Azoxybacilin, produced by Bacillus cereus, has a broad spectrum of antifungal activity in methionine-free medium and has been suggested to inhibit sulfite fixation. We have further investigated the mode of action by which azoxybacilin kills fungi. The compound inhibited the incorporation of [35S] sulfate into acid-insoluble fractions of Saccharomyces cerevisiae under conditions in which virtually no inhibition was observed for DNA, RNA, or protein synthesis. It did not interfere with the activity of the enzymes for sulfate assimilation but clearly inhibited the induction of those enzymes when S. cerevisiae cells were transferred from rich medium to a synthetic methionine-free medium. Particularly strong inhibition was observed in the induction of sulfite reductase. Northern (RNA) analysis revealed that azoxybacilin decreased the level of mRNA of genes for sulfate assimilation, including MET10 for sulfite reductase and MET4, the transactivator of MET10 and other sulfate assimilation genes. When activities of azoxybacilin were compared for mRNA and enzyme syntheses from MET10, the concentration required for inhibition of transcription of the gene was about 10 times higher (50% inhibitory concentration = 30 micrograms/ml) than that required for inhibition of induction of enzyme synthesis (50% inhibitory concentration = 3 micrograms/ml). The data suggest that azoxybacilin acts on at least two steps in the expression of sulfite reductase; the transcriptional activation of MET4 and a posttranscriptional regulation in MET10 expression. We conclude that azoxybacilin exhibits antifungal activity by interfering with the regulation of expression of sulfite reductase activity.
We tested the hypothesis that there is a connection between apolipoprotein E (APOE) genotype and age at menopause. A sample of women aged between 50 and 60 years who had reached natural menopause was studied. Survival analysis of data showed a significant relationship between APOE genotype and age at menopause, carriers of the APOE4 allele reaching menopause at an earlier age. Our findings can have a bearing on the question of the evolution of this major human polymorphism and human life history. These findings are also relevant to the question of the connection between reproductive parameters and age-associated diseases.
Iran, located in the Eastern Mediterranean, shares many geographical characteristics and common historical roots with the countries of the Mediterranean basin, which are home to the major known cultivars of olive. Iran, for its part, harbors numerous olive cultivars, whose morphological and biological characters are yet to be characterized. This is important both from commercial and nutritional points of view. Building upon earlier work and in conjunction with a molecular genetics program for molecular characterization of Iranian olive cultivars, we undertook to characterize olive germplasm of Iran on the basis of morphological characters. To reach this goal, we started our research with the study of two important cultivars in Iran, 'Zard' and 'Rowghani'. This survey was performed over a one-year period. Samples were gathered from 281 ('Zard', 212 and 'Rowghani', 69) adult trees in eight regions with different ecological condition in the North of country (Roodbar, Manjil, Aliabad, Joodaki, Vakhman, Bahramabad, and Gilvan). Forty samples of flower, fruit, endocarp and leaf were collected from each tree. Multivariate statistical methods including cluster analysis and Principal Component Analysis were used for data analysis. Our preliminary results indicate a considerable variation within the traditionally recognized cultivars of olive in Iran. A more detailed assessment of morphological characters is in progress.
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