Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease

The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.     

Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA

The extreme polymorphism in the human leukocyte antigen (HLA) class I region of the human genome is suggested to provide an advantage in pathogen defence mediated by CD8+ T cells. HLA class I molecules present pathogen-derived peptides on the surface of infected cells for recognition by CD8+ T cells. However, the relative contributions of HLA-A and -B alleles have not been evaluated. We performed a comprehensive analysis of the class I restricted CD8+ T-cell responses against human immunodeficiency virus (HIV-1), immune control of which is dependent upon virus-specific CD8+ T-cell activity. In 375 HIV-1-infected study subjects from southern Africa, a significantly greater number of CD8+ T-cell responses are HLA-B-restricted, compared to HLA-A (2.5-fold; P = 0.0033). Here we show that variation in viral set-point, in absolute CD4 count and, by inference, in rate of disease progression in the cohort, is strongly associated with particular HLA-B but not HLA-A allele expression (P < 0.0001 and P = 0.91, respectively). Moreover, substantially greater selection pressure is imposed on HIV-1 by HLA-B alleles than by HLA-A (4.4-fold, P = 0.0003). These data indicate that the principal focus of HIV-specific activity is at the HLA-B locus. Furthermore, HLA-B gene frequencies in the population are those likely to be most influenced by HIV disease, consistent with the observation that B alleles evolve more rapidly than A alleles. The dominant involvement of HLA-B in influencing HIV disease outcome is of specific relevance to the direction of HIV research and to vaccine design.     

Reduced growth of Alaskan white spruce in the twentieth century from temperature-induced drought stress

The extension of growing season at high northern latitudes seems increasingly clear from satellite observations of vegetation extent and duration. This extension is also thought to explain the observed increase in amplitude of seasonal variations in atmospheric CO2 concentration. Increased plant respiration and photosynthesis both correlate well with increases in temperature this century and are therefore the most probable link between the vegetation and CO2 observations. From these observations, it has been suggested that increases in temperature have stimulated carbon uptake in high latitudes and for the boreal forest system as a whole. Here we present multi-proxy tree-ring data (ring width, maximum late-wood density and carbon-isotope composition) from 20 productive stands of white spruce in the interior of Alaska. The tree-ring records show a strong and consistent relationship over the past 90 years and indicate that, in contrast with earlier predictions, radial growth has decreased with increasing temperature. Our data show that temperature-induced drought stress has disproportionately affected the most rapidly growing white spruce, suggesting that, under recent climate warming, drought may have been an important factor limiting carbon uptake in a large portion of the North American boreal forest. If this limitation in growth due to drought stress is sustained, the future capacity of northern latitudes to sequester carbon may be less than currently expected.     

模拟结果为什么比实际更暖:简化气候模型结果（英文）

设计了一个非专业人士能够使用、最简化的气候敏感模型,用来研究人类活动所导致的全球变暖的幅度问题.在1990年的第一次IPCC评估报告中,IPCC对其报告中预测的未来全球变暖幅度很有信心,但是随后的观测结果显示全球的变暖幅度只有预测的一半.而自2001年起,全球变暖出现停滞,但是仅仅考虑到二氧化碳浓度的增加,很少有模型能够模拟出这一变化.在已出版的IPCC第五次评估报告的草稿中,IPCC大幅度削减了近期变暖的幅度,并以专家评估代替了模型预测.但是报告中关于未来气候长期变化的预测仍被保留.如果把IPCC模型的总反馈从1.9 W m–2 K–1调整到1.5 W m–2 K–1,气候敏感模型中模拟的温度将从3.2 K降至2.2 K.同时由于反馈很可能是净负反馈,更合适的估计应该是1.0 K.1.0 K是一个能够实现的增幅,21世纪的实际变暖将会小于1 K.即使燃烧所有可开采的化石燃料也不会使全球变暖的幅度超过2.2 K,这一增加幅度也将趋于平稳.本文认为解决IPCC第四、五次报告中评估方法的差异非常关键.一旦这些差异得到解决,人类活动导致的全球变暖在22世纪以及几个世纪以后的平稳态将有可能不会超过IPCC当前模型预测的1/3~1/2.     

智能流域管理的关键问题与模型技术

在总结流域问题现状及流域管理决策需求的基础上,基于仿生学原理,类比人的思维特征和决策过程,提出了包括流域信息获取、输入-输出因果关联模拟以及优化决策等步骤在内的智能流域管理模式,并对比分析了智能流域管理和传统流域管理的差异性。提出了智能流域管理的4个关键问题：管理目标的确定、基于智能因子关联与流动的模型开发与信息获取、...     

Radio harness system for bobcat kittens

Eight bobcat kittens were fitted with a specially designed harness system supporting a radio transmitter. These kittens were the youngest known to be radio-instrumented. This system was used successfully through two seasons, from June 1989 to January 1991. Litters of kittens were located soon after birth for weighing, marking, and aging (by tooth eruption). During the first year when kittens were at least eight weeks old and six weeks old the second year, attempts were made to radio-instrument kittens in each litter. This harness system allowed litters to be located periodically until their death or dispersal. We were able to collect important data during the most crucial and least known weeks of the lives of bobcat kittens.     

Complete nucleotide sequence of an influenza virus haemagglutinin gene from cloned DNA

A synthetic fowl plague virus (FPV) haemagglutinin gene has been cloned in bacteria and the complete sequence of the RNA gene deduced. It is 1,742 nucleotides long and the mRNA codes for 56.3 amino acids in an uninterrupted sequence. The nature of some of the important domains in the haemagglutinin has been established, and their structure is discussed in relation to their function. Extensive amino acid sequence homologies exist between FPV and human influenza haemagglutinins.