@article{WissenbachSixBongaertsetal.1995, author = {Wissenbach, U. and Six, S. and Bongaerts, Johannes and Ternes, D. and Steinwachs, S. and Unden, G.}, title = {A third periplasmic transport system for l-arginine in Escherichia coli: molecular characterization of the artPIQMJ genes, arginine binding and transport}, series = {Molecular microbiology}, volume = {Vol. 17}, journal = {Molecular microbiology}, number = {Iss. 4}, issn = {1365-2958 (E-Journal); 0950-382x (Print)}, pages = {675 -- 686}, year = {1995}, language = {en} } @article{NaithaniKlostermeyerLangeetal.1971, author = {Naithani, V. K and Klostermeyer, Henning and Lange, H. R. and [u.a.], and Berndt, Heinz and [u.a.],}, title = {Preparation of peptide derivatives for porcine proinsulin-synthesis}, series = {Biological Chemistry}, volume = {352}, journal = {Biological Chemistry}, number = {1}, publisher = {De Gruyter}, issn = {1437-4315}, doi = {10.1515/bchm2.1971.352.1.1}, pages = {2 -- 3}, year = {1971}, language = {en} } @article{MatoniBerndt1980, author = {Matoni, Georg and Berndt, Heinz}, title = {Thermal synthesis of the optical pure pentapeptide derivative Z-(L)-Ala-(L)-Phe-Gly-(L)-Phe-Gly-OMe}, series = {Tetrahedron letters}, volume = {21}, journal = {Tetrahedron letters}, number = {1}, issn = {0040-4039}, doi = {10.1016/S0040-4039(00)93618-9}, pages = {37 -- 40}, year = {1980}, language = {en} } @article{NokiharaBerndt1978, author = {Nokihara, Kiyoshi and Berndt, Heinz}, title = {Studies on sulfur-containing peptides : tert-butyloxycarbonylsulfenyl and benzyloxycarbonylsulfenyl derivatives as protecting groups for cysteine}, series = {The journal of organic chemistry}, volume = {43}, journal = {The journal of organic chemistry}, number = {25}, publisher = {American Chemical Society}, address = {Washington}, issn = {0022-3263}, doi = {10.1021/jo00419a046}, pages = {4893 -- 4895}, year = {1978}, language = {en} } @article{NokiharaBerndt1978, author = {Nokihara, Kiyoshi and Berndt, Heinz}, title = {Synthesis of hapten-polypeptide conjugates as antigen models for the N-terminal region of the α-2-chain of rabbit skin collagen}, series = {Journal of the Royal Society of Chemistry: Perkin Transactions 1}, volume = {1978}, journal = {Journal of the Royal Society of Chemistry: Perkin Transactions 1}, number = {3}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1364-5463}, doi = {10.1039/P19780000260}, pages = {260 -- 263}, year = {1978}, abstract = {Synthesis of derivatives of the peptide sequence L-pyroglutamyl-L-phenylalanyl-L-aspartyl-glycyl-L-lysyl-glycyl-glycyl-glycine as the antigenic determinant representing the N-terminal non-helical region of the α-2-chain of rabbit skin collagen, and conjugation to two different polypeptide carriers, are described.}, language = {en} } @article{DuttaHartkopfFroederWitteetal.2013, author = {Dutta, Suryendu and Hartkopf-Fr{\"o}der, Christoph and Witte, Karin and Brocke, Rainer and Mann, Ulrich}, title = {Molecular characterization of fossil palynomorphs by transmission micro-FTIR spectroscopy: implications for hydrocarbon source evaluation}, series = {International journal of coal geology}, volume = {Vol. 115}, journal = {International journal of coal geology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1872-7840 (E-Journal); 0166-5162 (Print)}, pages = {13 -- 23}, year = {2013}, language = {en} } @article{BerndtKrueger1985, author = {Berndt, Heinz and Kr{\"u}ger, G{\"o}tz}, title = {Resolution of enantiomeric amino acid derivatives by high-performance liquid chromatography on chiral stationary phases}, series = {Journal of chromatography A}, volume = {1985}, journal = {Journal of chromatography A}, number = {348}, issn = {0021-9673}, doi = {10.1016/S0021-9673(01)92461-6}, pages = {275 -- 279}, year = {1985}, language = {en} } @article{DanhoNaithaniSasakietal.1980, author = {Danho, Waleed and Naithani, Vinod K. and Sasaki, Andr{\´e} N. and F{\"o}hles, Joseph and Berndt, Heinz and [u.a.],}, title = {Human proinsulin, VII : synthesis of two protected peptides corresponding to the sequences 1—45 and 46—86 of the prohormone}, series = {Hoppe-Seyler's Zeitschrift f{\"u}r physiologische Chemie}, volume = {361}, journal = {Hoppe-Seyler's Zeitschrift f{\"u}r physiologische Chemie}, number = {1}, issn = {1437-4315}, doi = {10.1515/bchm2.1980.361.1.857}, pages = {857 -- 863}, year = {1980}, language = {en} } @article{WangDruckenmuellerElbersetal.2014, author = {Wang, Ren-Qi and Druckenm{\"u}ller, Katharina and Elbers, Gereon and Guenther, Klaus and Crou{\´e}, Jean-Philippe}, title = {Analysis of aquatic-phase natural organic matter by optimized LDI-MS method}, series = {Journal of mass spectrometry}, volume = {49}, journal = {Journal of mass spectrometry}, number = {2}, publisher = {Wiley}, address = {Bognor Regis}, issn = {1096-9888}, doi = {10.1002/jms.3321}, pages = {154 -- 160}, year = {2014}, abstract = {The composition and physiochemical properties of aquatic-phase natural organic matter (NOM) are most important problems for both environmental studies and water industry. Laser desorption/ionization (LDI) mass spectrometry facilitated successful examinations of NOM, as humic and fulvic acids in NOM are readily ionized by the nitrogen laser. In this study, hydrophobic NOMs (HPO NOMs) from river, reservoir and waste water were characterized by this technique. The effect of analytical variables like concentration, solvent composition and laser energy was investigated. The exact masses of small molecular NOM moieties in the range of 200-1200 m/z were determined in reflectron mode. In addition, spectra of post-source-decay experiments in this range showed that some compounds from different natural NOMs had the same fragmental ions. In the large mass range of 1200-15 000 Da, macromolecules and their aggregates were found in HPO NOMs from natural waters. Highly humic HPO exhibited mass peaks larger than 8000 Da. On the other hand, the waste water and reservoir water mainly had relatively smaller molecules of about 2000 Da. The LDI-MS measurements indicated that highly humic river waters were able to form large aggregates and membrane foulants, while the HPO NOMs from waste water and reservoir water were unlikely to form large aggregates. Copyright © 2014 John Wiley \& Sons, Ltd.}, language = {en} } @article{SchroeterHoffmannVoigtetal.2014, author = {Schroeter, Rebecca and Hoffmann, Tamara and Voigt, Birgit and Meyer, Hanna and Bleisteiner, Monika and Muntel, Jan and J{\"u}rgen, Britta and Albrecht, Dirk and Becher, D{\"o}rte and Lalk, Michael and Evers, Stefan and Bongaerts, Johannes and Maurer, Karl-Heinz and Putzer, Harald and Hecker, Michael and Schweder, Thomas and Bremer, Erhard}, title = {Stress responses of the industrial workhorse Bacillus licheniformis to osmotic challenges}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {11}, publisher = {PLOS}, address = {San Francisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0080956}, pages = {e80956}, year = {2014}, abstract = {The Gram-positive endospore-forming bacterium Bacillus licheniformis can be found widely in nature and it is exploited in industrial processes for the manufacturing of antibiotics, specialty chemicals, and enzymes. Both in its varied natural habitats and in industrial settings, B. licheniformis cells will be exposed to increases in the external osmolarity, conditions that trigger water efflux, impair turgor, cause the cessation of growth, and negatively affect the productivity of cell factories in biotechnological processes. We have taken here both systems-wide and targeted physiological approaches to unravel the core of the osmostress responses of B. licheniformis. Cells were suddenly subjected to an osmotic upshift of considerable magnitude (with 1 M NaCl), and their transcriptional profile was then recorded in a time-resolved fashion on a genome-wide scale. A bioinformatics cluster analysis was used to group the osmotically up-regulated genes into categories that are functionally associated with the synthesis and import of osmostress-relieving compounds (compatible solutes), the SigB-controlled general stress response, and genes whose functional annotation suggests that salt stress triggers secondary oxidative stress responses in B. licheniformis. The data set focusing on the transcriptional profile of B. licheniformis was enriched by proteomics aimed at identifying those proteins that were accumulated by the cells through increased biosynthesis in response to osmotic stress. Furthermore, these global approaches were augmented by a set of experiments that addressed the synthesis of the compatible solutes proline and glycine betaine and assessed the growth-enhancing effects of various osmoprotectants. Combined, our data provide a blueprint of the cellular adjustment processes of B. licheniformis to both sudden and sustained osmotic stress.}, language = {en} } @article{HeineHerrmannSelmeretal.2014, author = {Heine, A. and Herrmann, G. and Selmer, Thorsten and Terwesten, F. and Buckel, W. and Reuter, K.}, title = {High resolution crystal structure of clostridium propionicum β-Alanyl-CoA:Ammonia Lyase, a new member of the "Hot Dog Fold" protein superfamily}, series = {Proteins}, volume = {82}, journal = {Proteins}, number = {9}, publisher = {Wiley-Liss}, address = {New York}, issn = {1097-0134 (E-Journal); 0887-3585 (Print)}, doi = {10.1002/prot.24557}, pages = {2041 -- 2053}, year = {2014}, abstract = {Clostridium propionicum is the only organism known to ferment β-alanine, a constituent of coenzyme A (CoA) and the phosphopantetheinyl prosthetic group of holo-acyl carrier protein. The first step in the fermentation is a CoA-transfer to β-alanine. Subsequently, the resulting β-alanyl-CoA is deaminated by the enzyme β-alanyl-CoA:ammonia lyase (Acl) to reversibly form ammonia and acrylyl-CoA. We have determined the crystal structure of Acl in its apo-form at a resolution of 0.97 {\AA} as well as in complex with CoA at a resolution of 1.59 {\AA}. The structures reveal that the enyzme belongs to a superfamily of proteins exhibiting a so called "hot dog fold" which is characterized by a five-stranded antiparallel β-sheet with a long α-helix packed against it. The functional unit of all "hot dog fold" proteins is a homodimer containing two equivalent substrate binding sites which are established by the dimer interface. In the case of Acl, three functional dimers combine to a homohexamer strongly resembling the homohexamer formed by YciA-like acyl-CoA thioesterases. Here, we propose an enzymatic mechanism based on the crystal structure of the Acl·CoA complex and molecular docking. Proteins 2014; 82:2041-2053. © 2014 Wiley Periodicals, Inc.}, language = {en} } @article{TakenagaBiselliSchnitzleretal.2014, author = {Takenaga, Shoko and Biselli, Manfred and Schnitzler, Thomas and {\"O}hlschl{\"a}ger, Peter and Wagner, Torsten and Sch{\"o}ning, Michael Josef}, title = {Toward multi-analyte bioarray sensors: LAPS-based on-chip determination of a Michaelis-Menten-like kinetics for cell culturing}, series = {Physica status solidi A : Applications and materials science}, volume = {211}, journal = {Physica status solidi A : Applications and materials science}, number = {6}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1521-396X (E); 1862-6319 (E-Journal); 0031-8965 (Print); 1862-6300 (Print)}, doi = {10.1002/pssa.201330464}, pages = {1410 -- 1415}, year = {2014}, abstract = {The metabolic activity of Chinese hamster ovary (CHO) cells was observed using a light-addressable potentiometric sensor (LAPS). The dependency toward different glucose concentrations (17-200 mM) follows a Michaelis-Menten kinetics trajectory with Kₘ = 32.8 mM, and the obtained Kₘ value in this experiment was compared with that found in literature. In addition, the pH shift induced by glucose metabolism of tumor cells transfected with the HPV-16 genome (C3 cells) was successfully observed. These results indicate the possibility to determine the tumor cells metabolism with a LAPS-based measurement device.