@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{AdelsMonakhova2024,
  author    = {Adels, Klaudia and Monakhova, Yulia},
  title     = {Low-field NMR spectroscopic study of e-cigarettes: Is determination of only nicotine and organic carrier solvents possible?},
  series = {Microchemical Journal},
  volume    = {203},
  journal   = {Microchemical Journal},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {1095-9149},
  doi       = {10.1016/j.microc.2024.110859},
  pages     = {9 Seiten},
  year      = {2024},
  abstract  = {Electronic cigarettes (e-cigarettes) have become popular worldwide with the market growing exponentially in some countries. The absence of product standards and safety regulations requires urgent development of analytical methodologies for the holistic control of the growing diversity of such products. An approach based on low-field nuclear magnetic resonance (LF-NMR) at 80 MHz is presented for the simultaneous determination of key parameters: carrier solvents (vegetable glycerine (VG), propylene glycol (PG) and water), total nicotine as well as free-base nicotine fraction. Moreover, qualitative and quantitative determination of fourteen weak organic acids deliberately added to enhance sensory characteristics of e-cigarettes was possible. In most cases these parameters can be rapidly and conveniently determined without using any sample manipulation such as dilution, extraction or derivatization steps. The method was applied for 37 authentic e-cigarettes samples. In particular, eight different organic acids with the content up to 56 mg/mL were detected. Due to its simplicity, the method can be used in routine regulatory control as well as to study release behaviour of nicotine and other e-cigarettes constituents in different products.},
  language  = {en}
}
@article{HaegerProbstJaegeretal.2023,
  author    = {Haeger, Gerrit and Probst, Johanna and Jaeger, Karl-Erich and Bongaerts, Johannes and Siegert, Petra},
  title     = {Novel aminoacylases from Streptomyces griseus DSM 40236 and their recombinant production in Streptomyces lividans},
  series = {FEBS Open Bio},
  volume    = {13},
  journal   = {FEBS Open Bio},
  number    = {12},
  publisher = {Wiley},
  address   = {Hoboken, NJ},
  issn      = {2211-5463},
  doi       = {10.1002/2211-5463.13723},
  pages     = {2224 -- 2238},
  year      = {2023},
  abstract  = {Amino acid-based surfactants are valuable compounds for cosmetic formulations. The chemical synthesis of acyl-amino acids is conventionally performed by the Schotten-Baumann reaction using fatty acyl chlorides, but aminoacylases have also been investigated for use in biocatalytic synthesis with free fatty acids. Aminoacylases and their properties are diverse; they belong to different peptidase families and show differences in substrate specificity and biocatalytic potential. Bacterial aminoacylases capable of synthesis have been isolated from Burkholderia, Mycolicibacterium, and Streptomyces. Although several proteases and peptidases from S. griseus have been described, no aminoacylases from this species have been identified yet. In this study, we investigated two novel enzymes produced by S. griseus DSM 40236ᵀ . We identified and cloned the respective genes and recombinantly expressed an α-aminoacylase (EC 3.5.1.14), designated SgAA, and an ε-lysine acylase (EC 3.5.1.17), designated SgELA, in S. lividans TK23. The purified aminoacylase SgAA was biochemically characterized, focusing on its hydrolytic activity to determine temperature- and pH optima and stabilities. The aminoacylase could hydrolyze various acetyl-amino acids at the Nα -position with a broad specificity regarding the sidechain. Substrates with longer acyl chains, like lauroyl-amino acids, were hydrolyzed to a lesser extent. Purified aminoacylase SgELA specific for the hydrolysis of Nε -acetyl-L-lysine was unstable and lost its enzymatic activity upon storage for a longer period but could initially be characterized. The pH optimum of SgELA was pH 8.0. While synthesis of acyl-amino acids was not observed with SgELA, SgAA catalyzed the synthesis of lauroyl-methionine.},
  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{FalkenbergKohnBottetal.2023,
  author    = {Falkenberg, Fabian and Kohn, Sophie and Bott, Michael and Bongaerts, Johannes and Siegert, Petra},
  title     = {Biochemical characterisation of a novel broad pH spectrum subtilisin from Fictibacillus arsenicus DSM 15822ᵀ},
  series = {FEBS Open Bio},
  volume    = {13},
  journal   = {FEBS Open Bio},
  number    = {11},
  publisher = {Wiley},
  address   = {Hoboken, NJ},
  issn      = {2211-5463},
  doi       = {10.1002/2211-5463.13701},
  pages     = {2035 -- 2046},
  year      = {2023},
  abstract  = {Subtilisins from microbial sources, especially from the Bacillaceae family, are of particular interest for biotechnological applications and serve the currently growing enzyme market as efficient and novel biocatalysts. Biotechnological applications include use in detergents, cosmetics, leather processing, wastewater treatment and pharmaceuticals. To identify a possible candidate for the enzyme market, here we cloned the gene of the subtilisin SPFA from Fictibacillus arsenicus DSM 15822ᵀ (obtained through a data mining-based search) and expressed it in Bacillus subtilis DB104. After production and purification, the protease showed a molecular mass of 27.57 kDa and a pI of 5.8. SPFA displayed hydrolytic activity at a temperature optimum of 80 °C and a very broad pH optimum between 8.5 and 11.5, with high activity up to pH 12.5. SPFA displayed no NaCl dependence but a high NaCl tolerance, with decreasing activity up to concentrations of 5 m NaCl. The stability enhanced with increasing NaCl concentration. Based on its substrate preference for 10 synthetic peptide 4-nitroanilide substrates with three or four amino acids and its phylogenetic classification, SPFA can be assigned to the subgroup of true subtilisins. Moreover, SPFA exhibited high tolerance to 5\% (w/v) SDS and 5\% H₂O₂ (v/v). The biochemical properties of SPFA, especially its tolerance of remarkably high pH, SDS and H₂O₂, suggest it has potential for biotechnological applications.},
