@misc{VolckmarHanPuetteretal.2016, author = {Volckmar, Anna-Lena and Han, Chung-Ting and P{\"u}tter, Carolin and Haas, Stefan and Vogel, Carla I. G. and Knoll, Nadja and Struve, Christoph and G{\"o}bel, Maria and Haas, Katharina and Herrfurth, Nikolas and Jarick, Ivonne and Grallert, Harald and Sch{\"u}rmann, Annette and Al- Hasani, Hadi and Hebebrand, Johannes and Sauer, Sascha and Hinney, Anke}, title = {Analysis of genes involved in body weight regulation by targeted re-sequencing}, series = {PLoS ONE}, journal = {PLoS ONE}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-410289}, pages = {16}, year = {2016}, abstract = {Introduction Genes involved in body weight regulation that were previously investigated in genome-wide association studies (GWAS) and in animal models were target-enriched followed by massive parallel next generation sequencing. Methods We enriched and re-sequenced continuous genomic regions comprising FTO, MC4R, TMEM18, SDCCAG8, TKNS, MSRA and TBC1D1 in a screening sample of 196 extremely obese children and adolescents with age and sex specific body mass index (BMI) >= 99th percentile and 176 lean adults (BMI <= 15th percentile). 22 variants were confirmed by Sanger sequencing. Genotyping was performed in up to 705 independent obesity trios (extremely obese child and both parents), 243 extremely obese cases and 261 lean adults. Results and Conclusion We detected 20 different non-synonymous variants, one frame shift and one nonsense mutation in the 7 continuous genomic regions in study groups of different weight extremes. For SNP Arg695Cys (rs58983546) in TBC1D1 we detected nominal association with obesity (p(TDT) = 0.03 in 705 trios). Eleven of the variants were rare, thus were only detected heterozygously in up to ten individual(s) of the complete screening sample of 372 individuals. Two of them (in FTO and MSRA) were found in lean individuals, nine in extremely obese. In silico analyses of the 11 variants did not reveal functional implications for the mutations. Concordant with our hypothesis we detected a rare variant that potentially leads to loss of FTO function in a lean individual. For TBC1D1, in contrary to our hypothesis, the loss of function variant (Arg443Stop) was found in an obese individual. Functional in vitro studies are warranted.}, language = {en} } @article{EngeliLehmannKaminskietal.2014, author = {Engeli, Stefan and Lehmann, Anne-Christin and Kaminski, Jana and Haas, Verena and Janke, Urgen and Janke, J{\"u}rgen and Zoerner, Alexander A. and Luft, Friedrich C. and Tsikas, Dimitrios and Jordan, Jens}, title = {Influence of dietary fat intake on the endocannabinoid system in lean and obese subjects}, series = {Obesity}, volume = {22}, journal = {Obesity}, number = {5}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1930-7381}, doi = {10.1002/oby.20728}, pages = {E70 -- E76}, year = {2014}, abstract = {Objective: Endocannabinoid system (ECS) activation promotes obesity-associated metabolic disease. Increased dietary fat intake increases blood endocannabinoids and alters adipose and skeletal muscle ECS gene expression in human. Methods: Two weeks isocaloric low- (LFD) and high-fat diets (HFD) in obese (n = 12) and normal- weight (n = 17) subjects in a randomized cross-over study were compared. Blood endocannabinoids were measured in the fasting condition and after food intake using mass spectrometry. Adipose and skeletal muscle gene expression was determined using real-time RT-PCR. Results: Baseline fasting plasma endocannabinoids were similar with both diets. Anandamide decreased similarly with high- or low-fat test meals in both groups. Baseline arachidonoylglycerol plasma concentrations were similar between groups and diets, and unresponsive to eating. In subcutaneous adipose tissue, DAGL-alpha mRNA was upregulated and fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) mRNAs were down-regulated in obese subjects, but the diets had no influence. In contrast, the HFD produced pronounced reductions in skeletal muscle CB1-R and MAGL mRNA expression, whereas obesity did not affect muscular gene expression. Conclusions: Weight-neutral changes in dietary fat intake cannot explain excessive endocannabinoid availability in human obesity. Obesity and dietary fat intake affect ECS gene expression in a tissue-specific manner.}, language = {en} } @article{KottmeierAgnonAlHalbounietal.2016, author = {Kottmeier, Christoph and Agnon, Amotz and Al-Halbouni, Djamil and Alpert, Pinhas and Corsmeier, Ulrich and Dahm, Torsten and Eshel, Adam and Geyer, Stefan and Haas, Michael and Holohan, Eoghan and Kalthoff, Norbert and Kishcha, Pavel and Krawczyk, Charlotte and Lati, Joseph and Laronne, Jonathan B. and Lott, Friederike and Mallast, Ulf and Merz, Ralf and Metzger, Jutta and Mohsen, Ayman and Morin, Efrat and Nied, Manuela and Roediger, Tino and Salameh, Elias and Sawarieh, Ali and Shannak, Benbella and Siebert, Christian and Weber, Michael}, title = {New perspectives on interdisciplinary earth science at the Dead Sea: The DESERVE project}, series = {The science of the total environment : an international journal for scientific research into the environment and its relationship with man}, volume = {544}, journal = {The science of the total environment : an international journal for scientific research into the environment and its relationship with man}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0048-9697}, doi = {10.1016/j.scitotenv.2015.12.003}, pages = {1045 -- 1058}, year = {2016}, abstract = {The Dead Sea region has faced substantial environmental challenges in recent decades, including water resource scarcity, similar to 1 m annual decreases in the water level, sinkhole development, ascending-brine freshwater pollution, and seismic disturbance risks. Natural processes are significantly affected by human interference as well as by climate change and tectonic developments over the long term. To get a deep understanding of processes and their interactions, innovative scientific approaches that integrate disciplinary research and education are required. The research project DESERVE (Helmholtz Virtual Institute Dead Sea Research Venue) addresses these challenges in an interdisciplinary approach that includes geophysics, hydrology, and meteorology. The project is implemented by a consortium of scientific institutions in neighboring countries of the Dead Sea (Israel, Jordan, Palestine Territories) and participating German Helmholtz Centres (KIT, GFZ, UFZ). A new monitoring network of meteorological, hydrological, and seismic/geodynamic stations has been established, and extensive field research and numerical simulations have been undertaken. For the first time, innovative measurement and modeling techniques have been applied to the extreme conditions of the Dead Sea and its surroundings. The preliminary results show the potential of these methods. First time ever performed eddy covariance measurements give insight into the governing factors of Dead Sea evaporation. High-resolution bathymetric investigations reveal a strong correlation between submarine springs and neo-tectonic patterns. Based on detailed studies of stratigraphy and borehole information, the extension of the subsurface drainage basin of the Dead Sea is now reliably estimated. Originality has been achieved in monitoring flash floods in an arid basin at its outlet and simultaneously in tributaries, supplemented by spatio-temporal rainfall data. Low-altitude, high resolution photogrammetry, allied to satellite image analysis and to geophysical surveys (e.g. shear-wave reflections) has enabled a more detailed characterization of sinkhole morphology and temporal development and the possible subsurface controls thereon. All the above listed efforts and scientific results take place with the interdisciplinary education of young scientists. They are invited to attend joint thematic workshops and winter schools as well as to participate in field experiments. (C) 2015 The Authors. Published by Elsevier B.V.}, language = {en} }