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21.
Identification of cold-inducible downstream genes of the Arabidopsis DREB1A/CBF3 transcriptional factor using two microarray systems 总被引:20,自引:0,他引:20
22.
Yoshizumi T Takahashi H Ohtake N Jona H Sato Y Kishino H Sakamoto T Ozaki S Takahashi H Shibata Y Ishii Y Saito M Okada M Hayama T Nishikibe M 《Bioorganic & medicinal chemistry》2004,12(9):2139-2150
The synthesis and structure-activity relationships of a series of 5,7-diarylcyclopenteno[1,2-b]pyridine-6-carboxylic acids are described. Our efforts have been focused on modification of the aryl ring at the 5-position and the alkyl substituent at the 2-position of the bottom 4-methoxyphenyl ring in an effort to develop orally available ET(A) selective antagonists with safer profiles in terms of the P-450 enzyme inhibitory activity. Incorporation of a hydroxymethyl group as an alkyl substituent in methylenedioxyphenyl and 6-dihydrobenzofuran derivatives led to the identification of orally bioavailable ET(A) selective antagonists 1f and 7f. These compounds also showed not only excellent binding affinity (IC(50) < 0.10nM, more than 800-fold selectivity for the ET(A) receptor over the ET(B) receptor) but also sufficient oral bioavailability, 48% and 56%, respectively, in rats. Furthermore, these compounds did not exhibit either competitive or mechanism-based inhibition of human cytochrome P450 enzymes. 相似文献
23.
Vacuolar processing enzymes are essential for proper processing of seed storage proteins in Arabidopsis thaliana 总被引:1,自引:0,他引:1
Shimada T Yamada K Kataoka M Nakaune S Koumoto Y Kuroyanagi M Tabata S Kato T Shinozaki K Seki M Kobayashi M Kondo M Nishimura M Hara-Nishimura I 《The Journal of biological chemistry》2003,278(34):32292-32299
The proprotein precursors of storage proteins are post-translationally processed to produce their respective mature forms within the protein storage vacuoles of maturing seeds. To investigate the processing mechanism in vivo, we isolated Arabidopsis mutants that accumulate detectable amounts of the precursors of the storage proteins, 12 S globulins and 2 S albumins, in their seeds. All six mutants isolated have a defect in the beta VPE gene. VPE (vacuolar processing enzyme) is a cysteine proteinase with substrate specificity toward an asparagine residue. We further generated various mutants lacking different VPE isoforms: alpha VPE, beta VPE, and/or gamma VPE. More than 90% of VPE activity is abolished in the beta vpe-3 seeds, and no VPE activity is detected in the alpha vpe-1/beta vpe-3/gamma vpe-1 seeds. The triple mutant seeds accumulate no properly processed mature storage proteins. Instead, large amounts of storage protein precursors are found in the seeds of this mutant. In contrast to beta vpe-3 seeds, which accumulate both precursors and mature storage proteins, the other single (alpha vpe-1 and gamma vpe-1) and double (alpha vpe-1/gamma vpe-1) mutants accumulate no precursors in their seeds at all. Therefore, the vegetative VPEs, alpha VPE and gamma VPE, are not necessary for precursor processing in the presence of beta VPE, but partly compensates for the deficiency in beta VPE in beta vpe-3 seeds. In the absence of functional VPEs, a proportion of pro2S albumin molecules are alternatively cleaved by aspartic proteinase. This cleavage by aspartic proteinase is promoted by the initial processing of pro2S albumins by VPE. Our overall results suggest that seed-type beta VPE is most essential for the processing of storage proteins, and that the vegetative-type VPEs and aspartic proteinase complement beta VPE activity in this processing. 相似文献
24.
Preferential paternal origin of microdeletions caused by prezygotic chromosome or chromatid rearrangements in Sotos syndrome 总被引:3,自引:0,他引:3
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Miyake N Kurotaki N Sugawara H Shimokawa O Harada N Kondoh T Tsukahara M Ishikiriyama S Sonoda T Miyoshi Y Sakazume S Fukushima Y Ohashi H Nagai T Kawame H Kurosawa K Touyama M Shiihara T Okamoto N Nishimoto J Yoshiura K Ohta T Kishino T Niikawa N Matsumoto N 《American journal of human genetics》2003,72(5):1331-1337
Sotos syndrome (SoS) is characterized by pre- and postnatal overgrowth with advanced bone age; a dysmorphic face with macrocephaly and pointed chin; large hands and feet; mental retardation; and possible susceptibility to tumors. It has been shown that the major cause of SoS is haploinsufficiency of the NSD1 gene at 5q35, because the majority of patients had either a common microdeletion including NSD1 or a truncated type of point mutation in NSD1. In the present study, we traced the parental origin of the microdeletions in 26 patients with SoS by the use of 16 microsatellite markers at or flanking the commonly deleted region. Deletions in 18 of the 20 informative cases occurred in the paternally derived chromosome 5, whereas those in the maternally derived chromosome were found in only two cases. Haplotyping analysis of the marker loci revealed that the paternal deletion in five of seven informative cases and the maternal deletion in one case arose through an intrachromosomal rearrangement, and two other cases of the paternal deletion involved an interchromosomal event, suggesting that the common microdeletion observed in SoS did not occur through a uniform mechanism but preferentially arose prezygotically. 相似文献
25.
