@article{SchiffelsSelmer2019, author = {Schiffels, Johannes and Selmer, Thorsten}, title = {Combinatorial assembly of ferredoxin-linked modules in Escherichia coli yields a testing platform for Rnf-complexes}, series = {Biotechnology and Bioengineering}, journal = {Biotechnology and Bioengineering}, number = {accepted article}, publisher = {Wiley}, address = {Weinheim}, doi = {10.1002/bit.27079}, pages = {1 -- 36}, year = {2019}, language = {en} } @article{SchiffelsPinkenburgScheldenetal.2013, author = {Schiffels, Johannes and Pinkenburg, Olaf and Schelden, Maximilian and Aboulnaga, El-Hussiny A. A. and Baumann, Marcus and Selmer, Thorsten}, title = {An innovative cloning platform enables large-scale production and maturation of an oxygen-tolerant [NiFe]-hydrogenase from cupriavidus necator in Escherichia coli}, series = {PLOS one. 2013}, journal = {PLOS one. 2013}, publisher = {Public Library of Science}, address = {San Francisco, California}, issn = {1932-6203}, doi = {10.1371/journal.pone.0068812}, year = {2013}, language = {en} } @article{SchiffelsBaumannSelmer2011, author = {Schiffels, Johannes and Baumann, Marcus and Selmer, Thorsten}, title = {Facile analysis of short-chain fatty acids as 4-nitrophenyl esters in complex anaerobic fermentation samples by high performance liquid chromatography}, series = {Journal of Chromatography A. 1218 (2011), H. 34}, journal = {Journal of Chromatography A. 1218 (2011), H. 34}, publisher = {Elsevier}, address = {Amsterdam}, isbn = {0021-9673}, pages = {5848 -- 5851}, year = {2011}, language = {en} } @article{SchiedermeierRettnerHeilmannetal.2019, author = {Schiedermeier, Maximilian and Rettner, Cornelius and Heilmann, Marcel and Schneider, Felix and Marz, Martin}, title = {Interference of automotive HV-DC-systems by traction voltage-source-inverters (VSI)}, series = {2019 IEEE Transportation Electrification Conference (ITEC-India)}, journal = {2019 IEEE Transportation Electrification Conference (ITEC-India)}, publisher = {IEEE}, address = {New York}, doi = {10.1109/ITEC-India48457.2019.ITECINDIA2019-37}, pages = {1 -- 6}, year = {2019}, language = {en} } @article{SchererZimmermannGoberetal.1993, author = {Scherer, Ulrich W. and Zimmermann, H. P. and Gober, M. K. and Kratz, J. V.}, title = {Chemical Properties of Element 105 in Aqueous Solution: Back Extraction from Triisooctyl Amine into 0.5M HCl / H.P. Zimmermann, M.K. Gober, J.V. Kratz, M. Sch{\"a}del, E. Schimpf, K.E. Gregorich, A. T{\"u}rler, K.R. Czerwinski, N.J. Hannink, B. Kadkhodayan, D.M.}, series = {Radiochimica Acta. 60 (1993)}, journal = {Radiochimica Acta. 60 (1993)}, isbn = {0033-8230}, pages = {11}, year = {1993}, language = {en} } @article{SchererTuerlerGaeggeleretal.1988, author = {Scherer, Ulrich W. and T{\"u}rler, A. and G{\"a}ggeler, H. W. and Jost, D. T.}, title = {Determination of the Partial Electron-Capture- and Spontaneous-Fission Half-Lives of 254No / A. T{\"u}rler, H.W. G{\"a}ggeler, D.T. Jost, P. Armbruster, W. Br{\"u}chle, H. Folger, F.P. Heßberger, S. Hofmann,}, series = {Zeitschrift f{\"u}r Physik A Hadrons and Nuclei. 331 (1988), H. 3}, journal = {Zeitschrift f{\"u}r Physik A Hadrons and Nuclei. 331 (1988), H. 3}, isbn = {0939-7922}, pages = {363 -- 364}, year = {1988}, language = {en} } @article{SchererTuerlerGaeggeleretal.1992, author = {Scherer, Ulrich W. and T{\"u}rler, A. and G{\"a}ggeler, H. W. and Gregorich, K. E.}, title = {Gas phase chromatography of halides of elements 104 and 105 / A. T{\"u}rler, H. W. G{\"a}ggeler, K. E. Gregorich, H. Barth, W. Br{\"u}chle, K. R. Czerwinski, M. K. Gober, N. J. Hannink, R. A. Henderson, D. C. Hoffman, D. T. Jost, C. D. Kacher, B. Kadkhodayan, J. Kova}, series = {Journal of Radioanalytical and Nuclear Chemistry. 160 (1992), H. 2}, journal = {Journal of Radioanalytical and Nuclear Chemistry. 160 (1992), H. 2}, isbn = {0236-5731}, pages = {327 -- 339}, year = {1992}, language = {en} } @article{SchererTomasbergerVeltkampetal.2001, author = {Scherer, Ulrich W. and Tomasberger, T. and Veltkamp, T. C. and Booij, A. S.}, title = {Radiocesium Removal from High Level Liquid Waste and Immobilisation in Sodium SilicoTitanate for Geological Disposal / T. Tomasberger, T.C. Veltkamp, A.S. Booij, U.W. Scherer}, series = {Radiochimica Acta. 89 (2001), H. 3}, journal = {Radiochimica Acta. 89 (2001), H. 3}, isbn = {0033-8230}, pages = {145 -- 150}, year = {2001}, language = {en} } @article{SchererSrivastavaSinghetal.2006, author = {Scherer, Ulrich W. and Srivastava, Alok and Singh, Vivendra and Chandra, Amita}, title = {Electrical conductivity studies of swift heavy ion modified PVC and PVC-PANI composite / Alok Srivastava ,Virendra Singh, Amita Chandra, K.Witte, U.W.Scherer and T.V.Singh}, series = {Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms. 245 (2006), H. 1}, journal = {Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms. 245 (2006), H. 1}, isbn = {0168-583X}, pages = {277 -- 280}, year = {2006}, language = {en} } @article{SchererSchaedelBruechleetal.1992, author = {Scherer, Ulrich W. and Sch{\"a}del, M. and Br{\"u}chle, W. and Schimpf, E.