@article{LempiaeinenCouttetBolognanietal.2012,
  author    = {Lempi{\"a}inen, Harri and Couttet, Philippe and Bolognani, Federico and M{\"u}ller, Arne and Dubost, Val{\´e}rie and Luisier, Rapha{\"e}lle and Rio-Espinola, Alberto del and Vitry, Veronique and Unterberger, Elif B. and Thomson, John P. and Treindl, Fridolin and Metzger, Ute and Wrzodek, Clemens and Hahne, Florian and Zollinger, Tulipan and Brasa, Sarah and Kalteis, Magdalena and Marcellin, Magali and Giudicelli, Fanny and Braeuning, Albert and Morawiec, Laurent and Zamurovic, Natasa and L{\"a}ngle, Ulrich and Scheer, Nico and Sch{\"u}beler, Dirk and Goodman, Jay and Chibout, Salah-Dine and Marlowe, Jennifer and Theil, Dietlinde and Heard, David J. and Grenet, Olivier and Zell, Andreas and Templin, Markus F. and Meehan, Richard R. and Wolf, Roland C. and Elcombe, Clifford R. and Schwarz, Michael and Moulin, Pierre and Terranova, R{\´e}mi and Moggs, Jonathan G.},
  title     = {Identification of Dlk1-Dio3 imprinted gene cluster non-coding RNAs as novel candidate biomarkers for liver tumor promotion},
  series = {Toxicological Sciences},
  volume    = {131},
  journal   = {Toxicological Sciences},
  number    = {2},
  publisher = {Oxford University Press},
  address   = {Oxford},
  issn      = {1094-2025},
  doi       = {10.1093/toxsci/kfs303},
  pages     = {375 -- 386},
  year      = {2012},
  abstract  = {The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.},
  language  = {en}
}
@article{ScheerBalimaneHaywardetal.2012,
  author    = {Scheer, Nico and Balimane, Praveen and Hayward, Michael D. and Buechel, Sandra and Kauselmann, Gunther and Wolf, C. Roland},
  title     = {Generation and Characterization of a Novel Multidrug Resistance Protein 2 Humanized Mouse Line},
  series = {Drug Metabolism and Disposition},
  volume    = {40},
  journal   = {Drug Metabolism and Disposition},
  number    = {11},
  publisher = {ASPET},
  address   = {Bethesda, Md.},
  issn      = {1521-0111},
  doi       = {10.1124/dmd.112.047605},
  pages     = {2212 -- 2218},
  year      = {2012},
  abstract  = {The multidrug resistance protein (MRP) 2 is predominantly expressed in liver, intestine, and kidney, where it plays an important role in the excretion of a range of drugs and their metabolites or endogenous compounds into bile, feces, and urine. Mrp knockout [Mrp2(-/-)] mice have been used recently to study the role of MRP2 in drug disposition. Here, we describe the first generation and initial characterization of a mouse line humanized for MRP2 (huMRP2), which is nulled for the mouse Mrp2 gene and expresses the human transporter in the organs and cell types where MRP2 is normally expressed. Analysis of the mRNA expression for selected cytochrome P450 and transporter genes revealed no major changes in huMRP2 mice compared with wild-type controls. We show that human MRP2 is able to compensate functionally for the loss of the mouse transporter as demonstrated by comparable bilirubin levels in the humanized mice and wild-type controls, in contrast to the hyperbilirubinemia phenotype that is observed in MRP2(-/-) mice. The huMRP2 mouse provides a model to study the role of the human transporter in drug disposition and in assessing the in vivo consequences of inhibiting this transporter by compounds interacting with human MRP2.},
  language  = {en}
}
@article{ScheerKapelyukhRodeetal.2012,
  author    = {Scheer, Nico and Kapelyukh, Yury and Rode, Anja and Buechel, Sandra and Wolf, C. Roland},
  title     = {Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines},
  series = {Molecular Pharmacology},
  volume    = {82},
  journal   = {Molecular Pharmacology},
  number    = {6},
  publisher = {ASPET},
  address   = {Bethesda, Md.},
  issn      = {1521-0111},
  doi       = {10.1124/mol.112.080036},
  pages     = {1022 -- 1029},
  year      = {2012},
