排序方式: 共有49条查询结果,搜索用时 15 毫秒
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Chiang C Jacobsen JC Ernst C Hanscom C Heilbut A Blumenthal I Mills RE Kirby A Lindgren AM Rudiger SR McLaughlan CJ Bawden CS Reid SJ Faull RL Snell RG Hall IM Shen Y Ohsumi TK Borowsky ML Daly MJ Lee C Morton CC MacDonald ME Gusella JF Talkowski ME 《Nature genetics》2012,44(4):390-7, S1
We defined the genetic landscape of balanced chromosomal rearrangements at nucleotide resolution by sequencing 141 breakpoints from cytogenetically interpreted translocations and inversions. We confirm that the recently described phenomenon of 'chromothripsis' (massive chromosomal shattering and reorganization) is not unique to cancer cells but also occurs in the germline, where it can resolve to a relatively balanced state with frequent inversions. We detected a high incidence of complex rearrangements (19.2%) and substantially less reliance on microhomology (31%) than previously observed in benign copy-number variants (CNVs). We compared these results to experimentally generated DNA breakage-repair by sequencing seven transgenic animals, revealing extensive rearrangement of the transgene and host genome with similar complexity to human germline alterations. Inversion was the most common rearrangement, suggesting that a combined mechanism involving template switching and non-homologous repair mediates the formation of balanced complex rearrangements that are viable, stably replicated and transmitted unaltered to subsequent generations. 相似文献
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Resolution of acute inflammation is an active process essential for appropriate host responses, tissue protection and the return to homeostasis. During resolution, specific omega-3 polyunsaturated fatty-acid-derived mediators are generated within resolving exudates, including resolvin E1 (RvE1) and protectin D1 (PD1). It is thus important to pinpoint specific actions of RvE1 and PD1 in regulating tissue resolution. Here we report that RvE1 and PD1 in nanogram quantities promote phagocyte removal during acute inflammation by regulating leukocyte infiltration, increasing macrophage ingestion of apoptotic polymorphonuclear neutrophils in vivo and in vitro, and enhancing the appearance of phagocytes carrying engulfed zymosan in lymph nodes and spleen. In this tissue terrain, inhibition of either cyclooxygenase or lipoxygenases--pivotal enzymes in the temporal generation of both pro-inflammatory and pro-resolving mediators--caused a 'resolution deficit' that was rescued by RvE1, PD1 or aspirin-triggered lipoxin A4 analogue. Also, new resolution routes were identified that involve phagocytes traversing perinodal adipose tissues and non-apoptotic polymorphonuclear neutrophils carrying engulfed zymosan to lymph nodes. Together, these results identify new active components for postexudate resolution traffic, and demonstrate that RvE1 and PD1 are potent agonists for resolution of inflamed tissues. 相似文献
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本文研究了控制量变化率受限时的MRAS控制。在文献[1~3]的启发下,本文提出了控制量变化率受限时的MRAS鲁棒变结构控制问题;给出了控制器结构、控制律、自适应律,分析了系统的稳定性和渐近收敛性。 相似文献
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Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10 总被引:35,自引:0,他引:35
Chiang SH Baumann CA Kanzaki M Thurmond DC Watson RT Neudauer CL Macara IG Pessin JE Saltiel AR 《Nature》2001,410(6831):944-948
The stimulation of glucose uptake by insulin in muscle and adipose tissue requires translocation of the GLUT4 glucose transporter protein from intracellular storage sites to the cell surface. Although the cellular dynamics of GLUT4 vesicle trafficking are well described, the signalling pathways that link the insulin receptor to GLUT4 translocation remain poorly understood. Activation of phosphatidylinositol-3-OH kinase (PI(3)K) is required for this trafficking event, but it is not sufficient to produce GLUT4 translocation. We previously described a pathway involving the insulin-stimulated tyrosine phosphorylation of Cbl, which is recruited to the insulin receptor by the adapter protein CAP. On phosphorylation, Cbl is translocated to lipid rafts. Blocking this step completely inhibits the stimulation of GLUT4 translocation by insulin. Here we show that phosphorylated Cbl recruits the CrkII-C3G complex to lipid rafts, where C3G specifically activates the small GTP-binding protein TC10. This process is independent of PI(3)K, but requires the translocation of Cbl, Crk and C3G to the lipid raft. The activation of TC10 is essential for insulin-stimulated glucose uptake and GLUT4 translocation. The TC10 pathway functions in parallel with PI(3)K to stimulate fully GLUT4 translocation in response to insulin. 相似文献
5.
