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2篇 您的检索式:作者名="Chuanyin Shi"
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1MKRN3 regulates the epigenetic switch of mammalian puberty via ubiquitination of MBD3显示文摘Central precocious puberty(CPP)refers to a human syndrome of early puberty initiation with characteristic increase in hypothalamic production and release of gonadotropin-releasing hormone(GnRH).Previously,loss-of-function mutations in human MKRN3,encoding a putative E3 ubiquitin ligase,were found to contribute to about 30%of cases of familial CPP.MKRN3 was thereby suggested to serve as a‘brake’of mammalian puberty onset,but the underlying mechanisms remain as yet unknown.Here,we report that genetic ablation of Mkrn3 did accelerate mouse puberty onset with increased production of hypothalamic GnRH1.MKRN3 interacts with and ubiquitinates MBD3,which epigenetically silences GNRH1 through disrupting the MBD3 binding to the GNRH1 promoter and recruitment of DNA demethylase TET2.Our findings have thus delineated a molecular mechanism through which the MKRN3-MBD3 axis controls the epigenetic switch in the onset of mammalian puberty.Chuanyin Li Wenli Lu Liguang Yang Zhengwei Li Xiaoyi Zhou Rong Guo Junqi Wang Zhebao Wu Zhiya Dong Guang Ning Yujiang Shi Yinmin Gu Peng Chen Zijian Hao Tianting Han Meiqiang Yang Wei Wang Xuehui Huang Yixue Li Shan Gao Ronggui Hu 2020National Science Review2020,7,3:2
2Scalable manufacturing methodologies for improving adeno-associated virus-based pharmaprojects显示文摘Adeno-associated virus(AAV)is a promising viral vector and meets most requirements of being a safe biological agent.However,the commercialization of AAV has been hampered due to the limitation of large-scale production,and only a small number of clinical trials have been launched.In recent years,progresses in scalable manufacturing of AAV have dramatically improved AAVbased clinical researches,and have assisted the development of investigational drug products.An AAV1-based investigational product,Glybera,has been formally approved by European Commission for the treatment of lipoprotein lipase deficiency(LPLD).Glybera was the first gene therapy product in the western world,and the production process involves a scalable baculovirus-insect cell system.However,many problems still need to be solved to improve the productivity and quality of AAV.The present review gives critical insights into current state-of-the-art scalable producing methodologies of AAV,such as baculovirus-insect cell system,HSV complementation system,and Ad complementation system,along with a discussion on the problems,solutions,and developmental trends.Novel AAV-producing platforms in Saccharomyces cerevisiae and vaccinia virus complementation system will also be discussed.Zenghui Xu Chuanyin Shi Qijun Qian 2014Chinese Science Bulletin2014,59,16:2
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