The anti-inflammatory CASPASE-12 gene does not influence SLE phenotype in African-Americans.

In the vast majority of human populations, the gene encoding CASPASE-12 (CASP12) has a premature termination codon that precludes the production of protein. However, approximately 20% of persons of recent African descent have a single nucleotide polymorphism (#rs497116; A->G) that turns the stop codon into one encoding Arg. The subsequent functional allele is a risk factor for sepsis as it uniquely downregulates inflammatory cytokines in African-Americans (AA).

CASPASE-12 and rheumatoid arthritis in African-Americans.

CASPASE-12 (CASP12) has a downregulatory function during infection and thus may protect against inflammatory disease. We investigated the distribution of CASP12 alleles (#rs497116) in African-Americans (AA) with rheumatoid arthritis (RA). CASP12 alleles were genotyped in 953 RA patients and 342 controls.

A possible mechanism for maintenance of the deleterious allele of human CASPASE-12.

In humans, a functional CASPASE-12 (CASP12) gene has been identified only in persons of African heritage and has been suggested to play a regulatory role in response to bacterial pathogens and in promoting and increased susceptibility to sepsis. The existence of a gene whose effect is deleterious, and which has been the subject of extensive negative selection in the rest of the human population, implies the simultaneous presence of some selective benefit for persons having CASP12. Given the importance of inflammatory immune responses in controlling the initial stages of infection, and the role that CASP12 plays in down-regulating inflammation, we hypothesize that pathogens which exploit the inflammatory response are restrained by an active CASP12 gene product.

Design, synthesis, and evaluation of indole compounds as novel inhibitors targeting Gp41.

A series of indole ring containing compounds were designed based on the structure of the gp41 complex in the region of the hydrophobic pocket. These compounds were synthesized using a Suzuki Coupling reaction, and evaluated using a fluorescence binding assay and cell-cell fusion assay. The observed inhibition constant of compound 7 was 2.

Proteolytic cleavage of ataxin-7 by caspase-7 modulates cellular toxicity and transcriptional dysregulation.

Spinocerebellar ataxia type 7 (SCA7) is a polyglutamine (polyQ) disorder characterized by specific degeneration of cerebellar, brainstem, and retinal neurons. Although they share little sequence homology, proteins implicated in polyQ disorders have common properties beyond their characteristic polyQ tract. These include the production of proteolytic fragments, nuclear accumulation, and processing by caspases.

Polymorphism and conservation of the genes encoding Qa1 molecules.

To evaluate the polymorphism and conservation of the major histocompatibility complex class Ib molecule Qa1 in wild mouse populations, we determined the nucleotide sequence of exons 1-3 of Qa1 of eight mouse haplotypes derived from wild mice, including Mus musculus domesticus, M. m. castaneus, M.

Inhibition of calpain cleavage of huntingtin reduces toxicity: accumulation of calpain/caspase fragments in the nucleus.

Huntington's disease (HD) is a neurodegenerative disorder caused by a polyglutamine (polyQ) tract expansion near the N terminus of huntingtin (Htt). Proteolytic processing of mutant Htt and abnormal calcium signaling may play a critical role in disease progression and pathogenesis. Recent work indicates that calpains may participate in the increased and/or altered patterns of Htt proteolysis leading to the selective toxicity observed in HD striatum.

Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78.

Alterations in Ca(2+) homeostasis and accumulation of unfolded proteins in the endoplasmic reticulum (ER) lead to an ER stress response. Prolonged ER stress may lead to cell death. Glucose-regulated protein (GRP) 78 (Bip) is an ER lumen protein whose expression is induced during ER stress.