@article{RaueWambachGloeggleretal.2014, author = {Raue, Markus and Wambach, M. and Gl{\"o}ggler, S. and Grefen, Dana and Kaufmann, R. and Abetz, C. and Georgopanos, P. and Handge, U. A. and Mang, Thomas and Bl{\"u}mich, B. and Abetz, V.}, title = {Investigation of historical hard rubber ornaments of Charles Goodyear}, series = {Macromolecular chemistry and physics}, volume = {Vol. 215}, journal = {Macromolecular chemistry and physics}, number = {No. 3}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1022-1352}, pages = {245 -- 254}, year = {2014}, language = {en} } @article{PilasIkenSelmeretal.2015, author = {Pilas, Johanna and Iken, Heiko and Selmer, Thorsten and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Development of a multi-parameter sensor chip for the simultaneous detection of organic compounds in biogas processes}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201431894}, pages = {1306 -- 1312}, year = {2015}, abstract = {An enzyme-based multi-parameter biosensor is developed for monitoring the concentration of formate, d-lactate, and l-lactate in biological samples. The sensor is based on the specific dehydrogenation by an oxidized β-nicotinamide adenine dinucleotide (NAD+)-dependent dehydrogenase (formate dehydrogenase, d-lactic dehydrogenase, and l-lactic dehydrogenase, respectively) in combination with a diaphorase from Clostridium kluyveri (EC 1.8.1.4). The enzymes are immobilized on a platinum working electrode by cross-linking with glutaraldehyde (GA). The principle of the determination scheme in case of l-lactate is as follows: l-lactic dehydrogenase (l-LDH) converts l-lactate into pyruvate by reaction with NAD+. In the presence of hexacyanoferrate(III), the resulting reduced β-nicotinamide adenine dinucleotide (NADH) is then regenerated enzymatically by diaphorase. The electrochemical detection is based on the current generated by oxidation of hexacyanoferrate(II) at an applied potential of +0.3 V vs. an Ag/AgCl reference electrode. The biosensor will be electrochemically characterized in terms of linear working range and sensitivity. Additionally, the successful practical application of the sensor is demonstrated in an extract from maize silage.}, language = {en} } @article{BreuerRaueKirschbaumetal.2015, author = {Breuer, Lars and Raue, Markus and Kirschbaum, M. and Mang, Thomas and Sch{\"o}ning, Michael Josef and Thoelen, R. and Wagner, Torsten}, title = {Light-controllable polymeric material based on temperature-sensitive hydrogels with incorporated graphene oxide}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201431944}, pages = {1368 -- 1374}, year = {2015}, abstract = {Poly(N-isopropylacrylamide) (PNIPAAm) hydrogel films with incorporated graphene oxide (GO) were developed and tested as light-stimulated actuators. GO dispersions were synthesized via Hummers method and characterized toward their optical properties and photothermal energy conversion. The hydrogels were prepared by means of photopolymerization. In addition, the influence of GO within the hydrogel network on the lower critical solution temperature (LCST) was investigated by differential scanning calorimetry (DSC). The optical absorbance and the response to illumination were determined as a function of GO concentration for thin hydrogel films. A proof of principle for the stimulation with light was performed.}, language = {en} } @article{SchiffelsSelmer2015, author = {Schiffels, Johannes and Selmer, Thorsten}, title = {A flexible toolbox to study protein-assisted metalloenzyme assembly in vitro}, series = {Biotechnology and Bioengineering}, volume = {112}, journal = {Biotechnology and Bioengineering}, number = {11}, publisher = {Wiley}, address = {Weinheim}, issn = {1097-0290}, doi = {10.1002/bit.25658}, pages = {2360 -- 2372}, year = {2015}, language = {en} } @article{PilasMarianoKeusgenetal.2015, author = {Pilas, Johanna and Mariano, K. and Keusgen, M. and Selmer, Thorsten and Sch{\"o}ning, Michael Josef}, title = {Optimization of an Enzyme-based Multi-parameter Biosensor for Monitoring Biogas Processes}, series = {Procedia Engineering}, volume = {120}, journal = {Procedia Engineering}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1877-7058}, doi = {10.1016/j.proeng.2015.08.702}, pages = {532 -- 535}, year = {2015}, language = {en} } @misc{O'ConnellSiegertMaureretal.2010, author = {O'Connell, Timothy and Siegert, Petra and Maurer, Karl-Heinz and Schiedel, Marc-Steffen and Vockenroth, Inga Kerstin}, title = {Method for improving the cleaning action of a detergent or cleaning agent [Internationale Patentanmeldung]}, publisher = {WIPO}, address = {Genf}, pages = {1 -- 15}, year = {2010}, language = {en} } @article{CehreliAkpinarTemizArtmannetal.2015, author = {Cehreli, Ruksan and Akpinar, Hale and Temiz Artmann, Ayseg{\"u}l and Sagol, Ozgul}, title = {Effects of Glutamine and Omega-3 Fatty Acids on Erythrocyte Deformability and Oxidative Damage in Rat Model of Enterocolitis}, series = {Gastroenterology Research}, volume = {8}, journal = {Gastroenterology Research}, number = {5}, issn = {1918-2813}, doi = {10.14740/gr683w}, pages = {265 -- 273}, year = {2015}, language = {en} } @incollection{SrivastavaKnolleHoyleretal.2015, author = {Srivastava, Alok and Knolle, Friedhart and Hoyler, Friedrich and Scherer, Ulrich W. and Schnug, Ewald}, title = {Uranium Toxicity in the State of Punjab in North-Western India}, series = {Management of Natural Resources in a Changing Environment}, booktitle = {Management of Natural Resources in a Changing Environment}, publisher = {Springer}, address = {Cham}, isbn = {978-3-319-12559-6}, doi = {10.1007/978-3-319-12559-6_21}, pages = {271 -- 275}, year = {2015}, abstract = {Lately there has been an increasing concern about uranium toxicity in some districts of Punjab State located in the North Western part of India after the publication of a report (Blaurock-Busch et al. 2010) which showed that the concentration of uranium in hair and urine of children suffering from physical deformities, neurological and mental disorder from Malwa region (Fig. 1) of Punjab State was manifold higher than the reference ranges. A train which connects the affected region with the nearby city of Bikaner which has a Cancer Hospital has been nicknamed as Cancer Express due to the frenzy generated on account of uranium related toxicity.}, language = {en} } @article{NachtrodtTietschMostaccietal.2014, author = {Nachtrodt, Frederik and Tietsch, Wolfgang and Mostacci, Domiziano and Scherer, Ulrich W.}, title = {Set-up and first operation of a plasma oven for treatment of low level radioactive wastes}, series = {Nuclear technology and radiation protection}, volume = {29}, journal = {Nuclear technology and radiation protection}, number = {Suppl.}, publisher = {VINČA Institute of Nuclear Sciences}, address = {Belgrad}, issn = {1451-3994}, doi = {10.2298/NTRP140SS47N}, pages = {47 -- 51}, year = {2014}, language = {en} } @misc{BesslerMaurerMerkeletal.2009, author = {Bessler, Cornelius and Maurer, Karl-Heinz and Merkel, Marion and Siegert, Petra and Wieland, Susanne}, title = {Subtilisin from Bacillus Pumilus and detergent and cleaning agents containing said novel subtilisin [US Patentanmeldung / Internationale Patentanmeldung]}, publisher = {USPTO; WIPO}, address = {Washington; Genf}, pages = {1 -- 39}, year = {2009}, language = {en} } @article{RatkeMilowLisinskietal.2014, author = {Ratke, Lorenz and Milow, Barbara and Lisinski, Susanne and Hoepfner, Sandra}, title = {On an effect of fine ceramic particles on the structure of aerogels}, series = {Microgravity science and technology}, volume = {26}, journal = {Microgravity science and technology}, publisher = {Springer Nature}, address = {Heidelberg}, issn = {0938-0108 ; 1875-0494}, doi = {10.1007/s12217-014-9380-2}, pages = {103 -- 110}, year = {2014}, language = {en} } @article{SeiblerKleinriddersKueterLuksetal.2007, author = {Seibler, Jost and Kleinridders, Andre and K{\"u}ter-Luks, Birgit and Niehaves, Sandra and Br{\"u}ning, Jens C. and Schwenk, Frieder}, title = {Reversible gene knockdown in mice using a tight, inducible shRNA expression system}, series = {Nucleic Acids Research}, volume = {35}, journal = {Nucleic Acids Research}, number = {7}, issn = {1362-4962}, doi = {10.1093/nar/gkm122}, pages = {e54}, year = {2007}, language = {en} } @article{PlumMaHampeletal.2006, author = {Plum, Leona and Ma, Xiaosong and Hampel, Brigitte and Balthasar, Nina and Coppari, Roberto and M{\"u}nzberg, Heike and Shanabrough, Marya and Burdakov, Denis and Rother, Eva and Janoschek, Ruth and Alber, Jens and Belgardt, Bengt F. and Koch, Linda and Seibler, Jost and Schenk, Frieder and Fekete, Csaba and Suzuki, Akira and Mak, Tak W. and Krone, Wilhelm and Horvath, Tamas L. and Ashcroft, Frances M. and Br{\"u}ning, Jens C.}, title = {Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity}, series = {The Journal of Clinical Investigation (JCI)}, volume = {116}, journal = {The Journal of Clinical Investigation (JCI)}, number = {7}, issn = {1558-8238}, doi = {10.1172/JCI27123}, pages = {1886 -- 1901}, year = {2006}, language = {en} } @article{SeiblerKueterLuksKernetal.2005, author = {Seibler, Jost and K{\"u}ter-Luks, Birgit and Kern, Heidrun and Streu, Sandra and Plum, Leona and Maurer, Jan and K{\"u}hn, Ralf and Br{\"u}ning, Jens C. and Schwenk, Frieder}, title = {Single copy shRNA configuration for ubiquitous gene knockdown in mice}, series = {Nucleic Acids Research}, volume = {33}, journal = {Nucleic Acids Research}, number = {7}, issn = {1362-4962}, doi = {10.1093/nar/gni065}, pages = {e67}, year = {2005}, language = {en} } @article{SeiblerZevnikKueterLuksetal.2003, author = {Seibler, Jost and Zevnik, Branko and K{\"u}ter-Luks, Birgit and Andreas, Susanne and Kern, Heidrun and Hennek, Thomas and Rode, Anja and Heimann, Cornelia and Faust, Nicole and Kauselmann, Gunther and Schoor, Michael and Jaenisch, Rudolf and Rajewsky, Klaus and K{\"u}hn, Ralf and Schwenk, Frieder}, title = {Rapid generation of inducible mouse mutants}, series = {Nucleic Acids Research}, volume = {33}, journal = {Nucleic Acids Research}, number = {4}, issn = {1362-4962}, doi = {10.1093/nar/gng012}, pages = {e12}, year = {2003}, language = {en} } @article{GoetzeBaerWinkelmannetal.2005, author = {Goetze, Sandra and Baer, Alexandra and Winkelmann, Silke and Nehlsen, Kristina and Seibler, Jost and Maass, Karin and Bode, J{\"u}rgen}, title = {Performance of genomic bordering elements at predefined genomic loci}, series = {Molecular and Cellular Biology}, volume = {25}, journal = {Molecular and Cellular Biology}, number = {6}, issn = {1098-5549}, doi = {10.1128/MCB.25.6.2260-2272.2005}, pages = {2260 -- 2272}, year = {2005}, language = {en} } @article{TakenagaSchneiderErbayetal.2015, author = {Takenaga, Shoko and Schneider, Benno and Erbay, E. and Biselli, Manfred and Schnitzler, Thomas and Sch{\"o}ning, Michael Josef and Wagner, Torsten}, title = {Fabrication of biocompatible lab-on-chip devices for biomedical applications by means of a 3D-printing process}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201532053}, pages = {1347 -- 1352}, year = {2015}, abstract = {A new microfluidic assembly method for semiconductor-based biosensors using 3D-printing technologies was proposed for a rapid and cost-efficient design of new sensor systems. The microfluidic unit is designed and printed by a 3D-printer in just a few hours and assembled on a light-addressable potentiometric sensor (LAPS) chip using a photo resin. The cell growth curves obtained from culturing cells within microfluidics-based LAPS systems were compared with cell growth curves in cell culture flasks to examine biocompatibility of the 3D-printed chips. Furthermore, an optimal cell culturing within microfluidics-based LAPS chips was achieved by adjusting the fetal calf serum concentrations of the cell culture medium, an important factor for the cell proliferation.