}, title = {Chemical Properties of Element 105 in Aqueous Solution: Cation Exchange Separations with \&\#945;-Hydroxyisobutyric Acid / M. Sch{\"a}del, W. Br{\"u}chle, E. Schimpf, H.P. Zimmermann, M.K. Gober, J.V. Kratz, N. Trautmann, H. G{\"a}ggeler, D. Jost, J. Kovacs, U.W. Sche}, series = {Radiochimica Acta. 57 (1992)}, journal = {Radiochimica Acta. 57 (1992)}, isbn = {0033-8230}, pages = {85 -- 92}, year = {1992}, language = {en} } @article{SchererSchaedelBruechleetal.1989, author = {Scherer, Ulrich W. and Sch{\"a}del, M. and Br{\"u}chle, W. and J{\"a}ger, E.}, title = {ARCA II - A New Apparatus for Fast Repetitive HPLC-Separations / M. Sch{\"a}del, W. Br{\"u}chle, E. J{\"a}ger, E. Schimpf, J.V. Kratz, U.W. Scherer, H.P. Zimmermann}, series = {Radiochimica Acta. 48 (1989)}, journal = {Radiochimica Acta. 48 (1989)}, isbn = {0033-8230}, pages = {171}, year = {1989}, language = {en} } @article{SchererSantanaMaieretal.2009, author = {Scherer, Ulrich W. and Santana, H. H. S. and Maier, G. and Rodenas, J.}, title = {Analysis of mechanical strength in ceramic pellets of nuclear fuel / Santana, H. H. S. ; Maier, G. ; Scherer, U. W. ; Rodenas, J.}, series = {Radiation effects and defects in solids. 164 (2009), H. 5-6}, journal = {Radiation effects and defects in solids. 164 (2009), H. 5-6}, publisher = {Taylor \& Francis}, address = {London}, isbn = {1042-0150}, pages = {313 -- 318}, year = {2009}, language = {en} } @article{SchererKratzZimmermannetal.1989, author = {Scherer, Ulrich W. and Kratz, J. V. and Zimmermann, H. P. and Sch{\"a}del, M.}, title = {Chemical Properties of Element 105 in Aqueous Solutions: Halide Complex Formation and Anion Exchange into Triisooctylamine / J.V. Kratz, H.P. Zimmermann, U.W. Scherer, M. Sch{\"a}del, W. Br{\"u}chle, K.E. Gregorich, C.M. Gannett, H.L. Hall, R.A. Henderson, D.M. L}, series = {Radiochimica Acta. 48 (1989)}, journal = {Radiochimica Acta. 48 (1989)}, isbn = {0033-8230}, pages = {121}, year = {1989}, language = {en} } @article{SchererKratzSchaedeletal.1988, author = {Scherer, Ulrich W. and Kratz, J. V. and Sch{\"a}del, M. and Br{\"u}chle, W.}, title = {Lawrencium Chemistry: No Evidence for Oxidation States Lower than 3+ in Aqueous Solution / U.W. Scherer, J.V. Kratz, M. Sch{\"a}del, W. Br{\"u}chle, K.E. Gregorich, R.A. Henderson, D. Lee, M. Nurmia, D.C. Hoffman}, series = {Inorganica Chimica Acta. 146 (1988)}, journal = {Inorganica Chimica Acta. 146 (1988)}, isbn = {0020-1693}, pages = {249 -- 254}, year = {1988}, language = {en} } @article{SchererKratzGoberetal.1992, author = {Scherer, Ulrich W. and Kratz, J. V. and Gober, M. K. and Zimmermann, H. P.}, title = {New nuclide 263 105 / J.V. Kratz, M.K. Gober, H.P. Zimmermann, M. Sch{\"a}del, W. Br{\"u}chle, E. Schimpf, K.E. Gregorich, A. T{\"u}rler, N.J. Hannink, K.R. Czerwinski, B. Kadkhodayan, D.M. Lee, M.J. Nurmia, D.C. Hoffman, H. G{\"a}ggeler, D. Jost, U.W. Scherer, A. Weber}, series = {Physical Review C . 45 (1992)}, journal = {Physical Review C . 45 (1992)}, pages = {1064 -- 1069}, year = {1992}, language = {en} } @article{SchererJacobiCastilloetal.2009, author = {Scherer, Ulrich W. and Jacobi, M. and Castillo, J. and Foerstel, D. H.}, title = {Ultra-low-level measurements of 3H and 14C in wines and champagne / Scherer, U. W. ; Jacobi, M. ; Castillo, J. ; Foerstel, D. H.}, series = {Radiation effects and defects in solids. 164 (2009), H. 5-6}, journal = {Radiation effects and defects in solids. 164 (2009), H. 5-6}, isbn = {1042-0150}, pages = {382 -- 385}, year = {2009}, language = {en} } @article{SchererHoerKranertetal.1998, author = {Scherer, Ulrich W. and H{\"o}r, G. and Kranert, W. T. and Maul, F. D.}, title = {Gated Metabolic Positron Emission Tomography (GAPET) of Myocardium: 18F-FDG/PET to optimize Recognition of Myocardial Hibernation / G. H{\"o}r, W.T. Kranert, F.D. Maul, O. Schr{\"o}der, A. Karimian-Tatriz, O. Geb, R.P. Baum, U.W. Scherer}, series = {Nuclear Medicine Communications. 19 (1998)}, journal = {Nuclear Medicine Communications. 