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The molecular pathogenesis of renal cell carcinoma (RCC) is poorly understood. Whole-genome and exome sequencing followed by innovative tumorgraft analyses (to accurately determine mutant allele ratios) identified several putative two-hit tumor suppressor genes, including BAP1. The BAP1 protein, a nuclear deubiquitinase, is inactivated in 15% of clear cell RCCs. BAP1 cofractionates with and binds to HCF-1 in tumorgrafts. Mutations disrupting the HCF-1 binding motif impair BAP1-mediated suppression of cell proliferation but not deubiquitination of monoubiquitinated histone 2A lysine 119 (H2AK119ub1). BAP1 loss sensitizes RCC cells in vitro to genotoxic stress. Notably, mutations in BAP1 and PBRM1 anticorrelate in tumors (P = 3 × 10(-5)), and combined loss of BAP1 and PBRM1 in a few RCCs was associated with rhabdoid features (q = 0.0007). BAP1 and PBRM1 regulate seemingly different gene expression programs, and BAP1 loss was associated with high tumor grade (q = 0.0005). Our results establish the foundation for an integrated pathological and molecular genetic classification of RCC, paving the way for subtype-specific treatments exploiting genetic vulnerabilities.  相似文献   
425.
The anonymous set of astronomical tables preserved in Paris, Bibliothèque nationale de France, MS lat. 10262, is the first set of displaced tables to be found in a medieval Latin text. These tables are a reworking of the standard Alfonsine tables and yield the same results. However, the mean motions are defined differently, the presentation of the tables is unprecedented, and some new functions are introduced for computing true planetary longitudes. The absence of any instructions as well as unusual technical terms in the headings make it difficult to appreciate the cleverness that went into the construction of these tables that are extant in a unique copy. In this article we provide a detailed analysis of these tables and their underlying parameters. The displaced tables are typical of a pervasive tendency in Islamic science to provide extensive and elegant numerical tables for the convenience of practitioners. The underlying astronomical theory is neither questioned nor affected. Edward S. Kennedy   相似文献   
426.
Exotic quantum phenomena may appear in material systems with multiple orders or phases,where the mutual interactions can give rise to new physics beyond that of...  相似文献   
427.
When fibroblasts from chick embryos were treated with Ricinus lectin, the effects observed depended on the stage of development of the embryo from which the cells were prepared. Thus, in 16-day fibroblasts, which have a weak proliferative capacity, nucleic acid synthesis was less sensitive to the effect of this lectin than that in 8-day fibroblasts, whose proliferative capacity is high.  相似文献   
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We have isolated a purified preparation of the vascular plasminogen activator. Plasma obtained from post occlusion venous blood has been chromatographed with low and high ionic strength buffers. The purified protein has a relative molecular weight of 71,000.  相似文献   
429.
Rats were fed on a 20% fat diet; 30 min. or 2 hrs later intestinal jejunal cells were fixed in situ; samples were taken and processed for subsequent study by electron microscopy. Chylomicron secretion was followed from the enterocyte to the lymphatic capillary lumen. Chylomicrons entered the lamina propria through breaks in the basal membrane at intercellular space level. Their penetration into the lymphatic capillary lumen occurred through the open junctions of the endothelial cells normally kept closed by desmosomal formations.  相似文献   
430.
The proliferative capacity of Chick embryo fibroblasts was modified by Con A treatment. Con A decreased the growth of fibroblasts from young embryos (8 days), whereas the lectin stimulated the growth of fibroblasts from older embryos (16 days). This differential effect of Con A did not result from changes in cellular permeability to thymidine, but rather from Con A induced modifications of hexose transport. Changes in hexose transport would cause, as a response, parallel modifications in glycolysis and hence energy charge, which would alter proliferative capacity.  相似文献   
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