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| 1 | Prioritizing natural-selection signals from the deep-sequencing genomic data suggests multi-variant adaptation in Tibetan highlanders显示文摘Human genetic adaptation to high altitudes(>2500 m)has been extensively studied over the last few years,but few functional adaptive genetic variants have been identified,largely owing to the lack of deep-genome sequencing data available to previous studies.Here,w e build a list of putative adaptive variants,including 63 missense,7 loss-of-function;1,298 evolutionarily conserved variants and 509 expression quantitative traits loci.Notably,the top signal of selection is located in TMEM 247,a transmembrane protein-coding gene.The Tibetan version of TMEM 247 harbors one high-frequency(76.3%)missense variant,rsl 16983452(c.248C>T;p.Ala83Val);with the T allele derived from archaic ancestry and carried by>94%of Tibetans but absent or in low frequencies(<3%)in non-Tibetan populations.The rsl 16983452-T is strongly and positively correlated with altitude and significantly associated with reduced hemoglobin concentration(p=5.78×10^-5),red blood cell count(p=5.72×10^-7)and hematocrit(p=2.57×10^-6).In particular,TMEM247-rs 116983452 shows greater effect size and better predicts the phenotypic outcome than any E P A S1 variants in association with adaptive traits in Tibetans.Modeling the interaction between TM£M247-rsl 16983452 and EPAS1 variants indicates weak but statistically significant epistatic effects.Our results support that multiple variants may jointly deliver the fitness of the Tibetans on the plateau,where a complex model is needed to elucidate the adaptive evolution mechanism. | Lian Deng Chao Zhang Kai Yuan Yang Gao Yuwen Pan Xueling Ge Yaoxi He Yuan Yuan Yan Lu Xiaoxi Zhang Hao Chen Haiyi Lou Xiaoji Wang Dongsheng Lu Jiaojiao Liu Lei Tian Qidi Feng Asifullah Khan Yajun Yang Zi-Bing Jin Jian Yang Fan Lu Jia Qu Longli Kang Bing Su Shuhua Xu | 2019 | National Science Review2019，6，6： | 9 |
| 2 | Activin A maintains cerebral cortex neuronal survival and increases voltage-gated Na^+ neuronal current显示文摘Activin A,which was first described in 1986,has been shown to maintain hippocampal neuronal survival.Activin A increases intracellular free Ca2+ via L-type Ca2+ channels.Our previous study showed that activin A promotes neurite growth of dorsal root ganglia in embryonic chickens and inhibits nitric oxide secretion.The present study demonstrated for the first time that activin A could maintain cerebral cortex neuronal survival in vitro for a long period,and that activin A was shown to increase voltage-gated Na+ current(INa) in Neuro-2a cells,which was recorded by patch clamp technique.The present study revealed a novel mechanism for activin A,as well as the influence of activin A on neurons by regulating expressions of vasoactive intestine peptide and inducible nitric oxide synthase. | Jingyan Ge Yinan Wang Haiyan Liu Fangfang Chen Xueling Cui Zhonghui Liu | 2010 | Neural Regeneration Research2010，5，19： | 4 |
