The modular structure of functional connectomes in the human brain undergoes substantial reorganization during development. However, previous studies have implicitly assumed that each region participates in one single module, ignoring the potential spatial overlap between modules. How the overlapping functional modules develop and whether this development is related to gray and white matter features remain unknown. Using longitudinal multimodal structural, functional, and diffusion MRI data from 305 children (aged 6 to 14 years), we investigated the maturation of overlapping modules of functional networks and further revealed their structural associations. An edge-centric network model was used to identify the overlapping modules, and the nodal overlap in module affiliations was quantified using the entropy measure. We showed a regionally heterogeneous spatial topography of the overlapping extent of brain nodes in module affiliations in children, with higher entropy (i.e., more module involvement) in the ventral attention, somatomotor, and subcortical regions and lower entropy (i.e., less module involvement) in the visual and default-mode regions. The overlapping modules developed in a linear, spatially dissociable manner, with decreased entropy (i.e., decreased module involvement) in the dorsomedial prefrontal cortex, ventral prefrontal cortex, and putamen and increased entropy (i.e., increased module involvement) in the parietal lobules and lateral prefrontal cortex. The overlapping modular patterns captured individual brain maturity as characterized by chronological age and were predicted by integrating gray matter morphology and white matter microstructural properties. Our findings highlight the maturation of overlapping functional modules and their structural substrates, thereby advancing our understanding of the principles of connectome development.
{"title":"Functional network modules overlap and are linked to interindividual connectome differences during human brain development","authors":"Tianyuan Lei, Xuhong Liao, Xinyuan Liang, Lianglong Sun, Mingrui Xia, Yunman Xia, Tengda Zhao, Xiaodan Chen, Weiwei Men, Yanpei Wang, Leilei Ma, Ningyu Liu, Jing Lu, Gai Zhao, Yuyin Ding, Yao Deng, Jiali Wang, Rui Chen, Haibo Zhang, Shuping Tan, Jia-Hong Gao, Shaozheng Qin, Sha Tao, Qi Dong, Yong He","doi":"10.1371/journal.pbio.3002653","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002653","url":null,"abstract":"The modular structure of functional connectomes in the human brain undergoes substantial reorganization during development. However, previous studies have implicitly assumed that each region participates in one single module, ignoring the potential spatial overlap between modules. How the overlapping functional modules develop and whether this development is related to gray and white matter features remain unknown. Using longitudinal multimodal structural, functional, and diffusion MRI data from 305 children (aged 6 to 14 years), we investigated the maturation of overlapping modules of functional networks and further revealed their structural associations. An edge-centric network model was used to identify the overlapping modules, and the nodal overlap in module affiliations was quantified using the entropy measure. We showed a regionally heterogeneous spatial topography of the overlapping extent of brain nodes in module affiliations in children, with higher entropy (i.e., more module involvement) in the ventral attention, somatomotor, and subcortical regions and lower entropy (i.e., less module involvement) in the visual and default-mode regions. The overlapping modules developed in a linear, spatially dissociable manner, with decreased entropy (i.e., decreased module involvement) in the dorsomedial prefrontal cortex, ventral prefrontal cortex, and putamen and increased entropy (i.e., increased module involvement) in the parietal lobules and lateral prefrontal cortex. The overlapping modular patterns captured individual brain maturity as characterized by chronological age and were predicted by integrating gray matter morphology and white matter microstructural properties. Our findings highlight the maturation of overlapping functional modules and their structural substrates, thereby advancing our understanding of the principles of connectome development.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"29 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260212","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}
Pub Date : 2024-09-18DOI: 10.1371/journal.pbio.3002801
David Anaguano, Opeoluwa Adewale-Fasoro, Grace W. Vick, Sean Yanik, James Blauwkamp, Manuel A. Fierro, Sabrina Absalon, Prakash Srinivasan, Vasant Muralidharan
Malaria is a global and deadly human disease caused by the apicomplexan parasites of the genus Plasmodium. Parasite proliferation within human red blood cells (RBCs) is associated with the clinical manifestations of the disease. This asexual expansion within human RBCs begins with the invasion of RBCs by P. falciparum, which is mediated by the secretion of effectors from 2 specialized club-shaped secretory organelles in merozoite-stage parasites known as rhoptries. We investigated the function of the Rhoptry Neck Protein 11 (RON11), which contains 7 transmembrane domains and calcium-binding EF-hand domains. We generated conditional mutants of the P. falciparum RON11. Knockdown of RON11 inhibits parasite growth by preventing merozoite invasion. The loss of RON11 did not lead to any defects in processing of rhoptry proteins but instead led to a decrease in the amount of rhoptry proteins. We utilized ultrastructure expansion microscopy (U-ExM) to determine the effect of RON11 knockdown on rhoptry biogenesis. Surprisingly, in the absence of RON11, fully developed merozoites had only 1 rhoptry each. The single rhoptry in RON11-deficient merozoites were morphologically typical with a bulb and a neck oriented into the apical polar ring. Moreover, rhoptry proteins are trafficked accurately to the single rhoptry in RON11-deficient parasites. These data show that in the absence of RON11, the first rhoptry is generated during schizogony but upon the start of cytokinesis, the second rhoptry never forms. Interestingly, these single-rhoptry merozoites were able to attach to host RBCs but are unable to invade RBCs. Instead, RON11-deficient merozoites continue to engage with RBC for prolonged periods eventually resulting in echinocytosis, a result of secreting the contents from the single rhoptry into the RBC. Together, our data show that RON11 triggers the de novo biogenesis of the second rhoptry and functions in RBC invasion.
