TY - JOUR A1 - Schwab, Lukas A1 - Hojdis, Nils A1 - Lacayo, Jorge A1 - Wilhelm, Manfred T1 - Fourier-Transform Rheology of Unvulcanized, Carbon Black Filled Styrene Butadiene Rubber JF - Macromolecular Materials and Engineering N2 - Rubber materials filled with reinforcing fillers display nonlinear rheological behavior at small strain amplitudes below γ0 < 0.1. Nevertheless, rheological data are analyzed mostly in terms of linear parameters, such as shear moduli (G′, G″), which loose their physical meaning in the nonlinear regime. In this work styrene butadiene rubber filled with carbon black (CB) under large amplitude oscillatory shear (LAOS) is analyzed in terms of the nonlinear parameter I3/1. Three different CB grades are used and the filler load is varied between 0 and 70 phr. It is found that I3/1(φ) is most sensitive to changes of the total accessible filler surface area at low strain amplitudes (γ0 = 0.32). The addition of up to 70 phr CB leads to an increase of I3/1(φ) by a factor of more than ten. The influence of the measurement temperature on I3/1 is pronounced for CB levels above the percolation threshold. Y1 - 2016 U6 - http://dx.doi.org/10.1002/mame.201500356 SN - 1439-2054 VL - 301 IS - 4 SP - 457 EP - 468 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Harish, Ajay B. A1 - Wriggers, Peter A1 - Jungk, Juliane A1 - Hojdis, Nils A1 - Recker, Carla T1 - Mesoscale Constitutive Modeling of Non-Crystallizing Filled Elastomers JF - Computational Mechanics N2 - Elastomers are exceptional materials owing to their ability to undergo large deformations before failure. However, due to their very low stiffness, they are not always suitable for industrial applications. Addition of filler particles provides reinforcing effects and thus enhances the material properties that render them more versatile for applications like tyres etc. However, deformation behavior of filled polymers is accompanied by several nonlinear effects like Mullins and Payne effect. To this day, the physical and chemical changes resulting in such nonlinear effect remain an active area of research. In this work, we develop a heterogeneous (or multiphase) constitutive model at the mesoscale explicitly considering filler particle aggregates, elastomeric matrix and their mechanical interaction through an approximate interface layer. The developed constitutive model is used to demonstrate cluster breakage, also, as one of the possible sources for Mullins effect observed in non-crystallizing filled elastomers. Y1 - 2016 U6 - http://dx.doi.org/10.1007/s00466-015-1251-1 SN - 1432-0924 VL - 57 SP - 653 EP - 677 PB - Springer CY - Berlin ER - TY - JOUR A1 - Seifarth, Volker A1 - Goßmann, Matthias A1 - Grosse, J. O. A1 - Becker, C. A1 - Heschel, I. A1 - Artmann, Gerhard A1 - Temiz Artmann, Aysegül T1 - Development of a Bioreactor to Culture Tissue Engineered Ureters Based on the Application of Tubular OPTIMAIX 3D Scaffolds JF - Urologia Internationalis Y1 - 2015 U6 - http://dx.doi.org/10.1159/000368419 SN - 0042-1138 VL - 2015 IS - 95 SP - 106 EP - 113 PB - Karger CY - Basel ER - TY - JOUR A1 - Kusch, Peter A1 - Rieser, Claudia A1 - Knupp, Gerd A1 - Mang, Thomas T1 - Characterization of copolymers of methacrylic acid with poly(ethylene glycol) methyl ether methacrylate macromonomers by analytical pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) JF - Journal of Analytical and Applied Pyrolysis Y1 - 2015 U6 - http://dx.doi.org/10.1016/j.jaap.2015.03.003 SN - 0165-2370 VL - Vol. 113 SP - 412 EP - 418 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Pilas, Johanna A1 - Iken, Heiko A1 - Selmer, Thorsten A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Development of a multi‐parameter sensor chip for the simultaneous detection of