19 (1998)}, isbn = {0143-3636}, pages = {535 -- 545}, year = {1998}, language = {en} } @article{SchererHoer1997, author = {Scherer, Ulrich W. and H{\"o}r, G.}, title = {Artifacts and Pitfalls in FDG-PET Whole-Body Scans / U.W. Scherer, G. H{\"o}r}, series = {Radionuclides for Mammary Gland - Current Status and Future Aspects / G. S. Limouris [Hrsg.]}, journal = {Radionuclides for Mammary Gland - Current Status and Future Aspects / G. S. Limouris [Hrsg.]}, publisher = {Mediterra Publishers}, address = {Athen}, isbn = {960-85227-6-5}, pages = {37 -- 42}, year = {1997}, language = {en} } @article{SchererHessbergerGaeggeleretal.1989, author = {Scherer, Ulrich W. and Heßberger, F. P. and G{\"a}ggeler, H. W. and Armbruster, P.}, title = {The New Nuclide 225U / F.P. Heßberger, H. G{\"a}ggeler, P. Armbruster, W. Br{\"u}chle, H. Folger, S. Hofmann, D. Jost, J.V. Kratz, M.E. Leino, G. M{\"u}nzenberg, V. Ninov, M. Sch{\"a}del, U.W. Scherer, K. S{\"u}mmerer, A. T{\"u}rler, D. Ackerman}, series = {Zeitschrift f{\"u}r Physik A Hadrons and Nuclei. 333 (1989), H. 1}, journal = {Zeitschrift f{\"u}r Physik A Hadrons and Nuclei. 333 (1989), H. 1}, isbn = {0939-7922}, pages = {111 -- 112}, year = {1989}, language = {en} } @article{SchererGaeggelerJostetal.1989, author = {Scherer, Ulrich W. and G{\"a}ggeler, H. W. and Jost, D. T. and T{\"u}rler, A.}, title = {Cold Fusion Reactions with 48Ca / H.W. G{\"a}ggeler, D.T. Jost, A. T{\"u}rler, P. Armbruster, W. Br{\"u}chle, H. Folger, F.P. Heßberger, S. Hofmann, G. M{\"u}nzenberg, V. Ninov, W. Reisdorf, M. Sch{\"a}del, K. S{\"u}mmerer, J.V. Kratz, U. Scherer, M.E. Leino}, series = {Nuclear Physics A . 502 (1989), H. 1}, journal = {Nuclear Physics A . 502 (1989), H. 1}, isbn = {0375-9474}, pages = {561 -- 570}, year = {1989}, language = {en} } @article{SchererGaeggelerJostetal.1992, author = {Scherer, Ulrich W. and G{\"a}ggeler, H. W. and Jost, D. T. and Kovacs, J.}, title = {Gas Phase Chromatography Experiments with Bromides of Tantalum and Element 105 / H.W. G{\"a}ggeler, D.T. Jost, J. Kovacs, U.W. Scherer, A. Weber, D. Vermeulen, A. T{\"u}rler, K.E. Gregorich, R.A. Henderson, K.R. Czerwinski, B. Kadkhodayan, D.M. Lee, M. Nurmia, D.}, series = {Radiochimica Acta. 57 (1992)}, journal = {Radiochimica Acta. 57 (1992)}, isbn = {0033-8230}, pages = {93 -- 100}, year = {1992}, language = {en} } @article{SchererGoberKratzetal.1992, author = {Scherer, Ulrich W. and Gober, M. K. and Kratz, J. V. and Zimmermann, H. P.}, title = {Chemical Properties of Element 105 in Aqueous Solution: Extractions into Diisobutylcarbinol / M.K. Gober, J.V. Kratz, H.P. Zimmermann, M. Sch{\"a}del, W. Br{\"u}chle, E. Schimpf, K.E. Gregorich, A. T{\"u}rler, N.J. Hannink, K.R. Czerwinski, B. Kadkhodayan, D.M. Lee,}, series = {Radiochimica Acta. 57 (1992)}, journal = {Radiochimica Acta. 57 (1992)}, isbn = {0033-8230}, pages = {77 -- 84}, year = {1992}, language = {en} } @article{SchererBruechleSchaedeletal.1988, author = {Scherer, Ulrich W. and Br{\"u}chle, W. and Sch{\"a}del, M. and Kratz, J. V.}, title = {The Hydration Enthalpies of Md3+ and Lr3+ / W. Br{\"u}chle, M. Sch{\"a}del, U.W. Scherer, J.V. Kratz, K.E. Gregorich, D. Lee, M. Nurmia, R.M. Chasteler, H.L. Hall, R.A. Henderson, D.C. Hoffman}, series = {Inorganica Chimica Acta. 146 (1988), H. 2}, journal = {Inorganica Chimica Acta. 146 (1988), H. 2}, isbn = {0020-1693}, pages = {267 -- 276}, year = {1988}, language = {en} } @article{SchererBruechleBrueggeretal.1990, author = {Scherer, Ulrich W. and Br{\"u}chle, W. and Br{\"u}gger, M. and Frink, C.}, title = {Reactions of 40Ar with 233U,,235U, and 238U at the Barrier / U.W. Scherer, W. Br{\"u}chle, M. Br{\"u}gger, C. Frink, H. G{\"a}ggeler, G. Herrmann, J.V. Kratz, K.J. Moody, M. Sch{\"a}del, K. S{\"u}mmerer, N. Trautmann, G. Wirth}, series = {Zeitschrift f{\"u}r Physik A Hadrons and Nuclei. 335 (1990), H. 4}, journal = {Zeitschrift f{\"u}r Physik A Hadrons and Nuclei. 335 (1990), H. 4}, isbn = {0939-7922}, pages = {421 -- 430}, year = {1990}, language = {en} } @article{SchererBaltenspergerAmmannetal.1993, author = {Scherer, Ulrich W. and Baltensperger, Urs and Ammann, Markus and Bochert, Ulrich K.}, title = {Use of 13N for Studies of the Selective Reduction of NO by NH3 over Vanadia/Titania Catalyst at Very Low Reactant Concentrations / Urs Baltensperger, Markus Ammann, Ulrich K. Bochert, Bernd Eichler, Heinz W. G{\"a}ggeler, Dieter T. Jost, Joseph A. Kovacs, An}, series = {Journal of Physical Chemistry. 97 (1993)}, journal = {Journal of Physical Chemistry. 97 (1993)}, isbn = {0022-3654}, pages = {12325 -- 12330}, year = {1993}, language = {en} } @article{Scherer2006, author = {Scherer, Ulrich W.