  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{FalkenbergVossBottetal.2023,
  author    = {Falkenberg, Fabian and Voß, Leonie and Bott, Michael and Bongaerts, Johannes and Siegert, Petra},
  title     = {New robust subtilisins from halotolerant and halophilic Bacillaceae},
  series = {Applied Microbiology and Biotechnology},
  volume    = {107},
  journal   = {Applied Microbiology and Biotechnology},
  publisher = {Springer Nature},
  address   = {Berlin},
  issn      = {1432-0614},
  doi       = {10.1007/s00253-023-12553-w},
  pages     = {3939 -- 3954},
  year      = {2023},
  abstract  = {The aim of the present study was the characterisation of three true subtilisins and one phylogenetically intermediate subtilisin from halotolerant and halophilic microorganisms. Considering the currently growing enzyme market for efficient and novel biocatalysts, data mining is a promising source for novel, as yet uncharacterised enzymes, especially from halophilic or halotolerant Bacillaceae, which offer great potential to meet industrial needs. Both halophilic bacteria Pontibacillus marinus DSM 16465ᵀ and Alkalibacillus haloalkaliphilus DSM 5271ᵀ and both halotolerant bacteria Metabacillus indicus DSM 16189 and Litchfieldia alkalitelluris DSM 16976ᵀ served as a source for the four new subtilisins SPPM, SPAH, SPMI and SPLA. The protease genes were cloned and expressed in Bacillus subtilis DB104. Purification to apparent homogeneity was achieved by ethanol precipitation, desalting and ion-exchange chromatography. Enzyme activity could be observed between pH 5.0-12.0 with an optimum for SPPM, SPMI and SPLA around pH 9.0 and for SPAH at pH 10.0. The optimal temperature for SPMI and SPLA was 70 °C and for SPPM and SPAH 55 °C and 50 °C, respectively. All proteases showed high stability towards 5\% (w/v) SDS and were active even at NaCl concentrations of 5 M. The four proteases demonstrate potential for future biotechnological applications.},
  language  = {en}
}
@article{HaegerBongaertsSiegert2022,
  author    = {Haeger, Gerrit and Bongaerts, Johannes and Siegert, Petra},
  title     = {A convenient ninhydrin assay in 96-well format for amino acid-releasing enzymes using an air-stable reagent},
  series = {Analytical Biochemistry},
  journal   = {Analytical Biochemistry},
  number    = {624},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {1096-0309},
  doi       = {10.1016/j.ab.2022.114819},
  pages     = {Artikel 114819},
  year      = {2022},
  abstract  = {An improved and convenient ninhydrin assay for aminoacylase activity measurements was developed using the commercial EZ Nin™ reagent. Alternative reagents from literature were also evaluated and compared. The addition of DMSO to the reagent enhanced the solubility of Ruhemann's purple (RP). Furthermore, we found that the use of a basic, aqueous buffer enhances stability of RP. An acidic protocol for the quantification of lysine was developed by addition of glacial acetic acid. The assay allows for parallel processing in a 96-well format with measurements microtiter plates.},
  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}
}
@inproceedings{EngelThieringerTippkoetter2016,
  author    = {Engel, Mareike and Thieringer, Julia and Tippk{\"o}tter, Nils},
  title     = {Linking bioprocess engineering and electrochemistry for sustainable biofuel production},
  series = {Young Researchers Symposium, YRS 2016. Proceedings},
  booktitle = {Young Researchers Symposium, YRS 2016. Proceedings},
  publisher = {Fraunhofer Verlag},
  address   = {Karlsruhe},
  pages     = {49 -- 53},
  year      = {2016},
  abstract  = {Electromicrobial engineering is an emerging, highly interdisciplinary research area linking bioprocesses with electrochemistry. In this work, microbial electrosynthesis (MES) of biobutanol is carried out during acetone-butanol-ethanol (ABE) fermentations with Clostridium acetobutylicum. A constant electric potential of -600mV (vs. Ag/AgCl) with simultaneous addition of the soluble redox mediator neutral red is used in order to study the electron transfer between the working electrode and the bacterial cells. The results show an earlier initiation of solvent production for all fermentations with applied potential compared to the conventional ABE fermentation. The f inal butanol concentration can be more than doubled by the application of a negative potential combined with addition of neutral red. Moreover a higher biofilm formation on the working electrode compared to control cultivations has been observed. In contrast to previous studies, our results also indicate that direct electron transfer (DET) might be possible with C. acetobutylicum. The presented results make microbial butanol production economically attractive and therefore support the development of sustainable production processes in the chemical industry aspired by the "Centre for resource-efficient chemistry and raw material change" as well as the the project "NanoKat" working on nanostructured catalysts in Kaiserslautern.},
