Research strategies to improve snakebite treatment: challenges and progress

Antivenom is an effective treatment of snakebite but, because of the complex interplay of fiscal, epidemiological, therapeutic efficacy and safety issues, the mortality of snakebite remains unacceptably high. Efficiently combating this high level of preventable death amongst the world's most disadvantaged communities requires the globally-coordinated action of multiple intervention programmes. This is the overall objective of the Global Snakebite Initiative. This paper describes the challenges facing the research community to develop snakebite treatments that are more efficacious, safe and affordable than current therapy.     

Hochstetter's frog (Leiopelma hochstetteri) egg,mobile larvae and froglet development

Egg strings and larvae of Hochstetter's frog (Leiopelma hochstetteri) were located at three widely separated North Island sites: in seeps at Brynderwyns in December 2004, in an open pool at Wharerino in March 2009, and in an underground pool near the Kaipawa Track, Coromandel, in late May 2009. Ten egg strings were also laid by captive frogs in water courses at Hamilton Zoo in April 2009. All egg strings held from 11 to 13 eggs. The egg strings laid in the Brynderwyns were regularly observed until metamorphosis was completed in March 2005. Twenty-four swimming larvae emerged from 25 capsules at c. 40 days after discovery, and at least 14 froglets were produced at c. 90 days. All of them developed in darkness, in a 120 ml pool <30 mm deep. The emerged froglets ranged from 9.8 to 10.8 mm snout-vent length. The detection of eggs, larvae and <11 mm froglets indicates that the egg laying period is at least from late September to May.     

Location and Dynamics of the Immunodominant CD8 T Cell Response to SIVΔnef Immunization and SIVmac251 Vaginal Challenge

Live-attenuated SIV vaccines (LAVs) have been the most effective to date in preventing or partially controlling infection by wild-type SIV in non-human primate models of HIV-1 transmission to women acting by mechanisms of protection that are not well understood. To gain insights into mechanisms of protection by LAVs that could aid development of effective vaccines to prevent HIV-1 transmission to women, we used in situ tetramer staining to determine whether increased densities or changes in the local distribution of SIV-specific CD8 T cells correlated with the maturation of SIVΔnef vaccine-induced protection prior to and after intra-vaginal challenge with wild-type SIVmac251. We evaluated the immunodominant Mamu-A1*001:01/Gag (CM9) and Mamu-A1*001:01/Tat (SL8) epitope response in genital and lymphoid tissues, and found that tetramer+ cells were present at all time points examined. In the cervical vaginal tissues, most tetramer+ cells were distributed diffusely throughout the lamina propria or co-localized with other CD8 T cells within lymphoid aggregates. The distribution and densities of the tetramer+ cells at the portal of entry did not correlate with the maturation of protection or change after challenge. Given these findings, we discuss the possibility that changes in other aspects of the immune system, including the quality of the resident population of virus-specific effector CD8 T cells could contribute to maturation of protection, as well as the potential for vaccine strategies that further increase the size and quality of this effector population to prevent HIV-1 transmission.     

Adaptive evolution of recently duplicated accessory gland protein genes in desert Drosophila

The relationship between animal mating system variation and patterns of protein polymorphism and divergence is poorly understood. Drosophila provides an excellent system for addressing this issue, as there is abundant interspecific mating system variation. For example, compared to D. melanogaster subgroup species, repleta group species have higher remating rates, delayed sexual maturity, and several other interesting differences. We previously showed that accessory gland protein genes (Acp's) of Drosophila mojavensis and D. arizonae evolve more rapidly than Acp's in the D. melanogaster subgroup and that adaptive Acp protein evolution is likely more common in D. mojavensis/D. arizonae than in D. melanogaster/D. simulans. These findings are consistent with the idea that greater postcopulatory selection results in more adaptive evolution of seminal fluid proteins in the repleta group flies. Here we report another interesting evolutionary difference between the repleta group and the D. melanogaster subgroup Acp's. Acp gene duplications are present in D. melanogaster, but their high sequence divergence indicates that the fixation rate of duplicated Acp's has been low in this lineage. Here we report that D. mojavensis and D. arizonae genomes contain several very young duplicated Acp's and that these Acp's have experienced very rapid, adaptive protein divergence. We propose that rapid remating of female desert Drosophila generates selection for continuous diversification of the male Acp complement to improve male fertilization potential. Thus, mating system variation may be associated with adaptive protein divergence as well as with duplication of Acp's in Drosophila.