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991.
Morelli G Song Y Mazzoni CJ Eppinger M Roumagnac P Wagner DM Feldkamp M Kusecek B Vogler AJ Li Y Cui Y Thomson NR Jombart T Leblois R Lichtner P Rahalison L Petersen JM Balloux F Keim P Wirth T Ravel J Yang R Carniel E Achtman M 《Nature genetics》2010,42(12):1140-1143
Plague is a pandemic human invasive disease caused by the bacterial agent Yersinia pestis. We here report a comparison of 17 whole genomes of Y. pestis isolates from global sources. We also screened a global collection of 286 Y. pestis isolates for 933 SNPs using Sequenom MassArray SNP typing. We conducted phylogenetic analyses on this sequence variation dataset, assigned isolates to populations based on maximum parsimony and, from these results, made inferences regarding historical transmission routes. Our phylogenetic analysis suggests that Y. pestis evolved in or near China and spread through multiple radiations to Europe, South America, Africa and Southeast Asia, leading to country-specific lineages that can be traced by lineage-specific SNPs. All 626 current isolates from the United States reflect one radiation, and 82 isolates from Madagascar represent a second radiation. Subsequent local microevolution of Y. pestis is marked by sequential, geographically specific SNPs. 相似文献
992.
Pan Li Guoying Zheng Yan Yang Chunguang Zhang Ping Xiong Yong Xu Min Fang Zheng Tan Fang Zheng Feili Gong 《Cellular and molecular life sciences : CMLS》2010,67(18):3197-3208
When they recognize a target cell, natural killer (NK) cells mount an attack to kill the target by exerting their cytotoxicity
via the exocytosis of cytotoxic granules. Although the details of this process (which includes the movement of cytotoxic granules
in the immune synapse and their fusion with the plasma membrane, releasing granzymes and perforin into the synaptic cleft)
are relatively better understood, the post-exocytosis regulation of the process is still largely unknown. Here we show that
a clathrin-dependent endocytosis stimulated by target cell occurs in NK92 cell line, which is closely correlated with granzyme
B recovery. Inhibition of the endocytosis significantly attenuates the cytotoxicity of NK92 cells. The NK cell recovery of
its released effector molecules, in turn, suggests that endocytosis may well play a key role in the post exocytosis regulation
of immune cells. 相似文献
993.
Kai Zhao Xingyu Zhao Yaping Tu Qi Miao Dongxu Cao Wenjuan Duan Yang Sun Jincheng Wang Taotao Wei Fuyu Yang 《Cellular and molecular life sciences : CMLS》2010,67(15):2665-2678
We have reported that chymotrypsin B (CtrB) is not just a digestive enzyme but is also stored in lysosomes. Herein, we demonstrated a broad distribution of CtrB and explored the involvement of CtrB in apoptosis. Exposure of RH-35 cells to H2O2 or palmitate induced the redistribution of lysosomal CtrB into the cytoplasm as a result of lysosomal membrane permeabilization (LMP). Suppression of CtrB significantly blocked apoptosis, while overexpression of CtrB sensitized apoptosis markedly. CtrB could cleave Bid under neutral conditions. In RH-35 cells with Bid silenced, apoptosis induced by CtrB protein was attenuated, suggesting that CtrB mediates apoptosis of RH-35 cells mainly through processing Bid. Our data also suggest that LMP occurs earlier than mitochondrial outer membrane permeabilization; Bid activation initiated by caspase-8 might be reinforced by CtrB in consequence of LMP, which causes a positive feedback loop leading to the accumulation of tBid, and results in lysosome- and mitochondrion-dependent apoptosis. 相似文献
994.
物联网(internet of things,IOT)拥有无处不在的识别、传感和通信能力,体域网(body area network,BAN)属于物联网中和人体相关的领域,其应用广泛,可以在日常生活中对人们进行监测及提供帮助.行走是许多日常活动的基本环节,因而步态分析能为体域网应用提供重要的生理行为信息.现有的步态分析已取得一定的研究成果,但仍存在一些问题,例如大多数步态特征提取是对加速度信号进行6重以上的变换,使得特征达到了45维以上,最后需要通过降维或优化来简化特征,较为复杂.本文设计一种灵活便捷的数据采集系统,并利用小波变换、傅里叶变换和四分位差提取出加速度信号中比较简单、低维度但能反应运动特征的步态参数,之后通过模式识别算法进行步态行为识别验证.实验结果表明该系统使用方便,特征提取方法简单实用,识别精确度为97%,EER(equal error rate)最小可到0.9%. 相似文献
995.