}, title = {Controlled ion track etching / J. George; M. Irkens ; S. Neumann ; U. W. Scherer ; A. Srivastava ; D. Sinha ; D. Fink}, series = {Radiation Effects and Defects in Solids. 161 (2006), H. 3}, journal = {Radiation Effects and Defects in Solids. 161 (2006), H. 3}, pages = {161 -- 175}, year = {2006}, language = {en} } @article{ScheerWolf2014, author = {Scheer, Nico and Wolf, C. Roland}, title = {Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications}, series = {Xenobiotica}, volume = {44}, journal = {Xenobiotica}, number = {2}, publisher = {Taylor \& Francis}, address = {Abingdon}, issn = {1366-5928}, doi = {10.3109/00498254.2013.815831}, pages = {96 -- 108}, year = {2014}, abstract = {1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug-drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described. 2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created. 3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug-drug interactions as well as in human metabolite testing and risk assessment. 4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed.}, language = {en} } @article{ScheerWolf2013, author = {Scheer, Nico and Wolf, C. Roland}, title = {Xenobiotic receptor humanized mice and their utility}, series = {Drug Metabolism Reviews}, journal = {Drug Metabolism Reviews}, number = {1}, publisher = {Taylor \& Francis}, address = {London}, issn = {1097-9883}, doi = {10.3109/03602532.2012.738687}, pages = {110 -- 121}, year = {2013}, language = {en} } @article{ScheerWilson2016, author = {Scheer, Nico and Wilson, Ian D.}, title = {A comparison between genetically humanized and chimeric liver humanized mouse models for studies in drug metabolism and toxicity}, series = {Drug Discovery Today}, volume = {21}, journal = {Drug Discovery Today}, number = {2}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1359-6446}, doi = {10.1016/j.drudis.2015.09.002}, pages = {250 -- 263}, year = {2016}, abstract = {Mice that have been genetically humanized for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging and promising in vivo models for an improved prediction of the pharmacokinetic, drug-drug interaction and safety characteristics of compounds in humans. The specific advantages and disadvantages of these models should be carefully considered when using them for studies in drug discovery and development. Here, an overview on the corresponding genetically humanized and chimeric liver humanized mouse models described to date is provided and illustrated with examples of their utility in drug metabolism and toxicity studies. We compare the strength and weaknesses of the two different approaches, give guidance for the selection of the appropriate model for various applications and discuss future trends and perspectives.}, language = {en} } @article{ScheerSnaithWolfetal.2013, author = {Scheer, Nico and Snaith, Mike and Wolf, C. Roland and Seibler, Jost}, title = {Generation and utility of genetically humanized mouse models}, series = {Drug Discovery Today}, volume = {Vol 18}, journal = {Drug Discovery Today}, number = {23-24}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1359-6446}, doi = {10.1016/j.drudis.2013.07.007}, pages = {1200 -- 1211}, year = {2013}, language = {en} } @article{ScheerRossRodeetal.2008, author = {Scheer, Nico and Ross, Jillian and Rode, Anja and Zevnik, Branko and Niehaves, Sandra and Faust, Nicole and Wolf, C. Roland}, title = {A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response}, series = {Journal of Clinical Investigation}, volume = {118}, journal = {Journal of Clinical Investigation}, number = {9}, issn = {1558-8238}, doi = {https://doi.org/10.1172/JCI35483}, pages = {3228 -- 3239}, year = {2008}, language = {en} } @article{ScheerRossKapelyukhetal.2010, author = {Scheer, Nico and Ross, Jillian and Kapelyukh, Yury and Rode, Anja and Wolf, C. Roland}, title = {In vivo responses of the human and murine pregnane X receptor to dexamethasone in mice}, series = {Drug Metabolism and Disposition}, volume = {38}, journal = {Drug Metabolism and Disposition}, number = {7}, publisher = {ASPET}, address = {Bethesda}, issn = {1521-009X}, doi = {10.1124/dmd.109.031872}, pages = {1046 -- 1053}, year = {2010}, abstract = {Dexamethasone (DEX) is a potent and widely used anti-inflammatory and immunosuppressant glucocorticoid. It can bind and activate the pregnane X receptor (PXR), which plays a critical role as xenobiotic sensor in mammals to induce the expression of many enzymes, including cytochromes P450 in the CYP3A family. This induction results in its own