  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{WeldenJablonskiWegeetal.2021,
  author    = {Welden, Rene and Jablonski, Melanie and Wege, Christina and Keusgen, Michael and Wagner, Patrick Hermann and Wagner, Torsten and Sch{\"o}ning, Michael Josef},
  title     = {Light-Addressable Actuator-Sensor Platform for Monitoring and Manipulation of pH Gradients in Microfluidics: A Case Study with the Enzyme Penicillinase},
  series = {Biosensors},
  volume    = {11},
  journal   = {Biosensors},
  number    = {6},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2079-6374},
  doi       = {10.3390/bios11060171},
  pages     = {Artikel 171},
  year      = {2021},
  abstract  = {The feasibility of light-addressed detection and manipulation of pH gradients inside an electrochemical microfluidic cell was studied. Local pH changes, induced by a light-addressable electrode (LAE), were detected using a light-addressable potentiometric sensor (LAPS) with different measurement modes representing an actuator-sensor system. Biosensor functionality was examined depending on locally induced pH gradients with the help of the model enzyme penicillinase, which had been immobilized in the microfluidic channel. The surface morphology of the LAE and enzyme-functionalized LAPS was studied by scanning electron microscopy. Furthermore, the penicillin sensitivity of the LAPS inside the microfluidic channel was determined with regard to the analyte's pH influence on the enzymatic reaction rate. In a final experiment, the LAE-controlled pH inhibition of the enzyme activity was monitored by the LAPS.},
  language  = {en}
}
@misc{KrafftKukaUlberetal.2022,
  author    = {Krafft, Simone and Kuka, Katrin and Ulber, Roland and Tippk{\"o}tter, Nils},
  title     = {Utilization of Lolium perenne varieties as a renewable substrate for single-cell proteins, lactate, and composite materials},
  series = {Chemie Ingenieur Technik},
  volume    = {94},
  journal   = {Chemie Ingenieur Technik},
  number    = {9},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {0009-286X},
  doi       = {10.1002/cite.202255306},
  pages     = {1303 -- 1304},
  year      = {2022},
  abstract  = {Lolium perenne (perennial ryegrass) is aproductive and high-quality forage grass indigenous to Southern Europe, temperate Asia, and North Africa. Nowadays it is widespread and the dominant grass species on green areas in temperate climates. This abundant source of biomass is suitable for the development of bioeconomic processes because of its high cellulose and water-soluble carbohydrate content. In this work, novel breeds of the perennial ryegrass are being examined with regards to their quality parameters and biotechnological utilization options within the context of bioeconomy. Three processing operations are presented. In the first process, the perennial ryegrass is pretreated by pressing or hydrothermal extraction to derive glucosevia subsequent enzymatic hydrolysis of cellulose. A yield of up to 82 \% glucose was achieved when using the hydrothermal ex-traction as pretreatment. In a second process, the ryegrass is used to produce lactic acid in high concentrations. The influence of the growth conditions and the cutting time on the carboxylic acid yield is investigated. A yield of lactic acid of above 150 g kg⁻¹ dry matter was achieved. The third process is to use Lolium perenne as a substrate in the fermentation of K. marxianus for the microbial production of single-cell proteins. The perennial ryegrass is screw-pressed and the press juice is used as medium. When supplementing the press juice with yeast media components, a biomass concentration of up to 16 g L⁻¹ could be achieved.},
  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{CapitainWagnerHummeletal.2021,
  author    = {Capitain, Charlotte and Wagner, Sebastian and Hummel, Joana and Tippk{\"o}tter, Nils},
  title     = {Investigation of C-N Formation Between Catechols and Chitosan for the Formation of a Strong, Novel Adhesive Mimicking Mussel Adhesion},
  series = {Waste and Biomass Valorization},
  volume    = {12},
  journal   = {Waste and Biomass Valorization},
  publisher = {Springer Nature},
  address   = {Cham},
  issn      = {1877-265X},
  doi       = {10.1007/s12649-020-01110-5},
  pages     = {1761 -- 1779},
  year      = {2021},
  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{ElBerguiAbouabdillahBouriougetal.2023,
  author    = {El Bergui, Omnia and Abouabdillah, Aziz and Bourioug, Mohamed and Schmitz, Dominik and Biel, Markus and Aboudrare, Abdellah and Krauss, Manuel and Jomaa, Ahlem and Romuli, Sebastian and M{\"u}ller, Joachim and Fagroud, Mustapha and Bouabid, Rachid},
  title     = {Innovative solutions for drought: Evaluating hydrogel application on onion cultivation (Allium cepa) in Morocco},
  series = {Water},
  volume    = {15},
  journal   = {Water},
  number    = {11},
  publisher = {MDPI},
  address   = {Basel},
  doi       = {10.3390/w15111972},
  pages     = {Artikel 1972},
  year      = {2023},
