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391.
MRT-2 checkpoint protein is required for germline immortality and telomere replication in C. elegans 总被引:4,自引:0,他引:4
The germ line is an immortal cell lineage that is passed indefinitely from one generation to the next. To identify the genes that are required for germline immortality, we isolated Caenorhabditis elegans mutants with mortal germ lines--worms that can reproduce for several healthy generations but eventually become sterile. One of these mortal germline (mrt) mutants, mrt-2, exhibits progressive telomere shortening and accumulates end-to-end chromosome fusions in later generations, indicating that the MRT-2 protein is required for telomere replication. In addition, the germ line of mrt-2 is hypersensitive to X-rays and to transposon activity. Therefore, mrt-2 has defects in responding both to damaged DNA and to normal double-strand breaks present at telomeres. mrt-2 encodes a homologue of a checkpoint gene that is required to sense DNA damage in yeast. These results indicate that telomeres may be identified as a type of DNA damage and then repaired by the telomere-replication enzyme telomerase. 相似文献
392.
The genome sequence of the rice blast fungus Magnaporthe grisea 总被引:8,自引:0,他引:8
Dean RA Talbot NJ Ebbole DJ Farman ML Mitchell TK Orbach MJ Thon M Kulkarni R Xu JR Pan H Read ND Lee YH Carbone I Brown D Oh YY Donofrio N Jeong JS Soanes DM Djonovic S Kolomiets E Rehmeyer C Li W Harding M Kim S Lebrun MH Bohnert H Coughlan S Butler J Calvo S Ma LJ Nicol R Purcell S Nusbaum C Galagan JE Birren BW 《Nature》2005,434(7036):980-986
Magnaporthe grisea is the most destructive pathogen of rice worldwide and the principal model organism for elucidating the molecular basis of fungal disease of plants. Here, we report the draft sequence of the M. grisea genome. Analysis of the gene set provides an insight into the adaptations required by a fungus to cause disease. The genome encodes a large and diverse set of secreted proteins, including those defined by unusual carbohydrate-binding domains. This fungus also possesses an expanded family of G-protein-coupled receptors, several new virulence-associated genes and large suites of enzymes involved in secondary metabolism. Consistent with a role in fungal pathogenesis, the expression of several of these genes is upregulated during the early stages of infection-related development. The M. grisea genome has been subject to invasion and proliferation of active transposable elements, reflecting the clonal nature of this fungus imposed by widespread rice cultivation. 相似文献
393.
Chen Huang Xiaohua Geng Qinfei Ke Xiumei Mo Salem S. Al-Dey Mohamed El-Newehy 《自然科学进展(英文版)》2012,22(2):108-114
A novel type of composite vascular graft was developed via electrospinning in the present investigation.Collagen and chitosan were blended to form the inner and outer layer.Poly(1-lactide-co-caprolacto... 相似文献
394.
395.
李惠玲 《玉林师范学院学报》2004,25(2):115-118
从高校非中文专业学生知识结构的现状出发,阐述加强人文素质教育的重要性;“中国古典文学鉴赏”课的课程特点及其在人文素质教育中所起的作用决定了在高校非中文专业学生中开设这门课程的必要性和可行性。 相似文献
396.
RNAi-mediated gene silencing in non-human primates 总被引:2,自引:0,他引:2
Zimmermann TS Lee AC Akinc A Bramlage B Bumcrot D Fedoruk MN Harborth J Heyes JA Jeffs LB John M Judge AD Lam K McClintock K Nechev LV Palmer LR Racie T Röhl I Seiffert S Shanmugam S Sood V Soutschek J Toudjarska I Wheat AJ Yaworski E Zedalis W Koteliansky V Manoharan M Vornlocher HP MacLachlan I 《Nature》2006,441(7089):111-114
The opportunity to harness the RNA interference (RNAi) pathway to silence disease-causing genes holds great promise for the development of therapeutics directed against targets that are otherwise not addressable with current medicines. Although there are numerous examples of in vivo silencing of target genes after local delivery of small interfering RNAs (siRNAs), there remain only a few reports of RNAi-mediated silencing in response to systemic delivery of siRNA, and there are no reports of systemic efficacy in non-rodent species. Here we show that siRNAs, when delivered systemically in a liposomal formulation, can silence the disease target apolipoprotein B (ApoB) in non-human primates. APOB-specific siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP) and administered by intravenous injection to cynomolgus monkeys at doses of 1 or 2.5 mg kg(-1). A single siRNA injection resulted in dose-dependent silencing of APOB messenger RNA expression in the liver 48 h after administration, with maximal silencing of >90%. This silencing effect occurred as a result of APOB mRNA cleavage at precisely the site predicted for the RNAi mechanism. Significant reductions in ApoB protein, serum cholesterol and low-density lipoprotein levels were observed as early as 24 h after treatment and lasted for 11 days at the highest siRNA dose, thus demonstrating an immediate, potent and lasting biological effect of siRNA treatment. Our findings show clinically relevant RNAi-mediated gene silencing in non-human primates, supporting RNAi therapeutics as a potential new class of drugs. 相似文献
397.