metabolism. We have used a series of transgenic mouse lines, including a novel, improved humanized PXR line, to compare the induction profile of PXR-regulated drug-metabolizing enzymes after DEX administration, as well as looking at hepatic responses to rifampicin (RIF). The new humanized PXR model has uncovered further intriguing differences between the human and mouse receptors in that RIF only induced Cyp2b10 in the new humanized model. DEX was found to be a much more potent inducer of Cyp3a proteins in wild-type mice than in mice humanized for PXR. To assess whether PXR is involved in the detoxification of DEX in the liver, we analyzed the consequences of high doses of the glucocorticoid on hepatotoxicity on different PXR genetic backgrounds. We also studied these effects in an additional mouse model in which functional mouse Cyp3a genes have been deleted. These strains exhibited different sensitivities to DEX, indicating a protective role of the PXR and CYP3A proteins against the hepatotoxicity of this compound.}, language = {en} } @article{ScheerRiedlWarrenetal.2002, author = {Scheer, Nico and Riedl, Iris and Warren, J.T. and Kuwada, John Y. and Campos-Ortega, Jos{\´e} A.}, title = {A quantitative analysis of the kinetics of Gal4 activator and effector gene expression in the zebrafish}, series = {Mechanism of Development}, volume = {112}, journal = {Mechanism of Development}, number = {1-2}, issn = {0925-4773}, doi = {10.1016/S0925-4773(01)00621-9}, pages = {9 -- 14}, year = {2002}, language = {en} } @article{ScheerMclaughlinRodeetal.2014, author = {Scheer, Nico and Mclaughlin, Lesley A. and Rode, Anja and MacLeod, Alastair Kenneth and Henderson, Colin J. and Wolf, Roland C.}, title = {Deletion of thirty murine cytochrome P450 genes results in viable mice with compromised drug metabolism}, series = {Drug Metabolism and Disposition}, volume = {42}, journal = {Drug Metabolism and Disposition}, number = {6}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-009X}, doi = {10.1124/dmd.114.057885}, pages = {1022 -- 1030}, year = {2014}, abstract = {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.}, language = {en} } @article{ScheerKapelyukhRodeetal.2015, author = {Scheer, Nico and Kapelyukh, Yury and Rode, Anja and Oswald, Stefan and Busch, Diana and Mclaughlin, Lesley A. and Lin, De and Henderson, Colin J. and Wolf, C. Roland}, title = {Defining Human Pathways of Drug Metabolism In Vivo through the Development of a Multiple Humanized Mouse Model}, series = {Drug Metabolism and Disposition}, volume = {43}, journal = {Drug Metabolism and Disposition}, number = {11}, publisher = {ASPET}, address = {Bethesda}, issn = {1521-009x}, doi = {10.1124/dmd.115.065656}, pages = {1679 -- 1690}, year = {2015}, 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{ScheerKapelyukhMcEwanetal.2012, author = {Scheer, Nico and Kapelyukh, Yury and McEwan, Jillian and Beuger, Vincent and Stanley, Lesley A. and Rode, Anja and Wolf, C. Roland}, title = {Modeling Human Cytochrome P450 2D6 Metabolism and Drug-drug Interaction by a Novel Panel of Knockout and Humanized Mouse Lines}, series = {Molecular Pharmacology}, volume = {81}, journal = {Molecular Pharmacology}, number = {1}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.111.075192}, pages = {63 -- 72}, year = {2012}, abstract = {The highly polymorphic human cytochrome P450 2D6 enzyme is involved in the metabolism of up to 25\% of all marketed drugs and accounts for significant individual differences in response to CYP2D6 substrates. Because of the differences in the multiplicity and substrate specificity of CYP2D family members among species, it is difficult to predict pathways of human CYP2D6-dependent drug metabolism on the basis of animal studies. To create animal models that reflect the human situation more closely and that allow an in vivo assessment of the consequences of differential CYP2D6 drug metabolism, we have developed a novel straightforward approach to delete the entire murine Cyp2d gene cluster and replace it with allelic variants of human CYP2D6. By using this approach, we have generated mouse lines expressing the two frequent human protein isoforms CYP2D6.1 and CYP2D6.2 and an as yet undescribed variant of this enzyme, as well as a Cyp2d cluster knockout mouse. We demonstrate that the various transgenic mouse lines cover a wide spectrum of different human CYP2D6 metabolizer phenotypes. The novel humanization strategy described here provides a robust approach for the expression of different CYP2D6 allelic variants in transgenic mice and thus can help to evaluate potential CYP2D6-dependent interindividual differences in drug response in the context of personalized medicine.