selleckchem contortus gen ome and have the same genomic structure, suggesting that diversity has arisen through recent gene duplication. Reflecting this, most CBLs encoded in the H. contortus genome form large monophyletic groups dis tinct from C. elegans, hookworm or other stron gylid CBLs, suggesting that duplication and divergence has occurred separately following speciation. Inhibitors,Modulators,Libraries It is possible that gene amplification has occurred as a mechanism of increasing overall CBL expression associated with the need for H. contortus to digest the huge quantities of host blood it takes in during feeding. The cbl genes show increased expression in L4 and adult stages and many are significantly enriched in gut tissue, identifying these as potentially important control targets. These include both novel and previously identified cbl genes.

while other cbl transcripts are signifi cantly up regulated in the L4 Inhibitors,Modulators,Libraries stage and in adult male worms, but not in the gut, suggesting a role in develop ment and reproduction rather than feeding. The CBLs identified here contain a putative amino terminal signal peptide and several have been identified in adult worm excretory secretory products. It has also been pro posed that sequence variation of Hc CBLs may confer antigenic diversity, and presentation to the host immune system through secretion may therefore drive the maintenance of the diversity of Hc cbl genes. Three dimensional modeling of the CBL repertoire and epitope mapping will clarify this issue.

Other cathepsin cysteine protease genes are not expanded for example, a cpr 6 like single copy gene is highly conserved in a number of parasitic and free living nematodes, suggesting a house keeping role, and there is no expansion found for cathepsin L, F or Z genes in H. contortus. Furthermore, there is less Inhibitors,Modulators,Libraries expansion of genes encoding other vaccine candidates H gal GP composed predominantly of pepsinogen like aspartic and metallo proteases, and H11 aminopeptidases. These are integral gut membrane proteins, consid ered hidden from the immune system during natural infection, and lower diversity should be advanta geous in vaccination studies. Significant expansion is, however, seen in the cathe psin aspartic protease family. Importantly, the genome data identify a novel, single copy apr gene with 84% amino acid identity to APR 1 of the dog hookworm Ancylostoma caninum and that is significantly enriched in gut tissue.

Vaccination with Inhibitors,Modulators,Libraries recombinant Ac APR 1 significantly Inhibitors,Modulators,Libraries reduced fecal www.selleckchem.com/products/Dasatinib.html egg counts, worm burdens and anemia, warranting investigation of the protective potential of the Hae monchus APR 1 related protease. Other novel Hc apr genes group phylogenetically with C. elegans asp genes and are increased in the environmental L1 stage, indicating a developmental role, consistent with C. elegans data and ruling these out as potential vaccine targets. Conclusions H.