{"title":"Plasmodium RON11 triggers biogenesis of the merozoite rhoptry pair and is essential for erythrocyte invasion","authors":"David Anaguano, Opeoluwa Adewale-Fasoro, Grace W. Vick, Sean Yanik, James Blauwkamp, Manuel A. Fierro, Sabrina Absalon, Prakash Srinivasan, Vasant Muralidharan","doi":"10.1371/journal.pbio.3002801","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002801","url":null,"abstract":"Malaria is a global and deadly human disease caused by the apicomplexan parasites of the genus <jats:italic>Plasmodium</jats:italic>. Parasite proliferation within human red blood cells (RBCs) is associated with the clinical manifestations of the disease. This asexual expansion within human RBCs begins with the invasion of RBCs by <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic>, which is mediated by the secretion of effectors from 2 specialized club-shaped secretory organelles in merozoite-stage parasites known as rhoptries. We investigated the function of the Rhoptry Neck Protein 11 (RON11), which contains 7 transmembrane domains and calcium-binding EF-hand domains. We generated conditional mutants of the <jats:italic>P</jats:italic>. <jats:italic>falciparum</jats:italic> RON11. Knockdown of RON11 inhibits parasite growth by preventing merozoite invasion. The loss of RON11 did not lead to any defects in processing of rhoptry proteins but instead led to a decrease in the amount of rhoptry proteins. We utilized ultrastructure expansion microscopy (U-ExM) to determine the effect of RON11 knockdown on rhoptry biogenesis. Surprisingly, in the absence of RON11, fully developed merozoites had only 1 rhoptry each. The single rhoptry in RON11-deficient merozoites were morphologically typical with a bulb and a neck oriented into the apical polar ring. Moreover, rhoptry proteins are trafficked accurately to the single rhoptry in RON11-deficient parasites. These data show that in the absence of RON11, the first rhoptry is generated during schizogony but upon the start of cytokinesis, the second rhoptry never forms. Interestingly, these single-rhoptry merozoites were able to attach to host RBCs but are unable to invade RBCs. Instead, RON11-deficient merozoites continue to engage with RBC for prolonged periods eventually resulting in echinocytosis, a result of secreting the contents from the single rhoptry into the RBC. Together, our data show that RON11 triggers the de novo biogenesis of the second rhoptry and functions in RBC invasion.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"41 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260213","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}
Organelles have unique structures and molecular compositions for their functions and have been classified accordingly. However, many organelles are heterogeneous and in the process of maturation and differentiation. Because traditional methods have a limited number of parameters and spatial resolution, they struggle to capture the heterogeneous landscapes of organelles. Here, we present a method for multiparametric particle-based analysis of organelles. After disrupting cells, fluorescence microscopy images of organelle particles labeled with 6 to 8 different organelle markers were obtained, and their multidimensional data were represented in two-dimensional uniform manifold approximation and projection (UMAP) spaces. This method enabled visualization of landscapes of 7 major organelles as well as the transitional states of endocytic organelles directed to the recycling and degradation pathways. Furthermore, endoplasmic reticulum–mitochondria contact sites were detected in these maps. Our proposed method successfully detects a wide array of organelles simultaneously, enabling the analysis of heterogeneous organelle landscapes.