}, language = {en} } @article{KueppersSteffenHellmuthetal.2014, author = {K{\"u}ppers, Tobias and Steffen, Victoria and Hellmuth, Hendrik and O'Connell, Timothy and Bongaerts, Johannes and Maurer, Karl-Heinz and Wiechert, Wolfgang}, title = {Developing a new production host from a blueprint: Bacillus pumilus as an industrial enzyme producer}, series = {Microbial cell factories}, volume = {13}, journal = {Microbial cell factories}, publisher = {BioMed Central}, address = {London}, issn = {1475-2859 (E-Journal)}, doi = {10.1186/1475-2859-13-46}, pages = {Article No. 46}, year = {2014}, language = {en} } @article{GuoMiyamotoWagneretal.2014, author = {Guo, Yuanyuan and Miyamoto, Ko-ichiro and Wagner, Torsten and Sch{\"o}ning, Michael Josef and Yoshinobu, Tatsuo}, title = {Theoretical study and simulation of light-addressable potentiometric sensors}, series = {Physica status solidi (A) : applications and materials}, volume = {211}, journal = {Physica status solidi (A) : applications and materials}, number = {6}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0031-8965}, doi = {10.1002/pssa.201330354}, pages = {1467 -- 1472}, year = {2014}, abstract = {The light-addressable potentiometric sensor (LAPS) is a semiconductor-based potentiometric sensor using a light probe with an ability of detecting the concentration of biochemical species in a spatially resolved manner. As an important biomedical sensor, research has been conducted to improve its performance, for instance, to realize high-speed measurement. In this work, the idea of facilitating the device-level simulation, instead of using an equivalent-circuit model, is presented for detailed analysis and optimization of the performance of the LAPS. Both carrier distribution and photocurrent response have been simulated to provide new insight into both amplitude-mode and phase-mode operations of the LAPS. Various device parameters can be examined to effectively design and optimize the LAPS structures and setups for enhanced performance.}, language = {en} } @article{SmithBaumannWilsonetal.1987, author = {Smith, Walker O. and Baumann, Marcus and Wilson, David L. and Aletsee, Ludwig}, title = {Phytoplankton biomass and productivity in the marginal ice zone of the Fram Strait during summer 1984}, series = {Journal of geophysical research}, volume = {Vol. 92}, journal = {Journal of geophysical research}, number = {Iss. C7}, issn = {2156-2202 (E-Journal); 2169-9291 (E-Journal); 0148-0227 (Print); 2169-9275 (Print)}, pages = {6777 -- 6786}, year = {1987}, language = {en} } @article{JahnkeBaumann1987, author = {Jahnke, J. and Baumann, Marcus}, title = {Differentiation between Phaeocystis pouchetii (Har.) Lagerheim and Phaeocystis globosa Scherffel}, series = {Hydrobiological bulletin}, volume = {Vol. 21}, journal = {Hydrobiological bulletin}, number = {Iss. 2}, issn = {0165-1404 (Print); 1573-5125 (E-Journal)}, pages = {141 -- 147}, year = {1987}, language = {en} } @article{AletseeBaumann1991, author = {Aletsee, Ludwig and Baumann, Marcus}, title = {A laboratory incubator equipped with facilities to automatically simulate natural irradiance}, series = {Boletim do Instituto Oceanogr{\´a}fico / Universidade de S{\~a}o Paulo}, volume = {Vol. 39}, journal = {Boletim do Instituto Oceanogr{\´a}fico / Universidade de S{\~a}o Paulo}, number = {No. 2}, issn = {1982-436X; 0080-6331}, pages = {155 -- 159}, year = {1991}, language = {en} } @article{TuegBaumann1994, author = {T{\"u}g, Helmut and Baumann, Marcus}, title = {Problems of UV-B radiation measurements in biological research : critical remarks on current techniques and suggestions for improvements}, series = {Geophysical research letters}, volume = {Vol. 21}, journal = {Geophysical research letters}, number = {Iss. 8}, issn = {1944-8007 (E-Journal); 0094-8276 (Print)}, pages = {689 -- 692}, year = {1994}, language = {en} } @article{MedlinLangeBaumann1994, author = {Medlin, L. K. and Lange, M. and Baumann, Marcus}, title = {Genetic differentiation among three colony-forming species of Phaeocystis : further evidence for the phylogeny of the Prymnesiophyta}, series = {Phycologia}, volume = {Vol. 33}, journal = {Phycologia}, number = {Iss. 3}, issn = {0031-8884}, pages = {199 -- 212}, year = {1994}, language = {en} } @article{TuegBaumann1995, author = {T{\"u}g, Helmut and Baumann, Marcus}, title = {Reply to the comments by R.L. McKenzie and P.V. Johnston on our paper "Problems of UV-B radiation measurements in biological research: Critical Remarks on current techniques and suggestions for improvements"}, series = {Geophysical research letters}, volume = {Vol. 22}, journal = {Geophysical research letters}, number = {Iss. 9}, issn = {1944-8007 (E-Journal); 0094-8276 (Print)}, pages = {1159 -- 1160}, year = {1995}, language = {en} } @article{MartinezJakobTuetal.2013, author = {Martinez, Ronny and Jakob, Felix and Tu, Ran and Siegert, Petra and Maurer, Karl-Heinz and Schwaneberg, Ulrich}, title = {Increasing activity and thermal resistance of Bacillus gibsonii alkaline protease (BgAP) by directed evolution}, series = {Biotechnology and bioengineering}, volume = {Vol. 110}, journal = {Biotechnology and bioengineering}, number = {Iss. 3}, publisher = {Wiley}, address = {Weinheim}, issn = {1097-0290 (E-Journal); 0006-3592 (Print); 0368-1467 (Print)}, pages = {711 -- 720}, year = {2013}, language = {en} } @article{JakobMartinezMandaweetal.2013, author = {Jakob, Felix and Martinez, Ronny and Mandawe, John and Hellmuth, Hendrik and Siegert, Petra and Maurer, Karl-Heinz and Schwaneberg, Ulrich}, title = {Surface charge engineering of a Bacillus gibsonii subtilisin protease}, series = {Applied microbiology and biotechnology}, volume = {Vol. 97}, journal = {Applied microbiology and biotechnology}, number = {Iss. 15}, publisher = {Springer}, address = {Berlin}, issn = {1432-0614 (E-Journal); 0171-1741 (Print); 0175-7598 (Print); 0340-2118 (Print)}, pages = {6793 -- 6802}, year = {2013}, language = {en} } @article{NiehausGaborWielandetal.2011, author = {Niehaus, F. and Gabor, E. and Wieland, S. and Siegert, Petra and Maurer, Karl-Heinz and Eck, J.}, title = {Enzymes for the laundry industries: tapping the vast metagenomic pool of alkaline proteases}, series = {Microbial biotechnology}, volume = {Vol. 4}, journal = {Microbial biotechnology}, number = {Iss. 6}, publisher = {Springer}, address = {Berlin}, issn = {1432-0614 (E-Journal); 0171-1741 (Print); 0175-7598 (Print); 0340-2118 (Print)}, pages = {767 -- 776}, year = {2011}, language = {en} } @article{RibitschHeumannKarletal.2012, author = {Ribitsch, D. and Heumann, S. and Karl, W. and Gerlach, J. and Leber, R. and Birner-Gruenberger, R. and Gruber, K. and Eiteljoerg, I. and Remler, P. and Siegert, Petra and Lange, J. and Maurer, Karl-Heinz and Berg, G. and Guebitz, G. M. and Schwab, H.}, title = {Extracellular serine proteases from Stenotrophomonas maltophilia: Screening, isolation and heterologous expression in E. coli}, series = {Journal of biotechnology}, volume = {157}, journal = {Journal of biotechnology}, number = {1}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-4863 (E-Journal); 0168-1656 (Print)}, doi = {10.1016/j.jbiotec.2011.09.025}, pages = {140 -- 147}, year = {2012}, abstract = {A large strain collection comprising antagonistic bacteria was screened for novel detergent proteases. Several strains displayed protease activity on agar plates containing skim milk but were inactive in liquid media. Encapsulation of cells in alginate beads induced protease production. Stenotrophomonas maltophilia emerged as best performer under washing conditions. For identification of wash-active proteases, four extracellular serine proteases called StmPr1, StmPr2, StmPr3 and StmPr4 were cloned. StmPr2 and StmPr4 were sufficiently overexpressed in E. coli. Expression of StmPr1 and StmPr3 resulted in unprocessed, insoluble protein. Truncation of most of the C-terminal domain which has been identified by enzyme modeling succeeded in expression of soluble, active StmPr1 but failed in case of StmPr3. From laundry application tests StmPr2 turned out to be a highly wash-active protease at 45 °C. Specific activity of StmPr2 determined with suc-l-Ala-l-Ala-l-Pro-l-Phe-p-nitroanilide as the substrate was 17 ± 2 U/mg. In addition we determined the kinetic parameters and cleavage preferences of protease StmPr2.}, language = {en} } @article{RibitschKarlBirnerGruenbergeretal.2010, author = {Ribitsch, D. and Karl, W. and Birner-Gruenberger, R. and Gruber, K. and Eiteljoerg, I. and Remler, P. and Wieland, S. and Siegert, Petra and Maurer, Karl-Heinz and Schwab, H.}, title = {C-terminal truncation of a metagenome-derived detergent protease for effective expression in E. coli}, series = {Journal of biotechnology}, volume = {150}, journal = {Journal of biotechnology}, number = {3}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-4863 (E-Journal); 0168-1656 (Print)}, doi = {10.1016/j.jbiotec.2010.09.947}, pages = {408 -- 416}, year = {2010}, abstract = {Recently, a new alkaline protease named HP70 showing highest homology to extracellular serine proteases of Stenotrophomonas maltophilia and Xanthomonas campestris was found in the course of a metagenome screening for detergent proteases (Niehaus et al., submitted for publication). Attempts to efficiently express the enzyme in common expression hosts had failed. This study reports on the realization of overexpression in Escherichia coli after structural modification of HP70. Modelling of HP70 resulted in a two-domain structure, comprising the catalytic domain and a C-terminal domain which includes about 100 amino acids. On the basis of the modelled structure the enzyme was truncated by deletion of most of the C-terminal domain yielding HP70-C477. This structural modification allowed effective expression of active enzyme using E. coli BL21-Gold as the host. Specific activity of HP70-C477 determined with suc-l-Ala-l-Ala-l-Pro-l-Phe-p-nitroanilide as the substrate was 30 ± 5 U/mg compared to 8 ± 1 U/mg of the native enzyme. HP70-C477 was most active at 40 °C and pH 7-11; these conditions are prerequisite for a potential application as detergent enzyme. Determination of kinetic parameters at 40 °C and pH = 9.5 resulted in KM = 0.23 ± 0.01 mM and kcat = 167.5 ± 3.6 s⁻¹. MS-analysis of peptide fragments obtained from incubation of HP70 and HP70-C477 with insulin B indicated that the C-terminal domain influences the cleavage preferences of the enzyme. Washing experiments confirmed the high potential of HP70-C477 as detergent protease.