Scaffold proteins LACK and TRACK as potential drug targets in kinetoplastid parasites: Development of inhibitors.

Parasitic diseases cause ∼ 500,000 deaths annually and remain a major challenge for therapeutic development. Using a rational design based approach, we developed peptide inhibitors with anti-parasitic activity that were derived from the sequences of parasite scaffold proteins LACK (Leishmania's receptor for activated C-kinase) and TRACK (Trypanosoma receptor for activated C-kinase). We hypothesized that sequences in LACK and TRACK that are conserved in the parasites, but not in the mammalian ortholog, RACK (Receptor for activated C-kinase), may be interaction sites for signaling proteins that are critical for the parasites' viability. One of these peptides exhibited leishmanicidal and trypanocidal activity in culture. Moreover, in infected mice, this peptide was also effective in reducing parasitemia and increasing survival without toxic effects. The identified peptide is a promising new anti-parasitic drug lead, as its unique features may limit toxicity and drug-resistance, thus overcoming central limitations of most anti-parasitic drugs.

Mercury concentrations in surface water and harvested waterfowl from the prairie pothole region of Saskatchewan.

Mercury cycling in prairie ecosystems is poorly understood. We examined methylmercury (MeHg) concentrations in whole water from 49 diverse prairie wetlands and lakes in Saskatchewan. We also determined total Hg (THg) concentrations in waterfowl harvested by hunters for consumption. Average whole water MeHg concentrations ranged from 0.02 to over 4 ng L(-1) and were higher in water from wetland ponds compared to those in lakes. High MeHg concentrations in prairie wetlands present the possibility of increased Hg concentrations in biota inhabiting these and other similar systems. We therefore measured THg in 72 birds representing 13 species of waterfowl that commonly use prairie aquatic habitats. A large range in THg concentrations was observed among individual birds, with values ranging from below the detection limit to over 435 ng g(-1). When waterfowl were classified according to diet, we observed clear evidence of THg biomagnification with increasing proportion of animal prey consumed. THg concentrations in waterfowl collected by hunters did not exceed consumption guidelines of 0.5 mg kg(-1) developed for fish. This is the first study that has reported MeHg concentrations in water from the prairie pothole region of southern Saskatchewan.