@article{ScheerWolf2014, author = {Scheer, Nico and Wolf, C. Roland}, title = {Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications}, series = {Xenobiotica}, volume = {44}, journal = {Xenobiotica}, number = {2}, publisher = {Taylor \& Francis}, address = {Abingdon}, issn = {1366-5928}, doi = {10.3109/00498254.2013.815831}, pages = {96 -- 108}, year = {2014}, abstract = {1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug-drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described. 2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created. 3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug-drug interactions as well as in human metabolite testing and risk assessment. 4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed.}, language = {en} } @article{HentschkeHagerHojdis2014, author = {Hentschke, Reinhard and Hager, Jonathan and Hojdis, Nils}, title = {Molecular Modeling Approach to the Prediction of Mechanical Properties of Silica-Reinforced Rubbers}, series = {Journal of Applied Polymer Science}, volume = {131}, journal = {Journal of Applied Polymer Science}, number = {18}, publisher = {Wiley}, address = {New York, NY}, issn = {1097-4628}, doi = {10.1002/app.40806}, pages = {1 -- 9}, year = {2014}, abstract = {Recently, we have suggested a nanomechanical model for dissipative loss in filled elastomer networks in the context of the Payne effect. The mechanism is based on a total interfiller particle force exhibiting an intermittent loop, due to the combination of short-range repulsion and dispersion forces with a long-range elastic attraction. The sum of these forces leads, under external strain, to a spontaneous instability of "bonds" between the aggregates in a filler network and attendant energy dissipation. Here, we use molecular dynamics simulations to obtain chemically realistic forces between surface modified silica particles. The latter are combined with the above model to estimate the loss modulus and the low strain storage modulus in elastomers containing the aforementioned filler-compatibilizer systems. The model is compared to experimental dynamic moduli of silica filled rubbers. We find good agreement between the model predictions and the experiments as function of the compatibilizer's molecular structure and its bulk concentration.}, 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{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{SchiffelsPinkenburgScheldenetal.2013, author = {Schiffels, Johannes and Pinkenburg, Olaf and Schelden, Maximilian and Aboulnaga, El-Hussiny A. A. and Baumann, Marcus and Selmer, Thorsten}, title = {An innovative cloning platform enables large-scale production and maturation of an oxygen-tolerant [NiFe]-hydrogenase from cupriavidus necator in Escherichia coli}, series = {PLOS one. 2013}, journal = {PLOS one. 2013}, publisher = {Public Library of Science}, address = {San Francisco, California}, issn = {1932-6203}, doi = {10.1371/journal.pone.0068812}, year = {2013}, language = {en} } @article{AbulnagaPinkenburgSchiffelsetal.2013, author = {Abulnaga, El-Hussiny and Pinkenburg, Olaf and Schiffels, Johannes and E-Refai, Ahmed and Buckel, Wolfgang and Selmer, Thorsten}, title = {Effect of an Oxygen-Tolerant Bifurcating Butyryl Coenzyme A Dehydrogenase/Electron-Transferring Flavoprotein Complex from Clostridium difficile on Butyrate Production in Escherichia coli}, series = {Journal of bacteriology}, volume = {195}, journal = {Journal of bacteriology}, number = {16}, issn = {1098-5530 [E-Journal]}, pages = {3704 -- 3713}, year = {2013}, language = {en} } @article{AboulnagaPinkenburgSchiffelsetal.2013, author = {Aboulnaga, E. H. and Pinkenburg, O. and Schiffels, Johannes and El-Refai, A. and Buckel, W. and Selmer, Thorsten}, title = {Butyrate production in Escherichia coli: Exploitation of an oxygen tolerant bifurcating butyryl-CoA dehydrogenase/electron transferring flavoprotein complex from Clostridium