}, language = {en} } @article{InagakiSleddensLinkelsWassenaaretal.2011, author = {Inagaki, Akiko and Sleddens-Linkels, Esther and Wassenaar, Evelyne and Ooms, Marja and Cappellen, Wiggert A. van and Hoeijmakers, Jan H. J. and Seibler, Jost and Vogt, Thomas F. and Shin, Myung K. and Grootegoed, J. Anton and Baarends, Willy M.}, title = {Meiotic functions of RAD18}, series = {Journal of Cell Science}, volume = {124}, journal = {Journal of Cell Science}, number = {16}, publisher = {Company of Biologists Limited}, address = {Cambridge}, issn = {1477-9137}, doi = {10.1242/jcs.081968}, pages = {2837 -- 2850}, year = {2011}, language = {en} } @article{RaabKappelKraemeretal.2011, author = {Raab, Monika and Kappel, Sven and Kr{\"a}mer, Andrea and Sanhaji, Mourad and Matthess, Yves and Kurunci-Csacsko, Elisabeth and Calzada-Wack, Julia and Rathkolb, Birgit and Rosman, Jan and Adler, Thure and Busch, Dirk H. and Esposito, Irene and Fuchs, Helmut and Gailus-Durner, Val{\´e}rie and Klingenspor, Martin and Wolf, Eckhard and S{\"a}nger, Nicole and Prinz, Florian and Hrabe de Angelis, Martin and Seibler, Jost and Yuan, Juping and Bergmann, Martin and Knecht, Rainald and Kreft, Bertolt and Strebhardt, Klaus}, title = {Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells}, series = {Nature Communications}, volume = {2}, journal = {Nature Communications}, number = {395}, publisher = {Nature}, address = {London}, issn = {2041-1723}, doi = {10.1038/ncomms1395}, pages = {1 -- 11}, year = {2011}, language = {en} } @article{HasegawaKapelyukhTaharaetal.2011, author = {Hasegawa, Maki and Kapelyukh, Yury and Tahara, Harunobu and Seibler, Jost and Rode, Anja and Krueger, Sylvia and Lee, Dongtao N. and Wolf, C. Roland and Scheer, Nico}, title = {Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line}, series = {Molecular Pharmacology}, volume = {80}, journal = {Molecular Pharmacology}, number = {33}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.111.071845}, pages = {518 -- 528}, year = {2011}, language = {en} } @article{JordanKruegerWillmesetal.2011, author = {Jordan, Sabine D. and Kr{\"u}ger, Markus and Willmes, Diana M. and Redemann, Nora and Wunderlich, F. Thomas and Br{\"o}nneke, Hella S. and Merkwirth, Carsten and Kashkar, Hamid and Olkkonen, Vesa M. and B{\"o}ttger, Thomas and Braun, Thomas and Seibler, Jost and Br{\"u}ning, Jens C.}, title = {Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism}, series = {Nature Cell Biology}, volume = {13}, journal = {Nature Cell Biology}, number = {4}, publisher = {Nature}, address = {New York}, issn = {1465-7392}, doi = {10.1038/ncb2211}, pages = {434 -- 446}, year = {2011}, abstract = {The contribution of altered post-transcriptional gene silencing to the development of insulin resistance and type 2 diabetes mellitus so far remains elusive. Here, we demonstrate that expression of microRNA (miR)-143 and 145 is upregulated in the liver of genetic and dietary mouse models of obesity. Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis. Conversely, mice deficient for the miR-143-145 cluster are protected from the development of obesity-associated insulin resistance. Quantitative-mass-spectrometry-based analysis of hepatic protein expression in miR-143-overexpressing mice revealed miR-143-dependent downregulation of oxysterol-binding-protein-related protein (ORP) 8. Reduced ORP8 expression in cultured liver cells impairs the ability of insulin to induce AKT activation, revealing an ORP8-dependent mechanism of AKT regulation. Our experiments provide direct evidence that dysregulated post-transcriptional gene silencing contributes to the development of obesity-induced insulin resistance, and characterize the miR-143-ORP8 pathway as a potential target for the treatment of obesity-associated diabetes.}, language = {en} } @incollection{SeiblerSchwenk2010, author = {Seibler, Jost and Schwenk, Frieder}, title = {Transgenic RNAi Applications in the Mouse}, series = {Methods in Enzymology : Guide to Techniques in Mouse Development, Part B: Mouse Molecular Genetics. 2nd Edition}, booktitle = {Methods in Enzymology : Guide to Techniques in Mouse Development, Part B: Mouse Molecular Genetics. 2nd Edition}, publisher = {Elsevier}, address = {Amsterdam}, isbn = {978-0-12-384880-2}, pages = {367 -- 386}, year = {2010}, language = {en} } @article{GlaserLubitzLovelandetal.2009, author = {Glaser, Stefan and Lubitz, Sandra and Loveland, Kate L. and Ohbo, Kazu and Robb, Lorraine and Schwenk, Frieder and Seibler, Jost and Roellig, Daniela and Kranz, Andrea and Anastassiadis, Konstantinos and Stewart, A. Francis}, title = {The histone 3 lysine 4 methyltransferase, Mll2, is only required briefly in development and spermatogenesis}, series = {Epigenetics \& Chromatin}, volume = {2}, journal = {Epigenetics \& Chromatin}, number = {5}, issn = {1756-8935}, doi = {10.1186/1756-8935-2-5}, pages = {1 -- 16}, year = {2009}, language = {en} } @article{KotnikPopovaTodirasetal.2009, author = {Kotnik, Katarina and Popova, Elena and Todiras, Mihail and Mori, Marcelo A. and Alenina, Natalia and Seibler, Jost and Bader, Michael}, title = {Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown}, series = {Plos One}, volume = {4}, journal = {Plos One}, number = {4}, publisher = {Plos}, address = {San Francisco, California, US}, doi = {10.1371/journal.pone.0005124}, pages = {e5124}, year = {2009}, language = {en} } @article{HeroldBrandtSeibleretal.2008, author = {Herold, Marco J. and Brandt, Jens van den and Seibler, Jost and Reichardt, Holger M.}, title = {Inducible and reversible gene silencing by stable integration of an shRNA-encoding lentivirus in transgenic rats}, series = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {47}, issn = {1091-6490}, doi = {10.1073/pnas.0806213105}, pages = {18507 -- 18512}, year = {2008}, language = {en} } @article{KochWunderlichSeibleretal.2008, author = {Koch, Linda and Wunderlich, F. Thomas and Seibler, Jost and K{\"o}nner, A. Christine and Hampel, Brigitte and Irlenbusch, Sigrid and Brabant, Georg and Kahn, C. Ronald and Schwenk, Frieder and Br{\"u}ning, Jens C.}, title = {Central insulin action regulates peripheral glucose and fat metabolism in mice}, series = {The Journal of Clinical Investigation (JCI)}, volume = {118}, journal = {The Journal of Clinical Investigation (JCI)}, number = {6}, issn = {1558-8238}, doi = {10.1172/JCI31073}, pages = {2132 -- 2147}, year = {2008}, language = {en} } @article{ChristophBahrenbergVryetal.2008, author = {Christoph, Thomas and Bahrenberg, Gregor and Vry, Jean de and Englberger, Werner and Erdmann, Volker A. and Frech, Moritz and K{\"o}gel, Babette and R{\"o}hl, Thomas and Schiene, Klaus and Schr{\"o}der, Wolfgang and Seibler, Jost and Kurreck, Jens}, title = {Investigation of TRPV1 loss-of-function phenotypes in transgenic shRNA expressing and knockout mice}, series = {Molecular and Cellular Neuroscience}, volume = {37}, journal = {Molecular and Cellular Neuroscience}, number = {3}, issn = {1044-7431}, doi = {10.1016/j.mcn.2007.12.006}, pages = {579 -- 589}, year = {2008}, language = {en} } @article{CesariRennekampffVinterstenetal.2004, author = {Cesari, Francesca and Rennekampff, Verena and Vintersten, Kristina and Vuong, Lam Giang and Seibler, Jost and Bode, J{\"u}rgen and Wiebel, Franziska F. and Nordheim, Alfred}, title = {Elk-1 knock-out mice engineered by Flp recombinase-mediated cassette exchange}, series = {Genesis : The Journal of Genetics and Development}, volume = {38}, journal = {Genesis : The Journal of Genetics and Development}, number = {2}, issn = {1526-968X}, doi = {10.1002/gene.20003}, pages = {87 -- 92}, year = {2004}, language = {en} } @article{BodeSchlakeIberetal.2000, author = {Bode, J{\"u}rgen and Schlake, Thomas and Iber, Michaela and Sch{\"u}beler, Dirk and Seibler, Jost and Snezhkov, Evgeney and Nikolaev, Lev}, title = {The transgeneticist's toolbox: novel methods for the targeted modification of eukaryotic genomes}, series = {Biological Chemistry}, volume = {381}, journal = {Biological Chemistry}, number = {9-10}, issn = {1431-6730}, doi = {10.1515/BC.2000.103}, pages = {801 -- 813}, year = {2000}, language = {en} } @article{FengSeiblerAlamietal.1999, author = {Feng, Yong-Qing and Seibler, Jost and Alami, Raouf and Eisen, Andrew and Westerman, Karen A. and Leboulch, Philippe and Fiering, Steven and Bouhassira, Eric E.}, title = {Site-specific chromosomal integration in mammalian cells: highly efficient CRE recombinase-mediated cassette exchange}, series = {Journal of Molecular Biology}, volume = {292}, journal = {Journal of Molecular Biology}, number = {4}, issn = {0022-2836}, doi = {10.1006/jmbi.1999.3113}, pages = {779 -- 785}, year = {1999}, language = {en} } @article{SeiblerSchuebelerFieringetal.1998, author = {Seibler, Jost and Sch{\"u}beler, Dirk and Fiering, Steven and Groudine, Mark and Bode, J{\"u}rgen}, title = {DNA cassette exchange in ES cells mediated by Flp recombinase: an efficient strategy for repeated modification of tagged loci by marker-free constructs}, series = {Biochemistry}, volume = {37}, journal = {Biochemistry}, number = {18}, issn = {1520-4995}, doi = {10.1021/bi980288t}, pages = {6229 -- 6234}, year = {1998}, language = {en} } @article{SeiblerBode1997, author = {Seibler, Jost and Bode, J{\"u}rgen}, title = {Double-reciprocal crossover mediated by FLP-recombinase: a concept and an assay}, series = {Biochemistry}, volume = {36}, journal = {Biochemistry}, number = {7}, issn = {1520-4995}, pages = {1740 -- 1747}, year = {1997}, language = {en} } @article{BodeBartschBoulikasetal.1998, author = {Bode, J. and Bartsch, J. and Boulikas, T. and Iber, M. and Mielke, C. and Sch{\"u}beler, D. and Seibler, Jost and Benham, C.