丝裂原活化蛋白激酶磷酸酶-2(MKP-2/DUSP4)具有酪氨酸磷酸酶和丝氨酸/苏氨酸磷酸酶活性,可以作用于MAPKs(Mitogen-activated protein kinases)底物,使其去磷酸化。但dusp4在脊椎动物胚胎发育中的功能还所知甚少。为深入了解dusp4在发育...丝裂原活化蛋白激酶磷酸酶-2(MKP-2/DUSP4)具有酪氨酸磷酸酶和丝氨酸/苏氨酸磷酸酶活性,可以作用于MAPKs(Mitogen-activated protein kinases)底物,使其去磷酸化。但dusp4在脊椎动物胚胎发育中的功能还所知甚少。为深入了解dusp4在发育中的作用,文章首先检测了其在斑马鱼胚胎的表达。通过整胚原位杂交实验,发现dusp4是斑马鱼母源表达的基因,并且随着发育的进行,在原肠早期特异表达在中内胚层区域。进一步的实验表明,Nodal信号对dusp4的表达至关重要。过表达Nodal信号的配体sqt、dusp4的表达水平明显升高,而在缺失Nodal信号的突变体MZoep中,几乎检测不到dusp4的表达。此外,文章利用反义核苷酸Morpholino(MO)敲降dusp4的表达,中内胚层标识基因gsc、sox17和sox32的表达水平显著升高,而过表达dusp4对中内胚层的形成没有明显的影响,表明dusp4对中内胚层形成的抑制作用是必需的,但不是充分的,可能还有其他未被鉴定的协同作用因子。以上研究结果表明,dusp4基因的表达受到Nodal信号调控,在原肠期具有抑制中内胚层形成的作用。展开更多
A methodology for topology optimization based on element independent nodal density(EIND) is developed.Nodal densities are implemented as the design variables and interpolated onto element space to determine the densit...A methodology for topology optimization based on element independent nodal density(EIND) is developed.Nodal densities are implemented as the design variables and interpolated onto element space to determine the density of any point with Shepard interpolation function.The influence of the diameter of interpolation is discussed which shows good robustness.The new approach is demonstrated on the minimum volume problem subjected to a displacement constraint.The rational approximation for material properties(RAMP) method and a dual programming optimization algorithm are used to penalize the intermediate density point to achieve nearly 0-1 solutions.Solutions are shown to meet stability,mesh dependence or non-checkerboard patterns of topology optimization without additional constraints.Finally,the computational efficiency is greatly improved by multithread parallel computing with OpenMP.展开更多
文摘TGF-β/Nodal信号通路在斑马鱼胚胎背腹分化过程中发挥重要作用。为了进一步探究该信号通路的功能及作用机制,文章采用酵母双杂交的方法,以斑马鱼Smad2/3a为诱饵蛋白筛选得到一系列Smad2/3a的互作蛋白,其中之一为Rbb4l(Retinoblastoma binding protein 4,like)。已有的报道表明,Rbb4l的人类同源蛋白RBBP4(Retino blastoma binding protein 4)是染色质修饰相关的复合体的组成成分,但它在脊椎动物胚胎发育过程中的作用还知之甚少。文章通过体外及体内的一系列实验表明,Rbb4l能直接与Smad3a互作,增强TGF-β/Nodal信号。在斑马鱼胚胎中过表达rbb4l导致胚胎的背部化,伴随着背部标记基因表达区域的扩大和腹部标记基因表达区域的缩小。相反,在胚胎中下调rbb4l的表达,可以导致胚胎在24 hpf(hours post-fertilization)左右出现腹部化的表型。文章进一步通过一系列的挽救实验,证明在缺少Nodal信号的情况下,rbb4l的过表达不能引起胚胎的背部化。综上所述,Rbb4l可以增强Nodal/Smad2/3信号,并且这种正向调节的功能依赖于Nodal信号本身。
文摘丝裂原活化蛋白激酶磷酸酶-2(MKP-2/DUSP4)具有酪氨酸磷酸酶和丝氨酸/苏氨酸磷酸酶活性,可以作用于MAPKs(Mitogen-activated protein kinases)底物,使其去磷酸化。但dusp4在脊椎动物胚胎发育中的功能还所知甚少。为深入了解dusp4在发育中的作用,文章首先检测了其在斑马鱼胚胎的表达。通过整胚原位杂交实验,发现dusp4是斑马鱼母源表达的基因,并且随着发育的进行,在原肠早期特异表达在中内胚层区域。进一步的实验表明,Nodal信号对dusp4的表达至关重要。过表达Nodal信号的配体sqt、dusp4的表达水平明显升高,而在缺失Nodal信号的突变体MZoep中,几乎检测不到dusp4的表达。此外,文章利用反义核苷酸Morpholino(MO)敲降dusp4的表达,中内胚层标识基因gsc、sox17和sox32的表达水平显著升高,而过表达dusp4对中内胚层的形成没有明显的影响,表明dusp4对中内胚层形成的抑制作用是必需的,但不是充分的,可能还有其他未被鉴定的协同作用因子。以上研究结果表明,dusp4基因的表达受到Nodal信号调控,在原肠期具有抑制中内胚层形成的作用。
基金Projects(11372055,11302033)supported by the National Natural Science Foundation of ChinaProject supported by the Huxiang Scholar Foundation from Changsha University of Science and Technology,ChinaProject(2012KFJJ02)supported by the Key Labortory of Lightweight and Reliability Technology for Engineering Velicle,Education Department of Hunan Province,China
文摘A methodology for topology optimization based on element independent nodal density(EIND) is developed.Nodal densities are implemented as the design variables and interpolated onto element space to determine the density of any point with Shepard interpolation function.The influence of the diameter of interpolation is discussed which shows good robustness.The new approach is demonstrated on the minimum volume problem subjected to a displacement constraint.The rational approximation for material properties(RAMP) method and a dual programming optimization algorithm are used to penalize the intermediate density point to achieve nearly 0-1 solutions.Solutions are shown to meet stability,mesh dependence or non-checkerboard patterns of topology optimization without additional constraints.Finally,the computational efficiency is greatly improved by multithread parallel computing with OpenMP.
