TY - JOUR A1 - Seibler, Jost A1 - Zevnik, Branko A1 - Küter-Luks, Birgit A1 - Andreas, Susanne A1 - Kern, Heidrun A1 - Hennek, Thomas A1 - Rode, Anja A1 - Heimann, Cornelia A1 - Faust, Nicole A1 - Kauselmann, Gunther A1 - Schoor, Michael A1 - Jaenisch, Rudolf A1 - Rajewsky, Klaus A1 - Kühn, Ralf A1 - Schwenk, Frieder T1 - Rapid generation of inducible mouse mutants JF - Nucleic Acids Research Y1 - 2003 U6 - https://doi.org/10.1093/nar/gng012 SN - 1362-4962 VL - 33 IS - 4 SP - e12 ER - TY - JOUR A1 - Goetze, Sandra A1 - Baer, Alexandra A1 - Winkelmann, Silke A1 - Nehlsen, Kristina A1 - Seibler, Jost A1 - Maass, Karin A1 - Bode, Jürgen T1 - Performance of genomic bordering elements at predefined genomic loci JF - Molecular and Cellular Biology Y1 - 2005 U6 - https://doi.org/10.1128/MCB.25.6.2260-2272.2005 SN - 1098-5549 VL - 25 IS - 6 SP - 2260 EP - 2272 ER - TY - JOUR A1 - Takenaga, Shoko A1 - Schneider, Benno A1 - Erbay, E. A1 - Biselli, Manfred A1 - Schnitzler, Thomas A1 - Schöning, Michael Josef A1 - Wagner, Torsten T1 - Fabrication of biocompatible lab-on-chip devices for biomedical applications by means of a 3D-printing process JF - Physica status solidi (a) N2 - 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. Y1 - 2015 U6 - https://doi.org/10.1002/pssa.201532053 SN - 1862-6319 VL - 212 IS - 6 SP - 1347 EP - 1352 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Inagaki, Akiko A1 - Sleddens-Linkels, Esther A1 - Wassenaar, Evelyne A1 - Ooms, Marja A1 - Cappellen, Wiggert A. van A1 - Hoeijmakers, Jan H. J. A1 - Seibler, Jost A1 - Vogt, Thomas F. A1 - Shin, Myung K. A1 - Grootegoed, J. Anton A1 - Baarends, Willy M. T1 - Meiotic functions of RAD18 JF - Journal of Cell Science Y1 - 2011 U6 - https://doi.org/10.1242/jcs.081968 SN - 1477-9137 VL - 124 IS - 16 SP - 2837 EP - 2850 PB - Company of Biologists Limited CY - Cambridge ER - TY - JOUR A1 - Raab, Monika A1 - Kappel, Sven A1 - Krämer, Andrea A1 - Sanhaji, Mourad A1 - Matthess, Yves A1 - Kurunci-Csacsko, Elisabeth A1 - Calzada-Wack, Julia A1 - Rathkolb, Birgit A1 - Rosman, Jan A1 - Adler, Thure A1 - Busch, Dirk H. A1 - Esposito, Irene A1 - Fuchs, Helmut A1 - Gailus-Durner, Valérie A1 - Klingenspor, Martin A1 - Wolf, Eckhard A1 - Sänger, Nicole A1 - Prinz, Florian A1 - Hrabe de Angelis, Martin A1 - Seibler, Jost A1 - Yuan, Juping A1 - Bergmann, Martin A1 - Knecht, Rainald A1 - Kreft, Bertolt A1 - Strebhardt, Klaus T1 - Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells JF - Nature Communications Y1 - 2011 U6 - https://doi.org/10.1038/ncomms1395 SN - 2041-1723 VL - 2 IS - 395 SP - 1 EP - 11 PB - Nature CY - London ER - TY - JOUR A1 - Hasegawa, Maki A1 - Kapelyukh, Yury A1 - Tahara, Harunobu A1 - Seibler, Jost A1 - Rode, Anja A1 - Krueger, Sylvia A1 - Lee, Dongtao N. A1 - Wolf, C. Roland A1 - Scheer, Nico T1 - Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line JF - Molecular Pharmacology Y1 - 2011 U6 - https://doi.org/10.1124/mol.111.071845 SN - 1521-0111 VL - 80 IS - 33 SP - 518 EP - 528 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Jordan, Sabine D. A1 - Krüger, Markus A1 - Willmes, Diana M. A1 - Redemann, Nora A1 - Wunderlich, F. Thomas A1 - Brönneke, Hella S. A1 - Merkwirth, Carsten A1 - Kashkar, Hamid A1 - Olkkonen, Vesa M. A1 - Böttger, Thomas A1 - Braun, Thomas A1 - Seibler, Jost A1 - Brüning, Jens C. T1 - Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism JF - Nature Cell Biology N2 - 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. Y1 - 2011 U6 - https://doi.org/10.1038/ncb2211 SN - 1465-7392 VL - 13 IS - 4 SP - 434 EP - 446 PB - Nature CY - New York ER - TY - JOUR A1 - Glaser, Stefan A1 - Lubitz, Sandra A1 - Loveland, Kate L. A1 - Ohbo, Kazu A1 - Robb, Lorraine A1 - Schwenk, Frieder A1 - Seibler, Jost A1 - Roellig, Daniela A1 - Kranz, Andrea A1 - Anastassiadis, Konstantinos A1 - Stewart, A. Francis T1 - The histone 3 lysine 4 methyltransferase, Mll2, is only required briefly in development and spermatogenesis JF - Epigenetics & Chromatin Y1 - 2009 U6 - https://doi.org/10.1186/1756-8935-2-5 SN - 1756-8935 VL - 2 IS - 5 SP - 1 EP - 16 ER - TY - JOUR A1 - Kotnik, Katarina A1 - Popova, Elena A1 - Todiras, Mihail A1 - Mori, Marcelo A. A1 - Alenina, Natalia A1 - Seibler, Jost A1 - Bader, Michael T1 - Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown JF - Plos One Y1 - 2009 U6 - https://doi.org/10.1371/journal.pone.0005124 VL - 4 IS - 4 SP - e5124 PB - Plos CY - San Francisco, California, US ER - TY - JOUR A1 - Herold, Marco J. A1 - Brandt, Jens van den A1 - Seibler, Jost A1 - Reichardt, Holger M. T1 - Inducible and reversible gene silencing by stable integration of an shRNA-encoding lentivirus in transgenic rats JF - Proceedings of the National Academy of Sciences of the United States of America Y1 - 2008 U6 - https://doi.org/10.1073/pnas.0806213105 SN - 1091-6490 VL - 105 IS - 47 SP - 18507 EP - 18512 ER - TY - JOUR A1 - Koch, Linda A1 - Wunderlich, F. Thomas A1 - Seibler, Jost A1 - Könner, A. Christine A1 - Hampel, Brigitte A1 - Irlenbusch, Sigrid A1 - Brabant, Georg A1 - Kahn, C. Ronald A1 - Schwenk, Frieder A1 - Brüning, Jens C. T1 - Central insulin action regulates peripheral glucose and fat metabolism in mice JF - The Journal of Clinical Investigation (JCI) Y1 - 2008 U6 - https://doi.org/10.1172/JCI31073 SN - 1558-8238 VL - 118 IS - 6 SP - 2132 EP - 2147 ER - TY - JOUR A1 - Christoph, Thomas A1 - Bahrenberg, Gregor A1 - Vry, Jean de A1 - Englberger, Werner A1 - Erdmann, Volker A. A1 - Frech, Moritz A1 - Kögel, Babette A1 - Röhl, Thomas A1 - Schiene, Klaus A1 - Schröder, Wolfgang A1 - Seibler, Jost A1 - Kurreck, Jens T1 - Investigation of TRPV1 loss-of-function phenotypes in transgenic shRNA expressing and knockout mice JF - Molecular and Cellular Neuroscience Y1 - 2008 U6 - https://doi.org/10.1016/j.mcn.2007.12.006 SN - 1044-7431 VL - 37 IS - 3 SP - 579 EP - 589 ER - TY - JOUR A1 - Cesari, Francesca A1 - Rennekampff, Verena A1 - Vintersten, Kristina A1 - Vuong, Lam Giang A1 - Seibler, Jost A1 - Bode, Jürgen A1 - Wiebel, Franziska F. A1 - Nordheim, Alfred T1 - Elk-1 knock-out mice engineered by Flp recombinase-mediated cassette exchange JF - Genesis : The Journal of Genetics and Development Y1 - 2004 U6 - https://doi.org/10.1002/gene.20003 SN - 1526-968X VL - 38 IS - 2 SP - 87 EP - 92 ER - TY - JOUR A1 - Bode, Jürgen A1 - Schlake, Thomas A1 - Iber, Michaela A1 - Schübeler, Dirk A1 - Seibler, Jost A1 - Snezhkov, Evgeney A1 - Nikolaev, Lev T1 - The transgeneticist's toolbox: novel methods for the targeted modification of eukaryotic genomes JF - Biological Chemistry Y1 - 2000 U6 - https://doi.org/10.1515/BC.2000.103 SN - 1431-6730 VL - 381 IS - 9-10 SP - 801 EP - 813 ER - TY - JOUR A1 - Feng, Yong-Qing A1 - Seibler, Jost A1 - Alami, Raouf A1 - Eisen, Andrew A1 - Westerman, Karen A. A1 - Leboulch, Philippe A1 - Fiering, Steven A1 - Bouhassira, Eric E. T1 - Site-specific chromosomal integration in mammalian cells: highly efficient CRE recombinase-mediated cassette exchange JF - Journal of Molecular Biology Y1 - 1999 U6 - https://doi.org/10.1006/jmbi.1999.3113 SN - 0022-2836 VL - 292 IS - 4 SP - 779 EP - 785 ER - TY - JOUR