| 3 | Direct Effects of Activin A on the Activation of Mouse Macrophage RAW264.7 Cells显示文摘Macrophages play critical roles in innate immune and acquired immune via secreting pro-inflammatory mediators, phagocytosing microorganisms and presenting antigens. Activin A, a member of transforming growth factor β (TGF-β) superfamily, is produced by macrophages and microglia cells. In this study, we reported a direct effect of activin A as a pro-inflammatory factor on mouse macrophage cell line RAW264.7 cells. Our data revealed that activin A could not only increase IL-1β and IL-6 production from RAW264.7 cells, but also promote pinocytic and phagocytic activities of RAW264.7 cells. In addition, activin A obviously up-regulated MHC II expression on the surface of RAW264.7 cells, whereas did not influence MHC I expression. Activin A also enhanced CD80 expression, which is a marker of activated macrophages, but did not influence RAW264.7 cell proliferation. These data suggest that activin A may regulate primary macrophage-mediated innate and acquired immune response via promoting the activation of rest macrophages. | Jingyan Ge Yinan Wang Ye Feng Haiyan Liu Xueling Cui Guixiang Tai Zhonghui Liu | 2009 | Cellular & Molecular Immunology2009，6，2： | 4 |
| 4 | A Critical Role of Activin A in Maturation of Mouse Peritoneal Macrophages in vitro and in vivo显示文摘Activin A,转变生长因素贝它(TGF-) 的一个多功能的因素总科,被 microglia 和巨噬细胞主要生产,并且它的反煽动性并且支持 inflammatory 活动是与巨噬细胞功能有关的两个。然而,在 vivo 的剩余的巨噬细胞上的 activin A 的直接效果仍然保持不清楚。在现在的学习,结果显示出那 activin A 不仅不增加了并且 IL-1 版本,而且在 vitro 并且在 vivo 的鼠标腹巨噬细胞的支持的吞噬细胞的能力,而它没影响 MHC 我和 MHC II 表示。而且,我们显著地发现那 activin A upregulated CD14 和 CD68 的表情,成熟巨噬细胞的标记,在在 vitro 并且在 vivo 的巨噬细胞的表面上。这些数据建议 activin A 能在 vitro 并且在 vivo 导致主要巨噬细胞成熟,但是不能经由调整涉及抗原的表示的 MHC 分子的表示触发获得的有免疫力的反应。 | Yinan Wang Xueling Cui Guixiang Tai Jingyan Ge Nan Li Fangfang Chen Fang Yu Zhonghui Liu | 2009 | Cellular & Molecular Immunology2009，6，5： | 2 |
| 5 | SET1A催化YAP甲基化修饰调控YAP细胞核转运和促进肿瘤发生显示文摘文章简介YAP作为Hippo信号通路主要效应因子之一,在Hippo通路受抑的条件下,从细胞质转运至细胞核调控基因表达和促进肿瘤发生。虽然YAP锚定在细胞质中的调控机制已经被广泛研究,但是YAP激活后入核在细胞核中持续积累的分子机制并不十分清楚。 | 方兰 滕鸿琦 王益林 廖光红 Linjun Weng Yaxu Li Xinbo Wang Jiali Jin Chenchen Jiao Lei Chen Xiaoping Peng Jiayu Chen Yongzhi Yang Houqin Fang Dongyan Han Cheng Li Xueling Jin Shihao Zhang Zhongchen Liu Min Liu Qing Wei Lujian Liao Xin Ge Bin Zhao Dawang Zhou HuanLong Qin Jun Zhou 王平 | 2019 | 科学新闻2019，0，2： | 0 |
| 6 | Micro-coevolution of host genetics with gut microbiome in three Chinese ethnic groups显示文摘Understanding the micro-coevolution of the human gut microbiome with host genetics is challenging but essential in both evolutionary and medical studies.To gain insight into the interactions between host genetic variation and the gut microbiome,we analyzed both the human genome and gut microbiome collected from a cohort of 190 students in the same boarding college and representing 3 ethnic groups,Uyghur,Kazakh,and Han Chinese.We found that differences in gut microbiome were greater between genetically distinct ethnic groups than those genetically closely related ones in taxonomic composition,functional composition,enterotype stratification,and microbiome genetic differentiation.We also observed considerable correlations between host genetic variants and the abundance of a subset of gut microbial species.Notably,interactions between gut microbiome species and host genetic variants might have coordinated effects on specific human phenotypes.Bacteroides ovatus,previously reported to modulate intestinal immunity,is significantly correlated with the host genetic variant rs12899811(meta-P=5.55×10^(-5)),which regulates the VPS33B expression in the colon,acting as a tumor suppressor of colorectal cancer.These results advance our understanding of the micro-coevolution of the human gut microbiome and their interactive effects with host genetic variation on phenotypic diversity. | Mingyue Cheng Xueling Ge Chaofang Zhong Ruiqing Fu Kang Ning Shuhua Xu | 2021 | Journal of Genetics and Genomics2021，48，11： | 0 |
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