The exocyst complex is required for targeting of Glut4 to the plasma membrane by insulin 总被引:20,自引:0,他引:20
Insulin stimulates glucose transport by promoting exocytosis of the glucose transporter Glut4 (refs 1, 2). The dynamic processes involved in the trafficking of Glut4-containing vesicles, and in their targeting, docking and fusion at the plasma membrane, as well as the signalling processes that govern these events, are not well understood. We recently described tyrosine-phosphorylation events restricted to subdomains of the plasma membrane that result in activation of the G protein TC10 (refs 3, 4). Here we show that TC10 interacts with one of the components of the exocyst complex, Exo70. Exo70 translocates to the plasma membrane in response to insulin through the activation of TC10, where it assembles a multiprotein complex that includes Sec6 and Sec8. Overexpression of an Exo70 mutant blocked insulin-stimulated glucose uptake, but not the trafficking of Glut4 to the plasma membrane. However, this mutant did block the extracellular exposure of the Glut4 protein. So, the exocyst might have a crucial role in the targeting of the Glut4 vesicle to the plasma membrane, perhaps directing the vesicle to the precise site of fusion. 相似文献
6.
The local Universe displays a rich hierarchical pattern of galaxy clusters and superclusters. The early Universe, however, was almost smooth, with only slight 'ripples' as seen in the cosmic microwave background radiation. Models of the evolution of cosmic structure link these observations through the effect of gravity, because the small initially overdense fluctuations are predicted to attract additional mass as the Universe expands. During the early stages of this expansion, the ripples evolve independently, like linear waves on the surface of deep water. As the structures grow in mass, they interact with each other in nonlinear ways, more like waves breaking in shallow water. We have recently shown how cosmic structure can be characterized by phase correlations associated with these nonlinear interactions, but it was not clear how to use that information to obtain quantitative insights into the growth of structures. Here we report a method of revealing phase information, and show quantitatively how this relates to the formation of filaments, sheets and clusters of galaxies by nonlinear collapse. We develop a statistical method based on information entropy to separate linear from nonlinear effects, and thereby are able to disentangle those aspects of galaxy clustering that arise from initial conditions (the ripples) from the subsequent dynamical evolution. 相似文献
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Farmers in drought-prone regions of Andean South America have historically made observations of changes in the apparent brightness of stars in the Pleiades around the time of the southern winter solstice in order to forecast interannual variations in summer rainfall and in autumn harvests. They moderate the effect of reduced rainfall by adjusting the planting dates of potatoes, their most important crop. Here we use data on cloud cover and water vapour from satellite imagery, agronomic data from the Andean altiplano and an index of El Nino variability to analyse this forecasting method. We find that poor visibility of the Pleiades in June-caused by an increase in subvisual high cirrus clouds-is indicative of an El Nino year, which is usually linked to reduced rainfall during the growing season several months later. Our results suggest that this centuries-old method of seasonal rainfall forecasting may be based on a simple indicator of El Nino variability. 相似文献
8.
The fecundity of the blood-feeding insect,Rhodnius prolixus, was observed to increase in successive periods of egg production, each period being triggered by a single large blood meal. As previously published, the fecundity of mated animals was significantly higher than that of unmated animals for the first period of egg production. For a second period of egg production, fecundity increased significantly in both mated and unmated animals. By the fourth period, fecundity had returned to first-feed values for mated animals, but remained high for unmated animals, and the fecundity of mated and unmated animals was not significantly different. Thus, during successive periods of egg production, the processes which maintain fecundity of unmated animals below that of mated animals are overcome. 相似文献
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本文研究了多环烃异构物的分子轨道能量与电子活动性能的关系,包括各种并苯、联苯类异构物的分子轨道能级以及电子光谱等有关性能。每组异构物中,与最高占有分子轨道能级E_1及直接相关的性能以最长直链物为最低级限,带有侧位环的异构物则依侧位环数目递增,与E_(-1)及其直接相关性能,则以最长直链物为最高极限,依直环数的缩减而递减。各组异构物之间,性能~环数图线上形成的同系列曲线和等直环线都表明分子中直链的长度是主要因素。 相似文献