A Guanine Nucleotide-independent Inwardly Rectifying Cation Permeability Is Associated with P2Y 1 Receptor Expression in Xenopus Oocytes

The functional properties of the G protein-coupled P2Y1 receptor were investigated in Xenopus oocytes. Incubation of oocytes expressing either the human or turkey P2Y1 receptor with adenine nucleotide agonists resulted in an increase in Cl- current and activation of a novel cation current with an inwardly rectifying current-voltage relationship. Activation of either the human P2Y2 (P2U-purinergic) or M1 muscarinic receptor expressed in oocytes resulted in an increase in Cl- current similar to that observed in P2Y1 receptor-expressing oocytes but had no effect on cation current. P2 receptor agonists stimulated both the cation current and Cl- current in P2Y1 receptor-expressing oocytes with EC50 values and an order of potency (2-methylthioadenosine diphosphate > 2-methylthioadenosine triphosphate (2MeSATP) > ATP > UTP) that were similar to those previously observed for activation of phospholipase C in 1321N1 human astrocytoma cells stably expressing the human or turkey P2Y1 receptor. The P2Y receptor antagonists suramin and pyridoxal phosphate 6-azophenyl-2'-4'-disulfonic acid both shifted to the right the concentration-response relationship for 2MeSATP for stimulation of oocyte currents. Although injection of oocytes with either GDPbetaS (guanyl-5'-yl thiophosphate) or GTPgammaS (guanosine 5'-3-O-(thio)triphosphate) resulted in loss of adenine nucleotide-promoted Cl- channel activation, neither guanine nucleotide altered the 2MeSATP-stimulated cation current. These data are consistent with the view that activation of the novel cation current by the P2Y1 receptor does not involve a G protein. Tail current analysis of the novel P2Y1 receptor-associated cation conductance revealed that the open channel current-voltage relationship was outwardly rectifying with a reversal potential of -38 mV for the turkey P2Y1 receptor and -36 mV for the human P2Y1 receptor. Replacement of Na+ with K+ ions in the bathing solution produced a shift in reversal potential to near zero mV, but significant outward rectification remained. The cation current was not permeable to either Ca2+ or Ba2+ and exhibited steady-state inactivation at holding potentials below -60 mV. These results indicate that the P2Y1 receptor exhibits both metabotropic properties and a novel G protein-independent ionotropic response when expressed in Xenopus oocytes

Rescue leadless pacemaker implantation in a pacemaker-dependent patient with congenital heart disease and no alternative routes for pacing

Congenital heart disease patients are considered a unique group of patients regarding their high risk of conduction abnormalities, whether de novo or surgically induced, and the challenges in both implantation and management of device related complications. We present a case of a pacemaker-dependent patient with congenital heart disease who experienced complications of both previous epicardial and transvenous pacing which rendered her a non-suitable candidate of both routes

Impairment of the Plasmodium falciparum Erythrocytic Cycle Induced by Angiotensin Peptides

Plasmodium falciparum causes the most serious complications of malaria and is a public health problem worldwide with over 2 million deaths each year. The erythrocyte invasion mechanisms by Plasmodium sp. have been well described, however the physiological aspects involving host components in this process are still poorly understood. Here, we provide evidence for the role of renin-angiotensin system (RAS) components in reducing erythrocyte invasion by P. falciparum. Angiotensin II (Ang II) reduced erythrocyte invasion in an enriched schizont culture of P. falciparum in a dose-dependent manner. Using mass spectroscopy, we showed that Ang II was metabolized by erythrocytes to Ang IV and Ang-(1–7). Parasite infection decreased Ang-(1–7) and completely abolished Ang IV formation. Similar to Ang II, Ang-(1–7) decreased the level of infection in an A779 (specific antagonist of Ang-(1–7) receptor, MAS)-sensitive manner. 10−7 M PD123319, an AT2 receptor antagonist, partially reversed the effects of Ang-(1–7) and Ang II. However, 10−6 M losartan, an antagonist of the AT1 receptor, had no effect. Gs protein is a crucial player in the Plasmodium falciparum blood cycle and angiotensin peptides can modulate protein kinase A (PKA) activity; 10−8 M Ang II or 10−8 M Ang-(1–7) inhibited this activity in erythrocytes by 60% and this effect was reversed by 10−7 M A779. 10−6 M dibutyryl-cAMP increased the level of infection and 10−7 M PKA inhibitor decreased the level of infection by 30%. These results indicate that the effect of Ang-(1–7) on P. falciparum blood stage involves a MAS-mediated PKA inhibition. Our results indicate a crucial role for Ang II conversion into Ang-(1–7) in controlling the erythrocytic cycle of the malaria parasite, adding new functions to peptides initially described to be involved in the regulation of vascular tonus

