Genome-wide association study identifies novel breast cancer susceptibility loci

Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2 > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10(-7)). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.     

Mobile reactive centre of serpins and the control of thrombosis

Two protease inhibitors in human plasma play a key part in the control of thrombosis: antithrombin inhibits coagulation and the plasminogen activator inhibitor PAI-1 inhibits fibrinolysis, the dissolving of clots. Both inhibitors are members of the serpin family and both exist in the plasma in latent or inactive forms. We show here that the reactive centre of the serpins can adopt varying conformations and that mobility of the reactive centre is necessary for the function of antithrombin and its binding and activation by heparin; the identification of a new locked conformation explains the latent inactive state of PAI-1. This ability to vary conformation not only allows the modulation of inhibitory activity but also protects the circulating inhibitor against proteolytic attack. Together these findings explain the retention by the serpins of a large and unconstrained reactive centre as compared to the small fixed peptide loop of other families of serine protease inhibitors.     

Structure, flame retarding and smoke suppressing properties of Zn-Mg-Al-CO3 layered double hydroxides

Zn-Mg-Al-CO3 layered double hydroxides (LDHs) have been synthesized by a new method involving separate nucleation and aging steps. The Zn-Mg-Al-CO3 LDHs were characterized by XRD, FT-IR, ICP and TG-DTA. The limiting oxygen index and smoke density of composites of the LDHs with EVA-28 were determined. Incorporation of Zn^2 in the layers of the LDHs was found promoting material charring and smoke suppression. The mechanism of flame retardation and smoke suppression is discussed. The results show that Zn-Mg-Al-CO3 LDHs have better flam eretarding and smoke suppressing effects than Mg-Al-CO3 LDHs.     

钼系络离子［O{MoO(O2)2}2]2-插层锌铝水滑石

采用离子交换法，以锌铝碳酸根型水滑石(Zn/Al-CO₃-LDHs)为前体，进行了钼系络离子［O{MoO(O₂)₂}₂］^2-插层水滑石的研究，利用X射线衍射(XRD)、红外光谱(FT-IR)和元素分析等手段对插层产物结构和组成进行了分析。结果表明：离子交换法可制备出钼系络离子［O{MoO(O₂)₂}₂］^2-插层Zn/Al-CO₃-LDHs的产物，插层产物保持了原有水滑石的层状结构，而且升高温度有利于层间阴离子交换完全，从而使晶体结构趋于完整。     

Dissolved organic carbon trends resulting from changes in atmospheric deposition chemistry

Several hypotheses have been proposed to explain recent, widespread increases in concentrations of dissolved organic carbon (DOC) in the surface waters of glaciated landscapes across eastern North America and northern and central Europe. Some invoke anthropogenic forcing through mechanisms related to climate change, nitrogen deposition or changes in land use, and by implication suggest that current concentrations and fluxes are without precedent. All of these hypotheses imply that DOC levels will continue to rise, with unpredictable consequences for the global carbon cycle. Alternatively, it has been proposed that DOC concentrations are returning toward pre-industrial levels as a result of a gradual decline in the sulphate content of atmospheric deposition. Here we show, through the assessment of time series data from 522 remote lakes and streams in North America and northern Europe, that rising trends in DOC between 1990 and 2004 can be concisely explained by a simple model based solely on changes in deposition chemistry and catchment acid-sensitivity. We demonstrate that DOC concentrations have increased in proportion to the rates at which atmospherically deposited anthropogenic sulphur and sea salt have declined. We conclude that acid deposition to these ecosystems has been partially buffered by changes in organic acidity and that the rise in DOC is integral to recovery from acidification. Over recent decades, deposition-driven increases in organic matter solubility may have increased the export of DOC to the oceans, a potentially important component of regional carbon balances. The increase in DOC concentrations in these regions appears unrelated to other climatic factors.