These sex specific gene expression patterns were confirmed by comparison between adult female and male parasites, and it is clear that many genes are highly Lenalidomide TNF-alpha enriched in male worms, being expressed only at low levels in other stages. The large set of genes highly expressed in both eggs and adult females were again apparent. Finally, we investigated gene expression in the H. contortus intestine, the major organ of digestion and detoxification in the nematode, by comparing the female gut sample with the whole female worm. Consistent with data from H. contortus gut EST libraries, increased expression of genes with protein kinase, cysteine type peptidase and cysteine type peptidase inhibitor activities predominated.

Genes associated with sugar and cobalamin binding were significantly up regulated, as were genes associated with transport of cations, anions and oligopeptides. Oxidoreductase activ ity was also increased, consistent with the expression pattern of detoxification genes in C. elegans. Metabolic pathways and chokepoint analysis Comparisons Inhibitors,Modulators,Libraries between H. contortus and the free living nematodes revealed 22 enzyme classifications that were restricted to the parasite. While more detailed analysis is required, metabo lism of amino acids and carbohydrates clearly differ between these two groups. For example, lysine 6 amino Inhibitors,Modulators,Libraries transferase catalyzes lysine to glutamate, which can be further converted to a ketoglutarate, an intermediate of the tricarboxylic acid cycle. Lysine 6 aminotransferase was previously considered restricted to prokaryotes. thus, its activity in H.

contortus needs to be confirmed. A summary of up and down regulated metabolic enzymes across all life stages is shown in Table S10 in Additional file 1. The transition through eggs, L1, L3 and L4 showed a striking pattern from L1 to L3, most enzyme classifications were down regulated, including those involved in carbohydrate, lipid Inhibitors,Modulators,Libraries and energy meta bolism, but many of these were up regulated again in the transition to L4. This is consistent with the L3 being a stage in which development is arrested, analogous to the dauer larva in C. elegans. Further support for this comparison is the up regulation of two enzymes that independently convert Inhibitors,Modulators,Libraries isocitrate to 2 oxo glutarate, while most other parts of the tricarboxylic acid cycle are down regulated.

Furthermore, 2 oxo glutarate is an entry metabolite into the ascorbate and aldarate meta bolic pathway, which is implicated in increased lifespan in Drosophila. The L4 to male transition shows a decrease in Inhibitors,Modulators,Libraries lipid metabolism coupled with an increase in amino acid selleckchem metabolism. Metabolic chokepoints reactions that uniquely con sume or produce a metabolite are enzymes that seem likely to be essential to the parasite and so may be poten tial targets for future drug development. Analysis of the H.