Caspase-12 and the inflammatory response to Yersinia pestis.

Background: Caspase-12 functions as an antiinflammatory enzyme inhibiting caspase-1 and the NOD2/RIP2 pathways. Due to increased susceptibility to sepsis in individuals with functional caspase-12, an early-stop mutation leading to the loss of caspase-12 has replaced the ancient genotype in Eurasia and a significant proportion of individuals from African populations. In African-Americans, it has been shown that caspase-12 inhibits the pro-inflammatory cytokine production.

Suppression extends to major histocompatibility antigens linked to tolerizing minor histocompatibility antigens, but not the other way round.

'Active suppression', a mechanism of transplantation tolerance, can spread to newly introduced minor antigens once these antigens are linked to tolerizing antigens. We explored whether this suppression can extend to major histocompatibility (MHC) antigens and whether this phenomenon can be demonstrated once tolerance is induced to a MHC antigen. Mice were tolerized using donor bone marrow plus CD4 and CD8 monoclonal antibodies.

Adenoviral vectors expressing siRNAs for discovery and validation of gene function.

RNA interference is a powerful tool for studying gene function and for drug target discovery in diverse organisms and cell types. In mammalian systems, small interfering RNAs (siRNAs), or DNA plasmids expressing these siRNAs, have been used to down-modulate gene expression. However, inefficient transfection protocols, in particular, for primary cell types, have hampered the use of these tools in disease-relevant cellular assays.