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This study explores and examines the geomorphology of a large endorheic basin, approximately twice the size of Luxemburg, situated in the Etosha National Park, Namibia. The main focus is directed on how and when this depression, known as Etosha Pan, came into being. Geomorphological investigation was complemented and guided primarily by the application and interpretation of satellite-derived information. Etosha Pan has attracted scientific investigations for nearly a century. Unfortunately, their efforts resulted into two diverging and mutually exclusive views with respect to its development. The first and oldest view dates back to the 1920s. It hypothesized Etosha Pan as a desiccated palaeolake which was abandoned following the river capture of its major fluvial system, the Kunene River. The river capture was assumed to have taken place in the Pliocene/Early Pleistocene. In spite of the absence of fluvial input that the Kunene contributed, the original lake was thought to have persisted until some 35 ka ago, long after the Kunene severed its ties with the basin. The current size of the basin and its playa status was interpreted to have resulted from deteriorating climatic conditions. The opposing view emerged in the 1980s and gained prominence in the 1990s. This view assumed that there were an innumerable number of small pans on the then surface of what later to become Etosha Pan. Since the turn of the Pliocene to Early Pleistocene, these individual pans started to experience a combined effect of fluvial erosion during the rainy season and wind deflation during the dry period. The climatic regime during that entire period was postulated to be semi-arid as today. This climatic status was used to rule out any existence of a perennial lake within the boundary of Etosha since the Quaternary. Ultimately, these denudational processes, taking place in a seasonal rhythm, caused the individual pans to deepen and widen laterally into each other and formed a super-pan that we call Etosha today. Thus the Kunene River had no role to play in the development of the Etosha Pan according to this model. However, proponents of this model acknowledged that the Kunene once fed into the Owambo Basin and assigned the end of the Tertiary to the terminal phase of that inflow. Findings of this study included field evidence endorsing the postulation that the Kunene River had once flowed into the Owambo Basin. Its infilled valley, bounding with the contemporary valley of the Kunene near Calueque, was identified and points towards the Etosha Pan. It is deliberated that a large lake, called Lake Kunene, existed in the basin during the time. Following the deflection of the Kunene River to the coast under the influence of river incision and neo-tectonic during the Late Pliocene, new dynamics were introduced over the Owambo Basin surface. After the basin was deprived of its major water and sediment budget that the Kunene River contributed, it was left with only smaller rivers, most notably the Cuvelai System, as the only remaining supplier. This resulted in the Cuvelai System concentrating and limiting its collective load deposition to a lobe of Lake Kunene basin floor. The accident of that lobe is unclear, but it is likely that it constituted the deepest part of the basin at the time or it was influenced by neo-tectonic that helped divert the Kunene River or both. Against the backdrop of fluvial action that was initiating the new lake, most parts of the rest of the basin, then denied of lacustrine activity, were intermittently riddled with a veneer of sediment, especially during phases of intensified aeolian activity. In the mean time, the area that was regularly receiving fluvial input started to shape up as a distinct lake with the depositions of sediments around the water-body, primarily via littoral action, serving as embankment. Gradually, a shoreline is formed and assisted in fixing and delineating the spatial extent of the new and much smaller lake, called Lake Etosha. That Lake Etosha is the predecessor of the modern day Etosha Pan. Indicators for a perennial lake found in this study at Etosha include fossil fragments of Clariidae species comparable to modern species measuring some 90 cm, and those of sitatunga dated to approximately 5 ka. None of these creatures exist today at Etosha because of their ecological requirements, which among others, include permanent water. The sitatunga, in addition, is known as the only truly amphibious antelope in the world. Since its inception, the new lake underwent a number of geomorphological modifications. A prominent character amongst these modifications is the orientation of the lake, which has its long-axis oriented in the ENE-WSW direction. It resulted from wave action affected by the prevailing dominant northeasterly wind, which is believed to have been in force since the Middle Pleistocene. Lake Etosha has also witnessed phases of waning and waxing under the influence of the prevailing climatic regime. Over the last 150 ka, the available data intercepted about seven phases of high lake levels. These data are generally in agreement with regional palaeoclimatic data, particularly when compared with those obtained from neighbouring Makgadikgadi Pans in Botswana. The last recorded episode of the wet phase at Etosha was some 2,400 years before the present.