}, language = {en} } @article{SiegertMcLeishBaumannetal.2005, author = {Siegert, Petra and McLeish, Michael J. and Baumann, Martin and Iding, Hans and Kneen, Malea M. and Kenyon, George L. and Pohl, Martina}, title = {Exchanging the substrate specificities of pyruvate decarboxylase from Zymomonas mobilis and benzoylformate decarboxylase from Pseudomonas putida}, series = {Protein engineering, design, and selection : peds}, volume = {Vol. 18}, journal = {Protein engineering, design, and selection : peds}, number = {Iss. 7}, issn = {1460-213X (E-Journal); 1741-0134 (E-Journal); 0269-2139 (Print); 1741-0126 (Print)}, pages = {345 -- 357}, year = {2005}, language = {en} } @article{DuenkelmannKolterJungNitscheetal.2002, author = {D{\"u}nkelmann, Pascal and Kolter-Jung, Doris and Nitsche, Adam and Demir, Ayhan S. and Siegert, Petra and Lingen, Bettina and Baumann, Martin and Pohl, Martina and M{\"u}ller, Michael}, title = {Development of a donor-acceptor concept for enzymatic cross-coupling reactions of adehydes : the first asymmetric cross-benzoin condensation}, series = {Journal of the American Chemical Society}, volume = {Vol. 124}, journal = {Journal of the American Chemical Society}, issn = {1520-5126 (E-Journal); 0002-7863 (Print)}, pages = {12084 -- 12085}, year = {2002}, language = {en} } @article{DuennwaldDemirSiegertetal.2001, author = {D{\"u}nnwald, Thomas and Demir, Ayhan S. and Siegert, Petra and Pohl, Martina and M{\"u}ller, Michael}, title = {ChemInform Abstract: Enantioselective synthesis of (S)-2-Hydroxypropanone derivatives by Benzoylformate Decarboxylase Catalyzed C—C Bond Formation}, series = {Cheminform}, volume = {Vol. 32}, journal = {Cheminform}, number = {Iss. 4}, issn = {1522-2667 (E-Journal); 0931-7597 (Print)}, pages = {Publ. online}, year = {2001}, language = {en} } @article{DuennwaldDemirSiegertetal.2000, author = {D{\"u}nnwald, Thomas and Demir, Ayhan S. and Siegert, Petra and Pohl, Martina and M{\"u}ller, Michael}, title = {Enantioselective Synthesis of (S)-2-Hydroxypropanone Derivatives by Benzoylformate Decarboxylase Catalyzed C-C Bond Formation}, series = {European journal of organic chemistry}, volume = {Vol. 2000}, journal = {European journal of organic chemistry}, number = {Iss. 11}, issn = {0365-5490 (E-Journal); 1099-0690 (E-Journal); 0075-4617 (Print); 0170-2041 (Print); 0947-3440 (Print); 1434-193X (Print); 1434-243X (Print)}, pages = {2161 -- 2170}, year = {2000}, language = {en} } @article{IdingDuennwaldGreineretal.2000, author = {Iding, Hans and D{\"u}nnwald, Thomas and Greiner, Lasse and Liese, Andreas and M{\"u}ller, Michael and Siegert, Petra and Gr{\"o}tzinger, Joachim and Demir, Ayhan S. and Pohl, Martina}, title = {Benzoylformate Decarboxylase from Pseudomonas putida as Stable Catalyst for the Synthesis of Chiral 2-Hydroxy Ketones}, series = {Chemistry - a European journal}, volume = {Vol. 6}, journal = {Chemistry - a European journal}, number = {Iss. 8}, issn = {1521-3765 (E-Journal); 0947-6539 (Print)}, pages = {1483 -- 1495}, year = {2000}, language = {en} } @article{WhiteheadOehlschlaegerAlmajhdietal.2014, author = {Whitehead, Mark and {\"O}hlschl{\"a}ger, Peter and Almajhdi, Fahad N. and Alloza, Leonor and Marz{\´a}bal, Pablo and Meyers, Ann E. and Hitzeroth, Inga I. and Rybicki, Edward P.}, title = {Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice}, series = {BMC cancer}, journal = {BMC cancer}, number = {14:367}, publisher = {BioMed Central}, address = {London}, issn = {1471-2407}, doi = {10.1186/1471-2407-14-367}, pages = {1 -- 15}, year = {2014}, language = {en} } @article{IdingSiegertMeschetal.1998, author = {Iding, Hans and Siegert, Petra and Mesch, K. and Pohl, Martina}, title = {Application of α-keto acid decarboxylases in biotransformations}, series = {Biochimica et biophysica acta (BBA) - Protein structure and molecular enzymology}, volume = {Vol. 1385}, journal = {Biochimica et biophysica acta (BBA) - Protein structure and molecular enzymology}, number = {Iss. 2}, issn = {1879-2588 (E-Journal); 0167-4838 (Print)}, pages = {307 -- 322}, year = {1998}, language = {en} } @article{PohlSiegertMeschetal.1998, author = {Pohl, Martina and Siegert, Petra and Mesch, K. and Bruhn, H. and Gr{\"o}tzinger, Joachim}, title = {Active site mutants of pyruvate decarboxylase from Zymomonas mobilis : a site-directed mutagenesis study of L112, I472, I476, E473 and N482}, series = {European journal of biochemistry}, volume = {Vol. 257}, journal = {European journal of biochemistry}, number = {Iss. 3}, issn = {1432-1033 (E-Journal); 1742-4658 (E-Journal); 0014-2956 (Print); 1742-464X (Print)}, pages = {538 -- 546}, year = {1998}, language = {en} } @article{RaueWambachGloeggleretal.2014, author = {Raue, Markus and Wambach, M. and Gl{\"o}ggler, S. and Grefen, Dana and Kaufmann, R. and Abetz, C. and Georgopanos, P. and Handge, U. A. and Mang, Thomas and Bl{\"u}mich, B. and Abetz, V.}, title = {Investigation of historical hard rubber ornaments of Charles Goodyear}, series = {Macromolecular chemistry and physics}, volume = {Vol. 215}, journal = {Macromolecular chemistry and physics}, number = {No. 3}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1022-1352}, pages = {245 -- 254}, year = {2014}, language = {en} } @article{SeifarthGossmannGrosseetal.2015, author = {Seifarth, Volker and Goßmann, Matthias and Grosse, J. O. and Becker, C. and Heschel, I. and Artmann, Gerhard and Temiz Artmann, Ayseg{\"u}l}, title = {Development of a Bioreactor to Culture Tissue Engineered Ureters Based on the Application of Tubular OPTIMAIX 3D Scaffolds}, series = {Urologia Internationalis}, volume = {2015}, journal = {Urologia Internationalis}, number = {95}, publisher = {Karger}, address = {Basel}, issn = {0042-1138}, doi = {10.1159/000368419}, pages = {106 -- 113}, year = {2015}, language = {en} } @article{PilasIkenSelmeretal.2015, author = {Pilas, Johanna and Iken, Heiko and Selmer, Thorsten and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Development of a multi-parameter sensor chip for the simultaneous detection of organic compounds in biogas processes}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201431894}, pages = {1306 -- 1312}, year = {2015}, abstract = {An enzyme-based multi-parameter biosensor is developed for monitoring the concentration of formate, d-lactate, and l-lactate in biological samples. The sensor is based on the specific dehydrogenation by an oxidized β-nicotinamide adenine dinucleotide (NAD+)-dependent dehydrogenase (formate dehydrogenase, d-lactic dehydrogenase, and l-lactic dehydrogenase, respectively) in combination with a diaphorase from Clostridium kluyveri (EC 1.8.1.4). The enzymes are immobilized on a platinum working electrode by cross-linking with glutaraldehyde (GA). The principle of the determination scheme in case of l-lactate is as follows: l-lactic dehydrogenase (l-LDH) converts l-lactate into pyruvate by reaction with NAD+. In the presence of hexacyanoferrate(III), the resulting reduced β-nicotinamide adenine dinucleotide (NADH) is then regenerated enzymatically by diaphorase. The electrochemical detection is based on the current generated by oxidation of hexacyanoferrate(II) at an applied potential of +0.3 V vs. an Ag/AgCl reference electrode. The biosensor will be electrochemically characterized in terms of linear working range and sensitivity. Additionally, the successful practical application of the sensor is demonstrated in an extract from maize silage.}, language = {en} } @article{BreuerRaueKirschbaumetal.2015, author = {Breuer, Lars and Raue, Markus and Kirschbaum, M. and Mang, Thomas and Sch{\"o}ning, Michael Josef and Thoelen, R. and Wagner, Torsten}, title = {Light-controllable polymeric material based on temperature-sensitive hydrogels with incorporated graphene oxide}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201431944}, pages = {1368 -- 1374}, year = {2015}, abstract = {Poly(N-isopropylacrylamide) (PNIPAAm) hydrogel films with incorporated graphene oxide (GO) were developed and tested as light-stimulated actuators. GO dispersions were synthesized via Hummers method and characterized toward their optical properties and photothermal energy conversion. The hydrogels were prepared by means of photopolymerization. In addition, the influence of GO within the hydrogel network on the lower critical solution temperature (LCST) was investigated by differential scanning calorimetry (DSC). The optical absorbance and the response to illumination were determined as a function of GO concentration for thin hydrogel films. A proof of principle for the stimulation with light was performed.}, language = {en} } @article{SchiffelsSelmer2015, author = {Schiffels, Johannes and Selmer, Thorsten}, title = {A flexible toolbox to study protein-assisted metalloenzyme assembly in vitro}, series = {Biotechnology and Bioengineering}, volume = {112}, journal = {Biotechnology and Bioengineering}, number = {11}, publisher = {Wiley}, address = {Weinheim}, issn = {1097-0290}, doi = {10.1002/bit.25658}, pages = {2360 -- 2372}, year = {2015}, language = {en} } @article{VoigtAlbrechtSieversetal.2015, author = {Voigt, Birgit and Albrecht, Dirk and Sievers, Susanne and Becher, D{\"o}rte and Bongaerts, Johannes and Evers, Stefan and Schweder, Thomas and Maurer, Karl-Heinz and Hecker, Michael}, title = {High-resolution proteome maps of Bacillus licheniformis cells growing in minimal medium}, series = {Proteomics}, volume = {15}, journal = {Proteomics}, number = {15}, publisher = {Wiley}, address = {Weinheim}, issn = {1615-9861}, doi = {10.1002/pmic.201400504}, pages = {2629 -- 2633}, year = {2015}, language = {en} } @article{MolinnusBaeckerSiegertetal.2015, author = {Molinnus, Denise and B{\"a}cker, Matthias and Siegert, Petra and Willenberg, H. and Poghossian, Arshak and Keusgen, M. and Sch{\"o}ning, Michael Josef}, title = {Detection of Adrenaline Based on Substrate Recycling Amplification}, series = {Procedia Engineering}, volume = {120}, journal = {Procedia Engineering}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1877-7058}, doi = {10.1016/j.proeng.2015.08.708}, pages = {540 -- 543}, year = {2015}, abstract = {An amperometric enzyme biosensor has been applied for the detection of adrenaline. The adrenaline biosensor has been prepared by modification of an oxygen electrode with the enzyme laccase that operates at a broad pH range between pH 3.5 to pH 8. The enzyme molecules were immobilized via cross-linking with glutaraldehyde. The sensitivity of the developed adrenaline biosensor in different pH buffer solutions has been studied.}, language = {en} } @article{PilasMarianoKeusgenetal.2015, author = {Pilas, Johanna and Mariano, K. and Keusgen, M. and Selmer, Thorsten and Sch{\"o}ning, Michael Josef}, title = {Optimization of an Enzyme-based Multi-parameter Biosensor for Monitoring Biogas Processes}, series = {Procedia Engineering}, volume = {120}, journal = {Procedia Engineering}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1877-7058}, doi = {10.1016/j.proeng.2015.08.702}, pages = {532 -- 535}, year = {2015}, language = {en} } @article{CehreliAkpinarTemizArtmannetal.2015, author = {Cehreli, Ruksan and Akpinar, Hale and Temiz Artmann, Ayseg{\"u}l and Sagol, Ozgul}, title = {Effects of Glutamine and Omega-3 Fatty Acids on Erythrocyte Deformability and Oxidative Damage in Rat Model of Enterocolitis}, series = {Gastroenterology Research}, volume = {8}, journal = {Gastroenterology Research}, number = {5}, issn = {1918-2813}, doi = {10.14740/gr683w}, pages = {265 -- 273}, year = {2015}, language = {en} } @article{HandtkeSchroeterJuergenetal.2014, author = {Handtke, Stefan and Schroeter, Rebecca and J{\"u}rgen, Britta and Methling, Karen and Schl{\"u}ter, Rabea and Albrecht, Dirk and Hijum, Sacha A. F. T. van and Bongaerts, Johannes and Maurer, Karl-Heinz and Lalk, Michael and Schweder, Thomas and Hecker, Michael and Voigt, Birgit}, title = {Bacillus pumilus reveals a remarkably high resistance to hydrogen peroxide provoked oxidative stress}, series = {PLOS one}, volume = {9}, journal = {PLOS one}, number = {1}, publisher = {PLOS}, address = {San Francisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0085625}, pages = {e85625}, year = {2014}, abstract = {Bacillus pumilus is characterized by a higher oxidative stress resistance than other comparable industrially relevant Bacilli such as B. subtilis or B. licheniformis. In this study the response of B. pumilus to oxidative stress was investigated during a treatment with high concentrations of hydrogen peroxide at the proteome, transcriptome and metabolome level. Genes/proteins belonging to regulons, which are known to have important functions in the oxidative stress response of other organisms, were found to be upregulated, such as the Fur, Spx, SOS or CtsR regulon. Strikingly, parts of the fundamental PerR regulon responding to peroxide stress in B. subtilis are not encoded in the B. pumilus genome. Thus, B. pumilus misses the catalase KatA, the DNA-protection protein MrgA or the alkyl hydroperoxide reductase AhpCF. Data of this study suggests that the catalase KatX2 takes over the function of the missing KatA in the oxidative stress response of B. pumilus. The genome-wide expression analysis revealed an induction of bacillithiol (Cys-GlcN-malate, BSH) relevant genes. An analysis of the intracellular metabolites detected high intracellular levels of this protective metabolite, which indicates the importance of bacillithiol in the peroxide stress resistance of B. pumilus.