organic compounds in biogas processes JF - Physica status solidi (a) N2 - 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. Y1 - 2015 U6 - http://dx.doi.org/10.1002/pssa.201431894 SN - 1862-6319 VL - 212 IS - 6 SP - 1306 EP - 1312 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Breuer, Lars A1 - Raue, Markus A1 - Kirschbaum, M. A1 - Mang, Thomas A1 - Schöning, Michael Josef A1 - Thoelen, R. A1 - Wagner, Torsten T1 - Light-controllable polymeric material based on temperature-sensitive hydrogels with incorporated graphene oxide JF - Physica status solidi (a) N2 - 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. Y1 - 2015 U6 - http://dx.doi.org/10.1002/pssa.201431944 SN - 1862-6319 VL - 212 IS - 6 SP - 1368 EP - 1374 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Schiffels, Johannes A1 - Selmer, Thorsten T1 - A flexible toolbox to study protein-assisted metalloenzyme assembly in vitro JF - Biotechnology and Bioengineering Y1 - 2015 U6 - http://dx.doi.org/10.1002/bit.25658 SN - 1097-0290 VL - 112 IS - 11 SP - 2360 EP - 2372 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Voigt, Birgit A1 - Albrecht, Dirk A1 - Sievers, Susanne A1 - Becher, Dörte A1 - Bongaerts, Johannes A1 - Evers, Stefan A1 - Schweder, Thomas A1 - Maurer, Karl-Heinz A1 - Hecker, Michael T1 - High-resolution proteome maps of Bacillus licheniformis cells growing in minimal medium JF - Proteomics Y1 - 2015 U6 - http://dx.doi.org/10.1002/pmic.201400504 SN - 1615-9861 VL - 15 IS - 15 SP - 2629 EP - 2633 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Molinnus, Denise A1 - Bäcker, Matthias A1 - Siegert, Petra A1 - Willenberg, H. A1 - Poghossian, Arshak A1 - Keusgen, M. A1 - Schöning, Michael Josef T1 - Detection of Adrenaline Based on Substrate Recycling Amplification JF - Procedia Engineering N2 - 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. Y1 - 2015 U6 - http://dx.doi.org/10.1016/j.proeng.2015.08.708 SN - 1877-7058 N1 - Eurosensors 2015 VL - 120 SP - 540 EP - 543 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Pilas, Johanna A1 - Mariano, K. A1 - Keusgen, M. A1 - Selmer, Thorsten A1 - Schöning, Michael Josef T1 - Optimization of an Enzyme-based Multi-parameter Biosensor for Monitoring Biogas Processes JF - Procedia Engineering Y1 - 2015 U6 - http://dx.doi.org/10.1016/j.proeng.2015.08.702 SN - 1877-7058 N1 - Part of special issue "Eurosensors 2015" VL - 120 SP - 532 EP - 535 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Takenaga, Shoko A1 - Schneider, Benno A1 - Erbay, E. A1 - Biselli, Manfred A1 - Schnitzler, Thomas A1 - Schöning, Michael Josef A1 - Wagner, Torsten T1 - Fabrication of biocompatible lab-on-chip devices for biomedical applications by means of a 3D-printing process JF - Physica status solidi (a) N2 - A new microfluidic assembly method for semiconductor-based biosensors using 3D-printing technologies was proposed for a rapid and cost-efficient design of new sensor systems. The microfluidic unit is designed and printed by a 3D-printer in just a few hours and assembled on a light-addressable potentiometric sensor (LAPS) chip using a photo resin. The cell growth curves obtained from culturing cells within microfluidics-based LAPS systems were compared with cell growth curves in cell culture flasks to examine biocompatibility of the 3D-printed chips. Furthermore, an optimal cell culturing within microfluidics-based LAPS chips was achieved by adjusting the fetal calf serum concentrations of the cell culture medium, an important factor for the cell proliferation. Y1 - 2015 U6 - http://dx.doi.org/10.1002/pssa.201532053 SN - 1862-6319 VL - 212 IS - 6 SP - 1347 EP - 1352 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Cehreli, Ruksan A1 - Akpinar, Hale A1 - Temiz Artmann, Aysegül A1 - Sagol, Ozgul T1 - Effects of Glutamine and Omega-3 Fatty Acids on Erythrocyte Deformability and Oxidative Damage in Rat Model of Enterocolitis JF - Gastroenterology Research Y1 - 2015 U6 - http://dx.doi.org/10.14740/gr683w SN - 1918-2813 VL - 8 IS - 5 SP - 265 EP - 273 ER - TY - JOUR A1 - Al-Kaidy, Huschyar A1 - Duwe, Anna A1 - Huster, Manuel A1 - Muffler, Kai A1 - Schlegel, Christin A1 - Tim, Sieker A1 - Stadtmüller, Ralf A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Biotechnology and bioprocess engineering – from the first ullmann's article to recent trends JF - ChemBioEng Reviews N2 - For several thousand years, biotechnology and its associated technical processes have had a great impact on the development of mankind. Based on empirical methods, in particular for the production of foodstuffs and daily commodities, these disciplines have become one of the most innovative future issues. Due to the increasing detailed understanding of cellular processes, production strains can now be optimized. In combination with modern bioprocesses, a variety of bulk and fine chemicals as well as pharmaceuticals can be produced efficiently. In this article, some of the current trends in biotechnology are discussed. Y1 - 2015 U6 - http://dx.doi.org/10.1002/cben.201500008 VL - 2 IS - 3 SP - 175 EP - 184 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Thiel, Alexander A1 - Muffler, Kai A1 - Tippkötter, Nils A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Hruschka, Steffen M. A1 - Ulber, Roland T1 - A novel integrated downstream processing approach to recover sinapic acid, phytic acid and proteins from rapeseed meal JF - Journal of Chemical Technology and Biotechnology N2 - BACKGROUND Currently, several techniques exist for the downstream processing of protein, phytic acid and sinapic acid from rapeseed and rapeseed meal, but no technique has been developed to separate all of the components in one process. In this work, two new downstream processing strategies focusing on recovering sinapic acid, phytic acid and protein from rapeseed meal were established. RESULTS The sinapic acid content was enhanced by a factor of 4.5 with one method and 5.1 with the other. The isolation of sinapic acid was accomplished using a zeolite-based adsorbent with high adsorptive and optimal desorption characteristics. Phytic acid was isolated using the anion-exchange resin Purolite A200®. In addition, the processes resulted in two separated protein fractions. The ratios of globulin and albumin ratio to the total protein were 59.2% and 40.1%, respectively. The steps were then combined in two different ways: (a) a ‘sequential process’ using the zeolite and A200 in batch processes; and (b) a ‘parallel process’ using only A200 in a chromatographic system to separate all of the compounds. CONCLUSIONS It can be concluded that isolation of all three components was possible in both processes. These could enhance the added value of current processes using rapeseed meal as a protein source. © 2015 Society of Chemical Industry Y1 - 2015 U6 - http://dx.doi.org/10.1002/jctb.4664 VL - 90 IS - 11 SP - 1999 EP - 2006 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Schumann, Christiane A1 - Rogin, Sabine A1 - Schneider, Horst A1 - Tippkötter, Nils A1 - Oster, Jürgen A1 - Kampeis, Percy T1 - Simultane Atline-Quantifizierung von Magnetpartikeln und Mikroorganismen bei einer HGMS-Filtration JF - Chemie Ingenieur Technik N2 - Es wird eine neue Atline-Messmethode vorgestellt, mit der während einer Hochgradienten-Magnetseparation (HGMS)-Filtration eine simultane Quantifizierung von Magnetpartikeln und Mikroorganismen im Filtrat vorgenommen werden kann. Dabei gelingt die Quantifizierung signifikant besser als mit bisher verwendeten Messmethoden. Mit