}, title = {Transcription-promoting genomic sites in mammalia: their elucidation and architectural principles}, series = {Gene therapy \& molecular biology}, volume = {1}, journal = {Gene therapy \& molecular biology}, number = {1}, issn = {1529-9120}, pages = {1 -- 29}, year = {1998}, language = {en} } @article{IberSchuebelerSeibleretal.1998, author = {Iber, Michaela and Sch{\"u}beler, Dirk and Seibler, Jost and H{\"o}xter, Maria and Bode, J{\"u}rgen}, title = {Efficient FACS selection procedure for cells undergoing Flp-mediated site-specific conversions}, series = {Technical Tips Online}, volume = {4}, journal = {Technical Tips Online}, number = {1}, doi = {10.1016/S1366-2120(08)70132-6}, pages = {25 -- 29}, year = {1998}, language = {en} } @article{HenkenOosterhuisOehlschlaegeretal.2012, author = {Henken, F. E. and Oosterhuis, K. and {\"O}hlschl{\"a}ger, Peter and Bosch, L. and Hooijberg, E. and Haanen, J. B. A. G. and Steenbergen, R. D. M.}, title = {Preclinical safety evaluation of DNA vaccines encoding modified HPV16 E6 and E7}, series = {Vaccine}, volume = {30}, journal = {Vaccine}, number = {28}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0264-410X}, doi = {10.1016/j.vaccine.2012.04.013}, pages = {4259 -- 4266}, year = {2012}, abstract = {Persistent infection with high-risk human papillomaviruses (hrHPV) can result in the formation of anogenital cancers. As hrHPV proteins E6 and E7 are required for cancer initiation and maintenance, they are ideal targets for immunotherapeutic interventions. Previously, we have described the development of DNA vaccines for the induction of HPV16 E6 and E7 specific T cell immunity. These vaccines consist of 'gene-shuffled' (SH) versions of HPV16 E6 and E7 that were fused to Tetanus Toxin Fragment C domain 1 (TTFC) and were named TTFC-E6SH and TTFC-E7SH. Gene-shuffling was performed to avoid the risk of inducing malignant transformation at the vaccination site. Here, we describe the preclinical safety evaluation of these candidate vaccines by analysis of their transforming capacity in vitro using established murine fibroblasts (NIH 3T3 cells) and primary human foreskin keratinocytes (HFKs). We demonstrate that neither ectopic expression of TTFC-E6SH and TTFC-E7SH alone or in combination enabled NIH 3T3 cells to form colonies in soft agar. In contrast, expression of HPV16 E6WT and E7WT alone or in combination resulted in effective transformation. Similarly, retroviral transduction of HFKs from three independent donors with both TTFC-E6SH and TTFC-E7SH alone or in combination did not show any signs of immortalization. In contrast, the combined expression of E6WT and E7WT induced immortalization in HFKs from all donors. Based on these results we consider it justified to proceed to clinical evaluation of DNA vaccines encoding TTFC-E6SH and TTFC-E7SH in patients with HPV16 associated (pre)malignancies.}, language = {en} } @article{ImmelGruetzkeSpaeteetal.2012, author = {Immel, Timo and Gr{\"u}tzke, Martin and Sp{\"a}te, Anne-Katrin and Groth, Ulrich and {\"O}hlschl{\"a}ger, Peter and Huhn, Thomas}, title = {Synthesis and X-ray structure analysis of a heptacoordinate titanium(IV)-bis-chelate with enhanced in vivo antitumor efficacy}, series = {Chemical Communications}, volume = {48}, journal = {Chemical Communications}, number = {46}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1364-548X}, doi = {10.1039/C2CC31624B}, pages = {5790 -- 5792}, year = {2012}, abstract = {Chelate stabilization of a titanium(IV)-salan alkoxide by ligand exchange with 2,6-pyridinedicarboxylic acid (dipic) resulted in heptacoordinate complex 3 which is not redox-active, stable on silica gel and has increased aqueous stability. 3 is highly toxic in HeLa S3 and Hep G2 and has enhanced antitumor efficacy in a mouse cervical-cancer model.}, 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{BouwmanGuldenHeijdenetal.2013, author = {Bouwman, Peter and Gulden, Hanneke van der and Heijden, Ingrid van der and Drost, Rinske and Klijn, Christiaan N. and Prasetyanti, Pramudita and Pieterse, Mark and Wientjens, Ellen and Seibler, Jost and Hogervorst, Frank B. L. and Jonkers, Jos}, title = {A High-Throughput Functional Complementation Assay for Classification of BRCA1 Missense Variants}, series = {Cancer Discovery}, journal = {Cancer Discovery}, number = {3}, issn = {2159-8290}, doi = {10.1158/2159-8290.CD-13-0094}, pages = {1142 -- 1152}, year = {2013}, language = {en} } @article{MichalakNacerddinePietersenetal.2013, author = {Michalak, Ewa Malgorzata and Nacerddine, Karim and Pietersen, Alexandra and Beuger, Vincent and Pawlitzky, Inka and Cornelissen-Steijger, Paulien and Wientjens, Ellen and Tanger, Ellen and Seibler, Jost and Lohuizen, Maarten van and Jonkers, Jos}, title = {Polycomb group gene Ezh2 regulates mammary gland morphogenesis and maintains the luminal progenitor pool}, series = {Stem Cells}, volume = {Vol 31}, journal = {Stem Cells}, number = {9}, publisher = {Oxford University Press}, address = {Oxford}, issn = {1549-4918}, doi = {10.1002/stem.1437}, pages = {1910 -- 1920}, year = {2013}, language = {en} } @article{GebeshuberKornauthDongetal.2013, author = {Gebeshuber, Christoph A. and Kornauth, Christoph and Dong, Lihua and Sierig, Ralph and Seibler, Jost and Reiss, Martina and Tauber, Stefanie and Bilban, Martin and Wang, Shijun and Kain, Renate and B{\"o}hmig, Georg A. and Moeller, Marcus J. and Gr{\"o}ne, Hermann-Josef and Englert, Christoph and Martinez, Javier and Kerjaschki, Dontscho}, title = {Focal segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1}, series = {Nature Medicine}, volume = {19}, journal = {Nature Medicine}, number = {4}, issn = {1078-8956}, doi = {10.1038/nm.3142}, pages = {481 -- 487}, year = {2013}, language = {en} } @article{KornfeldBaitzelKoenneretal.2013, author = {Kornfeld, Jan-Wilhelm and Baitzel, Catherina and K{\"o}nner, A. Christine and Nicholls, Hayley T. and Vogt, Merly C. and Herrmanns, Karolin and Scheja, Ludger and Haumaitre, C{\´e}cile and Wolf, Anna M. and Knippschild, Uwe and Seibler, Jost and Cereghini, Silvia and Heeren, Joerg and Stoffel, Markus and Br{\"u}ning, Jens C.}, title = {Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b}, series = {Nature}, volume = {494}, journal = {Nature}, number = {7435}, publisher = {Springer Nature}, address = {Cham}, isbn = {0028-0836}, doi = {10.1038/nature11793}, pages = {111 -- 115}, year = {2013}, language = {en} } @inproceedings{BreuerRaueMangetal.2015, author = {Breuer, Lars and Raue, Markus and Mang, Thomas and Sch{\"o}ning, Michael Josef and Thoelen, Ronald and Wagner, Torsten}, title = {Light-stimulated hydrogel actuators with incorporated graphene oxide for microfluidic applications}, series = {12. Dresdner Sensor-Symposium 2015}, booktitle = {12. Dresdner Sensor-Symposium 2015}, doi = {10.5162/12dss2015/P5.8}, pages = {206 -- 209}, year = {2015}, language = {en} } @article{BreuerRaueStrobeletal.2016, author = {Breuer, Lars and Raue, Markus and Strobel, M. and Mang, Thomas and Sch{\"o}ning, Michael Josef and Thoelen, R. and Wagner, Torsten}, title = {Hydrogels with incorporated graphene oxide as light-addressable actuator materials for cell culture environments in lab-on-chip systems}, series = {Physica status solidi (a)}, volume = {213}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1862-6300}, doi = {10.1002/pssa.201533056}, pages = {1520 -- 1525}, year = {2016}, abstract = {Abstractauthoren Graphene oxide (GO) nanoparticles were incorporated in temperature-sensitive Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels. The nanoparticles increase the light absorption and convert light energy into heat efficiently. Thus, the hydrogels with GO can be stimulated spatially resolved by illumination as it was demonstrated by IR thermography. The temporal progression of the temperature maximum was detected for different concentrations of GO within the polymer network. Furthermore, the compatibility of PNIPAAm hydrogels with GO and cell cultures was investigated. For this purpose, culture medium was incubated with hydrogels containing GO and the viability and morphology of chinese hamster ovary (CHO) cells was examined after several days of culturing in presence of this medium.}, language = {en} } @inproceedings{KasperSchiffelsKrafftetal.2016, author = {Kasper, Katharina and Schiffels, Johannes and Krafft, Simone and Kuperjans, Isabel and Elbers, Gereon and Selmer, Thorsten}, title = {Biogas Production on Demand Regulated by Butyric Acid Addition}, series = {IOP Conference Series: Earth and Environmental Science. Bd. 32}, volume = {32}, booktitle = {IOP Conference Series: Earth and Environmental Science. Bd. 32}, issn = {1755-1315}, doi = {10.1088/1755-1315/32/1/012009}, pages = {012009/1 -- 012009/4}, year = {2016}, language = {en} } @article{PolenKraemerBongaertsetal.2005, author = {Polen, T. and Kr{\"a}mer, Marco and Bongaerts, Johannes and Wubbolts, Marcel and Wendisch, V. F.}, title = {The global gene expression response of Escherichia coli to L-phenylalanine}, series = {Journal of biotechnology}, volume = {Vol. 115}, journal = {Journal of biotechnology}, number = {Iss. 3}, issn = {1873-4863 (E-Journal); 0168-1656 (Print)}, pages = {221 -- 237}, year = {2005}, language = {en} } @article{BongaertsKraemerMuelleretal.2001, author = {Bongaerts, Johannes and Kr{\"a}mer, Marco and M{\"u}ller, Ulrike and Raeven, Leon and Wubbolts, Marcel}, title = {Metabolic engineering for microbial production of aromatic amino acids and derived compounds}, series = {Metabolic engineering}, volume = {Vol. 3}, journal = {Metabolic engineering}, number = {Iss. 4}, issn = {1096-7184 (E-Journal); 1096-7176 (Print)}, pages = {289 -- 300}, year = {2001}, language = {en} } @article{BongaertsEsserLorbachetal.2011, author = {Bongaerts, Johannes and Esser, Simon and Lorbach, Volker and Al-Momani, L{\´o}ay and M{\"u}ller, Michael A. and Franke, Dirk and Grondal, Christoph and Kurutsch, Anja and Bujnicki, Robert and Takors, Ralf and Raeven, Leon and Wubbolts, Marcel and Bovenberg, Roel and Nieger, Martin and Sch{\"u}rmann, Melanie and Trachtmann, Natalie and Kozak, Stefan and Sprenger, Georg A. and M{\"u}ller, Michael}, title = {Diversity-oriented production of metabolites derived from chorismate and their use in organic synthesis}, series = {Angewandte Chemie International Edition}, volume = {Vol. 50}, journal = {Angewandte Chemie International Edition}, number = {Iss. 34}, publisher = {Wiley}, address = {Weinheim}, issn = {1521-3773 (E-Journal); 0570-0833 (Print); 1433-7851 (Print)}, pages = {7781 -- 7786}, year = {2011}, language = {en} } @article{MuellerBeckersMussmannetal.2018, author = {M{\"u}ller, Janina and Beckers, Mario and Mußmann, Nina and Bongaerts, Johannes and B{\"u}chs, Jochen}, title = {Elucidation of auxotrophic deficiencies of Bacillus pumilus DSM 18097 to develop a defined minimal medium}, series = {Microbial Cell Factories}, volume = {17}, journal = {Microbial Cell Factories}, number = {1}, publisher = {BioMed Central}, issn = {1475-2859}, doi = {10.1186/s12934-018-0956-1}, pages = {Article No. 106}, year = {2018}, abstract = {Background Culture media containing complex compounds like yeast extract or peptone show numerous disadvantages. The chemical