The genus Pogonomyrmex is predisposed for analyzing the evolution of ant colony characteristics in general and the sociogenetic structure in particular, due to the renowned biology of several species and the diversity of mating frequency and queen number. This variation in the sociogenetic structure of colonies produces a high variance in intracolonial relatedness which can be a major component driving the evolution of various colony characteristics. To exactly determine the variability of the intracolonial relatedness in the genus Pogonomyrmex both were analyzed, the number of matrilines and patrilines, in selected members of Pogonomyrmex, namely P. (sensu stricto) rugosus, P. (sensu stricto) badius and P. (Ephebomyrmex) pima using DNA fingerprint techniques. The evolution of these colony characteristics were tried to be explained within a phylogenetic framework. For that purpose we constructed a gene-tree of 39 species of the genus Pogonomyrmex. The taxon sampling covered about 83 % of the North American species and 43 % of the South American species. Effective multiple mating of queens was confirmed for P. rugosus (me=4.1) and P. badius (me=6.7). Additionally, both species are monogynous. These results corroborate behavioral observations of multiple mating for these species. Multiple mating is now known from 9 Pogonomyrmex species (behavioral evidence for 3 species – genetic evidence for 6 species). However, in P. (E.) pima all queens that were analyzed were single mated (me=1.0). Therefore, multiple mating may have either evolved early during the evolution of the genus Pogonomyrmex and has subsequently been lost in the subgenus Ephebomyrmex (plesiomorphic hypothesis), or it has first been evolved in the subgenus Pogonomyrmex sensu stricto (apomorphic hypothesis). In P. huachucanus, a species basal to the North- American sensu stricto complex, smaller effective mating number of queens compared to its sensu stricto relatives (J. Gadau and C.-P. Strehl, unpublished) probably do mirror a change from monandry to polyandry during the evolution of more advanced sensu stricto species, which would support the apomorphic hypothesis. The intracolonial relatedness in P. (E.) pima is however rather low. This is probably the result of multiple reproducing queens (polygyny). Polygyny is also documented for at least four other species of the subgenus Ephebomyrex, but so far P. (E.) pima is the only species with genetic evidence. It might be that there was an evolutionary trade-off within the subgenus Ephebomyrmex between polyandry and polygyny. Therefore, both subgenera retained a high intracolonial genetic diversity. This high genetic diversity might be one cause for the success and radiation of the genus Pogonomyrmex in arid environments. Evolution might have favored high genetic diversity of Pogonomyrmex colonies, because it helps colonies to improve their colonial organization and efficiency in performing external tasks. At least in P. badius a link between patrilines and physical polyethism was found, indicative of an improvement of colonial organization via polyandry. Furthermore, the documented extreme levels of polyandry might help P. badius females to overcome the possibility of inbreeding due to restricted dispersal. Restricted dispersal is also found in P. (E.) pima due to wingless, intermorphic queens. However, in P. (E.) pima inbreeding is probably prevented by outcrossing via males because no significant inbreeding is found. In the presented gene trees the subgenus Pogonomyrmex Ephebomyrmex was separated from the subgenus Pogonomyrmex sensu stricto. Therefore, P. Ephebomyrmex might be elevated to generic status, also due to its distinct morphological and life history characters. Nevertheless, for a precise taxonomic revision a broader complement of species has to be applied. Regularly a low number of unrelated workers was found in P. rugosus colonies, which probably stem from brood raids between mature and founding colonies. It is well known that most founding colonies are destroyed by neighboring conspecific mature colonies, but so far it was assumed that the brood of these colonies was also destroyed. This often neglected aspect might be an important fitness token for mature colonies.