  abstract  = {Throughout the last decade, and particularly in 2022, water scarcity has become a critical concern in Morocco and other Mediterranean countries. The lack of rainfall during spring was worsened by a succession of heat waves during the summer. To address this drought, innovative solutions, including the use of new technologies such as hydrogels, will be essential to transform agriculture. This paper presents the findings of a study that evaluated the impact of hydrogel application on onion (Allium cepa) cultivation in Meknes, Morocco. The treatments investigated in this study comprised two different types of hydrogel-based soil additives (Arbovit® polyacrylate and Huminsorb® polyacrylate), applied at two rates (30 and 20 kg/ha), and irrigated at two levels of water supply (100\% and 50\% of daily crop evapotranspiration; ETc). Two control treatments were included, without hydrogel application and with both water amounts. The experiment was conducted in an open field using a completely randomized design. The results indicated a significant impact of both hydrogel-type dose and water dose on onion plant growth, as evidenced by various vegetation parameters. Among the hydrogels tested, Huminsorb® Polyacrylate produced the most favorable outcomes, with treatment T9 (100\%, HP, 30 kg/ha) yielding 70.55 t/ha; this represented an increase of 11 t/ha as compared to the 100\% ETc treatment without hydrogel application. Moreover, the combination of hydrogel application with 50\% ETc water stress showed promising results, with treatment T4 (HP, 30 kg, 50\%) producing almost the same yield as the 100\% ETc treatment without hydrogel while saving 208 mm of water.},
  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{JablonskiMuenstermannNorketal.2021,
  author    = {Jablonski, Melanie and M{\"u}nstermann, Felix and Nork, Jasmina and Molinnus, Denise and Muschallik, Lukas and Bongaerts, Johannes and Wagner, Torsten and Keusgen, Michael and Siegert, Petra and Sch{\"o}ning, Michael Josef},
  title     = {Capacitive field-effect biosensor applied for the detection of acetoin in alcoholic beverages and fermentation broths},
  series = {physica status solidi (a) applications and materials science},
  volume    = {218},
  journal   = {physica status solidi (a) applications and materials science},
  number    = {13},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {1862-6319},
  doi       = {10.1002/pssa.202000765},
  pages     = {7 Seiten},
  year      = {2021},
  abstract  = {An acetoin biosensor based on a capacitive electrolyte-insulator-semiconductor (EIS) structure modified with the enzyme acetoin reductase, also known as butane-2,3-diol dehydrogenase (Bacillus clausii DSM 8716ᵀ), is applied for acetoin detection in beer, red wine, and fermentation broth samples for the first time. The EIS sensor consists of an Al/p-Si/SiO₂/Ta₂O₅ layer structure with immobilized acetoin reductase on top of the Ta₂O₅ transducer layer by means of crosslinking via glutaraldehyde. The unmodified and enzyme-modified sensors are electrochemically characterized by means of leakage current, capacitance-voltage, and constant capacitance methods, respectively.},
  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{HoffstadtCheenakulaNikolauszetal.2023,
  author    = {Hoffstadt, Kevin and Cheenakula, Dheeraja and Nikolausz, Marcell and Krafft, Simone and Harms, Hauke and Kuperjans, Isabel},
  title     = {Design and construction of a new reactor for flexible biomethanation of hydrogen},
  series = {Fermentation},
  volume    = {9},
  journal   = {Fermentation},
  number    = {8},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2311-5637},
  doi       = {10.3390/fermentation9080774},
  pages     = {1 -- 16},
  year      = {2023},
  abstract  = {The increasing share of renewable electricity in the grid drives the need for sufficient storage capacity. Especially for seasonal storage, power-to-gas can be a promising approach. Biologically produced methane from hydrogen produced from surplus electricity can be used to substitute natural gas in the existing infrastructure. Current reactor types are not or are poorly optimized for flexible methanation. Therefore, this work proposes a new reactor type with a plug flow reactor (PFR) design. Simulations in COMSOL Multiphysics ® showed promising properties for operation in laminar flow. An experiment was conducted to support the simulation results and to determine the gas fraction of the novel reactor, which was measured to be 29\%. Based on these simulations and experimental results, the reactor was constructed as a 14 m long, 50 mm diameter tube with a meandering orientation. Data processing was established, and a step experiment was performed. In addition, a kLa of 1 h-1 was determined. The results revealed that the experimental outcomes of the type of flow and gas fractions are in line with the theoretical simulation. The new design shows promising properties for flexible methanation and will be tested.},
  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}
}
@inproceedings{PothMonzonTippkoetteretal.2010,
  author    = {Poth, Sebastian and Monzon, Magaly and Tippk{\"o}tter, Nils and Ulber, Roland},
  title     = {Lignocellulosic biorefinery : process integration of hydrolysis and fermentation},
  series = {Proceedings / 11th European Workshop on Lignocellulosics and Pulp : August 16 - 19, 2010, Hamburg, Germany},
  booktitle = {Proceedings / 11th European Workshop on Lignocellulosics and Pulp : August 16 - 19, 2010, Hamburg, Germany},
  publisher = {vTi},
  address   = {Hamburg},
  pages     = {65 -- 68},
  year      = {2010},
  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}
}
@article{CheenakulaHoffstadtKrafftetal.2022,
  author    = {Cheenakula, Dheeraja and Hoffstadt, Kevin and Krafft, Simone and Reinecke, Diana and Klose, Holger and Kuperjans, Isabel and Gr{\"o}mping, Markus},
  title     = {Anaerobic digestion of algal-bacterial biomass of an Algal Turf Scrubber system},
  series = {Biomass Conversion and Biorefinery},
