45 research outputs found

    Apolipoprotein O is mitochondrial and promotes lipotoxicity in heart

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    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

    Ensuring Interoperability for the Internet of Things: Experience with CoAP Protocol Testing

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    Constrained Application Protocol (CoAP) is a specialized web transfer protocol, designed for realizing interoperation with constrained networks and nodes for machine to machine applications like smart energy, building automation, etc. As an important ubiquitous application protocol for the future Internet of Things, CoAP will be potentially implemented by a wide range of smart devices to achieve cooperative services. Therefore, a high level of interoperability of CoAP implementations is crucial. In this context, CoAP Plugtest – the first formal CoAP interoperability testing event was held in Paris, March 2012 to motivate vendors to verify the interoperability of their equipments. The event turned to be successful due to our contribution, including the test method and tool. This paper presents the testing method and procedure for the CoAP Plugtest event. To carry out the tests, a set of test objectives concerning the most important properties of CoAP have been selected and used to measure the interoperability of CoAP implementations. The process of verification has been automated by implementing a test validation tool based on the technique of passive testing. By using the test tool, a number of devices were successfully tested.Constrained Application Protocol (CoAP) je specijalizirani prijenosni protokol, dizajniran za realizaciju međuoperabilnosti uz ograničene mrežame i čvorove za primjene poput pametne energije, automatizacije u zgradarstvu itd. Kao važan i sveprisutan protokol za Internet stvari CoAP bi mogao biti implementiran kod velikog broja pametnih uređaja kako bi se ostvarile kooperativne usluge. Zbog toga je od velike važnosti postic´i visoku razinu međuoperabilnosti CoAP implementacija. U tom kontekstu, CoAP Pluqtest - prvo formalno testiranje CoAP međuoperabilnosti je održano u Parizu u ožujku 2012. kako bi se motivirali prodavači da provjere međuoperabilnost svoje opreme. Testiranje je bilo uspješno zahvaljujući našem doprinosu koji uključuje metodu i alate za testiranje. U ovom radu prikazana je metoda i procedura testiranja za CoAP Pluqtest. Kako bi se proveli testovi odabran je skup ciljeva koji se odnose na najvažnija svojstva CoAP protokola i oni su korišteni za mjerenje međuoperabilnosti CoAP implementacija. Proces verifikacije je automatiziran implementacijom alata za provjeru testa koji se temelji na tehnici pasivnog testiranja. Korištenjem alata za testiranje uspješno su testirani brojni uređaji

    Application of reverse‐DEPT polarization transfer pulse sequence to study the metabolism of carbon‐13‐labeled substrates in perfused organs by 1H NMR Spectroscopy

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    Metabolism of C‐enriched metabolites can be advantageously studied by reverse‐polarization transfer methods. In this work an improved reverse‐DEPT sequence has been applied for the first time on perfused organs in a 20‐mm probe. The metabolic fate of 99% enriched [ 2‐C] acetate perfused in excised rat liver and heart has been documented. © 1990 Academic Press, Inc

    Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa).

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    Obesity is associated with increased risks for development of cardiovascular diseases. Epidemiological studies report an inverse association between dietary flavonoid consumption and mortality from cardiovascular diseases. We studied the potential beneficial effects of dietary supplementation of red wine polyphenol extract, Provinols, on obesity-associated alterations with respect to metabolic disturbances and cardiovascular functions in Zucker fatty (ZF) rats
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