A1 - Seibler, Jost A1 - Schübeler, Dirk A1 - Fiering, Steven A1 - Groudine, Mark A1 - Bode, Jürgen T1 - DNA cassette exchange in ES cells mediated by Flp recombinase: an efficient strategy for repeated modification of tagged loci by marker-free constructs JF - Biochemistry Y1 - 1998 U6 - https://doi.org/10.1021/bi980288t SN - 1520-4995 VL - 37 IS - 18 SP - 6229 EP - 6234 ER - TY - JOUR A1 - Seibler, Jost A1 - Bode, Jürgen T1 - Double-reciprocal crossover mediated by FLP-recombinase: a concept and an assay JF - Biochemistry Y1 - 1997 SN - 1520-4995 VL - 36 IS - 7 SP - 1740 EP - 1747 ER - TY - JOUR A1 - Bode, J. A1 - Bartsch, J. A1 - Boulikas, T. A1 - Iber, M. A1 - Mielke, C. A1 - Schübeler, D. A1 - Seibler, Jost A1 - Benham, C. T1 - Transcription-promoting genomic sites in mammalia: their elucidation and architectural principles JF - Gene therapy & molecular biology Y1 - 1998 SN - 1529-9120 VL - 1 IS - 1 SP - 1 EP - 29 ER - TY - JOUR A1 - Iber, Michaela A1 - Schübeler, Dirk A1 - Seibler, Jost A1 - Höxter, Maria A1 - Bode, Jürgen T1 - Efficient FACS selection procedure for cells undergoing Flp-mediated site-specific conversions JF - Technical Tips Online Y1 - 1998 U6 - https://doi.org/10.1016/S1366-2120(08)70132-6 VL - 4 IS - 1 SP - 25 EP - 29 ER - TY - JOUR A1 - Henken, F. E. A1 - Oosterhuis, K. A1 - Öhlschläger, Peter A1 - Bosch, L. A1 - Hooijberg, E. A1 - Haanen, J. B. A. G. A1 - Steenbergen, R. D. M. T1 - Preclinical safety evaluation of DNA vaccines encoding modified HPV16 E6 and E7 JF - Vaccine N2 - 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. Y1 - 2012 U6 - https://doi.org/10.1016/j.vaccine.2012.04.013 SN - 0264-410X VL - 30 IS - 28 SP - 4259 EP - 4266 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Immel, Timo A1 - Grützke, Martin A1 - Späte, Anne-Katrin A1 - Groth, Ulrich A1 - Öhlschläger, Peter A1 - Huhn, Thomas T1 - Synthesis and X-ray structure analysis of a heptacoordinate titanium(IV)-bis-chelate with enhanced in vivo antitumor efficacy JF - Chemical Communications N2 - 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. Y1 - 2012 U6 - https://doi.org/10.1039/C2CC31624B SN - 1364-548X VL - 48 IS - 46 SP - 5790 EP - 5792 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Scheer, Nico A1 - Snaith, Mike A1 - Wolf, C. Roland A1 - Seibler, Jost T1 - Generation and utility of genetically humanized mouse models JF - Drug Discovery Today Y1 - 2013 U6 - https://doi.org/10.1016/j.drudis.2013.07.007 SN - 1359-6446 VL - Vol 18 IS - 23-24 SP - 1200 EP - 1211 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Bouwman, Peter A1 - Gulden, Hanneke van der A1 - Heijden, Ingrid van der A1 - Drost, Rinske A1 - Klijn, Christiaan N. A1 - Prasetyanti, Pramudita A1 - Pieterse, Mark A1 - Wientjens, Ellen A1 - Seibler, Jost A1 - Hogervorst, Frank B. L. A1 - Jonkers, Jos T1 - A High-Throughput Functional Complementation Assay for Classification of BRCA1 Missense Variants JF - Cancer Discovery Y1 - 2013 U6 - https://doi.org/10.1158/2159-8290.CD-13-0094 SN - 2159-8290 IS - 3 SP - 1142 EP - 1152 ER - TY - JOUR A1 - Michalak, Ewa Malgorzata A1 - Nacerddine, Karim A1 - Pietersen, Alexandra A1 - Beuger, Vincent A1 - Pawlitzky, Inka A1 - Cornelissen-Steijger, Paulien A1 - Wientjens, Ellen A1 - Tanger, Ellen A1 - Seibler, Jost A1 - Lohuizen, Maarten van A1 - Jonkers, Jos T1 - Polycomb group gene Ezh2 regulates mammary gland morphogenesis and maintains the luminal progenitor pool JF - Stem Cells Y1 - 2013 U6 - https://doi.org/10.1002/stem.1437 SN - 1549-4918 VL - Vol 31 IS - 9 SP - 1910 EP - 1920 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Gebeshuber, Christoph A. A1 - Kornauth, Christoph A1 - Dong, Lihua A1 - Sierig, Ralph A1 - Seibler, Jost A1 - Reiss, Martina A1 - Tauber, Stefanie A1 - Bilban, Martin A1 - Wang, Shijun A1 - Kain, Renate A1 - Böhmig, Georg A. A1 - Moeller, Marcus J. A1 - Gröne, Hermann-Josef A1 - Englert, Christoph A1 - Martinez, Javier A1 - Kerjaschki, Dontscho T1 - Focal segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1 JF - Nature Medicine Y1 - 2013 U6 - https://doi.org/10.1038/nm.3142 SN - 1078-8956 VL - 19 IS - 4 SP - 481 EP - 487 ER - TY - JOUR A1 - Kornfeld, Jan-Wilhelm A1 - Baitzel, Catherina A1 - Könner, A. Christine A1 - Nicholls, Hayley T. A1 - Vogt, Merly C. A1 - Herrmanns, Karolin A1 - Scheja, Ludger A1 - Haumaitre, Cécile A1 - Wolf, Anna M. A1 - Knippschild, Uwe A1 - Seibler, Jost A1 - Cereghini, Silvia A1 - Heeren, Joerg A1 - Stoffel, Markus A1 - Brüning, Jens C. T1 - Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b JF - Nature Y1 - 2013 SN - 0028-0836 U6 - https://doi.org/10.1038/nature11793 VL - 494 IS - 7435 SP - 111 EP - 115 PB - Springer Nature CY - Cham ER - TY - JOUR A1 - Breuer, Lars A1 - Raue, Markus A1 - Strobel, M. A1 - Mang, Thomas A1 - Schöning, Michael Josef A1 - Thoelen, R. A1 - Wagner, Torsten T1 - Hydrogels with incorporated graphene oxide as light-addressable actuator materials for cell culture environments in lab-on-chip systems JF - Physica status solidi (a) N2 - 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. Y1 - 2016 U6 - https://doi.org/10.1002/pssa.201533056 SN - 1862-6300 VL - 213 IS - 6 SP - 1520 EP - 1525 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Polen, T. A1 - Krämer, Marco A1 - Bongaerts, Johannes A1 - Wubbolts, Marcel A1 - Wendisch, V. F. T1 - The global gene expression response of Escherichia coli to L-phenylalanine JF - Journal of biotechnology Y1 - 2005 SN - 1873-4863 (E-Journal); 0168-1656 (Print) VL - Vol. 115 IS - Iss. 3 SP - 221 EP - 237 ER - TY - JOUR A1 - Bongaerts, Johannes A1 - Krämer, Marco A1 - Müller, Ulrike A1 - Raeven, Leon A1 - Wubbolts, Marcel T1 - Metabolic engineering for microbial production of aromatic amino acids and derived compounds JF - Metabolic engineering Y1 - 2001 SN - 1096-7184 (E-Journal); 1096-7176 (Print) VL - Vol. 3 IS - Iss. 4 SP - 289 EP - 300 ER - TY - JOUR A1 - Bongaerts, Johannes A1 - Esser, Simon A1 - Lorbach, Volker A1 - Al-Momani, Lóay A1 - Müller, Michael A. A1 - Franke, Dirk A1 - Grondal, Christoph A1 - Kurutsch, Anja A1 - Bujnicki, Robert A1 - Takors, Ralf A1 - Raeven, Leon A1 - Wubbolts, Marcel A1 - Bovenberg, Roel A1 - Nieger, Martin A1 - Schürmann, Melanie A1 - Trachtmann, Natalie A1 - Kozak, Stefan A1 - Sprenger, Georg A. A1 - Müller, Michael T1 - Diversity-oriented production of metabolites derived from chorismate and their use in organic synthesis JF - Angewandte Chemie International Edition Y1 - 2011 SN - 1521-3773 (E-Journal); 0570-0833 (Print); 1433-7851 (Print) VL - Vol. 50 IS - Iss. 34 SP - 7781 EP - 7786 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Müller, Janina A1 - Beckers, Mario A1 - Mußmann, Nina A1 - Bongaerts, Johannes A1 - Büchs, Jochen T1 - Elucidation of auxotrophic deficiencies of Bacillus pumilus DSM 18097 to develop a defined minimal medium JF - Microbial Cell Factories N2 - 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. Y1 - 2018 U6 - https://doi.org/10.1186/s12934-018-0956-1 SN - 1475-2859 VL - 17 IS - 1 SP - Article No. 106 PB - BioMed Central ER - TY - JOUR A1 - Scheele, S. A1 - Bongaerts, Johannes A1 - Maurer, K.