Die zellvorgänge bei der entwicklung der flügelschuppen von ephestia kühniella Z

Ohne ZusammenfassungAls Dissertation angenommen von der Mathematisch-naturwissenschaftlichen Fakultät der Universität Göttingen (D 7).     

The transcription factor Grainyhead like 3 (GRHL3) affects endothelial cell apoptosis and migration in a NO-dependent manner

Migratory capacity and resistance to apoptosis are crucial for proper endothelial function. In a screen for anti-apoptotic genes in a breast cancer cell line, we identified Grainyhead like 3 (GRHL3). Therefore, the aim of our study was to investigate whether GRHL3 is expressed in endothelial cells and moreover, to determine its role in migration, apoptosis and senescence. GRHL3 is expressed in human endothelial cells. GRHL3 is required for endothelial cell migration. The underlying mechanism is independent of vascular endothelial growth factor. GRHL3 induces Akt and endothelial nitric oxide synthase phosphorylation and its expression is increased by physiological concentrations of nitric oxide. Nitric oxide dependent migration is completely dependent on GRHL3 expression. Moreover, GRHL3 inhibits apoptosis of endothelial cells in an eNOS-dependent manner. Thus, loss of GRHL3 may result in endothelial dysfunction in vivo. One may consider new therapeutic strategies with the aim to conserve GRHL3 expression in the vasculature.     

Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor

The lead optimisation of the diaminopyrimidine carboxamide series of spleen tyrosine kinase inhibitors is described. The medicinal chemistry strategy was focused on optimising the human whole blood activity whilst achieving a sufficient margin over liability kinases and hERG activity. GSK143 is a potent and highly selective SYK inhibitor showing good efficacy in the rat Arthus model.     

Altitudinal and temporal distribution of Plagiometriona Spaeth, 1899 (Coleoptera, Chrysomelidae, Cassidinae) in a tropical forest in southeast Brazil

Species richness and abundance of seven Plagiometriona species on their host plants were studied along a single trail in the mountainous Serra dos Órgãos National Park in the State of Rio de Janeiro, Brazil. Six sites were chosen along an altitudinal gradient ranging from 1300 m to 2050 m, where all Solanaceae host plants were inspected in search of adults every two months from June 2006 to June 2007. Species richness did not vary clearly with altitude, but abundance increased up to 1800 m, where the highest mean host plant density was found, and abruptly decreased at the last elevational site. Most species showed a restricted distribution and just one occurred across the entire gradient. For at least four species, altitudinal distribution seems to be strongly related to host plant availability, while for the others it is difficult to access which factors are decisive, due to their low numbers. Only in October all species were found in the field, although February was the month with the highest total abundance. Over the course of the study, the greatest abundances were recorded from October to February, comprehending the hottest and rainiest months, and the lowest abundances were found from June to August, which include the coldest and driest months. Thus, species seasonal distribution, supported by other studies in the same area, seems to be related to the local climate.     

From proteomic multimarker profiling to interesting proteins: thymosin-β(4) and kininogen-1 as new potential biomarkers for inflammatory hepatic lesions

Despite tremendous efforts in disclosing the pathophysiological and epidemiological factors associated with liver fibrogenesis, non-invasive diagnostic measures to estimate the clinical outcome and progression of liver fibrogenesis are presently limited. Therefore, there is a mandatory need for methodologies allowing the reasonable and reliable assessment of the severity and/or progression of hepatic fibrogenesis. We here performed proteomic serum profiling by matrix-assisted laser desorption ionization time-of-flight mass spectrometry in 179 samples of patients chronically infected with hepatitis C virus and 195 control sera. Multidimensional analysis of spectra allowed the definition of algorithms capable to distinguish class-specific protein expression profiles in serum samples. Overall about 100 peaks could be detected per single spectrum. Different algorithms including protein peaks in the range of 2000 and 10,000 Da were generated after pre-fractionation on a weak cation exchange surface. A specificity of 93% with a sensitivity of 86% as mean of the test set results was found, respectively. The nature of three of these protein peaks that belonged to kininogen-1 and thymosin-β(4) was further analysed by tandem mass spectrometry (MS)/MS. We further found that kininogen-1 mRNA was significantly down-regulated in cirrhotic livers. We have identified kininogen-1 and thymosin-β(4) as potential new biomarkers for human chronic hepatitis C and conclude that serum profiling is a reliable technique to identify hepatitis-associated expression patterns. Based on the high throughput capability, the identified differential protein panel may serve as a diagnostic marker and warrants further validation in larger cohorts.     

Numeric and structural chromosome polymorphism in Rineloricaria lima (Siluriformes: Loricariidae): fusion points carrying 5S rDNA or telomere sequence vestiges

The karyotypes and chromosome polymorphism in Rineloricaria lima have been examined using both conventional (Giemsa-staining, C-banding and silver impregnation) and fluorescence in situ hybridization with 18S rDNA, 5S rDNA and telomeric (TTAGGG)n probes protocols. A variation in chromosome number of 2n?=?70?C66 was detected in the analyzed populations, with the fundamental number (FN) ranging from 72 to 74. The 2n?=?70 chromosomes and karyotypic formula?2st?+?68a (NF?=?72) was establish the start point of the current polymorphism. Based on this karyotype, seven fusioned and/or inverted chromosomes types (without vestiges of interstitial telomeric sites??ITS; with ITS and; carrying 5S rDNA fusion points) were described and eight karyotypes were established. It was hypothesized that one Rineloricaria branch, originally having a diploid number of 2n?=?54 which appears the ancestral 2n for Loricariidae, diversified through centric fissions generating unstable sites at the break points. These unstable sites may have triggered Robertsonian fusions generating the currently observed polymorphism of 70?C66 chromosomes. The formation of the chromosomes variants could have possibly led to the formation of different gametic combinations (balanced and unbalanced), which may have generated alterations in the FN above 72. These results demonstrate an important case that ITS and 5S rDNA were observed in fused chromosomes, implying that rDNA could serve as breakpoint for the fusion in Rinelocaria. Thus, all these mechanisms promote an increase in variability and assist in the maintenance of the observed polymorphism.