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Extracellular suppression allows mating by pheromone-deficient sterile mutants of Saccharomyces cerevisiae 总被引:14,自引:1,他引:13
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MAT alpha haploids with mutations in the STE13 or KEX2 gene, and MATa haploids with mutations in the STE6 or STE14 gene, do not mate with wild-type cells of the opposite mating type. We found that such mutants were able to mate with partners that carry mutations (sst1 and sst2) that cause cells to be supersensitive to yeast mating pheromone action. Mating ability of MAT alpha ste13 and MAT alpha kex2 mutants could also be restored by adding normal MAT alpha cells to mating mixtures or by adding just the appropriate purified pheromone (alpha-factor). Therefore, the mating deficiencies caused by the ste13 and kex2 lesions, and by inference, the ste6 and ste14 mutations, appear to result only from secretion of an insufficient amount of pheromone or a nonfunctional pheromone. 相似文献
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Sergio M. Villordo Claudia V. Filomatori Irma Sánchez-Vargas Carol D. Blair Andrea V. Gamarnik 《PLoS pathogens》2015,11(1)
Many viral pathogens cycle between humans and insects. These viruses must have evolved strategies for rapid adaptation to different host environments. However, the mechanistic basis for the adaptation process remains poorly understood. To study the mosquito-human adaptation cycle, we examined changes in RNA structures of the dengue virus genome during host adaptation. Deep sequencing and RNA structure analysis, together with fitness evaluation, revealed a process of host specialization of RNA elements of the viral 3’UTR. Adaptation to mosquito or mammalian cells involved selection of different viral populations harvesting mutations in a single stem-loop structure. The host specialization of the identified RNA structure resulted in a significant viral fitness cost in the non-specialized host, posing a constraint during host switching. Sequence conservation analysis indicated that the identified host adaptable stem loop structure is duplicated in dengue and other mosquito-borne viruses. Interestingly, functional studies using recombinant viruses with single or double stem loops revealed that duplication of the RNA structure allows the virus to accommodate mutations beneficial in one host and deleterious in the other. Our findings reveal new concepts in adaptation of RNA viruses, in which host specialization of RNA structures results in high fitness in the adapted host, while RNA duplication confers robustness during host switching. 相似文献
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Alexander Blair 《BMJ (Clinical research ed.)》1924,2(3338):1177-1178
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In this study we present evidence to suggest that gastroduodenal mucosal defects may occur in gastric fistula dogs actively immunized with PGE2-thyroglobulin conjugate. One of four PGE2-immunized dogs developed a chronic pyloroduodenal ulcer with penetration into the pancreas and the other three had endoscopic evidence of gastric and/or duodenal erosions. In contrast, no gastroduodenal mucosal defects were seen in control dogs immunized with thyroglobulin alone. Occurrence of gastroduodenal ulcers or erosions was temporally related to formation of specific antibody to PGE2 suggesting that PGE2 antibody may be responsible for lesion formation. An increase in gastric acid secretion was not observed in PGE2-immunized dogs. Thus, it is likely that mucosal defects occur as a result of an impairment of PGE2-mediated mucosal defense mechanisms. Since gastroduodenal lesions can be visualized by endoscopy, the dog may prove to be useful in studying the role of endogenous PG in ulcer diseases. 相似文献
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Ian A. Blair 《Biological trace element research》1987,12(1):259-260
The group of arachidonic acid metabolites comprising the prostaglandins, thromboxanes, and leukotrienes (eicosanoids) are
extremely potent, biologically active compounds. Their properties include proaggregatory anti-aggregatory activity for platelets,
chemotactic activity for neutrophils, vasoactive activity, and contractile activity to smooth muscle. In order to determine
the role of these substances in pathophysiological conditions, it is essential to have highly sensitive methods available
for their analysis.
It is generally accepted that combined gas chromatography/mass spectrometry is the most specific technique available for the
quantitative analysis of eicosanoids. However, methods based on electron impact ionization and positive ion chemical ionization
are relatively insensitive, and many investigators have preferred the use of less specific but more sensitive methods based
on radioimmunoassay. We have explored the use of negative ion chemical ionization mass spectrometry to improve sensitivity
coupled with capillary column chromatography to maximize specificity.
Conversion of the terminal carboxyl group (present in all eicosanoids) to the pentafluorobenzyl ester derivative confers excellent
electron capturing properties to the molecule. The derivative undergoes highly efficient thermal electron capture in the gas
phase, and any fragmentation that occurs subsequently is directed almost entirely away from the analyte molecule. The stabilized
carboxylate anion that results carries at least 30% of the total ion current. Using selected ion monitoring techniques it
is possible to detect eicosanoids in the range 1–8 pg on column.
This methodology has been applied to the development of stable isotope dilution assays for plasma 6-oxo-prostaglandin (PG)
F1α (1) and for the simultaneous analysis of six biologically important PGs in biological fluids (2). In addition, stable isotope dilution techniques have been developed for the analysis of serum thromboxane B2 and serum leukotriene B4 (3). The application of this technology to understanding the role of arachidonic acid metabolism in humans will be discussed. 相似文献
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