  volume    = {13},
  journal   = {Biomass Conversion and Biorefinery},
  publisher = {Springer},
  address   = {Berlin},
  issn      = {2190-6823},
  doi       = {10.1007/s13399-022-03236-z},
  pages     = {15 Seiten},
  year      = {2022},
  abstract  = {This study investigated the anaerobic digestion of an algal-bacterial biofilm grown in artificial wastewater in an Algal Turf Scrubber (ATS). The ATS system was located in a greenhouse (50°54′19ʺN, 6°24′55ʺE, Germany) and was exposed to seasonal conditions during the experiment period. The methane (CH4) potential of untreated algal-bacterial biofilm (UAB) and thermally pretreated biofilm (PAB) using different microbial inocula was determined by anaerobic batch fermentation. Methane productivity of UAB differed significantly between microbial inocula of digested wastepaper, a mixture of manure and maize silage, anaerobic sewage sludge, and percolated green waste. UAB using sewage sludge as inoculum showed the highest methane productivity. The share of methane in biogas was dependent on inoculum. Using PAB, a strong positive impact on methane productivity was identified for the digested wastepaper (116.4\%) and a mixture of manure and maize silage (107.4\%) inocula. By contrast, the methane yield was significantly reduced for the digested anaerobic sewage sludge (50.6\%) and percolated green waste (43.5\%) inocula. To further evaluate the potential of algal-bacterial biofilm for biogas production in wastewater treatment and biogas plants in a circular bioeconomy, scale-up calculations were conducted. It was found that a 0.116 km2 ATS would be required in an average municipal wastewater treatment plant which can be viewed as problematic in terms of space consumption. However, a substantial amount of energy surplus (4.7-12.5 MWh a-1) can be gained through the addition of algal-bacterial biomass to the anaerobic digester of a municipal wastewater treatment plant. Wastewater treatment and subsequent energy production through algae show dominancy over conventional technologies.},
  language  = {en}
}
@incollection{MufflerTippkoetterUlber2010,
  author    = {Muffler, Kai and Tippk{\"o}tter, Nils and Ulber, Roland},
  title     = {Chemical feedstocks and fine chemicals from other substrates},
  series = {Handbook of hydrocarbon and lipid microbiology. Volume 4: Consequences of microbial interactions with hydrocarbons, oils and lipids. - (Springer reference)},
  booktitle = {Handbook of hydrocarbon and lipid microbiology. Volume 4: Consequences of microbial interactions with hydrocarbons, oils and lipids. - (Springer reference)},
  editor    = {Timmis, Kenneth N.},
  publisher = {Springer},
  address   = {Berlin [u.a.]},
  isbn      = {978-3-540-77588-1},
  doi       = {10.1007\%2F978-3-540-77587-4_214},
  pages     = {2891 -- 2902},
  year      = {2010},
  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{HafidiElHatkaSchmitzetal.2024,
  author    = {Hafidi, Youssef and El Hatka, Hicham and Schmitz, Dominik and Krauss, Manuel and Pettrak, J{\"u}rgen and Biel, Markus and Ittobane, Najim},
  title     = {Sustainable soil additives for water and micronutrient supply: swelling and chelating properties of polyaspartic acid hydrogels utilizing newly developed crosslinkers},
  series = {Gels},
  volume    = {10},
  journal   = {Gels},
  number    = {3},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2310-2861},
  doi       = {10.3390/gels10030170},
  pages     = {Artikel 170},
  year      = {2024},
  abstract  = {Drought and water shortage are serious problems in many arid and semi-arid regions. This problem is getting worse and even continues in temperate climatic regions due to climate change. To address this problem, the use of biodegradable hydrogels is increasingly important for the application as water-retaining additives in soil. Furthermore, efficient (micro-)nutrient supply can be provided by the use of tailored hydrogels. Biodegradable polyaspartic acid (PASP) hydrogels with different available (1,6-hexamethylene diamine (HMD) and L-lysine (LYS)) and newly developed crosslinkers based on diesters of glycine (GLY) and (di-)ethylene glycol (DEG and EG, respectively) were synthesized and characterized using Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) and regarding their swelling properties (kinetic, absorbency under load (AUL)) as well as biodegradability of PASP hydrogel. Copper (II) and zinc (II), respectively, were loaded as micronutrients in two different approaches: in situ with crosslinking and subsequent loading of prepared hydrogels. The results showed successful syntheses of di-glycine-ester-based crosslinkers. Hydrogels with good water-absorbing properties were formed. Moreover, the developed crosslinking agents in combination with the specific reaction conditions resulted in higher water absorbency with increased crosslinker content used in synthesis (10\% vs. 20\%). The prepared hydrogels are candidates for water-storing soil additives due to the biodegradability of PASP, which is shown in an exemple. The incorporation of Cu(II) and Zn(II) ions can provide these micronutrients for plant growth.},
  language  = {en}
}
@incollection{HahnKellyMuffleretal.2011,
  author    = {Hahn, Thomas and Kelly, Svenja and Muffler, Kai and Tippk{\"o}tter, Nils and Ulber, Roland},
  title     = {Extraction of lignocellulose and algae for the production of bulk and fine chemicals},
  series = {Industrial scale natural products extraction},
  booktitle = {Industrial scale natural products extraction},