  abstract  = {Compared with rodents and many other animal species, the human cytochrome P450 (P450) Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the substrate specificity of its enzymes. As a consequence, the use of wild-type animal models to predict the role of human CYP2C enzymes in drug metabolism and drug-drug interactions is limited. Within the human CYP2C cluster CYP2C9 is of particular importance, because it is one of the most abundant P450 enzymes in human liver, and it is involved in the metabolism of a wide variety of important drugs and environmental chemicals. To investigate the in vivo functions of cytochrome P450 Cyp2c genes and to establish a model for studying the functions of CYP2C9 in vivo, we have generated a mouse model with a deletion of the murine Cyp2c gene cluster and a corresponding humanized model expressing CYP2C9 specifically in the liver. Despite the high number of functional genes in the mouse Cyp2c cluster and the reported roles of some of these proteins in different biological processes, mice deleted for Cyp2c genes were viable and fertile but showed certain phenotypic alterations in the liver. The expression of CYP2C9 in the liver also resulted in viable animals active in the metabolism and disposition of a number of CYP2C9 substrates. These mouse lines provide a powerful tool for studying the role of Cyp2c genes and of CYP2C9 in particular in drug disposition and as a factor in drug-drug interaction.},
  language  = {en}
}
@article{RibitschHeumannKarletal.2012,
  author    = {Ribitsch, Doris and Heumann, Sonja and Karl, Wolfgang and Gerlach, Jochen and Leber, Regina and Birner-Gruenberger, Ruth and Gruber, Karl and Eiteljoerg, Inge and Remler, Peter and Siegert, Petra and Lange, Jennifer and Maurer, Karl-Heinz and Berg, Gabriele and Guebitz, G. M. and Schwab, H.},
  title     = {Extracellular serine proteases from Stenotrophomonas maltophilia: Screening, isolation and heterologous expression in E. coli},
  series = {Journal of biotechnology},
  volume    = {157},
  journal   = {Journal of biotechnology},
  number    = {1},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {1873-4863 (E-Journal); 0168-1656 (Print)},
  doi       = {10.1016/j.jbiotec.2011.09.025},
  pages     = {140 -- 147},
  year      = {2012},
  abstract  = {A large strain collection comprising antagonistic bacteria was screened for novel detergent proteases. Several strains displayed protease activity on agar plates containing skim milk but were inactive in liquid media. Encapsulation of cells in alginate beads induced protease production. Stenotrophomonas maltophilia emerged as best performer under washing conditions. For identification of wash-active proteases, four extracellular serine proteases called StmPr1, StmPr2, StmPr3 and StmPr4 were cloned. StmPr2 and StmPr4 were sufficiently overexpressed in E. coli. Expression of StmPr1 and StmPr3 resulted in unprocessed, insoluble protein. Truncation of most of the C-terminal domain which has been identified by enzyme modeling succeeded in expression of soluble, active StmPr1 but failed in case of StmPr3. From laundry application tests StmPr2 turned out to be a highly wash-active protease at 45 °C. Specific activity of StmPr2 determined with suc-l-Ala-l-Ala-l-Pro-l-Phe-p-nitroanilide as the substrate was 17 ± 2 U/mg. In addition we determined the kinetic parameters and cleavage preferences of protease StmPr2.},
  language  = {en}
}
@article{AggarwalDhimanKumaretal.2012,
  author    = {Aggarwal, Pranav and Dhiman, Shashi K. and Kumar, G. and Scherer, Ulrich W. and Singla, M. L. and Srivastava, Alok},
  title     = {Optical study of poly(ethyleneterephthalate) modified by different ionizing radiation dose},
  series = {Indian Journal of Pure and Applied Physics},
  volume    = {50},
  journal   = {Indian Journal of Pure and Applied Physics},
  number    = {2},
  publisher = {Council Of Scientific And Industrial Research (CSIR), National Institute Of Science Communication and Policy Research (NIScPR)},
  address   = {New Delhi},
  issn      = {0019-5596},
  pages     = {129 -- 132},
  year      = {2012},
  abstract  = {Thin films of poly(ethyleneterephthalate) [PET]were exposed to radiation dose ranging from 10 to 30 kGy by using gamma rays in the range 12.8-177.8 MGy using swift light ions of hydrogen. There was no effect of the radiation dose on the optical behaviour of PET as a result of exposure to radiation dose up to 30 kGy brought about by gamma rays but a significant decrease in the optical band gap values was observed when PET was exposed to swift light ions of hydrogen. The data obtained are discussed in terms of optical studies carried out on PET using swift heavy ions.},
  language  = {en}
}