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11.
Mao JH Perez-Losada J Wu D Delrosario R Tsunematsu R Nakayama KI Brown K Bryson S Balmain A 《Nature》2004,432(7018):775-779
The FBXW7/hCDC4 gene encodes a ubiquitin ligase implicated in the control of chromosome stability. Here we identify the mouse Fbxw7 gene as a p53-dependent tumour suppressor gene by using a mammalian genetic screen for p53-dependent genes involved in tumorigenesis. Radiation-induced lymphomas from p53+/- mice, but not those from p53-/- mice, show frequent loss of heterozygosity and a 10% mutation rate of the Fbxw7 gene. Fbxw7+/- mice have greater susceptibility to radiation-induced tumorigenesis, but most tumours retain and express the wild-type allele, indicating that Fbxw7 is a haploinsufficient tumour suppressor gene. Loss of Fbxw7 alters the spectrum of tumours that develop in p53 deficient mice to include a range of tumours in epithelial tissues such as the lung, liver and ovary. Mouse embryo fibroblasts from Fbxw7-deficient mice, or wild-type mouse cells expressing Fbxw7 small interfering RNA, have higher levels of Aurora-A kinase, c-Jun and Notch4, but not of cyclin E. We propose that p53-dependent loss of Fbxw7 leads to genetic instability by mechanisms that might involve the activation of Aurora-A, providing a rationale for the early occurrence of these mutations in human cancers. 相似文献
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Phenotype-driven recessive genetic screens in diploid organisms require a strategy to render the mutation homozygous. Although homozygous mutant mice can be generated by breeding, a reliable method to make homozygous mutations in cultured cells has not been available, limiting recessive screens in culture. Cultured embryonic stem (ES) cells provide access to all of the genes required to elaborate the fundamental components and physiological systems of a mammalian cell. Here we have exploited the high rate of mitotic recombination in Bloom's syndrome protein (Blm)-deficient ES cells to generate a genome-wide library of homozygous mutant cells from heterozygous mutations induced with a revertible gene trap retrovirus. We have screened this library for cells with defects in DNA mismatch repair (MMR), a system that detects and repairs base-base mismatches. We demonstrate the recovery of cells with homozygous mutations in known and novel MMR genes. We identified Dnmt1(ref. 5) as a novel MMR gene and confirmed that Dnmt1-deficient ES cells exhibit micro-satellite instability, providing a mechanistic explanation for the role of Dnmt1 in cancer. The combination of insertional mutagenesis in Blm-deficient ES cells establishes a new approach for phenotype-based recessive genetic screens in ES cells. 相似文献
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TCE的物理化学特性及其生物降解作用 总被引:3,自引:2,他引:1
宋汉周 《河海大学学报(自然科学版)》2000,28(1):52-56
以加拿大一厂址区碳酸盐岩水是中地下受到三氯惭烯(TCE)化合物的污染作为实例,对TCE的物理化学特性及其降解作用进行论述,指出TCE污染物的生物降解作用的存在的,但是不完全,因此,当TCE污染物深度明显超标时,仍应考虑采取去除污染措施。 相似文献
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Allan Chapman 《Annals of science》2013,70(5):431-463
When Thomas Hornsby commissioned John Bird to build a set of five major astronomical instruments for the new Radcliffe Observatory, Oxford, the order included an Equatorial Sector. This was an instrument of experimental design, intended to measure angles out of the meridian. Although in itself a transitional instrument, the Equatorial Sector's capacity for extra-meridional measurement, especially for the observation of comets, encouraged craftsmen to develop the design first into the Equatorial Circle, and then into the large equatorially mounted refracting telescope used in conjunction with micrometers. Although other Equatorial Sectors were made, Bird's instrument for Oxford is the only one that survives intact. The present study examines this unique artefact within the context of changing astronomical demands between the 1770s and the 1820s. 相似文献
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Summary The genetically diabetic and obesedb/db mice responded lipolytically to isoproterenol and propranolol similarly to normal mice in vivo. However, considering the large amount of triglyceride in adb/db mouse, we conclude that the in vivo response ofdb/db adipose tissue is deficient in magnitude. 相似文献