dieser Methode ist es möglich, die Trennleistung einer HGMS-Filtration zu bestimmen und einen Filterdurchbruch durch Konzentrationsanstiege im Bereich einiger µg L−1 von Magnetpartikeln im Filtrat frühzeitig zu detektieren, ohne dass nennenswerte Partikelmengen verloren gehen. Y1 - 2015 U6 - http://dx.doi.org/10.1002/cite.201300158 N1 - Englischer Titel: Simultaneous Atline Quantification of Magnetic Particles and Microorganisms in the HGMS Filtration VL - 87 IS - 1-2 SP - 137 EP - 149 ER - TY - JOUR A1 - Thiel, Alexander A1 - Muffler, Kai A1 - Tippkötter, Nils A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Ruf, Friedrich A1 - Ulber, Roland T1 - Aufarbeitung von Polyphenolen aus Weizen mittels Zeolithen am Beispiel der Ferulasäure JF - Chemie IngenieurTechnik N2 - Aufarbeitung von Polyphenolen aus Weizenmittels Zeolithen am Beispiel der Ferulasa¨ ureAlexander Thiel1, Kai Muffler1, Nils Tippko¨ tter1, Kirstin Suck2, Ulrich Sohling2, Friedrich Ruf3und Roland Ulber1,*DOI: 10.1002/cite.201400031Bei der Ferulasa¨ure handelt es sich um einen Wertstoff, der aus Weizen gewonnen und in der Lebensmittel- und Pharma-industrie eingesetzt werden kann. Der Einsatz von Weizen als nachwachsende Rohstoffquelle ist allerdings nur dann wirt-schaftlich durchfu¨hrbar, wenn eine Prozessintegration in die bestehenden industriellen Verfahren gewa¨hrleistet oder einedirekte Konkurrenz zur Mehl- und Sta¨rkeindustrie vermieden werden kann. In diesem Artikel wird ein Verfahren aufge-zeigt, welches hohe Ausbeuten ermo¨glicht und eine Konkurrenz zu bestehenden Verwertungspfaden vermeidet. Y1 - 2015 U6 - http://dx.doi.org/10.1002/cite.201400031 N1 - Englischer Titel: Downstream Processing of Polyphenols from Wheat by Zeolites using the Example of Ferulic Acid VL - 87 IS - 1-2 SP - 128 EP - 136 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Wiesen, Sebastian A1 - Tippkötter, Nils A1 - Muffler, Kai A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Ruf, Friedrich A1 - Ulber, Roland T1 - Adsorption of fatty acids to layered double hydroxides in aqueous systems JF - Adsorption N2 - Due to their anion exchange characteristics, layered double hydroxides (LDHs) are suitable for the detoxification of aqueous, fatty acid containing fermentation substrates. The aim of this study is to examine the adsorption mechanism, using crude glycerol from plant oil esterification as a model system. Changes in the intercalation structure in relation to the amount of fatty acids adsorbed are monitored by X-ray diffraction and infra-red spectroscopy. Additionally, calcination of LDH is investigated in order to increase the binding capacity for fatty acids. Our data propose that, at ambient temperature, fatty acids can be bound to the hydrotalcite by adsorption or in addition by intercalation, depending on fatty acid concentration. The adsorption of fatty acids from crude glycerol shows a BET-like behavior. Above a fatty acid concentration of 3.5 g L−1, intercalation of fatty acids can be shown by the appearance of an increased interlayer spacing. This observation suggests a two phase adsorption process. Calcination of LDHs allows increasing the binding capacity for fatty acids by more than six times, mainly by reduction of structural CO32−. Y1 - 2015 VL - 21 IS - 6-7 SP - 459 EP - 466 PB - Springer CY - Berlin ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Hoehr, Cornelia A1 - Hou, Xinchi A1 - Hanemaayer, Victoire A1 - Zeisler, Stefan A1 - Adam, Michael J. A1 - Ruth, Thomas J. A1 - Celler, Anna A1 - Buckley, Ken A1 - Benard, Francois A1 - Schaffer, Paul T1 - Production of Y-86 and other radiometals for research purposes using a solution target system JF - Nuclear medicine and biology Y1 - 2015 U6 - http://dx.doi.org/10.1016/j.nucmedbio.2015.06.005 