difficile}, series = {Journal of bacteriology. June 14, 2013}, journal = {Journal of bacteriology. June 14, 2013}, issn = {1098-5530 (E-Journal) ; 0021-9193 (Print)}, pages = {Epub ahead of print}, year = {2013}, language = {de} } @article{ScheeleOertelBongaertsetal.2013, author = {Scheele, Sandra and Oertel, Dan and Bongaerts, Johannes and Evers, Stefan and Hellmuth, Hendrik and Maurer, Karl-Heinz and Bott, Michael and Freudl, Roland}, title = {Secretory production of an FAD cofactor-containing cytosolic enzyme (sorbitol-xylitol oxidase from Streptomyces coelicolor) using the twin-arginine translocation (Tat) pathway of Corynebacterium glutamicum}, series = {Microbial biotechnology}, journal = {Microbial biotechnology}, publisher = {Wiley-Blackwell}, address = {Oxford}, issn = {1751-7915}, pages = {202 -- 206}, year = {2013}, language = {en} } @article{WilmingBegemannKuhneetal.2013, author = {Wilming, Anja and Begemann, Jens and Kuhne, Stefan and Regestein, Lars and Bongaerts, Johannes and Evers, Stefan and Maurer, Karl-Heinz and B{\"u}chs, Jochen}, title = {Metabolic studies of γ-polyglutamic acid production in Bacillus licheniformis by small-scale continuous cultivations}, series = {Biochemical engineering journal}, volume = {Vol. 73}, journal = {Biochemical engineering journal}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-295X (E-Journal); 1369-703X (Print)}, pages = {29 -- 37}, year = {2013}, language = {en} } @article{VoigtSchroeterJuergenetal.2013, author = {Voigt, Birgit and Schroeter, Rebecca and J{\"u}rgen, Britta and Albrecht, Dirk and Evers, Stefan and Bongaerts, Johannes and Maurer, Karl-Heinz and Schweder, Thomas and Hecker, Michael}, title = {The response of Bacillus licheniformis to heat and ethanol stress and the role of the SigB regulon}, series = {Proteomics}, volume = {Vol. 13}, journal = {Proteomics}, number = {Iss. 14}, publisher = {Wiley}, address = {Weinheim}, issn = {1615-9861 (E-Journal); 1615-9853 (Print)}, pages = {2140 -- 2146}, year = {2013}, language = {en} } @article{RachingerBauchStrittmatteretal.2013, author = {Rachinger, Michael and Bauch, Melanie and Strittmatter, Axel and Bongaerts, Johannes and Evers, Stefan and Maurer, Karl-Heinz and Daniel, Rolf and Liebl, Wolfgang and Liesegang, Heiko and Ehrenreich, Armin}, title = {Size unlimited markerless deletions by a transconjugative plasmid-system in Bacillus licheniformis}, series = {Journal of biotechnology}, volume = {Vol. 164}, journal = {Journal of biotechnology}, number = {Iss. 4}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-4863 (E-Journal); 0168-1656 (Print)}, pages = {365 -- 369}, year = {2013}, language = {en} } @article{WiegandDietrichHerteletal.2013, author = {Wiegand, Sandra and Dietrich, Sascha and Hertel, Robert and Bongaerts, Johannes and Evers, Stefan and Volland, Sonja and Daniel, Rolf and Liesegang, Heiko}, title = {RNA-Seq of Bacillus licheniformis: active regulatory RNA features expressed within a productive fermentation}, series = {BMC genomics}, volume = {Vol. 14}, journal = {BMC genomics}, publisher = {BioMed Central}, address = {London}, issn = {1471-2164}, pages = {667}, year = {2013}, 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} } @inproceedings{TakenagaHerreraWerneretal.2013, author = {Takenaga, Shoko and Herrera, Cony F. and Werner, Frederik and Biselli, Manfred and Schnitzler, Thomas and Sch{\"o}ning, Michael Josef and {\"O}hlschl{\"a}ger, Peter and Wagner, Torsten}, title = {Detection of the metabolic activity of cells by differential measurements based on a single light-addressable potentiometric sensor chip}, series = {11. Dresdner Sensor-Symposium : 9.-11.12.2013}, booktitle = {11. Dresdner Sensor-Symposium : 9.-11.12.2013}, organization = {Dresdner Sensor-Symposium <11, 2013>}, isbn = {978-3-9813484-5-3}, pages = {63 -- 67}, year = {2013}, 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{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} }