The rhesus macaque(Macaca mulatta)is a crucial experimental animal that shares many genetic,brain organizational,and behavioral characteristics with humans.A macaque brain atlas is fundamental to biomedical and evolut...The rhesus macaque(Macaca mulatta)is a crucial experimental animal that shares many genetic,brain organizational,and behavioral characteristics with humans.A macaque brain atlas is fundamental to biomedical and evolutionary research.However,even though connectivity is vital for understanding brain functions,a connectivity-based whole-brain atlas of the macaque has not previously been made.In this study,we created a new whole-brain map,the Macaque Brainnetome Atlas(MacBNA),based on the anatomical connectivity profiles provided by high angular and spatial resolution ex vivo diffusion MRI data.The new atlas consists of 248 cortical and 56 subcortical regions as well as their structural and functional connections.The parcellation and the diffusion-based tractography were evaluated with invasive neuronal-tracing and Nissl-stained images.As a demonstrative application,the structural connectivity divergence between macaque and human brains was mapped using the Brainnetome atlases of those two species to uncover the genetic underpinnings of the evolutionary changes in brain structure.The resulting resource includes:(1)the thoroughly delineated Macaque Brainnetome Atlas(MacBNA),(2)regional connectivity profiles,(3)the postmortem high-resolution macaque diffusion and T2-weighted MRI dataset(Brainnetome-8),and(4)multi-contrast MRI,neuronal-tracing,and histological images collected from a single macaque.MacBNA can serve as a common reference frame for mapping multifaceted features across modalities and spatial scales and for integrative investigation and characterization of brain organization and function.Therefore,it will enrich the collaborative resource platform for nonhuman primates and facilitate translational and comparative neuroscience research.展开更多
The emergence of farming has long been construed as a fundamental stepping stone on the path of human progress.Within archaeological research,that emergence has remained a major focus of enquiry,typically with an emph...The emergence of farming has long been construed as a fundamental stepping stone on the path of human progress.Within archaeological research,that emergence has remained a major focus of enquiry,typically with an emphasis on the advantages it conveys upon human societies.Recent studies have opened up a wider range of perspectives.展开更多
微小染色体维持蛋白2(minichromosome maintenance protein 2,MCM2)的异常表达与多种恶性肿瘤的发生发展密切相关。为探索MCM2基因对胆管癌细胞肿瘤生物学行为的影响及其潜在的作用机制,本研究首先采用cell counting kit-8(CCK-8)、平...微小染色体维持蛋白2(minichromosome maintenance protein 2,MCM2)的异常表达与多种恶性肿瘤的发生发展密切相关。为探索MCM2基因对胆管癌细胞肿瘤生物学行为的影响及其潜在的作用机制,本研究首先采用cell counting kit-8(CCK-8)、平板细胞克隆形成、Transwell和Invasion实验证实,MCM2可促进胆管癌细胞的增殖、迁移和侵袭能力;流式细胞术检测结果显示,MCM2可加快细胞周期进程,抑制细胞凋亡。进一步通过对胆管癌组织RNA测序数据集的分析发现,MCM2基因与p53信号通路的激活显著负相关。采用实时定量PCR(quantitative real time polymerase chain reaction,qRT-PCR)和蛋白质免疫印迹(Western blotting,WB)实验发现,在胆管癌细胞中MCM2可显著下调p53和BAX的mRNA和蛋白表达水平,显著上调BCL2和CCND1的mRNA和蛋白表达水平。采用流式细胞术、qRT-PCR和WB实验进一步证实MCM2基因依赖于p53通路发挥影响胆管癌细胞周期和凋亡的功能。最后,通过分析MCM2的表达水平与胆管癌患者临床预后的相关性发现,MCM2在胆管癌组织中的表达显著高于癌旁组织,且其高表达与患者的不良预后显著相关。综上所述,本研究初步揭示MCM2可能通过抑制p53信号通路促进胆管癌的发生发展,并提示MCM2的高表达与胆管癌的不良预后显著相关,为未来胆管癌新的临床诊治措施的研发提供了理论依据。展开更多