Impairment of the Plasmodium falciparum Erythrocytic Cycle Induced by Angiotensin Peptides

Plasmodium falciparum causes the most serious complications of malaria and is a public health problem worldwide with over 2 million deaths each year. The erythrocyte invasion mechanisms by Plasmodium sp. have been well described, however the physiological aspects involving host components in this process are still poorly understood. Here, we provide evidence for the role of renin-angiotensin system (RAS) components in reducing erythrocyte invasion by P. falciparum. Angiotensin II (Ang II) reduced erythrocyte invasion in an enriched schizont culture of P. falciparum in a dose-dependent manner. Using mass spectroscopy, we showed that Ang II was metabolized by erythrocytes to Ang IV and Ang-(1–7). Parasite infection decreased Ang-(1–7) and completely abolished Ang IV formation. Similar to Ang II, Ang-(1–7) decreased the level of infection in an A779 (specific antagonist of Ang-(1–7) receptor, MAS)-sensitive manner. 10−7 M PD123319, an AT2 receptor antagonist, partially reversed the effects of Ang-(1–7) and Ang II. However, 10−6 M losartan, an antagonist of the AT1 receptor, had no effect. Gs protein is a crucial player in the Plasmodium falciparum blood cycle and angiotensin peptides can modulate protein kinase A (PKA) activity; 10−8 M Ang II or 10−8 M Ang-(1–7) inhibited this activity in erythrocytes by 60% and this effect was reversed by 10−7 M A779. 10−6 M dibutyryl-cAMP increased the level of infection and 10−7 M PKA inhibitor decreased the level of infection by 30%. These results indicate that the effect of Ang-(1–7) on P. falciparum blood stage involves a MAS-mediated PKA inhibition. Our results indicate a crucial role for Ang II conversion into Ang-(1–7) in controlling the erythrocytic cycle of the malaria parasite, adding new functions to peptides initially described to be involved in the regulation of vascular tonus

Prevalence & Correlates of Eating Disordered Behaviors Among Students at the University of Wisconsin--Eau Claire.

Color poster with text and tables (Spring 2009)Eating disorders (EDs) are a concern among college counselors. Prevalence rates of diagnosed EDs on college campuses range between 1-3%. We sought to determine whether depression, self-esteem, and body shape satisfaction measures as well as standard demographic descriptors correlated with a diagnosed ED and a measure of eating disordered behavior among college students at UWEC. Our goal was to assess and target possible preventative or therapeutic interventions.University of Wisconsin--Eau Claire Office of Research and Sponsored Programs

