TY - JOUR A1 - Scheer, Nico A1 - Mclaughlin, Lesley A. A1 - Rode, Anja A1 - MacLeod, Alastair Kenneth A1 - Henderson, Colin J. A1 - Wolf, Roland C. T1 - Deletion of thirty murine cytochrome P450 genes results in viable mice with compromised drug metabolism JF - Drug Metabolism and Disposition N2 - In humans, 75% of all drugs are metabolized by the cytochrome P450-dependent monooxygenase system. Enzymes encoded by the CYP2C, CYP2D, and CYP3A gene clusters account for ∼80% of this activity. There are profound species differences in the multiplicity of cytochrome P450 enzymes, and the use of mouse models to predict pathways of drug metabolism is further complicated by overlapping substrate specificity between enzymes from different gene families. To establish the role of the hepatic and extrahepatic P450 system in drug and foreign chemical disposition, drug efficacy, and toxicity, we created a unique mouse model in which 30 cytochrome P450 genes from the Cyp2c, Cyp2d, and Cyp3a gene clusters have been deleted. Remarkably, despite a wide range of putative important endogenous functions, Cyp2c/2d/3a KO mice were viable and fertile, demonstrating that these genes have evolved primarily as detoxification enzymes. Although there was no overt phenotype, detailed examination showed Cyp2c/2d/3a KO mice had a smaller body size (15%) and larger livers (20%). Changes in hepatic morphology and a decreased blood glucose (30%) were also noted. A five-drug cocktail of cytochrome P450 isozyme probe substrates were used to evaluate changes in drug pharmacokinetics; marked changes were observed in either the pharmacokinetics or metabolites formed from Cyp2c, Cyp2d, and Cyp3a substrates, whereas the metabolism of the Cyp1a substrate caffeine was unchanged. Thus, Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the P450 system in drug metabolism and efficacy, as well as in chemical toxicity. Y1 - 2014 U6 - http://dx.doi.org/10.1124/dmd.114.057885 SN - 1521-009X VL - 42 IS - 6 SP - 1022 EP - 1030 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Vögele, Stefan A1 - Rübbelke, Dirk A1 - Govorukha, Kristina A1 - Grajewski, Matthias T1 - Socio-technical scenarios for energy-intensive industries: the future of steel production in Germany JF - Climatic Change Y1 - 2019 U6 - http://dx.doi.org/10.1007/s10584-019-02366-0 SN - 0165-0009 SP - 1 EP - 16 PB - Springer CY - Berlin ER - TY - JOUR A1 - Campen, R. A1 - Kowalski, Julia A1 - Lyons, W.B. A1 - Tulaczyk, S. A1 - Dachwald, Bernd A1 - Pettit, E. A1 - Welch, K. A. A1 - Mikucki, J.A. T1 - Microbial diversity of an Antarctic subglacial community and high‐resolution replicate sampling inform hydrological connectivity in a polar desert JF - Environmental Microbiology Y1 - 2019 U6 - http://dx.doi.org/10.1111/1462-2920.14607 SN - 1462-2920 IS - accepted article PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Lyons, W. Berry A1 - Mikucki, Jill A. A1 - German, Laura A. A1 - Welch, Kathleen A. A1 - Welch, Susan A. A1 - Gardener, Christopher B. A1 - Tulaczyk, Slawek M. A1 - Pettit, Erin C. A1 - Kowalski, Julia A1 - Dachwald, Bernd T1 - The Geochemistry of Englacial Brine from Taylor Glacier, Antarctica JF - Journal of Geophysical Research: Biogeosciences Y1 - 2019 U6 - http://dx.doi.org/10.1029/2018JG004411 SN - 2169-8961 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Funke, Harald A1 - Beckmann, Nils A1 - Abanteriba, Sylvester T1 - An overview on dry low NOx micromix combustor development for hydrogen-rich gas turbine applications JF - International Journal of Hydrogen Energy Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.ijhydene.2019.01.161 SN - 0360-3199 VL - 44 IS - 13 SP - 6978 EP - 6990 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Breuer, Lars A1 - Pilas, Johanna A1 - Guthmann, Eric A1 - Schöning, Michael Josef A1 - Thoelen, Ronald A1 - Wagner, Torsten T1 - Towards light-addressable flow control: responsive hydrogels with incorporated graphene oxide as laser-driven actuator structures within microfluidic channels JF - Sensor and Actuators B: Chemical Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.snb.2019.02.086 SN - 0925-4005 VL - 288 SP - 579 EP - 585 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Jung, Alexander A1 - Müller, Wolfram A1 - Staat, Manfred T1 - Optimization of the flight technique in ski jumping: the influence of wind Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.jbiomech.2019.03.023 IS - Early view PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Klubert, Joachim A1 - Malecha, Hartmut A1 - Sparla, Peter T1 - Modernisierung der geodätischen Messtechnik der Urfttalsperre JF - Wasserwirtschaft T2 - Modernisation of the geodetic measurement technology of the Urft dam Y1 - 2018 SN - 0043-0978 N1 - gedruckt in der Bereichsbibliothek Bayernallee vorhanden VL - 108 IS - 10 SP - 14 EP - 18 PB - Springer Vieweg CY - Wiesbaden ER - TY - JOUR A1 - Scheer, Nico A1 - Henderson, Colin James A1 - Kapelyukh, Yury A1 - Rode, Anja A1 - Mclaren, Aileen W. A1 - MacLeod, Alastair Kenneth A1 - Lin, De A1 - Wright, Jayne A1 - Stanley, Lesley A1 - Wolf, C. Roland T1 - An extensively humanised mouse model to predict pathways of drug disposition, drug/drug interactions, and to facilitate the design of clinical trials JF - Drug Metabolism and Disposition Y1 - 2019 U6 - http://dx.doi.org/10.1124/dmd.119.086397 IS - Early view ER - TY - JOUR A1 - Jan Thimo, Grundmann A1 - Bauer, Waldemar A1 - Biele, Jens A1 - Boden, Ralf A1 - Ceriotti, Matteo A1 - Cordero, Federico A1 - Dachwald, Bernd A1 - Dumont, Etienne A1 - Grimm, Christian D. A1 - Hercik, David T1 - Capabilities of Gossamer-1 derived small spacecraft solar sails carrying Mascot-derived nanolanders for in-situ surveying of NEAs JF - Acta Astronautica Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.actaastro.2018.03.019 SN - 0094-5765 VL - 156 IS - 3 SP - 330 EP - 362 PB - Elsevier CY - Amsterdam ER -