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In this thesis I have investigated the regulation of eicosanoid synthesizing-enzymes by cannabinoid receptor agonists. Rat renal mesangial cells were used as a model system. I could show that all three (CB1, CB2, and GPR55) cannabinoid receptors are expressed on the mRNA level in rat renal mesangial cells – but with differing expression profiles. The CB1 and GPR55 receptors are expressed in comparable amounts, whereas the CB2 receptor is considerably less expressed than the CB1 and the GPR55 receptors. Furthermore I could show that stimulation of renal mesangial cells with CB1 receptor agonists, such as R(+)MA or ACEA, increased IL-1β-induced cPLA2, sPLA2-IIa, and COX2 protein and mRNA expression which subsequently led to an enhanced IL-1β-induced PGE2 formation. Additionally, the IL-1β- induced sPLA2-IIa promoter activity was also increased by CB1 receptor stimulation. Besides the modulated expression of the eicosanoid synthesizing enzymes, I could show that CB1 agonists also led to an increase of IL-1β-induced iNOS expression and subsequent NO formation. In contrast, stimulation with CB2 selective agonists led to a decrease in IL-1β- induced sPLA2-IIa protein expression and PGE2 formation. Accordingly, the IL-1β-induced sPLA2-IIa promoter activity was also reduced by CB2 receptor agonists. IL-1β-induced iNOS expression and subsequent NO formation were not influenced by CB2 recptor activation. Matching the results I obtained with CB1 receptor agonists on IL-1β-induced PGE2 formation, I could observe an increased cPLA2 protein and mRNA expression with a subsequent increase in IL-1β-induced PGE2 formation by GPR55 stimulation. Stimulation with THC, an unselective CB agonist, increased the IL-1β-induced sPLA2-IIa protein expression and subsequently led to an enhanced IL-1β-induced PGE2 formation. Subjecting the cells to higher THC concentrations surprisingly led to a reduction of the IL-1b-induced sPLA2-IIa protein expression and PGE2 formation. A possible explanation may be the differential expression of the three CB receptors. At low concentrations THC may predominantly activate CB1 and GPR55 and with increasing concentration CB2 receptors may also be activated, slightly reversing the enhancing effect. Moreover, I could show that the CB1 receptor stimulation mediated phosphorylation and hence the activation of ERK1/2 MAPK. Additionally to ERK1/2, there was also a phosphorylation and activation of NFkB observed by CB1 receptor stimulation. In my thesis I could show for the first time that PPARα was activated by IL-1β in rMC. The IL-1β-induced PPARα promoter activity was completely inhibited by addition of the CB2 receptor agonist, JWH015. These findings were confirmed by inhibition of the IL-1β-induced PGE2 formation by a PPARα antagonist (MK-886). In summary, I could show that activation of CB1 receptors in our system led to a worsening of an inflammatory condition, whereas activation of the CB2 receptors led to the complete opposite; namely a reduction of the inflammatory response by reducing the sPLA2-IIa expression and PGE2 formation. GPR55 activation did not display any alteration of inflammatory conditions, since the classical inflammatory pathway was not influenced.
The moderate halophile Halobacillus halophilus is the paradigm for chloride dependent growth in prokaryotes. Recent experiments shed light on the molecular basis of the chloride dependence that is reviewed here. In the presence of moderate salinities Halobacillus halophilus mainly accumulates glutamine and glutamate to adjust turgor. The transcription of glnA2 (encoding a glutamine synthetase) as well as the glutamine synthetase activity were identified as chloride dependent steps. Halobacillus halophilus switches its osmolyte strategy and produces proline as the main compatible solute at high salinities. Furthermore, Halobacillus halophilus also shifts its osmolyte strategy at the transition from the exponential to the stationary phase where proline is exchanged by ectoine. Glutamate was found as a second messenger" essential for proline production. This observation leads to a new model of sensing salinity by sensing the physico-chemical properties of different anions.
Reinhard Berger verstorben
(2008)
Reinheit als hermeneutisches und als paranoides Kalkül : der Rassediskurs der 1920er und '30er Jahre
(2008)
Eine kulturwissenschaftlich orientierte Untersuchung der nationalsozialistischen Rassenideologie muß sich möglicherweise zunächst grundsätzlich rechtfertigen. Jeder Versuch, die historischen Verbrechen des 20. Jahrhunderts und ihre ideologischen Vorbereitungen in historischen und kulturellen Kontexten zu beschreiben, scheint diesen a priori ihre Singularitat zu nehmen und sie mithin entschuldigen zu wollen. Dennoch versucht der folgende Beitrag, die Idee der "Reinheit" im deutschen Rassediskurs der 1920er und '30er Jahre zu analysieren. Das Konzept der "Reinheit: welches in jener Zeit als ein wesentliches Element von kultureller "Bedeutung" interpretiert wurde,' bildet eine prominente Verbindung zwischen Ideologie und Biologie, und infolgedessen auch zwischen kulturellen Diskursen und politischen Entscheidungen. Die folgende Untersuchung der Vorstellung "rassischer Reinheit" in den Rassediskursen versucht diese Übergänge nachzuzeichnen, und gleichzeitig zu zeigen, daß die "kulturelle" Logik hier eine alles andere als harmlose Wirkung entfaltet. Gerade dort, wo bestimmte "Ideen" nicht bruchlos auf die historische (und in diesem Fall: biologische) Realitat übertragen werden können, wurde eine zunehmende Radikalisierung möglich. Diese Radikalisierung der Idee der Reinheit möchte der folgende Beitrag beschreiben. Paradigmatisch sollen dabei ein "physiognomisches" Konzept von "Reinheit": (Ludwig Ferdinand Claus) und ein "ethisches Konzept" (Martin Staemmler) diskutiert werden.