-H. A1 - Freudl, R. T1 - Sekretion einer Kofaktor-haltigen Oxidase durch Corynebacterium glutamicum JF - Chemie - Ingenieur - Technik (CIT) Y1 - 2009 SN - 1522-2640 (E-Journal); 0009-286X (Print) VL - Vol. 81 IS - Iss. 8 SP - 1309 ER - TY - JOUR A1 - Falkenberg, Fabian A1 - Kohn, Sophie A1 - Bott, Michael A1 - Bongaerts, Johannes A1 - Siegert, Petra T1 - Biochemical characterisation of a novel broad pH spectrum subtilisin from Fictibacillus arsenicus DSM 15822ᵀ JF - FEBS Open Bio N2 - 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. KW - Bacillaceae KW - Biotechnological application KW - Broad pH spectrum KW - Subtilases KW - Subtilisin Y1 - 2023 U6 - https://doi.org/10.1002/2211-5463.13701 SN - 2211-5463 N1 - Corresponding author: Petra Siegert VL - 13 IS - 11 SP - 2035 EP - 2046 PB - Wiley CY - Hoboken, NJ ER - TY - JOUR A1 - Rachinger, Michael A1 - Bauch, Melanie A1 - Strittmatter, Axel A1 - Bongaerts, Johannes A1 - Evers, Stefan A1 - Maurer, Karl-Heinz A1 - Daniel, Rolf A1 - Liebl, Wolfgang A1 - Liesegang, Heiko A1 - Ehrenreich, Armin T1 - Size unlimited markerless deletions by a transconjugative plasmid-system in Bacillus licheniformis JF - Journal of biotechnology Y1 - 2013 SN - 1873-4863 (E-Journal); 0168-1656 (Print) VL - Vol. 164 IS - Iss. 4 SP - 365 EP - 369 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Wissenbach, U. A1 - Six, S. A1 - Bongaerts, Johannes A1 - Ternes, D. A1 - Steinwachs, S. A1 - Unden, G. T1 - A third periplasmic transport system for l-arginine in Escherichia coli: molecular characterization of the artPIQMJ genes, arginine binding and transport JF - Molecular microbiology Y1 - 1995 SN - 1365-2958 (E-Journal); 0950-382x (Print) VL - Vol. 17 IS - Iss. 4 SP - 675 EP - 686 ER - TY - JOUR A1 - Thiel, Alexander A1 - Muffler, Kai A1 - Tippkötter, Nils A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Hruschka, Steffen M. A1 - Ulber, Roland T1 - A novel integrated downstream processing approach to recover sinapic acid, phytic acid and proteins from rapeseed meal JF - Journal of Chemical Technology and Biotechnology N2 - 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 Y1 - 2015 U6 - https://doi.org/10.1002/jctb.4664 VL - 90 IS - 11 SP - 1999 EP - 2006 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Al-Kaidy, Huschyar A1 - Tippkötter, Nils T1 - Superparamagnetic hydrophobic particles as shell material for digital microfluidic droplets and proof-of-principle reaction assessments with immobilized laccase JF - Engineering in Life Sciences N2 - 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. Y1 - 2016 U6 - https://doi.org/10.1002/elsc.201400124 VL - 16 IS - 3 SP - 222 EP - 230 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Engel, Mareike A1 - Bayer, Hendrik A1 - Holtmann, Dirk A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Flavin secretion of Clostridium acetobutylicum in a bioelectrochemical system - Is an iron limitation involved? JF - Bioelectrochemistry Y1 - 2019 U6 - https://doi.org/10.1016/j.bioelechem.2019.05.014 SN - 1567-5394 IS - In Press, Accepted Manuscript PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Sieker, Tim A1 - Neuner, Andreas A1 - Dimitrova, Darina A1 - Tippkötter, Nils A1 - Bart, Hans-Jörg A1 - Heinzle, Elmar A1 - Ulber, Roland T1 - Grassilage als Rohstoff für die chemische Industrie JF - Chemie Ingenieur Technik N2 - Grassilage stellt einen nachwachsenden Rohstoff mit großem Potenzial dar. Neben Cellulose und Hemicellulose enthält sie auch organische Säuren, insbesondere Milchsäure. In einem Bioraffinerie-Projekt wird die Milchsäure aus der Silage isoliert und mit gentechnisch optimierten Stämmen zu L-Lysin weiterverarbeitet. Die Lignocellulose wird hydrolysiert und zu Ethanol fermentiert. Ein besonderes Augenmerk liegt auf der Integration der unterschiedlichen Prozesse sowie der einzelnen Prozessschritte zu einem Gesamtprozess, der sämtliche Inhaltsstoffe der Silage verwertet. Y1 - 2010 U6 - https://doi.org/10.1002/cite.201000088 SN - 1522-2640 VL - 82 IS - 8, Special Issue: Industrielle Nutzung nachwachsender Rohstoffe SP - 1153 EP - 1159 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Sieker, Tim A1 - Neuner, Andreas A1 - Dimitrova, Darina A1 - Tippkötter, Nils A1 - Muffler, Kai A1 - Bart, Hans-Jörg A1 - Heinzle, Elmar A1 - Ulber, Roland T1 - Ethanol production from grass silage by simultaneous pretreatment, saccharification and fermentation: First steps in the process development JF - Engineering in Life Sciences N2 - 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. Y1 - 2011 U6 - https://doi.org/10.1002/elsc.201000160 N1 - Special Issue "Bioprocess‐oriented plant design" VL - 11 IS - 4 SP - 436 EP - 442 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Capitain, Charlotte A1 - Wagner, Sebastian A1 - Hummel, Joana A1 - Tippkötter, Nils T1 - Investigation of C–N Formation Between Catechols and Chitosan for the Formation of a Strong, Novel Adhesive Mimicking Mussel Adhesion JF - Waste and Biomass Valorization Y1 - 2021 U6 - https://doi.org/10.1007/s12649-020-01110-5 SN - 1877-265X N1 - Corresponding author: Nils Tippkötter VL - 12 SP - 1761 EP - 1779 PB - Springer Nature CY - Cham ER - TY - JOUR A1 - Handtke, Stefan A1 - Schroeter, Rebecca A1 - Jürgen, Britta A1 - Methling, Karen A1 - Schlüter, Rabea A1 - Albrecht, Dirk A1 - Hijum, Sacha A. F. T. van A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Lalk, Michael A1 - Schweder, Thomas A1 - Hecker, Michael A1 - Voigt, Birgit T1 - Bacillus pumilus reveals a remarkably high resistance to hydrogen peroxide provoked oxidative stress JF - PLOS one N2 - 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. Y1 - 2014 U6 - https://doi.org/10.1371/journal.pone.0085625 SN - 1932-6203 VL - 9 IS - 1 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Kappler-Tanudyaya, Nathalie A1 - Schmitt, Heike A1 - Tippkötter, Nils A1 - Meyer, Lina A1 - Lenzen, Sigurd A1 - Ulber, Roland T1 - Combination of biotransformation and chromatography for the isolation and purification of mannoheptulose JF - Biotechnology Journal N2 - 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. Y1 - 2007 U6 - https://doi.org/10.1002/biot.200700004 SN - 1860-7314 VL - 2 IS - 6 SP - 692 EP - 699 ER - TY - JOUR A1 - Muschallik, Lukas A1 - Kipp, Carina Ronja A1 - Recker, Inga A1 - Bongaerts, Johannes A1 - Pohl, Martina A1 - Gelissen, Melanie A1 - Schöning, Michael Josef A1 - Selmer, Thorsten A1 - Siegert, Petra T1 - Synthesis of α-hydroxy ketones and vicinal diols with the Bacillus licheniformis DSM 13T butane-2, 3-diol dehydrogenase JF - Journal of Biotechnology N2 - 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. Y1 - 2020 SN - 2590-1559 U6 - https://doi.org/10.1016/j.jbiotec.2020.09.016 VL - 202 IS - Vol. 324 SP - 61 EP - 70 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Jablonski, Melanie A1 - Münstermann, Felix A1 - Nork, Jasmina A1 - Molinnus, Denise A1 - Muschallik, Lukas A1 - Bongaerts, Johannes A1 - Wagner, Torsten A1 - Keusgen, Michael A1 - Siegert, Petra A1 - Schöning, Michael Josef T1 - Capacitive field‐effect biosensor applied for the detection of acetoin in alcoholic beverages and fermentation