Two phases of reef sampling were carried out. The first included regular samples taken along the coastline of Aqaba (27km long) at depths of 4-15m, and used to determine spatial distribution of pollution. The second phase included three 20cm-deep cores obtained from within the industrial zone. These cores were drilled from pre-dated communities, where the growth rate was determined earlier to be 10mm y-1, therefore the core obtained represented a period of 20 years (i.e. 1980-2000). The cores were used to reconstruct the metal pollution history at the most heavily used site along the coast (industrial zone).All samples were examined with respect to their metal content of Cd, Pb, Cu, Zn, Ni, and Cr. Almost all of them have shown records above the calculated background values. Mean values of Cd, Pb, Cu, Zn, Ni and Cr recorded along the coast were 1,25; 4,26; 9,76; 11,40; 2,29 and 10,522, µg g-1 respectively, and for core samples 1.4; 4.2; 5.7; 6.4; 2.3 and 8.21 µg g-1 respectively. Spatial distribution of metal enrichment in reef samples have shown a general and clear increasing trend towards the south. Same increasing trend was also in core samples where the six metals have shown a prominent increasing trend towards the core surface indicating an increase of coastal activities during the last twenty years. High and relatively high values were recorded at the oil port, the industrial area and main port, and thus categorized as highly impacted areas. Intermediate metal content were recorded in samples of the north beach, and thus classified as being relatively impacted, where the lowest metal concentrations were observed at the marine reserve, the least impacted site along the coast. The high enrichment of metal is attributed mainly to anthropogenic impacts. The natural inputs of the six metals studied in the Gulf of Aqaba are generally very low, due to the geographic positions and the absence of wadi discharge and as a result of low rainfall. Several potential sources of heavy metals were investigated. The industrial-related activities, port operations and phosphate dust were among the main sources currently threatening the marine ecosystem in Aqaba. Applying the Principle Components Analysis method (PCA) to all samples taken along the coastline has resulted in categorizing three different groups according to their metal enrichment, the first is composed of samples taken from the north beach and the main port with intermediate to high enrichment, the second joined the samples of the marine park and the marine reserve with low and relatively low enrichment, and the last group joined samples of the industrial zone and the oil port with high enrichment. The Principle Component Scores were also utilized to confirm the spatial distribution and relationships of the examined heavy metals along the coast. Two models (interpolated by SURFER  7.0 and ArcView 3.2a) were developed, the first was based on the PC scores of the first component, and shows clearly the positive anomalies in metal concentrations along the coast. The second model was developed by plotting the second factor scores on a landuse map of Aqaba. According to these models, it has shown that the positive anomalies are associated with three different zones; industrial area, the main port and the oil port. The results have shown that coral reefs can be used as good environmental indicator for assessments and monitoring processes, and they can provide data and information on both the spatial distribution of pollution and their history. The present work is the first to document the environmental status along the whole coast of Aqaba and the first to use coral reef as a tool/ indicator.
Corynebacterium glutamicum is together with C. callunae and C. efficiens a member of the diverse group of mycolic-acid containing actinomycetes, the mycolata. These bacteria are potent producer of glutamate, lysine and other amino acids on industrial scale. The cell walls of most actinomycetes contain besides an arabinogalactan-peptidoglycan complex large amounts of mycolic acids. This three-layer envelope is called MAP (mycolyl-arabinogalactan-peptidoglycan) complex and it represents a second permeability barrier beside the cytoplasmic membrane similar to the outer membrane of Gram-negative bacteria. In analogy to the situation in the outer membrane of Gram-negative bacteria, channels are present in the mycolic acid layer of the mycobacterial cell wall for the passage of hydrophilic solutes. Molecular studies have provided far-reaching findings on the amino acid flux and its balance in C. glutamicum in general, but the L-glutamate export still remains unknown. The properties of the outer