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《医学前沿（英文）》 2016年 第10卷 第3期 页码 311-319 doi: 10.1007/s11684-016-0460-0
We evaluated the roles of calpain cleavage-related mutations of the integrin β3 cytoplasmic tail in integrin αIIbβ3 bidirectional signaling using a trans-dominant inhibition model. Chimeric Tac-β3 proteins (i.e., Tac-β3, Tac-β3D741, Tac-β3D747, Tac-β3D754, Tac-β3D759, and Tac-β3DNITY) consisting of the extracellular and transmembrane domains of human IL-2 receptor (Tac) and the human integrin β3 cytoplasmic domain were stably expressed in the 123 CHO cells harboring human glycoprotein Ib-IX and wild-type integrin αIIbβ3. The different cells were assayed for stable adhesion and spreading on immobilized fibrinogen, and for binding soluble fibrinogen representing outside-in and inside-out signaling events, respectively. The chimeric protein Tac-β3 inhibited, and Tac-β3DNITY partially attenuated stable adhesion and spreading. Tac-β3, Tac-β3D759, Tac-β3DNITY, and Tac-β3D754, but not Tac-β3D747 or Tac-β3D741, impaired the soluble fibrinogen binding. Results indicated that the bidirectional signaling was significantly inhibited by Tac-β3 and Tac-β3DNITY, albeit to a much lesser extent. Moreover, only inside-out signaling was impaired in the 123/Tac-β3D759 and 123/Tac-β3D754 cells in contrast to an intact bidirectional signaling in the 123/Tac-β3D747 and 123/Tac-β3D741 cells. In conclusion, the calpain cleavage of integrin β3 resulted in the regulatory effects on signaling by interrupting its interaction with cytoplasmic proteins rather than altering its conformation, and may thus regulate platelet function.
关键词： integrin β3 signal transduction trans-dominant inhibition model
Treatment of gingival hyperplasia induced by cyclosporine A
MA Jingzhi, LI Ming, CAO Yingguang
《医学前沿（英文）》 2008年 第2卷 第3期 页码 290-294 doi: 10.1007/s11684-008-0055-5
关键词： post-transplantation Gingival cytoplasmic CsA-induced further
Embryo-mediated genome editing for accelerated genetic improvement of livestock
Zachariah MCLEAN, Björn OBACK, Götz LAIBLE
《农业科学与工程前沿（英文）》 2020年 第7卷 第2期 页码 148-160 doi: 10.15302/J-FASE-2019305
Selecting beneficial DNA variants is the main goal of animal breeding. However, this process is inherently inefficient because each animal only carries a fraction of all desirable variants. Genome editing technology with its ability to directly introduce beneficial sequence variants offers new opportunities to modernize animal breeding by overcoming this biological limitation and accelerating genetic gains. To realize rapid genetic gain, precise edits need to be introduced into genomically-selected embryos, which minimizes the genetic lag. However, embryo-mediated precision editing by homology-directed repair (HDR) mechanisms is currently an inefficient process that often produces mosaic embryos and greatly limits the numbers of available edited embryos. This review provides a summary of genome editing in bovine embryos and proposes an embryo-mediated accelerated breeding scheme that overcomes the present efficiency limitations of HDR editing in bovine embryos. It integrates embryo-based genomic selection with precise multi-editing and uses embryonic cloning with elite edited blastomeres or embryonic pluripotent stem cells to resolve mosaicism, enable multiplex editing and multiply rare elite genotypes. Such a breeding strategy would enable a more targeted, accelerated approach for livestock improvement that allows stacking of beneficial variants, even including novel traits from outside the breeding population, in the most recent elite genetic background, essentially within a single generation.
关键词： animal breeding cattle cloning CRISPR/Cas9 cytoplasmic injection embryo genome editing germline chimaeras HDR livestock improvement TALENs
标题 作者 时间 类型 操作
Roles of integrin β3 cytoplasmic tail in bidirectional signal transduction in a trans-dominant inhibition
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