broths JF - physica status solidi (a) applications and materials science N2 - 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. KW - acetoin KW - acetoin reductase KW - alcoholic beverages KW - biosensors KW - capacitive field-effect sensors Y1 - 2021 U6 - https://doi.org/10.1002/pssa.202000765 SN - 1862-6319 N1 - Corresponding author: Melanie Jablonski VL - 218 IS - 13 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Krämer, Marco A1 - Bongaerts, Johannes A1 - Bovenberg, Roel A1 - Kremer, Susanne A1 - Müller, Ulrike A1 - Orf, Sonja A1 - Wubbolts, Marcel A1 - Raeven, Leon T1 - Metabolic engineering for microbial production of shikimic acid JF - Metabolic engineering Y1 - 2003 SN - 1096-7184 (E-Journal); 1096-7176 (Print) VL - Vol. 5 IS - Iss. 4 SP - 277 EP - 283 ER - TY - JOUR A1 - Hoffstadt, Kevin A1 - Cheenakula, Dheeraja A1 - Nikolausz, Marcell A1 - Krafft, Simone A1 - Harms, Hauke A1 - Kuperjans, Isabel T1 - Design and construction of a new reactor for flexible biomethanation of hydrogen JF - Fermentation N2 - 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. KW - methanation KW - plug flow reactor KW - bubble column KW - bio-methane KW - power-to-gas Y1 - 2023 U6 - https://doi.org/10.3390/fermentation9080774 SN - 2311-5637 N1 - The article belongs to the Special Issue Fermentation Processes: Modeling, Optimization and Control VL - 9 IS - 8 SP - 1 EP - 16 PB - MDPI CY - Basel ER - TY - JOUR A1 - Capitain, Charlotte A1 - Ross-Jones, Jesse A1 - Möhring, Sophie A1 - Tippkötter, Nils T1 - Differential scanning calorimetry for quantification of polymer biodegradability in compost JF - International Biodeterioration & Biodegradation N2 - 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. Y1 - 2020 U6 - https://doi.org/10.1016/j.ibiod.2020.104914 SN - 0964-8305 VL - 149 SP - In Press, Article number 104914 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Tippkötter, Nils A1 - Roikaew, N. A1 - Ulber, Roland T1 - Nitratentfernung aus Molkekonzentrat mit biotechnologischer Regeneration der Abwässer JF - Deutsche Milchwirtschaft Y1 - 2007 SN - 0012-0480 VL - 58 IS - 15 SP - 540 EP - 542 ER - TY - JOUR A1 - Engel, Mareike A1 - Holtmann, Dirk A1 - Ulber, Roland A1 - Tippkötter, Nils T1 - Increased Biobutanol Production by Mediator‐Less Electro‐Fermentation JF - Biotechnology Journal N2 - 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. Y1 - 2018 U6 - https://doi.org/10.1002/biot.201800514 SN - 1860-7314 VL - 14 IS - 4 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Engel, Mareike A1 - Gemünde, Andre A1 - Holtmann, Dirk A1 - Müller-Renno, Christine A1 - Ziegler, Christiane A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Clostridium acetobutylicum’s connecting world: cell appendage formation in bioelectrochemical systems JF - ChemElectroChem N2 - 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. Y1 - 2019 U6 - https://doi.org/10.1002/celc.201901656 SN - 2196-0216 VL - 7 IS - 2 SP - 414 EP - 420 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Tippkötter, Nils A1 - Roikaew, Wipa A1 - Ulber, Roland A1 - Hoffmann, Alexander A1 - Denzler, Hans-Jörg A1 - Buchholz, Heinrich T1 - Paracoccus denitrificans for the effluent recycling during continuous denitrification of liquid food JF - Biotechnology Progress N2 - 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. Y1 - 2010 U6 - https://doi.org/10.1002/btpr.384 SN - 8756-7938 VL - 26 IS - 3 SP - 756 EP - 762 PB - Wiley CY - Hoboken, NJ ER - TY - JOUR A1 - Voigt, Birgit A1 - Albrecht, Dirk A1 - Sievers, Susanne A1 - Becher, Dörte A1 - Bongaerts, Johannes A1 - Evers, Stefan A1 - Schweder, Thomas A1 - Maurer, Karl-Heinz A1 - Hecker, Michael T1 - High-resolution proteome maps of Bacillus licheniformis cells growing in minimal medium JF - Proteomics Y1 - 2015 U6 - https://doi.org/10.1002/pmic.201400504 SN - 1615-9861 VL - 15 IS - 15 SP - 2629 EP - 2633 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Hoffstadt, Kevin A1 - Nikolausz, Marcell A1 - Krafft, Simone A1 - Bonatelli, Maria A1 - Kumar, Vivekanantha A1 - Harms, Hauke A1 - Kuperjans, Isabel T1 - Optimization of the ex situ biomethanation of hydrogen and carbon dioxide in a novel meandering plug flow reactor: start-up phase and flexible operation JF - Bioengineering KW - methanation KW - plug flow reactor KW - bubble column KW - biomethane KW - P2G Y1 - 2024 U6 - https://doi.org/10.3390/bioengineering11020165 SN - 2306-5354 VL - 11 IS - 2 PB - MDPI CY - Basel ER - TY - JOUR A1 - Cheenakula, Dheeraja A1 - Hoffstadt, Kevin A1 - Krafft, Simone A1 - Reinecke, Diana A1 - Klose, Holger A1 - Kuperjans, Isabel A1 - Grömping, Markus T1 - Anaerobic digestion of algal–bacterial biomass of an Algal Turf Scrubber system JF - Biomass Conversion and Biorefinery N2 - 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. KW - Biogas KW - Methane KW - Algal Turf Scrubber KW - Algal–bacterial bioflm KW - Circular bioeconomy Y1 - 2022 U6 - https://doi.org/10.1007/s13399-022-03236-z SN - 2190-6823 N1 - Corresponding author: Dheeraja Cheenakula VL - 13 SP - 15 Seiten PB - Springer CY - Berlin ER - TY - JOUR A1 - Sieker, Tim A1 - Ulber, Roland A1 - Dimitrova, Darina A1 - Bart, Hans-Jörg A1 - Neuner, Andreas A1 - Heinzle, Elmar A1 - Tippkötter, Nils T1 - Silage : Fermentationsrohstoff für die chemische Industrie? JF - labor&more N2 - In Anbetracht des zu erwartenden Rückgangs der Verfügbarkeit fossiler Rohstoffe müssen nicht nur für den Energiesektor, sondern auch für die Herstellung industrieller Produkte alternative Rohstoffe gefunden werden. Ein Beispiel für einen nicht in Nahrungsmittelkonkurrenz stehenden nachwachsenden Rohstoff ist grüne Biomasse wie Gras und Klee. Diese lassen sich in Deutschland auf großen Flächen anbauen und enthalten eine Vielzahl potenzieller Substrate für Fermentationen. Y1 - 2009 IS - 2 SP - 44 EP - 45 ER - TY - JOUR A1 - Gerigk, M. A1 - Maaß, D. A1 - Kreutzer, A. A1 - Sprenger, G. A1 - Bongaerts, Johannes A1 - Wubbolts, Marcel A1 - Takors, Ralf T1 - Enhanced pilot-scale fed-batch L-phenylalanine production with recombinant Escherichia coli by fully integrated reactive extraction JF - Bioprocess and biosystems engineering Y1 - 2002 SN - 1432-0797 (E-Journal); 1615-7605 (E-Journal); 0178-515X (Print); 1615-7591 (Print) VL - Vol. 25 IS - Iss. 1 SP - 43 EP - 52 ER - TY - JOUR A1 - Tippkötter, Nils A1 - Stückmann, Henning A1 - Kroll, Stephen A1 - Winkelmann, Gunda A1 - Noack, Udo A1 - Scheper, Thomas A1 - Ulber, Roland T1 - A semi-quantitative dipstick assay for microcystin JF - Analytical and Bioanalytical Chemistry N2 - 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. Y1 - 2009 U6 - https://doi.org/10.1007/s00216-009-2750-8 SN - 1618-2650 VL - 394 IS - 3 SP - 863 EP - 869 PB - springer CY - Berlin ER - TY - JOUR A1 - Muschallik, Lukas A1 - Molinnus, Denise A1 - Jablonski, Melanie A1 - Kipp, Carina Ronja A1 - Bongaerts, Johannes A1 - Pohl, Martina A1 - Wagner, Torsten A1 - Schöning, Michael Josef A1 - Selmer, Thorsten A1 - Siegert, Petra T1 - Synthesis of α-hydroxy ketones and vicinal (R, R)-diols by Bacillus clausii DSM 8716ᵀ butanediol dehydrogenase JF - RSC Advances N2 - 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. Y1 - 2020 U6 - https://doi.org/10.1039/D0RA02066D SN - 2046-2069 VL - 10 SP - 12206 EP - 12216 PB - Royal Society of Chemistry (RSC) CY - Cambridge ER - TY - JOUR A1 - Küppers, Tobias A1 - Steffen, Victoria A1 - Hellmuth, Hendrik A1 - O'Connell, Timothy A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Wiechert, Wolfgang T1 - Developing a new production host from a blueprint: Bacillus pumilus as an industrial enzyme producer JF - Microbial cell factories Y1 - 2014 U6 - https://doi.org/10.1186/1475-2859-13-46 SN - 1475-2859 (E-Journal) VL - 13 SP - Article No. 46 PB - BioMed Central CY - London ER - TY - JOUR A1 - Al-Kaidy, Huschyar A1 - Kuthan, Kai A1 - Hering, Thomas A1 - Tippkötter, Nils T1 - Aqueous droplets used as enzymatic microreactors and their electromagnetic actuation JF - Journal of Visualized Experiments N2 - 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. Y1 - 2016 U6 - https://doi.org/10.3791/54643 SN - 1940-087X IS - Issue 126 ER - TY - JOUR A1 - Heinze, D. A1 - Mang, Thomas A1 - Popescu, C. A1 - Weichold, O. T1 - Effect of side chain length and degree of polymerization on the decomposition and crystallization behaviour of chlorinated poly(vinyl ester) oligomers JF - Thermochimica Acta N2 - 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. Y1 - 2016 U6 - https://doi.org/10.1016/j.tca.2016.05.015 SN - 0040-6031 (electronic) VL - 637 SP - 143 EP - 153 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Pinkenburg, Olaf A1 - Schiffels, Johannes A1 - Selmer, Thorsten T1 - Das CoLibry-Konzept – ein Werkzeugkasten für die Synthetische Biologie: Bioproduktion JF - BIOspektrum N2 - Regardless of size or destination, synthetic biology starts with com-parably small information units, which need to be combined and properly arranged in order to achieve a certain goal. This may be the de novo synthesis of individual genes from oligonucleotides, a shuffling of protein domains in order to create novel biocatalysts, the assembly of multiple enzyme encoding genes in metabolic pathway design, or strain development at the production stage. The CoLibry concept has been designed in order to close the gap between recombinant production of individual genes and genome editing. Y1 - 2016 U6 - https://doi.org/10.1007/s12268-016-0734-8 VL - 22 IS - 6 SP - 593 EP - 595 PB - Springer CY - Berlin ER - TY - JOUR A1 - Ghosch, S. A1 - Baier, M. A1 - Schütz, J. A1 - Schneider, Felix A1 - Scherer, Ulrich W. T1 - Analysis of electronic autoradiographs by mathematical post-processing JF - Radiation Effects and Defects in Solids: Incorporating plasma science and plasma technology N2 - 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. Y1 - 2016 U6 - https://doi.org/10.1080/10420150.2016.1155587 SN - 1029-4953 VL - 171 IS - 1-2 SP - 161 EP - 172 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Aboulnaga, E. A. A1 - Zou, H. A1 - Selmer, Thorsten A1 - Xian, M. T1 - Development of a plasmid-based, tunable, tolC-derived expression system for application in Cupriavidus necator H16 JF - Journal of Biotechnology N2 - 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. Y1 - 2018 U6 - https://doi.org/10.1016/j.jbiotec.2018.03.007 SN - 0168-1656 VL - 274 SP - 15 EP - 27 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Druckenmüller, Katharina A1 - Günther, Klaus A1 - Elbers, Gereon T1 - Near-infrared spectroscopy (NIRS) as a tool to monitor exhaust air from poultry operations JF - Science of the Total Environment N2 - 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. Y1 - 2018 U6 - https://doi.org/10.1016/j.scitotenv.2018.02.072 SN - 0048-9697 VL - 630 SP - 536 EP - 543 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Pilas, Johanna A1 - Yazici, Y. A1 - Selmer, Thorsten A1 - Keusgen, M. A1 - Schöning, Michael Josef T1 - Application of a portable multi-analyte biosensor for organic acid determination in silage JF - Sensors N2 - 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. Y1 - 2018 U6 - https://doi.org/10.3390/s18051470 SN - 1424-8220 VL - 18 IS - 5 PB - MDPI CY - Basel ER - TY - JOUR A1 - Wilson, C. E. A1 - Dickie, A. P. A1 - Schreiter, K. A1 - Wehr, R. A1 - Wilson, E. M. A1 - Bial, J. A1 - Scheer, Nico A1 - Wilson, I. D. A1 - Riley, R. J. T1 - The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice JF - Archives of Toxicology N2 - 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. Y1 - 2018 U6 - https://doi.org/10.1007/s00204-018-2212-1 SN - 1432-0738 VL - 92 IS - 6 SP - 1953 EP - 1967 PB - Springer ER - TY - JOUR A1 - Ross, Jillian A1 - Plummer, Simon M. A1 - Rode, Anja A1 - Scheer, Nico A1 - Bower, Conrad C. A1 - Vogel, Ortwin A1 - Henderson, Colin J. A1 - Wolf, C. Roland A1 - Elcombe, Clifford R. T1 - Human constitutive androstane receptor (CAR) and pregnane X receptor (PXR) support the hypertrophic but not the hyperplastic response to the murine nongenotoxic hepatocarcinogens phenobarbital and chlordane in vivo JF - Toxicological Sciences N2 - Mouse nongenotoxic hepatocarcinogens phenobarbital (PB) and chlordane induce hepatomegaly characterized by hypertrophy and hyperplasia. Increased cell proliferation is implicated in the mechanism of tumor induction. The relevance of these tumors to human health is unclear. The xenoreceptors, constitutive androstane receptors (CARs), and pregnane X receptor (PXR) play key roles in these processes. Novel “humanized” and knockout models for both receptors were developed to investigate potential species differences in hepatomegaly. The effects of PB (80 mg/kg/4 days) and chlordane (10 mg/kg/4 days) were investigated in double humanized PXR and CAR (huPXR/huCAR), double knockout PXR and CAR (PXRKO/CARKO), and wild-type (WT) C57BL/6J mice. In WT mice, both compounds caused increased liver weight, hepatocellular hypertrophy, and cell proliferation. Both compounds caused alterations to a number of cell cycle genes consistent with induction of cell proliferation in WT mice. However, these gene expression changes did not occur in PXRKO/CARKO or huPXR/huCAR mice. Liver hypertrophy without hyperplasia was demonstrated in the huPXR/huCAR animals in response to both compounds. Induction of the CAR and PXR target genes, Cyp2b10 and Cyp3a11, was observed in both WT and huPXR/huCAR mouse lines following treatment with PB or chlordane. In the PXRKO/CARKO mice, neither liver growth nor induction of Cyp2b10 and Cyp3a11 was seen following PB or chlordane treatment, indicating that these effects are CAR/PXR dependent. These data suggest that the human receptors are able to support the chemically induced hypertrophic responses but not the hyperplastic (cell proliferation) responses. At this time, we cannot be certain that hCAR and hPXR when expressed in the mouse can function exactly as the genes do when they are expressed in human cells. However, all parameters investigated to date suggest that much of their functionality is maintained. Y1 - 2010 U6 - https://doi.org/10.1093/toxsci/kfq118 SN - 1096-0929 VL - 116 IS - 2 SP - 452 EP - 466 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Scheer, Nico A1 - Ross, Jillian