{"title":"Organelle landscape analysis using a multiparametric particle-based method","authors":"Yoshitaka Kurikawa, Ikuko Koyama-Honda, Norito Tamura, Seiichi Koike, Noboru Mizushima","doi":"10.1371/journal.pbio.3002777","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002777","url":null,"abstract":"Organelles have unique structures and molecular compositions for their functions and have been classified accordingly. However, many organelles are heterogeneous and in the process of maturation and differentiation. Because traditional methods have a limited number of parameters and spatial resolution, they struggle to capture the heterogeneous landscapes of organelles. Here, we present a method for multiparametric particle-based analysis of organelles. After disrupting cells, fluorescence microscopy images of organelle particles labeled with 6 to 8 different organelle markers were obtained, and their multidimensional data were represented in two-dimensional uniform manifold approximation and projection (UMAP) spaces. This method enabled visualization of landscapes of 7 major organelles as well as the transitional states of endocytic organelles directed to the recycling and degradation pathways. Furthermore, endoplasmic reticulum–mitochondria contact sites were detected in these maps. Our proposed method successfully detects a wide array of organelles simultaneously, enabling the analysis of heterogeneous organelle landscapes.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"215 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260214","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}
Pub Date : 2024-09-13DOI: 10.1371/journal.pbio.3002782
Nhung Hoang, Neda Sardaripour, Grace D. Ramey, Kurt Schilling, Emily Liao, Yiting Chen, Jee Hyun Park, Xavier Bledsoe, Bennett A. Landman, Eric R. Gamazon, Mary Lauren Benton, John A. Capra, Mikail Rubinov
An understanding of human brain individuality requires the integration of data on brain organization across people and brain regions, molecular and systems scales, as well as healthy and clinical states. Here, we help advance this understanding by leveraging methods from computational genomics to integrate large-scale genomic, transcriptomic, neuroimaging, and electronic-health record data sets. We estimated genetically regulated gene expression (gr-expression) of 18,647 genes, across 10 cortical and subcortical regions of 45,549 people from the UK Biobank. First, we showed that patterns of estimated gr-expression reflect known genetic–ancestry relationships, regional identities, as well as inter-regional correlation structure of directly assayed gene expression. Second, we performed transcriptome-wide association studies (TWAS) to discover 1,065 associations between individual variation in gr-expression and gray-matter volumes across people and brain regions. We benchmarked these associations against results from genome-wide association studies (GWAS) of the same sample and found hundreds of novel associations relative to these GWAS. Third, we integrated our results with clinical associations of gr-expression from the Vanderbilt Biobank. This integration allowed us to link genes, via gr-expression, to neuroimaging and clinical phenotypes. Fourth, we identified associations of polygenic gr-expression with structural and functional MRI phenotypes in the Human Connectome Project (HCP), a small neuroimaging-genomic data set with high-quality functional imaging data. Finally, we showed that estimates of gr-expression and magnitudes of TWAS were generally replicable and that the p-values of TWAS were replicable in large samples. Collectively, our results provide a powerful new resource for integrating gr-expression with population genetics of brain organization and disease.
要了解人类大脑的个性，就必须整合不同人群和脑区、分子和系统尺度以及健康和临床状态的大脑组织数据。在这里，我们利用计算基因组学的方法整合了大规模基因组、转录组、神经影像学和电子健康记录数据集，从而帮助加深对这一问题的理解。我们估算了英国生物库中 45,549 人的 10 个皮层和皮层下区域中 18,647 个基因的基因调控表达（gr-expression）。首先，我们发现估计的基因表达模式反映了已知的遗传-后裔关系、区域特征以及直接测定的基因表达的区域间相关结构。其次，我们进行了全转录组关联研究（TWAS），发现了 1,065 种不同人群和脑区的 gr 表达量个体差异与灰质体积之间的关联。我们将这些关联与同一样本的全基因组关联研究（GWAS）结果进行了比对，发现了数百种与这些 GWAS 相关的新关联。第三，我们将研究结果与范德比尔特生物库（Vanderbilt Biobank）中的 gr 表达临床关联进行了整合。这种整合使我们能够通过 gr 表达将基因与神经影像和临床表型联系起来。第四，我们在人类连接组计划（Human Connectome Project，HCP）中发现了多基因 gr 表达与结构性和功能性 MRI 表型的关联，HCP 是一个具有高质量功能成像数据的小型神经成像基因组数据集。最后，我们表明，gr 表达的估计值和 TWAS 的量级通常是可复制的，TWAS 的 p 值在大样本中也是可复制的。总之，我们的研究结果为将 gr 表达与大脑组织和疾病的群体遗传学结合起来提供了强大的新资源。
