GPAT1 Deficiency in Mice Modulates NASH Progression in a Model-Dependent Manner.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD), and its more severe form, nonalcoholic steatohepatitis (NASH), is the leading cause for liver failure and liver cancer. Although the etiology is likely multifactorial, genes involved in regulating lipid metabolism are enriched in human NAFLD genome-wide association studies (GWAS), pointing to dysregulated lipid metabolism as a major pathogenic factor. Glycerol-3-phosphate acyltransferase 1 (GPAT1), encoded by GPAM, converts acyl-CoAs and glycerol-3-phosphate into lysophosphatidic acid and has been shown to regulate lipid accumulation in the liver.

Structure-based charge calculations for predicting isoelectric point, viscosity, clearance, and profiling antibody therapeutics.

The effect of hydrophobicity on antibody aggregation is well understood, and it has been shown that charge calculations can be useful for high-concentration viscosity and pharmacokinetic (PK) clearance predictions. In this work, structure-based charge descriptors are evaluated for their predictive performance on recently published antibody pI, viscosity, and clearance data. From this, we devised four rules for therapeutic antibody profiling which address developability issues arising from hydrophobicity and charged-based solution behavior, PK, and the ability to enrich for those that are approved by the U.

De novo lipogenesis is essential for platelet production in humans.

Acetyl-CoA carboxylase (ACC) catalyses the first step of de novo lipogenesis (DNL). Pharmacologic inhibition of ACC has been of interest for therapeutic intervention in a wide range of diseases. We demonstrate here that ACC and DNL are essential for platelet production in humans and monkeys, but in not rodents or dogs.

Acetyl-CoA Carboxylase Inhibition Improves Multiple Dimensions of NASH Pathogenesis in Model Systems.

Background & Aims: Disordered metabolism, steatosis, hepatic inflammation, and fibrosis contribute to the pathogenesis of nonalcoholic steatohepatitis (NASH). Acetyl-CoA carboxylase (ACC) catalyzes the first committed step in de novo lipogenesis (DNL) and modulates mitochondrial fatty acid oxidation. Increased hepatic DNL flux and reduced fatty acid oxidation are hypothesized to contribute to steatosis.

Antibody modeling assessment.

A blinded study to assess the state of the art in three-dimensional structure modeling of the variable region (Fv) of antibodies was conducted. Nine unpublished high-resolution x-ray Fab crystal structures covering a wide range of antigen-binding site conformations were used as benchmark to compare Fv models generated by four structure prediction methodologies. The methodologies included two homology modeling strategies independently developed by CCG (Chemical Computer Group) and Accerlys Inc, and two fully automated antibody modeling servers: PIGS (Prediction of ImmunoGlobulin Structure), based on the canonical structure model, and Rosetta Antibody Modeling, based on homology modeling and Rosetta structure prediction methodology.

Traumatic noncombat-related hand injuries in U.S. troops in the combat zone.

Background: The epidemiology of traumatic, nonbattle, Combat Zone hand injuries has not been well explored.

Methods: This was a retrospective chart review of Emergency Department visits occurring at the Ibn Sina Hospital in Baghdad Iraq.

Results: During the 24-month period from May 2007 to June 2009, 7,520 patients were seen at the Ibn Sina Hospital Emergency Department.