layers, typical of mycolata, seem to be of major importance in this process, and diffusion seems to play a key role for this part of the cell wall. The major aim of this thesis was to identify and study novel channel-forming proteins of the amino acid producers C. glutamicum, C. callunae and C. efficiens. Cell wall extracts of the organisms were investigated and a novel pore-forming protein, named PorH, that is homologue in all three organisms, was detected and characterized. PorHC.glut was isolated from C. glutamicum cells cultivated in minimal medium. The protein was identified in lipid bilayer experiments and purified to homogeneity by fast-protein liquid chromatography across a HiTrap-Q column. The purified protein forms cation-selective channels with a diameter of about 2.2 nm and an average single-channel conductance of about 2.5 nS in 1 M KCl in the lipid bilayer assay. Organic solvent extracts were used to study the permeability properties of the cell wall of C. callunae and C.efficiens. The cell extracts contained channel-forming activity, the corresponding proteins were purified to homogeneity by fast-protein liquid chromatography across a HiTrap-Q column and named PorHC.call and PorHC.eff. Channels formed by PorHC.call are cation-selective with a diameter of about 2.2 nm and an average single-channel conductance of 3 nS, whereas PorHC.eff forms slightly anion selective channels with an average single-channel conductance of 2.3 nS in 1 M KCl in the lipid bilayer assay. The PorH proteins were partially sequenced and the corresponding genes, which were designated as porH, were identified in the published genome sequence of C. glutamicum and C. efficiens. The chromosome of C. callunae is not sequenced, but PorHC.call shows a high homology to PorHC.eff and PorHC.glut. The proteins have no N-terminal extension, only the inducer methionine, which suggests that secretion of the proteins could be very similar to that of PorAC.glut of C. glutamicum. PorHC.glut is coded in the bacterial chromosome by a gene that is localized in the vincinity of the porAC.glut gene, within a putative operon formed by 13 genes that are encoded by the minus strand. Both porins are cotranscribed and coexist in the cell wall, which was demonstrated in RT-PCR and immunological detection experiments. The arrangement of porHC.glut and porAC.glut on the chromosome is similar to that of porBC.glut and porCC.glut and it was found that PorAC.glut, PorHC.glut, PorBC.glut and PorCC.glut coexist in the cell wall of C. glutamicum. The molecular mass of about 6 kDa of the PorH channel forming proteins is rather small and suggests that the cell wall channels are formed by oligomers. A possibly hexameric form was demonstrated for PorHC.glut in Western blot analysis with anti- PorHC.glut antibodies. Secondary structure predictions for PorHC.glut, PorHC.call and PorHC.eff predict that a stretch of about 42 amino acids of PorHC.glut and 28 amino acids of PorHC.call and PorHC.eff forms amphipathic -helices with a total length of 6.3 nm and 4.2 nm respectively. This should be sufficient to cross the mycolic acid layer. Another objective of this work was to establish an heterologous expression system for corynebacterial channel-forming proteins, to investigate the channel-forming properties of the up to now only hypothetical porins PorA, PorB, PorC from C. efficiens and PorC from C. glutamicum. We could demonstrate with recombinant expression experiments in E. coli that porBC.eff and porCC.eff encode for channel-forming proteins. They are, like PorBC.glut, anion-selective with a similar single-channel conductance of 1 nS in 1 M KCl.
In a first aspect of this work, the development of photonic crystal based widely tunable laser diodes and their monolithic integration with photonic crystal based passive waveguide and coupler structures is explored theoretically and experimentally. In these devices, the photonic crystal is operated in the photonic bandgap which can be used for the realization of effective reflectors and waveguide structures. Such tunable light sources are of great interest for the development of optical network systems that are based on wavelength division multiplexing. In a second aspect of this work, the operation of a photonic crystal block near the photonic band edge is investigated with respect to the so-called superprism effect. After a few introductory remarks that serve to motivate this work, chapter 3 recapitulates some aspects of semiconductor lasers and photonic crystals that are essential for the understanding of this work so that the reader should be readily equipped with the tools to appreciate the results presented in this work.
