“West Central Africa has been implicated as the epicenter of the HIV-1 epidemic, and almost all group M subtypes can be found there. Previous analysis of early HIV-1 group M sequences from Kinshasa in the Democratic Republic of Congo, formerly Zaire, revealed that isolates from a number of individuals fall in different positions in phylogenetic trees constructed from sequences from opposite ends of the genome as a result of recombination between viruses of different subtypes. Here, we use discrete ancestral trait mapping BIX 1294 cost to develop
a procedure for quantifying HIV-1 group M intersubtype recombination across phylogenies, using individuals’ gag (p17) and env (gp41) subtypes. The method was applied to previously described HIV-1 group M sequences from samples obtained in Kinshasa early in the global radiation of HIV. Nine different p17 and gp41 intersubtype recombinant combinations were present in the data set. The mean number of excess ancestral subtype transitions (NEST) required to map individuals’ p17 subtypes onto the gp14 phylogeny samples, compared to the number required to map them onto the p17 phylogenies, and vice versa, indicated that excess subtype transitions occurred at a rate of approximately 7 X 10(-3) to 8 X 10(-3) per lineage
per year as a result of intersubtype recombination. Our results imply that intersubtype recombination may have occurred in approximately 20% of lineages evolving over a period of 30 years and confirm intersubtype recombination learn more as a substantial force in generating HIV-1 group M diversity.”
“Cannabinoid CB(1) receptor agonists vary in efficacy in vitro; however, relationships between efficacy and behavioral effects are unclear.
This https://www.selleck.cn/products/ag-881.html study examined the relationship between apparent CB(1) agonist efficacy and in vivo effects.
Male C57BL/6J mice responded for food under a fixed ratio 30 schedule; rectal temperature was measured. Sensitivity of the mice to cannabinoid agonists (rank order efficacy in vitro reported
to be CP 55940 > anandamide > Delta(9)-tetrahydrocannabinol; Delta(9)-THC) and a non-cannabinoid (the benzodiazepine midazolam) was determined before, during, and after discontinuation of daily Delta(9)-THC treatment (32 mg/kg/day, i.p.). Rimonabant was combined with cannabinoids to examine whether CB(1) receptors mediated effects on response rate.
Delta(9)-THC, CP 55940, anandamide, and midazolam decreased responding at doses smaller than those producing hypothermia. Rimonabant antagonized the rate-decreasing effects of Delta(9)-THC and CP 55940, but not those of anandamide. Delta(9)-THC treatment produced tolerance for both rate-decreasing and hypothermic effects. Delta(9)-THC treatment did not change sensitivity to the rate-decreasing effects of CP 55940, but produced cross-tolerance to CP 55940 for hypothermic effects.