Pregnenolone stabilizes microtubules and promotes zebrafish embryonic cell movement

Embryonic cell movement is essential for morphogenesis and the establishment of body shapes, but little is known about its mechanism. Here we report that pregnenolone, which is produced from cholesterol by the steroidogenic enzyme Cyp11a1 (cholesterol side-chain cleavage enzyme, P450scc), functions in promoting cell migration during epiboly. Epiboly is a process in which embryonic cells spread from the animal pole to cover the underlying yolk. During epiboly, cyp11a1 is expressed in an extra-embryonic yolk syncytial layer. Reducing cyp11a1 expression in zebrafish using antisense morpholino oligonucleotides did not perturb cell fates, but caused epibolic delay. This epibolic defect was partially rescued by the injection of cyp11a1 RNA or the supplementation of pregnenolone. We show that the epibolic delay is accompanied by a decrease in the level of polymerized microtubules, and that pregnenolone can rescue this microtubule defect. Our results indicate that pregnenolone preserves microtubule abundance and promotes cell movement during epiboly.     

Evidence for two independent prostate cancer risk-associated loci in the HNF1B gene at 17q12

We carried out a fine-mapping study in the HNF1B gene at 17q12 in two study populations and identified a second locus associated with prostate cancer risk, approximately 26 kb centromeric to the first known locus (rs4430796); these loci are separated by a recombination hot spot. We confirmed the association with a SNP in the second locus (rs11649743) in five additional populations, with P = 1.7 x 10(-9) for an allelic test of the seven studies combined. The association at each SNP remained significant after adjustment for the other SNP.     

Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model

Individuals with 22q11.2 microdeletions show behavioral and cognitive deficits and are at high risk of developing schizophrenia. We analyzed an engineered mouse strain carrying a chromosomal deficiency spanning a segment syntenic to the human 22q11.2 locus. We uncovered a previously unknown alteration in the biogenesis of microRNAs (miRNAs) and identified a subset of brain miRNAs affected by the microdeletion. We provide evidence that the abnormal miRNA biogenesis emerges because of haploinsufficiency of the Dgcr8 gene, which encodes an RNA-binding moiety of the 'microprocessor' complex and contributes to the behavioral and neuronal deficits associated with the 22q11.2 microdeletion.     

Selective development of CD4+ T cells in transgenic mice expressing a class II MHC-restricted antigen receptor

T lymphocytes are predisposed to recognition of foreign protein fragments bound to cell-surface molecules encoded by the major histocompatibility complex (MHC). There is now compelling evidence that this specificity is a consequence of a selection process operating on developing T lymphocytes in the thymus. As a result of this positive selection, thymocytes that express antigen receptors with a threshold affinity for self MHC-encoded glycoproteins preferentially emigrate from the thymus and seed peripheral lymphoid organs. The specificity for both foreign antigen and MHC molecules is imparted by the alpha and beta chains of the T-cell antigen receptor (TCR). Two other T-cell surface proteins, CD4 and CD8, which bind non-polymorphic regions of class II and class I MHC molecules respectively, are also involved in these recognition events and play an integral role in thymic selection. In order to elucidate the developmental pathways of class II MHC-restricted T cells in relation to these essential accessory molecules, we have produced TCR-transgenic mice expressing a receptor specific for a fragment of pigeon cytochrome c and the Ek (class II MHC) molecule. The transgenic TCR is expressed on virtually all T cells in mice expressing Ek. The thymuses of these mice contain an abnormally high percentage of mature CD4+CD8- cells. In addition, the peripheral T-cell population is almost exclusively CD4+, demonstrating that the MHC specificity of the TCR determines the phenotype of T cells during selection in the thymus.     

