Phenotypic variation in respiratory metabolism and complementation of murine hepatic mitochondria

Summary Genetically standardized inbred mice exhibit interstrain differences in hepatic mitochondrial respiration rate, respiratory control, efficiency of oxidative phosphorylation with Krebs cycle substrates, and quantity of protein in the mitochondrial fraction. Mitochondria of females of strains with positive combining ability for postweaning growth mixed in vitro show complementation for respiratory traits. Mitochondria of males when mixed do not exhibit complementation. Mitochondria isolated from female mice respire more rapidly, are more tightly coupled and have higher phosphorylation efficiencies compared to those from male mice across all strains assayed. Direct evaluation of androgen effects on mitochondrial respiratory capacity supported this conclusion.Journal paper no. 4277 of the Arizona Agricultural Experiment Station. Supported in part by a University of Arizona Foundation fellowship (DRB)     

Novel hepatitis C virus replicon inhibitors: synthesis and structure-activity relationships of fused pyrimidine derivatives

The synthesis of several pyrido[2,3-d]pyrimidine and pyrimido[4,5-d]pyrimidine analogs is described with one such analog possessing subnanomolar potency in both genotype 1a and 1b cell culture HCV replicon assays.     

Inhibitors of HCV NS5B polymerase: synthesis and structure-activity relationships of N-alkyl-4-hydroxyquinolon-3-yl-benzothiadiazine sulfamides

Substituted N-alkyl-4-hydroxyquinolon-3-yl-benzothiadiazine sulfamides were investigated as inhibitors of genotype 1 HCV polymerase. Structure-activity relationship patterns for this class of compounds are discussed.     

Strategic light manipulation as a restoration strategy to reduce alien grasses and encourage native regeneration in Hawaiian mesic forests

Question: Is there a light level at which alien grass biomass is reduced while still supporting growth and survival of native woody species, allowing for native species regeneration in abandoned pastures? Location: Island of Hawaii, USA. Methods: In a two‐part study we examined the effect of light availability on common native woody and alien grass species found in secondary forests in Hawaii. A field survey was conducted to examine the relationship between light availability and canopy type (open pasture, planted canopy and secondary forest) on understory grass biomass and litter accumulation. We then experimentally manipulated light levels to determine the effect of light availability on growth and survival of six native woody species and three alien grasses. Low‐light (5%), medium‐light (10%) and high‐light (20‐30%) treatments were created using shade structures erected beneath the existing secondary koa canopy. Results: In the field survey, alien grass biomass was greatest under the open pasture and lowest in the secondary forest. There was a positive correlation between understory light availability and alien grass biomass. In the experimental study, large reductions in relative growth rates were documented for all of the grass species and four of the six woody species under the lowest light level. Although growth at 5% light is substantially reduced, survival is still high (84‐100%), indicating that these species may persist under closed canopy. Conclusion: Low‐light conditions result in the greatest reduction in alien grass biomass while creating an environment in which native woody species can grow and survive.     

Alterations in rat liver microsomal and lysosomal β-glucuronidase by compounds which induce hepatic drug-metabolizing enzymes

Chlordane, dieldrin, piperonyl butoxide, and benzpyrene, which induce the hepatic microsomal mixed function oxidases and UDP glucuronyltransferases, decreased activity of smooth and rough endoplasmic reticulum β-glucuronidase. The reduction occurred when either p-nitrophenyl β-D-glucuronide or phenolphthalein mono-β-glucuronide was used as the substrate. Chlordane or dieldrin pretreatment of rats for 3 days resulted in a 2.5-fold reduction in endoplasmic reticulum activity while the reduction was less for piperonyl butoxide or benzpyrene. On the other hand, aminopyrine demethylase and UDP glucuronyltransferase were increased 2-fold by chlordane or dieldrin pretreatments. Decreases in microsomal β-glucuronidase activity might be directly or indirectly involved in the induction process since decreases in β-glucuronidase activity are quantitatively similar to increases in activity of the drug-metabolizing enzymes. Lysosomal β-glucuronidase also decreased following pretreatment of rats with inducing agents, but the reduction was less than that observed in the endoplasmic reticulum fractions. Analysis of pH optima, temperature optima, K_m values, heat denaturation data, and effects of Triton X-100 on activities of various liver fractions suggests that β-glucuronidase from the endoplasmic reticulum and lysosomes have similar properties.