Bioluminescent Imaging of Trypanosoma brucei Shows Preferential Testis Dissemination Which May Hamper Drug Efficacy in Sleeping Sickness

Monitoring Trypanosoma spread using real-time imaging in vivo provides a fast method to evaluate parasite distribution especially in immunoprivileged locations. Here, we generated monomorphic and pleomorphic recombinant Trypanosoma brucei expressing the Renilla luciferase. In vitro luciferase activity measurements confirmed the uptake of the coelenterazine substrate by live parasites and light emission. We further validated the use of Renilla luciferase-tagged trypanosomes for real-time bioluminescent in vivo analysis. Interestingly, a preferential testis tropism was observed with both the monomorphic and pleomorphic recombinants. This is of importance when considering trypanocidal drug development, since parasites might be protected from many drugs by the blood-testis barrier. This hypothesis was supported by our final study of the efficacy of treatment with trypanocidal drugs in T. brucei-infected mice. We showed that parasites located in the testis, as compared to those located in the abdominal cavity, were not readily cleared by the drugs

OPET-Seminar: Erdgekoppelte Waermepumpen zum Heizen und Klimatisieren von Gebaeuden Tagungsband

Low-depth geothermal energy is available down to a depth of about 400-500 m. It has a low temperature level as a rule and can be utilized either via soil-to-water heat pumps or underground thermal energy storage. Soil-to-water heat pumps were introduced in the USA in 1945 and in Europe in the late sixties. By 1980, the first ground source heat pumps were constructed in Germany and Switzerland. After a dramatic increase of sales in the wake of the oil crises and the decline that followed in most countries (with the exception of Switzerland), the number of ground source heat pumps has been increasing again since the mid-nineties. The per capita number of soil-to-water heat pumps is still highest in Switzerland, where the number of ground source heat pumps alone exceeds 20,000. An upward trend is repported from Germany and Austria as well. This conference proceedings volume shows important trends in Germany and other states like Austria, Poland, Switzerland and the NetherlandsOberflaechennahe Geothermie ist die in Form von Waerme gespeicherte Energie von der Oberflaeche der festen Erde bis in eine Tiefe von etwa 400-500 m. Diese Energie wird in der Regel auf einem niedrigen Temperaturniveau angetroffen und kann im wesentlichen mit zwei Methoden genutzt werden, der erdgekoppelten Waermepumpe und der unterirdischen thermischen Energiespeicherung. Erdgekoppelte Waermepumpen werden seit 1945 in den USA verwendet und haben Ende der 60er Jahre den Weg nach Europa genommen. Um 1980 wurden die ersten Waermepumpenanlagen mit Erdwaermesonden in Deutschland und in der Schweiz gebaut. Nach einer grossen Anzahl neuer Anlagen in der Zeit der Oelpreiskrisen und einer anschliessenden Flaute in den meisten Laendern (ausser der Schweiz) ist die Zahl erdgekoppelter Waermepumpen seit Mitte der 90er Jahre wieder stetig gestiegen. In der Schweiz sind pro Kopf der Bevoelkerung nach wie vor weltweit die meisten erdgekoppelten Waermepumpen installiert, allein die Zahl der Erdwaermesondenanlagen uebersteigt 20.000. Doch auch in Deutschland und Oesterreich gibt es viele Anlagen, mit steigender Tendenz. In dem Tagungsband sollen einige wichtige Trends in Deutschland und den Nachbarlaendern aufgezeigt werden. Andere Laender wie Oesterreich, Polen, die Schweiz und die Niederlande sind durch eigene Vortraege auf dem Seminar vertreten. (orig./AKF)SIGLEAvailable from TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Characterization of CD8+ T-cell response in acute and resolved hepatitis A virus infection.

Abstract BACKGROUND & AIMS: In contrast to the infection with other hepatotropic viruses, hepatitis A virus (HAV) always causes acute self-limited hepatitis, although the role for virus-specific CD8 T cells in viral containment is unclear. Herein, we analyzed the T cell response in patients with acute hepatitis by utilizing a set of overlapping peptides and predicted HLA-A2 binders from the polyprotein. METHODS: A set of 11 predicted peptides from the HAV polyprotein, identified as potential binders, were synthesized. Peripheral blood mononuclear cells (PBMCs) from patients were tested for IFNγ secretion after stimulation with these peptides and ex vivo with HLA-A2 tetramers. Phenotyping was carried out by staining with the activation marker CD38 and the memory marker CD127. RESULTS: Eight out of 11 predicted HLA-A2 binders showed a high binding affinity and five of them were recognized by CD8+ T cells from patients with hepatitis A. There were significant differences in the magnitude of the responses to these five peptides. One was reproducibly immunodominant and the only one detectable ex vivo by tetramer staining of CD8+ T cells. These cells have an activated phenotype (CD38hi CD127lo) during acute infection. Three additional epitopes were identified in HLA-A2 negative patients, most likely representing epitopes restricted by other HLA-class I-alleles (HLA-A11, B35, B40). CONCLUSIONS: Patients with acute hepatitis A have a strong multi-specific T cell response detected by ICS. With the tetramer carrying the dominant HLA-A2 epitope, HAV-specific and activated CD8+ T cells could be detected ex vivo. This first description of the HAV specific CTL-epitopes will allow future studies on strength, breadth, and kinetics of the T-cell response in hepatitis A