  editor    = {Hans-J{\"o}rg, Bart and Pilz, Stephan},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  isbn      = {978-3-527-32504-7 (Print)},
  doi       = {10.1002/9783527635122},
  pages     = {221 -- 245},
  year      = {2011},
  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{HengsbachEngelCwienczeketal.2023,
  author    = {Hengsbach, Jan-Niklas and Engel, Mareike and Cwienczek, Marcel and Stiefelmaier, Judith and Tippk{\"o}tter, Nils and Ulber, Roland},
  title     = {Scalable unseparated bioelectrochemical reactors by using a carbon fiber brush as stirrer and working electrode},
  series = {ChemElectroChem},
  volume    = {10},
  journal   = {ChemElectroChem},
  number    = {21},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {2196-0216},
  doi       = {10.1002/celc.202300440},
  pages     = {9 Seiten},
  year      = {2023},
  abstract  = {The concept of energy conversion into platform chemicals using bioelectrochemical systems (BES) has gained increasing attention in recent years, as the technology simultaneously provides an opportunity for sustainable chemical production and tackles the challenge of Power-to-X technologies. There are many approaches to realize the industrial scale of BES. One concept is to equip standard bioreactors with static electrodes. However, large installations resulted in a negative influence on various reactor parameters. In this study, we present a new single-chamber BES based on a stirred tank reactor in which the stirrer was replaced by a carbon fiber brush, performing the functions of the working electrode and the stirrer. The reactor is characterized in abiotic studies and electro-fermentations with Clostridium acetobutylicum. Compared to standard reactors an increase in butanol production of 20.14±3.66 \% shows that the new BES can be efficiently used for bioelectrochemical processes.},
  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}
}
@misc{VarrialeKukaTippkoetteretal.2022,
  author    = {Varriale, Ludovica and Kuka, Katrin and Tippk{\"o}tter, Nils and Ulber, Roland},
  title     = {Use of a green biomass in a biorefinery platform},
  series = {Chemie Ingenieur Technik},
  volume    = {94},
  journal   = {Chemie Ingenieur Technik},
  number    = {9},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {0009-286X},
  doi       = {10.1002/cite.202255095},
  pages     = {1299},
  year      = {2022},
  abstract  = {The emerging environmental issues due to the use of fossil resources are encouraging the exploration of new renewable resources. Biomasses are attracting more interest due to the low environmental impacts, low costs, and high availability on earth. In this scenario, green biorefineries are a promising platform in which green biomasses are used as feedstock. Grasses are mainly composed of cellulose and hemicellulose, and lignin is available in a small amount. In this work, a perennial ryegrass was used as feedstock to develop a green bio-refinery platform. Firstly, the grass was mechanically pretreated, thus obtaining a press juice and a press cake fraction. The press juice has high nutritional values and can be employed as part of fermentation media. The press cake can be employed as a substrate either in enzymatic hydrolysis or in solid-state fermentation. The overall aim of this work was to demonstrate different applications of both the liquid and the solid fractions. For this purpose, the filamentous fungus A. niger and the yeast Y. lipolythica were selected for their ability to produce citric acid. Finally, the possibility was assessed to use the press juice as part of fermentation media to cultivate S. cerevisiae and lactic acid bacteria for ethanol and lactic acid fermentation.},
  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}
}
@misc{BraunKrafftTippkoetter2022,
  author    = {Braun, Lena and Krafft, Simone and Tippk{\"o}tter, Nils},
  title     = {Combined supercritical carbon dioxide extraction and chromatography of the algae fatty linoleic and linolenic acid},
  series = {Chemie Ingenieur Technik},
  volume    = {94},
  journal   = {Chemie Ingenieur Technik},
  number    = {9},
  publisher = {Wiley-VCH},
  address   = {Weinheim},
  issn      = {0009-286X},
  doi       = {10.1002/cite.202255308},
  pages     = {1304},
  year      = {2022},
  abstract  = {A method for the integrated extraction and separation of fatty acids from algae using supercritical CO2 is presented. Desmodesmus obliquus and Chlorella sorokiniana were used as algae. First, a method for chromatographic separation of fatty acids of different degrees of saturation was established and optimized. Then, an integrated method for supercritical extraction was developed for both algal species. It was also verified whether prior cell disruption was beneficial for extraction. In developing the method for chromatographic separation, statistical experimental design was used to determine the optimal parameter settings. The methanol content in the mobile phase proved to be the most important parameter for successful separation of the three unsaturated fatty acids oleic acid, linoleic acid, and linolenic acid. Supercritical extraction with dried algae showed that about four times more fatty acids can be extracted from C. sorokiniana relative to the dry mass used.},
  language  = {en}
}
@article{WeldenSeverinsPoghossianetal.2022,
  author    = {Welden, Melanie and Severins, Robin and Poghossian, Arshak and Wege, Christina and Bongaerts, Johannes and Siegert, Petra and Keusgen, Michael and Sch{\"o}ning, Michael Josef},