Rhodococcus equi is a Gram-positive intracellular pathogen which can cause severe bronchopneumonia in foals. In recent years, the role of this bacterium as human pathogen has been noted, as R.equi infections in humans have increase in frequency. This increase is associated with the rise in immunosupressed individuals, specially AIDS patients, where infection leads to symptoms and pathology similar to those seen in foals with a high mortality rate. Due to its capability to survive and multiply in murine and equine macrophages, R.equi has been classified as a facultative intracellular bacterium. R.equi is found frequently in macrophages in alveolar infiltrate from infected animals. The pathogenicity of R.equi depends on its ability to exist and multiply inside macrophages and has been associated with the presence of virulence plasmids. It has been observed that, inside foal alveolar macrophages, R.equi-containing vacuoles (RCVs) do not mature into phagolysosomes. However, most of the intracellular events during R.equi infection have not been investigated in detail. The aim of this study was to elucidate the intracellular compartmentation of R.equi and the mechanism by which the bacteria avoid destruction in host macrophages. The importance of the virulence-associated plasmids of R.equi for the establishment of RCVs was also evaluated. Furthermore, the intracellular fate of viable and non-viable R.equi was compared in order to study whether viability of R.equi influeciantes the establishment of RCVs. In this study, the RCV was characterized by using a variety of endocytic markers to follow the path of the bacteria trhough murine macropages. Transmission electron microscopy-base analysis showed that R.equi was found equally frequently in phagosomes with loosely or thightly apposed membranes, and RCV often contains numerous membranous vesicles. Laser scanning microscopy of infected macrophages showed that the majority of phagosomes containing R.equi acquired transiently the early endosomal markers Rab5, Ptlns3P, and EEA-1, suggesting initially undisturbed phagosome maturation. Although the RCV acquired some late endosomal markers, such as Rab7, LAMP-1, and Lamp-2, they did not acquired vATPase, did not interact with pre-labeled lysosomes, and failed to acidify. These data clearly suggest that the RCV is a compartment which has left vacuoles that resemble multivesicular body compartments (MVB), which are transport intermediates between early and late endosomes and display internal vesicles very similar to the ones observed within RCVs. Analyisis of several R.equi strains containing either VapA- or VapB-expressing plasmids or neither demonstrated that the possession of the virulence-associated plasmids does not affect phagosome trafficking over a two hour period of infection. The finding that non-viable R.equi was still able to inhibit phagosome maturation (although not to the same extent as viable R.equi did) suggests that heat-insensitive factors, such as cell periphery lipids, may play a major role in inhibition of phagosome maturation, although heat-sensitive factors may also be involved.
Nonlinear frequency conversion of low-energy fs laser pulses was investigated in solid-state media. Raman conversion in the white-light-free regime of impulsive stimulated Raman scattering was achieved by pumping KGW crystal with Bessel beam. Efficient supercontinuum generation was demonstrated for sub-microjule pulses focused into microstructure fiber. Application of four-wave mixing techniques to monitoring of the excited-state dynamics in polyatomic molecules was demonstrated. Time constants of the processes related to vibrational energy redistribution upon the initial photoexcitation of stilbene-3 were determined by means of pump-CARS technique, where CARS process served as an effective mode-selective filter. Spectral as well as temporal properties of electronic relaxation pathway in azulene derivatives were explored by using transient population gratings and pump-probe transient absorption techniques.
Very small, thioglycerol (TG)-capped CdS nanoparticles were synthesized by a wet chemical technique and investigated in the framework of this thesis. Also glutathione-capped particles were investigated for a comparison of the capping agents. High-resolution photoelectron spectroscopy using high-brilliance synchrotron radiation was applied as the major tool for the characterization of these particles. Additionally, the particles were investigated with UV-VIS absorption spectroscopy, XPS using a laboratory source, valence band photoemission spectroscopy (VBPES), near-edge x-ray absorption spectroscopy (NEXAFS), and micro-Raman spectroscopy to address various aspects of the particles. In the beginning, an overview on size quantization effects is given to create a theoretical background behind the work presented in this thesis. Furthermore, an overview of various conventional techniques for size determination is presented. Exact information about size, shape and size distribution of nanoparticles is not yet achievable because of experimental limitations of the various size determination methods. Nanoparticles, with a range of sizes from 1.1 to 4. 2 nm, were synthesized using non-aqueous preparation and a TG capping. It is demonstrated that the use of the non-aqueous wet chemical synthesis method enables the production of very small particles and prohibits the aging of the particles. Furthermore, TG capping leads to a significant improvement for a narrow size distribution. Moreover, the results are very reproducible with TG capping and non-aqueous synthesis. Monodispersed particles can be produced by a size selective precipitation method, however, the reproducibility is questionable due to the aqueous medium of the synthesis in this case. High-resolution photoemission measurements on the small particles, i.e., 1.1 nm (CdS-A), 1.4 nm (CdS-B), 1.7 nm (CdS-C), and 1.8 nm (CdS-D, glutathione-capped), revealed five components as constituents of the S 2p signal after a careful data evaluation. Furthermore, it was observed that the particles with different sizes and capping show differences in the photoemission spectra