{"title":"Integration of estimated regional gene expression with neuroimaging and clinical phenotypes at biobank scale","authors":"Nhung Hoang, Neda Sardaripour, Grace D. Ramey, Kurt Schilling, Emily Liao, Yiting Chen, Jee Hyun Park, Xavier Bledsoe, Bennett A. Landman, Eric R. Gamazon, Mary Lauren Benton, John A. Capra, Mikail Rubinov","doi":"10.1371/journal.pbio.3002782","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002782","url":null,"abstract":"An understanding of human brain individuality requires the integration of data on brain organization across people and brain regions, molecular and systems scales, as well as healthy and clinical states. Here, we help advance this understanding by leveraging methods from computational genomics to integrate large-scale genomic, transcriptomic, neuroimaging, and electronic-health record data sets. We estimated genetically regulated gene expression (gr-expression) of 18,647 genes, across 10 cortical and subcortical regions of 45,549 people from the UK Biobank. First, we showed that patterns of estimated gr-expression reflect known genetic–ancestry relationships, regional identities, as well as inter-regional correlation structure of directly assayed gene expression. Second, we performed transcriptome-wide association studies (TWAS) to discover 1,065 associations between individual variation in gr-expression and gray-matter volumes across people and brain regions. We benchmarked these associations against results from genome-wide association studies (GWAS) of the same sample and found hundreds of novel associations relative to these GWAS. Third, we integrated our results with clinical associations of gr-expression from the Vanderbilt Biobank. This integration allowed us to link genes, via gr-expression, to neuroimaging and clinical phenotypes. Fourth, we identified associations of polygenic gr-expression with structural and functional MRI phenotypes in the Human Connectome Project (HCP), a small neuroimaging-genomic data set with high-quality functional imaging data. Finally, we showed that estimates of gr-expression and magnitudes of TWAS were generally replicable and that the <jats:italic>p</jats:italic>-values of TWAS were replicable in large samples. Collectively, our results provide a powerful new resource for integrating gr-expression with population genetics of brain organization and disease.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"10 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269549","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}
Pub Date : 2024-09-12DOI: 10.1371/journal.pbio.3002809
Peter S. Back, Vignesh Senthilkumar, Charles P. Choi, Justin J. Quan, Qing Lou, Anne K. Snyder, Andrew M. Ly, Justin G. Lau, Z. Hong Zhou, Gary E. Ward, Peter J. Bradley
Apicomplexan parasites possess several specialized structures to invade their host cells and replicate successfully. One of these is the inner membrane complex (IMC), a peripheral membrane-cytoskeletal system underneath the plasma membrane. It is composed of a series of flattened, membrane-bound vesicles and a cytoskeletal subpellicular network (SPN) comprised of intermediate filament-like proteins called alveolins. While the alveolin proteins are conserved throughout the Apicomplexa and the broader Alveolata, their precise functions and interactions remain poorly understood. Here, we describe the function of one of these alveolin proteins in Toxoplasma, IMC6. Disruption of IMC6 resulted in striking morphological defects that led to aberrant invasion and replication but surprisingly minor effects on motility. Deletion analyses revealed that the alveolin domain alone is largely sufficient to restore localization and partially sufficient for function. As this highlights the importance of the IMC6 alveolin domain, we implemented unnatural amino acid photoreactive crosslinking to the alveolin domain and identified multiple binding interfaces between IMC6 and 2 other cytoskeletal IMC proteins—IMC3 and ILP1. This provides direct evidence of protein–protein interactions in the alveolin domain and supports the long-held hypothesis that the alveolin domain is responsible for filament formation. Collectively, our study features the conserved alveolin proteins as critical components that maintain the parasite’s structural integrity and highlights the alveolin domain as a key mediator of SPN architecture.