Ataxin-2 is a novel protein, within which the unstable expansion of a polyglutamine domain can cause Spinocerebellar Ataxia type 2 (SCA2), a neurodegenerative disease which belongs to the group of polyglutamine disorders. SCA2 is characterised by a progressive loss of neurons that first affects the cerebellum and brain stem and then may extend to other areas of the brain, like substantia nigra, motoneurons and thalamus. Several lines of research have attempted to determine therole of ataxin-2 in its normal and mutant version. Different animal models and cell culture approaches to study ataxin-2 function implicated ataxin-2 in RNA processing, embryonic development, apoptosis and cytoskeleton. However, the function of ataxin-2 still remains unclear. In this thesis, a protein interaction approach was chosen as an alternative to gain insights into the cellular function of ataxin-2. Full-length ataxin-2 was used as bait in a yeast two-hybrid screen of human adult brain cDNA. Among five candidate interactor proteins identified, two were the endophilins A1 and A3, proteins involved in vesicle endocytosis. Co-immunoprecipitation studies confirmed the association of these proteins in an endogenous complex of mouse brain. In vitro binding experiments narrowed the binding interfaces down to two proline-rich domains on ataxin-2, which interacted with the SH3 domain of endophilins A1/A3. Ataxin-2 and endophilins A1/A3 colocalised at the endoplasmic reticulum as determined by immunofluorescence microscopy of transfected cell lines, and by centrifugation fractionation studies of mouse brain. Importantly, the pattern observed in transfected cells was conserved in untransfected rat hippocampal neurons. In mouse brain, associations of ataxin-2 with endocytic proteins such as the adaptor CIN85, the ubiquitin ligase c-Cbl and also GRB2, in the last case by means of a SH3 domain array chip, were also demonstrated. GST pull-down assays showed ataxin-2 to interact directly with the SH3 domains A and C of CIN85, the C-terminal SH3 domain of GRB2, and the SH3 domain of Src, a kinase activated after receptor stimulation. Functional studies demonstrated that ataxin-2 affects endocytic trafficking of the epidermal growth factor receptor (EGFR) by reducing the EGFR internalisation after EGF stimulation. Taken together, these data implicate ataxin-2 to play a role in endocytic receptor cycling.
Background Medical students come into contact with infectious diseases early on their career. Immunity against vaccine-preventable diseases is therefore vital for both medical students and the patients with whom they come into contact. Methods The purpose of this study was to compare the medical history and serological status of selected vaccine-preventable diseases of medical students in Germany. Results The overall correlation between medical history statements and serological findings among the 150 students studied was 86.7 %, 66.7 %, 78 % and 93.3 % for measles, mumps, rubella and varicella, conditional on sufficient immunity being achieved after one vaccination. Conclusions Although 81.2 % of the students medical history data correlated with serological findings, significant gaps in immunity were found. Our findings indicate that medical history alone is not a reliable screening tool for immunity against the vaccine-preventable diseases studied.
Religious conversion has become a dangerous social and individual problem. In Latin America, a traditional Catholic area, Protestant sects are successfully con-verting more and more Catholics into their own communities. Therefore the Pope demands a strict control of these activities. In India e.g., the Catholic hierarchy is critizising the Indian governments which have forbidden conversion on non-spiritual reasons. Hindu organizations have started even very successfully to re-convert Indian Christians particularly of Dalit and tribal background. Buddhists are very successful in indirect and even direct conversion of many Westerners. Wah-habit missionaries spread their Neo-Islam in the Muslim societies and get more and more even non-Muslim converts. We should add the forcible and sometimes ex-tremely cruel conversions the atheistic states had executed since the last century. ...
It has been suggested that the existence of a non-Gaussian fixed point in general relativity might cure the ultraviolet problems of this theory. Such a fixed point is connected to an effective running of the gravitational coupling. We calculate the effect of the running gravitational coupling on the black hole production cross section in models with large extra dimensions.
In 2007, a project named Adriatic Montenegro 2007 was initiated and realised under the protection of IDF. Stimulated by the suggestion of Vincent Kalkman from the European Invertebrate Survey, The Netherlands, distribution data for the Odonata of Adriatic Montenegro were collected and used to create distribution maps. These data and maps should then be used in the evaluation of conservation measures for individual odonate species as well as for the IUCN Red List of the Mediterranean countries (organized by the IUCN Centre for Mediterranean Cooperation) and the Project on an atlas of European dragonflies (a co-operation of all European countries organised by the European Invertebrate Survey, The Netherlands).