"Yirong He, Debin Zeng, Qiongling Li, Lei Chu, Xiaoxi Dong, Xinyuan Liang, Lianglong Sun, Xuhong Liao, Tengda Zhao, Xiaodan Chen, Tianyuan Lei, Weiwei Men, Yanpei Wang, Daoyang Wang, Mingming Hu, Zhiying Pan, Haibo Zhang, Ningyu Liu, Shuping Tan, Jia-Hong Gao, Shaozheng Qin, Sha Tao, Qi Dong, Yong He, Shuyu Li","doi":"10.1371/journal.pbio.3002710","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002710","url":null,"abstract":"<p><p>From childhood to adolescence, the structural organization of the human brain undergoes dynamic and regionally heterogeneous changes across multiple scales, from synapses to macroscale white matter pathways. However, during this period, the developmental process of multiscale structural architecture, its association with cortical morphological changes, and its role in the maturation of functional organization remain largely unknown. Here, using two independent multimodal imaging developmental datasets aged 6-14 years, we investigated developmental process of multiscale cortical organization by constructing an in vivo multiscale structural connectome model incorporating white matter tractography, cortico-cortical proximity, and microstructural similarity. By employing the gradient mapping method, the principal gradient derived from the multiscale structural connectome effectively recapitulated the sensory-association axis. Our findings revealed a continuous expansion of the multiscale structural gradient space during development, characterized by enhanced differentiation between primary sensory and higher-order transmodal regions along the principal gradient. This age-related differentiation paralleled regionally heterogeneous changes in cortical morphology. Furthermore, the developmental changes in coupling between multiscale structural and functional connectivity were correlated with functional specialization refinement, as evidenced by changes in the participation coefficient. Notably, the differentiation of the principal multiscale structural gradient was associated with improved cognitive abilities, such as enhanced working memory and attention performance, and potentially underpinned by synaptic and hormone-related biological processes. These findings advance our understanding of the intricate maturation process of brain structural organization and its implications for cognitive performance.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 4","pages":"e3002710"},"PeriodicalIF":9.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765541","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}

{"title":"Mdga2 deficiency leads to an aberrant activation of BDNF/TrkB signaling that underlies autism-relevant synaptic and behavioral changes in mice.","authors":"Dongdong Zhao, Yuanhui Huo, Naizhen Zheng, Xiang Zhu, Dingting Yang, Yunqiang Zhou, Shengya Wang, Yiru Jiang, Yili Wu, Yun-Wu Zhang","doi":"10.1371/journal.pbio.3003047","DOIUrl":"10.1371/journal.pbio.3003047","url":null,"abstract":"<p><p>Memprin/A5/mu (MAM) domain containing glycosylphosphatidylinositol anchor 2 (MDGA2) is an excitatory synaptic suppressor and its mutations have been associated with autism spectrum disorder (ASD). However, the detailed physiological function of MDGA2 and the mechanism underlying MDGA2 deficiency-caused ASD has yet to be elucidated. Herein, we not only confirm that Mdga2 +/- mice exhibit increased excitatory synapse transmission and ASD-like behaviors, but also identify aberrant brain-derived neurotrophic factor/tyrosine kinase B (BDNF/TrkB) signaling activation in these mice. We demonstrate that MDGA2 interacts with TrkB through its memprin/A5/mu domain, thereby competing the binding of BDNF to TrkB. Both loss of MDGA2 and the ASD-associated MDGA2 V930I mutation promote the BDNF/TrkB signaling activity. Importantly, we demonstrate that inhibiting the BDNF/TrkB signaling by both small molecular compound and MDGA2-derived peptide can attenuate the increase of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated excitatory synaptic activity and social deficits in MDGA2-deficient mice. These results highlight a novel MDGA2-BDNF/TrkB-dependent mechanism underlying the synaptic function regulation, which may become a therapeutic target for ASD.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 4","pages":"e3003047"},"PeriodicalIF":9.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765521","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}

{"title":"Stimulus selection enhances value-modulated somatosensory processing in the superior colliculus.","authors":"Yun Wen Chu, Suma Chinta, Hayagreev V S Keri, Shreya Beri, Scott R Pluta","doi":"10.1371/journal.pbio.3003057","DOIUrl":"10.1371/journal.pbio.3003057","url":null,"abstract":"<p><p>A fundamental trait of intelligent behavior is the ability to respond selectively to stimuli with higher value. Where along the neural hierarchy does somatosensory processing transition from a map of stimulus location to a map of stimulus value? To address this question, we recorded single-unit activity from populations of neurons in somatosensory cortex (S1) and midbrain superior colliculus (SC) in mice conditioned to respond to a positive-valued stimulus and withhold responses to an adjacent, negative-valued stimulus. The stimulus preference of the S1 population was equally weighted towards either stimulus, in line with a somatotopic map. Surprisingly, we discovered a large population of SC neurons that were disproportionately biased towards the positive stimulus. This disproportionate bias was largely driven by enhanced spike suppression for the negative stimulus. Removing the opportunity for mice to behaviorally select the positive stimulus reduced positive stimulus bias and spontaneous firing rates in SC but not S1, suggesting that neural selectivity was augmented by task readiness. Similarly, the spontaneous firing rates of SC but not S1 neurons predicted reaction times, suggesting that SC neurons played a persistent role in perceptual decision-making. Taken together, these data indicate that the somatotopic map in S1 is transformed into a value-based map in SC that encodes stimulus priority.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003057"},"PeriodicalIF":9.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755369","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}

