University of Konstanz

About: University of Konstanz is a education organization based out in Konstanz, Baden-Württemberg, Germany. It is known for research contribution in the topics: Population & Membrane. The organization has 12115 authors who have published 27401 publications receiving 951162 citations. The organization is also known as: University of Constance & Universität Konstanz.

Toxicity Testing in the 21st Century: Progress in the Past Decade and Future Perspectives

Abstract: Advances in the biological sciences have led to an ongoing paradigm shift in toxicity testing based on expanded application of high-throughput in vitro screening and in silico methods to assess potential health risks of environmental agents. This review examines progress on the vision for toxicity testing elaborated by the US National Research Council (NRC) during the decade that has passed since the 2007 NRC report on Toxicity Testing in the 21st Century (TT21C). Concomitant advances in exposure assessment, including computational approaches and high-throughput exposomics, are also documented. A vision for the next generation of risk science, incorporating risk assessment methodologies suitable for the analysis of new toxicological and exposure data, resulting in human exposure guidelines is described. Case study prototypes indicating how these new approaches to toxicity testing, exposure measurement, and risk assessment are beginning to be applied in practice are presented. Overall, progress on the 20-year transition plan laid out by the US NRC in 2007 has been substantial. Importantly, government agencies within the United States and internationally are beginning to incorporate the new approach methodologies envisaged in the original TT21C vision into regulatory practice. Future perspectives on the continued evolution of toxicity testing to strengthen regulatory risk assessment are provided.

Geometric morphometric analyses provide evidence for the adaptive character of the tanganyikan cichlid fish radiations

Abstract: The cichlids of East Africa are renowned as one of the most spectacular examples of adaptive radiation. They provide a unique opportunity to investigate the relationships between ecology, morphological diversity, and phylogeny in producing such remarkable diversity. Nevertheless, the parameters of the adaptive radiations of these fish have not been satisfactorily quantified yet. Lake Tanganyika possesses all of the major lineages of East African cichlid fish, so by using geometric morphometrics and comparative analyses of ecology and morphology, in an explicitly phylogenetic context, we quantify the role of ecology in driving adaptive speciation. We used geometric morphometric methods to describe the body shape of over 1000 specimens of East African cichlid fish, with a focus on the Lake Tanganyika species assemblage, which is composed of more than 200 endemic species. The main differences in shape concern the length of the whole body and the relative sizes of the head and caudal peduncle. We investigated the influence of phylogeny on similarity of shape using both distance-based and variance partitioning methods, finding that phylogenetic inertia exerts little influence on overall body shape. Therefore, we quantified the relative effect of major ecological traits on shape using phylogenetic generalized least squares and disparity analyses. These analyses conclude that body shape is most strongly predicted by feeding preferences (i.e., trophic niches) and the water depths at which species occur. Furthermore, the morphological disparity within tribes indicates that even though the morphological diversification associated with explosive speciation has happened in only a few tribes of the Tanganyikan assemblage, the potential to evolve diverse morphologies exists in all tribes. Quantitative data support the existence of extensive parallelism in several independent adaptive radiations in Lake Tanganyika. Notably, Tanganyikan mouthbrooders belonging to the C-lineage and the substrate spawning Lamprologini have evolved a multitude of different shapes from elongated and Lamprologus-like hypothetical ancestors. Together, these data demonstrate strong support for the adaptive character of East African cichlid radiations.

Near-infrared dyes and fluorophores based on diketopyrrolopyrroles.

