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 - http://dx.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 - 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 - http://dx.doi.org/10.1124/mol.112.080036 SN - 1521-0111 VL - 82 IS - 6 SP - 1022 EP - 1029 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Borgmeier, Claudia A1 - Bongaerts, Johannes A1 - Meinhardt, Friedhelm T1 - Genetic analysis of the Bacillus licheniformis degSU operon and the impact of regulatory mutations on protease production JF - Journal of biotechnology N2 - Disruption experiments targeted at the Bacillus licheniformis degSU operon and GFP-reporter analysis provided evidence for promoter activity immediately upstream of degU. pMutin mediated concomitant introduction of the degU32 allele – known to cause hypersecretion in Bacillus subtilis – resulted in a marked increase in protease activity. Application of 5-fluorouracil based counterselection through establishment of a phosphoribosyltransferase deficient Δupp strain eventually facilitated the marker-free introduction of degU32 leading to further protease enhancement achieving levels as for hypersecreting wild strains in which degU was overexpressed. Surprisingly, deletion of rapG – known to interfere with DegU DNA-binding in B. subtilis – did not enhance protease production neither in the wild type nor in the degU32 strain. The combination of degU32 and Δupp counterselection in the type strain is not only equally effective as in hypersecreting wild strains with respect to protease production but furthermore facilitates genetic strain improvement aiming at biological containment and effectiveness of biotechnological processes. KW - Marker-free mutagenesis KW - Extracellular enzymes KW - Uracil-phosphoribosyltransferase KW - Hypersecretion Y1 - 2012 U6 - http://dx.doi.org/10.1016/j.jbiotec.2012.02.011 SN - 1873-4863 (E-Journal); 0168-1656 (Print) VL - 159 IS - 1-2 SP - 12 EP - 20 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Feiser, Johannes ED - Vismann, Ulrich T1 - Geotechnik T2 - Wendehorst Bautechnische Zahlentafeln N2 - In der nationalen und der europäischen Normung werden die geotechnischen Aufgaben zwecks Mindestanforderungen an Baugrunduntersuchung, rechnerische Nachweise und Überwachung der Ausführung in drei Klassen (Kategorien) eingeteilt. Sie richten sich nach der zu erwartenden Reaktion des Baugrundes, nach dem geotechnischen Schwierigkeitsgrad des Tragwerks und seiner Einflüsse auf dieUmgebung. Y1 - 2012 SN - 978-3-8348-0960-5 U6 - http://dx.doi.org/10.1007/978-3-8348-8613-2_17 N1 - Kapitel 17 SP - 1221 EP - 1332 PB - Vieweg + Teubner CY - Wiesbaden ET - 34 ER - TY - CHAP A1 - Feiser, Johannes T1 - Geotechnik T2 - Wendehorst Beispiele aus der Baupraxis. - 4. Aufl. Y1 - 2012 SN - 978-3-8348-0999-5 ; 978-3-8348-8229-5 U6 - http://dx.doi.org/10.1007/978-3-8348-8229-5_14 SP - 453 EP - 495 PB - Springer Vieweg CY - Wiesbaden ER - TY - JOUR A1 - Schneider, Bettina A1 - Schneider, Wilhelm T1 - Grundlagen der Unternehmensbesteuerung JF - Das Wirtschaftsstudium : wisu ; Zeitschrift für Ausbildung, Examen, Berufseinstieg und Fortbildung Y1 - 2012 SN - 0340-3084 VL - 41 IS - 10 SP - 1312 EP - 1318 PB - Lange CY - Düsseldorf ER - TY - JOUR A1 - Grinsven, Bart van A1 - Bon, Natalie vanden A1 - Strauven, Hannelore A1 - Grieten, Lars A1 - Murib, Mohammed A1 - Jiménez Monroy, Kathia L. A1 - Janssens, Stoffel D. A1 - Haenen, Ken A1 - Schöning, Michael Josef A1 - Vermeeren, Veronique A1 - Ameloot, Marcel A1 - Michiels, Luc A1 - Thoelen, Ronald A1 - Ceuninck, Ward de A1 - Wagner, Patrick T1 - Heat-Transfer Resistance at Solid-Liquid Interfaces: A Tool for The