}, language = {en} } @article{ScheerHendersonKapelyukhetal.2019, author = {Scheer, Nico and Henderson, Colin James and Kapelyukh, Yury and Rode, Anja and Mclaren, Aileen W. and MacLeod, Alastair Kenneth and Lin, De and Wright, Jayne and Stanley, Lesley and Wolf, C. Roland}, title = {An extensively humanised mouse model to predict pathways of drug disposition, drug/drug interactions, and to facilitate the design of clinical trials}, series = {Drug Metabolism and Disposition}, journal = {Drug Metabolism and Disposition}, number = {Early view}, doi = {10.1124/dmd.119.086397}, pages = {69 Seiten}, year = {2019}, language = {en} } @article{ScheerGrothHansetal.2001, author = {Scheer, Nico and Groth, Anne and Hans, Stefan and Campos-Ortega, Jos{\´e} A.}, title = {An instructive function for Notch in promoting gliogenesis in the zebrafish retina}, series = {Development}, volume = {128}, journal = {Development}, number = {7}, issn = {0950-1991}, pages = {1099 -- 1107}, year = {2001}, language = {en} } @incollection{ScheerChuSalphatietal.2016, author = {Scheer, Nico and Chu, Xiaoyan and Salphati, Laurent and Zamek-Gliszczynski, Maciej J.}, title = {Knockout and humanized animal models to study membrane transporters in drug development}, series = {Drug Transporters: Volume 1: Role and Importance in ADME and Drug Development}, booktitle = {Drug Transporters: Volume 1: Role and Importance in ADME and Drug Development}, editor = {Nicholls, Glynis}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, isbn = {978-1-78262-379-3}, doi = {10.1039/9781782623793-00298}, pages = {298 -- 332}, year = {2016}, language = {en} } @article{ScheerCamposOrtega1999, author = {Scheer, Nico and Campos-Ortega, Jos{\´e} A.}, title = {Use of the Gal4-UAS technique for targeted gene expression in the zebrafish}, series = {Mechanism of Development}, volume = {80}, journal = {Mechanism of Development}, number = {2}, issn = {0925-4773}, doi = {10.1016/S0925-4773(98)00209-3}, pages = {153 -- 158}, year = {1999}, 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{ScheeleOertelBongaertsetal.2013, author = {Scheele, Sandra and Oertel, Dan and Bongaerts, Johannes and Evers, Stefan and Hellmuth, Hendrik and Maurer, Karl-Heinz and Bott, Michael and Freudl, Roland}, title = {Secretory production of an FAD cofactor-containing cytosolic enzyme (sorbitol-xylitol oxidase from Streptomyces coelicolor) using the twin-arginine translocation (Tat) pathway of Corynebacterium glutamicum}, series = {Microbial biotechnology}, journal = {Microbial biotechnology}, publisher = {Wiley-Blackwell}, address = {Oxford}, issn = {1751-7915}, pages = {202 -- 206}, year = {2013}, language = {en} } @incollection{SamuelssonScheerWilsonetal.2017, author = {Samuelsson, K. and Scheer, Nico and Wilson, I. and Wolf, C.R. and Henderson, C.J.}, title = {Genetically Humanized Animal Models}, series = {Comprehensive Medicinal Chemistry III. 3rd Edition}, booktitle = {Comprehensive Medicinal Chemistry III. 3rd Edition}, editor = {Chackalamannil, Samuel}, publisher = {Elsevier}, address = {Saint Louis}, isbn = {978-0-12-803201-5}, doi = {10.1016/B978-0-12-409547-2.12376-5}, pages = {130 -- 149}, year = {2017}, abstract = {Genetically humanized mice for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging as promising in vivo models for improved prediction of the pharmacokinetic, drug-drug interaction, and safety characteristics of compounds in humans. This is an overview on the genetically humanized and chimeric liver-humanized mouse models, which are illustrated with examples of their utility in drug metabolism and toxicity studies. The models are compared to give guidance for selection of the most appropriate model by highlighting advantages and disadvantages to be carefully considered when used for studies in drug discovery and development.