}, language = {en} } @article{NachtrodtTietschMostaccietal.2014, author = {Nachtrodt, Frederik and Tietsch, Wolfgang and Mostacci, Domiziano and Scherer, Ulrich W.}, title = {Set-up and first operation of a plasma oven for treatment of low level radioactive wastes}, series = {Nuclear technology and radiation protection}, volume = {29}, journal = {Nuclear technology and radiation protection}, number = {Suppl.}, publisher = {VINČA Institute of Nuclear Sciences}, address = {Belgrad}, issn = {1451-3994}, doi = {10.2298/NTRP140SS47N}, pages = {47 -- 51}, year = {2014}, language = {en} } @article{HandtkeVollandMethlingetal.2014, author = {Handtke, Stefan and Volland, Sonja and Methling, Karen and Albrecht, Dirk and Becher, D{\"o}rte and Nehls, Jenny and Bongaerts, Johannes and Maurer, Karl-Heinz and Lalk, Michael and Liesegang, Heiko and Voigt, Birgit and Daniel, Rolf and Hecker, Michael}, title = {Cell physiology of the biotechnological relevant bacterium Bacillus pumilus - An omics-based approach}, series = {Journal of Biotechnology}, journal = {Journal of Biotechnology}, number = {192(A)}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-4863 (E-Journal); 0168-1656 (Print)}, doi = {10.1016/j.jbiotec.2014.08.028}, pages = {204 -- 214}, year = {2014}, abstract = {Members of the species Bacillus pumilus get more and more in focus of the biotechnological industry as potential new production strains. Based on exoproteome analysis, B. pumilus strain Jo2, possessing a high secretion capability, was chosen for an omics-based investigation. The proteome and metabolome of B. pumilus cells growing either in minimal or complex medium was analyzed. In total, 1542 proteins were identified in growing B. pumilus cells, among them 1182 cytosolic proteins, 297 membrane and lipoproteins and 63 secreted proteins. This accounts for about 43\% of the 3616 proteins encoded in the B. pumilus Jo2 genome sequence. By using GC-MS, IP-LC/MS and H NMR methods numerous metabolites were analyzed and assigned to reconstructed metabolic pathways. In the genome sequence a functional secretion system including the components of the Sec- and Tat-secretion machinery was found. Analysis of the exoproteome revealed secretion of about 70 proteins with predicted secretion signals. In addition, selected production-relevant genome features such as restriction modification systems and NRPS clusters of B. pumilus Jo2 are discussed.}, language = {en} } @article{RatkeMilowLisinskietal.2014, author = {Ratke, Lorenz and Milow, Barbara and Lisinski, Susanne and Hoepfner, Sandra}, title = {On an effect of fine ceramic particles on the structure of aerogels}, series = {Microgravity science and technology}, volume = {26}, journal = {Microgravity science and technology}, publisher = {Springer Nature}, address = {Heidelberg}, issn = {0938-0108 ; 1875-0494}, doi = {10.1007/s12217-014-9380-2}, pages = {103 -- 110}, year = {2014}, language = {en} } @article{SeiblerKleinriddersKueterLuksetal.2007, author = {Seibler, Jost and Kleinridders, Andre and K{\"u}ter-Luks, Birgit and Niehaves, Sandra and Br{\"u}ning, Jens C. and Schwenk, Frieder}, title = {Reversible gene knockdown in mice using a tight, inducible shRNA expression system}, series = {Nucleic Acids Research}, volume = {35}, journal = {Nucleic Acids Research}, number = {7}, issn = {1362-4962}, doi = {10.1093/nar/gkm122}, pages = {e54}, year = {2007}, language = {en} } @article{PlumMaHampeletal.2006, author = {Plum, Leona and Ma, Xiaosong and Hampel, Brigitte and Balthasar, Nina and Coppari, Roberto and M{\"u}nzberg, Heike and Shanabrough, Marya and Burdakov, Denis and Rother, Eva and Janoschek, Ruth and Alber, Jens and Belgardt, Bengt F. and Koch, Linda and Seibler, Jost and Schenk, Frieder and Fekete, Csaba and Suzuki, Akira and Mak, Tak W. and Krone, Wilhelm and Horvath, Tamas L. and Ashcroft, Frances M. and Br{\"u}ning, Jens C.}, title = {Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity}, series = {The Journal of Clinical Investigation (JCI)}, volume = {116}, journal = {The Journal of Clinical Investigation (JCI)}, number = {7}, issn = {1558-8238}, doi = {10.1172/JCI27123}, pages = {1886 -- 1901}, year = {2006}, language = {en} } @article{SeiblerKueterLuksKernetal.2005, author = {Seibler, Jost and K{\"u}ter-Luks, Birgit and Kern, Heidrun and Streu, Sandra and Plum, Leona and Maurer, Jan and K{\"u}hn, Ralf and Br{\"u}ning, Jens C. and Schwenk, Frieder}, title = {Single copy shRNA configuration for ubiquitous gene knockdown in mice}, series = {Nucleic Acids Research}, volume = {33}, journal = {Nucleic Acids Research}, number = {7}, issn = {1362-4962}, doi = {10.1093/nar/gni065}, pages = {e67}, year = {2005}, language = {en} } @article{SeiblerZevnikKueterLuksetal.2003, author = {Seibler, Jost and Zevnik, Branko and K{\"u}ter-Luks, Birgit and Andreas, Susanne and Kern, Heidrun and Hennek, Thomas and Rode, Anja and Heimann, Cornelia and Faust, Nicole and Kauselmann, Gunther and Schoor, Michael and Jaenisch, Rudolf and Rajewsky, Klaus and K{\"u}hn, Ralf and Schwenk, Frieder}, title = {Rapid generation of inducible mouse mutants}, series = {Nucleic Acids Research}, volume = {33}, journal = {Nucleic Acids Research}, number = {4}, issn = {1362-4962}, doi = {10.1093/nar/gng012}, pages = {e12}, year = {2003}, language = {en} } @article{GoetzeBaerWinkelmannetal.2005, author = {Goetze, Sandra and Baer, Alexandra and Winkelmann, Silke and Nehlsen, Kristina and Seibler, Jost and Maass, Karin and Bode, J{\"u}rgen}, title = {Performance of genomic bordering elements at predefined genomic loci}, series = {Molecular and Cellular Biology}, volume = {25}, journal = {Molecular and Cellular Biology}, number = {6}, issn = {1098-5549}, doi = {10.1128/MCB.25.6.2260-2272.2005}, pages = {2260 -- 2272}, year = {2005}, language = {en} } @article{TakenagaSchneiderErbayetal.2015, author = {Takenaga, Shoko and Schneider, Benno and Erbay, E. and Biselli, Manfred and Schnitzler, Thomas and Sch{\"o}ning, Michael Josef and Wagner, Torsten}, title = {Fabrication of biocompatible lab-on-chip devices for biomedical applications by means of a 3D-printing process}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201532053}, pages = {1347 -- 1352}, year = {2015}, abstract = {A new microfluidic assembly method for semiconductor-based biosensors using 3D-printing technologies was proposed for a rapid and cost-efficient design of new sensor systems. The microfluidic unit is designed and printed by a 3D-printer in just a few hours and assembled on a light-addressable potentiometric sensor (LAPS) chip using a photo resin. The cell growth curves obtained from culturing cells within microfluidics-based LAPS systems were compared with cell growth curves in cell culture flasks to examine biocompatibility of the 3D-printed chips. Furthermore, an optimal cell culturing within microfluidics-based LAPS chips was achieved by adjusting the fetal calf serum concentrations of the cell culture medium, an important factor for the cell proliferation.}, language = {en} } @article{InagakiSleddensLinkelsWassenaaretal.2011, author = {Inagaki, Akiko and Sleddens-Linkels, Esther and Wassenaar, Evelyne and Ooms, Marja and Cappellen, Wiggert A. van and Hoeijmakers, Jan H. J. and Seibler, Jost and Vogt, Thomas F. and Shin, Myung K. and Grootegoed, J. Anton and Baarends, Willy M.}, title = {Meiotic functions of RAD18}, series = {Journal of Cell Science}, volume = {124}, journal = {Journal of Cell Science}, number = {16}, publisher = {Company of Biologists Limited}, address = {Cambridge}, issn = {1477-9137}, doi = {10.1242/jcs.081968}, pages = {2837 -- 2850}, year = {2011}, language = {en} } @article{RaabKappelKraemeretal.2011, author = {Raab, Monika and Kappel, Sven and Kr{\"a}mer, Andrea and Sanhaji, Mourad and Matthess, Yves and Kurunci-Csacsko, Elisabeth and Calzada-Wack, Julia and Rathkolb, Birgit and Rosman, Jan and Adler, Thure and Busch, Dirk H. and Esposito, Irene and Fuchs, Helmut and Gailus-Durner, Val{\´e}rie and Klingenspor, Martin and Wolf, Eckhard and S{\"a}nger, Nicole and Prinz, Florian and Hrabe de Angelis, Martin and Seibler, Jost and Yuan, Juping and Bergmann, Martin and Knecht, Rainald and Kreft, Bertolt and Strebhardt, Klaus}, title = {Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells}, series = {Nature Communications}, volume = {2}, journal = {Nature Communications}, number = {395}, publisher = {Nature}, address = {London}, issn = {2041-1723}, doi = {10.1038/ncomms1395}, pages = {1 -- 11}, year = {2011}, language = {en} } @article{HasegawaKapelyukhTaharaetal.2011, author = {Hasegawa, Maki and Kapelyukh, Yury and Tahara, Harunobu and Seibler, Jost and Rode, Anja and Krueger, Sylvia and Lee, Dongtao N. and Wolf, C. Roland and Scheer, Nico}, title = {Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line}, series = {Molecular Pharmacology}, volume = {80}, journal = {Molecular Pharmacology}, number = {33}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.111.071845}, pages = {518 -- 528}, year = {2011}, language = {en} } @article{JordanKruegerWillmesetal.2011, author = {Jordan, Sabine D. and Kr{\"u}ger, Markus and Willmes, Diana M. and Redemann, Nora and Wunderlich, F. Thomas and Br{\"o}nneke, Hella S. and Merkwirth, Carsten and Kashkar, Hamid and Olkkonen, Vesa M. and B{\"o}ttger, Thomas and Braun, Thomas and Seibler, Jost and Br{\"u}ning, Jens C.}, title = {Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism}, series = {Nature Cell Biology}, volume = {13}, journal = {Nature Cell Biology}, number = {4}, publisher = {Nature}, address = {New York}, issn = {1465-7392}, doi = {10.1038/ncb2211}, pages = {434 -- 446}, year = {2011}, abstract = {The contribution of altered post-transcriptional gene silencing to the development of insulin resistance and type 2 diabetes mellitus so far remains elusive. Here, we demonstrate that expression of microRNA (miR)-143 and 145 is upregulated in the liver of genetic and dietary mouse models of obesity. Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis. Conversely, mice deficient for the miR-143-145 cluster are protected from the development of obesity-associated insulin resistance. Quantitative-mass-spectrometry-based analysis of hepatic protein expression in miR-143-overexpressing mice revealed miR-143-dependent downregulation of oxysterol-binding-protein-related protein (ORP) 8. Reduced ORP8 expression in cultured liver cells impairs the ability of insulin to induce AKT activation, revealing an ORP8-dependent mechanism of AKT regulation. Our experiments provide direct evidence that dysregulated post-transcriptional gene silencing contributes to the development of obesity-induced insulin resistance, and characterize the miR-143-ORP8 pathway as a potential target for the treatment of obesity-associated diabetes.