排序方式: 共有4条查询结果,搜索用时 15 毫秒
1
1.
Ford CB Lin PL Chase MR Shah RR Iartchouk O Galagan J Mohaideen N Ioerger TR Sacchettini JC Lipsitch M Flynn JL Fortune SM 《Nature genetics》2011,43(5):482-486
Tuberculosis poses a global health emergency, which has been compounded by the emergence of drug-resistant Mycobacterium tuberculosis (Mtb) strains. We used whole-genome sequencing to compare the accumulation of mutations in Mtb isolated from cynomolgus macaques with active, latent or reactivated disease. We sequenced 33 Mtb isolates from nine macaques with an average genome coverage of 93% and an average read depth of 117×. Based on the distribution of SNPs observed, we calculated the mutation rates for these disease states. We found a similar mutation rate during latency as during active disease or in a logarithmically growing culture over the same period of time. The pattern of polymorphisms suggests that the mutational burden in vivo is because of oxidative DNA damage. We show that Mtb continues to acquire mutations during disease latency, which may explain why isoniazid monotherapy for latent tuberculosis is a risk factor for the emergence of isoniazid resistance. 相似文献
2.
Gene-target recognition among members of the myc superfamily and implications for oncogenesis 总被引:16,自引:0,他引:16
O'Hagan RC Schreiber-Agus N Chen K David G Engelman JA Schwab R Alland L Thomson C Ronning DR Sacchettini JC Meltzer P DePinho RA 《Nature genetics》2000,24(2):113-119
Myc and Mad family proteins regulate multiple biological processes through their capacity to influence gene expression directly. Here we show that the basic regions of Myc and Mad proteins are not functionally equivalent in oncogenesis, have separable E-box-binding activities and engage both common and distinct gene targets. Our data support the view that the opposing biological actions of Myc and Mxi1 extend beyond reciprocal regulation of common gene targets. Identification of differentially regulated gene targets provides a framework for understanding the mechanism through which the Myc superfamily governs the growth, proliferation and survival of normal and neoplastic cells. 相似文献
3.
本文证明了公式β(n)=σ(n-1)+1其中α(n-1)是n-1次多项式微分系统的不为直线的最多条数,βn)是n次多项式微分系统的不变直线的不同斜率的最大个数。这里假设所讨论的多项式系统只有限条不变直线。 相似文献
4.
Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase 总被引:49,自引:0,他引:49
McKinney JD Höner zu Bentrup K Muñoz-Elías EJ Miczak A Chen B Chan WT Swenson D Sacchettini JC Jacobs WR Russell DG 《Nature》2000,406(6797):735-738
Mycobacterium tuberculosis claims more human lives each year than any other bacterial pathogen. Infection is maintained in spite of acquired immunity and resists eradication by antimicrobials. Despite an urgent need for new therapies targeting persistent bacteria, our knowledge of bacterial metabolism throughout the course of infection remains rudimentary. Here we report that persistence of M. tuberculosis in mice is facilitated by isocitrate lyase (ICL), an enzyme essential for the metabolism of fatty acids. Disruption of the icl gene attenuated bacterial persistence and virulence in immune-competent mice without affecting bacterial growth during the acute phase of infection. A link between the requirement for ICL and the immune status of the host was established by the restored virulence of delta icl bacteria in interferon-gamma knockout mice. This link was apparent at the level of the infected macrophage: Activation of infected macrophages increased expression of ICL, and the delta icl mutant was markedly attenuated for survival in activated but not resting macrophages. These data suggest that the metabolism of M. tuberculosis in vivo is profoundly influenced by the host response to infection, an observation with important implications for the treatment of chronic tuberculosis. 相似文献
1