Genetic structure among Thai populations of Aedes aegypti mosquitoes

Thirty‐one field populations of Aedes aegypti (L.) were compared using isozyme starch gel electrophoresis to characterize genetic variation between populations. Ae. aegypti were collected from seven provinces in Thailand. Thirty‐one isozyme encoding loci, including 19 polymorphic loci, were characterized. Only small levels of genetic differentiation were observed among the 31 district populations in the seven provinces. Isolation by distance among populations from the seven provinces showed no correlation between genetic variation and geographical distance.     

Genetic structure and gene flow of Anopheles minimus and Anopheles harrisoni in Kanchanaburi Province, Thailand

Isozyme frequencies were compared in seven field collections of Anopheles minimus complex using starch gel electrophoresis. Mosquito collections were sampled from four districts in Kanchanaburi Province where malaria is endemic. From eight enzyme systems, nine loci and seven polymorphisms were detected, indicating limited genetic differentiation among the seven collections (F(ST) = 0.061). The highest percent polymorphic loci were observed in Bong Ti Noi (BTN) Village (55.6%), whereas the least percent polymorphism was seen in Tha Kradan (TK) Village (22.2%). Comparing villages Pra Jedee (PJ) with Pu Teuy C (PTC) and Huai Khayeng (HK) with Pra Jedee (PJ), gene flow among collections varied from 3.72 to 62.25 reproductive migrants per generation. Among the seven collections, no correlation was seen between genetic and geographical distances (P > 0.05). Anopheles minimus (former species A) and Anopheles harrisoni (former species C) from Pu Teuy fit most closely in the same cluster, possibly indicating relatively recent divergence between taxa. The genetic and epidemiological ramifications of these findings are discussed.     

Modeling Colitis-Associated Cancer with Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS)

Individuals with inflammatory bowel disease (IBD), such as Crohn''s disease (CD) or ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC) over healthy individuals. This risk is proportional to the duration and extent of disease, with a cumulative incidence as high as 30% in individuals with longstanding UC with widespread colonic involvement.¹ Colonic dysplasia in IBD and colitis associated cancer (CAC) are believed to develop as a result of repeated cycles of epithelial cell injury and repair while these cells are bathed in a chronic inflammatory cytokine milieu.² While spontaneous and colitis-associated cancers share the quality of being adenocarcinomas, the sequence of underlying molecular events is believed to be different.³ This distinction argues the need for specific animal models of CAC.Several mouse models currently exist for the study of CAC. Dextran sulfate sodium (DSS), an agent with direct toxic effects on the colonic epithelium, can be administered in drinking water to mice in multiple cycles to create a chronic inflammatory state. With sufficient duration, some of these mice will develop tumors.⁴ Tumor development is hastened in this model if administered in a pro-carcinogenic setting. These include mice with genetic mutations in tumorigenesis pathways (APC, p53, Msh2), as well as mice pre-treated with genotoxic agents (azoxymethane [AOM], 1,2-dimethylhydrazine [DMH]).⁵ The combination of DSS with AOM as a model for colitis associated cancer has gained popularity for its reproducibility, potency, low price, and ease of use. Though they have a shared mechanism, AOM has been found to be more potent and stable in solution than DMH. While tumor development in other models generally requires several months, mice injected with AOM and subsequently treated with DSS develop adequate tumors in as little as 7-10 weeks.^{6, 7} Finally, AOM and DSS can be administered to mice of any genetic background (knock out, transgenic, etc.) without cross-breeding to a specific tumorigenic strain. Here, we demonstrate a protocol for inflammation-driven colonic tumorigenesis in mice utilizing a single injection of AOM followed by three seven-day cycles of DSS over a 10 week period. This model induces tumors with histological and molecular changes closely resembling those occurring in human CAC and provides a highly valuable model for the study of oncogenesis and chemoprevention in this disease.⁸