}, language = {en} } @article{GlaserLubitzLovelandetal.2009, author = {Glaser, Stefan and Lubitz, Sandra and Loveland, Kate L. and Ohbo, Kazu and Robb, Lorraine and Schwenk, Frieder and Seibler, Jost and Roellig, Daniela and Kranz, Andrea and Anastassiadis, Konstantinos and Stewart, A. Francis}, title = {The histone 3 lysine 4 methyltransferase, Mll2, is only required briefly in development and spermatogenesis}, series = {Epigenetics \& Chromatin}, volume = {2}, journal = {Epigenetics \& Chromatin}, number = {5}, issn = {1756-8935}, doi = {10.1186/1756-8935-2-5}, pages = {1 -- 16}, year = {2009}, language = {en} } @article{KotnikPopovaTodirasetal.2009, author = {Kotnik, Katarina and Popova, Elena and Todiras, Mihail and Mori, Marcelo A. and Alenina, Natalia and Seibler, Jost and Bader, Michael}, title = {Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown}, series = {Plos One}, volume = {4}, journal = {Plos One}, number = {4}, publisher = {Plos}, address = {San Francisco, California, US}, doi = {10.1371/journal.pone.0005124}, pages = {e5124}, year = {2009}, language = {en} } @article{HeroldBrandtSeibleretal.2008, author = {Herold, Marco J. and Brandt, Jens van den and Seibler, Jost and Reichardt, Holger M.}, title = {Inducible and reversible gene silencing by stable integration of an shRNA-encoding lentivirus in transgenic rats}, series = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {47}, issn = {1091-6490}, doi = {10.1073/pnas.0806213105}, pages = {18507 -- 18512}, year = {2008}, language = {en} } @article{KochWunderlichSeibleretal.2008, author = {Koch, Linda and Wunderlich, F. Thomas and Seibler, Jost and K{\"o}nner, A. Christine and Hampel, Brigitte and Irlenbusch, Sigrid and Brabant, Georg and Kahn, C. Ronald and Schwenk, Frieder and Br{\"u}ning, Jens C.}, title = {Central insulin action regulates peripheral glucose and fat metabolism in mice}, series = {The Journal of Clinical Investigation (JCI)}, volume = {118}, journal = {The Journal of Clinical Investigation (JCI)}, number = {6}, issn = {1558-8238}, doi = {10.1172/JCI31073}, pages = {2132 -- 2147}, year = {2008}, language = {en} } @article{ChristophBahrenbergVryetal.2008, author = {Christoph, Thomas and Bahrenberg, Gregor and Vry, Jean de and Englberger, Werner and Erdmann, Volker A. and Frech, Moritz and K{\"o}gel, Babette and R{\"o}hl, Thomas and Schiene, Klaus and Schr{\"o}der, Wolfgang and Seibler, Jost and Kurreck, Jens}, title = {Investigation of TRPV1 loss-of-function phenotypes in transgenic shRNA expressing and knockout mice}, series = {Molecular and Cellular Neuroscience}, volume = {37}, journal = {Molecular and Cellular Neuroscience}, number = {3}, issn = {1044-7431}, doi = {10.1016/j.mcn.2007.12.006}, pages = {579 -- 589}, year = {2008}, language = {en} } @article{CesariRennekampffVinterstenetal.2004, author = {Cesari, Francesca and Rennekampff, Verena and Vintersten, Kristina and Vuong, Lam Giang and Seibler, Jost and Bode, J{\"u}rgen and Wiebel, Franziska F. and Nordheim, Alfred}, title = {Elk-1 knock-out mice engineered by Flp recombinase-mediated cassette exchange}, series = {Genesis : The Journal of Genetics and Development}, volume = {38}, journal = {Genesis : The Journal of Genetics and Development}, number = {2}, issn = {1526-968X}, doi = {10.1002/gene.20003}, pages = {87 -- 92}, year = {2004}, language = {en} } @article{BodeSchlakeIberetal.2000, author = {Bode, J{\"u}rgen and Schlake, Thomas and Iber, Michaela and Sch{\"u}beler, Dirk and Seibler, Jost and Snezhkov, Evgeney and Nikolaev, Lev}, title = {The transgeneticist's toolbox: novel methods for the targeted modification of eukaryotic genomes}, series = {Biological Chemistry}, volume = {381}, journal = {Biological Chemistry}, number = {9-10}, issn = {1431-6730}, doi = {10.1515/BC.2000.103}, pages = {801 -- 813}, year = {2000}, language = {en} } @article{FengSeiblerAlamietal.1999, author = {Feng, Yong-Qing and Seibler, Jost and Alami, Raouf and Eisen, Andrew and Westerman, Karen A. and Leboulch, Philippe and Fiering, Steven and Bouhassira, Eric E.}, title = {Site-specific chromosomal integration in mammalian cells: highly efficient CRE recombinase-mediated cassette exchange}, series = {Journal of Molecular Biology}, volume = {292}, journal = {Journal of Molecular Biology}, number = {4}, issn = {0022-2836}, doi = {10.1006/jmbi.1999.3113}, pages = {779 -- 785}, year = {1999}, language = {en} } @article{SeiblerSchuebelerFieringetal.1998, author = {Seibler, Jost and Sch{\"u}beler, Dirk and Fiering, Steven and Groudine, Mark and Bode, J{\"u}rgen}, title = {DNA cassette exchange in ES cells mediated by Flp recombinase: an efficient strategy for repeated modification of tagged loci by marker-free constructs}, series = {Biochemistry}, volume = {37}, journal = {Biochemistry}, number = {18}, issn = {1520-4995}, doi = {10.1021/bi980288t}, pages = {6229 -- 6234}, year = {1998}, language = {en} } @article{SeiblerBode1997, author = {Seibler, Jost and Bode, J{\"u}rgen}, title = {Double-reciprocal crossover mediated by FLP-recombinase: a concept and an assay}, series = {Biochemistry}, volume = {36}, journal = {Biochemistry}, number = {7}, issn = {1520-4995}, pages = {1740 -- 1747}, year = {1997}, language = {en} } @article{BodeBartschBoulikasetal.1998, author = {Bode, J. and Bartsch, J. and Boulikas, T. and Iber, M. and Mielke, C. and Sch{\"u}beler, D. and Seibler, Jost and Benham, C.}, title = {Transcription-promoting genomic sites in mammalia: their elucidation and architectural principles}, series = {Gene therapy \& molecular biology}, volume = {1}, journal = {Gene therapy \& molecular biology}, number = {1}, issn = {1529-9120}, pages = {1 -- 29}, year = {1998}, language = {en} } @article{IberSchuebelerSeibleretal.1998, author = {Iber, Michaela and Sch{\"u}beler, Dirk and Seibler, Jost and H{\"o}xter, Maria and Bode, J{\"u}rgen}, title = {Efficient FACS selection procedure for cells undergoing Flp-mediated site-specific conversions}, series = {Technical Tips Online}, volume = {4}, journal = {Technical Tips Online}, number = {1}, doi = {10.1016/S1366-2120(08)70132-6}, pages = {25 -- 29}, year = {1998}, language = {en} } @article{WiegandVoigtAlbrechtetal.2013, author = {Wiegand, Sandra and Voigt, Birgit and Albrecht, Dirk and Bongaerts, Johannes and Evers, Stefan and Hecker, Michael and Daniel, Rolf and Liesegang, Heiko}, title = {Fermentation stage-dependent adaptations of Bacillus licheniformis during enzyme production}, series = {Microbial Cell Factories}, volume = {12}, journal = {Microbial Cell Factories}, publisher = {Biomed Central}, address = {London}, issn = {1475-2859}, doi = {10.1186/1475-2859-12-120}, pages = {120}, year = {2013}, language = {en} } @article{HenkenOosterhuisOehlschlaegeretal.2012, author = {Henken, F. E. and Oosterhuis, K. and {\"O}hlschl{\"a}ger, Peter and Bosch, L. and Hooijberg, E. and Haanen, J. B. A. G. and Steenbergen, R. D. M.}, title = {Preclinical safety evaluation of DNA vaccines encoding modified HPV16 E6 and E7}, series = {Vaccine}, volume = {30}, journal = {Vaccine}, number = {28}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0264-410X}, doi = {10.1016/j.vaccine.2012.04.013}, pages = {4259 -- 4266}, year = {2012}, abstract = {Persistent infection with high-risk human papillomaviruses (hrHPV) can result in the formation of anogenital cancers. As hrHPV proteins E6 and E7 are required for cancer initiation and maintenance, they are ideal targets for immunotherapeutic interventions. Previously, we have described the development of DNA vaccines for the induction of HPV16 E6 and E7 specific T cell immunity. These vaccines consist of 'gene-shuffled' (SH) versions of HPV16 E6 and E7 that were fused to Tetanus Toxin Fragment C domain 1 (TTFC) and were named TTFC-E6SH and TTFC-E7SH. Gene-shuffling was performed to avoid the risk of inducing malignant transformation at the vaccination site. Here, we describe the preclinical safety evaluation of these candidate vaccines by analysis of their transforming capacity in vitro using established murine fibroblasts (NIH 3T3 cells) and primary human foreskin keratinocytes (HFKs). We demonstrate that neither ectopic expression of TTFC-E6SH and TTFC-E7SH alone or in combination enabled NIH 3T3 cells to form colonies in soft agar. In contrast, expression of HPV16 E6WT and E7WT alone or in combination resulted in effective transformation. Similarly, retroviral transduction of HFKs from three independent donors with both TTFC-E6SH and TTFC-E7SH alone or in combination did not show any signs of immortalization. In contrast, the combined expression of E6WT and E7WT induced immortalization in HFKs from all donors. Based on these results we consider it justified to proceed to clinical evaluation of DNA vaccines encoding TTFC-E6SH and TTFC-E7SH in patients with HPV16 associated (pre)malignancies.}, language = {en} } @article{ImmelGruetzkeSpaeteetal.2012, author = {Immel, Timo and Gr{\"u}tzke, Martin and Sp{\"a}te, Anne-Katrin and Groth, Ulrich and {\"O}hlschl{\"a}ger, Peter and Huhn, Thomas}, title = {Synthesis and X-ray structure analysis of a heptacoordinate titanium(IV)-bis-chelate with enhanced in vivo antitumor efficacy}, series = {Chemical Communications}, volume = {48}, journal = {Chemical Communications}, number = {46}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1364-548X}, doi = {10.1039/C2CC31624B}, pages = {5790 -- 5792}, year = {2012}, abstract = {Chelate stabilization of a titanium(IV)-salan alkoxide by ligand exchange with 2,6-pyridinedicarboxylic acid (dipic) resulted in heptacoordinate complex 3 which is not redox-active, stable on silica gel and has increased aqueous stability. 3 is highly toxic in HeLa S3 and Hep G2 and has enhanced antitumor efficacy in a mouse cervical-cancer model.}, language = {en} } @article{ScheerSnaithWolfetal.2013, author = {Scheer, Nico and Snaith, Mike and Wolf, C. Roland and Seibler, Jost}, title = {Generation and utility of genetically humanized mouse models}, series = {Drug Discovery Today}, volume = {Vol 18}, journal = {Drug Discovery Today}, number = {23-24}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1359-6446}, doi = {10.1016/j.drudis.2013.07.007}, pages = {1200 -- 1211}, year = {2013}, language = {en} } @article{BouwmanGuldenHeijdenetal.2013, author = {Bouwman, Peter and Gulden, Hanneke van der and Heijden, Ingrid van der and Drost, Rinske and Klijn, Christiaan N. and Prasetyanti, Pramudita and Pieterse, Mark and Wientjens, Ellen and Seibler, Jost and Hogervorst, Frank B. L. and Jonkers, Jos}, title = {A High-Throughput Functional Complementation Assay for Classification of BRCA1 Missense Variants}, series = {Cancer Discovery}, journal = {Cancer Discovery}, number = {3}, issn = {2159-8290}, doi = {10.1158/2159-8290.CD-13-0094}, pages = {1142 -- 1152}, year = {2013}, language = {en} } @article{MichalakNacerddinePietersenetal.2013, author = {Michalak, Ewa Malgorzata and Nacerddine, Karim and Pietersen, Alexandra and Beuger, Vincent and Pawlitzky, Inka and Cornelissen-Steijger, Paulien and Wientjens, Ellen and Tanger, Ellen and Seibler, Jost and Lohuizen, Maarten van and Jonkers, Jos}, title = {Polycomb group gene Ezh2 regulates mammary gland morphogenesis and maintains the luminal progenitor pool}, series = {Stem Cells}, volume = {Vol 31}, journal = {Stem Cells}, number = {9}, publisher = {Oxford University Press}, address = {Oxford}, issn = {1549-4918}, doi = {10.1002/stem.1437}, pages = {1910 -- 1920}, year = {2013}, language = {en} } @article{GebeshuberKornauthDongetal.2013, author = {Gebeshuber, Christoph A. and Kornauth, Christoph and Dong, Lihua and Sierig, Ralph and Seibler, Jost and Reiss, Martina and Tauber, Stefanie and Bilban, Martin and Wang, Shijun and Kain, Renate and B{\"o}hmig, Georg A. and Moeller, Marcus J. and Gr{\"o}ne, Hermann-Josef and Englert, Christoph and Martinez, Javier and Kerjaschki, Dontscho}, title = {Focal segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1}, series = {Nature Medicine}, volume = {19}, journal = {Nature Medicine}, number = {4}, issn = {1078-8956}, doi = {10.1038/nm.3142}, pages = {481 -- 487}, year = {2013}, language = {en} } @article{KornfeldBaitzelKoenneretal.2013, author = {Kornfeld, Jan-Wilhelm and Baitzel, Catherina and K{\"o}nner, A. Christine and Nicholls, Hayley T. and Vogt, Merly C. and Herrmanns, Karolin and Scheja, Ludger and Haumaitre, C{\´e}cile and Wolf, Anna M. and Knippschild, Uwe and Seibler, Jost and Cereghini, Silvia and Heeren, Joerg and Stoffel, Markus and Br{\"u}ning, Jens C.}, title = {Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b}, series = {Nature}, volume = {494}, journal = {Nature}, number = {7435}, publisher = {Springer Nature}, address = {Cham}, isbn = {0028-0836}, doi = {10.1038/nature11793}, pages = {111 -- 115}, year = {2013}, language = {en} } @article{BreuerRaueStrobeletal.2016, author = {Breuer, Lars and Raue, Markus and Strobel, M. and Mang, Thomas and Sch{\"o}ning, Michael Josef and Thoelen, R. and Wagner, Torsten}, title = {Hydrogels with incorporated graphene oxide as light-addressable actuator materials for cell culture environments in lab-on-chip systems}, series = {Physica status solidi (a)}, volume = {213}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1862-6300}, doi = {10.1002/pssa.201533056}, pages = {1520 -- 1525}, year = {2016}, abstract = {Abstractauthoren Graphene oxide (GO) nanoparticles were incorporated in temperature-sensitive Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels. The nanoparticles increase the light absorption and convert light energy into heat efficiently. Thus, the hydrogels with GO can be stimulated spatially resolved by illumination as it was demonstrated by IR thermography. The temporal progression of the temperature maximum was detected for different concentrations of GO within the polymer network. Furthermore, the compatibility of PNIPAAm hydrogels with GO and cell cultures was investigated. For this purpose, culture medium was incubated with hydrogels containing GO and the viability and morphology of chinese hamster ovary (CHO) cells was examined after several days of culturing in presence of this medium.}, language = {en} } @article{HeinzeMangPopescuetal.2016, author = {Heinze, D. and Mang, Thomas and Popescu, C. and Weichold, O.}, title = {Effect of side chain length and degree of polymerization on the decomposition and crystallization behaviour of chlorinated poly(vinyl ester) oligomers}, series = {Thermochimica Acta}, volume = {637}, journal = {Thermochimica Acta}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0040-6031 (electronic)}, doi = {10.1016/j.tca.2016.05.015}, pages = {143 -- 153}, year = {2016}, abstract = {Four members of a homologous series of chlorinated poly(vinyl ester) oligomers CCl₃-(CH₂CH (OCO(CH₂)ₘCH₃))ₙ-Cl with degrees of polymerization of 10 and 20 were prepared by telomerisation using carbon tetrachloride. The number of side chain carbon atoms ranges from 2 (poly(vinyl acetate) to 18 (poly(vinyl stearate)). The effect of the n-alkyl side chain length and of the degree of polymerization on the thermal stability and crystallization behaviour of the synthesized compounds was investigated. All oligomers degrade in two major steps by first losing HCl and side chains with subsequent breakdown of the backbone. The members with short side chains, up to poly(vinyl octanoate), are amorphous and show internal plasticization, whereas those with high number of side chain carbon atoms are semi-crystalline due to side-chain crystallization. A better packing for poly(vinyl stearate) is also noticeable. The glass transition and melting temperatures as well as the onset temperature of decomposition are influenced to a larger extent by the side chain length than by the degree of polymerization. Thermal stability is improved if both the size and number of side chains increase, but only a long side chain causes a significant increase of the resistance to degradation. This results in a stabilization of PVAc so that oligomers from poly(vinyl octanoate) on are stable under atmospheric conditions. Thus, the way to design stable, chlorinated PVEs oligomers is to use a long n-alkyl side chain.}, language = {en} } @article{MolinnusSorichBartzetal.2016, author = {Molinnus, Denise and Sorich, Maren and Bartz, Alexander and Siegert, Petra and Willenberg, Holger S. and Lisdat, Fred and Poghossian, Arshak and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Towards an adrenaline biosensor based on substrate recycling amplification in combination with an enzyme logic gate}, series = {Sensors and Actuators B: Chemical}, volume = {237}, journal = {Sensors and Actuators B: Chemical}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0925-4005}, doi = {10.1016/j.snb.2016.06.064}, pages = {190 -- 195}, year = {2016}, abstract = {An amperometric biosensor using a substrate recycling principle was realized for the detection of low adrenaline concentrations (1 nM) by measurements in phosphate buffer and Ringer's solution at pH 6.5 and pH 7.4, respectively. In proof-of-concept experiments, a Boolean logic-gate principle has been applied to develop a digital adrenaline biosensor based on an enzyme AND logic gate. The obtained results demonstrate that the developed digital biosensor is capable for a rapid qualitative determination of the presence/absence of adrenaline in a YES/NO statement. Such digital biosensor could be used in clinical diagnostics for the control of a correct insertion of a catheter in the adrenal veins during adrenal venous-sampling procedure.}, language = {en} } @article{GhoschBaierSchuetzetal.2016, author = {Ghosch, S. and Baier, M. and Sch{\"u}tz, J. and Schneider, Felix and Scherer, Ulrich W.}, title = {Analysis of electronic autoradiographs by mathematical post-processing}, series = {Radiation Effects and Defects in Solids: Incorporating plasma science and plasma technology}, volume = {171}, journal = {Radiation Effects and Defects in Solids: Incorporating plasma science and plasma technology}, number = {1-2}, publisher = {Taylor \& Francis}, address = {London}, issn = {1029-4953}, doi = {10.1080/10420150.2016.1155587}, pages = {161 -- 172}, year = {2016}, abstract = {Autoradiography is a well-established method of nuclear imaging. When different radionuclides are present simultaneously, additional processing is needed to distinguish distributions of radionuclides. In this work, a method is presented where aluminium absorbers of different thickness are used to produce images with different cut-off energies. By subtracting images pixel-by-pixel one can generate images representing certain ranges of β-particle energies. The method is applied to the measurement of irradiated reactor graphite samples containing several radionuclides to determine the spatial distribution of these radionuclides within pre-defined energy windows. The process was repeated under fixed parameters after thermal treatment of the samples. The greyscale images of the distribution after treatment were subtracted from the corresponding pre-treatment images. Significant changes in the intensity and distribution of radionuclides could be observed in some samples. Due to the thermal treatment parameters the most significant differences were observed in the ³H and ¹⁴C inventory and distribution.}, language = {en} } @article{TeumerCapitainRossJonesetal.2018, author = {Teumer, T. and Capitain, C. and Ross-Jones, J. and Tippk{\"o}tter, Nils and R{\"a}dle, M. and Methner, F.-J.}, title = {In-line Haze Monitoring Using a Spectrally Resolved Back Scattering Sensor}, series = {BrewingScience}, volume = {71}, journal = {BrewingScience}, number = {5/6}, publisher = {Fachverlag Hans Carl}, address = {N{\"u}rnberg}, issn = {1613-2041}, pages = {49 -- 55}, year = {2018}, abstract = {In the present work an optical sensor in combination with a spectrally resolved detection device for in-line particle-size-monitoring for quality control in beer production is presented. The principle relies on the size and wavelength dependent backscatter of growing particles in fluids. Measured interference structures of backscattered light are compared with calculated theoretical values, based on Mie-Theory, and fitted with a linear least square method to obtain particle size distributions. For this purpose, a broadband light source in combination with a process-CCD-spectrometer (charge ? coupled device spectrometer) and process adapted fiber optics are used. The goal is the development of an easy and flexible measurement device for in-line-monitoring of particle size. The presented device can be directly installed in product fill tubes or vessels, follows CIP- (cleaning in place) and removes the need of sample taking. A proof of concept and preliminary results, measuring protein precipitation, are presented.}, language = {en} } @article{AboulnagaZouSelmeretal.2018, author = {Aboulnaga, E. A. and Zou, H. and Selmer, Thorsten and Xian, M.}, title = {Development of a plasmid-based, tunable, tolC-derived expression system for application in Cupriavidus necator H16}, series = {Journal of Biotechnology}, volume = {274}, journal = {Journal of Biotechnology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0168-1656}, doi = {10.1016/j.jbiotec.2018.03.007}, pages = {15 -- 27}, year = {2018}, abstract = {Cupriavidus necator H16 gains increasing attention in microbial research and biotechnological application due to its diverse metabolic features. Here we present a tightly controlled gene expression system for C. necator including the pBBR1-vector that contains hybrid promoters originating from C. necator native tolC-promoter in combination with a synthetic tetO-operator. The expression of the reporter gene from these plasmids relies on the addition of the exogenous inducer doxycycline (dc). The novel expression system offers a combination of advantageous features as; (i) high and dose-dependent recombinant protein production, (ii) tight control with a high dynamic range (On/Off ratio), which makes it applicable for harmful pathways or for toxic protein production, (iii) comparable cheap inducer (doxycycline, dc), (iv) effective at low inducer concentration, that makes it useful for large scale application, (v) rapid, diffusion controlled induction, and (vi) the inducer does not interfere within the cell metabolism. As applications of the expression system in C. necator H16, the growth ability on glycerol was enhanced by constitutively expressing the E. coli glpk gene-encoding for glycerol kinase. Likewise, we used the system to overcome the expression toxicity of mevalonate pathway in C. necator H16. With this system, the mevalonate-genes were successfully introduced in the host and the recombinant strains could produce about 200 mg/l mevalonate.}, language = {en} } @article{DruckenmuellerGuentherElbers2018, author = {Druckenm{\"u}ller, Katharina and G{\"u}nther, Klaus and Elbers, Gereon}, title = {Near-infrared spectroscopy (NIRS) as a tool to monitor exhaust air from poultry operations}, series = {Science of the Total Environment}, volume = {630}, journal = {Science of the Total Environment}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0048-9697}, doi = {10.1016/j.scitotenv.2018.02.072}, pages = {536 -- 543}, year = {2018}, abstract = {Intensive poultry operation systems emit a considerable volume of inorganic and organic matter in the surrounding environment. Monitoring cleaning properties of exhaust air cleaning systems and to detect small but significant changes in emission characteristics during a fattening cycle is important for both emission and fattening process control. In the present study, we evaluated the potential of near-infrared spectroscopy (NIRS) combined with chemometric techniques as a monitoring tool of exhaust air from poultry operation systems. To generate a high-quality data set for evaluation, the exhaust air of two poultry houses was sampled by applying state-of-the-art filter sampling protocols. The two stables were identical except for one crucial difference, the presence or absence of an exhaust air cleaning system. In total, twenty-one exhaust air samples were collected at the two sites to monitor spectral differences caused by the cleaning device, and to follow changes in exhaust air characteristics during a fattening period. The total dust load was analyzed by gravimetric determination and included as a response variable in multivariate data analysis. The filter samples were directly measured with NIR spectroscopy. Principal component analysis (PCA), linear discriminant analysis (LDA), and factor analysis (FA) were effective in classifying the NIR exhaust air spectra according to fattening day and origin. The results indicate that the dust load and the composition of exhaust air (inorganic or organic matter) substantially influence the NIR spectral patterns. In conclusion, NIR spectroscopy as a tool is a promising and very rapid way to detect differences between exhaust air samples based on still not clearly defined circumstances triggered during a fattening period and the availability of an exhaust air cleaning system.