{"title":"Alveolin proteins in the Toxoplasma inner membrane complex form a highly interconnected structure that maintains parasite shape and replication","authors":"Peter S. Back, Vignesh Senthilkumar, Charles P. Choi, Justin J. Quan, Qing Lou, Anne K. Snyder, Andrew M. Ly, Justin G. Lau, Z. Hong Zhou, Gary E. Ward, Peter J. Bradley","doi":"10.1371/journal.pbio.3002809","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002809","url":null,"abstract":"Apicomplexan parasites possess several specialized structures to invade their host cells and replicate successfully. One of these is the inner membrane complex (IMC), a peripheral membrane-cytoskeletal system underneath the plasma membrane. It is composed of a series of flattened, membrane-bound vesicles and a cytoskeletal subpellicular network (SPN) comprised of intermediate filament-like proteins called alveolins. While the alveolin proteins are conserved throughout the Apicomplexa and the broader Alveolata, their precise functions and interactions remain poorly understood. Here, we describe the function of one of these alveolin proteins in <jats:italic>Toxoplasma</jats:italic>, IMC6. Disruption of IMC6 resulted in striking morphological defects that led to aberrant invasion and replication but surprisingly minor effects on motility. Deletion analyses revealed that the alveolin domain alone is largely sufficient to restore localization and partially sufficient for function. As this highlights the importance of the IMC6 alveolin domain, we implemented unnatural amino acid photoreactive crosslinking to the alveolin domain and identified multiple binding interfaces between IMC6 and 2 other cytoskeletal IMC proteins—IMC3 and ILP1. This provides direct evidence of protein–protein interactions in the alveolin domain and supports the long-held hypothesis that the alveolin domain is responsible for filament formation. Collectively, our study features the conserved alveolin proteins as critical components that maintain the parasite’s structural integrity and highlights the alveolin domain as a key mediator of SPN architecture.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"38 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195494","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}
Pub Date : 2024-09-12DOI: 10.1371/journal.pbio.3002798
Lena Spieth,Mikael Simons
Our understanding of Alzheimer's disease (AD) has evolved from focusing solely on neurons to recognizing the role of glia. A recent study in PLOS Biology revealed that oligodendrocytes are an important source of Aβ that impairs neuronal function.
{"title":"Remember oligodendrocytes: Uncovering their overlooked role in Alzheimer's disease.","authors":"Lena Spieth,Mikael Simons","doi":"10.1371/journal.pbio.3002798","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002798","url":null,"abstract":"Our understanding of Alzheimer's disease (AD) has evolved from focusing solely on neurons to recognizing the role of glia. A recent study in PLOS Biology revealed that oligodendrocytes are an important source of Aβ that impairs neuronal function.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"83 1","pages":"e3002798"},"PeriodicalIF":9.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260215","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}
Pub Date : 2024-09-11DOI: 10.1371/journal.pbio.3002784
Wen Wen, Shrey Grover, Douglas Hazel, Peyton Berning, Frederik Baumgardt, Vighnesh Viswanathan, Olivia Tween, Robert M. G. Reinhart
Maintaining and removing information in mind are 2 fundamental cognitive processes that decline sharply with age. Using a combination of beta-band neural oscillations, which have been implicated in the regulation of working memory contents, and cross-trial neural variability, an undervalued property of brain dynamics theorized to govern adaptive cognitive processes, we demonstrate an age-related dissociation between distinct working memory functions—information maintenance and post-response deletion. Load-dependent decreases in beta variability during maintenance predicted memory performance of younger, but not older adults. Surprisingly, the post-response phase emerged as the predictive locus of working memory performance for older adults, with post-response beta variability correlated with memory performance of older, but not younger adults. Single-trial analysis identified post-response beta power elevation as a frequency-specific signature indexing memory deletion. Our findings demonstrate the nuanced interplay between age, beta dynamics, and working memory, offering valuable insights into the neural mechanisms of cognitive decline in agreement with the inhibition deficit theory of aging.