Abstract: Our research activities over the last few decades have concerned correlations between molecular structure and fluorescence. 2] A central theme of the research has been the synthesis and spectroscopic investigations of near-infrared (NIR) dyes to get insights into what degree the obtainable fluorescence quantum yields are restricted by the S0$S1 energy gap. Our results on the condensation of 1,4phthalazinediones with heteroarylacetonitriles in POCl3 prompted us to carry out the reaction with diketopyrrolopyrroles (DPPs) 1. Herein we report the results of the investigations. To date, attempts to activate the carbonyl group of DPPs with POCl3, and to subsequently convert the intermediates with nucleophiles, only led to monosubstitution or to ring opening. 10] The reaction of 1 and 2 in refluxing toluene with an excess of POCl3 according to Scheme 1 afforded disubstituted NIR dyes 3. The progress of the reaction was controlled by recording absorption spectra and stopping the heating as soon as the DPP was used up and/or products absorbing at short wavelengths appeared. Purification was carried out by digesting the product in acetone and subsequent flash chromatography (silica gel/CHCl3 or CH2Cl2). The NIR dyes 3a–3h (the structures and spectroscopic data of 3b–3h can be found in the Supporting Information) were synthesized according to this procedure (Scheme 1) from the reaction of 1 and 2. The course of the reactions was the same in all cases and side-products with strong absorptions below 350 nm were observed. These side-products are most likely compounds formed by the opening of the DPPs pentalene ring system. Prerequisite for the reactions is a certain solubility of the DPPs. This is a feature of all of the DPPs used here with the exception of the 4-methoxy derivative 1b. Remarkably, the 4(N-methyl-N-octyl amino) derivative 1e has a much better solubility than all the other DPPs used. Only in the case of the reaction of 1e with 2a were we able to isolate the 1:1 condensation product (13% yield). The heteroarylacetonitriles 2a and 2b substituted with a tert-butyl group were used to improve the solubility of the condensation products 3. In general, satisfying yields were obtained only if the solubility of both condensation partners was improved by having longer alkyl groups (Table 1). From these observations we draw the following conclusion concerning the reaction pathway: DPP reacts with POCl3 to form a monophosphorylated intermediate, which reacts with the Scheme 1. Reagents and conditions: a) absolute toluene/POCl3, reflux; b) 1,2-dichlorobenzene/BF3·Et2O, reflux, diisopropylethylamine; c) xylene/chlorodiphenylborane, reflux; DPPs 1: R=4-octyloxy (1a), R=4-methoxy (1b), R=4-butyloxy (1c), R=4-(hex-5-enyloxy) (1d), R=4-(N-methyl-N-octylamino) (1e); heteroarylacetonitriles 2 : 2-(6tert-butylquinolin-2-yl)acetonitrile (2a), 2-(6-tert-butylbenzothiazol-2yl)acetonitrile (2b), 2-(quinoxalin-2-yl)acetonitrile (2c), 2-(6-methylpyridin-2-yl)acetonitrile (2d). A: aromatic ring.

Radiation induced apoptosis.

Abstract: The response to ionising radiation, in terms of level of cell killing, depends on a number of factors that may be grouped into those that are genetically controlled, radiation quality and dosage, and environmental factors. There is a range of genetically controlled cellular properties such as stage of differentiation, mutations in specific genes (such as p53 and bcl-2) and stage of transformation that will determine the ability of the target cell to enter apoptosis. The so-called normal cells, are usually more radiosensitive and the majority of the cell population will enter into an apoptotic death. However, in response to high doses of ionising radiation and complex DNA damage as produced by high-LET radiation, an increased fraction of these cells will die by necrosis. There are several examples of environmental factors with relevance for the combined action of radiation and xenobiotics on carcinogenesis and in tumour therapy. In the case of normal cells, agents such as growth factors and tumour promoters, may decrease radiosensitivity. For certain type of tumour cells, radiation sensitivity can be increased in the presence of agents such as hormones, and the cells may die an apoptotic death. Removal of heavily compromised cells is essential to prevent a potential spreading of mutated clones. However, if apoptosis is inhibited (e.g., by tumour promoter), an increased fraction of damaged cells carrying genotoxic lesions may survive. This would significantly increase the risk of proliferation of precancerous cells. As discussed above, it is probably incorrect to make predictions about relative radiosensitivity based solely on mode of death. Intrinsic characteristics deriving from the cell type of origin of a line may be more important in determining radiosensitivity. The rapidly increasing knowledge about the process of radiation induced apoptosis has opened new frontiers in radiation biology, genetic toxicology, and cancer therapy and strongly motivates further research in this field.