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排序方式: 共有497条查询结果,搜索用时 937 毫秒
191.
Motor axons receive retrograde signals from skeletal muscle that are essential for the differentiation and stabilization of motor nerve terminals. Identification of these retrograde signals has proved elusive, but their production by muscle depends on the receptor tyrosine kinase, MuSK (muscle, skeletal receptor tyrosine-protein kinase), and Lrp4 (low-density lipoprotein receptor (LDLR)-related protein 4), an LDLR family member that forms a complex with MuSK, binds neural agrin and stimulates MuSK kinase activity. Here we show that Lrp4 also functions as a direct muscle-derived retrograde signal for early steps in presynaptic differentiation. We demonstrate that Lrp4 is necessary, independent of MuSK activation, for presynaptic differentiation in vivo, and we show that Lrp4 binds to motor axons and induces clustering of synaptic-vesicle and active-zone proteins. Thus, Lrp4 acts bidirectionally and coordinates synapse formation by binding agrin, activating MuSK and stimulating postsynaptic differentiation, and functioning in turn as a muscle-derived retrograde signal that is necessary and sufficient for presynaptic differentiation. 相似文献
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194.
The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups 总被引:1,自引:0,他引:1
Curtis C Shah SP Chin SF Turashvili G Rueda OM Dunning MJ Speed D Lynch AG Samarajiwa S Yuan Y Gräf S Ha G Haffari G Bashashati A Russell R McKinney S;METABRIC Group Langerød A Green A Provenzano E Wishart G Pinder S Watson P Markowetz F Murphy L Ellis I Purushotham A Børresen-Dale AL Brenton JD Tavaré S Caldas C Aparicio S 《Nature》2012,486(7403):346-352
195.
This paper deals with the problem of H∞ fault estimation for linear time-delay systems in finite frequency domain. First a generalized coordinate change is applied to the original system such that in the new coordinates all the time-delay terms are injected by the system’s input and output. Then an observer-based H∞ fault estimator with input and output injections is proposed for fault estimation with known frequency range. With the aid of Generalized Kalman-Yakubovich-Popov lemma, sufficient conditions on the existence of the H∞ fault estimator are derived and a solution to the observer gain matrices is obtained by solving a set of linear matrix inequalities. Finally, a numerical example is given to illustrate the effectiveness of the proposed method. 相似文献
196.
Amstrup SC Deweaver ET Douglas DC Marcot BG Durner GM Bitz CM Bailey DA 《Nature》2010,468(7326):955-958
On the basis of projected losses of their essential sea-ice habitats, a United States Geological Survey research team concluded in 2007 that two-thirds of the world's polar bears (Ursus maritimus) could disappear by mid-century if business-as-usual greenhouse gas emissions continue. That projection, however, did not consider the possible benefits of greenhouse gas mitigation. A key question is whether temperature increases lead to proportional losses of sea-ice habitat, or whether sea-ice cover crosses a tipping point and irreversibly collapses when temperature reaches a critical threshold. Such a tipping point would mean future greenhouse gas mitigation would confer no conservation benefits to polar bears. Here we show, using a general circulation model, that substantially more sea-ice habitat would be retained if greenhouse gas rise is mitigated. We also show, with Bayesian network model outcomes, that increased habitat retention under greenhouse gas mitigation means that polar bears could persist throughout the century in greater numbers and more areas than in the business-as-usual case. Our general circulation model outcomes did not reveal thresholds leading to irreversible loss of ice; instead, a linear relationship between global mean surface air temperature and sea-ice habitat substantiated the hypothesis that sea-ice thermodynamics can overcome albedo feedbacks proposed to cause sea-ice tipping points. Our outcomes indicate that rapid summer ice losses in models and observations represent increased volatility of a thinning sea-ice cover, rather than tipping-point behaviour. Mitigation-driven Bayesian network outcomes show that previously predicted declines in polar bear distribution and numbers are not unavoidable. Because polar bears are sentinels of the Arctic marine ecosystem and trends in their sea-ice habitats foreshadow future global changes, mitigating greenhouse gas emissions to improve polar bear status would have conservation benefits throughout and beyond the Arctic. 相似文献
197.
Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima. 总被引:27,自引:0,他引:27
K E Nelson R A Clayton S R Gill M L Gwinn R J Dodson D H Haft E K Hickey J D Peterson W C Nelson K A Ketchum L McDonald T R Utterback J A Malek K D Linher M M Garrett A M Stewart M D Cotton M S Pratt C A Phillips D Richardson J Heidelberg G G Sutton R D Fleischmann J A Eisen O White S L Salzberg H O Smith J C Venter C M Fraser 《Nature》1999,399(6734):323-329
The 1,860,725-base-pair genome of Thermotoga maritima MSB8 contains 1,877 predicted coding regions, 1,014 (54%) of which have functional assignments and 863 (46%) of which are of unknown function. Genome analysis reveals numerous pathways involved in degradation of sugars and plant polysaccharides, and 108 genes that have orthologues only in the genomes of other thermophilic Eubacteria and Archaea. Of the Eubacteria sequenced to date, T. maritima has the highest percentage (24%) of genes that are most similar to archaeal genes. Eighty-one archaeal-like genes are clustered in 15 regions of the T. maritima genome that range in size from 4 to 20 kilobases. Conservation of gene order between T. maritima and Archaea in many of the clustered regions suggests that lateral gene transfer may have occurred between thermophilic Eubacteria and Archaea. 相似文献
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199.
北京大气细粒子PM2.5的化学组成 总被引:38,自引:0,他引:38
杨复沫 贺克斌 马永亮 张强 姚小红 Chak K.Chan Steven Cadle Tai Chan Patricia Mulawa 《清华大学学报(自然科学版)》2002,42(12):1605-1608
为了解北京大气细粒子(PM2.5)的污染水平和污染特征,在车公庄和清华园进行了连续1年、每周1次同步采样和全样品分析。2个采样点PM2.5的化学组成相似。含碳组分和水溶性离子是主要的组分,其质量浓度之和超过PM2.5的50%。有机碳、元素碳和细粒子PM2.5的季节变化一致,即冬季质量浓度最高,夏季最低。夏季NO-3的质量浓度最低且在采样过程中从特氟隆滤膜上有近50%的挥发。SO2-4不同于PM2.5的季节变化主要取决于SO2的转化率。地壳元素的质量浓度从冬季到春季大幅度上升,春季沙尘天气频是一个重要原因。 相似文献
200.
Raj L Ide T Gurkar AU Foley M Schenone M Li X Tolliday NJ Golub TR Carr SA Shamji AF Stern AM Mandinova A Schreiber SL Lee SW 《Nature》2011,475(7355):231-234
Malignant transformation, driven by gain-of-function mutations in oncogenes and loss-of-function mutations in tumour suppressor genes, results in cell deregulation that is frequently associated with enhanced cellular stress (for example, oxidative, replicative, metabolic and proteotoxic stress, and DNA damage). Adaptation to this stress phenotype is required for cancer cells to survive, and consequently cancer cells may become dependent upon non-oncogenes that do not ordinarily perform such a vital function in normal cells. Thus, targeting these non-oncogene dependencies in the context of a transformed genotype may result in a synthetic lethal interaction and the selective death of cancer cells. Here we used a cell-based small-molecule screening and quantitative proteomics approach that resulted in the unbiased identification of a small molecule that selectively kills cancer cells but not normal cells. Piperlongumine increases the level of reactive oxygen species (ROS) and apoptotic cell death in both cancer cells and normal cells engineered to have a cancer genotype, irrespective of p53 status, but it has little effect on either rapidly or slowly dividing primary normal cells. Significant antitumour effects are observed in piperlongumine-treated mouse xenograft tumour models, with no apparent toxicity in normal mice. Moreover, piperlongumine potently inhibits the growth of spontaneously formed malignant breast tumours and their associated metastases in mice. Our results demonstrate the ability of a small molecule to induce apoptosis selectively in cells that have a cancer genotype, by targeting a non-oncogene co-dependency acquired through the expression of the cancer genotype in response to transformation-induced oxidative stress. 相似文献