and also in the beam damage behaviour. The different components of CdS-B were assigned as S atoms with different Cd neighbors, S atoms from thiol and S atoms in a partially oxidized state, based on the observed intensity changes of these components as a function of photon energy and beam damage, and on previous photoemission work on CdS nanoparticles [23, 45]. Furthermore, it was found that this assignment cannot be directly transferred to other particles. A new approach of structural model-based photoemission intensity calculations in comparison with the experimental data is presented. This enables us to understand subtle features in the photoemission spectra, in particular the intensity changes of the different components as a function of photon energy and beam exposure. This approach is especially applied to CdS-B (as some structural information for this particle is avialable from XRD), using three different structural models. It is found that a structural model with 33 S atoms can explain the experimental intensity changes of CdS-B. Furthermore, it is found that the photoemission spectra can be used to determine the particle size indirectly, as other plausible models show significant deviation from the experimental data. To study the various aspects by calculations, such as the influence of the particle shape and of the value of the mean free path, a program developed with L. Weinhardt and O. Fuchs is used for the intensity calculations. In order to determine a reasonable value of the mean free path for the used photon energies, two different equations from previous reports (Seah et al. and Powell et al.) are applied. As average mean free path values for the two photon energies we chose 5.5 ± 2 Å (254 eV) and 14 ± 2 Å (720 eV). The program calculation confirms the result of simple “manual” calculations of the different models. Moreover, it is tested that the value of , used in the calculations does not produce any significant influence on the calculation results. Another interesting feature is derived from the calculations that a model with a rather round shape produces similar intensity ratios for the different components to those of the data. Thus this new approach of analysis of photoemission spectra offers a way to determine particle sizes and to some extent to give an impression of the approximate particle shape. Furthermore, it is observed that the electronic band gap is larger compared to the optical band gap, which was attributed to an enhanced electron-hole correlation for optical absorption in small particles. The XPS experiments performed in the laboratory using an x-ray tube, show that the thin films produced from a freshly synthesized nanoparticle solution are fairly homogeneous and non-charging. Moreover, annealing experiments indicated that TG-capped particles posses less thermal stability as compared to MPA-capped particles. It was demonstrated that beam-induced effects play a major role. However, the knowledge of the time scale for such effects gives the possibility to record photoemission spectra with fairly good signal quality and to extrapolate to zero radiation damage. Further, particles with different sizes and capping show different beam damage behaviour. The thin film preparation by electrophoresis results in significant changes in the spectrum indicating agglomeration, while the drop-deposition technique points towards spectral changes on the rim of the sample, which can be avoided by focusing the radiation to the centre of the deposited dried drop. Micro-Raman experiments carried out in collaboration with C. Dem, Dr. M. Schmitt and Prof. W. Kiefer exhibited major differences in the spectra of nanoparticles as compared to those of the capping molecule thioglycerol. For instance, the absence of the S-H vibrational modes indicates the consumption or removal of all unreacted capping molecules. There is definitely a need for further detailed investigations concerning various interesting aspects of this work. For instance, it would be of significance to extend the program calculations to more models. Also more information about the band gap opening has to be gathered in order to find out the reason for the larger electronic band gap as compared to the optical band gap. The photoemission analysis approach using a model calculation has to be extended to differently prepared nanoparticles, in particular, to address the differences in the location of the various species in the particle as a function of preparation. The efforts of XRD simulations by C. Kumpf et al. [50] may reveal significant new information about the particle size and the size distribution. It can be expected that the program calculations, if extended to more models, can prove the potential of photoelectron spectroscopy to serve as a tool for size and shape determination of nanoparticles, which is a new contribution to the investigation of nanoparticles.
Within the studies concerning metallo-silanols, halfsandwich-tungsten complexes have been silanol-functionalized at the cyclopentadienyl ligand. The stability and the condensation behavior have been investigated. Thus, it was shown that these complexes are stable enough for isolation but they are reactiv enough for time-effective condensation reactions with diverse chlorosilanes, chlorostannanes or metalhalogenides. These processes are characterized by an increased reactivity in contrast to metallo-silanols with a direct metal-bonded silanol group and proves that the separation of the silanol group has to be regarded as a successful manipulation. In addition, this modification allows a wide variation of the ligand sphere of the metal which was shown by H/Cl exchange, methylation, silylation or phosphine substitution. These changes evoke a small but significant influence on the silanol group. For example leads an introduced phosphine to an enhanced stability of the silanol function. A further separation of the silanol group from the metal by an additional alkylidene spacer leads to the complete lost of the stabilizing effect of the metal fragment and generates silanols which show a condensation behavior very similar to those of ordinary organosilanols.
