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991.
Denby KJ Jason LJ Murray SL Last RL 《The Plant journal : for cell and molecular biology》2005,41(5):673-684
We report the characterization of an Arabidopsis thaliana mutant, ups1, isolated on the basis of reduced expression of phosphoribosylanthranilate transferase, a tryptophan biosynthetic enzyme. ups1 also exhibits defects in a wide range of defence responses. After infection with Pseudomonas syringae or Botrytis cinerea, the expression of genes regulated by both the salicylic acid and jasmonic acid/ethylene pathways is reduced in ups1 compared with wild type. Camalexin accumulation in ups1 is greatly reduced after infection with these two pathogens, as well as after amino acid starvation or oxidative stress. Reactive oxygen species (ROS)-mediated gene expression is also compromised in ups1 indicating that this mutant is defective in signalling pathways activated in response to both biotic and abiotic stress. The fact that all three major defence signalling pathways are disrupted in ups1, together with the oxidative stress phenotype, leads us to suggest that UPS1 is involved in ROS signal transduction. 相似文献
992.
993.
Robert?M.?Ewers Raphael?K.?DidhamEmail author Stephen D.?Wratten Jason?M.?Tylianakis 《Biodiversity and Conservation》2005,14(6):1469-1485
The widespread conversion of natural habitats to agricultural land has created a need to integrate intensively managed landscapes into conservation management priorities. However, there are no clearly defined methods for assessing the conservation value of managed landscapes at the local scale. We used remotely sensed landscape heterogeneity as a rapid practical tool for the assessment of local biodiversity value within a predominantly agricultural landscape in Canterbury, New Zealand. Bird diversity was highly significantly correlated with landscape heterogeneity, distance from rivers and the Christchurch central business district, altitude and average annual household income, indicating that remotely sensed landscape heterogeneity is a good predictor of local biodiversity patterns. We discuss the advantages and limitations of using geographic information systems to determine local areas of high conservation value. 相似文献
994.
Black E Breed J Breeze AL Embrey K Garcia R Gero TW Godfrey L Kenny PW Morley AD Minshull CA Pannifer AD Read J Rees A Russell DJ Toader D Tucker J 《Bioorganic & medicinal chemistry letters》2005,15(10):2503-2507
Using structure-based design, a new class of inhibitors of protein tyrosine phosphatase-1B (PTP1B) has been identified, which incorporate the 1,2,5-thiadiazolidin-3-one-1,1-dioxide template. 相似文献
995.
Teall M Oakley P Harrison T Shaw D Kay E Elliott J Gerhard U Castro JL Shearman M Ball RG Tsou NN 《Bioorganic & medicinal chemistry letters》2005,15(10):2685-2688
The development of a novel series of 4-aryl, 4-phenylsulfonyl cyclohexananone-derived gamma-secretase inhibitors for the potential treatment of Alzheimer's disease is described. 相似文献
996.
Synthesis and structure-activity relationships of 1,2,4-triazoles as a novel class of potent tubulin polymerization inhibitors 总被引:1,自引:0,他引:1
Ouyang X Chen X Piatnitski EL Kiselyov AS He HY Mao Y Pattaropong V Yu Y Kim KH Kincaid J Smith L Wong WC Lee SP Milligan DL Malikzay A Fleming J Gerlak J Deevi D Doody JF Chiang HH Patel SN Wang Y Rolser RL Kussie P Labelle M Tuma MC 《Bioorganic & medicinal chemistry letters》2005,15(23):5154-5159
A novel triazole-containing chemical series was shown to inhibit tubulin polymerization and cause cell cycle arrest in A431 cancer cells with EC(50) values in the single digit nanomolar range. Binding experiments demonstrated that representative active compounds of this class compete with colchicine for its binding site on tubulin. The syntheses and structure-activity relationship studies for the triazole derivatives are described herein. 相似文献
997.
