Crossing the Rift valley: using complete mitogenomes to infer the diversification and biogeographic history of ethiopian highlands Ptychadena (anura: Ptychadenidae).

The Ethiopian Highlands are considered a biodiversity hotspot, harboring a high number of endemic species. Some of the endemic species probably diversified in situ; this is, for example, the case of a monophyletic clade containing 12 known species of grass frogs of the genus Ptychadena. The different species occur at elevations ranging from 1,500 to above 3,400 m and constitute excellent models to study the process of diversification in the highlands as well as adaptations to high elevations. In this study, we sampled 294 specimens across the distribution of this clade and used complete mitogenomes and genome-wide SNP data to better understand how landscape features influenced the population structure and dispersal of these grass frogs across time and space. Using phylogenetic inference, population structure analyses, and biogeographic reconstructions, we found that the species complex probably first diversified on the south-east side of the Great Rift Valley. Later on, species dispersed to the north-west side, where more recent diversification occurred. We further demonstrate that Ptychadena species have dispersed across the Great Rift Valley at different times. Our analyses allowed for a more complete understanding of the contribution of geological events, biogeographic barriers and climatic changes as drivers of species diversification and adaptation in this important biogeographic region.

beta-Carotene fails to act as a tumor promoter, induces RAR expression, and prevents carcinoma formation in a two-stage model of skin carcinogenesis in male Sencar mice.

Clinical trials have shown a significant increase in incidence of lung cancer among smokers and asbestos workers supplemented with beta-carotene, suggesting a tumor-promoting activity for this agent. We set out to test possible tumor-promoting and chemopreventive activities of dietary and topical beta-carotene in the two-stage 7,12-dimethylbenz[a]anthracene-12-O-tetradecanoylphorbol 13-acetate (TPA) model of mouse skin carcinogenesis. In the first study, the effects of three levels of dietary beta-carotene (6, 60, and 600 micrograms/g purified diet containing no other retinoid or carotenoid) were assessed over a period of 42 weeks. Carcinoma yield was reduced by approximately 50% in the 600 micrograms/g diet group (mean 0.22 carcinomas/mouse) compared with the 6 micrograms/g diet group (mean 0.44 carcinomas/mouse, p = 0.003). The 60 micrograms/g diet group showed a pattern of inhibition similar to the 600 micrograms/g diet group. A protective effect (25% reduction) of beta-carotene (in the 600 micrograms/g diet group) on papilloma formation was also found. However, the intermediate 60 micrograms/g diet group showed the same incidence as the low 6 micrograms/g diet group. This points to a lack of correlation between papilloma and carcinoma incidence, as we also found in previous work on dietary retinoids and carotenoids. The purpose of the second study was to assess whether topical beta-carotene (2 micrograms) has tumor-promoting or chemopreventive activity in the two-stage protocol. In the absence of TPA, beta-carotene had no significant tumor-promoting activity. Instead, papilloma yield induced by TPA was decreased by topical beta-carotene from an average of 20 to approximately 10 papillomas/mouse (p = 2.5 x 10(-7)). The effect of topical beta-carotene persisted beyond the treatment period (Week 24) until the termination of the study at Week 42. Western blot analysis of mouse skin extracts showed that topical beta-carotene upregulated retinoic acid receptor-alpha and -gamma expression in the dorsal skin. This finding suggests that beta-carotene may work as a chemopreventive agent by upregulating the expression of retinoid receptors in mouse skin. In conclusion, our data show that beta-carotene prevents skin carcinoma formation, induces retinoic acid receptor expression, and fails to act as a tumor promoter in the two-stage model of skin tumorigenesis.

Ovariectomy increases squamous metaplasia of the uterine horns and survival of SENCAR mice fed a vitamin A-deficient diet.

BACKGROUND: Retinoic acid is necessary for the growth and differentiation of organisms and exerts its molecular actions by binding to specific nuclear receptors that belong to the thyroid-steroid hormone receptor superfamily. Steroids and retinoids control the differentiation of the female reproductive epithelia: estrogen maintains the squamous differentiation of vaginal and ectocervical epithelia, whereas retinoic acid maintains the simple columnar endocervical and uterine epithelia. These lining epithelia transform into a squamous metaplastic phenotype in vitamin A-deficient animals. Furthermore, mortality due to vitamin A deficiency is usually attributed to infection resulting in part from dysfunction of the protective epithelia. OBJECTIVE: Our objective was to test the hypothesis that estrogen depletion might change the squamous metaplastic response to vitamin A deficiency and affect animal survival. DESIGN: We used female SENCAR mice maintained on a purified vitamin A-deficient diet containing either 0 or 3 microg retinoic acid/g diet. Mice were either ovariectomized or intact. Squamous cells arising in the normally simple columnar epithelium of the endocervix and uterine cavity were monitored by keratin 5 expression with immunohistochemistry. RESULTS: Ovariectomy did not change the time to onset of vitamin A deficiency. It increased the number of squamous metaplastic cells and prolonged survival in mice consuming a vitamin A-deficient diet by as much as 40%. CONCLUSIONS: Factors other than epithelial differentiation per se control survival outcome of vitamin A-deficient mice. The results also show a significant increase in longevity of vitamin A- deficient mice when ovariectomized.