The P2Y1 receptor is involved in the maintenance of glucose homeostasis and in insulin secretion in mice

Pancreatic β cells express several P2 receptors including P2Y1 and the modulation of insulin secretion by extracellular nucleotides has suggested that these receptors may contribute to the regulation of glucose homeostasis. To determine whether the P2Y1 receptor is involved in this process, we performed studies in P2Y1 mice. In baseline conditions, P2Y1-mice exhibited a 15% increase in glycemia and a 40% increase in insulinemia, associated with a 10% increase in body weight, pointing to a role of the P2Y1 receptor in the control of glucose metabolism. Dynamic experiments further showed that P2Y1-mice exhibited a tendency to glucose intolerance. These features were associated with a decrease in the plasma levels of free fatty acid and triglycerides. When fed a lipids and sucrose enriched diet for 15 weeks, the two genotypes no longer displayed any significant differences. To determine whether the P2Y1 receptor was directly involved in the control of insulin secretion, experiments were carried out in isolated Langerhans islets. In the presence of high concentrations of glucose, insulin secretion was significantly greater in islets from P2Y1-mice. Altogether, these results show that the P2Y1 receptor plays a physiological role in the maintenance of glucose homeostasis at least in part by regulating insulin secretion

Cardiac Alterations in Human African Trypanosomiasis (T.b. gambiense) with Respect to the Disease Stage and Antiparasitic Treatment

In Human African Trypanosomiasis (HAT), neurological symptoms dominate and cardiac involvement has been suggested. Because of increasing resistance to the available drugs for HAT, new compounds are desperately needed. Evaluation of cardiotoxicity is one parameter of drug safety, but without knowledge of the baseline heart involvement in HAT, cardiologic findings and drug-induced alterations will be difficult to interpret. The electrocardiogram (ECG) is a tool to evaluate cardiac involvement and the risk of arrythmias. We analysed the ECG of 465 HAT patients and compared them with the ECG of 61 healthy volunteers. In HAT patients the QTc interval was prolonged. This comprises a risk of fatal arrhythmias if new drugs with antiarrhythmic potential will be used. Further, repolarization changes and low voltage were more frequent than in healthy controls. This could be explained by an inflammation of the heart. Treatment of HAT was associated with appearance of repolarization changes but not with a QTc prolongation. These changes appear to be associated with the disease, but not with a specific drug. The main conclusion of this study is that heart involvement is frequent in HAT and mostly well tolerated. However, it can become relevant, if new compounds with antiarrhythmic potential will be used

Search for Pauli Exclusion Principle Violating Atomic Transitions and Electron Decay with a P-type Point Contact Germanium Detector

A search for Pauli-exclusion-principle-violating K-alpha electron transitions was performed using 89.5 kg-d of data collected with a p-type point contact high-purity germanium detector operated at the Kimballton Underground Research Facility. A lower limit on the transition lifetime of 5.8x10^30 seconds at 90% C.L. was set by looking for a peak at 10.6 keV resulting from the x-ray and Auger electrons present following the transition. A similar analysis was done to look for the decay of atomic K-shell electrons into neutrinos, resulting in a lower limit of 6.8x10^30 seconds at 90 C.L. It is estimated that the MAJORANA DEMONSTRATOR, a 44 kg array of p-type point contact detectors that will search for the neutrinoless double-beta decay of 76-Ge, could improve upon these exclusion limits by an order of magnitude after three years of operation

The MAJORANA DEMONSTRATOR: A Search for Neutrinoless Double-beta Decay of Germanium-76

The {\sc Majorana} collaboration is searching for neutrinoless double beta decay using $^{76}$Ge, which has been shown to have a number of advantages in terms of sensitivities and backgrounds. The observation of neutrinoless double-beta decay would show that lepton number is violated and that neutrinos are Majorana particles and would simultaneously provide information on neutrino mass. Attaining sensitivities for neutrino masses in the inverted hierarchy region, $15 - 50$ meV, will require large, tonne-scale detectors with extremely low backgrounds, at the level of $\sim$1 count/t-y or lower in the region of the signal. The {\sc Majorana} collaboration, with funding support from DOE Office of Nuclear Physics and NSF Particle Astrophysics, is constructing the {\sc Demonstrator}, an array consisting of 40 kg of p-type point-contact high-purity germanium (HPGe) detectors, of which $\sim$30 kg will be enriched to 87% in $^{76}$Ge. The {\sc Demonstrator} is being constructed in a clean room laboratory facility at the 4850' level (4300 m.w.e.) of the Sanford Underground Research Facility (SURF) in Lead, SD. It utilizes a compact graded shield approach with the inner portion consisting of ultra-clean Cu that is being electroformed and machined underground. The primary aim of the {\sc Demonstrator} is to show the feasibility of a future tonne-scale measurement in terms of backgrounds and scalability.Comment: Proceedings for the MEDEX 2013 Conferenc