Evidence for substantial fine-scale variation in recombination rates across the human genome

Characterizing fine-scale variation in human recombination rates is important, both to deepen understanding of the recombination process and to aid the design of disease association studies. Current genetic maps show that rates vary on a megabase scale, but studying finer-scale variation using pedigrees is difficult. Sperm-typing experiments have characterized regions where crossovers cluster into 1-2-kb hot spots, but technical difficulties limit the number of studies. An alternative is to use population variation to infer fine-scale characteristics of the recombination process. Several surveys reported 'block-like' patterns of diversity, which may reflect fine-scale recombination rate variation, but limitations of available methods made this impossible to assess. Here, we applied a new statistical method, which overcomes these limitations, to infer patterns of fine-scale recombination rate variation in 74 genes. We found extensive rate variation both within and among genes. In particular, recombination hot spots are a common feature of the human genome: 47% (35 of 74) of genes showed substantive evidence for a hot spot, and many more showed evidence for some rate variation. No primary sequence characteristics are consistently associated with precise hot-spot location, although G+C content and nucleotide diversity are correlated with local recombination rate.     

The effect of temperature variation on spontaneous potential production from explants of brain tissue in culture

Zusammenfassung Bei zwei verschiedenen Explantaten von Telencephalogewebe 14tägiger Hühnchenembryonen ergab sich als Temperaturabhängigkeit der Aktionspotentiale: Frequenz und Amplitudenabnahme bei sinkender, Zunahme bei steigender Temperatur bis zwischen 37 und 42,5°C. Weitere Temperatursteigerung bringt die Potentiale nach stetiger Verkleinerung bei 47°C schliesslich zum Verschwinden.

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This research was supported by a grant from the Office of Naval Research, U.S. Navy Contract NONR 1598(04).     

Towards the clarity limit in optical fibre

An important scientific and technological goal in the field of optical communications is the achievement of the clarity limit in optical fibres--that is, ensuring that the SiO2 glass from which fibres are made is as transparent as possible. The clarity of the wavelength transmission window (and the width of that window) in existing fibres is already sufficient to form the basis of a world-wide optical communication system, yet it is still limited by contamination of the fibre by water. Here we measure the spatial distribution of water in the glass rods from which optical fibres are drawn and explain the distribution quantitatively with a mathematical model of diffusion in a medium with essentially perfect cylindrical symmetry. Our analysis shows that the water enters from the outside of the rod and diffuses into the molten, flowing glass much faster than is expected from extrapolation of low-temperature measurements. Our elucidation of the physics underlying the contamination process has already led to the fabrication of dry fibres, which have a clarified and broadened communications window. The improved operational range of wavelengths should yield applications for new lasers, optical amplifiers and detectors, and should substantially increase the information-carrying capacity of optical communications systems.     

Colorectal carcinomas in mice lacking the catalytic subunit of PI(3)Kgamma

Phosphoinositide-3-OH kinases (PI(3)Ks) constitute a family of evolutionarily conserved lipid kinases that regulate a vast array of fundamental cellular responses, including proliferation, transformation, differentiation and protection from apoptosis. PI(3)K-mediated activation of the cell survival kinase PKB/Akt, and negative regulation of PI(3)K signalling by the tumour suppressor PTEN (refs 3, 4) are key regulatory events in tumorigenesis. Thus, a model has arisen that PI(3)Ks promote development of cancers. Here we report that genetic inactivation of the p110gamma catalytic subunit of PI(3)Kgamma (ref. 8) leads to development of invasive colorectal adenocarcinomas in mice. In humans, p110gamma protein expression is lost in primary colorectal adenocarcinomas from patients and in colon cancer cell lines. Overexpression of wild-type or kinase-dead p110gamma in human colon cancer cells with mutations of the tumour suppressors APC and p53, or the oncogenes beta-catenin and Ki-ras, suppressed tumorigenesis. Thus, loss of p110gamma in mice leads to spontaneous, malignant epithelial tumours in the colorectum and p110gamma can block the growth of human colon cancer cells.     