基金partially supported by the Science and Technology Innovation 2030-Brain Science and Brain-Inspired Intelligence Project(2021ZD0200200)the National Natural Science Foundation of China(62327805,82151307,82072099,82202253)。
文摘The rhesus macaque(Macaca mulatta)is a crucial experimental animal that shares many genetic,brain organizational,and behavioral characteristics with humans.A macaque brain atlas is fundamental to biomedical and evolutionary research.However,even though connectivity is vital for understanding brain functions,a connectivity-based whole-brain atlas of the macaque has not previously been made.In this study,we created a new whole-brain map,the Macaque Brainnetome Atlas(MacBNA),based on the anatomical connectivity profiles provided by high angular and spatial resolution ex vivo diffusion MRI data.The new atlas consists of 248 cortical and 56 subcortical regions as well as their structural and functional connections.The parcellation and the diffusion-based tractography were evaluated with invasive neuronal-tracing and Nissl-stained images.As a demonstrative application,the structural connectivity divergence between macaque and human brains was mapped using the Brainnetome atlases of those two species to uncover the genetic underpinnings of the evolutionary changes in brain structure.The resulting resource includes:(1)the thoroughly delineated Macaque Brainnetome Atlas(MacBNA),(2)regional connectivity profiles,(3)the postmortem high-resolution macaque diffusion and T2-weighted MRI dataset(Brainnetome-8),and(4)multi-contrast MRI,neuronal-tracing,and histological images collected from a single macaque.MacBNA can serve as a common reference frame for mapping multifaceted features across modalities and spatial scales and for integrative investigation and characterization of brain organization and function.Therefore,it will enrich the collaborative resource platform for nonhuman primates and facilitate translational and comparative neuroscience research.
文摘The emergence of farming has long been construed as a fundamental stepping stone on the path of human progress.Within archaeological research,that emergence has remained a major focus of enquiry,typically with an emphasis on the advantages it conveys upon human societies.Recent studies have opened up a wider range of perspectives.
基金supported by the National Natural Science Foundation of China (22275073,22005119,21731002,21975104 and 22150004)Guangdong Major Project of Basic and Applied Research (2019B030302009)+2 种基金Guangdong Basic and Applied Basic Research Foundation (2020A1515110404)Guangzhou Basic and Applied Basic Research Foundation (202102020444)the Fundamental Research Funds for the Central Universities (21622409)。
文摘微小染色体维持蛋白2(minichromosome maintenance protein 2,MCM2)的异常表达与多种恶性肿瘤的发生发展密切相关。为探索MCM2基因对胆管癌细胞肿瘤生物学行为的影响及其潜在的作用机制,本研究首先采用cell counting kit-8(CCK-8)、平板细胞克隆形成、Transwell和Invasion实验证实,MCM2可促进胆管癌细胞的增殖、迁移和侵袭能力;流式细胞术检测结果显示,MCM2可加快细胞周期进程,抑制细胞凋亡。进一步通过对胆管癌组织RNA测序数据集的分析发现,MCM2基因与p53信号通路的激活显著负相关。采用实时定量PCR(quantitative real time polymerase chain reaction,qRT-PCR)和蛋白质免疫印迹(Western blotting,WB)实验发现,在胆管癌细胞中MCM2可显著下调p53和BAX的mRNA和蛋白表达水平,显著上调BCL2和CCND1的mRNA和蛋白表达水平。采用流式细胞术、qRT-PCR和WB实验进一步证实MCM2基因依赖于p53通路发挥影响胆管癌细胞周期和凋亡的功能。最后,通过分析MCM2的表达水平与胆管癌患者临床预后的相关性发现,MCM2在胆管癌组织中的表达显著高于癌旁组织,且其高表达与患者的不良预后显著相关。综上所述,本研究初步揭示MCM2可能通过抑制p53信号通路促进胆管癌的发生发展,并提示MCM2的高表达与胆管癌的不良预后显著相关,为未来胆管癌新的临床诊治措施的研发提供了理论依据。
基金supported by grants from the Great Key Project of China National Social Science Fund(No.12&ZD024)the National Natural Science Fund(No.71373054/No.71073029)
