This pattern is consis tent with the progression from a developing embryo nated egg to a motile and actively feeding larval stage. In the transition to somehow the L3 stage, a decrease in the expression of genes associated with the myosin complex and motor activity Inhibitors,Modulators,Libraries and various metabolic processes are consistent with the nematode entering a quiescent state. Among the up regulated genes there is an association with oxygen transport and heme binding. Oxidoreductase enzymes are over represented and may reflect the increased need to detoxify a build up of endogenous waste, consistent with previous studies showing higher cytochrome P450 activity in the H. contortus L3 than in L1 or adult stages. CYPs have also been shown to be up regulated in response to reduced food intake.

This is consistent with the significant increase in gluconeogenesis Inhibitors,Modulators,Libraries from the L1 to L3 which is also increased in the C. elegans dauer and the up regulation of acetyl CoA metabolic process, likely to reflect metabolism of fat Inhibitors,Modulators,Libraries stores in the non feeding L3. Genes associated with binding of cobalamin are also up regulated. Cobalamin has been shown to be strongly concentrated and stored in the infective L3 of other gastrointestinal nematodes and a ready sup ply may be required for rapid larval development after ingestion by the host. The Inhibitors,Modulators,Libraries L4 is the first blood feeding stage of H. contortus. The transition from the quiescent L3 stage to the motile L4 stage is reflected in significant up regulation of many genes, including genes associated with motor activity, the myosin complex and locomotion as well as various metabolic processes.

The binding of oxygen, lipids and sugars, possibly associated with active feeding, is also up regulated, as are changes in the expression of genes linked to response to oxidative stress that may reflect the reactivation of the parasite from its dormant stage. Inhibitors,Modulators,Libraries A significant increase in the expression of genes asso ciated with collagen and cuticle development and body morphogenesis, consistent with parasite growth, is also observed. Interestingly, heme binding genes were both up and down regulated, perhaps reflecting an increase in heme load from blood feeding and a decrease in CYP activity. Transition from the L4 to the adult stages is charac terized by several changes.

In the transition to the selleck products female stage, 1,658 genes are up regulated and correlate with gender specific development as well as embryogen esis, such as genitalia development, embryo development, oogenesis, ovulation, germ line cell cycle switching, meiosis regulation and regulation of vulval development. A significant increase in DNA repli cation processes is also apparent. Between the L4 and adult male stage, lower expression in the adult male of genes linked with body morphogenesis, molting, col lagen and cuticle development, oxidoreductase activity, heme binding and response to oxidative stress were observed among the various alterations in expression.