composition of the complex compounds is prone to significant variations from batch to batch and quality control is difficult. Therefore, the use of chemically defined media receives more and more attention in commercial fermentations. This concept results in better reproducibility, it simplifies downstream processing of secreted products and enable rapid scale-up. Culturing bacteria with unknown auxotrophies in chemically defined media is challenging and often not possible without an extensive trial-and-error approach. In this study, a respiration activity monitoring system for shake flasks and its recent version for microtiter plates were used to clarify unknown auxotrophic deficiencies in the model organism Bacillus pumilus DSM 18097. Results Bacillus pumilus DSM 18097 was unable to grow in a mineral medium without the addition of complex compounds. Therefore, a rich chemically defined minimal medium was tested containing basically all vitamins, amino acids and nucleobases, which are essential ingredients of complex components. The strain was successfully cultivated in this medium. By monitoring of the respiration activity, nutrients were supplemented to and omitted from the rich chemically defined medium in a rational way, thus enabling a systematic and fast determination of the auxotrophic deficiencies. Experiments have shown that the investigated strain requires amino acids, especially cysteine or histidine and the vitamin biotin for growth. Conclusions The introduced method allows an efficient and rapid identification of unknown auxotrophic deficiencies and can be used to develop a simple chemically defined tailor-made medium. B. pumilus DSM 18097 was chosen as a model organism to demonstrate the method. However, the method is generally suitable for a wide range of microorganisms. By combining a systematic combinatorial approach based on monitoring the respiration activity with cultivation in microtiter plates, high throughput experiments with high information content can be conducted. This approach facilitates media development, strain characterization and cultivation of fastidious microorganisms in chemically defined minimal media while simultaneously reducing the experimental effort.}, language = {en} } @article{RachingerBauchStrittmatteretal.2013, author = {Rachinger, Michael and Bauch, Melanie and Strittmatter, Axel and Bongaerts, Johannes and Evers, Stefan and Maurer, Karl-Heinz and Daniel, Rolf and Liebl, Wolfgang and Liesegang, Heiko and Ehrenreich, Armin}, title = {Size unlimited markerless deletions by a transconjugative plasmid-system in Bacillus licheniformis}, series = {Journal of biotechnology}, volume = {Vol. 164}, journal = {Journal of biotechnology}, number = {Iss. 4}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-4863 (E-Journal); 0168-1656 (Print)}, pages = {365 -- 369}, year = {2013}, language = {en} } @article{WissenbachSixBongaertsetal.1995, author = {Wissenbach, U. and Six, S. and Bongaerts, Johannes and Ternes, D. and Steinwachs, S. and Unden, G.}, title = {A third periplasmic transport system for l-arginine in Escherichia coli: molecular characterization of the artPIQMJ genes, arginine binding and transport}, series = {Molecular microbiology}, volume = {Vol. 17}, journal = {Molecular microbiology}, number = {Iss. 4}, issn = {1365-2958 (E-Journal); 0950-382x (Print)}, pages = {675 -- 686}, year = {1995}, language = {en} } @misc{StadtmuellerTippkoetterUlber2013, author = {Stadtm{\"u}ller, Ralf and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {A method for production of single-stranded nucleic acids [Europ{\"a}ische Patentanmeldung]}, publisher = {Europ{\"a}isches Patentamt}, address = {Den Hague}, pages = {14 Seiten}, year = {2013}, language = {en} } @article{ThielMufflerTippkoetteretal.2015, author = {Thiel, Alexander and Muffler, Kai and Tippk{\"o}tter, Nils and Suck, Kirstin and Sohling, Ulrich and Hruschka, Steffen M. and Ulber, Roland}, title = {A novel integrated downstream processing approach to recover sinapic acid, phytic acid and proteins from rapeseed meal}, series = {Journal of Chemical Technology and Biotechnology}, volume = {90}, journal = {Journal of Chemical Technology and Biotechnology}, number = {11}, publisher = {Wiley}, address = {Weinheim}, doi = {10.1002/jctb.4664}, pages = {1999 -- 2006}, year = {2015}, abstract = {BACKGROUND Currently, several techniques exist for the downstream processing of protein, phytic acid and sinapic acid from rapeseed and rapeseed meal, but no technique has been developed to separate all of the components in one process. In this work, two new downstream processing strategies focusing on recovering sinapic acid, phytic acid and protein from rapeseed meal were established. RESULTS The sinapic acid content was enhanced by a factor of 4.5 with one method and 5.1 with the other. The isolation of sinapic acid was accomplished using a zeolite-based adsorbent with high adsorptive and optimal desorption characteristics. Phytic acid was isolated using the anion-exchange resin Purolite A200®. In addition, the processes resulted in two separated protein fractions. The ratios of globulin and albumin ratio to the total protein were 59.2\% and 40.1\%, respectively. The steps were then combined in two different ways: (a) a 'sequential process' using the zeolite and A200 in batch processes; and (b) a 'parallel process' using only A200 in a chromatographic system to separate all of the compounds. CONCLUSIONS It can be concluded that isolation of all three components was possible in both processes. These could enhance the added value of current processes using rapeseed meal as a protein source. © 2015 Society of Chemical Industry}, language = {en} } @article{AlKaidyTippkoetter2016, author = {Al-Kaidy, Huschyar and Tippk{\"o}tter, Nils}, title = {Superparamagnetic hydrophobic particles as shell material for digital microfluidic droplets and proof-of-principle reaction assessments with immobilized laccase}, series = {Engineering in Life Sciences}, volume = {16}, journal = {Engineering in Life Sciences}, number = {3}, publisher = {Wiley-VCH}, address = {Weinheim}, doi = {10.1002/elsc.201400124}, pages = {222 -- 230}, year = {2016}, abstract = {In the field of biotechnology and molecular biology, the use of small liquid volumes has significant advantages. In particular, screening and optimization runs with acceptable amounts of expensive and hardly available catalysts, reagents, or biomolecules are feasible with microfluidic technologies. The presented new microfluidic system is based on the inclusion of small liquid volumes by a protective shell of magnetizable microparticles. Hereby, discrete aqueous microreactor drops with volumes of 1-30 μL can be formed on a simple planar surface. A digital movement and manipulation of the microreactor is performed by overlapping magnetic forces. The magnetic forces are generated by an electrical coil matrix positioned below a glass plate. With the new platform technology, several discrete reaction compartments can be moved simultaneously on one surface. Due to the magnetic fields, the reactors can even be merged to initiate reactions by mixing or positioned above surface-immobilized catalysts and then opened by magnetic force. Comparative synthesis routes of the magnetizable shell particles and superhydrophobic glass slides including their performance and stability with the reaction platform are described. The influence of diffusive mass transport during the catalyzed reaction is discussed by evaluation finite element model of the microreactor. Furthermore, a first model dye reaction of the enzyme laccase has been established.}, language = {en} } @article{EngelBayerHoltmannetal.2019, author = {Engel, Mareike and Bayer, Hendrik and Holtmann, Dirk and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Flavin secretion of Clostridium acetobutylicum in a bioelectrochemical system - Is an iron limitation involved?}, series = {Bioelectrochemistry}, journal = {Bioelectrochemistry}, number = {In Press, Accepted Manuscript}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1567-5394}, doi = {10.1016/j.bioelechem.2019.05.014}, year = {2019}, language = {en} } @misc{TippkoetterUlber2009, author = {Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Eine magnetische horizontale Wirbelschicht f{\"u}r die Durchmischung und R{\"u}ckhaltung von magnetisierbaren Mikropartikeln im Durchfluss}, series = {Chemie Ingenieur Technik}, volume = {81}, journal = {Chemie Ingenieur Technik}, number = {8}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.200950076}, pages = {1168}, year = {2009}, abstract = {Magnetisierbare Partikel als Tr{\"a}ger von Katalysatoren k{\"o}nnen durch Anlegen eines magnetisches Feldes einfach und schnell abgetrennt werden. Die Wiedergewinnung von wertvollen Enzymen unter geringem Energie- und Materialeinsatz der magnetischen Abtrennung er{\"o}ffnet einen Wettbewerbsvorteil f{\"u}r Produktionsprozesse. Die Abtrennung von magnetisierbaren Partikeln vom {\"U}berstand wird {\"u}blicherweise entweder durch Anlegen eines {\"a}ußeren Magnetfelds und der resultierenden Ablagerung der Partikel an den Reaktorw{\"a}nden oder durch Hochgradientenmagnetseparation (HGMS)durchgef{\"u}hrt. Beide Verfahren resultieren meist in der Bildung eines Filterkuchens aus Magnetpartikeln und den Feststoffen des Reaktionsmediums. Das magnetische horizontale Wirbelbett erm{\"o}glicht simultan eine kontinuierliche Reaktionsf{\"u}hrung und die R{\"u}ckhaltung der Partikel im Durchfluss. Die Partikelsuspension fließt durch einen Rohrreaktor, der in einem Magnetfeld mit wechselnden Feldgradienten eingebracht ist. Die {\"A}nderung des Magnetfeldgradienten erfolgt entgegen der Str{\"o}mungsrichtung der Reaktionsl{\"o}sung. Durch alternierende Feldmaxima an den beiden Seiten des Reaktors werden die magnetisierbaren Partikel zu dessen W{\"a}nden gezogen. Bei Umkehrung des Feldes wandern die Partikel an die gegen{\"u}berliegende Reaktorwand. Durch Wahl einer geeigneten Wechselfrequenz kann eine kontinuierliche Durchmischung und R{\"u}ckhaltung der Mikropartikel im durchstr{\"o}mten Rohr erreicht werden. Somit k{\"o}nnen Immobilisierungsreaktionen und Biotransformationen mit den Partikelsystemen im Durchfluss durchgef{\"u}hrt werden.