Bone morphogenetic protein-3 is a negative regulator of bone density

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-beta) superfamily. Many BMPs are produced in bone and show osteogenic activity, suggesting that they may be determinants of bone mass. BMP3 was originally purified from bone as osteogenin, which induces osteogenic differentiation. Recombinant BMP3 (rhBMP3) has no biological activity, however, leaving its role in skeletal growth unclear. Here we show that BMP3 is an antagonist of osteogenic BMPs: BMP3 dorsalizes Xenopus laevis embryos, inhibits BMP2-mediated induction of Msx2 and blocks BMP2-mediated differentiation of osteoprogenitor cells into osteoblasts. These effects appear to be mediated through activin receptors. Finally, Bmp3(-/-) mice have twice as much trabecular bone as wild-type littermates, indicating that BMP3, the most abundant BMP in adult bone, is a negative determinant of bone density.     

A conditional knockout resource for the genome-wide study of mouse gene function

Gene targeting in embryonic stem cells has become the principal technology for manipulation of the mouse genome, offering unrivalled accuracy in allele design and access to conditional mutagenesis. To bring these advantages to the wider research community, large-scale mouse knockout programmes are producing a permanent resource of targeted mutations in all protein-coding genes. Here we report the establishment of a high-throughput gene-targeting pipeline for the generation of reporter-tagged, conditional alleles. Computational allele design, 96-well modular vector construction and high-efficiency gene-targeting strategies have been combined to mutate genes on an unprecedented scale. So far, more than 12,000 vectors and 9,000 conditional targeted alleles have been produced in highly germline-competent C57BL/6N embryonic stem cells. High-throughput genome engineering highlighted by this study is broadly applicable to rat and human stem cells and provides a foundation for future genome-wide efforts aimed at deciphering the function of all genes encoded by the mammalian genome.     

Mitochondrial activity: A possible determinant of anoxic injury in renal medulla

Summary In brain¹, heart² and kidney³, cell work in the absence of oxygen has been thought to precipitate anoxic damage by increasing the rate of depletion of cellular energy stores. In the medullary thick ascending limb of isolated perfused rat kidneys, however, reduction of ATP synthesis by a variety of mitochondrial or metabolic inhibitors caused ATP depletion comparable to that produced by oxygen deprivation but did not reproduce the lesions of anoxia. In these cells, unrestrained mitochondrial activity may be an important source of anoxic injury.     

一种实用监控系统的人脸检测定位算法

对基于监控系统中彩色图像的人脸检测与定位方法进行了探讨,利用颜色对方向的不敏感来减少人脸区域的搜索范围,将颜色空间与Hough变换相结合实现人脸定位.首先在颜色空间YCbCr上建立肤色模型,并对肤色区域进行初步检测,然后利用自适应模糊Hough变换检测瞳孔所在的圆心,从而实现对人脸区域的精确定位.在Georgia Tech彩色人脸数据库上的实验结果表明:该方法能够较好地检测肤色偏黄的人脸,并且在人眼的定位阶段平均用时为0.1秒,满足数字监控中实时性的要求.     

Structure and control of the actin regulatory WAVE complex

Members of the Wiskott-Aldrich syndrome protein (WASP) family control cytoskeletal dynamics by promoting actin filament nucleation with the Arp2/3 complex. The WASP relative WAVE regulates lamellipodia formation within a 400-kilodalton, hetero-pentameric WAVE regulatory complex (WRC). The WRC is inactive towards the Arp2/3 complex, but can be stimulated by the Rac GTPase, kinases and phosphatidylinositols. Here we report the 2.3-?ngstrom crystal structure of the WRC and complementary mechanistic analyses. The structure shows that the activity-bearing VCA motif of WAVE is sequestered by a combination of intramolecular and intermolecular contacts within the WRC. Rac and kinases appear to destabilize a WRC element that is necessary for VCA sequestration, suggesting the way in which these signals stimulate WRC activity towards the Arp2/3 complex. The spatial proximity of the Rac binding site and the large basic surface of the WRC suggests how the GTPase and phospholipids could cooperatively recruit the complex to membranes.     

硅灰石粒径对PP/PP-g-MMA/W复合体系非等温结晶的影响

以甲基丙烯酸甲酯接枝聚丙烯(PP-g-MMA)为硅灰石(W)填充聚丙烯(PP)复合材料(PP/W)的界面相容剂,研究了W粒径对聚丙烯/硅灰石(PP/PP-g-MMA/W)复合体系力学性能和非等温结晶行为的影响.用Avrami方程、Ozawa、Mo、和Kissinger方法分析了复合材料非等温结晶曲线,得到n、Kc、α、F(T)、TP、T1/2和△E等参数.结果表明,W粒径对n和α影响不大;在W异相成核、W粒径和增容荆共同作用下,W粒径为400目和800目的试样,K较大,F(T)、t1/2较小,TP较高,形成的晶粒较完善、细小,提高了复合材料的塑性和韧性,特别是800目的试样塑性和韧性最好.     

模拟失重对大鼠睾丸组织结构及AR和HSP70表达的影响

采用-30°尾部悬帛模拟失重生理效应,32只Wistar雄性大鼠随机分为7 d对照组、14 d对照组、悬吊7 d组和悬吊14 d组4组,运用HE染色和免疫组织化学染色方法,分别观察模拟失重7 d、14 d大鼠睾丸组织的组织病理学变化,同时定置对比观察了对照组、模拟失重组大鼠睾丸组织中AR和HSP70的表达和定位.结果显示,悬吊7 d和14 d的大鼠睾丸组织均出现了明显的组织病理学变化,表现为睾丸曲细精管内生精上皮细胞排列紊乱,出现不同程度的变性、坏死:悬吊14 d的大鼠睾丸的病变比悬吊7 d的更为明显.免疫组化染色结果表明,模拟失重7 d、14 d的大鼠睾丸组织中,AR表达量均极显著降低(P<0.01);而HSP70表达置均极显著升高(P<0.01).在组织间隙和间质渗出物中出现大量eHSP70.研究表明,模拟失重状态对雄性大鼠生殖器官睾丸的组织结构会造成严重的病理损伤,导致睾丸生精上皮不可逆损伤,使睾丸组织分泌表达AR的功能减退,引起HSP70的过量表达和大量释放形成eHSP70,以至造成睾丸实质的严重损伤.