Fras1 deficiency results in cryptophthalmos,renal agenesis and blebbed phenotype in mice

Loss of tight association between epidermis and dermis underlies several blistering disorders and is frequently caused by impaired function of extracellular matrix (ECM) proteins. Here we describe a new protein in mouse, Fras1, that is specifically detected in a linear fashion underlying the epidermis and the basal surface of other epithelia in embryos. Loss of Fras1 function results in the formation of subepidermal hemorrhagic blisters as well as unilateral or bilateral renal agenesis during mouse embryogenesis. Postnatally, homozygous Fras1 mutants have fusion of the eyelids and digits and unilateral renal agenesis or dysplasia. The defects observed in Fras1-/- mice phenocopy those of the existing bl (blebbed) mouse mutants, which have been considered a model for the human genetic disorder Fraser syndrome. We show that bl/bl homozygous embryos are devoid of Fras1 protein, consistent with the finding that Fras1 is mutated in these mice. In sum, our data suggest that perturbations in the composition of the extracellular space underlying epithelia could account for the onset of the blebbed phenotype in mouse and Fraser syndrome manifestation in human.     

iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human

We have previously shown that ASPP1 and ASPP2 are specific activators of p53; one mechanism by which wild-type p53 is tolerated in human breast carcinomas is through loss of ASPP activity. We have further shown that 53BP2, which corresponds to a C-terminal fragment of ASPP2, acts as a dominant negative inhibitor of p53 (ref. 1). Hence, an inhibitory form of ASPP resembling 53BP2 could allow cells to bypass the tumor-suppressor functions of p53 and the ASPP proteins. Here, we characterize such a protein, iASPP (inhibitory member of the ASPP family), encoded by PPP1R13L in humans and ape-1 in Caenorhabditis elegans. iASPP is an evolutionarily conserved inhibitor of p53; inhibition of iASPP by RNA-mediated interference or antisense RNA in C. elegans or human cells, respectively, induces p53-dependent apoptosis. Moreover, iASPP is an oncoprotein that cooperates with Ras, E1A and E7, but not mutant p53, to transform cells in vitro. Increased expression of iASPP also confers resistance to ultraviolet radiation and to cisplatin-induced apoptosis. iASPP expression is upregulated in human breast carcinomas expressing wild-type p53 and normal levels of ASPP. Inhibition of iASPP could provide an important new strategy for treating tumors expressing wild-type p53.     

Effect of vanadium and chromium on the microstructural features of V-Cr-Mn-Ni spheroidal carbide cast irons

The objective of this investigation is to study the influence of vanadium (5.0wt%–10.0wt%) and chromium (0–9.0wt%) on the microstructure and hardness of Cr-V-Mn-Ni white cast irons with spheroidal vanadium carbides. The alloys’ microstructural features are presented and discussed with regard to the distribution of phase elements. The structural constituents of the alloys are spheroidal VC, proeutectoid cementite, ledeburite eutectic, rosette-shaped carbide eutectic (based on M₇C₃), pearlite, martensite, and austenite. Their combinations and area fraction (AF) ratios are reported to be influenced by the alloys’ chemical composition. Spheroidized VC particles are found to be sites for the nucleation of carbide eutectics. Cr and V are shown to substitute each other in the VC and M₇C₃ carbides, respectively. Chromium alloying leads to the formation of a eutectic (γ-Fe + M₇C₃), preventing the appearance of proeutectoid cementite in the structure. Vanadium and chromium are revealed to increase the total carbide fraction and the amount of austenite in the matrix. Cr is observed to play a key role in controlling the metallic matrix microstructure.     

Perchlorates as Powerful Catalysts in Many Important Organic Transformations

1 Introduction For long times, metallic perchlorates have been considered dangerous compounds~([1]) in that they function as explosives and as incontrollable oxidizers.Therefore, the fear of the great hazard connected with their manufacture and uses had prevented an extensive use both in research laboratories and in industrial processes~([2]).However, recently it has been cleared that this bad reputation is due to the mistaken association of metallic perchlorates with the oxidizing potential o…     

云南马厂箐铜矿床氦同位素组成研究

众所周知,氦同位素对示踪地壳现代流体(如地下水、温泉、地热体系、海底热液、火山气体和天然气等)中有无幔源组分加入十分灵敏.但是,在示踪地壳古流体(如成矿流体)方面,则因长期以来难以评估氦在扩散丢失过程中所产生的同位素分馏,以及难以扣除原地放射性衰变对流体初始氦同位素组成的影响,而一直未发挥出应有的作用.只是80年代末至90年代初以来,随着对这些问题认识程度的加深,一些学者才先后以矿床中的矿物流体包裹体为测定对象,研究了部分成矿古流体的氦同位素组成,从而开拓了氦同位素在成矿古流体研究中的应用.这些工作主要包括对秘鲁Casapalca Ag-Pb-Zn-Cu矿床和Pasto Bueno W-贱金属矿床、韩国Dae Hwa W-Mo矿床以及一些洋中脊热水沉积黄铁矿等的研究.不过,至今国际上被研究过的矿床和矿种都极其有限.     

Silicon carbide resonant tuning fork for microsensing applications in high temperature and high G shock environments

We present the fabrication and testing of a silicon carbide(SiC)balanced mass double-ended tuning fork that survives harsh environments without compromising the device strain sensitivity and resolution bandwidth.The device features a material stack that survives corrosive environments and enables high-temperature operation.To perform high-temperature testing,a specialized setup was constructed that allows the tuning fork to be characterized using traditional silicon electronics.The tuning fork has been operated at 600 ℃ in the presence of dry steam for short durations.This tuning fork has also been tested to 64 000 G using a hard-launch,soft-catch shock implemented with a light gas gun.However,the device still has a strain sensitivity of 66 Hz/με and strain resolution of 0.045 με in a 10 kHz bandwidth.As such,this balanced-mass double-ended tuning fork can be used to create a variety of different sensors including strain gauges,accelerometers,gyroscopes,and pressure transducers.Given the adaptable fabrication process flow,this device could be useful to micro-electro-mechanical systems(MEMS) designers creating sensors for a variety of different applications.     

基因靶向药物的概念从西妥昔单抗扩展到血小板抑制药物

当对进展期结肠直肠癌患者使用药物如西妥昔单抗治疗研究进行观察时,Science Watch注意到这样一个问题——仅仅那些肿瘤为野生型、非KRAS基因突变型的患者才从这种治疗中获益（Science Watch,11／12月,2009）。     

计算金融学中的自然计算

近年来,自然计算算法（在本文中广义定义为计算机算法,其设计的思想来源于自然界的现象）的应用非常广泛。它可以用来解决金融模型和最优化问题。另一个相关的工作是对来源于自然计算算法的学习机制的应用,     

种群生物学的进化

此书是剑桥大学出版社为纪念Richard Lewontin教授而出版的三部著作中的第三部。第一部是《进化遗传学研究：从分子到形态》,为了纪念Lewontin教授在创立种群和进化遗传学中的研究方法所作的贡献;第二部是《思考进化：从历史学、哲学以及政治学角度》,纪念Lewontin教授在种群生物学的历史学和哲学研究中所做的贡献。