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Lupescu A.,University of Tubingen | Jilani K.,University of Tubingen | Zelenak C.,University of Tubingen | Zbidah M.,University of Tubingen | And 3 more authors.
Cellular Physiology and Biochemistry | Year: 2012

Gambogic acid, a xanthone from Garcinia hanburyi, stimulates apoptosis and has thus anticancer potency. Similar to apoptosis of nucleated cells, erythrocytes may undergo apoptosis-like suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine-exposure at the cell surface. Eryptosis could be triggered by increase of cytosolic Ca2+-activity ([Ca2+]i), ceramide formation, ATP-depletion and caspase activation. The present study explored, whether gambogic acid triggers eryptosis of human erythrocytes. [Ca2+]iwas estimated utilizing Fluo-3 fluorescence, cell volume from forward scatter, phosphatidylserine-exposure from annexin-V-binding, hemolysis from hemoglobin release, ceramide abundance utilizing antibodies, and cytosolic ATP with luciferin-luciferase. A 48 h exposure to gambogic acid (500 nM) significantly increased [Ca2+]i, stimulated ceramide formation, decreased forward scatter and increased annexin-V-binding. Gambogic acid exposure was followed by a slight but significant increase of hemolysis. Gambogic acid did not significantly modify cytosolic ATP-concentration. Removal of extracellular Ca2+ slightly, but significantly blunted the effect of gambogic acid (500 nM) on annexin-V-binding. The present observations disclose a novel effect of gambogic acid, i.e. stimulation of suicidal death of human erythrocytes or eryptosis, paralleled by Ca2+-entry, ceramide formation, cell shrinkage and phosphatidylserine-exposure. © 2012 S. Karger AG, Basel. Source


Kucherenko Y.,University of Tbingen | Kucherenko Y.,Ukrainian Academy of Sciences | Zelenak C.,University of Tbingen | Eberhard M.,University of Tbingen | And 3 more authors.
Cellular Physiology and Biochemistry | Year: 2012

Pharmacological modification of protein kinase CK1 (casein kinase 1) has previously been shown to influence suicidal erythrocyte death or eryptosis, which is triggered by activation of Cl--sensitive Ca 2+-permeable cation channels. Ca2+ entering through those channels stimulates cell membrane scrambling and opens Ca2+-activated K+-channels resulting in KCl exit and thus cell shrinkage. The specific CK1-inhibitor D4476 (1 μM) blunted, whereas the specific CK1 αactivator pyrvinium pamoate (10 μM) enhanced cell membrane scrambling. The substances were at least partially effective through modification of cytosolic Ca2+-activity. The present study explored, whether pyrvinium pamoate indeed influences Cl--sensitive cation-channels in erythrocytes. As a result, removal of Cl-increased Fluo3-fluorescence (reflecting cytosolic Ca2+-activity), triggered cell membrane scrambling (apparent from annexin-V-binding), and decreased forward scatter (pointing to cell shrinkage). Pyrvinium pamoate significantly augmented the effect of Cl--removal on Fluo3 fluorescence and annexin-V-binding, but blunted the effect on forward scatter. According to whole cell patch clamp recording, Cl-removal activated a cation current, which was significantly enhanced by pyrvinium pamoate. Pyrvinium pamoate inhibited Ca 2+-activated K+-channels. Ca2+-ionophore ionomycin (1 μM) decreased forward scatter, an effect significantly blunted by pyrvinium pamoate. In conclusion, pyrvinium pamoate activates Cl --sensitive Ca2+-permeable cation channels with subsequent Ca2+-entry and inhibits Ca2+-activated K +-channels thus blunting the stimulating effect of Ca2+ on those channels, K+-exit and thus cell shrinkage. © 2012 S. Karger AG, Basel. Source


Imkovic F.,Comenius University | Imkovic F.,Laboratory of Theoretical Physics | Krivoruchenko M.I.,Institute of Theoretical and Experimental Physics | Faessler A.,University Tbingen
Progress in Particle and Nuclear Physics | Year: 2011

The fundamental importance of searching for neutrinoless double-beta decay is widely recognized. Observation of the decay would tell us that the total lepton number is not conserved and that, consequently, neutrinos are massive Majorana fermions. The same statement could be made in the case of observing neutrinoless double-electron capture. We address the question of the sensitivity of the 0νεε decay to the effective mass of the Majorana neutrino. According to our estimates, in the case of 152Gd and 164Er the sensitivity can be comparable to the favored 0νββ decays of nuclei. The main uncertainty in the prediction of half-lives of the 0νεε decay stems from the lack of sufficient precision in measuring the mass difference between the parent and daughter atoms. More accurate measurements can be accomplished using the modern high-precision ion traps. © 2011 Elsevier B.V. All rights reserved. Source


Hodak R.,Comenius University | Simkovic F.,Comenius University | Simkovic F.,Laboratory of Theoretical Physics | Kovalenko S.,Federico Santa Maria Technical University | Faessler A.,University Tbingen
Progress in Particle and Nuclear Physics | Year: 2011

The standard Big Bang cosmology predicts that the universe is abundantly populated with neutrinos. As expected there are at least 114 neutrinos per cubic centimeter averaged over the whole space. Like the cosmic background radiation the cosmic neutrinos at present posses a very small kinetic energy due to expansion of the universe. This prediction is one of the cornerstones of modern cosmology. On the other hand the existence of cosmic neutrinos has not yet been confirmed by direct detection experiments. For now we only have a lower limit on the total mass of this free floating ghostly gas of neutrinos, but even so it is roughly equivalent to the total mass of all the visible stars in universe. There could be many more neutrinos at Earth because of condensation of neutrinos, now moving slowly under the gravitational pull of our galaxy. Here we discuss the possibility of detection of relic neutrinos in KATRIN and MARE experiments via neutrino capture on tritium and rhenium, respectively. We also examine single and double relic neutrino capture on double β-decaying nuclei which might be relevant in the context of the new generation double beta decay experiments. Further we explore feasibility of experiments for detection of heavy sterile neutrinos with masses in MeV region, which may have important astrophysical and cosmological implications. © 2011 Elsevier B.V. All rights reserved. Source


Weides M.,Leibniz Institute for Solid State and Materials Research | Weides M.,University of California at Santa Barbara | Peralagu U.,Leibniz Institute for Solid State and Materials Research | Peralagu U.,University of Glasgow | And 8 more authors.
Superconductor Science and Technology | Year: 2010

We present the latest generation of superconductor-insulator-ferromagnet- superconductor Josephson tunnel junctions with a step-like thickness of the ferromagnetic (F) layer. The F-layer thicknesses d1 and d2 in both halves were varied to obtain different combinations of positive and negative critical current densities jc,1 and jc,2. The measured dependences of the critical current on applied magnetic field can be well described by a model which takes into account different critical current densities (obtained from reference junctions) and different net magnetization of the multidomain ferromagnetic layer in both halves. © 2010 IOP Publishing Ltd. Source

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