A1 - Kapelyukh, Yury A1 - Rode, Anja A1 - Wolf, C. Roland T1 - In vivo responses of the human and murine pregnane X receptor to dexamethasone in mice JF - Drug Metabolism and Disposition N2 - Dexamethasone (DEX) is a potent and widely used anti-inflammatory and immunosuppressant glucocorticoid. It can bind and activate the pregnane X receptor (PXR), which plays a critical role as xenobiotic sensor in mammals to induce the expression of many enzymes, including cytochromes P450 in the CYP3A family. This induction results in its own metabolism. We have used a series of transgenic mouse lines, including a novel, improved humanized PXR line, to compare the induction profile of PXR-regulated drug-metabolizing enzymes after DEX administration, as well as looking at hepatic responses to rifampicin (RIF). The new humanized PXR model has uncovered further intriguing differences between the human and mouse receptors in that RIF only induced Cyp2b10 in the new humanized model. DEX was found to be a much more potent inducer of Cyp3a proteins in wild-type mice than in mice humanized for PXR. To assess whether PXR is involved in the detoxification of DEX in the liver, we analyzed the consequences of high doses of the glucocorticoid on hepatotoxicity on different PXR genetic backgrounds. We also studied these effects in an additional mouse model in which functional mouse Cyp3a genes have been deleted. These strains exhibited different sensitivities to DEX, indicating a protective role of the PXR and CYP3A proteins against the hepatotoxicity of this compound. Y1 - 2010 U6 - https://doi.org/10.1124/dmd.109.031872 SN - 1521-009X VL - 38 IS - 7 SP - 1046 EP - 1053 PB - ASPET CY - Bethesda ER - TY - JOUR A1 - Scheer, Nico A1 - Ross, Jillian A1 - Rode, Anja A1 - Zevnik, Branko A1 - Niehaves, Sandra A1 - Faust, Nicole A1 - Wolf, C. Roland T1 - A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response JF - Journal of Clinical Investigation Y1 - 2008 U6 - https://doi.org/https://doi.org/10.1172/JCI35483 SN - 1558-8238 VL - 118 IS - 9 SP - 3228 EP - 3239 ER - TY - JOUR A1 - Scheer, Nico A1 - Kapelyukh, Yury A1 - McEwan, Jillian A1 - Beuger, Vincent A1 - Stanley, Lesley A. A1 - Rode, Anja A1 - Wolf, C. Roland T1 - Modeling Human Cytochrome P450 2D6 Metabolism and Drug-drug Interaction by a Novel Panel of Knockout and Humanized Mouse Lines JF - Molecular Pharmacology N2 - The highly polymorphic human cytochrome P450 2D6 enzyme is involved in the metabolism of up to 25% of all marketed drugs and accounts for significant individual differences in response to CYP2D6 substrates. Because of the differences in the multiplicity and substrate specificity of CYP2D family members among species, it is difficult to predict pathways of human CYP2D6-dependent drug metabolism on the basis of animal studies. To create animal models that reflect the human situation more closely and that allow an in vivo assessment of the consequences of differential CYP2D6 drug metabolism, we have developed a novel straightforward approach to delete the entire murine Cyp2d gene cluster and replace it with allelic variants of human CYP2D6. By using this approach, we have generated mouse lines expressing the two frequent human protein isoforms CYP2D6.1 and CYP2D6.2 and an as yet undescribed variant of this enzyme, as well as a Cyp2d cluster knockout mouse. We demonstrate that the various transgenic mouse lines cover a wide spectrum of different human CYP2D6 metabolizer phenotypes. The novel humanization strategy described here provides a robust approach for the expression of different CYP2D6 allelic variants in transgenic mice and thus can help to evaluate potential CYP2D6-dependent interindividual differences in drug response in the context of personalized medicine. Y1 - 2012 U6 - https://doi.org/10.1124/mol.111.075192 SN - 1521-0111 VL - 81 IS - 1 SP - 63 EP - 72 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Reugels, Alexander M. A1 - Boggetti, Barbara A1 - Scheer, Nico A1 - Campos-Ortega, José A. T1 - Asymmetric localization of Numb:EGFP in dividing neuroepithelial cells during neurulation in Danio rerio JF - Developmental Dynamics Y1 - 2006 U6 - https://doi.org/10.1002/dvdy.20699 SN - 1097-0177 VL - 235 IS - 4 SP - 934 EP - 948 ER - TY - JOUR A1 - Hans, Stefan A1 - Scheer, Nico A1 - Riedl, Iris A1 - Weizäcker, Elisabeth von A1 - Blader, Patrick A1 - Campos-Ortega, José A. T1 - her3, a zebrafish member of the hairy-E(spl) family, is repressed by Notch signalling JF - Development Y1 - 2004 U6 - https://doi.org/10.1242/dev.01167 SN - 1477-9129 VL - 131 IS - 12 SP - 2957 EP - 2969 ER - TY - JOUR A1 - Scheer, Nico A1 - Riedl, Iris A1 - Warren, J.T. A1 - Kuwada, John Y. A1 - Campos-Ortega, José A. T1 - A quantitative analysis of the kinetics of Gal4 activator and effector gene expression in the zebrafish JF - Mechanism of Development Y1 - 2002 U6 - https://doi.org/10.1016/S0925-4773(01)00621-9 SN - 0925-4773 VL - 112 IS - 1-2 SP - 9 EP - 14 ER - TY - JOUR A1 - Lawson, Nathan D. A1 - Scheer, Nico A1 - Pham, Van N. A1 - Kim, Ceol-Hee A1 - Chitnis, Ajay B. A1 - Campos-Ortega, José A. A1 - Weinstein, Brant M. T1 - Notch signaling is required for arterial-venous differentiation during embryonic vascular development JF - Development Y1 - 2001 SN - 1477-9129 VL - 128 IS - 19 SP - 3675 EP - 3683 ER - TY - JOUR A1 - Scheer, Nico A1 - Groth, Anne A1 - Hans, Stefan A1 - Campos-Ortega, José A. T1 - An instructive function for Notch in promoting gliogenesis in the zebrafish retina JF - Development Y1 - 2001 SN - 0950-1991 VL - 128 IS - 7 SP - 1099 EP - 1107 ER - TY - JOUR A1 - Halbach, Thorsten A1 - Scheer, Nico T1 - Transcriptional activation by the PHD finger is inhibited through an adjacent leucine zipper that binds 14-3-3 proteins JF - Nucleic Acids Research Y1 - 2000 U6 - https://doi.org/10.1093/nar/28.18.3542 SN - 1362-4962 VL - 28 IS - 18 SP - 3542 EP - 3550 ER - TY - JOUR A1 - Scheer, Nico A1 - Campos-Ortega, José A. T1 - Use of the Gal4-UAS technique for targeted gene expression in the zebrafish JF - Mechanism of Development Y1 - 1999 U6 - https://doi.org/10.1016/S0925-4773(98)00209-3 SN - 0925-4773 VL - 80 IS - 2 SP - 153 EP - 158 ER - TY - JOUR A1 - Scheer, Nico A1 - Wilson, Ian D. T1 - A comparison between genetically humanized and chimeric liver humanized mouse models for studies in drug metabolism and toxicity JF - Drug Discovery Today N2 - Mice that have been genetically humanized for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging and promising in vivo models for an improved prediction of the pharmacokinetic, drug–drug interaction and safety characteristics of compounds in humans. The specific advantages and disadvantages of these models should be carefully considered when using them for studies in drug discovery and development. Here, an overview on the corresponding genetically humanized and chimeric liver humanized mouse models described to date is provided and illustrated with examples of their utility in drug metabolism and toxicity studies. We compare the strength and weaknesses of the two different approaches, give guidance for the selection of the appropriate model for various applications and discuss future trends and perspectives. Y1 - 2016 U6 - https://doi.org/10.1016/j.drudis.2015.09.002 SN - 1359-6446 VL - 21 IS - 2 SP - 250 EP - 263 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications JF - Xenobiotica N2 - 1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug–drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described. 