Caenorhabditis elegans: plague bacteria biofilm blocks food intake

Bubonic plague is transmitted to mammals, including humans, by the bites of fleas whose digestive tracts are blocked by a mass of the bacterium Yersinia pestis. In these fleas, the plague-causing bacteria are surrounded by an extracellular matrix of unknown composition, and the blockage depends on a group of bacterial genes known as the hmsHFRS operon. Here we show that Y. pestis creates an hmsHFRS-dependent extracellular biofilm to inhibit feeding by the nematode Caenorhabditis elegans. Our results suggest that feeding obstruction in fleas is a biofilm-mediated process and that biofilms may be a bacterial defence against predation by invertebrates.     

A sperm ion channel required for sperm motility and male fertility

Calcium and cyclic nucleotides have crucial roles in mammalian fertilization, but the molecules comprising the Ca2+-permeation pathway in sperm motility are poorly understood. Here we describe a putative sperm cation channel, CatSper, whose amino-acid sequence most closely resembles a single, six-transmembrane-spanning repeat of the voltage-dependent Ca2+-channel four-repeat structure. CatSper is located specifically in the principal piece of the sperm tail. Targeted disruption of the gene results in male sterility in otherwise normal mice. Sperm motility is decreased markedly in CatSper-/- mice, and CatSper-/- sperm are unable to fertilize intact eggs. In addition, the cyclic-AMP-induced Ca2+ influx is abolished in the sperm of mutant mice. CatSper is thus vital to cAMP-mediated Ca2+ influx in sperm, sperm motility and fertilization. CatSper represents an excellent target for non-hormonal contraceptives for both men and women.     

材料的相变研究及其应用

Fe-C和Fe-X-C合金马氏体相变热力学的研究成果使结构钢的Ms温度能以热力学预测。建立了铜基合金及Fe-Mn-Si基合金马氏体相变热力学,为铜基和铁基形状记忆合金的成分和工艺设计提供基础。提出了含ZrO2陶瓷Ms温度的热力学计算方法,以及其母相晶粒大小影响Ms的正确表达式,对陶瓷的生产和工业应用都具有意义。修正马氏体变温相变动力学方程,显示低碳钢中影响碳扩散系数的合金元素影响残余奥氏体量,这有利于低碳马氏体组织钢的开发。GCr15轴承钢中残余奥氏体→马氏体的等温动力学研究显示：钢经淬火后,再进行等温处理以形成很少量的等温马氏体,再作回火,提高钢件的尺寸稳定性（经1000d后与淬火-回火比较,在接触疲劳寿命并不降低的条件下（达34%。研究了Ni-Ti、Cu-Zn-Al、Fe-Mn-Si基合金及ZrO2陶瓷的马氏体相变及其逆相变特征,揭示了影响这些材料形状记忆效应（SME）的一些因素,并指出了改善SME的途径,有利于这些材料的开发应用。贝氏体相变的热力学研究,观察到生长台阶,母相强化对相变影响的研究以及内耗测量结果,均显示贝氏体相变属扩散型机制。Cu-Zn-Al中加入阻碍Zn和Al扩散的合金元素可能提高形状记忆使用寿命。揭示CeO2-ZrO2中存在贝氏体相变,并与其出现脆性有关。Cu-Zn中β相有序化研究对有序化合金的应用具有实际意义。三元合金spinodal分解判据的建立,对借spinodal分解呈现高阻尼或高强度合金的开发颇具价值。由群论导出呈现晶体学可逆性的条件为形成单变体马氏体。应用孤立子于相变的形核-长大模型初见成效。     

富气原油在湍流条件下的蜡沉积

采用自动化蜡沉积循环管道流动系统研究含蜡富气原油在现场的温度变化范围内和流动条件下的蜡沉积过程 .将油田现场取得的脱气原油在高压下加气加水配成富气油样 ,分别采用冷却测试和等温测试两种实验过程 ,测试在湍流条件下的蜡沉积规律 .冷却测试过程精确地测试含蜡原油从高于原油析蜡点温度到较低环境温度范围内在现场流速、油温和环境温度下的蜡沉积过程 ,同时结合等温测试过程研究蜡沉积的机理 .实验结果表明 :含蜡原油蜡沉积与环境温度、油温、油温与环境温度的温差有关 ;在湍流条件下 ,剪切效应不容忽视