{"title":"Beta-band neural variability reveals age-related dissociations in human working memory maintenance and deletion","authors":"Wen Wen, Shrey Grover, Douglas Hazel, Peyton Berning, Frederik Baumgardt, Vighnesh Viswanathan, Olivia Tween, Robert M. G. Reinhart","doi":"10.1371/journal.pbio.3002784","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002784","url":null,"abstract":"Maintaining and removing information in mind are 2 fundamental cognitive processes that decline sharply with age. Using a combination of beta-band neural oscillations, which have been implicated in the regulation of working memory contents, and cross-trial neural variability, an undervalued property of brain dynamics theorized to govern adaptive cognitive processes, we demonstrate an age-related dissociation between distinct working memory functions—information maintenance and post-response deletion. Load-dependent decreases in beta variability during maintenance predicted memory performance of younger, but not older adults. Surprisingly, the post-response phase emerged as the predictive locus of working memory performance for older adults, with post-response beta variability correlated with memory performance of older, but not younger adults. Single-trial analysis identified post-response beta power elevation as a frequency-specific signature indexing memory deletion. Our findings demonstrate the nuanced interplay between age, beta dynamics, and working memory, offering valuable insights into the neural mechanisms of cognitive decline in agreement with the inhibition deficit theory of aging.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"42 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195503","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}
Pub Date : 2024-09-10DOI: 10.1371/journal.pbio.3002790
Tim Rohe, Klaus Hesse, Ann-Christine Ehlis, Uta Noppeney
Hallucinations and perceptual abnormalities in psychosis are thought to arise from imbalanced integration of prior information and sensory inputs. We combined psychophysics, Bayesian modeling, and electroencephalography (EEG) to investigate potential changes in perceptual and causal inference in response to audiovisual flash-beep sequences in medicated individuals with schizophrenia who exhibited limited psychotic symptoms. Seventeen participants with schizophrenia and 23 healthy controls reported either the number of flashes or the number of beeps of audiovisual sequences that varied in their audiovisual numeric disparity across trials. Both groups balanced sensory integration and segregation in line with Bayesian causal inference rather than resorting to simpler heuristics. Both also showed comparable weighting of prior information regarding the signals’ causal structure, although the schizophrenia group slightly overweighted prior information about the number of flashes or beeps. At the neural level, both groups computed Bayesian causal inference through dynamic encoding of independent estimates of the flash and beep counts, followed by estimates that flexibly combine audiovisual inputs. Our results demonstrate that the core neurocomputational mechanisms for audiovisual perceptual and causal inference in number estimation tasks are largely preserved in our limited sample of medicated post-acute individuals with schizophrenia. Future research should explore whether these findings generalize to unmedicated patients with acute psychotic symptoms.
{"title":"Multisensory perceptual and causal inference is largely preserved in medicated post-acute individuals with schizophrenia","authors":"Tim Rohe, Klaus Hesse, Ann-Christine Ehlis, Uta Noppeney","doi":"10.1371/journal.pbio.3002790","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002790","url":null,"abstract":"Hallucinations and perceptual abnormalities in psychosis are thought to arise from imbalanced integration of prior information and sensory inputs. We combined psychophysics, Bayesian modeling, and electroencephalography (EEG) to investigate potential changes in perceptual and causal inference in response to audiovisual flash-beep sequences in medicated individuals with schizophrenia who exhibited limited psychotic symptoms. Seventeen participants with schizophrenia and 23 healthy controls reported either the number of flashes or the number of beeps of audiovisual sequences that varied in their audiovisual numeric disparity across trials. Both groups balanced sensory integration and segregation in line with Bayesian causal inference rather than resorting to simpler heuristics. Both also showed comparable weighting of prior information regarding the signals’ causal structure, although the schizophrenia group slightly overweighted prior information about the number of flashes or beeps. At the neural level, both groups computed Bayesian causal inference through dynamic encoding of independent estimates of the flash and beep counts, followed by estimates that flexibly combine audiovisual inputs. Our results demonstrate that the core neurocomputational mechanisms for audiovisual perceptual and causal inference in number estimation tasks are largely preserved in our limited sample of medicated post-acute individuals with schizophrenia. Future research should explore whether these findings generalize to unmedicated patients with acute psychotic symptoms.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"25 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195498","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}
Pub Date : 2024-09-10DOI: 10.1371/journal.pbio.3002815
Richard J. Abdill, Emma Talarico, Laura Grieneisen
In 2024, all biology is computational biology. Computer-aided analysis continues to spread into new fields, becoming more accessible to researchers trained in the wet lab who are eager to take advantage of growing datasets, falling costs, and novel assays that present new opportunities for discovery. It is currently much easier to find guidance for implementing these techniques than for reporting their use, leaving biologists to guess which details and files are relevant. In this essay, we review existing literature on the topic, summarize common tips, and link to additional resources for training. Following this overview, we then provide a set of recommendations for sharing code, with an eye toward guiding those who are comparatively new to applying open science principles to their computational work. Taken together, we provide a guide for biologists who seek to follow code sharing best practices but are unsure where to start.
