排序方式: 共有44条查询结果,搜索用时 937 毫秒
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Nijnik A Woodbine L Marchetti C Dawson S Lambe T Liu C Rodrigues NP Crockford TL Cabuy E Vindigni A Enver T Bell JI Slijepcevic P Goodnow CC Jeggo PA Cornall RJ 《Nature》2007,447(7145):686-690
Accumulation of DNA damage leading to adult stem cell exhaustion has been proposed to be a principal mechanism of ageing. Here we address this question by taking advantage of the highly specific role of DNA ligase IV in the repair of DNA double-strand breaks by non-homologous end-joining, and by the discovery of a unique mouse strain with a hypomorphic Lig4(Y288C) mutation. The Lig4(Y288C) mouse, identified by means of a mutagenesis screening programme, is a mouse model for human LIG4 syndrome, showing immunodeficiency and growth retardation. Diminished DNA double-strand break repair in the Lig4(Y288C) strain causes a progressive loss of haematopoietic stem cells and bone marrow cellularity during ageing, and severely impairs stem cell function in tissue culture and transplantation. The sensitivity of haematopoietic stem cells to non-homologous end-joining deficiency is therefore a key determinant of their ability to maintain themselves against physiological stress over time and to withstand culture and transplantation. 相似文献
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Toxicity of poly I: poly C for rabbit eyes 总被引:3,自引:0,他引:3
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A. R. Jones Denise Stevenson Primrose Hutton A. G. Dawson 《Cellular and molecular life sciences : CMLS》1981,37(4):340-341
Summary The male antifertility agent -chlorohydrin (I) is metabolized by rat and boar sperm to -chloroactaldehyde (III), -chlorolactate (IV) and Cl– and not to the proposed active metabolite, -chlorohydrin-1-phosphate (III). It is proposed that -chlorolactaldehyde is produced intracellularly by a specific enzyme and that this is the metabolite responsible for the species-specific antifertility activity of -chlorohydrin.This work was supported by The National Health and Medical Research Council of Australia. 相似文献
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Association of adenoviruses with bovine respiratory diseases 总被引:2,自引:0,他引:2
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Q X Li L S Young G Niedobitek C W Dawson M Birkenbach F Wang A B Rickinson 《Nature》1992,356(6367):347-350
Epstein-Barr virus, a human herpesvirus with oncogenic potential, infects two target tissues in vivo: B lymphocytes, where the infection is largely non-productive, and stratified squamous epithelium in which virus replication occurs. The interaction with B cells, initiated through virus binding to the B-cell surface molecule CR2 (ref. 4), has been studied in vitro and the virus 'latent' genes associated with B-cell growth transformation defined. By comparison, viral infection of epithelium remains poorly understood, reflecting the lack of an appropriate cell-culture model. Here we describe the development of such a model using as targets CR2-expressing transfected cells of two independent human epithelial lines. A high proportion of these cells bind virus and become actively infected, expressing the small EBER RNAs (small non-polyadenylated virus-coded RNAs) and the Epstein-Barr nuclear antigen 1 but not other latent proteins; thereafter, under conditions favouring epithelial differentiation, up to 30% of the cells can be induced to enter virus productive cycle with some progressing to full virus replication. We find significant differences between laboratory virus strains in their ability to infect epithelium that do not correlate with their B-cell growth-transforming activity. 相似文献
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J P Steiner T M Dawson M Fotuhi C E Glatt A M Snowman N Cohen S H Snyder 《Nature》1992,358(6387):584-587
The immunophilins cyclophilin and FK506 binding protein (FKBP) are small, predominantly soluble proteins that bind the immunosuppressant drugs cyclosporin A and FK506, respectively, with high affinity, and which seem to mediate their pharmacological actions. The Ca(2+)-dependent protein phosphatase, calcineurin, binds the cyclophilin-cyclosporin A and FKBP-FK506 complexes, indicating that calcineurin might mediate the actions of these drugs. A physiological role for the immunophilins in the nervous system is implied by a close homology between the structure of NINA A, a protein in the neural retina of Drosophila, and cyclophilin, as well as by the high density of FKBP messenger RNA in brain tissue. Here we report that the levels of FKBP and mRNA in rat brain are extraordinarily high and that their regional localization is virtually identical to that of calcineurin, indicating that there may be a physiological link between calcineurin and the immunophilins. We also show that at low concentrations FK506 and cyclosporin A enhance the phosphorylation of endogenous protein substrates in brain tissue and in intact PC12 cells, indicating that these drugs may inhibit phosphatase activity by interacting with the immunophilin-calcineurin complexes. 相似文献
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Plants in urban ecosystems are exposed to many pollutants and higher temperatures, CO2 and nitrogen deposition than plants in rural areas. Although each factor has a detrimental or beneficial influence on plant growth, the net effect of all factors and the key driving variables are unknown. We grew the same cottonwood clone in urban and rural sites and found that urban plant biomass was double that of rural sites. Using soil transplants, nutrient budgets, chamber experiments and multiple regression analyses, we show that soils, temperature, CO2, nutrient deposition, urban air pollutants and microclimatic variables could not account for increased growth in the city. Rather, higher rural ozone (O3) exposures reduced growth at rural sites. Urban precursors fuel the reactions of O3 formation, but NO(x) scavenging reactions resulted in lower cumulative urban O3 exposures compared to agricultural and forested sites throughout the northeastern USA. Our study shows the overriding effect of O3 despite a diversity of altered environmental factors, reveals 'footprints' of lower cumulative urban O3 exposures amidst a background of higher regional exposures, and shows a greater adverse effect of urban pollutant emissions beyond the urban core. 相似文献