The non-nucleoside inhibitor-binding pocket has a flexible structure whose mobility may be required for effective polymerization, and may be part of a hinge that permits relative movements of two subdomains of the p66 subunit denoted the 'palm' and 'thumb'. An understanding of the structure of the inhibitor-binding pocket, of the interactions between HIV-1 RT and alpha-APA, and of the locations of mutations that confer resistance to inhibitors provides a basis for structure-based design of chemotherapeutic agents for the treatment of AIDS.

The membrane organisation of erythrocytes from patients with Duchenne muscular dystrophy (DMD) and from asymptomatic carriers was studied by the electron spin resonance (ESR) spin label technique. Following the work of Sato et al [1978], we used 2-(14-carboxytetradecyl)-2-ethyl-4, 4-dimethyl-3-oxazolidinyloxyl as probe. We found no significant difference in lipid fluidity at 30 degrees C, measured by the ratio of the line height at central field to that at high field ho/h-1, in DMD patients or carriers compared to appropriate control persons. Our conclusions for the dystrophic boys differ from those of Sato et al [1978], although our data are consistent with theirs within experimental error. We also studied the variation of the ratio ho/h-1 over the temperature range 5-35 degrees C in these individuals. For normal erythrocytes there is a discontinuity in this plot around 15 degrees C that is absent in the erythrocytes of DMD patients [in agreement with the findings of Sato et al, 1978] and also absent in DMD carriers. We suggest the slope of this logarithmic temperature plot over the range 15-35 degrees C is a more useful empirical parameter as the presence of these discontinuities is sometimes uncertain, and using this parameter, we find a clear separation between carriers and controls.

The duration of the developmental period represents a fundamental axis of life history variation in animals, yet broad insights regarding the drivers of this diversity are currently lacking. Here using embryological data combined with information on incubation and fledging periods for 3096 species, we test key mechanistic and adaptive explanations for the evolutionary diversification of developmental durations in birds. First, using data on embryonic development for 20 model species, we show that developmental phases associated primarily with growth are longer and more variable than earlier phases, consistent with a role for allometric constraint in determining the duration of development. Second, using phylogenetic comparative methods, we find that avian developmental durations retain a strong imprint of deep evolutionary history, and that after accounting for these effects, body size differences among species explain less variation (5-22%) in developmental period lengths than previously thought. Finally, by collecting data for a suite of potential explanatory variables, our analyses reveal broad-scale ecological correlates of developmental durations, including variables associated with the relative safety of the developmental environment (e.g. nest height, insularity) and pressures of breeding phenology (e.g. migration). Overall, our results reveal that the combined effects of species’ body size, ecology, and phylogenetic history can account for 62-93% of the variation in developmental durations across birds, providing broad-scale quantitative insight into the relative importance of mechanistic constraints, adaptive evolution and evolutionary constraints in shaping the diversification of this key life-history trait.