2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created. 3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug–drug interactions as well as in human metabolite testing and risk assessment. 4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed. KW - transporters KW - human metabolites KW - drug metabolising enzymes KW - drug–drug interactions KW - bioavailability Y1 - 2014 U6 - https://doi.org/10.3109/00498254.2013.815831 SN - 1366-5928 VL - 44 IS - 2 SP - 96 EP - 108 PB - Taylor & Francis CY - Abingdon ER - TY - JOUR A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Xenobiotic receptor humanized mice and their utility JF - Drug Metabolism Reviews Y1 - 2013 U6 - https://doi.org/10.3109/03602532.2012.738687 SN - 1097-9883 IS - 1 SP - 110 EP - 121 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Henderson, Colin J. A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Advances in the generation of mouse models to elucidate the pathways of drug metabolism in rodents and man JF - Expert Review of Clinical Pharmacology Y1 - 2009 U6 - https://doi.org/10.1586/17512433.2.2.105 SN - 1751-2441 VL - 2 IS - 2 SP - 105 EP - 109 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Stanley, Lesley A. A1 - Horsburgh, Brian C. A1 - Ross, Jillian A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Drug transporters: Gatekeepers controlling access of xenobiotics to the cellular interior JF - Drug Metabolism Reviews Y1 - 2009 U6 - https://doi.org/10.1080/03602530802605040 SN - 1097-9883 VL - 41 IS - 1 SP - 27 EP - 65 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Stanley, Lesley A. A1 - Horsburgh, Brian C. A1 - Ross, Jillian A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Nuclear Receptors which play a pivotal role in drug disposition and chemical toxicity JF - Drug Metabolism Reviews Y1 - 2006 U6 - https://doi.org/10.1080/03602530600786232 SN - 1097-9883 VL - 38 IS - 3 SP - 515 EP - 597 ER - TY - JOUR A1 - Braband, Henrik A1 - Paulßen, Elisabeth A1 - Abram, Ulrich T1 - Nitridorhenium(V) Complexes with 1,3-Dialkyl-4,5-dimethylimidazole-2-ylidenes JF - Zeitschrift für anorganische und allgemeine Chemie : ZAAC = Journal of inorganic and general chemistry Y1 - 2006 U6 - https://doi.org/10.1002/zaac.200600002 SN - 1521-3749 VL - 632 IS - 6 SP - 1051 EP - 1056 ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Schweighöfer, Philip V. A1 - Abram, Ulrich T1 - Reactions of [ReOX3(PPh3)2] Complexes (X = Cl, Br) with Phenylacetylene and the Structures of the Products JF - Zeitschrift für anorganische und allgemeine Chemie : ZAAC = Journal of inorganic and general chemistry N2 - Oxorhenium(V) complexes [ReOX3(PPh3)2] (X = Cl, Br) react with phenylacetylene under formation of complexes with ylide-type ligands. Compounds of the compositions [ReOCl3(PPh3){C(Ph)C(H)(PPh3)}] (1), [ReOBr3(OPPh3){C(Ph)C(H)(PPh3)}] (2), and [ReOBr3(OPPh3){C(H)C(Ph)(PPh3)}] (3) were isolated and characterized by X-ray diffraction. They contain a ligand, which was formed by a nucleophilic attack of released PPh3 at coordinated phenylacetylene. The structures of the products show that there is no preferable position for this attack. Cleavage of the Re–C bond in 3 and dimerization of the organic ligand resulted in the formation of the [{(PPh3)(H)CC(Ph)}2]2+ cation, which crystallized as its [(ReOBr4)(OReO3)]2– salt. Y1 - 2010 U6 - https://doi.org/10.1002/zaac.200900478 SN - 1521-3749 VL - 636 IS - 5 SP - 779 EP - 783 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Kückmann, Theresa A1 - Abram, Ulrich T1 - Silver(I) Complexes of 1,3-Dialkyl-4,5-dimethylimidazol-2-ylidenes and their Use as Precursors for the Synthesis of Rhenium(V) NHC Complexes JF - Zeitschrift für anorganische und allgemeine Chemie : ZAAC = Journal of inorganic and general chemistry Y1 - 2007 U6 - https://doi.org/10.1002/zaac.200700021 SN - 1521-3749 VL - 633 IS - 5-6 SP - 830 EP - 834 ER - TY - JOUR A1 - Braband, Henrik A1 - Yegen, Eda A1 - Paulßen, Elisabeth A1 - Abram, Ulrich T1 - [{ReN(PMe2Ph)3}{ReO3N}]2 – Structural Evidence for the Nitridotrioxorhenate(VII) Anion, [ReO3N]2− JF - Zeitschrift für anorganische und allgemeine Chemie : ZAAC = Journal of inorganic and general chemistry Y1 - 2005 U6 - https://doi.org/10.1002/zaac.200500240 SN - 1521-3749 VL - 631 IS - 12 SP - 2408 EP - 2410 ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Alberto, Roger A1 - Abram, Ulrich T1 - Synthesis, Characterization, and Structures of R3EOTcO3 Complexes (E = C, Si, Ge, Sn, Pb) and Related Compounds JF - Inorganic Chemistry N2 - AgTcO4 reacts with R3ECl compounds (E = C, Si, Ge, Sn, Pb; R = Me, iPr, tBu, Ph), tBu2SnCl2, or PhMgCl under formation of novel trioxotechnetium(VII) derivatives. The carbon and silicon derivatives readily undergo decomposition, which was proven by 99Tc NMR spectroscopy and the isolation of decomposition products such as [TcOCl3(THF)(OH2)]. Compounds [Ph3GeOTcO3], [(THF)Ph3SnOTcO3], [(O3TcO)SntBu2(OH)]2, and [(THF)4Mg(OTcO3)2] are more stable and were isolated in crystalline form and characterized by X-ray diffraction. Y1 - 2010 U6 - https://doi.org/10.1021/ic1001094 SN - 1520-510X VL - 49 IS - 7 SP - 3525 EP - 3530 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Kong, Shushu A1 - Arciszewski, Pawel A1 - Wielbalck, Swantje A1 - Abram, Ulrich T1 - Aryl and NHC Compounds of Technetium and Rhenium JF - Journal of the American Chemical Society N2 - Air- and water-stable phenyl complexes with nitridotechnetium(V) cores can be prepared by straightforward procedures. [TcNPh2(PPh3)2] is formed by the reaction of [TcNCl2(PPh3)2] with PhLi. The analogous N-heterocyclic carbene (NHC) compound [TcNPh2(HLPh)2], where HLPh is 1,3,4-triphenyl-1,2,4-triazol-5-ylidene, is available from (NBu4)[TcNCl4] and HLPh or its methoxo-protected form. The latter compound allows the comparison of different Tc–C bonds within one compound. Surprisingly, the Tc chemistry with such NHCs does not resemble that of corresponding Re complexes, where CH activation and orthometalation dominate. Y1 - 2012 U6 - https://doi.org/10.1021/ja3033718 SN - 1520-5126 VL - 134 IS - 22 SP - 9118 EP - 9121 PB - ACS Publications CY - Washington, DC ER - TY - JOUR A1 - Barbazán, Paula A1 - Hagenbach, Adelheid A1 - Paulßen, Elisabeth A1 - Abram, Ulrich A1 - Carballo, Rosa A1 - Rodriguez-Hermida, Sabina A1 - Vázquez-López, Ezequiel M. T1 - Tricarbonyl Rhenium(I) and Technetium(I) Complexes with Hydrazones Derived from 4,5-Diazafluoren-9-one and 1,10-Phenanthroline-5,6-dione JF - European Journal of Inorganic Chemistry N2 - Tricarbonylrhenium(I) and -technetium(I) halide (halide = Cl and Br) complexes of ligands derived from 4,5-diazafluoren-9-one (df) and 1,10-phenanthroline-5,6-dione (phen) derivatives of benzoic