提出了可变频时钟写入方法和锁相环倍频时钟写入方法,给出了这两种写入法的读/写电路,并分析了其性能。结果证明,可变频时钟写入方法电路简单,刻写时钟周期短;锁相环倍频时钟写入过程较前者长,但其频率范围容易调整。两者均适合高密度小型温盘的时钟录写。 相似文献
398.
Inactivation of the apoptosis effector Apaf-1 in malignant melanoma 总被引:47,自引:0,他引:47
Soengas MS Capodieci P Polsky D Mora J Esteller M Opitz-Araya X McCombie R Herman JG Gerald WL Lazebnik YA Cordón-Cardó C Lowe SW 《Nature》2001,409(6817):207-211
Metastatic melanoma is a deadly cancer that fails to respond to conventional chemotherapy and is poorly understood at the molecular level. p53 mutations often occur in aggressive and chemoresistant cancers but are rarely observed in melanoma. Here we show that metastatic melanomas often lose Apaf-1, a cell-death effector that acts with cytochrome c and caspase-9 to mediate p53-dependent apoptosis. Loss of Apaf-1 expression is accompanied by allelic loss in metastatic melanomas, but can be recovered in melanoma cell lines by treatment with the methylation inhibitor 5-aza-2'-deoxycytidine (5aza2dC). Apaf-1-negative melanomas are invariably chemoresistant and are unable to execute a typical apoptotic programme in response to p53 activation. Restoring physiological levels of Apaf-1 through gene transfer or 5aza2dC treatment markedly enhances chemosensitivity and rescues the apoptotic defects associated with Apaf-1 loss. We conclude that Apaf-1 is inactivated in metastatic melanomas, which leads to defects in the execution of apoptotic cell death. Apaf-1 loss may contribute to the low frequency of p53 mutations observed in this highly chemoresistant tumour type. 相似文献
399.
S. Ali Ghafari Oskoei Ghyslaine McClure Department of Civil Engineering Applied Mechanics McGill University Montréal Québec HA K Canada 《清华大学学报》2008,13(Z1):53-57
At present, high-speed computing capabilities and advanced nonlinear dynamic finite element procedures enable detailed dynamic analysis of cable structures. Although deterministic approaches require considerable analysis time and effort in relation to modeling, running, and data processing, they seem to be the only alternative to obtain high accuracy. Detailed dynamic analysis of cable roof networks is sophisticated and requires advanced modeling expertise. This paper presents a comparison between detailed nonlinear dynamic analysis and a simplified frequency domain approach to estimate the maximum probable response of weakly nonlinear cable roofs. The approach can be considered as alternative to detailed time-domain analysis in the preliminary design phase, or can be used to validate results obtained from more elaborated numerical models. The proposed method is illustrated with two examples of cable net roofs that were also analysed in the time domain. 相似文献
400.
The p53 tumour suppressor gene 总被引:266,自引:0,他引:266
The cell cycle is composed of a series of steps which can be negatively or positively regulated by various factors. Chief among the negative regulators is the p53 protein. Alteration or inactivation of p53 by mutation, or by its interactions with oncogene products of DNA tumour viruses, can lead to cancer. These mutations seem to be the most common genetic change in human cancers. 相似文献