}, language = {en} } @article{SiekerNeunerDimitrovaetal.2011, author = {Sieker, Tim and Neuner, Andreas and Dimitrova, Darina and Tippk{\"o}tter, Nils and Muffler, Kai and Bart, Hans-J{\"o}rg and Heinzle, Elmar and Ulber, Roland}, title = {Ethanol production from grass silage by simultaneous pretreatment, saccharification and fermentation: First steps in the process development}, series = {Engineering in Life Sciences}, volume = {11}, journal = {Engineering in Life Sciences}, number = {4}, publisher = {Wiley}, address = {Weinheim}, doi = {10.1002/elsc.201000160}, pages = {436 -- 442}, year = {2011}, abstract = {Grass silage provides a great potential as renewable feedstock. Two fractions of the grass silage, a press juice and the fiber fraction, were evaluated for their possible use for bioethanol production. Direct production of ethanol from press juice is not possible due to high concentrations of organic acids. For the fiber fraction, alkaline peroxide or enzymatic pretreatment was used, which removes the phenolic acids in the cell wall. In this study, we demonstrate the possibility to integrate the enzymatic pretreatment with a simultaneous saccharification and fermentation to achieve ethanol production from grass silage in a one-process step. Achieved yields were about 53 g ethanol per kg silage with the alkaline peroxide pretreatment and 91 g/kg with the enzymatic pretreatment at concentrations of 8.5 and 14.6 g/L, respectively. Furthermore, it was shown that additional supplementation of the fermentation medium with vitamins, trace elements and nutrient salts is not necessary when the press juice is directly used in the fermentation step.}, language = {en} } @article{HandtkeSchroeterJuergenetal.2014, author = {Handtke, Stefan and Schroeter, Rebecca and J{\"u}rgen, Britta and Methling, Karen and Schl{\"u}ter, Rabea and Albrecht, Dirk and Hijum, Sacha A. F. T. van and Bongaerts, Johannes and Maurer, Karl-Heinz and Lalk, Michael and Schweder, Thomas and Hecker, Michael and Voigt, Birgit}, title = {Bacillus pumilus reveals a remarkably high resistance to hydrogen peroxide provoked oxidative stress}, series = {PLOS one}, volume = {9}, journal = {PLOS one}, number = {1}, publisher = {PLOS}, address = {San Francisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0085625}, pages = {e85625}, year = {2014}, abstract = {Bacillus pumilus is characterized by a higher oxidative stress resistance than other comparable industrially relevant Bacilli such as B. subtilis or B. licheniformis. In this study the response of B. pumilus to oxidative stress was investigated during a treatment with high concentrations of hydrogen peroxide at the proteome, transcriptome and metabolome level. Genes/proteins belonging to regulons, which are known to have important functions in the oxidative stress response of other organisms, were found to be upregulated, such as the Fur, Spx, SOS or CtsR regulon. Strikingly, parts of the fundamental PerR regulon responding to peroxide stress in B. subtilis are not encoded in the B. pumilus genome. Thus, B. pumilus misses the catalase KatA, the DNA-protection protein MrgA or the alkyl hydroperoxide reductase AhpCF. Data of this study suggests that the catalase KatX2 takes over the function of the missing KatA in the oxidative stress response of B. pumilus. The genome-wide expression analysis revealed an induction of bacillithiol (Cys-GlcN-malate, BSH) relevant genes. An analysis of the intracellular metabolites detected high intracellular levels of this protective metabolite, which indicates the importance of bacillithiol in the peroxide stress resistance of B. pumilus.}, language = {en} } @article{KapplerTanudyayaSchmittTippkoetteretal.2007, author = {Kappler-Tanudyaya, Nathalie and Schmitt, Heike and Tippk{\"o}tter, Nils and Meyer, Lina and Lenzen, Sigurd and Ulber, Roland}, title = {Combination of biotransformation and chromatography for the isolation and purification of mannoheptulose}, series = {Biotechnology Journal}, volume = {2}, journal = {Biotechnology Journal}, number = {6}, issn = {1860-7314}, doi = {10.1002/biot.200700004}, pages = {692 -- 699}, year = {2007}, abstract = {Mannoheptulose is a seven-carbon sugar. It is an inhibitor of glucose-induced insulin secretion due to its ability to selectively inhibit the enzyme glucokinase. An improved procedure for mannoheptulose isolation from avocados is described in this study (based upon the original method by La Forge). The study focuses on the combination of biotransformation and downstream processing (preparative chromatography) as an efficient method to produce a pure extract of mannoheptulose. The experiments were divided into two major phases. In the first phase, several methods and parameters were compared to optimize the mannoheptulose extraction with respect to efficiency and purity. In the second phase, a mass balance of mannoheptulose over the whole extraction process was undertaken to estimate the yield and efficiency of the total extraction process. The combination of biotransformation and preparative chromatography allowed the production of a pure mannoheptulose extract. In a biological test, the sugar inhibited the glucokinase enzyme activity efficiently.}, language = {en} } @article{MuschallikKippReckeretal.2020, author = {Muschallik, Lukas and Kipp, Carina Ronja and Recker, Inga and Bongaerts, Johannes and Pohl, Martina and Gelissen, Melanie and Sch{\"o}ning, Michael Josef and Selmer, Thorsten and Siegert, Petra}, title = {Synthesis of α-hydroxy ketones and vicinal diols with the Bacillus licheniformis DSM 13T butane-2, 3-diol dehydrogenase}, series = {Journal of Biotechnology}, volume = {202}, journal = {Journal of Biotechnology}, number = {Vol. 324}, publisher = {Elsevier}, address = {Amsterdam}, isbn = {2590-1559}, doi = {10.1016/j.jbiotec.2020.09.016}, pages = {61 -- 70}, year = {2020}, abstract = {The enantioselective synthesis of α-hydroxy ketones and vicinal diols is an intriguing field because of the broad applicability of these molecules. Although, butandiol dehydrogenases are known to play a key role in the production of 2,3-butandiol, their potential as biocatalysts is still not well studied. Here, we investigate the biocatalytic properties of the meso-butanediol dehydrogenase from Bacillus licheniformis DSM 13T (BlBDH). The encoding gene was cloned with an N-terminal StrepII-tag and recombinantly overexpressed in E. coli. BlBDH is highly active towards several non-physiological diketones and α-hydroxyketones with varying aliphatic chain lengths or even containing phenyl moieties. By adjusting the reaction parameters in biotransformations the formation of either the α-hydroxyketone intermediate or the diol can be controlled.}, language = {en} } @book{ArtmannTemizArtmannZhubanovaetal.2018, author = {Artmann, Gerhard and Temiz Artmann, Ayseg{\"u}l and Zhubanova, Azhar A. and Digel, Ilya}, title = {Biological, physical and technical basics of cell engineering}, editor = {Artmann, Gerhard and Temiz Artmann, Ayseg{\"u}l and Zhubanova, Azhar A. and Digel, Ilya}, publisher = {Springer}, address = {Singapore}, isbn = {978-981-10-7903-0}, pages = {xxiv, 481 Seiten ; Illustrationen, Diagramme}, year = {2018}, language = {en} } @article{KraemerBongaertsBovenbergetal.2003, author = {Kr{\"a}mer, Marco and Bongaerts, Johannes and Bovenberg, Roel and Kremer, Susanne and M{\"u}ller, Ulrike and Orf, Sonja and Wubbolts, Marcel and Raeven, Leon}, title = {Metabolic engineering for microbial production of shikimic acid}, series = {Metabolic engineering}, volume = {Vol. 5}, journal = {Metabolic engineering}, number = {Iss. 4}, issn = {1096-7184 (E-Journal); 1096-7176 (Print)}, pages = {277 -- 283}, year = {2003}, language = {en} } @article{CapitainRossJonesMoehringetal.2020, author = {Capitain, Charlotte and Ross-Jones, Jesse and M{\"o}hring, Sophie and Tippk{\"o}tter, Nils}, title = {Differential scanning calorimetry for quantification of polymer biodegradability in compost}, series = {International Biodeterioration \& Biodegradation}, volume = {149}, journal = {International Biodeterioration \& Biodegradation}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0964-8305}, doi = {10.1016/j.ibiod.2020.104914}, pages = {In Press, Article number 104914}, year = {2020}, abstract = {The objective of this study is the establishment of a differential scanning calorimetry (DSC) based method for online analysis of the biodegradation of polymers in complex environments. Structural changes during biodegradation, such as an increase in brittleness or crystallinity, can be detected by carefully observing characteristic changes in DSC profiles. Until now, DSC profiles have not been used to draw quantitative conclusions about biodegradation. A new method is presented for quantifying the biodegradation using DSC data, whereby the results were validated using two reference methods. The proposed method is applied to evaluate the biodegradation of three polymeric biomaterials: polyhydroxybutyrate (PHB), cellulose acetate (CA) and Organosolv lignin. The method is suitable for the precise quantification of the biodegradability of PHB. For CA and lignin, conclusions regarding their biodegradation can be drawn with lower resolutions. The proposed method is also able to quantify the biodegradation of blends or composite materials, which differentiates it from commonly used degradation detection methods.}, language = {en} } @article{EngelHoltmannUlberetal.2018, author = {Engel, Mareike and Holtmann, Dirk and Ulber, Roland and Tippk{\"o}tter, Nils}, title = {Increased Biobutanol Production by Mediator-Less Electro-Fermentation}, series = {Biotechnology Journal}, volume = {14}, journal = {Biotechnology Journal}, number = {4}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1860-7314}, doi = {10.1002/biot.201800514}, year = {2018}, abstract = {A future bio-economy should not only be based on renewable raw materials but also in the raise of carbon yields of existing production routes. Microbial electrochemical technologies are gaining increased attention for this purpose. In this study, the electro-fermentative production of biobutanol with C. acetobutylicum without the use of exogenous mediators is investigated regarding the medium composition and the reactor design. It is shown that the use of an optimized synthetic culture medium allows higher product concentrations, increased biofilm formation, and higher conductivities compared to a synthetic medium supplemented with yeast extract. Moreover, the optimization of the reactor system results in a doubling of the maximum product concentrations for fermentation products. When a working electrode is polarized at -600 mV vs. Ag/AgCl, a shift from butyrate to acetone and butanol production is induced. This leads to an increased final solvent yield of Yᴀᴃᴇ = 0.202 gg⁻¹ (control 0.103 gg⁻¹), which is also reflected in a higher carbon efficiency of 37.6\% compared to 23.3\% (control) as well as a fourfold decrease in simplified E-factor to 0.43. The results are promising for further development of biobutanol production in bioelectrochemical systems in order to fulfil the principles of Green Chemistry.