Yagami T Ueda K Asakura K Takasu N Sakaeda T Itoh N Sakaguchi G Kishino J Nakazato H Katsuyama Y Nagasaki T Okamura N Hori Y Hanasaki K Arimura A Fujimoto M 《Experimental cell research》2003,291(1):212-227
15-Deoxy-Delta12,14-prostaglandin J2 (15d-Delta12,14-PGJ2) is an endogenous ligand for a nuclear peroxysome proliferator activated receptor-gamma (PPAR). We found novel binding sites of 15d-Delta12,14-PGJ2 in the neuronal plasma membranes of the cerebral cortex. The binding sites of [3H]15d-Delta12,14-PGJ2 were displaced by 15d-Delta12,14-PGJ2 with a half-maximal concentration of 1.6 microM. PGD2 and its metabolites also inhibited the binding of [3H]15d-Delta12,14-PGJ2. Affinities for the novel binding sites were 15d-Delta12,14-PGJ2 > Delta12-PGJ2 > PGJ2 > PGD2. Other eicosanoids and PPAR agonists did not alter the binding of [3H]15d-Delta12,14-PGJ2. In primary cultures of rat cortical neurons, we examined the pathophysiologic roles of the novel binding sites. 15d-Delta12,14-PGJ2 triggered neuronal cell death in a concentration-dependent manner, with a half-maximal concentration of 1.1 microM. The neurotoxic potency of PGD2 and its metabolites was also 15d-Delta12,14-PGJ2 > Delta12-PGJ2 > PGJ2 > PGD2. The morphologic and ultrastructural characteristics of 15d-Delta12,14-PGJ2-induced neuronal cell death were apoptotic, as evidenced by condensed chromatin and fragmented DNA. On the other hand, we detected little neurotoxicity of other eicosanoids and PPAR agonists. In conclusion, we demonstrated that novel binding sites of 15d-Delta12,14-PGJ2 exist in the plasma membrane. The present study suggests that the novel binding sites might be involved in 15d-Delta12,14-PGJ2-induced neuronal apoptosis. 相似文献
26.
Performance of a divergence time estimation method under a probabilistic model of rate evolution 总被引:24,自引:0,他引:24
Rates of molecular evolution vary over time and, hence, among lineages. In contrast, widely used methods for estimating divergence times from molecular sequence data assume constancy of rates. Therefore, methods for estimation of divergence times that incorporate rate variation are attractive. Improvements on a previously proposed Bayesian technique for divergence time estimation are described. New parameterization more effectively captures the phylogenetic structure of rate evolution on a tree. Fossil information and other evidence can now be included in Bayesian analyses in the form of constraints on divergence times. Simulation results demonstrate that the accuracy of divergence time estimation is substantially enhanced when constraints are included. 相似文献
27.
Using pseudomaximum-likelihood approaches to phylogenetic inference and coalescent theory, we develop a computationally tractable method of estimating effective population size from serially sampled viral data. We show that the variance of the maximum-likelihood estimator of effective population size depends on the serial sampling design only because internal node times on a coalescent genealogy can be better estimated with some designs than with others. Given the internal node times and the number of sequences sampled, the variance of the maximum-likelihood estimator is independent of the serial sampling design. We then estimate the effective size of the HIV-1 population within nine hosts. If we assume that the mutation rate is 2.5 x 10(-5) substitutions/generation and is the same in all patients, estimated generation lengths vary from 0.73 to 2.43 days/generation and the mean (1.47) is similar to the generation lengths estimated by other researchers. If we assume that generation length is 1.47 days and is the same in all patients, mutation rate estimates vary from 1.52 x 10(-5) to 5.02 x 10(-5). Our results indicate that effective viral population size and evolutionary rate per year are negatively correlated among HIV-1 patients. 相似文献
28.
Hagiwara H Kunihiro S Nakajima K Sano M Masaki H Yamamoto M Pak JW Zhang Y Takase K Kuwabara I Maruyama IN Machida M 《Journal of biochemistry》2002,132(6):975-982
Phage display is a useful means of identifying and selecting proteins of interest that bind specific targets. In order to examine the potential of phage display for the genome-wide screening of DNA-binding proteins, we constructed yeast genomic libraries using lambda foo-based vectors devised in this work. After affinity selection using GAL4 UAS(G) as a probe, phages expressing GAL4 were enriched approximately 5 x 10(5)-fold from the library. Approximately 90% of polypeptides encoded in correct translation reading frames by the selected phages were known or putative polynucleotide-binding proteins. This result clearly indicates that the modified lambda phage display vector in combination with our enrichment technique has great potential for the enrichment of DNA-binding proteins in a sequence-specific manner. 相似文献
29.
30.
Narusaka Y Narusaka M Seki M Ishida J Nakashima M Kamiya A Enju A Sakurai T Satoh M Kobayashi M Tosa Y Park P Shinozaki K 《Plant & cell physiology》2003,44(4):377-387
The hypersensitive response (HR) was induced in a wild-type Arabidopsis thaliana plant (Columbia) (Col-wt) by inoculation with Alternaria brassicicola that causes the development of small brown necrotic lesions on the leaves. By contrast, pad3-1 mutants challenged with A. brassicicola produced spreading lesions. The cell death in pad3-1 mutants could not inhibit the pathogen growth and development, although both production of H(2)O(2) and localized cell death were similar in Col-wt and pad3-1 plants after the inoculation. The difference between Col-wt and pad3-1 plants is defense responses after the occurrence of cell death. In other words, PAD3 is necessary for defense response to A. brassicicola. Therefore, we examined the changes in the expression patterns of ca. 7,000 genes by cDNA microarray analysis after inoculation with A. brassicicola. The cDNA microarrays were also done to analyze Arabidopsis responses after treatment with signal molecules, reactive oxygen species (ROS)-inducing compounds and UV-C. The results suggested that the pad3-1 mutation altered not only the accumulation of camalexin but also the timing of expression of many defense-related genes in response to the challenge with A. brassicicola. Furthermore, the plants integrate two or more signals that act together for promoting the induction of multiple defense pathways. 相似文献