{"title":"Notch3 is an asymmetric gene and a modifier of heart looping defects in Nodal mouse mutants.","authors":"Tobias Holm Bønnelykke, Marie-Amandine Chabry, Emeline Perthame, Gregor Dombrowsky, Felix Berger, Sven Dittrich, Marc-Phillip Hitz, Audrey Desgrange, Sigolène M Meilhac","doi":"10.1371/journal.pbio.3002598","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002598","url":null,"abstract":"<p><p>The TGFβ secreted factor NODAL is a major left determinant required for the asymmetric morphogenesis of visceral organs, including the heart. Yet, when this signaling is absent, shape asymmetry, for example of the embryonic heart loop, is not fully abrogated, indicating that there are other factors regulating left-right patterning. Here, we used a tailored transcriptomic approach to screen for genes asymmetrically expressed in the field of heart progenitors. We thus identify Notch3 as a novel left-enriched gene and validate, by quantitative in situ hybridization, its transient asymmetry in the lateral plate mesoderm and node crown, overlapping with Nodal. In mutant embryos, we analyzed the regulatory hierarchy and demonstrate that Nodal in the lateral plate mesoderm amplifies Notch3 asymmetric expression. The function of Notch3 was uncovered in an allelic series of mutants. In single neonate mutants, we observe that Notch3 is required with partial penetrance for ventricle thickness, septation and aortic valve, in addition to its known role in coronary arteries. In compound mutants, we reveal that Notch3 acts as a genetic modifier of heart looping direction and shape defects in Nodal mutants. Whereas Notch3 was previously mainly associated with the CADASIL syndrome, our observations in the mouse and a human cohort support a novel role in congenital heart defects and laterality defects.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3002598"},"PeriodicalIF":9.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755368","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}

{"title":"The Hunchback transcription factor determines interneuron molecular identity, morphology, and presynapse targeting in the Drosophila NB5-2 lineage.","authors":"Heather Q Pollington, Chris Q Doe","doi":"10.1371/journal.pbio.3002881","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002881","url":null,"abstract":"<p><p>Interneuron diversity within the central nervous system (CNS) is essential for proper circuit assembly. Functional interneurons must integrate multiple features, including combinatorial transcription factor (TF) expression, axon/dendrite morphology, and connectivity to properly specify interneuronal identity. Yet, how these different interneuron properties are coordinately regulated remains unclear. Here we used the Drosophila neural progenitor, NB5-2, known to generate late-born interneurons in a proprioceptive circuit, to determine if the early-born temporal transcription factor (TTF), Hunchback (Hb), specifies early-born interneuron identity, including molecular profile, axon/dendrite morphology, presynapse targeting, and behavior. We found that prolonged Hb expression in NB5-2 increases the number of neurons expressing early-born TFs (Nervy, Nkx6, and Dbx) at the expense of late-born TFs (Runt and Zfh2); thus, Hb is sufficient to promote interneuron molecular identity. Hb is also sufficient to transform late-born neuronal morphology to early-born neuronal morphology. Furthermore, prolonged Hb promotes the relocation of late-born neuronal presynapses to early-born neuronal presynapse neuropil locations, consistent with a change in interneuron connectivity. Finally, we found that prolonged Hb expression led to defects in proprioceptive behavior, consistent with a failure to properly specify late-born interneurons in the proprioceptive circuit. We conclude that the Hb TTF is sufficient to specify multiple aspects of early-born interneuron identity, as well as disrupt late-born proprioceptive neuron function.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3002881"},"PeriodicalIF":9.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755370","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}

