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101.
Weng AP Ferrando AA Lee W Morris JP Silverman LB Sanchez-Irizarry C Blacklow SC Look AT Aster JC 《Science (New York, N.Y.)》2004,306(5694):269-271
Very rare cases of human T cell acute lymphoblastic leukemia (T-ALL) harbor chromosomal translocations that involve NOTCH1, a gene encoding a transmembrane receptor that regulates normal T cell development. Here, we report that more than 50% of human T-ALLs, including tumors from all major molecular oncogenic subtypes, have activating mutations that involve the extracellular heterodimerization domain and/or the C-terminal PEST domain of NOTCH1. These findings greatly expand the role of activated NOTCH1 in the molecular pathogenesis of human T-ALL and provide a strong rationale for targeted therapies that interfere with NOTCH signaling. 相似文献
102.
Katsanis N Ansley SJ Badano JL Eichers ER Lewis RA Hoskins BE Scambler PJ Davidson WS Beales PL Lupski JR 《Science (New York, N.Y.)》2001,293(5538):2256-2259
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by multiple clinical features that include pigmentary retinal dystrophy, polydactyly, obesity, developmental delay, and renal defects. BBS is considered an autosomal recessive disorder, and recent positional cloning efforts have identified two BBS genes (BBS2 and BBS6). We screened our cohort of 163 BBS families for mutations in both BBS2 and BBS6 and report the presence of three mutant alleles in affected individuals in four pedigrees. In addition, we detected unaffected individuals in two pedigrees who carry two BBS2 mutations but not a BBS6 mutation. We therefore propose that BBS may not be a single-gene recessive disease but a complex trait requiring three mutant alleles to manifest the phenotype. This triallelic model of disease transmission may be important in the study of both Mendelian and multifactorial disorders. 相似文献
103.
Lewis TH 《Science (New York, N.Y.)》1887,9(220):393-394
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Lewis J 《Science (New York, N.Y.)》2008,322(5900):399-403
We now have a wealth of information about the molecular signals that act on cells in embryos, but how do the control systems based on these signals generate pattern and govern the timing of developmental events? Here, I discuss four examples to show how mathematical modeling and quantitative experimentation can give some useful answers. The examples concern the Bicoid gradient in the early Drosophila embryo, the dorsoventral patterning of a frog embryo by bone morphogenetic protein signals, the auxin-mediated patterning of plant meristems, and the Notch-dependent somite segmentation clock. 相似文献
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Total carbon and nitrogen abundances were determined by using combustion-gas chromatographic techlniques. Weighited mean analyses for butlk fines were 225 and 140 ppm total carbon and 150 anid 100 ppm total nitrogen. Total carbon in fine breccia was 230 ppm; in coarse breccia, 100 ppmn; in fine-grained rock, 70 ppm; and in mediumn-grained rock, 64 ppm. The finest sieved fraction had the highest carbon content. Total nitrogen in fine breccia was 125 ppm; in coarse breccia, 100 ppm; in fine-grained rock, 115 ppm; and in medium-grained rock, 30 ppm. The total carbon and nitrogen finies appeat to be mixtuires of indigenous lunar material togetheer with meteoritic and solar wind components. 相似文献
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Assumption of a water-impermeable coat on bacterial spores is inconsistent with known permeabilities of organic materials. A low water content may arise through compressive contraction of the cortex during spore maturation. 相似文献
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