  title     = {Detection of acetoin and diacetyl by a tobacco mosaic virus-assisted field-effect biosensor},
  series = {Chemosensors},
  volume    = {10},
  journal   = {Chemosensors},
  number    = {6},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2227-9040},
  doi       = {10.3390/chemosensors10060218},
  pages     = {Artikel 218},
  year      = {2022},
  abstract  = {Acetoin and diacetyl have a major impact on the flavor of alcoholic beverages such as wine or beer. Therefore, their measurement is important during the fermentation process. Until now, gas chromatographic techniques have typically been applied; however, these require expensive laboratory equipment and trained staff, and do not allow for online monitoring. In this work, a capacitive electrolyte-insulator-semiconductor sensor modified with tobacco mosaic virus (TMV) particles as enzyme nanocarriers for the detection of acetoin and diacetyl is presented. The enzyme acetoin reductase from Alkalihalobacillus clausii DSM 8716ᵀ is immobilized via biotin-streptavidin affinity, binding to the surface of the TMV particles. The TMV-assisted biosensor is electrochemically characterized by means of leakage-current, capacitance-voltage, and constant capacitance measurements. In this paper, the novel biosensor is studied regarding its sensitivity and long-term stability in buffer solution. Moreover, the TMV-assisted capacitive field-effect sensor is applied for the detection of diacetyl for the first time. The measurement of acetoin and diacetyl with the same sensor setup is demonstrated. Finally, the successive detection of acetoin and diacetyl in buffer and in diluted beer is studied by tuning the sensitivity of the biosensor using the pH value of the measurement solution.},
  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{WilsonWilsonScheeretal.2017,
  author    = {Wilson, Ian D. and Wilson, Claire E. and Scheer, Nico and Dickie, A.P. and Schreiter, K. and Wilson, E. M. and Riley, R. J. and Wehr, R. and Bial, J.},
  title     = {The Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice},
  series = {Biochemical pharmacology},
  volume    = {Volume 135},
  journal   = {Biochemical pharmacology},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {1873-2968},
  doi       = {10.1016/j.bcp.2017.03.015},
  pages     = {139 -- 150},
  year      = {2017},
  language  = {en}
}
@article{ZhangHeimbachScheeretal.2016,
  author    = {Zhang, Jin and Heimbach, Tycho and Scheer, Nico and Barve, Avantika and Li, Wenkui and Lin, Wen and He, Handan},
  title     = {Clinical Exposure Boost Predictions by Integrating Cytochrome P450 3A4-Humanized Mouse Studies With PBPK Modeling},
  series = {Journal of Pharmaceutical Sciences},
  volume    = {Volume 105},
  journal   = {Journal of Pharmaceutical Sciences},
  number    = {Issue 4},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0022-3549},
  doi       = {doi.org/10.1016/j.xphs.2016.01.021},
  pages     = {1398 -- 1404},
  year      = {2016},
  abstract  = {NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir.},
  language  = {en}
}
@article{ScheerMclaughlinRodeetal.2014,
  author    = {Scheer, Nico and Mclaughlin, Lesley A. and Rode, Anja and MacLeod, Alastair Kenneth and Henderson, Colin J. and Wolf, Roland C.},
  title     = {Deletion of thirty murine cytochrome P450 genes results in viable mice with compromised drug metabolism},
  series = {Drug Metabolism and Disposition},
  volume    = {42},
  journal   = {Drug Metabolism and Disposition},
  number    = {6},
  publisher = {ASPET},
  address   = {Bethesda, Md.},
  issn      = {1521-009X},
  doi       = {10.1124/dmd.114.057885},
  pages     = {1022 -- 1030},
  year      = {2014},
  abstract  = {In humans, 75\% of all drugs are metabolized by the cytochrome P450-dependent monooxygenase system. Enzymes encoded by the CYP2C, CYP2D, and CYP3A gene clusters account for ∼80\% of this activity. There are profound species differences in the multiplicity of cytochrome P450 enzymes, and the use of mouse models to predict pathways of drug metabolism is further complicated by overlapping substrate specificity between enzymes from different gene families. To establish the role of the hepatic and extrahepatic P450 system in drug and foreign chemical disposition, drug efficacy, and toxicity, we created a unique mouse model in which 30 cytochrome P450 genes from the Cyp2c, Cyp2d, and Cyp3a gene clusters have been deleted. Remarkably, despite a wide range of putative important endogenous functions, Cyp2c/2d/3a KO mice were viable and fertile, demonstrating that these genes have evolved primarily as detoxification enzymes. Although there was no overt phenotype, detailed examination showed Cyp2c/2d/3a KO mice had a smaller body size (15\%) and larger livers (20\%). Changes in hepatic morphology and a decreased blood glucose (30\%) were also noted. A five-drug cocktail of cytochrome P450 isozyme probe substrates were used to evaluate changes in drug pharmacokinetics; marked changes were observed in either the pharmacokinetics or metabolites formed from Cyp2c, Cyp2d, and Cyp3a substrates, whereas the metabolism of the Cyp1a substrate caffeine was unchanged. Thus, Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the P450 system in drug metabolism and efficacy, as well as in chemical toxicity.},
  language  = {en}
}
@article{ScheerBalimaneHaywardetal.2012,
  author    = {Scheer, Nico and Balimane, Praveen and Hayward, Michael D. and Buechel, Sandra and Kauselmann, Gunther and Wolf, C. Roland},
  title     = {Generation and Characterization of a Novel Multidrug Resistance Protein 2 Humanized Mouse Line},