Structural insights into phosphoinositide 3-kinase catalysis and signalling

Phosphoinositide 3-kinases (PI3Ks) are ubiquitous lipid kinases that function both as signal transducers downstream of cell-surface receptors and in constitutive intracellular membrane and protein trafficking pathways. All PI3Ks are dual-specificity enzymes with a lipid kinase activity which phosphorylates phosphoinositides at the 3-hydroxyl, and a protein kinase activity. The products of PI3K-catalysed reactions, phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), PtdIns(3,4)P2 and PtdIns(3)P, are second messengers in a variety of signal transduction pathways, including those essential to cell proliferation, adhesion, survival, cytoskeletal rearrangement and vesicle trafficking. Here we report the 2.2 A X-ray crystallographic structure of the catalytic subunit of PI3Kgamma, the class I enzyme that is activated by heterotrimeric G-protein betagamma subunits and Ras. PI3Kgamma has a modular organization centred around a helical-domain spine, with C2 and catalytic domains positioned to interact with phospholipid membranes, and a Ras-binding domain placed against the catalytic domain where it could drive allosteric activation of the enzyme.     

Eisenstein判别法及（E，ρ）型数域的推广

Eisenstein判别法是高等代数中判定整系数多项式在有理数域中的可约性的重要方法,其推广形式很多,而最原始的形式应用代数数论中来定义（E,ρ）型数域。本文在原来Eisenstein判别法的基础上进行适当地推广,并将已知的（E,ρ）型数域也随其判别法的推广而推广,成为广（E,ρ）型数域,在此基础上研究此数域的性质：给出素数p在广（E,ρ）型数域中的素理想分解形式,并且给出了这个素数户的一个重要性质。其次,得到广（E,ρ）型数域中素数ρ及相关理想的一些性质,并给出相应的证明。这样,就推广了原本只讨论最原始定义的Eisenstein判别法及（E,ρ）型数域的相关性质,使此理论更加完善。     

钢斜拉桥的稳定性评估

通过比较容许应力设计法（ASD）与载荷抗力系数设计法（LRFD）来分析构件稳定,以达到钢斜拉桥主要受力构件设计节省和经济的原则.用ASD理论和LRFD理论中的轴向弯曲交互方程来检验钢斜拉桥主要构件的稳定性.计算梁和塔柱交叉点的交互方程的数值,通过计算的数值统计分析二者谁更节省以及节省的幅度,从而为梁和塔柱的设计提供指导.同时,分别运用ANSYS有限元程序进行特征值屈曲分析和非线性屈曲分析,比较二者确定的屈曲载荷,为稳定设计提供相关的参考和依据.     

点带石斑鱼鱼皮和鳞片胶原蛋白的提取及理化性质的研究

以点带石斑鱼为原料,分别从鱼皮和鱼鳞中提取酸溶性胶原蛋白,并研究其纯度、热变性温度、溶解度等理化性质.结果表明:(1)鱼皮和鱼鳞中胶原蛋白的提取率分别为76.21%和2.50%;(2)经紫外可见光谱扫描、傅里叶转换红外光谱和氨基酸分析,确定所提取的胶原蛋白是Ⅰ型胶原蛋白,具有完整的三螺旋结构;(3)SDS-PAGE电泳测定证明鱼皮和鱼鳞胶原蛋白均含有α1、α2、β和γ链,α1、α2链的相对分子质量分别为2.79×105和2.87×105,纯度分别为91%和85%;(4)鱼皮、鱼鳞胶原蛋白的热变性温度分别为40.16和42.06℃;(5)等电点分别为7.12和7.15;(6)两者在酸性pH(2～4)时具有高的溶解度,并且当NaCl的质量浓度分别为10和20 g/L时,溶解度最高.