SN - 1872-9614 VL - 42 IS - 11 SP - 842 EP - 849 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Scheer, Nico A1 - Kapelyukh, Yury A1 - Rode, Anja A1 - Oswald, Stefan A1 - Busch, Diana A1 - Mclaughlin, Lesley A. A1 - Lin, De A1 - Henderson, Colin J. A1 - Wolf, C. Roland T1 - Defining Human Pathways of Drug Metabolism In Vivo through the Development of a Multiple Humanized Mouse Model JF - Drug Metabolism and Disposition Y1 - 2015 U6 - http://dx.doi.org/10.1124/dmd.115.065656 SN - 1521-009x VL - 43 IS - 11 SP - 1679 EP - 1690 PB - ASPET CY - Bethesda ER - TY - JOUR A1 - Hough, Lindsay B. A1 - Nalwalk, Julia W. A1 - Ding, Xinxin A1 - Scheer, Nico T1 - Opioid Analgesia in P450 Gene Cluster Knockout Mice: A Search for Analgesia-Relevant Isoforms JF - Drug Metabolism and Disposition Y1 - 2015 U6 - http://dx.doi.org/10.1124/dmd.115.065490 SN - 1521-009x VL - 43 IS - 9 SP - 1326 EP - 1330 ER - TY - JOUR A1 - Henderson, Colin J. A1 - Mclaughlin, Lesley A. A1 - Scheer, Nico A1 - Stanley, Lesley A. A1 - Wolf, C. Roland T1 - Cytochrome b5 Is a Major Determinant of Human Cytochrome P450 CYP2D6 and CYP3A4 Activity In Vivo s JF - Molecular Pharmacology Y1 - 2015 U6 - http://dx.doi.org/10.1124/mol.114.097394 SN - 1521-0111 VL - 87 IS - 4 SP - 733 EP - 739 PB - ASPET CY - Bethesda ER - TY - JOUR A1 - Hager, Jonathan A1 - Hentschke, Reinhard A1 - Hojdis, Nils A1 - Karimi-Varzaneh, Hossein Ali T1 - Computer Simulation of Particle–Particle Interaction in a Model Polymer Nanocomposite JF - Macromolecules Y1 - 2015 U6 - http://dx.doi.org/10.1021/acs.macromol.5b01864 SN - 1520-5835 VL - 48 IS - 24 SP - 9039 EP - 9049 ER - TY - JOUR A1 - Winckler, Silvia A1 - Krueger, Rolf A1 - Schnitzler, Thomas A1 - Zang, Werner A1 - Fischer, Rainer A1 - Biselli, Manfred T1 - A sensitive monitoring system for mammalian cell cultivation processes: a PAT approach JF - Bioprocess and biosystems engineering N2 - Biopharmaceuticals such as antibodies are produced in cultivated mammalian cells, which must be monitored to comply with good manufacturing practice. We, therefore, developed a fully automated system comprising a specific exhaust gas analyzer, inline analytics and a corresponding algorithm to precisely determine the oxygen uptake rate, carbon dioxide evolution rate, carbon dioxide transfer rate, transfer quotient and respiratory quotient without interrupting the ongoing cultivation, in order to assess its reproducibility. The system was verified using chemical simulation experiments and was able to measure the respiratory activity of hybridoma cells and DG44 cells (derived from Chinese hamster ovary cells) with satisfactory results at a minimum viable cell density of ~2.0 × 10⁵ cells ml⁻¹. The system was suitable for both batch and fed-batch cultivations in bubble-aerated and membrane-aerated reactors, with and without the control of pH and dissolved oxygen. Y1 - 2014 U6 - http://dx.doi.org/10.1007/s00449-013-1062-8 SN - 1615-7591 (Print) 1615-7605 (Online) VL - 37 IS - 5 SP - 901 EP - 912 PB - Springer CY - Berlin, Heidelberg ER - TY - JOUR A1 - Heinze, Daniel A1 - Mang, Thomas A1 - Peter, Karin A1 - Möller, Martin A1 - Weichold, Oliver T1 - Synthesis of low molecular weight poly(vinyl acetate) and its application as plasticizer JF - Journal of applied polymer science N2 - Poly(vinyl acetate), PVAc, with a degree of polymerization Xn = 10 was prepared by chain-transfer radical polymerization using carbon tetrachloride and used as oligomeric plasticizer for commercial PVAc. However, the chlorinated chain ends cause a low thermal stability requiring mild Cl/H substitution. The product exhibits high thermal stability and excellent melt-compounding properties. Blends of oligomeric and commercial PVAc show single glass transition