}, language = {en} } @article{MolinnusMuschallikGonzalezetal.2018, author = {Molinnus, Denise and Muschallik, Lukas and Gonzalez, Laura Osorio and Bongaerts, Johannes and Wagner, Torsten and Selmer, Thorsten and Siegert, Petra and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Development and characterization of a field-effect biosensor for the detection of acetoin}, series = {Biosensors and Bioelectronics}, volume = {115}, journal = {Biosensors and Bioelectronics}, publisher = {Elsevier}, address = {Amsterdam}, doi = {10.1016/j.bios.2018.05.023}, pages = {1 -- 6}, year = {2018}, abstract = {A capacitive electrolyte-insulator-semiconductor (EIS) field-effect biosensor for acetoin detection has been presented for the first time. The EIS sensor consists of a layer structure of Al/p-Si/SiO₂/Ta₂O₅/enzyme acetoin reductase. The enzyme, also referred to as butane-2,3-diol dehydrogenase from B. clausii DSM 8716T, has been recently characterized. The enzyme catalyzes the (R)-specific reduction of racemic acetoin to (R,R)- and meso-butane-2,3-diol, respectively. Two different enzyme immobilization strategies (cross-linking by using glutaraldehyde and adsorption) have been studied. Typical biosensor parameters such as optimal pH working range, sensitivity, hysteresis, linear concentration range and long-term stability have been examined by means of constant-capacitance (ConCap) mode measurements. Furthermore, preliminary experiments have been successfully carried out for the detection of acetoin in diluted white wine samples.}, language = {en} } @article{PilasYaziciSelmeretal.2018, author = {Pilas, Johanna and Yazici, Y. and Selmer, Thorsten and Keusgen, M. and Sch{\"o}ning, Michael Josef}, title = {Application of a portable multi-analyte biosensor for organic acid determination in silage}, series = {Sensors}, volume = {18}, journal = {Sensors}, number = {5}, publisher = {MDPI}, address = {Basel}, issn = {1424-8220}, doi = {10.3390/s18051470}, pages = {12 Seiten}, year = {2018}, abstract = {Multi-analyte biosensors may offer the opportunity to perform cost-effective and rapid analysis with reduced sample volume, as compared to electrochemical biosensing of each analyte individually. This work describes the development of an enzyme-based biosensor system for multi-parametric determination of four different organic acids. The biosensor array comprises five working electrodes for simultaneous sensing of ethanol, formate, d-lactate, and l-lactate, and an integrated counter electrode. Storage stability of the biosensor was evaluated under different conditions (stored at +4 °C in buffer solution and dry at -21 °C, +4 °C, and room temperature) over a period of 140 days. After repeated and regular application, the individual sensing electrodes exhibited the best stability when stored at -21 °C. Furthermore, measurements in silage samples (maize and sugarcane silage) were conducted with the portable biosensor system. Comparison with a conventional photometric technique demonstrated successful employment for rapid monitoring of complex media.}, language = {en} } @article{WilsonDickieSchreiteretal.2018, author = {Wilson, C. E. and Dickie, A. P. and Schreiter, K. and Wehr, R. and Wilson, E. M. and Bial, J. and Scheer, Nico and Wilson, I. D. and Riley, R. J.}, title = {The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice}, series = {Archives of Toxicology}, volume = {92}, journal = {Archives of Toxicology}, number = {6}, publisher = {Springer}, issn = {1432-0738}, doi = {10.1007/s00204-018-2212-1}, pages = {1953 -- 1967}, year = {2018}, abstract = {The pharmacokinetics of diclofenac were investigated following single oral doses of 10 mg/kg to chimeric liver humanized and murinized FRG and C57BL/6 mice. In addition, the metabolism and excretion were investigated in chimeric liver humanized and murinized FRG mice. Diclofenac reached maximum blood concentrations of 2.43 ± 0.9 µg/mL (n = 3) at 0.25 h post-dose with an AUCinf of 3.67 µg h/mL and an effective half-life of 0.86 h (n = 2). In the murinized animals, maximum blood concentrations were determined as 3.86 ± 2.31 µg/mL at 0.25 h post-dose with an AUCinf of 4.94 ± 2.93 µg h/mL and a half-life of 0.52 ± 0.03 h (n = 3). In C57BL/6J mice, mean peak blood concentrations of 2.31 ± 0.53 µg/mL were seen 0.25 h post-dose with a mean AUCinf of 2.10 ± 0.49 µg h/mL and a half-life of 0.51 ± 0.49 h (n = 3). Analysis of blood indicated only trace quantities of drug-related material in chimeric humanized and murinized FRG mice. Metabolic profiling of urine, bile and faecal extracts revealed a complex pattern of metabolites for both humanized and murinized animals with, in addition to unchanged parent drug, a variety of hydroxylated and conjugated metabolites detected. The profiles in humanized mice were different to those of both murinized and wild-type animals, e.g., a higher proportion of the dose was detected in the form of acyl glucuronide metabolites and much reduced amounts as taurine conjugates. Comparison of the metabolic profiles obtained from the present study with previously published data from C57BL/6J mice and humans revealed a greater, though not complete, match between chimeric humanized mice and humans, such that the liver humanized FRG model may represent a model for assessing the biotransformation of such compounds in humans.}, language = {en} } @article{WilsonWilsonScheeretal.2017, author = {Wilson, Ian D. and Wilson, Claire E. and Scheer, Nico and Dickie, A.P. and Schreiter, K. and Wilson, E. M. and Riley, R. J. and Wehr, R. and Bial, J.}, title = {The Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice}, series = {Biochemical pharmacology}, volume = {Volume 135}, journal = {Biochemical pharmacology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-2968}, doi = {10.1016/j.bcp.2017.03.015}, pages = {139 -- 150}, year = {2017}, language = {en} } @article{ZhangHeimbachScheeretal.2016, author = {Zhang, Jin and Heimbach, Tycho and Scheer, Nico and Barve, Avantika and Li, Wenkui and Lin, Wen and He, Handan}, title = {Clinical Exposure Boost Predictions by Integrating Cytochrome P450 3A4-Humanized Mouse Studies With PBPK Modeling}, series = {Journal of Pharmaceutical Sciences}, volume = {Volume 105}, journal = {Journal of Pharmaceutical Sciences}, number = {Issue 4}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0022-3549}, doi = {doi.org/10.1016/j.xphs.2016.01.021}, pages = {1398 -- 1404}, year = {2016}, abstract = {NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir.}, language = {en} } @article{ScheerMclaughlinRodeetal.2014, author = {Scheer, Nico and Mclaughlin, Lesley A. and Rode, Anja and MacLeod, Alastair Kenneth and Henderson, Colin J. and Wolf, Roland C.}, title = {Deletion of thirty murine cytochrome P450 genes results in viable mice with compromised drug metabolism}, series = {Drug Metabolism and Disposition}, volume = {42}, journal = {Drug Metabolism and Disposition}, number = {6}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-009X}, doi = {10.1124/dmd.114.057885}, pages = {1022 -- 1030}, year = {2014}, abstract = {In humans, 75\% of all drugs are metabolized by the cytochrome P450-dependent monooxygenase system. Enzymes encoded by the CYP2C, CYP2D, and CYP3A gene clusters account for ∼80\% of this activity. There are profound species differences in the multiplicity of cytochrome P450 enzymes, and the use of mouse models to predict pathways of drug metabolism is further complicated by overlapping substrate specificity between enzymes from different gene families. To establish the role of the hepatic and extrahepatic P450 system in drug and foreign chemical disposition, drug efficacy, and toxicity, we created a unique mouse model in which 30 cytochrome P450 genes from the Cyp2c, Cyp2d, and Cyp3a gene clusters have been deleted. Remarkably, despite a wide range of putative important endogenous functions, Cyp2c/2d/3a KO mice were viable and fertile, demonstrating that these genes have evolved primarily as detoxification enzymes. Although there was no overt phenotype, detailed examination showed Cyp2c/2d/3a KO mice had a smaller body size (15\%) and larger livers (20\%). Changes in hepatic morphology and a decreased blood glucose (30\%) were also noted. A five-drug cocktail of cytochrome P450 isozyme probe substrates were used to evaluate changes in drug pharmacokinetics; marked changes were observed in either the pharmacokinetics or metabolites formed from Cyp2c, Cyp2d, and Cyp3a substrates, whereas the metabolism of the Cyp1a substrate caffeine was unchanged. Thus, Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the P450 system in drug metabolism and efficacy, as well as in chemical toxicity.}, language = {en} } @article{ScheerBalimaneHaywardetal.2012, author = {Scheer, Nico and Balimane, Praveen and Hayward, Michael D. and Buechel, Sandra and Kauselmann, Gunther and Wolf, C. Roland}, title = {Generation and Characterization of a Novel Multidrug Resistance Protein 2 Humanized Mouse Line}, series = {Drug Metabolism and Disposition}, volume = {40}, journal = {Drug Metabolism and Disposition}, number = {11}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/dmd.112.047605}, pages = {2212 -- 2218}, year = {2012}, abstract = {The multidrug resistance protein (MRP) 2 is predominantly expressed in liver, intestine, and kidney, where it plays an important role in the excretion of a range of drugs and their metabolites or endogenous compounds into bile, feces, and urine. Mrp knockout [Mrp2(-/-)] mice have been used recently to study the role of MRP2 in drug disposition. Here, we describe the first generation and initial characterization of a mouse line humanized for MRP2 (huMRP2), which is nulled for the mouse Mrp2 gene and expresses the human transporter in the organs and cell types where MRP2 is normally expressed. Analysis of the mRNA expression for selected cytochrome P450 and transporter genes revealed no major changes in huMRP2 mice compared with wild-type controls. We show that human MRP2 is able to compensate functionally for the loss of the mouse transporter as demonstrated by comparable bilirubin levels in the humanized mice and wild-type controls, in contrast to the hyperbilirubinemia phenotype that is observed in MRP2(-/-) mice. The huMRP2 mouse provides a model to study the role of the human transporter in drug disposition and in assessing the in vivo consequences of inhibiting this transporter by compounds interacting with human MRP2.