Anatomy, phylogeny, and palaeoecology of the basal thalattosuchians (Mesoeucrocodylia) from the Liassic of Central Europe

In the marine Jurassic deposits of Europe, a group of marine crocodilians, the Thalattosuchia, belongs to the frequently found reptiles. Thalattosuchia are widely spread in Central Europe from the Jurassic to Lower Cretaceous, and some taxa are also distributed worldwide. The task of the work was to examine all taxa known from the Liassic of Europe. The most frequently known taxa Steneosaurus bollensis and Pelagosaurus typus are anatomically revised. New discoveries at the skull of Pelagosaurus typus e.g., the fact of a partly paired frontal are described by means of computed tomography investigations. In addition, juvenile specimens of this taxon are studied in detail for the first time. The rarely occurring taxon Platysuchus multiscrobiculatus is anatomically described in detail for the first time. It shows both in the skull and in the postcranial material morphological differences to Steneosaurus bollensis and Pelagosaurus typus. Thus Pl. multiscrobiculatus possesses, e.g., an ilium with a deeper acetabulum and a femur with a distinctly flexed femoral head. A juvenile specimen of Pl. multiscrobiculatus is now discovered and is described in parts for the first time, too. Furthermore, Steneosaurus gracilirostris and Steneosaurus brevior known from Lower Jurassic deposits of England are examined and in parts revised. In this work, Steneosaurs brevior is discovered with one specimen from the Upper Liassic of Holzmaden, Germany for the first time, and provides new evidence for the palaeobiogeographical distribution of the taxon. Because of the high number of investigated specimens, it is possible to study ontogenetic development from juvenile to adult stage in Steneosaurus bollensis, Pelagosaurus typus, and Platysuchus multiscrobiculatus. Biometric data are collected from thalattosuchians and extant crocodilians (e.g. Gavialis gangeticus) to investigate intraspecific variation, ontogenetic development, and taxa differentiation. The skulls of Platysuchus multiscrobiculatus and Steneosaurus bollensis are reconstructed three-dimensionally as wax models. The skull reconstructions form the basis of the jaw muscle restoration of Steneosaurus bollensis in connection with comparative studies at extant crocodilians. By means of functional morphologic analysis of the jaw musculature, the dentition, and the locomotor system of S. bollensis, possible conclusions are drawn for the prey options and the hunting behaviour. To clarify the relationships within the Thalattosuchia, a computer-based cladistic phylogenetic in-group analyse of 25 Thalattosuchia taxa is performed. For the analysis, following Thalattosuchia taxa are studied likewise at original material for comparisons: Metriorhynchus superciliosus, Metriorhynchus hastifer, Metriorhynchus leedsi, Geosaurus gracilis, Geosaurus giganteus, Teleidosaurus calvadosi, Teleidosaurus gaudryi, Teleosaurus cadomensis, Teleosaurus geoffroyi, Steneosaurus priscus, Steneosaurus edwardsi, Steneosaurus heberti, Steneosaurus leedsi, Steneosaurus boutilieri, Steneosaurus megarhinus, Steneosaurus obtusidens, and Machimosaurus hugii. The phylogenetic in-group analyse based on 115 characters, reveals a sister-group relationship of the monophyletic Teleosauridae and monophyletic Metriorhynchidae. Within the groups, some taxa are probably paraphyletic. The taxon Pelagosaurus typus is nested inside the Teleosauridae and not outside or within the Metriorhynchidae, as many authors suggested it so far. Based on these results, a tentative palaeobiogeographical-evolutionary scenario is developed.

Imiquimod based transcutaneous immunization – insights and novel concepts

This work aims at developing a transcutaneous immunization (TCI) approach in order to activate cytotoxic T-cells. A tumor specific immune response was therefore generated by the TLR7-Agonist imiquimod. Five commercially available creams including the innovators product Aldara® 5% creme were assessed to ascertain their capability to induce an immune response in C57BL/6 mice after dermal administration. Moreover, creams were investigated regarding their imiquimod permeation in a Franz-diffusion cell model. Results obtained from this study were used to develop novel formulation approaches based on dissolved state imiquimod in a submicron scale range. High pressure homogenization ensured emulsification as well as particle size reduction. A freeze dried spreadable solid nanoemulsion based on sucrose fatty acid esters and oil components represented a major formulation approach. Within the scope of this approach the influence of pharmaceutical oils i.e. middle chain triglycerides, avocado oil, jojoba wax, and squalen was assessed towards their TCI performance. Furthermore, an aqueous jojoba wax based emulsion gel was developed. Unlike the innovators product, all formulations demonstrated a distinctly reduced imiquimod permeation across murine skin, a fact particularly evident in case of jojoba wax. Squalen significantly augmented in vivo immune response (p≤0.05 Mann-Whitney-Test). The emulsion gel demonstrated a 10fold decrease of imiquimod permeation. In comparison with the innovators product, the emulsion gel induced an equal immune response with a simultaneously enhanced tumor rejection in a mouse model.