Metabolic signature of electrosurgical liver dissection.

Background And Aims: High frequency electrosurgery has a key role in the broadening application of liver surgery. Its molecular signature, i.e.

Genetic and functional identification of the likely causative variant for cholesterol gallstone disease at the ABCG5/8 lithogenic locus.

Unlabelled: The sterolin locus (ABCG5/ABCG8) confers susceptibility for cholesterol gallstone disease in humans. Both the responsible variant and the molecular mechanism causing an increased incidence of gallstones in these patients have as yet not been identified. Genetic mapping utilized patient samples from Germany (2,808 cases, 2,089 controls), Chile (680 cases, 442 controls), Denmark (366 cases, 766 controls), India (247 cases, 224 controls), and China (280 cases, 244 controls).

Distinct DNA methylation patterns in cirrhotic liver and hepatocellular carcinoma.

Abberrant DNA methylation is one of the hallmarks of cancerogenesis. Our study aims to delineate differential DNA methylation in cirrhosis and hepatic cancerogenesis. Patterns of methylation of 27,578 individual CpG loci in 12 hepatocellular carcinomas (HCCs), 15 cirrhotic controls and 12 normal liver samples were investigated using an array-based technology.

Loci from a genome-wide analysis of bilirubin levels are associated with gallstone risk and composition.

Background & Aims: Genome-wide association studies have mapped loci that are associated with serum levels of bilirubin. Bilirubin is a major component of gallstones so we investigated whether these variants predict gallstone bilirubin content and overall risk for gallstones.

Methods: Loci that were identified in a meta-analysis to attain a genome-wide significance level of a P value less than 1.

Caspase recruitment domain-containing protein 8 (CARD8) negatively regulates NOD2-mediated signaling.

Caspase activating and recruitment domain 8 (CARD8) has been implicated as a co-regulator of several pro-inflammatory and apoptotic signaling pathways. In the present study, we demonstrate a specific modulation of NOD2-induced signaling by CARD8 in intestinal epithelial cells. We show that CARD8 physically interacts with NOD2 and inhibits nodosome assembly and subsequent signaling upon muramyl-dipeptide stimulation.

Investigation of innate immunity genes CARD4, CARD8 and CARD15 as germline susceptibility factors for colorectal cancer.

Background: Variation in genes involved in the innate immune response may play a role in the predisposition to colorectal cancer (CRC). Several polymorphisms of the CARD15 gene (caspase activating recruitment domain, member 15) have been reported to be associated with an increased susceptibility to Crohn disease. Since the CARD15 gene product and other CARD proteins function in innate immunity, we investigated the impact of germline variation at the CARD4, CARD8 and CARD15 loci on the risk for sporadic CRC, using a large patient sample from Northern Germany.

Protein-protein interactions in the archaeal transcriptional machinery: binding studies of isolated RNA polymerase subunits and transcription factors.

Transcription in Archaea is directed by a pol II-like RNA polymerase and homologues of TBP and TFIIB (TFB) but the crystal structure of the archaeal enzyme and the subunits involved in recruitment of RNA polymerase to the promoter-TBP-TFB-complex are unknown. We described here the cloning expression and purification of 11 bacterially expressed subunits of the Pyrococcus furiosus RNAP. Protein interactions of subunits with each other and of archaeal transcription factors TFB and TFB with RNAP subunits were studied by Far-Western blotting and reconstitution of subcomplexes from single subunits in solution.

A short isoform of NOD2/CARD15, NOD2-S, is an endogenous inhibitor of NOD2/receptor-interacting protein kinase 2-induced signaling pathways.

Alterations in splicing patterns of genes contribute to the regulation of gene function by generating endogenous inhibitor or activator molecules. Nucleotide-binding and oligomerization domain (NOD) 2 is an intracellular receptor for bacterial cell wall components and plays an important role in initiating immune responses against cytoinvasive pathogens. NOD2 overexpression sensitizes intestinal epithelial cells toward bacterial cell wall components, activates the proinflammatory transcription factor NF-kappaB, and induces the subsequent release of the chemotactic cytokine IL-8.