}, language = {en} } @article{SalpatiChuChenetal.2014, author = {Salpati, Laurent and Chu, Xiaoyan and Chen, Liangfu and Prasad, Bhagwat and Dallas, Shannon and Evers, Raymond and Mamaril-Fishman, Donna and Geier, Ethan G. and Kehler, Jonathan and Kunta, Jeevan and Mezler, Mario and Laplanche, Loic and Pang, Jodie and Soars, Matthew G. and Unadkat, Jashvant D. and van Waterschoot, Robert A.B. and Yabut, Jocelyn and Schinkel, Alfred H. and Scheer, Nico and Rode, Anja}, title = {Evaluation of organic anion transporting polypeptide 1B1 and 1B3 humanized mice as a translational model to study the pharmacokinetics of statins}, series = {Drug Metabolism and Disposition}, volume = {42}, journal = {Drug Metabolism and Disposition}, number = {8}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-009X}, doi = {10.1124/dmd.114.057976}, pages = {1301 -- 1313}, year = {2014}, abstract = {Organic anion transporting polypeptide (Oatp) 1a/1b knockout and OATP1B1 and -1B3 humanized mouse models are promising tools for studying the roles of these transporters in drug disposition. Detailed characterization of these models will help to better understand their utility for predicting clinical outcomes. To advance this approach, we carried out a comprehensive analysis of these mouse lines by evaluating the compensatory changes in mRNA expression, quantifying the amounts of OATP1B1 and -1B3 protein by liquid chromatography-tandem mass spectrometry, and studying the active uptake in isolated hepatocytes and the pharmacokinetics of some prototypical substrates including statins. Major outcomes from these studies were 1) mostly moderate compensatory changes in only a few genes involved in drug metabolism and disposition, 2) a robust hepatic expression of OATP1B1 and -1B3 proteins in the respective humanized mouse models, and 3) functional activities of the human transporters in hepatocytes isolated from the humanized models with several substrates tested in vitro and with pravastatin in vivo. However, the expression of OATP1B1 and -1B3 in the humanized models did not significantly alter liver or plasma concentrations of rosuvastatin and pitavastatin compared with Oatp1a/1b knockout controls under the conditions used in our studies. Hence, although the humanized OATP1B1 and -1B3 mice showed in vitro and/or in vivo functional activity with some statins, further characterization of these models is required to define their potential use and limitations in the prediction of drug disposition and drug-drug interactions in humans.}, language = {en} } @article{RoeschKratzHeringetal.2016, author = {R{\"o}sch, C. and Kratz, F. and Hering, T. and Trautmann, S. and Umanskaya, N. and Tippk{\"o}tter, Nils and M{\"u}ller-Renno, C.M. and Ulber, R. and Hannig, M. and Ziegler, C.}, title = {Albumin-lysozyme interactions: cooperative adsorption on titanium and enzymatic activity}, series = {Colloids and Surfaces B: Biointerfaces}, volume = {149}, journal = {Colloids and Surfaces B: Biointerfaces}, number = {1}, publisher = {Elsevier}, address = {Amsterdam}, doi = {10.1016/j.colsurfb.2016.09.048}, pages = {115 -- 121}, year = {2016}, abstract = {The interplay of albumin (BSA) and lysozyme (LYZ) adsorbed simultaneously on titanium was analyzed by gel electrophoresis and BCA assay. It was found that BSA and lysozyme adsorb cooperatively. Additionally, the isoelectric point of the respective protein influences the adsorption. Also, the enzymatic activity of lysozyme and amylase (AMY) in mixtures with BSA was considered with respect to a possible influence of protein-protein interaction on enzyme activity. Indeed, an increase of lysozyme activity in the presence of BSA could be observed. In contrast, BSA does not influence the activity of amylase.}, language = {en} } @article{RoehlenPilasSchoeningetal.2017, author = {R{\"o}hlen, Desiree and Pilas, Johanna and Sch{\"o}ning, Michael Josef and Selmer, Thorsten}, title = {Development of an amperometric biosensor platform for the combined determination of l-Malic, Fumaric, and l-Aspartic acid}, series = {Applied Biochemistry and Biotechnology}, volume = {183}, journal = {Applied Biochemistry and Biotechnology}, publisher = {Springer}, address = {Berlin}, issn = {1559-0291}, doi = {10.1007/s12010-017-2578-1}, pages = {566 -- 581}, year = {2017}, abstract = {Three amperometric biosensors have been developed for the detection of L-malic acid, fumaric acid, and L -aspartic acid, all based on the combination of a malate-specific dehydrogenase (MDH, EC 1.1.1.37) and diaphorase (DIA, EC 1.8.1.4). The stepwise expansion of the malate platform with the enzymes fumarate hydratase (FH, EC 4.2.1.2) and aspartate ammonia-lyase (ASPA, EC 4.3.1.1) resulted in multi-enzyme reaction cascades and, thus, augmentation of the substrate spectrum of the sensors. Electrochemical measurements were carried out in presence of the cofactor β-nicotinamide adenine dinucleotide (NAD+) and the redox mediator hexacyanoferrate (III) (HCFIII). The amperometric detection is mediated by oxidation of hexacyanoferrate (II) (HCFII) at an applied potential of + 0.3 V vs. Ag/AgCl. For each biosensor, optimum working conditions were defined by adjustment of cofactor concentrations, buffer pH, and immobilization procedure. Under these improved conditions, amperometric responses were linear up to 3.0 mM for L-malate and fumarate, respectively, with a corresponding sensitivity of 0.7 μA mM-1 (L-malate biosensor) and 0.4 μA mM-1 (fumarate biosensor). The L-aspartate detection system displayed a linear range of 1.0-10.0 mM with a sensitivity of 0.09 μA mM-1. The sensor characteristics suggest that the developed platform provides a promising method for the detection and differentiation of the three substrates.