Metrology for new generation nuclear power plants - MetroFission

Conference of 2013 3rd International Conference on Advancements in Nuclear Instrumentation, Measurement Methods and Their Applications, ANIMMA 2013 ; Conference Date: 23 June 2013 Through 27 June 2013; Conference Code:102802International audienceThis EMRP (European Metrology Research Programme) project, MetroFission, has been looking at solving metrological problems related to a new generation of nuclear power plants. The proposed Generation IV power plants are designed to run safely, make efficient use of natural resources, minimize the waste and maintain proliferation resistance. In order to reach these goals, the reactor operation involves higher temperatures, high-energy neutron fluence, different types of fuel where the minor actinides are included etc. In this multidisciplinary project, which has 12 partners in 10 countries, the work has focused on improved temperature measurements, investigation of thermal properties of advanced materials, determination of new and relevant nuclear data and development of measurement techniques for radionuclides suitable for Generation IV power plants. The improved temperature measurement for nuclear power plant applications includes the development of a new Fe-C fixed point. Robust, repeatable and versatile cells have been constructed and compared with success among the project participants and their melting temperatures have been determined. Furthermore, the methodology of self-validating thermocouples has proven efficient at several fixed point temperatures (Au, Cu, Co-C, Fe-C) using different designs. A practical acoustic thermometer has been tested at high temperature (1000 °C) with success thanks to the use of innovative signal processing methods. Mo/Nb thermocouples have been obtained with different sheath materials and tested with the aim to achieve for the first time a reference function determined with the best possible uncertainties. Following reviews of designs and technology proposed for fourth generation nuclear plants effort within this project, with regards to thermal properties of advanced materials for nuclear design, has concentrated on provision of thermodynamic data to support the development of the sodium cooled fast reactor (ASTRID). Data has been critically assessed to represent the potential interaction between the Na coolant and the nuclear fuel taken to be based on (U,Pu)O2 but incorporating minor actinides such as Np and Am. Data for the fission products and containment materials have also been reviewed and new data assessed to represent the interaction between them and the Na coolant, in order to permit calculation of phase and chemical equilibria for severe accident scenarios. The aim is to publish the data developed during this project within a revised version of "Thermochemical data for reactor materials and fission products", last published in 1990. Reference metrological facilities and methods have been developed or improved for the measurements of normal spectral emissivity and specific heat up to 1500 °C, and thermal diffusivity up to 2000 °C. The following actions were notably performed: Development of two complementary facilities based on different metrological approaches (calorimetric and optical methods) by PTB and LNE for the measurement of emissivity of solid materials at high temperature. Modification of the LNE diffusivimeter with the development and integration of a specific inductive furnace, and the adaptation of the associated IR detection systems. These facilities have now been used for the measurement of thermophysical properties of some materials (Ni, MgO and ZrO2), because they have thermal properties similar to those encountered in Generation IV reactors. Regarding neutron cross sections, the current nuclear databases concentrate on thermal energies, but new fast reactor designs will involve materials exposed to higher energy neutron fields. Advantage has been taken of National Measurement Institutes experience in neutron fluence measurements to improve high-energy cross-section measurements. A secondary fluence standard has been established and used to determine the cross sections of actual interest improving nuclear data standards in the form of reduced measurement uncertainties. The heavier actinides and their decay products have a role in the future development and adoption of nuclear power plants in whose fuels they will be present in controlled amounts. A list of specific needs for improved actinide decay data has recently been outlined in a review by the IAEA. Responding to those needs, an objective of the MetroFission project was to measure the alpha-particle emission probabilities of 238U with certified isotopic composition. The nuclear data from alpha spectrometry of 238U sources has been successful, obtaining data that will be provided to the international community and that further lower the uncertainties of the nuclear data. The quality of the alpha spectrum measurement, in terms of energy resolution and peak tailing of the 238U alpha spectra, was significantly better than in any previous measurement. Fission fragments containing more beta-decay isotopes will result from proposed fast reactors. Cryogenic detectors have been developed aimed at improving the measurement of beta spectra and verifying theoretical models. A beta spectrum shape of 63Ni has successfully been obtained. Improvements have been made in the source components and in the source production method in order to lower uncertainties. The exchange effect has been implemented in the calculation of theoretical beta spectra. The measurement of the beta spectrum of 63Ni has for the first time confirmed the exchange effect at very low energy. The energy threshold of the metallic magnetic calorimeter is 180 eV. At this energy, the enhancement of the beta emission due to the exchange effect is larger than 20 %. Nuclear power plants would benefit from on-site activity measurements of radionuclides including low-energy beta emitters that are abundant but can prove difficult to assay. Within this project, a primary liquid scintillation coincidence counting method called Triple to Double Coincidence Ratio (TDCR) has been modified for this purpose. Five partners have built miniature TDCR systems, miniaturising the instrument's detection chamber by using newer, smaller, more efficient photomultiplier tubes. The system also includes replacing the analogue electronic modules with digital acquisition systems and signal processing in order to significantly improve digital coincidence counting (DCC)