Four twist genes in zebrafish, four expression patterns.

Twist genes code for regulatory bHLH proteins essential for embryonic development and conserved across the metazoa. There are four genes that constitute the zebrafish twist family: twist1a, twist1b, twist2--orthologs of the mammalian twist1 and twist2 genes; and twist3--a gene from a new clade that does not exist in mammals. Presented here are their embryonic mRNA expression profiles. The study extends the known conservation of twist developmental patterns in tetrapods to the fish, e.g., expression in cephalic neural crest, sclerotome and lateral plate mesoderm. Some other expression domains are unique, like hypochord and dorsal aorta; some, like the notochord, may be ancestral patterns retained from protochordates; and the expression in invaginating/migrating cells may have been retained from the jellyfish. Perhaps this is one of the more ancient functions of twist--conserved from diploblasts to humans--to facilitate cell movement.

Preclinical evaluation of two neutralizing human monoclonal antibodies against hepatitis C virus (HCV): a potential treatment to prevent HCV reinfection in liver transplant patients.

Passive immunotherapy is potentially effective in preventing reinfection of liver grafts in hepatitis C virus (HCV)-associated liver transplant patients. A combination of monoclonal antibodies directed against different epitopes may be advantageous against a highly mutating virus such as HCV. Two human monoclonal antibodies (HumAbs) against the E2 envelope protein of HCV were developed and tested for the ability to neutralize the virus and prevent human liver infection. These antibodies, designated HCV-AB 68 and HCV-AB 65, recognize different conformational epitopes on E2. They were characterized in vitro biochemically and functionally. Both HumAbs are immunoglobulin G1 and have affinity constants to recombinant E2 constructs in the range of 10(-10) M. They are able to immunoprecipitate HCV particles from infected patients' sera from diverse genotypes and to stain HCV-infected human liver tissue. Both antibodies can fix complement and form immune complexes, but they do not activate complement-dependent or antibody-dependent cytotoxicity. Upon complement fixation, the monoclonal antibodies induce phagocytosis of the immune complexes by neutrophils, suggesting that the mechanism of viral clearance includes endocytosis. In vivo, in the HCV-Trimera model, both HumAbs were capable of inhibiting HCV infection of human liver fragments and of reducing the mean viral load in HCV-positive animals. The demonstrated neutralizing activities of HCV-AB 68 and HCV-AB 65 suggest that they have the potential to prevent reinfection in liver transplant patients and to serve as prophylactic treatment in postexposure events.