Apolipoprotein O is mitochondrial and promotes lipotoxicity in heart

Diabetic cardiomyopathy is a secondary complication of diabetes with an unclear etiology. Based on a functional genomic evaluation of obesity-associated cardiac gene expression, we previously identified and cloned the gene encoding apolipoprotein O (APOO), which is overexpressed in hearts from diabetic patients. Here, we generated APOO-Tg mice, transgenic mouse lines that expresses physiological levels of human APOO in heart tissue. APOO-Tg mice fed a high-fat diet exhibited depressed ventricular function with reduced fractional shortening and ejection fraction, and myocardial sections from APOO-Tg mice revealed mitochondrial degenerative changes. In vivo fluorescent labeling and subcellular fractionation revealed that APOO localizes with mitochondria. Furthermore, APOO enhanced mitochondrial uncoupling and respiration, both of which were reduced by deletion of the N-terminus and by targeted knockdown of APOO. Consequently, fatty acid metabolism and ROS production were enhanced, leading to increased AMPK phosphorylation and Ppara and Pgc1a expression. Finally, we demonstrated that the APOO-induced cascade of events generates a mitochondrial metabolic sink whereby accumulation of lipotoxic byproducts leads to lipoapoptosis, loss of cardiac cells, and cardiomyopathy, mimicking the diabetic heart-associated metabolic phenotypes. Our data suggest that APOO represents a link between impaired mitochondrial function and cardiomyopathy onset, and targeting APOO-dependent metabolic remodeling has potential as a strategy to adjust heart metabolism and protect the myocardium from impaired contractility

An Analysis of Solution Properties of the Graph Coloring Problem

This paper concerns the analysis of solution properties of the Graph Coloring Problem. For this purpose, we introduce a property based on the notion of representative sets which are sets of vertices that are always colored the same in a set of solutions. Experimental results on well-studied DIMACS graphs show that many of them contain such sets and give interesting information about the diversity of the solutions. We also show how such an analysis may be used to improve a tabu search algorithm

Recent Advances in Graph Partitioning

We survey recent trends in practical algorithms for balanced graph partitioning together with applications and future research directions

Scatter Search for Graph Coloring

In this paper, we present a first scatter search approach for the Graph Coloring Problem (GCP). The evolutionary strategy scatter search operates on a set of configurations by combining two or more elements. New configurations are improved before replacing others according to their quality (fitness), and sometimes, to their diversity. Scatter search has been applied recently to some combinatorial optimization problems with promising results. Nevertheless, it seems that no attempt of scatter search has been published for the GCP. This paper presents such an investigation and reports experimental results on some wellstudied DIMACS graphs