}, language = {en} } @article{EngelGemuendeHoltmannetal.2019, author = {Engel, Mareike and Gem{\"u}nde, Andre and Holtmann, Dirk and M{\"u}ller-Renno, Christine and Ziegler, Christiane and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Clostridium acetobutylicum's connecting world: cell appendage formation in bioelectrochemical systems}, series = {ChemElectroChem}, volume = {7}, journal = {ChemElectroChem}, number = {2}, publisher = {Wiley}, address = {Weinheim}, issn = {2196-0216}, doi = {10.1002/celc.201901656}, pages = {414 -- 420}, year = {2019}, abstract = {Bacterial cell appendix formation supports cell-cell interaction, cell adhesion and cell movement. Additionally, in bioelectrochemical systems (BES), cell appendages have been shown to participate in extracellular electron transfer. In this work, the cell appendix formation of Clostridium acetobutylicum in biofilms of a BES are imaged and compared with conventional biofilms. Under all observed conditions, the cells possess filamentous appendages with a higher number and density in the BES. Differences in the amount of extracellular polymeric substance in the biofilms of the electrodes lead to the conclusion that the cathode can be used as electron donor and the anode as electron acceptor by C. acetobutylicum. When using conductive atomic force microscopy, a current response of about 15 nA is found for the cell appendages from the BES. This is the first report of conductivity for clostridial cell appendices and represents the basis for further studies on their role for biofilm formation and electron transfer.}, language = {en} } @article{TippkoetterRoikaewUlberetal.2010, author = {Tippk{\"o}tter, Nils and Roikaew, Wipa and Ulber, Roland and Hoffmann, Alexander and Denzler, Hans-J{\"o}rg and Buchholz, Heinrich}, title = {Paracoccus denitrificans for the effluent recycling during continuous denitrification of liquid food}, series = {Biotechnology Progress}, volume = {26}, journal = {Biotechnology Progress}, number = {3}, publisher = {Wiley}, address = {Hoboken, NJ}, issn = {8756-7938}, doi = {10.1002/btpr.384}, pages = {756 -- 762}, year = {2010}, abstract = {Nitrate is an undesirable component of several foods. A typical case of contamination with high nitrate contents is whey concentrate, containing nitrate in concentrations up to 25 l. The microbiological removal of nitrate by Paracoccus denitrificans under formation of harmless nitrogen in combination with a cell retention reactor is described here. Focus lies on the resource-conserving design of a microbal denitrification process. Two methods are compared. The application of polyvinyl alcohol-immobilized cells, which can be applied several times in whey feed, is compared with the implementation of a two step denitrification system. First, the whey concentrate's nitrate is removed by ion exchange and subsequently the eluent regenerated by microorganisms under their retention by crossflow filtration. Nitrite and nitrate concentrations were determined by reflectometric color measurement with a commercially available Reflectoquant® device. Correction factors for these media had to be determined. During the pilot development, bioreactors from 4 to 250 mg·L-1 and crossflow units with membrane areas from 0.02 to 0.80 m2 were examined. Based on the results of the pilot plants, a scaling for the exemplary process of denitrifying 1,000 tons per day is discussed.}, language = {en} } @article{VoigtAlbrechtSieversetal.2015, author = {Voigt, Birgit and Albrecht, Dirk and Sievers, Susanne and Becher, D{\"o}rte and Bongaerts, Johannes and Evers, Stefan and Schweder, Thomas and Maurer, Karl-Heinz and Hecker, Michael}, title = {High-resolution proteome maps of Bacillus licheniformis cells growing in minimal medium}, series = {Proteomics}, volume = {15}, journal = {Proteomics}, number = {15}, publisher = {Wiley}, address = {Weinheim}, issn = {1615-9861}, doi = {10.1002/pmic.201400504}, pages = {2629 -- 2633}, year = {2015}, language = {en} } @incollection{DuweTippkoetterUlber2018, author = {Duwe, A. and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Lignocellulose-Biorefinery: Ethanol-Focused}, series = {Biorefineries}, booktitle = {Biorefineries}, publisher = {Springer}, address = {Cham}, doi = {10.1007/10_2016_72}, pages = {177 -- 215}, year = {2018}, abstract = {The development prospects of the world markets for petroleum and other liquid fuels are diverse and partly contradictory. However, comprehensive changes for the energy supply of the future are essential. Notwithstanding the fact that there are still very large deposits of energy resources from a geological point of view, the finite nature of conventional oil reserves is indisputable. To reduce our dependence on oil, the EU, the USA, and other major economic zones rely on energy diversification. For this purpose, alternative materials and technologies are being sought, and is most obvious in the transport sector. The objective is to progressively replace fossil fuels with renewable and more sustainable fuels. In this respect, biofuels have a pre-eminent position in terms of their capability of blending with fossil fuels and being usable in existing cars without substantial modification. Ethanol can be considered as the primary renewable liquid fuel. In this chapter enzymes, micro-organisms, and processes for ethanol production based on renewable resources are described.}, language = {en} } @article{HoffstadtNikolauszKrafftetal.2024, author = {Hoffstadt, Kevin and Nikolausz, Marcell and Krafft, Simone and Bonatelli, Maria and Kumar, Vivekanantha and Harms, Hauke and Kuperjans, Isabel}, title = {Optimization of the ex situ biomethanation of hydrogen and carbon dioxide in a novel meandering plug flow reactor: start-up phase and flexible operation}, series = {Bioengineering}, volume = {11}, journal = {Bioengineering}, number = {2}, publisher = {MDPI}, address = {Basel}, issn = {2306-5354}, doi = {10.3390/bioengineering11020165}, pages = {18 Seiten}, year = {2024}, language = {en} } @inproceedings{WulfhorstDuweMoehringetal.2016, author = {Wulfhorst, H. and Duwe, A. and M{\"o}hring, S. and Jurca, O. and Tippk{\"o}tter, Nils}, title = {Analysis of pretreated biomass by differential scanning 132 calorimetry and multivariate data analysis}, 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 = {132}, year = {2016}, language = {en} } @misc{StadtmuellerTippkoetterUlber2015, author = {Stadtm{\"u}ller, Ralf and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Method for production of single-stranded macronucleotides}, year = {2015}, abstract = {The invention relates to a method for production of single-stranded macronucleotides by amplifying and ligating an extended monomeric single-stranded target nucleic acid sequence (targetss) into a repetitive cluster of double-stranded target nucleic acid sequences (targetds), and subsequently cloning the construct into a vector (aptagene vector). The aptagene vector is transformed into host cells for replication of the aptagene and isolated in order to optain single-stranded target sequences (targetss). The invention also relates to single-stranded nucleic acids, produced by a method of the invention.}, language = {en} } @article{GerigkMaassKreutzeretal.2002, author = {Gerigk, M. and Maaß, D. and Kreutzer, A. and Sprenger, G. and Bongaerts, Johannes and Wubbolts, Marcel and Takors, Ralf}, title = {Enhanced pilot-scale fed-batch L-phenylalanine production with recombinant Escherichia coli by fully integrated reactive extraction}, series = {Bioprocess and biosystems engineering}, volume = {Vol. 25}, journal = {Bioprocess and biosystems engineering}, number = {Iss. 1}, issn = {1432-0797 (E-Journal); 1615-7605 (E-Journal); 0178-515X (Print); 1615-7591 (Print)}, pages = {43 -- 52}, year = {2002}, language = {en} } @article{TippkoetterStueckmannKrolletal.2009, author = {Tippk{\"o}tter, Nils and St{\"u}ckmann, Henning and Kroll, Stephen and Winkelmann, Gunda and Noack, Udo and Scheper, Thomas and Ulber, Roland}, title = {A semi-quantitative dipstick assay for microcystin}, series = {Analytical and Bioanalytical Chemistry}, volume = {394}, journal = {Analytical and Bioanalytical Chemistry}, number = {3}, publisher = {springer}, address = {Berlin}, issn = {1618-2650}, doi = {10.1007/s00216-009-2750-8}, pages = {863 -- 869}, year = {2009}, abstract = {An immunochromatographic lateral flow dipstick assay for the fast detection of microcystin-LR was developed. Colloid gold particles with diameters of 40 nm were used as red-colored antibody labels for the visual detection of the antigen. The new dipstick sensor is capable of detecting down to 5 µg·l-1 (ppb; total inversion of the color signal) or 1 ppb (observation of color grading) of microcystin-LR. The course of the labeling reaction was observed via spectrometric wave shifts caused by the change of particle size during the binding of antibodies. Different stabilizing reagents showed that especially bovine serum albumin (BSA) and casein increase the assays sensitivity and the conjugate stability. Performance of the dipsticks was quantified by pattern processing of capture zone CCD images. Storage stability of dipsticks and conjugate suspensions over 115 days under different conditions were monitored. The ready-to-use dipsticks were successfully tested with microcystin-LR-spiked samples of outdoor drinking- and salt water and applied to the tissue of microcystin-fed mussels.}, language = {en} } @article{MuschallikMolinnusJablonskietal.2020, author = {Muschallik, Lukas and Molinnus, Denise and Jablonski, Melanie and Kipp, Carina Ronja and Bongaerts, Johannes and Pohl, Martina and Wagner, Torsten and Sch{\"o}ning, Michael Josef and Selmer, Thorsten and Siegert, Petra}, title = {Synthesis of α-hydroxy ketones and vicinal (R, R)-diols by Bacillus clausii DSM 8716ᵀ butanediol dehydrogenase}, series = {RSC Advances}, volume = {10}, journal = {RSC Advances}, publisher = {Royal Society of Chemistry (RSC)}, address = {Cambridge}, issn = {2046-2069}, doi = {10.1039/D0RA02066D}, pages = {12206 -- 12216}, year = {2020}, abstract = {α-hydroxy ketones (HK) and 1,2-diols are important building blocks for fine chemical synthesis. Here, we describe the R-selective 2,3-butanediol dehydrogenase from B. clausii DSM 8716ᵀ (BcBDH) that belongs to the metal-dependent medium chain dehydrogenases/reductases family (MDR) and catalyzes the selective asymmetric reduction of prochiral 1,2-diketones to the corresponding HK and, in some cases, the reduction of the same to the corresponding 1,2-diols. Aliphatic diketones, like 2,3-pentanedione, 2,3-hexanedione, 5-methyl-2,3-hexanedione, 3,4-hexanedione and 2,3-heptanedione are well transformed. In addition, surprisingly alkyl phenyl dicarbonyls, like 2-hydroxy-1-phenylpropan-1-one and phenylglyoxal are accepted, whereas their derivatives with two phenyl groups are not substrates. Supplementation of Mn²⁺ (1 mM) increases BcBDH's activity in biotransformations. Furthermore, the biocatalytic reduction of 5-methyl-2,3-hexanedione to mainly 5-methyl-3-hydroxy-2-hexanone with only small amounts of 5-methyl-2-hydroxy-3-hexanone within an enzyme membrane reactor is demonstrated.