Existence Results for Periodic Boundary Value Problems with a Convenction Term

By using an abstract coincidence point theorem for sequentially weakly continuous maps the existence of at least one positive solution is obtained for a periodic second order boundary value problem with a reaction term involving the derivative of the solution u: the so called convention term. As a consequence of the main result also the existence of at least one positive solution is obtained for a parameter-depending problem

Opening a new window to other worlds with spectropolarimetry

A high level of diversity has already been observed among the planets of our own Solar System. As such, one expects extrasolar planets to present a wide range of distinctive features, therefore the characterisation of Earth- and super Earth-like planets is becoming of key importance in scientific research. The SEARCH (Spectropolarimetric Exoplanet AtmospheRe CHaracerisation) mission proposal of this paper represents one possible approach to realising these objectives. The mission goals of SEARCH include the detailed characterisation of a wide variety of exoplanets, ranging from terrestrial planets to gas giants. More specifically, SEARCH will determine atmospheric properties such as cloud coverage, surface pressure and atmospheric composition, and may also be capable of identifying basic surface features. To resolve a planet with a semi major axis of down to 1.4AU and 30pc distant SEARCH will have a mirror system consisting of two segments, with elliptical rim, cut out of a parabolic mirror. This will yield an effective diameter of 9 meters along one axis. A phase mask coronagraph along with an integral spectrograph will be used to overcome the contrast ratio of star to planet light. Such a mission would provide invaluable data on the diversity present in extrasolar planetary systems and much more could be learned from the similarities and differences compared to our own Solar System. This would allow our theories of planetary formation, atmospheric accretion and evolution to be tested, and our understanding of regions such as the outer limit of the Habitable Zone to be further improved.Comment: 23 pages, accepted for publication in Experimental Astronom

Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification

Changes in cardiac substrate utilisation leading to altered energy metabolism may underlie the development of diabetic cardiomyopathy. We studied cardiomyocyte substrate uptake and utilisation and the role of the fatty acid translocase CD36 in relation to in vivo cardiac function in rats fed a high-fat diet (HFD).Rats were exposed to an HFD or a low-fat diet (LFD). In vivo cardiac function was monitored by echocardiography. Substrate uptake and utilisation were determined in isolated cardiomyocytes.Feeding an HFD for 8 weeks induced left ventricular dilation in the systolic phase and decreased fractional shortening and the ejection fraction. Insulin-stimulated glucose uptake and proline-rich Akt substrate 40 phosphorylation were 41% (p <0.001) and 45% (p <0.05) lower, respectively, in cardiomyocytes from rats on the HFD. However, long-chain fatty acid (LCFA) uptake was 1.4-fold increased (p <0.001) and LCFA esterification into triacylglycerols and phospholipids was increased 1.4- and 1.5-fold, respectively (both p <0.05), in cardiomyocytes from HFD compared with LFD hearts. In the presence of the CD36 inhibitor sulfo-N-succinimidyloleate, LCFA uptake and esterification were similar in LFD and HFD cardiomyocytes. In HFD hearts CD36 was relocated to the sarcolemma, and basal phosphorylation of a mediator of CD36-trafficking, i.e. protein kinase B (PKB/Akt), was increased.Feeding rats an HFD induced cardiac contractile dysfunction, which was accompanied by the relocation of CD36 to the sarcolemma, and elevated basal levels of phosphorylated PKB/Akt. The permanent presence of CD36 at the sarcolemma resulted in enhanced rates of LCFA uptake and myocardial triacylglycerol accumulation, and may contribute to the development of insulin resistance and diabetic cardiomyopathy

Synergistic Activation of Cardiac Genes by Myocardin and Tbx5

Myocardial differentiation is associated with the activation and expression of an array of cardiac specific genes. However, the transcriptional networks that control cardiac gene expression are not completely understood. Myocardin is a cardiac and smooth muscle-specific expressed transcriptional coactivator of Serum Response Factor (SRF) and is able to potently activate cardiac and smooth muscle gene expression during development. We hypothesize that myocardin discriminates between cardiac and smooth muscle specific genes by associating with distinct co-factors. Here, we show that myocardin directly interacts with Tbx5, a member of the T-box family of transcription factors involved in the Holt-Oram syndrome. Tbx5 synergizes with myocardin to activate expression of the cardiac specific genes atrial natriuretic factor (ANF) and alpha myosin heavy chain (α-MHC), but not that of smooth muscle specific genes SM22 or smooth muscle myosin heavy chain (SM-MHC). We found that this synergistic activation of shared target genes is dependent on the binding sites for Tbx5, T-box factor-Binding Elements (TBEs). Myocardin and Tbx5 physically interact and their interaction domains were mapped to the basic domain and the coil domain of myocardin and Tbx5, respectively. Our analysis demonstrates that the Tbx5G80R mutation, which leads to the Holt-Oram syndrome in humans, failed to synergize with myocardin to activate cardiac gene expression. These data uncover a key role for Tbx5 and myocardin in establishing the transcriptional foundation for cardiac gene activation and suggest that the interaction of myocardin and Tbx5 maybe involved in cardiac development and diseases

Subcellular trafficking of the substrate transporters GLUT4 and CD36 in cardiomyocytes

Cardiomyocytes use glucose as well as fatty acids for ATP production. These substrates are transported into the cell by glucose transporter 4 (GLUT4) and the fatty acid transporter CD36. Besides being located at the sarcolemma, GLUT4 and CD36 are stored in intracellular compartments. Raised plasma insulin concentrations and increased cardiac work will stimulate GLUT4 as well as CD36 to translocate to the sarcolemma. As so far studied, signaling pathways that regulate GLUT4 translocation similarly affect CD36 translocation. During the development of insulin resistance and type 2 diabetes, CD36 becomes permanently localized at the sarcolemma, whereas GLUT4 internalizes. This juxtaposed positioning of GLUT4 and CD36 is important for aberrant substrate uptake in the diabetic heart: chronically increased fatty acid uptake at the expense of glucose. To explain the differences in subcellular localization of GLUT4 and CD36 in type 2 diabetes, recent research has focused on the role of proteins involved in trafficking of cargo between subcellular compartments. Several of these proteins appear to be similarly involved in both GLUT4 and CD36 translocation. Others, however, have different roles in either GLUT4 or CD36 translocation. These trafficking components, which are differently involved in GLUT4 or CD36 translocation, may be considered novel targets for the development of therapies to restore the imbalanced substrate utilization that occurs in obesity, insulin resistance and diabetic cardiomyopathy