temperatures which decrease with higher oligomer content and exhibit small negative deviations from Fox' linear additivity rule. This indicates plasticization and miscibility being mainly due to entropic effects. Injection-moulded thick specimens show ductile behaviour at oligomer contents >10 wt %, while sheets with a thickness of 0.2–0.5 mm appear flexible already at 7.5 wt %. The oxygen permeability coefficients are an order of magnitude lower than those of low-density polyethylene. Due to the sum of their properties, the plasticized sheets present a promising alternative in the preparation of barrier materials. Y1 - 2014 U6 - http://dx.doi.org/10.1002/app.40226 SN - 1097-4628 (E-Journal); 0021-8995 (Print) VL - 131 IS - 9 SP - Article No. 40226 PB - Wiley CY - New York ER - TY - JOUR A1 - Wang, Ren-Qi A1 - Druckenmüller, Katharina A1 - Elbers, Gereon A1 - Guenther, Klaus A1 - Croué, Jean-Philippe T1 - Analysis of aquatic-phase natural organic matter by optimized LDI-MS method JF - Journal of mass spectrometry N2 - 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. Y1 - 2014 U6 - http://dx.doi.org/10.1002/jms.3321 SN - 1096-9888 VL - 49 IS - 2 SP - 154 EP - 160 PB - Wiley CY - Bognor Regis ER - TY - JOUR A1 - Heine, A. A1 - Herrmann, G. A1 - Selmer, Thorsten A1 - Terwesten, F. A1 - Buckel, W. A1 - Reuter, K. T1 - High resolution crystal structure of clostridium propionicum β-Alanyl-CoA:Ammonia Lyase, a new member of the "Hot Dog Fold" protein superfamily JF - Proteins N2 - 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 Å as well as in complex with CoA at a resolution of 1.59 Å. 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. Y1 - 2014 U6 - http://dx.doi.org/10.1002/prot.24557 SN - 1097-0134 (E-Journal); 0887-3585 (Print) VL - 82 IS - 9 SP - 2041 EP - 2053 PB - Wiley-Liss CY - New York ER - TY - JOUR A1 - Takenaga, Shoko A1 - Biselli, Manfred A1 - Schnitzler, Thomas A1 - Öhlschläger, Peter A1 - Wagner, Torsten A1 - Schöning, Michael Josef T1 - Toward multi-analyte bioarray sensors: LAPS-based on-chip determination of a Michaelis–Menten-like kinetics for cell culturing JF - Physica status solidi A : Applications and materials science N2 - 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. Y1 - 2014 U6 - http://dx.doi.org/10.1002/pssa.201330464 SN - 1521-396X (E); 1862-6319 (E-Journal); 0031-8965 (Print); 1862-6300 (Print) VL - 211 IS - 6 SP - 1410 EP - 1415 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Whitehead, Mark A1 - Öhlschläger, Peter A1 - Almajhdi, Fahad N. A1 - Alloza, Leonor A1 - Marzábal, Pablo A1 - Meyers, Ann E. A1 - Hitzeroth, Inga I. A1 - Rybicki, Edward P. T1 - Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice JF - BMC cancer Y1 - 2014 U6 - http://dx.doi.org/10.1186/1471-2407-14-367 SN - 1471-2407 IS - 14:367 SP - 1 EP - 15 PB - BioMed Central CY - London ER - TY - JOUR A1 - Küppers, Tobias A1 - Steffen, Victoria A1 - Hellmuth, Hendrik A1 - O'Connell, Timothy A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Wiechert, Wolfgang T1 - Developing a new production host from a blueprint: Bacillus pumilus as an industrial enzyme producer JF - Microbial cell factories Y1 - 2014 U6 - http://dx.doi.org/10.1186/1475-2859-13-46 SN - 1475-2859 (E-Journal) VL - 13 SP - Article No. 46 PB - BioMed Central CY - London ER - TY - JOUR A1 - Guo, Yuanyuan A1 - Miyamoto, Ko-ichiro A1 - Wagner, Torsten A1 - Schöning, Michael Josef A1 - Yoshinobu, Tatsuo T1 - Theoretical study and simulation of light-addressable potentiometric sensors JF - Physica status solidi (A) : applications and materials N2 - 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. Y1 - 2014 U6 - http://dx.doi.org/10.1002/pssa.201330354 SN - 0031-8965 VL - 211 IS - 6 SP - 1467 EP - 1472 