}, language = {en} } @article{KueppersSteffenHellmuthetal.2014, author = {K{\"u}ppers, Tobias and Steffen, Victoria and Hellmuth, Hendrik and O'Connell, Timothy and Bongaerts, Johannes and Maurer, Karl-Heinz and Wiechert, Wolfgang}, title = {Developing a new production host from a blueprint: Bacillus pumilus as an industrial enzyme producer}, series = {Microbial cell factories}, volume = {13}, journal = {Microbial cell factories}, publisher = {BioMed Central}, address = {London}, issn = {1475-2859 (E-Journal)}, doi = {10.1186/1475-2859-13-46}, pages = {Article No. 46}, year = {2014}, language = {en} } @inproceedings{MoehringWulfhorstRothetal.2016, author = {M{\"o}hring, S. and Wulfhorst, H. and Roth, J. and Tippk{\"o}tter, Nils}, title = {Pretreatment strategies for lignocellulosic biomass}, 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 = {131}, year = {2016}, 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} } @article{AlKaidyKuthanHeringetal.2016, author = {Al-Kaidy, Huschyar and Kuthan, Kai and Hering, Thomas and Tippk{\"o}tter, Nils}, title = {Aqueous droplets used as enzymatic microreactors and their electromagnetic actuation}, series = {Journal of Visualized Experiments}, journal = {Journal of Visualized Experiments}, number = {Issue 126}, issn = {1940-087X}, doi = {10.3791/54643}, year = {2016}, abstract = {For the successful implementation of microfluidic reaction systems, such as PCR and electrophoresis, the movement of small liquid volumes is essential. In conventional lab-on-a-chip-platforms, solvents and samples are passed through defined microfluidic channels with complex flow control installations. The droplet actuation platform presented here is a promising alternative. With it, it is possible to move a liquid drop (microreactor) on a planar surface of a reaction platform (lab-in-a-drop). The actuation of microreactors on the hydrophobic surface of the platform is based on the use of magnetic forces acting on the outer shell of the liquid drops which is made of a thin layer of superhydrophobic magnetite particles. The hydrophobic surface of the platform is needed to avoid any contact between the liquid core and the surface to allow a smooth movement of the microreactor. On the platform, one or more microreactors with volumes of 10 µL can be positioned and moved simultaneously. The platform itself consists of a 3 x 3 matrix of electrical double coils which accommodate either neodymium or iron cores. The magnetic field gradients are automatically controlled. By variation of the magnetic field gradients, the microreactors' magnetic hydrophobic shell can be manipulated automatically to move the microreactor or open the shell reversibly. Reactions of substrates and corresponding enzymes can be initiated by merging the microreactors or bringing them into contact with surface immobilized catalysts.}, language = {en} } @article{HeinzeMangPopescuetal.2016, author = {Heinze, D. and Mang, Thomas and Popescu, C. and Weichold, O.}, title = {Effect of side chain length and degree of polymerization on the decomposition and crystallization behaviour of chlorinated poly(vinyl ester) oligomers}, series = {Thermochimica Acta}, volume = {637}, journal = {Thermochimica Acta}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0040-6031 (electronic)}, doi = {10.1016/j.tca.2016.05.015}, pages = {143 -- 153}, year = {2016}, abstract = {Four members of a homologous series of chlorinated poly(vinyl ester) oligomers CCl₃-(CH₂CH (OCO(CH₂)ₘCH₃))ₙ-Cl with degrees of polymerization of 10 and 20 were prepared by telomerisation using carbon tetrachloride. The number of side chain carbon atoms ranges from 2 (poly(vinyl acetate) to 18 (poly(vinyl stearate)). The effect of the n-alkyl side chain length and of the degree of polymerization on the thermal stability and crystallization behaviour of the synthesized compounds was investigated. All oligomers degrade in two major steps by first losing HCl and side chains with subsequent breakdown of the backbone. The members with short side chains, up to poly(vinyl octanoate), are amorphous and show internal plasticization, whereas those with high number of side chain carbon atoms are semi-crystalline due to side-chain crystallization. A better packing for poly(vinyl stearate) is also noticeable. The glass transition and melting temperatures as well as the onset temperature of decomposition are influenced to a larger extent by the side chain length than by the degree of polymerization. Thermal stability is improved if both the size and number of side chains increase, but only a long side chain causes a significant increase of the resistance to degradation. This results in a stabilization of PVAc so that oligomers from poly(vinyl octanoate) on are stable under atmospheric conditions. Thus, the way to design stable, chlorinated PVEs oligomers is to use a long n-alkyl side chain.}, language = {en} } @article{GhoschBaierSchuetzetal.2016, author = {Ghosch, S. and Baier, M. and Sch{\"u}tz, J. and Schneider, Felix and Scherer, Ulrich W.}, title = {Analysis of electronic autoradiographs by mathematical post-processing}, series = {Radiation Effects and Defects in Solids: Incorporating plasma science and plasma technology}, volume = {171}, journal = {Radiation Effects and Defects in Solids: Incorporating plasma science and plasma technology}, number = {1-2}, publisher = {Taylor \& Francis}, address = {London}, issn = {1029-4953}, doi = {10.1080/10420150.2016.1155587}, pages = {161 -- 172}, year = {2016}, abstract = {Autoradiography is a well-established method of nuclear imaging. When different radionuclides are present simultaneously, additional processing is needed to distinguish distributions of radionuclides. In this work, a method is presented where aluminium absorbers of different thickness are used to produce images with different cut-off energies. By subtracting images pixel-by-pixel one can generate images representing certain ranges of β-particle energies. The method is applied to the measurement of irradiated reactor graphite samples containing several radionuclides to determine the spatial distribution of these radionuclides within pre-defined energy windows. The process was repeated under fixed parameters after thermal treatment of the samples. The greyscale images of the distribution after treatment were subtracted from the corresponding pre-treatment images. Significant changes in the intensity and distribution of radionuclides could be observed in some samples. Due to the thermal treatment parameters the most significant differences were observed in the ³H and ¹⁴C inventory and distribution.}, language = {en} } @article{AboulnagaZouSelmeretal.2018, author = {Aboulnaga, E. A. and Zou, H. and Selmer, Thorsten and Xian, M.}, title = {Development of a plasmid-based, tunable, tolC-derived expression system for application in Cupriavidus necator H16}, series = {Journal of Biotechnology}, volume = {274}, journal = {Journal of Biotechnology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0168-1656}, doi = {10.1016/j.jbiotec.2018.03.007}, pages = {15 -- 27}, year = {2018}, abstract = {Cupriavidus necator H16 gains increasing attention in microbial research and biotechnological application due to its diverse metabolic features. Here we present a tightly controlled gene expression system for C. necator including the pBBR1-vector that contains hybrid promoters originating from C. necator native tolC-promoter in combination with a synthetic tetO-operator. The expression of the reporter gene from these plasmids relies on the addition of the exogenous inducer doxycycline (dc). The novel expression system offers a combination of advantageous features as; (i) high and dose-dependent recombinant protein production, (ii) tight control with a high dynamic range (On/Off ratio), which makes it applicable for harmful pathways or for toxic protein production, (iii) comparable cheap inducer (doxycycline, dc), (iv) effective at low inducer concentration, that makes it useful for large scale application, (v) rapid, diffusion controlled induction, and (vi) the inducer does not interfere within the cell metabolism. As applications of the expression system in C. necator H16, the growth ability on glycerol was enhanced by constitutively expressing the E. coli glpk gene-encoding for glycerol kinase. Likewise, we used the system to overcome the expression toxicity of mevalonate pathway in C. necator H16. With this system, the mevalonate-genes were successfully introduced in the host and the recombinant strains could produce about 200 mg/l mevalonate.}, language = {en} } @article{DruckenmuellerGuentherElbers2018, author = {Druckenm{\"u}ller, Katharina and G{\"u}nther, Klaus and Elbers, Gereon}, title = {Near-infrared spectroscopy (NIRS) as a tool to monitor exhaust air from poultry operations}, series = {Science of the Total Environment}, volume = {630}, journal = {Science of the Total Environment}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0048-9697}, doi = {10.1016/j.scitotenv.2018.02.072}, pages = {536 -- 543}, year = {2018}, abstract = {Intensive poultry operation systems emit a considerable volume of inorganic and organic matter in the surrounding environment. Monitoring cleaning properties of exhaust air cleaning systems and to detect small but significant changes in emission characteristics during a fattening cycle is important for both emission and fattening process control. In the present study, we evaluated the potential of near-infrared spectroscopy (NIRS) combined with chemometric techniques as a monitoring tool of exhaust air from poultry operation systems. To generate a high-quality data set for evaluation, the exhaust air of two poultry houses was sampled by applying state-of-the-art filter sampling protocols. The two stables were identical except for one crucial difference, the presence or absence of an exhaust air cleaning system. In total, twenty-one exhaust air samples were collected at the two sites to monitor spectral differences caused by the cleaning device, and to follow changes in exhaust air characteristics during a fattening period. The total dust load was analyzed by gravimetric determination and included as a response variable in multivariate data analysis. The filter samples were directly measured with NIR spectroscopy. Principal component analysis (PCA), linear discriminant analysis (LDA), and factor analysis (FA) were effective in classifying the NIR exhaust air spectra according to fattening day and origin. The results indicate that the dust load and the composition of exhaust air (inorganic or organic matter) substantially influence the NIR spectral patterns. In conclusion, NIR spectroscopy as a tool is a promising and very rapid way to detect differences between exhaust air samples based on still not clearly defined circumstances triggered during a fattening period and the availability of an exhaust air cleaning system.