Role of Esrrg in the Fibrate-Mediated Regulation of Lipid Metabolism Genes in Human ApoA-I Transgenic Mice

We have used a new ApoA-I transgenic mouse model to identify by global gene expression profiling, candidate genes that affect lipid and lipoprotein metabolism in response to fenofibrate treatment. Multilevel bioinformatical analysis and stringent selection criteria (2-fold change, 0% false discovery rate) identified 267 significantly changed genes involved in several molecular pathways. The fenofibrate-treated group did not have significantly altered levels of hepatic human APOA-I mRNA and plasma ApoA-I compared with the control group. However, the treatment increased cholesterol levels to 1.95-fold mainly due to the increase in high-density lipoprotein (HDL) cholesterol. The observed changes in HDL are associated with the upregulation of genes involved in phospholipid biosynthesis and lipid hydrolysis, as well as phospholipid transfer protein. Significant upregulation was observed in genes involved in fatty acid transport and β-oxidation, but not in those of fatty acid and cholesterol biosynthesis, Krebs cycle and gluconeogenesis. Fenofibrate changed significantly the expression of seven transcription factors. The estrogen receptor-related gamma gene was upregulated 2.36-fold and had a significant positive correlation with genes of lipid and lipoprotein metabolism and mitochondrial functions, indicating an important role of this orphan receptor in mediating the fenofibrate-induced activation of a specific subset of its target genes.National Institutes of Health (HL48739 and HL68216); European Union (LSHM-CT-2006-0376331, LSHG-CT-2006-037277); the Biomedical Research Foundation of the Academy of Athens; the Hellenic Cardiological Society; the John F Kostopoulos Foundatio

Increased Expression of Fatty-Acid and Calcium Metabolism Genes in Failing Human Heart

Heart failure (HF) involves alterations in metabolism, but little is known about cardiomyopathy-(CM)-specific or diabetes-independent alterations in gene expression of proteins involved in fatty-acid (FA) uptake and oxidation or in calcium-(Ca(2+))-handling in the human heart.RT-qPCR was used to quantify mRNA expression and immunoblotting to confirm protein expression in left-ventricular myocardium from patients with HF (n = 36) without diabetes mellitus of ischaemic (ICM, n = 16) or dilated (DCM, n = 20) cardiomyopathy aetiology, and non-diseased donors (CTL, n = 6).Significant increases in mRNA of genes regulating FA uptake (CD36) and intracellular transport (Heart-FA-Binding Protein (HFABP)) were observed in HF patients vs CTL. Significance was maintained in DCM and confirmed at protein level, but not in ICM. mRNA was higher in DCM than ICM for peroxisome-proliferator-activated-receptor-alpha (PPARA), PPAR-gamma coactivator-1-alpha (PGC1A) and CD36, and confirmed at the protein level for PPARA and CD36. Transcript and protein expression of Ca(2+)-handling genes (Two-Pore-Channel 1 (TPCN1), Two-Pore-Channel 2 (TPCN2), and Inositol 1,4,5-triphosphate Receptor type-1 (IP3R1)) increased in HF patients relative to CTL. Increases remained significant for TPCN2 in all groups but for TPCN1 only in DCM. There were correlations between FA metabolism and Ca(2+)-handling genes expression. In ICM there were six correlations, all distinct from those found in CTL. In DCM there were also six (all also different from those found in CTL): three were common to and three distinct from ICM.DCM-specific increases were found in expression of several genes that regulate FA metabolism, which might help in the design of aetiology-specific metabolic therapies in HF. Ca(2+)-handling genes TPCN1 and TPCN2 also showed increased expression in HF, while HF- and CM-specific positive correlations were found among several FA and Ca(2+)-handling genes

Hemodialysis Removes Uremic Toxins That Alter the Biological Actions of Endothelial Cells

Chronic kidney disease is linked to systemic inflammation and to an increased risk of ischemic heart disease and atherosclerosis. Endothelial dysfunction associates with hypertension and vascular disease in the presence of chronic kidney disease but the mechanisms that regulate the activation of the endothelium at the early stages of the disease, before systemic inflammation is established remain obscure. In the present study we investigated the effect of serum derived from patients with chronic kidney disease either before or after hemodialysis on the activation of human endothelial cells in vitro, as an attempt to define the overall effect of uremic toxins at the early stages of endothelial dysfunction. Our results argue that uremic toxins alter the biological actions of endothelial cells and the remodelling of the extracellular matrix before signs of systemic inflammatory responses are observed. This study further elucidates the early events of endothelial dysfunction during toxic uremia conditions allowing more complete understanding of the molecular events as well as their sequence during progressive renal failure

O pewnym algorytmie badania tautologii rachunku zdań

In the present paper we propose an algorithm deciding, whether a given formula a is a tautology of the propositional logic. The worst case complexity of the algorithm is of the order .W pracy został przedstawiony algorytm sprawdzania czy dana formuła rachunku zdań należąca do języka , zbudowana ze zmiennych, stałej zero, nawiasów oraz znaku implikacji, jest tautologią. Idea algorytmu jest oparta na regułach transformacji. Reguły te zachowują tautologiczność formuły, tzn. formuła , która jest tautologią po zastosowaniu odpowiedniej reguły w dalszym ciągu jest tautologią. Jeśli dana formuła jest różna od stałej lub zmiennej, to w formule znajdujemy ostanie wystąpienie znaku implikacji i stosujemy odpowiednią regułę otrzymując nowy ciąg formuł. Formuły przekształcamy do momentu, kiedy otrzymamy ciąg pusty (wtedy jest ona tautologią), bądź zmienną bądź stałą. Złożoność tego algorytmu, w najgorszym przypadku, wynosi , gdzie oznacza długość formuły

An application of the Orienteering Problem with Time Windows for tour planning problem in Bialystok region

Problem komiwojażera z profitami i oknami czasowymi jest dogodnym modelem dla problemu optymalnego planowania tras atrakcyjnych turystycznie. W pracy przedstawiono rozwiązanie tej odmiany problemu komiwojażera za pomocą algorytmu genetycznego GAPR. W miejsce krzyżowania zaproponowano wymianę obiektów między losowo wybranymi trasami. Rozwiązanie przetestowano na rzeczywistej sieci obiektów turystycznych okolicy Białegostoku. W wyniku testów otrzymano trasy o porównywalnej atrakcyjności jak w algorytmie genetycznym GA z krzyżowaniem (różnica jest na korzyść GAPR około 0.5%) i czasem generowania trasy nie przekraczającym 1.5 sekundy. Algorytm może być zastosowany w planerach tras turystycznych.Orienteering problem with time windows (OPTW) is a good model for the tour planning problem. In this article a genetic algorithm with path relinking (GAPR) is used for solving OPTW. The path relinking (PR) process is applied instead of a crossover. The solution has been tested on a real network of tourist points of interests in Bialystok region. Routes which are the test results are comparable with the routes generated by the previous GA with crossover (the GAPR exceeds profit result about 0.5% relative to GA, the execution time of GAPR does not exceed 1.5 s). The algorithm can be used in trip planners