996.
月地高速再入返回器热控设计及实现 总被引:3,自引:0,他引:3
针对月地高速再入返回器不同阶段大功率散热、小功率保温与高速返回过程中高温隔热之间的突出矛盾,以及狭小、局促空间内设备热量的收集、传输、排散与阻断等技术难题,首次构建一种基于柔性自适应"热开关"的小型再入返回类航天器热控体系,成功研制出一套基于异构式环路热管的一体化柔性、高效热管理系统.在轨飞行数据表明:核心热控产品环路热管控温运行模式下实际传热能力超过65 W,阻断模式下漏热量小于2 W,"热导比"大于30,能够很好地实现"热开关"功能,确保了返回器所有设备的温度水平优于指标要求. 相似文献
997.
We consider the problem of online prediction when it is uncertain what the best prediction model to use is. We develop a method called dynamic latent class model averaging, which combines a state‐space model for the parameters of each of the candidate models of the system with a Markov chain model for the best model. We propose a polychotomous regression model for the transition weights to assume that the probability of a change in time depends on the past through the values of the most recent time periods and spatial correlation among the regions. The evolution of the parameters in each submodel is defined by exponential forgetting. This structure allows the ‘correct’ model to vary over both time and regions. In contrast to existing methods, the proposed model naturally incorporates clustering and prediction analysis in a single unified framework. We develop an efficient Gibbs algorithm for computation, and we demonstrate the value of our framework on simulated experiments and on a real‐world problem: forecasting IBM's corporate revenue. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
998.
999.
Characterizing genetic diversity within and between populations has broad applications in studies of human disease and evolution. We propose a new approach, spatial ancestry analysis, for the modeling of genotypes in two- or three-dimensional space. In spatial ancestry analysis (SPA), we explicitly model the spatial distribution of each SNP by assigning an allele frequency as a continuous function in geographic space. We show that the explicit modeling of the allele frequency allows individuals to be localized on the map on the basis of their genetic information alone. We apply our SPA method to a European and a worldwide population genetic variation data set and identify SNPs showing large gradients in allele frequency, and we suggest these as candidate regions under selection. These regions include SNPs in the well-characterized LCT region, as well as at loci including FOXP2, OCA2 and LRP1B. 相似文献
1000.
Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm 总被引:2,自引:0,他引:2
ME Lindsay D Schepers NA Bolar JJ Doyle E Gallo J Fert-Bober MJ Kempers EK Fishman Y Chen L Myers D Bjeda G Oswald AF Elias HP Levy BM Anderlid MH Yang EM Bongers J Timmermans AC Braverman N Canham GR Mortier HG Brunner PH Byers J Van Eyk L Van Laer HC Dietz BL Loeys 《Nature genetics》2012,44(8):922-927
Loeys-Dietz syndrome (LDS) associates with a tissue signature for high transforming growth factor (TGF)-β signaling but is often caused by heterozygous mutations in genes encoding positive effectors of TGF-β signaling, including either subunit of the TGF-β receptor or SMAD3, thereby engendering controversy regarding the mechanism of disease. Here, we report heterozygous mutations or deletions in the gene encoding the TGF-β2 ligand for a phenotype within the LDS spectrum and show upregulation of TGF-β signaling in aortic tissue from affected individuals. Furthermore, haploinsufficient Tgfb2(+/-) mice have aortic root aneurysm and biochemical evidence of increased canonical and noncanonical TGF-β signaling. Mice that harbor both a mutant Marfan syndrome (MFS) allele (Fbn1(C1039G/+)) and Tgfb2 haploinsufficiency show increased TGF-β signaling and phenotypic worsening in association with normalization of TGF-β2 expression and high expression of TGF-β1. Taken together, these data support the hypothesis that compensatory autocrine and/or paracrine events contribute to the pathogenesis of TGF-β-mediated vasculopathies. 相似文献