{"title":"Incomplete lytic cycle of a widespread Bacteroides bacteriophage leads to the formation of defective viral particles.","authors":"Sol Vendrell-Fernández, Beatriz Beamud, Yasmina Abou Haydar, Jorge Am de Sousa, Julien Burlaud-Gaillard, Etienne Kornobis, Bertrand Raynal, Joelle Vinh, David Bikard, Jean-Marc Ghigo","doi":"10.1371/journal.pbio.3002787","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002787","url":null,"abstract":"<p><p>Advances in metagenomics have led to the identification of new intestinal temperate bacteriophages. However, their experimental characterization remains challenging due to a limited understanding of their lysogenic-lytic cycle and the common lack of plaque formation in vitro. In this study, we investigated the hankyphage, a widespread transposable phage of prominent Bacteroides symbionts. Hankyphages spontaneously produced virions in laboratory conditions even in the absence of inducer, but virions did not show any evidence of infectivity. To increase virion production and raise the chances of observing infection events, we identified a master repressor of the hankyphage lytic cycle, RepCHP, whose silencing amplified hankyphage gene expression, and enhanced replicative transposition and virion production. However, attempts to infect or lysogenize new host cells with different capsular types remained unsuccessful. Transmission electron microscopy and capsid DNA sequencing revealed an abnormal virion morphology and incomplete DNA packaging of the hankyphage, suggesting that it cannot complete its assembly in laboratory conditions for reasons that are yet to be identified. Still, metavirome and phylogenetic analyses were suggestive of hankyphage horizontal transmission. We could also detect the activity of diversity-generating retroelements (DGRs) that mutagenize the hankyphage tail fiber, and likely contribute to its broad host range. This study sheds light on the life cycle of this abundant intestinal bacteriophage and highlights important gaps in our understanding of the factors required for the completion of its life cycle. Elucidating this puzzle will be critical to gain a better understanding of the hankyphage biology and ecological role.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3002787"},"PeriodicalIF":9.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755367","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}

{"title":"Navigating your US bioscience career into the 2030s.","authors":"Peter J Hotez","doi":"10.1371/journal.pbio.3003089","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003089","url":null,"abstract":"<p><p>The coming decade might see major cuts to the United States Government funding for biomedicine and the mainstreaming of pseudoscience. But your biosciences PhD gives you the problem-solving skills to navigate this maelstrom, especially if you maintain flexibility, optimism, and enthusiasm for uncharted paths.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003089"},"PeriodicalIF":9.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736147","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}

{"title":"Neural mechanisms for the attention-mediated propagation of conceptual information in the human brain.","authors":"David Acunzo, Damiano Grignolio, Clayton Hickey","doi":"10.1371/journal.pbio.3003018","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003018","url":null,"abstract":"<p><p>The visual environment is complicated, and humans and other animals accordingly prioritize some sources of information over others through the deployment of spatial attention. Cognitive theories propose that one core purpose of this is to gather information that can be used in downstream cognitive processes, including the development of concepts and categories. However, neuroscientific investigation has focused closely on the identification of the systems and algorithms that support attentional control or that instantiate the effect of attention on sensation and perception. Much less is known about how attention impacts the acquisition and activation of concepts. Here, we use machine learning of EEG and concurrently recorded EEG/MRI to temporally and anatomically characterize the neural network that abstracts from attended perceptual information to activate and construct semantic and conceptual representations. We find that variance in the amplitude of N2pc-an event-related potential (ERP) component closely linked to selective attention-predicts the emergence of conceptual information in a network including VMPFC, posterior parietal cortex, and anterior insula. This network appears to play a key role in the attention-mediated translation of perceptual information to concepts, semantics, and action plans.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003018"},"PeriodicalIF":9.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736151","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}

{"title":"Editorial Note: How sex chromosomes get trapped into nonrecombination.","authors":"","doi":"10.1371/journal.pbio.3003107","DOIUrl":"https://doi.org/10.1371/journal.pbio.3003107","url":null,"abstract":"","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003107"},"PeriodicalIF":9.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732715","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}

{"title":"Soil biodiversity and function under global change.","authors":"Manuel Delgado-Baquerizo, David J Eldridge, Yu-Rong Liu, Zhong-Wen Liu, Claudia Coleine, Pankaj Trivedi","doi":"10.1371/journal.pbio.3003093","DOIUrl":"10.1371/journal.pbio.3003093","url":null,"abstract":"<p><p>Soil organisms represent the most abundant and diverse organisms on the planet and support almost every ecosystem function we know, and thus impact our daily lives. Some of these impacts have been well-documented, such as the role of soil organisms in regulating soil fertility and carbon sequestration; processes that have direct implications for essential ecosystem services including food security and climate change mitigation. Moreover, soil biodiversity also plays a critical role in supporting other aspects from One Health-the combined health of humans, animals, and the environment-to the conservation of historic structures such as monuments. Unfortunately, soil biodiversity is also highly vulnerable to a growing number of stressors associated with global environmental change. Understanding how and when soil biodiversity supports these functions, and how it will adapt to changing environmental conditions, is crucial for conserving soils and maintaining soil processes for future generations. In this Essay, we discuss the fundamental importance of soil biodiversity for supporting multiple ecosystem services and One Health, and further highlight essential knowledge gaps that need to be addressed to conserve soil biodiversity for the next generations.</p>","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 3","pages":"e3003093"},"PeriodicalIF":9.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732717","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}