}, language = {en} } @article{RoehlenPilasDahmenetal.2018, author = {R{\"o}hlen, Desiree and Pilas, Johanna and Dahmen, Markus and Keusgen, Michael and Selmer, Thorsten and Sch{\"o}ning, Michael Josef}, title = {Toward a Hybrid Biosensor System for Analysis of Organic and Volatile Fatty Acids in Fermentation Processes}, series = {Frontiers in Chemistry}, journal = {Frontiers in Chemistry}, number = {6}, publisher = {Frontiers}, address = {Lausanne}, doi = {10.3389/fchem.2018.00284}, pages = {Artikel 284}, year = {2018}, abstract = {Monitoring of organic acids (OA) and volatile fatty acids (VFA) is crucial for the control of anaerobic digestion. In case of unstable process conditions, an accumulation of these intermediates occurs. In the present work, two different enzyme-based biosensor arrays are combined and presented for facile electrochemical determination of several process-relevant analytes. Each biosensor utilizes a platinum sensor chip (14 × 14 mm²) with five individual working electrodes. The OA biosensor enables simultaneous measurement of ethanol, formate, d- and l-lactate, based on a bi-enzymatic detection principle. The second VFA biosensor provides an amperometric platform for quantification of acetate and propionate, mediated by oxidation of hydrogen peroxide. The cross-sensitivity of both biosensors toward potential interferents, typically present in fermentation samples, was investigated. The potential for practical application in complex media was successfully demonstrated in spiked sludge samples collected from three different biogas plants. Thereby, the results obtained by both of the biosensors were in good agreement to the applied reference measurements by photometry and gas chromatography, respectively. The proposed hybrid biosensor system was also used for long-term monitoring of a lab-scale biogas reactor (0.01 m³) for a period of 2 months. In combination with typically monitored parameters, such as gas quality, pH and FOS/TAC (volatile organic acids/total anorganic carbonate), the amperometric measurements of OA and VFA concentration could enhance the understanding of ongoing fermentation processes.}, language = {en} } @article{RothTippkoetter2016, author = {Roth, Jasmine and Tippk{\"o}tter, Nils}, title = {Evaluation of lignocellulosic material for butanol production using enzymatic hydrolysate medium}, series = {Cellulose Chemistry and Technology}, volume = {50}, journal = {Cellulose Chemistry and Technology}, number = {3-4}, publisher = {Editura Academiei Romane}, address = {Bukarest}, pages = {405 -- 410}, year = {2016}, abstract = {Butanol is a promising gasoline additive and platform chemical that can be readily produced via acetone-butanolethanol (ABE) fermentation from pretreated lignocellulosic materials. This article examines lignocellulosic material from beech wood for ABE fermentation, using Clostridium acetobutylicum. First, the utilization of both C₅₋ (xylose) and C₆₋ (glucose) sugars as sole carbon source was investigated in static cultivation, using serum bottles and synthetic medium. The utilization of pentose sugar resulted in a solvent yield of 0.231 g·g_sugar⁻¹, compared to 0.262 g·g_sugar⁻¹ using hexose. Then, the Organosolv pretreated crude cellulose fibers (CF) were enzymatically decomposed, and the resulting hydrolysate medium was analyzed for inhibiting compounds (furans, organic acids, phenolics) and treated with ionexchangers for detoxification. Batch fermentation in a bioreactor using CF hydrolysate medium resulted in a total solvent yield of 0.20 gABE·g_sugar⁻¹.}, language = {en} } @inproceedings{RothMoehringTippkoetter2016, author = {Roth, J. and M{\"o}hring, S. and Tippk{\"o}tter, Nils}, title = {Characterization and evaluation of lignocellulosic biomass 130 hydrolysates for ABE fermentation}, series = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, booktitle = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, publisher = {DECHEMA}, address = {Frankfurt am Main}, pages = {130}, year = {2016}, language = {en} }