TY - JOUR A1 - Luisier, Raphaëlle A1 - Lempiäinen, Harri A1 - Scherbichler, Nina A1 - Braeuning, Albert A1 - Geissler, Miriam A1 - Dubost, Valerie A1 - Müller, Arne A1 - Scheer, Nico A1 - Chibout, Salah-Dine A1 - Hara, Hisanori A1 - Picard, Frank A1 - Theil, Diethilde A1 - Couttet, Philippe A1 - Vitobello, Antonio A1 - Grenet, Olivier A1 - Grasl-Kraupp, Bettina A1 - Ellinger-Ziegelbauer, Heidrung A1 - Thomson, John P. A1 - Meehan, Richard R. A1 - Elcombe, Clifford R. A1 - Henderson, Colin J. A1 - Wolf, C. Roland A1 - Schwarz, Michael A1 - Moulin, Pierre A1 - Terranova, Remi A1 - Moggs, Jonathan G. T1 - Phenobarbital Induces Cell Cycle Transcriptional Responses in Mouse Liver Humanized for Constitutive Androstane and Pregnane X Receptors JF - Toxicological Sciences N2 - The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARᴷᴼ-PXRᴷᴼ), double humanized CAR and PXR (CARʰ-PXRʰ), and wild-type C57BL/6 mice. Wild-type and CARʰ-PXRʰ mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CARᴷᴼ-PXRᴷᴼ mouse livers and largely reversible in wild-type and CARʰ-PXRʰ mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARʰ-PXRʰ mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB. Y1 - 2014 U6 - https://doi.org/https://doi.org/10.1093/toxsci/kfu038 SN - 1094-2025 VL - 139 IS - 2 SP - 501 EP - 511 PB - Oxford University Press CY - Oxford ER - 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 - https://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 - CHAP A1 - Poghossian, Arshak A1 - Weiland, Maryam A1 - Schöning, Michael Josef ED - Lvova, Larisa ED - Kirsanov, Dmitry ED - di Natale, Corrado ED - Legin, Audrey T1 - Nanoplate field-effect capacitors: a new transducer structure for multiparameter (bio-)chemical sensing T2 - Multisensor system for chemical analysis : materials and sensors N2 - An array of electrically isolated nanoplate field-effect silicon-on-insulator (SOI) capacitors as a new transducer structure for multiparameter (bio-)chemical sensing is presented. The proposed approach allows addressable biasing and electrical readout of multiple nanoplate field-effect capacitive (bio-)chemical sensors on the same SOI chip, as well as differential-mode measurements. The realized sensor chip has been applied for pH and penicillin concentration measurements, electrical monitoring of polyelectrolyte multilayer formation, and the label-free electrical detection of consecutive deoxyribonucleic acid (DNA) hybridization and denaturation events. Y1 - 2014 SN - 978-981-4411-15-8 ; 978-981-4411-16-5 U6 - https://doi.org/10.1201/b15491-11 SP - 333 EP - 373 PB - Jenny Stanford Publishing CY - Singapore ET - 1 ER - TY - CHAP A1 - Fuchs, Britta A1 - Ritz, Thomas T1 - Usability for Blended Shopping - Solving Major Flaws by Applying Usability Engineering and Proven Integration Technologies T2 - Proceedings of the 11th International Conference on e-Business, ICE-B 2014, Vienna, Austria Y1 - 2014 SN - 978-989-758-043-7 U6 - https://doi.org/10.5220/0005113502160223 SP - 216 EP - 223 ER - TY - CHAP A1 - Heuermann, Holger A1 - Finger, Torsten ED - Günther, Michael T1 - Microwave Spark Plug for Very High-Pressure Conditions T2 - Ignition systems for gasoline engines Y1 - 2014 SP - 269 EP - 282 PB - DCM Druck CY - Meckenheim ER - TY - CHAP A1 - Bung, Daniel Bernhard T1 - Observations on non-aerated flow and air entrainment on moderately sloped stepped spillways T2 - 7th Chinese-German Joint Symposium on Hydraulic and Ocean Engineering : 8. - 12. Sept. 2014, Hannover Y1 - 2014 N1 - Kennwortgeschützter Zugang. Passwort bei Prof. Bung, Fachbereich Bauingenieurwesen SP - 1 EP - 8 ER - TY - CHAP A1 - Bung, Daniel Bernhard A1 - Oertel, Mario T1 - Manipulation of non-aerated cavity flow on a stepped spillway model T2 - 3rd European IAHR Congress : April 14 – 16, 2014, Porto Y1 - 2014 PB - Univ. of Porto CY - Porto ER - TY - JOUR A1 - Lévesque, Mathieu A1 - Siegwolf, Rolf A1 - Eilmann, Britta A1 - Saurer, Matthias A1 - Rigling, Andreas T1 - Increased water-use efficiency does not lead to enhanced tree growth under xeric and mesic conditions JF - New Phytologist Y1 - 2014 U6 - https://doi.org/10.1111/nph.12772 SN - 1469-8137 (Online) SN - 0028-646X (Print) VL - 203 IS - 1 SP - 94 EP - 109 PB - Wiley-Blackwell CY - Oxford ER - TY - JOUR A1 - Hafner, David A1 - Demetz, Oliver A1 - Weickert, Joachim A1 - Reißel, Martin T1 - Mathematical Foundations and Generalisations of the Census Transform for Robust Optic Flow Computation JF - Journal of Mathematical Imaging and Vision Y1 - 2014 U6 - https://doi.org/10.1007/s10851-014-0529-9 SN - 1573-7683 (Online) N1 - Springer Online First (ohne Seitenang. und Heftzuteilung) PB - Springer CY - New York ER - TY - CHAP A1 - Gebhardt, Andreas A1 - Ritz, Thomas A1 - Siekmann, Kirsten A1 - Wallenborn, Ramona ED - Demmer, Axel T1 - Additive manufacturing businesses in the process chain of individualized mass products T2 - DDMC 2014 : Proceedings of the Fraunhofer Direct Digital Manufacturing Conference Y1 - 2014 SN - 978-3-8396-9128-1 (E-Book) PB - Fraunhofer CY - Stuttgart ER -