and 2-hydroxybenzoic acid hydrazides have been prepared. The complexes have been characterized by elemental analysis, MS, IR, 1H NMR and absorption and emission UV/Vis spectroscopic methods. The metal centres (ReI and TcI) are coordinated through the nitrogen imine atoms and establish five-membered chelate rings, whereas the hydrazone groups stand uncoordinated. The 1H NMR spectra suggest the same behaviour in solution on the basis of only marginal variations in the chemical shifts of the hydrazine protons. Y1 - 2010 U6 - https://doi.org/10.1002/ejic.201000522 SN - 1099-0682 IS - 29 SP - 4622 EP - 4630 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Ngyugen, Hung Huy A1 - Kahlcke, Nils A1 - Deflon, Victor M. A1 - Abram, Ulrich T1 - Tricarbonyltechnetium(I) and -rhenium(I) complexes with N′-thiocarbamoylpicolylbenzamidines JF - Polyhedron N2 - N,N-Dialkylamino(thiocarbonyl)-N′-picolylbenzamidines react with (NEt4)2[M(CO)3X3] (M = Re, X = Br; M = Tc, X = Cl) under formation of neutral [M(CO)3L] complexes in high yields. The monoanionic NNS ligands bind in a facial coordination mode and can readily be modified at the (CS)NR1R2 moiety. The complexes [99Tc(CO)3(LPyMor)] and [Re(CO)3(L)] (L = LPyMor, LPyEt) were characterized by X-ray diffraction. Reactions of [99mTc(CO)3(H2O)3]+ with the N′-thiocarbamoylpicolylbenzamidines give the corresponding 99mTc complexes. The ester group in HLPyCOOEt allows linkage between biomolecules and the metal core. Y1 - 2012 U6 - https://doi.org/10.1016/j.poly.2012.04.008 SN - 0277-5387 VL - 40 IS - 1 SP - 153 EP - 158 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Pellegrini, Paul A. A1 - Howell, Nicholas R. A1 - Shepherd, Rachael K. A1 - Lengkeek, Nigel A. A1 - Paulßen, Elisabeth A1 - Katsifis, Andrew G. A1 - Greguric, Ivan T1 - Synthesis and Radiolabelling of DOTA-Linked Glutamine Analogues with 67,68Ga as Markers for Increased Glutamine Metabolism in Tumour Cells JF - Molecules Y1 - 2013 U6 - https://doi.org/10.3390/molecules18067160 SN - 1420-3049 VL - 18 IS - 6 SP - 7160 EP - 7178 PB - MDPI CY - Basel ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Le, Van So A1 - Lengkeek, Nigel A1 - Pellegrini, Paul A1 - Jackson, Tim A1 - Greguric, Ivan A1 - Weiner, Ron T1 - Influence of Metal Ions on the 68Ga-labeling of DOTATATE JF - Applied Radiation and Isotopes Y1 - 2013 U6 - https://doi.org/10.1016/j.apradiso.2013.08.010 SN - 1872-9800 VL - 82 SP - 232 EP - 238 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Lengkeek, Nigel A. A1 - Le, Van So A1 - Pellegrini, Paul A. A1 - Greguric, Ivan A1 - Weiner, Ron T1 - The role of additives in moderating the influence of Fe(III) and Cu(II) on the radiochemical yield of [⁶⁸Ga(DOTATATE)] JF - Applied Radiation and Isotopes N2 - [⁶⁸Ga(DOTATATE)] has demonstrated its clinical usefulness. Both Fe³⁺ and Cu²⁺, potential contaminants in Gallium-68 generator eluent, substantially reduce the radiochemical (RC) yield of [⁶⁸Ga(DOTATATE)] if the metal/ligand ratio of 1:1 is exceeded. A variety of compounds were examined for their potential ability to reduce this effect. Most had no effect on RC yield. However, addition of phosphate diminished the influence of Fe³⁺ by likely forming an insoluble iron salt. Addition of ascorbic acid reduced Cu²⁺ and Fe³⁺ to Cu⁺ and Fe²⁺ respectively, both of which have limited impact on RC yields. At low ligand amounts (5 nmol DOTATATE), the addition of 30 nmol phosphate (0.19 mM) increased the tolerance of Fe3⁺ from 4 nmol to 10 nmol (0.06 mM), while the addition of ascorbic acid allowed high RC yields (>95%) in the presence of 40 nmol Fe³⁺ (0.25 mM) and 100 nmol Cu²⁺ (0.63 mM). The effect of ascorbic acid was highly pH-dependant, and gave optimal results at pH 3. Y1 - 2016 U6 - https://doi.org/10.1016/j.apradiso.2015.09.008 SN - 1872-9800 VL - 107 SP - 13 EP - 16 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Hoehr, Cornelia A1 - Hou, Xinchi A1 - Hanemaayer, Victoire A1 - Zeisler, Stefan A1 - Adam, Michael J. A1 - Ruth, Thomas J. A1 - Celler, Anna A1 - Buckley, Ken A1 - Benard, Francois A1 - Schaffer, Paul T1 - Production of Y-86 and other radiometals for research purposes using a solution target system JF - Nuclear medicine and biology Y1 - 2015 U6 - https://doi.org/10.1016/j.nucmedbio.2015.06.005 SN - 1872-9614 VL - 42 IS - 11 SP - 842 EP - 849 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Hoehr, Cornelia A1 - Paulßen, Elisabeth A1 - Benard, Francois A1 - Lee, Chris Jaeil A1 - Hou, Xinchi A1 - Badesso, Brian A1 - Ferguson, Simon A1 - Miao, Qing A1 - Yang, Hua A1 - Buckley, Ken A1 - Hanemaayer, Victoire A1 - Zeisler, Stefan A1 - Ruth, Thomas A1 - Celler, Anna A1 - Schaffer, Paul T1 - ⁴⁴ᶢSc production using a water target on a 13 MeV cyclotron JF - Nuclear medicine and biology N2 - Access to promising radiometals as isotopes for novel molecular imaging agents requires that they are routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for the metal of interest is necessary, both of which can introduce significant hurdles in development of less common isotopes. Herein, we describe the production of ⁴⁴Sc (t₁⸝₂ = 3.97 h, Eavg,β⁺ = 1.47 MeV, branching ratio = 94.27%) in a solution target and an automated loading system which allows a quick turn-around between different radiometallic isotopes and therefore greatly improves their availability for tracer development. Experimental yields are compared to theoretical calculations. Y1 - 2014 U6 - https://doi.org/10.1016/j.nucmedbio.2013.12.016 SN - 1872-9614 VL - 41 IS - 5 SP - 401 EP - 406 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Infantino, Angelo A1 - Paulßen, Elisabeth A1 - Mostacci, Domiziano A1 - Schaffer, Paul A1 - Trinczek, Michael A1 - Hoehr, Cornelia T1 - Assessment of the production of medical isotopes using the Monte Carlo code FLUKA: Simulations against experimental measurements JF - Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms N2 - The Monte Carlo code FLUKA is used to simulate the production of a number of positron emitting radionuclides, ¹⁸F, ¹³N, ⁹⁴Tc, ⁴⁴Sc, ⁶⁸Ga, ⁸⁶Y, ⁸⁹Zr, ⁵²Mn, ⁶¹Cu and ⁵⁵Co, on a small medical cyclotron with a proton beam energy of 13 MeV. Experimental data collected at the TR13 cyclotron at TRIUMF agree within a factor of 0.6 ± 0.4 with the directly simulated data, except for the production of ⁵⁵Co, where the simulation underestimates the experiment by a factor of 3.4 ± 0.4. The experimental data also agree within a factor of 0.8 ± 0.6 with the convolution of simulated proton fluence and cross sections from literature. Overall, this confirms the applicability of FLUKA to simulate radionuclide production at 13 MeV proton beam energy. Y1 - 2016 U6 - https://doi.org/10.1016/j.nimb.2015.10.067 SN - 1872-9584 VL - 366 SP - 117 EP - 123 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Liu, Z. A1 - Schaap, K. S. A1 - Ballemans, L. A1 - de Blois, E. A1 - Rohde, M. A1 - Paulßen, Elisabeth T1 - Measurement of reaction kinetics of [177Lu]Lu-DOTA-TATE using a microfluidic system JF - Dalton Transactions Y1 - 2017 U6 - https://doi.org/10.1039/C7DT01830D SN - 1477-9234 VL - 46 IS - 42 SP - 14669 EP - 14676 ER -