Apolipoprotein(apo) A-V is a novel member of the class of exchangeable apo's involved in triacylglycerol(TG)homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilit...Apolipoprotein(apo) A-V is a novel member of the class of exchangeable apo's involved in triacylglycerol(TG)homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein Iipase-mediated TG hydrolysis,another portion is recovered intracellularly,in association with cytosolic lipid droplets.Loss of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease.Single nucleotide polymorphisms(SNP) in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions.Likewise,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction.Genetically engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type(WT) apoA-V may have therapeutic benefit.It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance.On the other hand,subjects with hypertriglyceridemia of independent origin(unrelated to apoA-V function) may not respond to apoA-V augmentation in this manner.Improvement in the ability to identify individuals predicted to benefit,advances in gene transfer technology and the strong connection between HTG and heart disease,point to apoA-V supplementation as a viable disease prevention / therapeutic strategy.Candidates would include individuals that manifest chronic TG elevation,have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.展开更多
Low desiccation resistance of Drosophila ananassae reflects its rarity outside the humid tropics. However, the ability of this sensitive species to evolve under seasonally varying subtropical areas is largely unknown....Low desiccation resistance of Drosophila ananassae reflects its rarity outside the humid tropics. However, the ability of this sensitive species to evolve under seasonally varying subtropical areas is largely unknown. D. ananassae flies are mostly lighter during the rainy season but darker and lighter flies occur in the autumn season in northern India. We tested the hypothesis whether seasonally varying alternative body color phenotypes of D. ananassae vary in their levels of environmental stress tolerances and mating behavior. Thus, we investigated D. ananassae flies collected during rainy and autumn seasons for changes in body melanization and their genetic basis, desiccation-related traits, cold tolerance and mating propensity. On the basis of genetic crosses, we found total body color dimorphism consistent with a single gene model in both sexes olD. ananassae. A significant increase in the frequency of the dark morph was observed during the drier autumn season, and body color phenotypes showed significant deviations from Hardy-Weinberg equilibrium, which suggests climatic selection plays a role. Resistance to desiccation as well as cold stress were two- to three-fold higher in the dark body color strain as compared with the light strain. On the basis of no-choice mating experiments, we observed significantly higher assortative matings between dark morphs under desiccation or cold stress, and between light morphs under hot or higher humidity conditions. To the best of our knowledge, this is the first report on the ecological significance of seasonally varying total body color dimorphism in a tropical species, D. ananassae.展开更多
基金Supported by a grant from NIH(R37-HL64159)an AHA Postdoctoral Fellowship Award(VS)
文摘Apolipoprotein(apo) A-V is a novel member of the class of exchangeable apo's involved in triacylglycerol(TG)homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein Iipase-mediated TG hydrolysis,another portion is recovered intracellularly,in association with cytosolic lipid droplets.Loss of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease.Single nucleotide polymorphisms(SNP) in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions.Likewise,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction.Genetically engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type(WT) apoA-V may have therapeutic benefit.It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance.On the other hand,subjects with hypertriglyceridemia of independent origin(unrelated to apoA-V function) may not respond to apoA-V augmentation in this manner.Improvement in the ability to identify individuals predicted to benefit,advances in gene transfer technology and the strong connection between HTG and heart disease,point to apoA-V supplementation as a viable disease prevention / therapeutic strategy.Candidates would include individuals that manifest chronic TG elevation,have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.
文摘Low desiccation resistance of Drosophila ananassae reflects its rarity outside the humid tropics. However, the ability of this sensitive species to evolve under seasonally varying subtropical areas is largely unknown. D. ananassae flies are mostly lighter during the rainy season but darker and lighter flies occur in the autumn season in northern India. We tested the hypothesis whether seasonally varying alternative body color phenotypes of D. ananassae vary in their levels of environmental stress tolerances and mating behavior. Thus, we investigated D. ananassae flies collected during rainy and autumn seasons for changes in body melanization and their genetic basis, desiccation-related traits, cold tolerance and mating propensity. On the basis of genetic crosses, we found total body color dimorphism consistent with a single gene model in both sexes olD. ananassae. A significant increase in the frequency of the dark morph was observed during the drier autumn season, and body color phenotypes showed significant deviations from Hardy-Weinberg equilibrium, which suggests climatic selection plays a role. Resistance to desiccation as well as cold stress were two- to three-fold higher in the dark body color strain as compared with the light strain. On the basis of no-choice mating experiments, we observed significantly higher assortative matings between dark morphs under desiccation or cold stress, and between light morphs under hot or higher humidity conditions. To the best of our knowledge, this is the first report on the ecological significance of seasonally varying total body color dimorphism in a tropical species, D. ananassae.