Role of ENPP1 on Adipocyte Maturation

BACKGROUND: It is recognized that the ability of adipose tissue to expand in response to energy excess, i.e. adipocyte maturation, is important in determining systemic abnormalities in glucose and lipid metabolism. Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1, also known as PC-1) has been recently reported to be involved in the pathogenesis of insulin resistance and related diseases. However, its role on adipose tissue physiology as a mechanism of systemic insulin resistance is not understood. This study was performed to evaluate whether ENPP1 is regulated during adipogenesis and whether over-expression in adipocytes can affect adipocyte maturation, a potential novel mechanism of ENPP1-related insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS: ENPP1 expression was found down-regulated during 3T3-L1 maturation, and over-expression of human ENPP1 in 3T3-L1 (pQCXIP-ENPP1 vector) resulted in adipocyte insulin resistance and in defective adipocyte maturation. Adipocyte maturation was more efficient in mesenchymal embryonal cells from ENPP1 knockout mice than from wild-type. CONCLUSIONS: We identify ENPP1 as a novel mechanism of defective adipocyte maturation. This mechanism could contribute to the pathogenesis of insulin resistance in absence of obesity

Enhanced mitochondrial superoxide scavenging does not Improve muscle insulin action in the high fat-fed mouse

Improving mitochondrial oxidant scavenging may be a viable strategy for the treatment of insulin resistance and diabetes. Mice overexpressing the mitochondrial matrix isoform of superoxide dismutase (sod2(tg) mice) and/or transgenically expressing catalase within the mitochondrial matrix (mcat(tg) mice) have increased scavenging of O2(˙-) and H2O2, respectively. Furthermore, muscle insulin action is partially preserved in high fat (HF)-fed mcat(tg) mice. The goal of the current study was to test the hypothesis that increased O2(˙-) scavenging alone or in combination with increased H2O2 scavenging (mtAO mice) enhances in vivo muscle insulin action in the HF-fed mouse. Insulin action was examined in conscious, unrestrained and unstressed wild type (WT), sod2(tg), mcat(tg) and mtAO mice using hyperinsulinemic-euglycemic clamps (insulin clamps) combined with radioactive glucose tracers following sixteen weeks of normal chow or HF (60% calories from fat) feeding. Glucose infusion rates, whole body glucose disappearance, and muscle glucose uptake during the insulin clamp were similar in chow- and HF-fed WT and sod2(tg) mice. Consistent with our previous work, HF-fed mcat(tg) mice had improved muscle insulin action, however, an additive effect was not seen in mtAO mice. Insulin-stimulated Akt phosphorylation in muscle from clamped mice was consistent with glucose flux measurements. These results demonstrate that increased O2(˙-) scavenging does not improve muscle insulin action in the HF-fed mouse alone or when coupled to increased H2O2 scavenging

A coalgebraic perspective on logical interpretations

In Computer Science stepwise refinement of algebraic specifications is a well-known formal methodology for rigorous program development. This paper illustrates how techniques from Algebraic Logic, in particular that of interpretation, understood as a multifunction that preserves and reflects logical consequence, capture a number of relevant transformations in the context of software design, reuse, and adaptation, difficult to deal with in classical approaches. Examples include data encapsulation and the decomposition of operations into atomic transactions. But if interpretations open such a new research avenue in program refinement, (conceptual) tools are needed to reason about them. In this line, the paper’s main contribution is a study of the correspondence between logical interpretations and morphisms of a particular kind of coalgebras. This opens way to the use of coalgebraic constructions, such as simulation and bisimulation, in the study of interpretations between (abstract) logics.Fundação para a Ciência e a Tecnologia (FCT

Modal Logics of Topological Relations

Logical formalisms for reasoning about relations between spatial regions play a fundamental role in geographical information systems, spatial and constraint databases, and spatial reasoning in AI. In analogy with Halpern and Shoham's modal logic of time intervals based on the Allen relations, we introduce a family of modal logics equipped with eight modal operators that are interpreted by the Egenhofer-Franzosa (or RCC8) relations between regions in topological spaces such as the real plane. We investigate the expressive power and computational complexity of logics obtained in this way. It turns out that our modal logics have the same expressive power as the two-variable fragment of first-order logic, but are exponentially less succinct. The complexity ranges from (undecidable and) recursively enumerable to highly undecidable, where the recursively enumerable logics are obtained by considering substructures of structures induced by topological spaces. As our undecidability results also capture logics based on the real line, they improve upon undecidability results for interval temporal logics by Halpern and Shoham. We also analyze modal logics based on the five RCC5 relations, with similar results regarding the expressive power, but weaker results regarding the complexity

Smokers' recall of Australian graphic cigarette packet warnings & awareness of associated health effects, 2005-2008

Extent: 11p.Background: In 2006, Australia introduced graphic cigarette packet warnings. The new warnings include one of 14 pictures, many depicting tobacco-related pathology. The warnings were introduced in two sets; Set A in March and Set B from November. This study explores their impact on smokers’ beliefs about smoking related illnesses. This study also examines the varying impact of different warnings, to see whether warnings with visceral images have greater impact on smokers’ beliefs than other images. Methods: Representative samples of South Australian smokers were interviewed in four independent cross-sectional omnibus surveys; in 2005 (n = 504), 2006 (n = 525), 2007 (n = 414) and 2008 (n = 464). Results: Unprompted recall of new graphic cigarette warnings was high in the months following their introduction, demonstrating that smokers’ had been exposed to them. Smokers also demonstrated an increase in awareness about smoking-related diseases specific to the warning messages. Warnings that conveyed new information and had emotive images demonstrated greater impact on recall and smokers’ beliefs than more familiar information and less emotive images. Conclusions: Overall graphic pack warnings have had the intended impact on smokers. Some have greater impact than others. The implications for policy makers in countries introducing similar warnings are that fresh messaging and visceral images have the greatest impact.Caroline L Miller, Pascale G Quester, David J Hill and Janet E Hille

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes