The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease

The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease.     

Genomic analysis of Bartonella identifies type IV secretion systems as host adaptability factors

The bacterial genus Bartonella comprises 21 pathogens causing characteristic intraerythrocytic infections. Bartonella bacilliformis is a severe pathogen representing an ancestral lineage, whereas the other species are benign pathogens that evolved by radial speciation. Here, we have used comparative and functional genomics to infer pathogenicity genes specific to the radiating lineage, and we suggest that these genes may have facilitated adaptation to the host environment. We determined the complete genome sequence of Bartonella tribocorum by shotgun sequencing and functionally identified 97 pathogenicity genes by signature-tagged mutagenesis. Eighty-one pathogenicity genes belong to the core genome (1,097 genes) of the radiating lineage inferred from genome comparison of B. tribocorum, Bartonella henselae and Bartonella quintana. Sixty-six pathogenicity genes are present in B. bacilliformis, and one has been lost by deletion. The 14 pathogenicity genes specific for the radiating lineage encode two laterally acquired type IV secretion systems, suggesting that these systems have a role in host adaptability.     

Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans

More than a billion humans worldwide are predicted to be completely deficient in the fast skeletal muscle fiber protein alpha-actinin-3 owing to homozygosity for a premature stop codon polymorphism, R577X, in the ACTN3 gene. The R577X polymorphism is associated with elite athlete status and human muscle performance, suggesting that alpha-actinin-3 deficiency influences the function of fast muscle fibers. Here we show that loss of alpha-actinin-3 expression in a knockout mouse model results in a shift in muscle metabolism toward the more efficient aerobic pathway and an increase in intrinsic endurance performance. In addition, we demonstrate that the genomic region surrounding the 577X null allele shows low levels of genetic variation and recombination in individuals of European and East Asian descent, consistent with strong, recent positive selection. We propose that the 577X allele has been positively selected in some human populations owing to its effect on skeletal muscle metabolism.     

Wnt-beta-catenin signaling initiates taste papilla development

Fungiform taste papillae form a regular array on the dorsal tongue. Taste buds arise from papilla epithelium and, unusually for epithelial derivatives, synapse with neurons, release neurotransmitters and generate receptor and action potentials. Despite the importance of taste as one of our five senses, genetic analyses of taste papilla and bud development are lacking. We demonstrate that Wnt-beta-catenin signaling is activated in developing fungiform placodes and taste bud cells. A dominant stabilizing mutation of epithelial beta-catenin causes massive overproduction of enlarged fungiform papillae and taste buds. Likewise, genetic deletion of epithelial beta-catenin or inhibition of Wnt-beta-catenin signaling by ectopic dickkopf1 (Dkk1) blocks initiation of fungiform papilla morphogenesis. Ectopic papillae are innervated in the stabilizing beta-catenin mutant, whereas ectopic Dkk1 causes absence of lingual epithelial innervation. Thus, Wnt-beta-catenin signaling is critical for fungiform papilla and taste bud development. Altered regulation of this pathway may underlie evolutionary changes in taste papilla patterning.     

Information processing along the course of a visual interneuron.

Locust ocellar retinal cells are innervated by giant second order cells, 2 mm long, which show discrete zones of integration along their course, including a major zone in the axonal length of the neuron. The complex synaptic arrangements which exist between higher-order afferent and efferent cells and these second order cells along their course suggests that transmission takes place by the electrotonic spread of slow potentials. The size and accessibility of these visual interneurons offers a unique preparation for examining mechanisms of graded synaptic transmission.     

Effect of ethanol on toxicity and metabolism of amphetamine in the mouse.

Ethanol, 3 g/kg i.p., did not significantly alter the acute toxicity of amphetamine in the mouse. However, the urinary metabolite pattern was changed, suggesting that ethanol suppressed metabolism of the stimulant during the initial 6 h period. After 24 h, the mouse metabolized the same fraction of a given dose of amphetamine, whether it was given as amphetamine alone or amphetamine mixed with 2,3 or 4 g/kg ethanol.     

基于SnowNLP的微博网络舆情分析系统

随着微博、抖音、贴吧等新兴网络社交媒体的发展,大量用户开始喜欢使用这些平台进行发布和获取信息,因此累积了大量舆情数据。为了能够及时监测网络舆论动向,更好的维护互联网的安全运营和网络安全,针对实时微博数据,研究设计了一种基于SnowNLP的微博网络舆情分析系统。该系统由舆情数据采集、舆情数据分析和舆情数据可视化组成,能够实现微博数据文本挖掘、网络舆情数据情感分析、舆情数据与关键词匹配结果统计等功能,并能够对微博内容情感分析结果、用户等级、内容分词结果等进行可视化展示。实验测试结果表明：本系统功能运行正常,同时验证了设计方案的可行性和有效性。系统在网络舆情监测领域具有重要的应用价值。     

极端降雨对黄土沟壑区隧洞施工力学效应影响分析

黄土地区输水隧洞的建设中,降雨入渗极大影响着输水隧洞围岩稳定性。本文利用非饱和渗流理论和数值模拟方法研究了极端降雨条件入渗与黄土沟壑区隧洞的开挖扰动耦合影响下围岩的变形和渗流场演变规律,通过Plaxis3D模型对降雨入渗下新奥法施工过程中围岩力学特性、初期支护过程进行流固耦合分析。结果显示,降雨等级越高,围岩孔隙水压力变化幅度越大,对围岩的稳定性越不利;降雨入渗与开挖扰动会加速土层中渗流场和应力场的重分布过程;基于沟道的汇水特性,隧洞围岩含水率在最初5~10 d呈台阶式增长,拱顶、拱腰和拱趾处的最大变形为17.8 mm、28.2 mm、24.6 mm,最大剪切应力为175.3 kPa、182.5 kPa、150.6 kPa,降雨结束约15~20 d围岩变形速率逐渐减小收敛至特定值,但围岩的应力持续增加,为避免围岩发生塑性变形,故可在15~20 d进行二次衬砌支护。本次研究结果可对极端降雨期黄土沟壑地区隧洞施工安全控制提供参考。