Local Environmental Knowledge,Talk, and Skepticism: Using ‘LES’ to Distinguish ‘LEK’ from ‘LET’ in Newfoundland

The actual evidence observed in studies of LEK (local environmental knowledge) is nearly always talk about the environment, or what we refer to as LET (local environmental talk), with the claim of studying LEK usually being built upon the implicit assumption that talk about the environment is the expression of knowledge about the environment. We suggest that it is critically important for researchers to question this assumption, especially when the distinction between LET and LEK is also emphasized by local people themselves. In the case we present here, residents of small fishing villages on the Northern Peninsula of Newfoundland are routinely skeptical about what other local residents say about the environment; that is, they engage in LES (local environmental skepticism). We suggest that paying explicit attention to LES can help distinguish LEK from LET.     

Reduced reproductive function in wild baboons (Papio hamadryas anubis) related to natural consumption of the African black plum (Vitex doniana)

Several authors have suggested that the consumption of plant compounds may have direct effects on wild primate reproductive biology, but no studies have presented physiological evidence of such effects. Here, for two troops of olive baboons (Papio hamadryas anubis) at Gashaka-Gumti National Park, Nigeria, we show major seasonal increases in levels of fecal progesterone metabolites in females, and provide evidence that this is linked to the consumption of natural plant compounds. Increases in fecal progestogen excretion occurred seasonally in all females, in all reproductive states, including lactation. Detailed feeding data on the study animals showed that only one food species is consumed by both troops at the time of observed progestogen peaks, and at no other times of the year: the African black plum, Vitex doniana. Laboratory tests demonstrated the presence of high concentrations of progestogen-like compounds in V. doniana. Together with published findings linking the consumption of a related Vitex species (Vitex agnus castus) to increased progestogen levels in humans, our data suggest that natural consumption of V. doniana was a likely cause of the observed increases in progestogens. Levels of progestogen excretion in the study baboons during periods of V. doniana consumption are higher than those found during pregnancy, and prevent the expression of the sexual swelling, which is associated with ovulatory activity. As consortship and copulatory activity in baboons occur almost exclusively in the presence of a sexual swelling, V. doniana appears to act on cycling females as both a physiological contraceptive (simulating pregnancy in a similar way to some forms of the human contraceptive pill) and a social contraceptive (preventing sexual swelling, thus reducing association and copulation with males). The negative effects of V. doniana on reproduction may be counter-balanced by the wide-range of medicinal properties attributed to plants in this genus. This is the first time that physiological evidence has been presented of direct effects of plant consumption on the reproductive biology of wild primates.     

Novel steroidal saponins, Sch 725737 and Sch 725739, from a marine starfish, Novodinia antillensis

Bioassay-guided fractionation of an active fraction from an extract of a marine starfish, Novodinia antillensis, led to the isolation and identification of two new saponins, Sch 725737 (1) and Sch 725739 (2). Compound 1 was identified as the NaV1.8 inhibitor with IC(50) of approximately 9 microM. The purification and the structure elucidation of these two saponins are described.     

(3R)-4-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes

Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 IC(50)=18nM) with 3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one gave dipeptidyl peptidase IV (DPP-4) inhibitor 1 which is potent (DPP-4 IC(50)=2.6nM), selective, and efficacious in an oral glucose tolerance test in mice. It was selected for extensive preclinical development as a potential back-up candidate to sitagliptin.     

Design, synthesis, and biological evaluation of triazolopiperazine-based beta-amino amides as potent, orally active dipeptidyl peptidase IV (DPP-4) inhibitors

Various beta-amino amides containing triazolopiperazine heterocycles have been prepared and evaluated as potent, selective, orally active dipeptidyl peptidase IV (DPP-4) inhibitors. These compounds display excellent oral bioavailability and good overall pharmacokinetic profiles in preclinical species. Moreover, in vivo efficacy in an oral glucose tolerance test in lean mice is demonstrated.     

Vaccinia virus N1L protein resembles a B cell lymphoma-2 (Bcl-2) family protein

Poxviruses encode immuno-modulatory proteins capable of subverting host defenses. The poxvirus vaccinia expresses a small 14-kDa protein, N1L, that is critical for virulence. We report the crystal structure of N1L, which reveals an unexpected but striking resemblance to host apoptotic regulators of the B cell lymphoma-2 (Bcl-2) family. Although N1L lacks detectable Bcl-2 homology (BH) motifs at the sequence level, we show that N1L binds with high affinity to the BH3 peptides of pro-apoptotic Bcl-2 family proteins in vitro, consistent with a role for N1L in modulating host antiviral defenses.     

Coding sequence polymorphism in avian mitochondrial genomes reflects population histories

Nucleotide sequence diversity at mitochondrial protein-coding loci from 72 species of birds from different geographical regions was analysed in order to test the hypothesis that temperate zone species show population genetic effects of past glaciation. Temperate zone species showed reduced nucleotide diversity in comparison to tropical mainland species, suggesting that the latter have long-term effective population sizes due to population bottleneck effects during the most recent glaciation. This hypothesis was further supported by evidence of an unusually high estimated rate of population growth in species breeding in North America and wintering in the New World tropics (Nearctic migrants), consistent with population expansion after a bottleneck. Nearctic migrants also showed evidence of an abundance of rare nonsynonymous (amino acid-altering) polymorphisms, a pattern suggesting that slightly deleterious polymorphisms drifted to high frequencies during a bottleneck and are now being eliminated by selection. Because the shape of the North American land mass limited the area available for refugia during glaciation, the bottleneck effects are predicted to have been particularly strong in Nearctic migrants, and this prediction was supported. The reduced genetic diversity of Nearctic migrants provides an additional basis for concern for the survival of these species, which are threatened by loss of habitat in the winter range and by introduced disease.