  series = {Drug Metabolism and Disposition},
  volume    = {40},
  journal   = {Drug Metabolism and Disposition},
  number    = {11},
  publisher = {ASPET},
  address   = {Bethesda, Md.},
  issn      = {1521-0111},
  doi       = {10.1124/dmd.112.047605},
  pages     = {2212 -- 2218},
  year      = {2012},
  abstract  = {The multidrug resistance protein (MRP) 2 is predominantly expressed in liver, intestine, and kidney, where it plays an important role in the excretion of a range of drugs and their metabolites or endogenous compounds into bile, feces, and urine. Mrp knockout [Mrp2(-/-)] mice have been used recently to study the role of MRP2 in drug disposition. Here, we describe the first generation and initial characterization of a mouse line humanized for MRP2 (huMRP2), which is nulled for the mouse Mrp2 gene and expresses the human transporter in the organs and cell types where MRP2 is normally expressed. Analysis of the mRNA expression for selected cytochrome P450 and transporter genes revealed no major changes in huMRP2 mice compared with wild-type controls. We show that human MRP2 is able to compensate functionally for the loss of the mouse transporter as demonstrated by comparable bilirubin levels in the humanized mice and wild-type controls, in contrast to the hyperbilirubinemia phenotype that is observed in MRP2(-/-) mice. The huMRP2 mouse provides a model to study the role of the human transporter in drug disposition and in assessing the in vivo consequences of inhibiting this transporter by compounds interacting with human MRP2.},
  language  = {en}
}
@article{ScheerKapelyukhRodeetal.2012,
  author    = {Scheer, Nico and Kapelyukh, Yury and Rode, Anja and Buechel, Sandra and Wolf, C. Roland},
  title     = {Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines},
  series = {Molecular Pharmacology},
  volume    = {82},
  journal   = {Molecular Pharmacology},
  number    = {6},
  publisher = {ASPET},
  address   = {Bethesda, Md.},
  issn      = {1521-0111},
  doi       = {10.1124/mol.112.080036},
  pages     = {1022 -- 1029},
  year      = {2012},
  abstract  = {Compared with rodents and many other animal species, the human cytochrome P450 (P450) Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the substrate specificity of its enzymes. As a consequence, the use of wild-type animal models to predict the role of human CYP2C enzymes in drug metabolism and drug-drug interactions is limited. Within the human CYP2C cluster CYP2C9 is of particular importance, because it is one of the most abundant P450 enzymes in human liver, and it is involved in the metabolism of a wide variety of important drugs and environmental chemicals. To investigate the in vivo functions of cytochrome P450 Cyp2c genes and to establish a model for studying the functions of CYP2C9 in vivo, we have generated a mouse model with a deletion of the murine Cyp2c gene cluster and a corresponding humanized model expressing CYP2C9 specifically in the liver. Despite the high number of functional genes in the mouse Cyp2c cluster and the reported roles of some of these proteins in different biological processes, mice deleted for Cyp2c genes were viable and fertile but showed certain phenotypic alterations in the liver. The expression of CYP2C9 in the liver also resulted in viable animals active in the metabolism and disposition of a number of CYP2C9 substrates. These mouse lines provide a powerful tool for studying the role of Cyp2c genes and of CYP2C9 in particular in drug disposition and as a factor in drug-drug interaction.},
  language  = {en}
}
@article{KapelyukhHendersonScheeretal.2019,
  author    = {Kapelyukh, Yury and Henderson, Colin James and Scheer, Nico and Rode, Anja and Wolf, Charles Roland},
  title     = {Defining the contribution of CYP1A1 and CYP1A2 to drug metabolism using humanized CYP1A1/1A2 and Cyp1a1/Cyp1a2 KO mice},
  series = {Drug Metabolism and Disposition},
  journal   = {Drug Metabolism and Disposition},
  number    = {Early view},
  doi       = {10.1124/dmd.119.087718},
  pages     = {43 Seiten},
  year      = {2019},
  language  = {en}
}
@article{LempiaeinenCouttetBolognanietal.2012,
  author    = {Lempi{\"a}inen, Harri and Couttet, Philippe and Bolognani, Federico and M{\"u}ller, Arne and Dubost, Val{\´e}rie and Luisier, Rapha{\"e}lle and Rio-Espinola, Alberto del and Vitry, Veronique and Unterberger, Elif B. and Thomson, John P. and Treindl, Fridolin and Metzger, Ute and Wrzodek, Clemens and Hahne, Florian and Zollinger, Tulipan and Brasa, Sarah and Kalteis, Magdalena and Marcellin, Magali and Giudicelli, Fanny and Braeuning, Albert and Morawiec, Laurent and Zamurovic, Natasa and L{\"a}ngle, Ulrich and Scheer, Nico and Sch{\"u}beler, Dirk and Goodman, Jay and Chibout, Salah-Dine and Marlowe, Jennifer and Theil, Dietlinde and Heard, David J. and Grenet, Olivier and Zell, Andreas and Templin, Markus F. and Meehan, Richard R. and Wolf, Roland C. and Elcombe, Clifford R. and Schwarz, Michael and Moulin, Pierre and Terranova, R{\´e}mi and Moggs, Jonathan G.},
  title     = {Identification of Dlk1-Dio3 imprinted gene cluster non-coding RNAs as novel candidate biomarkers for liver tumor promotion},
  series = {Toxicological Sciences},
  volume    = {131},
  journal   = {Toxicological Sciences},
  number    = {2},
  publisher = {Oxford University Press},
  address   = {Oxford},
  issn      = {1094-2025},
  doi       = {10.1093/toxsci/kfs303},
  pages     = {375 -- 386},
  year      = {2012},
  abstract  = {The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.},
  language  = {en}
}