Detection of Single Nucleotide Polymorphisms in DNA. JF - ACS Nano N2 - In this article, we report on the heat-transfer resistance at interfaces as a novel, denaturation-based method to detect single-nucleotide polymorphisms in DNA. We observed that a molecular brush of double-stranded DNA grafted onto synthetic diamond surfaces does not notably affect the heat-transfer resistance at the solid-to-liquid interface. In contrast to this, molecular brushes of single-stranded DNA cause, surprisingly, a substantially higher heat-transfer resistance and behave like a thermally insulating layer. This effect can be utilized to identify ds-DNA melting temperatures via the switching from low- to high heat-transfer resistance. The melting temperatures identified with this method for different DNA duplexes (29 base pairs without and with built-in mutations) correlate nicely with data calculated by modeling. The method is fast, label-free (without the need for fluorescent or radioactive markers), allows for repetitive measurements, and can also be extended toward array formats. Reference measurements by confocal fluorescence microscopy and impedance spectroscopy confirm that the switching of heat-transfer resistance upon denaturation is indeed related to the thermal on-chip denaturation of DNA. Y1 - 2012 U6 - http://dx.doi.org/10.1021/nn300147e SN - 1936-086X VL - 6 IS - 3 SP - 2712 EP - 2721 PB - ACS Publications CY - Washington, DC ER - TY - CHAP A1 - Sauerborn, Markus A1 - Hoffschmidt, Bernhard A1 - Telle, R. A1 - Wagner, M. T1 - Heatable optical analyse system for high temperature absorbers T2 - 30th ISES Biennial Solar World Congress 2011 : : Kassel, Germany, 28 August - 2 September 2011. Vol. 5 Y1 - 2012 SN - 978-1-61839-364-7 SP - 3852 EP - 3860 PB - Curran CY - Red Hook, NY ER - TY - CHAP A1 - Sieker, T. A1 - Duwe, A. A1 - Poth, S. A1 - Tippkötter, Nils A1 - Ulber, R. T1 - Herstellung von Itaconsäure aus Buchenholzhydrolysaten T2 - Kurzfassungsband / GVC-DECHEMA Vortrags- und Diskussionstagung Biopharmazeutische Produktion : 14. - 16. Mai 2012. Konzerthaus Freibung Y1 - 2012 SP - 57 PB - DECHEMA CY - Frankfurt, M. ER - TY - CHAP A1 - Digel, Ilya A1 - Mansurov, Zulkhair A1 - Biisenbaev, Makhmut A1 - Savitskaya, Irina A1 - Kistaubaeva, Aida A1 - Akimbekov, Nuraly A1 - Zhubanova, Azhar ED - Hu, Ning T1 - Heterogeneous Composites on the Basis of Microbial Cells and Nanostructured Carbonized Sorbents T2 - Composites and Their Applications N2 - The fact that microorganisms prefer to grow on liquid/solid phase surfaces rather than in the surrounding aqueous phase was noticed long time ago [1]. Virtually any surface – animal, mineral, or vegetable – is a subject for microbial colonization and subsequent biofilm formation. It would be adequate to name just a few notorious examples on microbial colonization of contact lenses, ship hulls, petroleum pipelines, rocks in streams and all kinds of biomedical implants. The propensity of microorganisms to become surface-bound is so profound and ubiquitous that it vindicates the advantages for attached forms over their free-ranging counterparts [2]. Indeed, from ecological and evolutionary standpoints, for many microorganisms the surface-bound state means dwelling in nutritionally favorable, non-hostile environments [3]. Therefore, in most of natural and artificial ecosystems surface-associated microorganisms vastly outnumber organisms in suspension and often organize into complex communities with features that differ dramatically from those of free cells [4]. Y1 - 2012 SN - 978-953-51-0706-4 U6 - http://dx.doi.org/10.5772/47796 SP - 249 EP - 272 PB - Intech CY - London ER -