BACKGROUND: Wee1 kinases delay entry into mitosis by phosphorylating and inactivating cyclin-dependent kinase 1 (Cdk1). Loss of this activity in many systems, including Drosophila, leads to premature mitotic entry. RESULTS: We report here that Drosophila Wee1 (dwee1) mutant embryos show mitotic-spindle defects that include ectopic foci of microtubule organization, formation of multipolar spindles from adjacent centrosome pairs, and promiscuous interactions between neighboring spindles. Furthermore, centrosomes are displaced from the embryo cortex in dwee1 mutants. These defects are not observed to the same extent in embryos in which nuclei also enter mitosis prematurely as a result of a lack of checkpoint control or in embryos with elevated Cdk1 activity. dWee1 physically interacts with members of the gamma-tubulin ring complex (gammaTuRC), and gamma-tubulin is phosphorylated in a dwee1-dependent manner in embryo extracts. CONCLUSIONS: Some of the abnormalities in dwee1 mutant embryos cannot be explained by premature entry into mitosis or bulk elevation of Cdk1 activity. Instead, dWee1 is also required for phosphorylation of gamma-tubulin, centrosome positioning, and mitotic-spindle integrity. We propose a model to account for these requirements. 相似文献
998.
Liou J Kim ML Heo WD Jones JT Myers JW Ferrell JE Meyer T 《Current biology : CB》2005,15(13):1235-1241
Ca(2+) signaling in nonexcitable cells is typically initiated by receptor-triggered production of inositol-1,4,5-trisphosphate and the release of Ca(2+) from intracellular stores. An elusive signaling process senses the Ca(2+) store depletion and triggers the opening of plasma membrane Ca(2+) channels. The resulting sustained Ca(2+) signals are required for many physiological responses, such as T cell activation and differentiation. Here, we monitored receptor-triggered Ca(2+) signals in cells transfected with siRNAs against 2,304 human signaling proteins, and we identified two proteins required for Ca(2+)-store-depletion-mediated Ca(2+) influx, STIM1 and STIM2. These proteins have a single transmembrane region with a putative Ca(2+) binding domain in the lumen of the endoplasmic reticulum. Ca(2+) store depletion led to a rapid translocation of STIM1 into puncta that accumulated near the plasma membrane. Introducing a point mutation in the STIM1 Ca(2+) binding domain resulted in prelocalization of the protein in puncta, and this mutant failed to respond to store depletion. Our study suggests that STIM proteins function as Ca(2+) store sensors in the signaling pathway connecting Ca(2+) store depletion to Ca(2+) influx. 相似文献
999.
There is currently great interest in comparing protein-ligand docking programs. A review of recent comparisons shows that it is difficult to draw conclusions of general applicability. Statistical hypothesis testing is required to ensure that differences in pose-prediction success rates and enrichment rates are significant. Numerical measures such as root-mean-square deviation need careful interpretation and may profitably be supplemented by interaction-based measures and visual inspection of dockings. Test sets must be of appropriate diversity and of good experimental reliability. The effects of crystal-packing interactions may be important. The method used for generating starting ligand geometries and positions may have an appreciable effect on docking results. For fair comparison, programs must be given search problems of equal complexity (e.g. binding-site regions of the same size) and approximately equal time in which to solve them. Comparisons based on rescoring require local optimization of the ligand in the space of the new objective function. Re-implementations of published scoring functions may give significantly different results from the originals. Ostensibly minor details in methodology may have a profound influence on headline success rates. 相似文献
1000.
Perry J 《Proteins》2005,61(4):699-703
Timeless (Tim) and Period (Per) are coordinately synthesized interacting proteins that in response to positional/environmental cues comigrate to the nucleus as obligate heterodimers where they act to suppress their own gene expression as part of the circadian rhythm network in Drosophila. There has been considerable controversy about the structural nature of Tim because of somewhat conflicting results generated by the automated threading algorithm 3D-PSSM. With use of a computer-assisted but largely manual approach, it is shown here that Tim is composed of repetitive structural elements and that those elements comprise two ARM repeat domains, validating the essence of the original 3D-PSSM prediction. Eleven individual ARM structural units are assigned, and a phylogenetic analysis showing their relatedness to one another is performed. In addition, there appears to be a small domain of prenyltransferase-like repeats C-terminal to the second ARM domain, which went undetected in previous analyses. Although we cannot know the precise conformation it adopts until a structure is solved, Tim emerges here as clearly a member of the helical repeat protein superfamily. Given its role in periodic nuclear translocation, Tim may, therefore, have a functional analogy with the photoperiod-responsive protein Phor1 and other karyopherin-like molecules. 相似文献