Protein kinase B (PKB), a serine threonine kinase, is highly involved in the regulation of cellular proliferation and survival. To characterize PKB’s function in lymphocyte development and activation, transgenic (tg) mice that express a membrane targeted constitutively active form of PKBa (myr PKB) in T and B cells were analysed. Thymocytes from myr PKB tg mice showed enhanced proliferation after T cell receptor (TCR) engagement compared to wild type (wt) mice. Astonishingly, myr PKB tg thymocytes were capable to proliferate in response to PMA only and were also less sensitive to inhibition by the calcineurin inhibitors CsA or FK506, which indicates the proliferative response of myr PKB tg T cells is relatively independent of calcium mobilisation and calcineurin activity. In addition, when TCR signalling was inhibited by the MEKinase inhibitor PD98059 or the Srckinase inhibitor PP1 myr PKB tg thymocytes again were more resistant to inhibition. Western blot analysis revealed myr PKB enhances activation of the kinases Lck, Raf and Erk after TCR/CD3 stimulation. Thus, myr PKB renders proliferative responses of thymocytes more sensitive to TCR signals by positive regulation of the Lck-Raf-MEK-Erk signalling pathway. Studies on the cellular location of the tg protein showed myr PKB is located in membrane socalled “lipid rafts”. Furthermore, we found that after TCR/CD3 ligation endogenous cytoplasmic PKB moves into “lipid rafts”, which highlights PKB as a crucial mediator of TCR proximal signalling events. Analysing three different TCR tg model systems for positive and negative selection of immature precursors in the thymus, we found myr PKB promotes positive selection of CD4+ but not CD8+ T cells. This most likely results from PKB’s positive cross-talk on Lck-Raf-Erk signalling, which is known to influence thymocyte selection and CD4/CD8-lineage choice. Furthermore, myr PKB enhances phosphorylation of glycogen synthase kinase 3 (GSK3), a negative regulator of the transcription factor NFAT (nuclear factor of activated T cells) and T cell activation, and of the adapter protein c-Cbl. Concerning negative selection, myr PKB enhanced (OT1 mice), reduced (HY mice) or had no influence (OT2 mice) on negative selection. Thus, myr PKB’s effect on negative selection strongly depends on the model system analysed and this most likely results from differences in TCR affinity/avidity and TCR specificity for MHC. 106 Peripheral CD4+ T cells from myr PKB tg mice showed enhanced production of both Th1 and Th2 cytokines. Furthermore, after TCR/CD3 stimulation in the presence of TGF-b1, wt CD4+ T cells showed a drastic inhibition of proliferation, whereas myr PKB tg CD4+ T cells proliferated even better, i.e. they were resistant to the inhibitory TGF-b1 signals. Expression of myr PKB in B cells leads to reduced Ca2+ flux and proliferation after BCR stimulation, but activation of Lyn, SLP-65, c-Cbl and GSK-3 were enhanced. When we analysed B cell subsets in myr PKB tg mice, a decrease in immature and mature B cells became obvious, whereas cell numbers for marginal zone (MZ) B cells were normal. In aged myr PKB tg mice we detected a very strong reduction of pro/pre and immature B cell populations in the bone marrow, indicating PKB is very important for maintenance of B cell development. Furthermore, myr PKB also lead to a strong reduction of peritoneal B-1 cells. However, expression of NFATc1, which is required for B-1 cell development, was comparable between wt and myr PKB tg B-1 cells. To analyse the effect of myr PKB on immunoglobulin production, mice were immunized with thymus dependent (TD) and independent (TI) antigens. In both cases, B cell responses were strongly elevated in myr PKB tg mice. Finally, RT-PCR analyses of in vitro expanded B cells revealed increased Blimp-1 and Notch3 expression in myr PKB tg B cells, which might be primary candidates involved in their enhanced effector function. In summary, this study clearly shows an important cross-talk between PKB and various critical signalling molecules downstream of the TCR and BCR. Thereby active PKB modulates and regulates the thresholds for thymocyte selection and T cell activation as well as for B cell development and function.