Multiple regions within 8q24 independently affect risk for prostate cancer

After the recent discovery that common genetic variation in 8q24 influences inherited risk of prostate cancer, we genotyped 2,973 SNPs in up to 7,518 men with and without prostate cancer from five populations. We identified seven risk variants, five of them previously undescribed, spanning 430 kb and each independently predicting risk for prostate cancer (P = 7.9 x 10(-19) for the strongest association, and P < 1.5 x 10(-4) for five of the variants, after controlling for each of the others). The variants define common genotypes that span a more than fivefold range of susceptibility to cancer in some populations. None of the prostate cancer risk variants aligns to a known gene or alters the coding sequence of an encoded protein.     

Parameters for reliable results in genetic association studies in common disease.

It is increasingly apparent that the identification of true genetic associations in common multifactorial disease will require studies comprising thousands rather than the hundreds of individuals employed to date. Using 2,873 families, we were unable to confirm a recently published association of the interleukin 12B gene in 422 type I diabetic families. These results emphasize the need for large datasets, small P values and independent replication if results are to be reliable.     

RanGAP mediates GTP hydrolysis without an arginine finger

GTPase-activating proteins (GAPs) increase the rate of GTP hydrolysis on guanine nucleotide-binding proteins by many orders of magnitude. Studies with Ras and Rho have elucidated the mechanism of GAP action by showing that their catalytic machinery is both stabilized by GAP binding and complemented by the insertion of a so-called 'arginine finger' into the phosphate-binding pocket. This has been proposed as a universal mechanism for GAP-mediated GTP hydrolysis. Ran is a nuclear Ras-related protein that regulates both transport between the nucleus and cytoplasm during interphase, and formation of the mitotic spindle and/or nuclear envelope in dividing cells. Ran-GTP is hydrolysed by the combined action of Ran-binding proteins (RanBPs) and RanGAP. Here we present the three-dimensional structure of a Ran-RanBP1-RanGAP ternary complex in the ground state and in a transition-state mimic. The structure and biochemical experiments show that RanGAP does not act through an arginine finger, that the basic machinery for fast GTP hydrolysis is provided exclusively by Ran and that correct positioning of the catalytic glutamine is essential for catalysis.     

Weiteres zum Lichtsinn augenloser Muscheln

Summary The cycless musselsAnodonta cygnea andPseudanodonta complanata do not show any phototaxis. In the Zweilichterversuch (two-light-experiment) they react to the decrease of light intensity. If light is increasing, the mussels will not react; if put in the shade, they immediately do so. If the shadow is moved, the mussels even react when the intensity of light decreases much less, which demonstrates the importance of motion. From this it follows that the reception of motion may be considered as possible where there is light sensitiveness of the skin, and where the experiment connects motion with shading.     

Polysaccharide aggregation as a potential sink of marine dissolved organic carbon

The formation and sinking of biogenic particles mediate vertical mass fluxes and drive elemental cycling in the ocean. Whereas marine sciences have focused primarily on particle production by phytoplankton growth, particle formation by the assembly of organic macromolecules has almost been neglected. Here we show, by means of a combined experimental and modelling study, that the formation of polysaccharide particles is an important pathway to convert dissolved into particulate organic carbon during phytoplankton blooms, and can be described in terms of aggregation kinetics. Our findings suggest that aggregation processes in the ocean cascade from the molecular scale up to the size of fast-settling particles, and give new insights into the cycling and export of biogeochemical key elements such as carbon, iron and thorium.     

Mei-P26 regulates microRNAs and cell growth in the Drosophila ovarian stem cell lineage

Drosophila neuroblasts and ovarian stem cells are well characterized models for stem cell biology. In both cell types, one daughter cell self-renews continuously while the other undergoes a limited number of divisions, stops to proliferate mitotically and differentiates. Whereas neuroblasts segregate the Trim-NHL (tripartite motif and Ncl-1, HT2A and Lin-41 domain)-containing protein Brain tumour (Brat) into one of the two daughter cells, ovarian stem cells are regulated by an extracellular signal from the surrounding stem cell niche. After division, one daughter cell looses niche contact. It undergoes 4 transit-amplifying divisions to form a cyst of 16 interconnected cells that reduce their rate of growth and stop to proliferate mitotically. Here we show that the Trim-NHL protein Mei-P26 (refs 7, 8) restricts growth and proliferation in the ovarian stem cell lineage. Mei-P26 expression is low in stem cells but is strongly induced in 16-cell cysts. In mei-P26 mutants, transit-amplifying cells are larger and proliferate indefinitely leading to the formation of an ovarian tumour. Like brat, mei-P26 regulates nucleolar size and can induce differentiation in Drosophila neuroblasts, suggesting that these genes act through the same pathway. We identify Argonaute-1, a component of the RISC complex, as a common binding partner of Brat and Mei-P26, and show that Mei-P26 acts by inhibiting the microRNA pathway. Mei-P26 and Brat have a similar domain composition that is also found in other tumour suppressors and might be a defining property of a new family of microRNA regulators that act specifically in stem cell lineages.     

室温下水-花岗岩作用时液相组分的演化

使用批反应器实验研究21℃时花岗岩与蒸馏水的作用来探讨水-岩作用以及液相随作用时间的地球化学演化。粒度为1～2mm，O．5～1mm和0．2～0．5mm的花岗岩样品各150g和750ml纯水加入用聚丙烯做成的3个批反应器中进行反应试验。试验过程中用电动马达连续转动反应器。试验时间为60d。结果表明，液相主要是Ca-(K)-HCO3型水或K-(Ca)-HCO3型水。K^ 主要来自钾长石的溶解，Ca^2 主要与斜长石中钙长石组分的溶解有关。K^ 很容易从含K^ 的原生矿物中被释放出来，同时K^ 也容易从水中析出形成次生矿物。水中“Ca过剩”可以很好地用斜长石的不一致性溶解反应来解释，钙长石和钠长石悬殊的溶解度差异也是水中“Ca过剩”可能的原因之一。实验结果与用表面反应控制速率模式的解释及Na^ 和H^ 的表面竞争交换相一致。