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Read TD Peterson SN Tourasse N Baillie LW Paulsen IT Nelson KE Tettelin H Fouts DE Eisen JA Gill SR Holtzapple EK Okstad OA Helgason E Rilstone J Wu M Kolonay JF Beanan MJ Dodson RJ Brinkac LM Gwinn M DeBoy RT Madpu R Daugherty SC Durkin AS Haft DH Nelson WC Peterson JD Pop M Khouri HM Radune D Benton JL Mahamoud Y Jiang L Hance IR Weidman JF Berry KJ Plaut RD Wolf AM Watkins KL Nierman WC Hazen A Cline R Redmond C Thwaite JE White O Salzberg SL Thomason B Friedlander AM Koehler TM Hanna PC 《Nature》2003,423(6935):81-86
Bacillus anthracis is an endospore-forming bacterium that causes inhalational anthrax. Key virulence genes are found on plasmids (extra-chromosomal, circular, double-stranded DNA molecules) pXO1 (ref. 2) and pXO2 (ref. 3). To identify additional genes that might contribute to virulence, we analysed the complete sequence of the chromosome of B. anthracis Ames (about 5.23 megabases). We found several chromosomally encoded proteins that may contribute to pathogenicity--including haemolysins, phospholipases and iron acquisition functions--and identified numerous surface proteins that might be important targets for vaccines and drugs. Almost all these putative chromosomal virulence and surface proteins have homologues in Bacillus cereus, highlighting the similarity of B. anthracis to near-neighbours that are not associated with anthrax. By performing a comparative genome hybridization of 19 B. cereus and Bacillus thuringiensis strains against a B. anthracis DNA microarray, we confirmed the general similarity of chromosomal genes among this group of close relatives. However, we found that the gene sequences of pXO1 and pXO2 were more variable between strains, suggesting plasmid mobility in the group. The complete sequence of B. anthracis is a step towards a better understanding of anthrax pathogenesis. 相似文献
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Many small proteins seem to fold by a simple process explicable by conventional chemical kinetics and transition-state theory. This assumes an instant equilibrium between reactants and a high-energy activated state. In reality, equilibration occurs on timescales dependent on the molecules involved, below which such analyses break down. The molecular timescale, normally too short to be seen in experiments, can be of a significant length for proteins. To probe it directly, we studied very rapidly folding mutants of the five-helix bundle protein lambda(6-85), whose activated state is significantly populated during folding. A time-dependent rate coefficient below 2 micro s signals the onset of the molecular timescale, and hence the ultimate speed limit for folding. A simple model shows that the molecular timescale represents the natural pre-factor for transition state models of folding. 相似文献
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Conditional inactivation of Fgf4 reveals complexity of signalling during limb bud development 总被引:12,自引:0,他引:12
Development of the vertebrate limb bud depends on reciprocal interactions between the zone of polarizing activity (ZPA) and the apical ectodermal ridge (AER). Sonic hedgehog (SHH) and fibroblast growth factors (FGFs) are key signalling molecules produced in the ZPA and AER, respectively. Experiments in chicks suggested that SHH expression in the ZPA is maintained by FGF4 expression in the AER, and vice versa, providing a molecular mechanism for coordinating the activities of these two signalling centres. This SHH/FGF4 feedback loop model is supported by genetic evidence showing that Fgf4 expression is not maintained in Shh-/- mouse limbs. We report here that Shh expression is maintained and limb formation is normal when Fgf4 is inactivated in mouse limbs, thus contradicting the model. We also found that maintenance of Fgf9 and Fgf17 expression is dependent on Shh, whereas Fgf8 expression is not. We discuss a model in which no individual Fgf expressed in the AER (AER-Fgf) is solely necessary to maintain Shh expression, but, instead, the combined activities of two or more AER-Fgfs function in a positive feedback loop with Shh to control limb development. 相似文献
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A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer's disease 总被引:21,自引:0,他引:21
Chen G Chen KS Knox J Inglis J Bernard A Martin SJ Justice A McConlogue L Games D Freedman SB Morris RG 《Nature》2000,408(6815):975-979
Mice that overexpress the human mutant amyloid precursor protein (hAPP) show learning deficits, but the apparent lack of a relationship between these deficits and the progressive beta-amyloid plaque formation that the hAPP mice display is puzzling. In the water maze, hAPP mice are impaired before and after amyloid plaque deposition. Here we show, using a new water-maze training protocol, that PDAPP mice also exhibit a separate age-related deficit in learning a series of spatial locations. This impairment correlates with beta-amyloid plaque burden and is shown in both cross-sectional and longitudinal experimental designs. Cued navigation and object-recognition memory are normal. These findings indicate that A beta overexpression and/or A beta plaques are associated with disturbed cognitive function and, importantly, suggest that some but not all forms of learning and memory are suitable behavioural assays of the progressive cognitive deficits associated with Alzheimer's-disease-type pathologies. 相似文献
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某些植物不能将它们的基因保持在体内,但这真的要紧吗?恶梦般的景象可能是这样展开的:农民用经过遗传工程处理使之带有战胜害虫和病害的基因的作物来覆盖他们的农田。这些作物将它们的基因传递给了野生亲缘植物,将它们变成具有超竞争力的杂草,这些杂草将整个农村闹得天翻地覆,消灭掉稀有的和脆弱的物种。环境保护主义者全线反击。面对造成严重损害的诉讼,生物工程公司提出申请破产。科林·梅里特对此感叹不已。在此以前他已经上千次听到过这样的说法,但他当时并不在意。‘“超级杂草”是这样一种带感情色彩的词汇,他说:“它还没有… 相似文献
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