{"title":"A how-to guide for code sharing in biology","authors":"Richard J. Abdill, Emma Talarico, Laura Grieneisen","doi":"10.1371/journal.pbio.3002815","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002815","url":null,"abstract":"In 2024, all biology is computational biology. Computer-aided analysis continues to spread into new fields, becoming more accessible to researchers trained in the wet lab who are eager to take advantage of growing datasets, falling costs, and novel assays that present new opportunities for discovery. It is currently much easier to find guidance for implementing these techniques than for reporting their use, leaving biologists to guess which details and files are relevant. In this essay, we review existing literature on the topic, summarize common tips, and link to additional resources for training. Following this overview, we then provide a set of recommendations for sharing code, with an eye toward guiding those who are comparatively new to applying open science principles to their computational work. Taken together, we provide a guide for biologists who seek to follow code sharing best practices but are unsure where to start.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"69 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195500","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}
Pub Date : 2024-09-10DOI: 10.1371/journal.pbio.3002791
Asma Sarah Khelifa, Maanasa Bhaskaran, Tom Boissavy, Thomas Mouveaux, Tatiana Araujo Silva, Cerina Chhuon, Marcia Attias, Ida Chiara Guerrera, Wanderley De Souza, David Dauvillee, Emmanuel Roger, Mathieu Gissot
Virulence of apicomplexan parasites is based on their ability to divide rapidly to produce significant biomass. The regulation of their cell cycle is therefore key to their pathogenesis. Phosphorylation is a crucial posttranslational modification that regulates many aspects of the eukaryotic cell cycle. The phosphatase PP1 is known to play a major role in the phosphorylation balance in eukaryotes. We explored the role of TgPP1 during the cell cycle of the tachyzoite form of the apicomplexan parasite Toxoplasma gondii. Using a conditional mutant strain, we show that TgPP1 regulates many aspects of the cell cycle including the proper assembly of the daughter cells’ inner membrane complex (IMC), the segregation of organelles, and nuclear division. Unexpectedly, depletion of TgPP1 also results in the accumulation of amylopectin, a storage polysaccharide that is usually found in the latent bradyzoite form of the parasite. Using transcriptomics and phospho-proteomics, we show that TgPP1 mainly acts through posttranslational mechanisms by dephosphorylating target proteins including IMC proteins. TgPP1 also dephosphorylates a protein bearing a starch-binding domain. Mutagenesis analysis reveals that the targeted phospho-sites are linked to the ability of the parasite to regulate amylopectin steady-state levels. Therefore, we show that TgPP1 has pleiotropic roles during the tachyzoite cell cycle regulation, but also regulates amylopectin accumulation.
{"title":"PP1 phosphatase controls both daughter cell formation and amylopectin levels in Toxoplasma gondii","authors":"Asma Sarah Khelifa, Maanasa Bhaskaran, Tom Boissavy, Thomas Mouveaux, Tatiana Araujo Silva, Cerina Chhuon, Marcia Attias, Ida Chiara Guerrera, Wanderley De Souza, David Dauvillee, Emmanuel Roger, Mathieu Gissot","doi":"10.1371/journal.pbio.3002791","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002791","url":null,"abstract":"Virulence of apicomplexan parasites is based on their ability to divide rapidly to produce significant biomass. The regulation of their cell cycle is therefore key to their pathogenesis. Phosphorylation is a crucial posttranslational modification that regulates many aspects of the eukaryotic cell cycle. The phosphatase PP1 is known to play a major role in the phosphorylation balance in eukaryotes. We explored the role of TgPP1 during the cell cycle of the tachyzoite form of the apicomplexan parasite <jats:italic>Toxoplasma gondii</jats:italic>. Using a conditional mutant strain, we show that TgPP1 regulates many aspects of the cell cycle including the proper assembly of the daughter cells’ inner membrane complex (IMC), the segregation of organelles, and nuclear division. Unexpectedly, depletion of TgPP1 also results in the accumulation of amylopectin, a storage polysaccharide that is usually found in the latent bradyzoite form of the parasite. Using transcriptomics and phospho-proteomics, we show that TgPP1 mainly acts through posttranslational mechanisms by dephosphorylating target proteins including IMC proteins. TgPP1 also dephosphorylates a protein bearing a starch-binding domain. Mutagenesis analysis reveals that the targeted phospho-sites are linked to the ability of the parasite to regulate amylopectin steady-state levels. Therefore, we show that TgPP1 has pleiotropic roles during the tachyzoite cell cycle regulation, but also regulates amylopectin accumulation.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"397 1","pages":""},"PeriodicalIF":9.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142195501","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：