Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration

Leber congenital amaurosis (LCA) is a blinding retinal disease that presents within the first year after birth. Using exome sequencing, we identified mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 in eight families with LCA, including the family in which LCA was originally linked to the LCA9 locus. Notably, all individuals with NMNAT1 mutations also have macular colobomas, which are severe degenerative entities of the central retina (fovea) devoid of tissue and photoreceptors. Functional assays of the proteins encoded by the mutant alleles identified in our study showed that the mutations reduce the enzymatic activity of NMNAT1 in NAD biosynthesis and affect protein folding. Of note, recent characterization of the slow Wallerian degeneration (Wld(s)) mouse model, in which prolonged axonal survival after injury is observed, identified NMNAT1 as a neuroprotective protein when ectopically expressed. Our findings identify a new disease mechanism underlying LCA and provide the first link between endogenous NMNAT1 dysfunction and a human nervous system disorder.     

Maize HapMap2 identifies extant variation from a genome in flux

Whereas breeders have exploited diversity in maize for yield improvements, there has been limited progress in using beneficial alleles in undomesticated varieties. Characterizing standing variation in this complex genome has been challenging, with only a small fraction of it described to date. Using a population genetics scoring model, we identified 55 million SNPs in 103 lines across pre-domestication and domesticated Zea mays varieties, including a representative from the sister genus Tripsacum. We find that structural variations are pervasive in the Z. mays genome and are enriched at loci associated with important traits. By investigating the drivers of genome size variation, we find that the larger Tripsacum genome can be explained by transposable element abundance rather than an allopolyploid origin. In contrast, intraspecies genome size variation seems to be controlled by chromosomal knob content. There is tremendous overlap in key gene content in maize and Tripsacum, suggesting that adaptations from Tripsacum (for example, perennialism and frost and drought tolerance) can likely be integrated into maize.     

A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis

To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.     

Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.     

不确定条件下纵向研发合作的投资决策研究

针对一个存在两个上游企业和两个下游企业的双层市场结构,对上下游企业实施纵向研发合作策略下的产量和利润进行了研究。并考虑了研发固有的不确定性和溢出效应的影响,从企业是否进行研发以及进行多大程度的研发两个方面,研究上下游企业实施纵向研发合作的投资决策。并在此基础上,探讨了企业研发成本分担比例和违约赔偿。     

石榴枯萎病的生防木霉菌株的筛选及鉴定

目的 石榴枯萎病是由甘薯长喙壳菌引起,对石榴有严重危害的土传病害。利用拮抗微生物抑制病原菌的繁殖是石榴枯萎病绿色防控的有效手段。通过筛选具有对石榴枯萎病原菌产生拮抗效果的微生物,研究其抑制菌作用,以期为石榴枯萎病生物防控提供菌种资源。方法 从石榴的根际土壤中分离出真菌,根据产孢量、生长速率、拮抗系数及平板对峙结果进行筛选,对防效较好的真菌根据形态学和分子系统学进行鉴定,通过盆栽实验评估其对石榴枯萎病的防治效果。结果 能有效抑制石榴枯萎病菌菌丝的生长的菌株T9经鉴定为非洲哈茨木霉菌（Trichoderma afroharzianum）,盆栽防治效果最高可达71.35%。结论 该菌株展现出了对石榴枯萎病的生物防治效果,具有应用价值。     

FDI对山东农副产品出口影响的相关分析与政策建议

通过对山东省农副产品出口和农业FDI现状进行分析,发现二者具有某些共同特点,运用SPSS软件对山东农副产品出口和农业FDI的关系做进一步的相关分析和回归分析发现,二者确实存在显著的线性相关关系,并确定出二者的一元线性回归方程为y=16.613 21.731x。针对目前山东省农业FDI存在的问题,提出山东省今后应采取进一步改善投资环境,加强对农业FDI的产业引导和区域布局规划,进一步壮大农业引资主体,落实农业FDI中的中方配套资金等措施。     

开源软件Linux内核的进化分析

开源软件各种版本的源代码和相关开发信息是软件工程研究者研究软件进化的重要数据源.文中研究了Linux的进化规律,归纳了开源软件项目的数据源及数据收集方法,并给出了Linux内核的软件进化的分析方法和相关分析结果.得出了Linux目前以超线性方式进化,而进化的主要推动力是适应系统硬件资源的进化的结论,并提出了快速测算大型开源软件复杂性的方法.     

关联交叉口短时交通流可预测性分析及组合预测算法

文中首先根据交叉口交通流参数时间序列的相关性对关联交叉口进行定义,给出关联交叉口短时交通流可预测分析的几个定量指标,以及交通流时间序列最大Lya-punov指数的计算方法;然后提出在短时交通流时间序列的可预测分析基础上,选取一组预测模型并建立基于RBF网络的非线性组合预测模型,提出了关联交叉口短时交通流的组合预测算法;最后对实测短时交通流进行仿真试验,结果表明组合预测方法相对于单项预测方法具有更好的预测性能.