A de novo paradigm for mental retardation

The per-generation mutation rate in humans is high. De novo mutations may compensate for allele loss due to severely reduced fecundity in common neurodevelopmental and psychiatric diseases, explaining a major paradox in evolutionary genetic theory. Here we used a family based exome sequencing approach to test this de novo mutation hypothesis in ten individuals with unexplained mental retardation. We identified and validated unique non-synonymous de novo mutations in nine genes. Six of these, identified in six different individuals, are likely to be pathogenic based on gene function, evolutionary conservation and mutation impact. Our findings provide strong experimental support for a de novo paradigm for mental retardation. Together with de novo copy number variation, de novo point mutations of large effect could explain the majority of all mental retardation cases in the population.     

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10?12) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10?11) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10??) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10?11) and a tag SNP for NAT2 acetylation status (P = 4 × 10?11), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.     

以树轮晚材宽度重建公元1726年以来贺兰山北部5~7月降水量

通过分析早材宽度(EWW)、晚材宽度(LWW)、整轮宽度(TRW)、最小密度(D_min)和最大密度(D_max)共计5个树轮标准年表的统计特征及其各自气候响应, 最终以晚材宽度对贺兰山北部公元1726年以来5~7月的降水进行了重建, 方差解释量42%(R²_adj=0.41, F = 31.46, P < 0.000001). 11年滑动平均后, 方差解释量达82%(F=156.9, P<0.05). 重建降水序列在10年际尺度上与内蒙古东部白音敖包地区4~7月上旬降水具有相当好的一致性, 在一定程度上反映了东亚夏季风锋面强弱的变化. 谱分析检测出贺兰山北部5~7月降水序列主要存在11和22年的波动周期.     

Initiation and re-initiation of DNA unwinding by the Escherichia coli Rep helicase

Helicases are motor proteins that couple conformational changes induced by ATP binding and hydrolysis with unwinding of duplex nucleic acid, and are involved in several human diseases. Some function as hexameric rings, but the functional form of non-hexameric helicases has been debated. Here we use a combination of a surface immobilization scheme and single-molecule fluorescence assays--which do not interfere with biological activity--to probe DNA unwinding by the Escherichia coli Rep helicase. Our studies indicate that a Rep monomer uses ATP hydrolysis to move toward the junction between single-stranded and double-stranded DNA but then displays conformational fluctuations that do not lead to DNA unwinding. DNA unwinding initiates only if a functional helicase is formed via additional protein binding. Partial dissociation of the functional complex during unwinding results in interruptions ('stalls') that lead either to duplex rewinding upon complete dissociation of the complex, or to re-initiation of unwinding upon re-formation of the functional helicase. These results suggest that the low unwinding processivity observed in vitro for Rep is due to the relative instability of the functional complex. We expect that these techniques will be useful for dynamic studies of other helicases and protein-DNA interactions.     

通气对硫化铜矿生物浸出过程中自由细菌和吸附细菌群落动态的影响研究

生物浸出回收低品位硫化铜矿中的铜金属具有操作简单、低能耗、节约经济等优点,成为了近年来的研究热点。然而低品位硫化铜矿生物浸出效率低是其面临的主要问题之一。本文为了促进生物浸出效率,研究了强制通气条件下的低品位硫化铜矿生物浸出过程中的铜浸出率、细菌群落动态演替等特征。结果表明,适当的通气可提高细菌浓度和铜浸出率。在通气时间为4 h·d?1时,浸矿14 d后的细菌浓度和铜离子浓度最高,分别为7.61×107 个·mL?1和704.9 mg·L?1。实验可得,吸附细菌在浸矿过程的前7 d起着重要作用,而自由细菌则是在第8 d到第14 d占主导地位。这一现象主要是由于浸出过程Fe3+水解形成钝化层所致,抑制了吸附细菌与矿石的接触。同时,通过16S rDNA分析可知,Acidithiobacillus ferrooxidans和Acidithiobacillus thiooxidans对低品位硫化铜矿生物浸出过程具有重要影响。     

石墨烯对铜纳米复合材料物理力学性能和摩擦学性能的影响

本文对铜–石墨烯纳米片（GN）纳米复合材料的力学性能和摩擦学性能进行了实验研究。我们采用化学包覆法将银粒子包覆在GNs上,以避免其与铜的反应和金属间相的形成。分析了GN含量对制备的纳米复合材料的结构、力学性能和摩擦学性能的影响。结果表明,化学镀是一种有效避免铜与碳反应和金属间相形成的方法。GNs的加入显著提高了Cu纳米复合材料的力学性能和摩擦学性能。然而,GNs的添加需要谨慎进行,因为在达到一定的阈值后,其机械性能和摩擦学性能会受到负面影响。结果表明,GN含量为0.5vol%时,复合材料的硬度、磨损率和摩擦系数分别比铜纳米复合材料提高了13%、81.9%和49.8%。这些改进的性能是由于降低的晶体尺寸,GNs的存在,以及复合材料成分的均匀分布。