}, language = {en} } @article{ScheerKapelyukhRodeetal.2012, author = {Scheer, Nico and Kapelyukh, Yury and Rode, Anja and Buechel, Sandra and Wolf, C. Roland}, title = {Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines}, series = {Molecular Pharmacology}, volume = {82}, journal = {Molecular Pharmacology}, number = {6}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.112.080036}, pages = {1022 -- 1029}, year = {2012}, abstract = {Compared with rodents and many other animal species, the human cytochrome P450 (P450) Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the substrate specificity of its enzymes. As a consequence, the use of wild-type animal models to predict the role of human CYP2C enzymes in drug metabolism and drug-drug interactions is limited. Within the human CYP2C cluster CYP2C9 is of particular importance, because it is one of the most abundant P450 enzymes in human liver, and it is involved in the metabolism of a wide variety of important drugs and environmental chemicals. To investigate the in vivo functions of cytochrome P450 Cyp2c genes and to establish a model for studying the functions of CYP2C9 in vivo, we have generated a mouse model with a deletion of the murine Cyp2c gene cluster and a corresponding humanized model expressing CYP2C9 specifically in the liver. Despite the high number of functional genes in the mouse Cyp2c cluster and the reported roles of some of these proteins in different biological processes, mice deleted for Cyp2c genes were viable and fertile but showed certain phenotypic alterations in the liver. The expression of CYP2C9 in the liver also resulted in viable animals active in the metabolism and disposition of a number of CYP2C9 substrates. These mouse lines provide a powerful tool for studying the role of Cyp2c genes and of CYP2C9 in particular in drug disposition and as a factor in drug-drug interaction.}, language = {en} } @article{KapelyukhHendersonScheeretal.2019, author = {Kapelyukh, Yury and Henderson, Colin James and Scheer, Nico and Rode, Anja and Wolf, Charles Roland}, title = {Defining the contribution of CYP1A1 and CYP1A2 to drug metabolism using humanized CYP1A1/1A2 and Cyp1a1/Cyp1a2 KO mice}, series = {Drug Metabolism and Disposition}, journal = {Drug Metabolism and Disposition}, number = {Early view}, doi = {10.1124/dmd.119.087718}, pages = {43 Seiten}, year = {2019}, language = {en} } @article{LempiaeinenCouttetBolognanietal.2012, author = {Lempi{\"a}inen, Harri and Couttet, Philippe and Bolognani, Federico and M{\"u}ller, Arne and Dubost, Val{\´e}rie and Luisier, Rapha{\"e}lle and Rio-Espinola, Alberto del and Vitry, Veronique and Unterberger, Elif B. and Thomson, John P. and Treindl, Fridolin and Metzger, Ute and Wrzodek, Clemens and Hahne, Florian and Zollinger, Tulipan and Brasa, Sarah and Kalteis, Magdalena and Marcellin, Magali and Giudicelli, Fanny and Braeuning, Albert and Morawiec, Laurent and Zamurovic, Natasa and L{\"a}ngle, Ulrich and Scheer, Nico and Sch{\"u}beler, Dirk and Goodman, Jay and Chibout, Salah-Dine and Marlowe, Jennifer and Theil, Dietlinde and Heard, David J. and Grenet, Olivier and Zell, Andreas and Templin, Markus F. and Meehan, Richard R. and Wolf, Roland C. and Elcombe, Clifford R. and Schwarz, Michael and Moulin, Pierre and Terranova, R{\´e}mi and Moggs, Jonathan G.}, title = {Identification of Dlk1-Dio3 imprinted gene cluster non-coding RNAs as novel candidate biomarkers for liver tumor promotion}, series = {Toxicological Sciences}, volume = {131}, journal = {Toxicological Sciences}, number = {2}, publisher = {Oxford University Press}, address = {Oxford}, issn = {1094-2025}, doi = {10.1093/toxsci/kfs303}, pages = {375 -- 386}, year = {2012}, abstract = {The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.}, language = {en} } @article{RossPlummerRodeetal.2010, author = {Ross, Jillian and Plummer, Simon M. and Rode, Anja and Scheer, Nico and Bower, Conrad C. and Vogel, Ortwin and Henderson, Colin J. and Wolf, C. Roland and Elcombe, Clifford R.}, title = {Human constitutive androstane receptor (CAR) and pregnane X receptor (PXR) support the hypertrophic but not the hyperplastic response to the murine nongenotoxic hepatocarcinogens phenobarbital and chlordane in vivo}, series = {Toxicological Sciences}, volume = {116}, journal = {Toxicological Sciences}, number = {2}, publisher = {Oxford University Press}, address = {Oxford}, issn = {1096-0929}, doi = {10.1093/toxsci/kfq118}, pages = {452 -- 466}, year = {2010}, abstract = {Mouse nongenotoxic hepatocarcinogens phenobarbital (PB) and chlordane induce hepatomegaly characterized by hypertrophy and hyperplasia. Increased cell proliferation is implicated in the mechanism of tumor induction. The relevance of these tumors to human health is unclear. The xenoreceptors, constitutive androstane receptors (CARs), and pregnane X receptor (PXR) play key roles in these processes. Novel "humanized" and knockout models for both receptors were developed to investigate potential species differences in hepatomegaly. The effects of PB (80 mg/kg/4 days) and chlordane (10 mg/kg/4 days) were investigated in double humanized PXR and CAR (huPXR/huCAR), double knockout PXR and CAR (PXRKO/CARKO), and wild-type (WT) C57BL/6J mice. In WT mice, both compounds caused increased liver weight, hepatocellular hypertrophy, and cell proliferation. Both compounds caused alterations to a number of cell cycle genes consistent with induction of cell proliferation in WT mice. However, these gene expression changes did not occur in PXRKO/CARKO or huPXR/huCAR mice. Liver hypertrophy without hyperplasia was demonstrated in the huPXR/huCAR animals in response to both compounds. Induction of the CAR and PXR target genes, Cyp2b10 and Cyp3a11, was observed in both WT and huPXR/huCAR mouse lines following treatment with PB or chlordane. In the PXRKO/CARKO mice, neither liver growth nor induction of Cyp2b10 and Cyp3a11 was seen following PB or chlordane treatment, indicating that these effects are CAR/PXR dependent. These data suggest that the human receptors are able to support the chemically induced hypertrophic responses but not the hyperplastic (cell proliferation) responses. At this time, we cannot be certain that hCAR and hPXR when expressed in the mouse can function exactly as the genes do when they are expressed in human cells. However, all parameters investigated to date suggest that much of their functionality is maintained.}, language = {en} } @article{ScheerRossKapelyukhetal.2010, author = {Scheer, Nico and Ross, Jillian and Kapelyukh, Yury and Rode, Anja and Wolf, C. Roland}, title = {In vivo responses of the human and murine pregnane X receptor to dexamethasone in mice}, series = {Drug Metabolism and Disposition}, volume = {38}, journal = {Drug Metabolism and Disposition}, number = {7}, publisher = {ASPET}, address = {Bethesda}, issn = {1521-009X}, doi = {10.1124/dmd.109.031872}, pages = {1046 -- 1053}, year = {2010}, abstract = {Dexamethasone (DEX) is a potent and widely used anti-inflammatory and immunosuppressant glucocorticoid. It can bind and activate the pregnane X receptor (PXR), which plays a critical role as xenobiotic sensor in mammals to induce the expression of many enzymes, including cytochromes P450 in the CYP3A family. This induction results in its own metabolism. We have used a series of transgenic mouse lines, including a novel, improved humanized PXR line, to compare the induction profile of PXR-regulated drug-metabolizing enzymes after DEX administration, as well as looking at hepatic responses to rifampicin (RIF). The new humanized PXR model has uncovered further intriguing differences between the human and mouse receptors in that RIF only induced Cyp2b10 in the new humanized model. DEX was found to be a much more potent inducer of Cyp3a proteins in wild-type mice than in mice humanized for PXR. To assess whether PXR is involved in the detoxification of DEX in the liver, we analyzed the consequences of high doses of the glucocorticoid on hepatotoxicity on different PXR genetic backgrounds. We also studied these effects in an additional mouse model in which functional mouse Cyp3a genes have been deleted. These strains exhibited different sensitivities to DEX, indicating a protective role of the PXR and CYP3A proteins against the hepatotoxicity of this compound.}, language = {en} } @article{ScheerRossRodeetal.2008, author = {Scheer, Nico and Ross, Jillian and Rode, Anja and Zevnik, Branko and Niehaves, Sandra and Faust, Nicole and Wolf, C. Roland}, title = {A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response}, series = {Journal of Clinical Investigation}, volume = {118}, journal = {Journal of Clinical Investigation}, number = {9}, issn = {1558-8238}, doi = {https://doi.org/10.1172/JCI35483}, pages = {3228 -- 3239}, year = {2008}, language = {en} } @article{ScheerKapelyukhMcEwanetal.2012, author = {Scheer, Nico and Kapelyukh, Yury and McEwan, Jillian and Beuger, Vincent and Stanley, Lesley A. and Rode, Anja and Wolf, C. Roland}, title = {Modeling Human Cytochrome P450 2D6 Metabolism and Drug-drug Interaction by a Novel Panel of Knockout and Humanized Mouse Lines}, series = {Molecular Pharmacology}, volume = {81}, journal = {Molecular Pharmacology}, number = {1}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.111.075192}, pages = {63 -- 72}, year = {2012}, abstract = {The highly polymorphic human cytochrome P450 2D6 enzyme is involved in the metabolism of up to 25\% of all marketed drugs and accounts for significant individual differences in response to CYP2D6 substrates. Because of the differences in the multiplicity and substrate specificity of CYP2D family members among species, it is difficult to predict pathways of human CYP2D6-dependent drug metabolism on the basis of animal studies. To create animal models that reflect the human situation more closely and that allow an in vivo assessment of the consequences of differential CYP2D6 drug metabolism, we have developed a novel straightforward approach to delete the entire murine Cyp2d gene cluster and replace it with allelic variants of human CYP2D6. By using this approach, we have generated mouse lines expressing the two frequent human protein isoforms CYP2D6.1 and CYP2D6.2 and an as yet undescribed variant of this enzyme, as well as a Cyp2d cluster knockout mouse. We demonstrate that the various transgenic mouse lines cover a wide spectrum of different human CYP2D6 metabolizer phenotypes. The novel humanization strategy described here provides a robust approach for the expression of different CYP2D6 allelic variants in transgenic mice and thus can help to evaluate potential CYP2D6-dependent interindividual differences in drug response in the context of personalized medicine.}, language = {en} } @article{ReugelsBoggettiScheeretal.2006, author = {Reugels, Alexander M. and Boggetti, Barbara and Scheer, Nico and Campos-Ortega, Jos{\´e} A.}, title = {Asymmetric localization of Numb:EGFP in dividing neuroepithelial cells during neurulation in Danio rerio}, series = {Developmental Dynamics}, volume = {235}, journal = {Developmental Dynamics}, number = {4}, issn = {1097-0177}, doi = {10.1002/dvdy.20699}, pages = {934 -- 948}, year = {2006}, language = {en} } @article{HansScheerRiedletal.2004, author = {Hans, Stefan and Scheer, Nico and Riedl, Iris and Weiz{\"a}cker, Elisabeth von and Blader, Patrick and Campos-Ortega, Jos{\´e} A.}, title = {her3, a zebrafish member of the hairy-E(spl) family, is repressed by Notch signalling}, series = {Development}, volume = {131}, journal = {Development}, number = {12}, issn = {1477-9129}, doi = {10.1242/dev.01167}, pages = {2957 -- 2969}, year = {2004}, language = {en} } @article{ScheerRiedlWarrenetal.2002, author = {Scheer, Nico and Riedl, Iris and Warren, J.T. and Kuwada, John Y. and Campos-Ortega, Jos{\´e} A.}, title = {A quantitative analysis of the kinetics of Gal4 activator and effector gene expression in the zebrafish}, series = {Mechanism of Development}, volume = {112}, journal = {Mechanism of Development}, number = {1-2}, issn = {0925-4773}, doi = {10.1016/S0925-4773(01)00621-9}, pages = {9 -- 14}, year = {2002}, language = {en} }