75 research outputs found

    Functional Interactions between KCNE1 C-Terminus and the KCNQ1 Channel

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    The KCNE1 gene product (minK protein) associates with the cardiac KvLQT1 potassium channel (encoded by KCNQ1) to create the cardiac slowly activating delayed rectifier, IKs. Mutations throughout both genes are linked to the hereditary cardiac arrhythmias in the Long QT Syndrome (LQTS). KCNE1 exerts its specific regulation of KCNQ1 activation via interactions between membrane-spanning segments of the two proteins. Less detailed attention has been focused on the role of the KCNE1 C-terminus in regulating channel behavior. We analyzed the effects of an LQT5 point mutation (D76N) and the truncation of the entire C-terminus (Δ70) on channel regulation, assembly and interaction. Both mutations significantly shifted voltage dependence of activation in the depolarizing direction and decreased IKs current density. They also accelerated rates of channel deactivation but notably, did not affect activation kinetics. Truncation of the C-terminus reduced the apparent affinity of KCNE1 for KCNQ1, resulting in impaired channel formation and presentation of KCNQ1/KCNE1 complexes to the surface. Complete saturation of KCNQ1 channels with KCNE1-Δ70 could be achieved by relative over-expression of the KCNE subunit. Rate-dependent facilitation of K+ conductance, a key property of IKs that enables action potential shortening at higher heart rates, was defective for both KCNE1 C-terminal mutations, and may contribute to the clinical phenotype of arrhythmias triggered by heart rate elevations during exercise in LQTS mutations. These results support several roles for KCNE1 C-terminus interaction with KCNQ1: regulation of channel assembly, open-state destabilization, and kinetics of channel deactivation

    Bio-Corrosion of Magnesium Alloys for Orthopaedic Applications

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    Three Mg alloys, Mg–1.34% Ca–3% Zn (MCZ), Mg–1.34% Ca–3% Zn–0.2% Sr (MCZS), and Mg–2% Sr (MS), were examined to understand their bio-corrosion behavior. Electrochemical impedance spectroscopy and polarization scans were performed after 6 days of immersion in cell culture medium, and ion release and changes in media pH were tracked over a 28 day time period. Scanning electron microscopy (SEM) of alloy microstructure was performed to help interpret the results of the electrochemical testing. Results indicate that corrosion resistance of the alloys is as follows: MCZ > MCZS > MS

    The Solar-Driven Coal/Fe3O4 Redox System

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    The solar-driven endothermic reaction of coal and magnetite was studied for mixing solar and fossil energies. The overall reaction can be represented by CHx + Fe3O4 = CO + 3FeO + 1/2xH2 where x depends on the coal(x= 0.2 in our study). Laboratory experimental studies with an equimolar mixture of anthracite coal and Fe3O4 powder using an infrared furnace showed rapid gas evolution above about 1200°C and 1bar, producing FeO(s) and a gas mixture containing a CO/CO2 molar ratio of 4.5. Solar-driven experiments were conducted using a high-flux solar furnace. Samples were directly exposed for short time intervals to a solar flux irradiation of 300 W/cm2. The carbon content decreased rapidly after only 1 second exposure, suggesting efficient heat transfer and chemical conversion by direct absorption of concentrated solar energy at the reaction site. The proposed solar thermochemical process offers the possibility of performing simultaneously the gasification of coal and reduction of iron oxide, and for producing a fuel with an upgraded calorific value

    Evaluation of a British-German postgraduate course in clinical pharmacy

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    Since 1997, a 4 week postgraduate course in clinical pharmacy has been offered annually at the University of Tübingen (Germany) in cooperation with the School of Pharmacy, University of London (United Kingdom). The course combines a theoretical and a practice-based module; a concept which is unique in Germany, but well established in the UK. The present study evaluated whether former participants found the course useful for their daily practice. A structured questionnaire was sent to all former participants (n = 102), 66 (65%) responded; 63 pharmacists (95%) found the course subjects useful. A total of 61 respondents (92%) were involved in 223 clinical pharmacy projects which were related to course subjects, including drug information services, participation in ward rounds and patient counselling. A lack of time was identified as the main barrier to implementing such services. Pharmacists felt more competent to work with doctors after completion of the course (40, 61%) though this was subjective. This collaborative programme helped to share expertise in teaching and clinical pharmacy practice across countries.Peer reviewe
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