TY  - JOUR
A1  - Bäcker, Matthias
A1  - Raue, Markus
A1  - Schusser, Sebastian
A1  - Jeitner, C.
A1  - Breuer, L.
A1  - Wagner, P.
A1  - Poghossian, Arshak
A1  - Förster, Arnold
A1  - Mang, Thomas
A1  - Schöning, Michael Josef
T1  - Microfluidic chip with integrated microvalves based on temperature- and pH-responsive hydrogel thin films
JF  - Physica Status Solidi  (a)
N2  - Two types of microvalves based on temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) and pH-responsive poly(sodium acrylate) (PSA) hydrogel films have been developed and tested. The PNIPAAm and PSA hydrogel films were prepared by means of in situ photopolymerization directly inside the fluidic channel of a microfluidic chip fabricated by combining Si and SU-8 technologies. The swelling/shrinking properties and height changes of the PNIPAAm and PSA films inside the fluidic channel were studied at temperatures of deionized water from 14 to 36 °C and different pH values (pH 3–12) of Titrisol buffer, respectively. Additionally, in separate experiments, the lower critical solution temperature (LCST) of the PNIPAAm hydrogel was investigated by means of a differential scanning calorimetry (DSC) and a surface plasmon resonance (SPR) method. Mass-flow measurements have shown the feasibility of the prepared hydrogel films to work as an on-chip integrated temperature- or pH-responsive microvalve capable to switch the flow channel on/off.
Y1  - 2012
U6  - https://doi.org/10.1002/pssa.201100763
SN  - 1862-6319
VL  - 209
IS  - 5
SP  - 839
EP  - 845
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Lempiäinen, Harri
A1  - Couttet, Philippe
A1  - Bolognani, Federico
A1  - Müller, Arne
A1  - Dubost, Valérie
A1  - Luisier, Raphaëlle
A1  - Rio-Espinola, Alberto del
A1  - Vitry, Veronique
A1  - Unterberger, Elif B.
A1  - Thomson, John P.
A1  - Treindl, Fridolin
A1  - Metzger, Ute
A1  - Wrzodek, Clemens
A1  - Hahne, Florian
A1  - Zollinger, Tulipan
A1  - Brasa, Sarah
A1  - Kalteis, Magdalena
A1  - Marcellin, Magali
A1  - Giudicelli, Fanny
A1  - Braeuning, Albert
A1  - Morawiec, Laurent
A1  - Zamurovic, Natasa
A1  - Längle, Ulrich
A1  - Scheer, Nico
A1  - Schübeler, Dirk
A1  - Goodman, Jay
A1  - Chibout, Salah-Dine
A1  - Marlowe, Jennifer
A1  - Theil, Dietlinde
A1  - Heard, David J.
A1  - Grenet, Olivier
A1  - Zell, Andreas
A1  - Templin, Markus F.
A1  - Meehan, Richard R.
A1  - Wolf, Roland C.
A1  - Elcombe, Clifford R.
A1  - Schwarz, Michael
A1  - Moulin, Pierre
A1  - Terranova, Rémi
A1  - Moggs, Jonathan G.
T1  - Identification of Dlk1-Dio3 imprinted gene cluster non-coding RNAs as novel candidate biomarkers for liver tumor promotion
JF  - Toxicological Sciences
N2  - 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.
Y1  - 2012
U6  - https://doi.org/10.1093/toxsci/kfs303
SN  - 1094-2025
VL  - 131
IS  - 2
SP  - 375
EP  - 386
PB  - Oxford University Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Scheer, Nico
A1  - Balimane, Praveen
A1  - Hayward, Michael D.
A1  - Buechel, Sandra
A1  - Kauselmann, Gunther
A1  - Wolf, C. Roland
T1  - Generation and Characterization of a Novel Multidrug Resistance Protein 2 Humanized Mouse Line
JF  - Drug Metabolism and Disposition
N2  - 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.
Y1  - 2012
U6  - https://doi.org/10.1124/dmd.112.047605
SN  - 1521-0111
VL  - 40
IS  - 11
SP  - 2212
EP  - 2218
PB  - ASPET
CY  - Bethesda, Md.
ER  - 
TY  - JOUR
A1  - Aggarwal, Pranav
A1  - Dhiman, Shashi K.
A1  - Kumar, G.
A1  - Scherer, Ulrich W.
A1  - Singla, M. L.
A1  - Srivastava, Alok
T1  - Optical study of poly(ethyleneterephthalate) modified by different ionizing radiation dose
JF  - Indian Journal of Pure and Applied Physics
N2  - 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.
Y1  - 2012
SN  - 0019-5596
VL  - 50
IS  - 2
SP  - 129
EP  - 132
ER  - 
TY  - JOUR
A1  - Scheer, Nico
A1  - Kapelyukh, Yury
A1  - Rode, Anja
A1  - Buechel, Sandra
A1  - Wolf, C. Roland
T1  - Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines
JF  - Molecular Pharmacology
N2  - 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.
Y1  - 2012
U6  - https://doi.org/10.1124/mol.112.080036
SN  - 1521-0111
VL  - 82
IS  - 6
SP  - 1022
EP  - 1029
PB  - ASPET
CY  - Bethesda, Md.
ER  -