}, language = {en} } @article{PilasYaziciSelmeretal.2018, author = {Pilas, Johanna and Yazici, Y. and Selmer, Thorsten and Keusgen, M. and Sch{\"o}ning, Michael Josef}, title = {Application of a portable multi-analyte biosensor for organic acid determination in silage}, series = {Sensors}, volume = {18}, journal = {Sensors}, number = {5}, publisher = {MDPI}, address = {Basel}, issn = {1424-8220}, doi = {10.3390/s18051470}, pages = {12 Seiten}, year = {2018}, abstract = {Multi-analyte biosensors may offer the opportunity to perform cost-effective and rapid analysis with reduced sample volume, as compared to electrochemical biosensing of each analyte individually. This work describes the development of an enzyme-based biosensor system for multi-parametric determination of four different organic acids. The biosensor array comprises five working electrodes for simultaneous sensing of ethanol, formate, d-lactate, and l-lactate, and an integrated counter electrode. Storage stability of the biosensor was evaluated under different conditions (stored at +4 °C in buffer solution and dry at -21 °C, +4 °C, and room temperature) over a period of 140 days. After repeated and regular application, the individual sensing electrodes exhibited the best stability when stored at -21 °C. Furthermore, measurements in silage samples (maize and sugarcane silage) were conducted with the portable biosensor system. Comparison with a conventional photometric technique demonstrated successful employment for rapid monitoring of complex media.}, language = {en} } @inproceedings{KazukiKobayashiHirabayashietal.2019, author = {Kazuki, Yasuhiro and Kobayashi, Kaoru and Hirabayashi, Masumi and Abe, Satoshi and Kajitani, Naoyo and Kazuki, Kanoko and Takehara, Shoko and Takiguchi, Masato and Satoh, Daisuke and Kuze, Jiro and Sakuma, Tetsushi and Kaneko, Takehito and Mashimo, Tomoji and Osamura, Minori and Hashimoto, Mari and Wakatsuki, Riko and Hirashima, Rika and Fujiwara, Ryoichi and Deguchi, Tsuneo and Kurihara, Atsushi and Tsukazaki, Yasuko and Senda, Naoto and Yamamoto, Takashi and Scheer, Nico and Oshimura, Mitsuo}, title = {Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism}, series = {PNAS Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, booktitle = {PNAS Proceedings of the National Academy of Sciences of the United States of America}, number = {8}, issn = {1091-6490}, doi = {10.1073/pnas.1808255116}, pages = {3072 -- 3081}, year = {2019}, language = {en} } @article{WilsonDickieSchreiteretal.2018, author = {Wilson, C. E. and Dickie, A. P. and Schreiter, K. and Wehr, R. and Wilson, E. M. and Bial, J. and Scheer, Nico and Wilson, I. D. and Riley, R. J.}, title = {The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice}, series = {Archives of Toxicology}, volume = {92}, journal = {Archives of Toxicology}, number = {6}, publisher = {Springer}, issn = {1432-0738}, doi = {10.1007/s00204-018-2212-1}, pages = {1953 -- 1967}, year = {2018}, abstract = {The pharmacokinetics of diclofenac were investigated following single oral doses of 10 mg/kg to chimeric liver humanized and murinized FRG and C57BL/6 mice. In addition, the metabolism and excretion were investigated in chimeric liver humanized and murinized FRG mice. Diclofenac reached maximum blood concentrations of 2.43 ± 0.9 µg/mL (n = 3) at 0.25 h post-dose with an AUCinf of 3.67 µg h/mL and an effective half-life of 0.86 h (n = 2). In the murinized animals, maximum blood concentrations were determined as 3.86 ± 2.31 µg/mL at 0.25 h post-dose with an AUCinf of 4.94 ± 2.93 µg h/mL and a half-life of 0.52 ± 0.03 h (n = 3). In C57BL/6J mice, mean peak blood concentrations of 2.31 ± 0.53 µg/mL were seen 0.25 h post-dose with a mean AUCinf of 2.10 ± 0.49 µg h/mL and a half-life of 0.51 ± 0.49 h (n = 3). Analysis of blood indicated only trace quantities of drug-related material in chimeric humanized and murinized FRG mice. Metabolic profiling of urine, bile and faecal extracts revealed a complex pattern of metabolites for both humanized and murinized animals with, in addition to unchanged parent drug, a variety of hydroxylated and conjugated metabolites detected. The profiles in humanized mice were different to those of both murinized and wild-type animals, e.g., a higher proportion of the dose was detected in the form of acyl glucuronide metabolites and much reduced amounts as taurine conjugates. Comparison of the metabolic profiles obtained from the present study with previously published data from C57BL/6J mice and humans revealed a greater, though not complete, match between chimeric humanized mice and humans, such that the liver humanized FRG model may represent a model for assessing the biotransformation of such compounds in humans.}, language = {en} } @article{RossPlummerRodeetal.2010, author = {Ross, Jillian and Plummer, Simon M. and Rode, Anja and Scheer, Nico and Bower, Conrad C. and Vogel, Ortwin and Henderson, Colin J. and Wolf, C. Roland and Elcombe, Clifford R.}, title = {Human constitutive androstane receptor (CAR) and pregnane X receptor (PXR) support the hypertrophic but not the hyperplastic response to the murine nongenotoxic hepatocarcinogens phenobarbital and chlordane in vivo}, series = {Toxicological Sciences}, volume = {116}, journal = {Toxicological Sciences}, number = {2}, publisher = {Oxford University Press}, address = {Oxford}, issn = {1096-0929}, doi = {10.1093/toxsci/kfq118}, pages = {452 -- 466}, year = {2010}, abstract = {Mouse nongenotoxic hepatocarcinogens phenobarbital (PB) and chlordane induce hepatomegaly characterized by hypertrophy and hyperplasia. Increased cell proliferation is implicated in the mechanism of tumor induction. The relevance of these tumors to human health is unclear. The xenoreceptors, constitutive androstane receptors (CARs), and pregnane X receptor (PXR) play key roles in these processes. Novel "humanized" and knockout models for both receptors were developed to investigate potential species differences in hepatomegaly. The effects of PB (80 mg/kg/4 days) and chlordane (10 mg/kg/4 days) were investigated in double humanized PXR and CAR (huPXR/huCAR), double knockout PXR and CAR (PXRKO/CARKO), and wild-type (WT) C57BL/6J mice. In WT mice, both compounds caused increased liver weight, hepatocellular hypertrophy, and cell proliferation. Both compounds caused alterations to a number of cell cycle genes consistent with induction of cell proliferation in WT mice. However, these gene expression changes did not occur in PXRKO/CARKO or huPXR/huCAR mice. Liver hypertrophy without hyperplasia was demonstrated in the huPXR/huCAR animals in response to both compounds. Induction of the CAR and PXR target genes, Cyp2b10 and Cyp3a11, was observed in both WT and huPXR/huCAR mouse lines following treatment with PB or chlordane. In the PXRKO/CARKO mice, neither liver growth nor induction of Cyp2b10 and Cyp3a11 was seen following PB or chlordane treatment, indicating that these effects are CAR/PXR dependent. These data suggest that the human receptors are able to support the chemically induced hypertrophic responses but not the hyperplastic (cell proliferation) responses. At this time, we cannot be certain that hCAR and hPXR when expressed in the mouse can function exactly as the genes do when they are expressed in human cells. However, all parameters investigated to date suggest that much of their functionality is maintained.}, 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{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{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{ReugelsBoggettiScheeretal.2006, author = {Reugels, Alexander M. and Boggetti, Barbara and Scheer, Nico and Campos-Ortega, Jos{\´e} A.}, title = {Asymmetric localization of Numb:EGFP in dividing neuroepithelial cells during neurulation in Danio rerio}, series = {Developmental Dynamics}, volume = {235}, journal = {Developmental Dynamics}, number = {4}, issn = {1097-0177}, doi = {10.1002/dvdy.20699}, pages = {934 -- 948}, year = {2006}, language = {en} } @article{HansScheerRiedletal.2004, author = {Hans, Stefan and Scheer, Nico and Riedl, Iris and Weiz{\"a}cker, Elisabeth von and Blader, Patrick and Campos-Ortega, Jos{\´e} A.}, title = {her3, a zebrafish member of the hairy-E(spl) family, is repressed by Notch signalling}, series = {Development}, volume = {131}, journal = {Development}, number = {12}, issn = {1477-9129}, doi = {10.1242/dev.01167}, pages = {2957 -- 2969}, year = {2004}, 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{LawsonScheerPhametal.2001, author = {Lawson, Nathan D. and Scheer, Nico and Pham, Van N. and Kim, Ceol-Hee and Chitnis, Ajay B. and Campos-Ortega, Jos{\´e} A. and Weinstein, Brant M.}, title = {Notch signaling is required for arterial-venous differentiation during embryonic vascular development}, series = {Development}, volume = {128}, journal = {Development}, number = {19}, issn = {1477-9129}, pages = {3675 -- 3683}, year = {2001}, 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{WolfKapelyukhScheeretal.2015, author = {Wolf, C. Roland and Kapelyukh, Yury and Scheer, Nico and Henderson, Colin J.}, title = {Application of Humanised and Other Transgenic Models to Predict Human Responses to Drugs}, editor = {Wilson, Alan G. E.}, publisher = {RSC Publ.}, address = {Cambridge}, isbn = {978-1-78262-778-4}, doi = {10.1039/9781782622376-00152}, pages = {152 -- 176}, year = {2015}, abstract = {The use of transgenic animal models has transformed our knowledge of complex biochemical pathways in vivo. It has allowed disease processes to be modelled and used in the development of new disease prevention and treatment strategies. They can also be used to define cell- and tissue-specific pathways of gene regulation. A further major application is in the area of preclinical development where such models can be used to define pathways of chemical toxicity, and the pathways that regulate drug disposition. One major application of this approach is the humanisation of mice for the proteins that control drug metabolism and disposition. Such models can have numerous applications in the development of drugs and in their more sophisticated use in the clinic.}, language = {en} } @incollection{HendersonWolfScheer2009, author = {Henderson, Colin J. and Wolf, C. Roland and Scheer, Nico}, title = {The use of transgenic animals to study drug metabolism}, series = {Handbook of Drug Metabolism. 2nd Edition}, booktitle = {Handbook of Drug Metabolism. 2nd Edition}, editor = {Woolf, Thomas F.}, publisher = {Informa Healthcare}, address = {New York}, isbn = {978-1-4200-7647-9}, pages = {637 -- 658}, year = {2009}, language = {en} } @article{HalbachScheer2000, author = {Halbach, Thorsten and Scheer, Nico}, title = {Transcriptional activation by the PHD finger is inhibited through an adjacent leucine zipper that binds 14-3-3 proteins}, series = {Nucleic Acids Research}, volume = {28}, journal = {Nucleic Acids Research}, number = {18}, issn = {1362-4962}, doi = {10.1093/nar/28.18.3542}, pages = {3542 -- 3550}, year = {2000}, 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{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{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} }