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Ratke, Lorenz A1 - Milow, Barbara A1 - Lisinski, Susanne A1 - Hoepfner, Sandra T1 - On an effect of fine ceramic particles on the structure of aerogels JF - Microgravity science and technology Y1 - 2014 U6 - http://dx.doi.org/10.1007/s12217-014-9380-2 SN - 0938-0108 ; 1875-0494 VL - 26 SP - 103 EP - 110 PB - Springer Nature CY - Heidelberg ER - TY - JOUR A1 - Handtke, Stefan A1 - Volland, Sonja A1 - Methling, Karen A1 - Albrecht, Dirk A1 - Becher, Dörte A1 - Nehls, Jenny A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Lalk, Michael A1 - Liesegang, Heiko A1 - Voigt, Birgit A1 - Daniel, Rolf A1 - Hecker, Michael T1 - Cell physiology of the biotechnological relevant bacterium Bacillus pumilus - An omics-based approach JF - Journal of Biotechnology N2 - 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. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.jbiotec.2014.08.028 SN - 1873-4863 (E-Journal); 0168-1656 (Print) IS - 192(A) SP - 204 EP - 214 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Nachtrodt, Frederik A1 - Tietsch, Wolfgang A1 - Mostacci, Domiziano A1 - Scherer, Ulrich W. T1 - Set-up and first operation of a plasma oven for treatment of low level radioactive wastes JF - Nuclear technology and radiation protection Y1 - 2014 U6 - http://dx.doi.org/10.2298/NTRP140SS47N SN - 1451-3994 VL - 29 IS - Suppl. SP - 47 EP - 51 PB - VINČA Institute of Nuclear Sciences CY - Belgrad ER - TY - JOUR A1 - Raue, Markus A1 - Wambach, M. A1 - Glöggler, S. A1 - Grefen, Dana A1 - Kaufmann, R. A1 - Abetz, C. A1 - Georgopanos, P. A1 - Handge, U. A. A1 - Mang, Thomas A1 - Blümich, B. A1 - Abetz, V. T1 - Investigation of historical hard rubber ornaments of Charles Goodyear JF - Macromolecular chemistry and physics Y1 - 2014 SN - 1022-1352 VL - Vol. 215 IS - No. 3 SP - 245 EP - 254 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Pasteur, Aline A1 - Tippkötter, Nils A1 - Kampeis, Percy A1 - Ulber, Roland T1 - Optimization of high gradient magnetic separation filter units for the purification of fermentation products JF - IEEE TRANSACTIONS ON MAGNETICS N2 - High gradient magnetic separation (HGMS) has been established since the early 1970s. A more recent application of these systems is the use in bioprocesses. To integrate the HGMS in a fermentation process, it is necessary to optimize the separation matrix with regard to the magnetic separation characteristics and permeability of the non-magnetizable components of the fermentation broth. As part of the work presented here, a combined fluidic and magnetic force finite element model simulation was created using the software COMSOL Multiphysics and compared with separation experiments. Finally, as optimal lattice orientation of the separation matrix, a transversal rhombohedral arrangement was defined. The high suitability of the new filter matrix has been verified by separation experiments. Y1 - 2014 U6 - http://dx.doi.org/10.1109/TMAG.2014.2325535 SN - 0018-9464 N1 - Article Sequence Number: 5000607 INSPEC Accession Number: 14663042 VL - 50 IS - 10 SP - Artikel 5000607 PB - IEEE CY - New York, NY ER - TY - JOUR A1 - Tippkötter, Nils A1 - Wollny, Steffen A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Ruf, Friedrich A1 - Ulber, Roland T1 - Recycling of spent oil bleaching earth as source of glycerol for the anaerobic production of acetone, butanol, and ethanol with Clostridium diolis and lipolytic Clostridium lundense JF - Engineering in Life Sciences N2 - A major part of edible oil is subjected to bleaching procedures, primarily with minerals applied as adsorbers. Their recycling is currently done either by regaining the oil via organic solvent extraction or by using the spent bleaching earth (SBE) as additive for animal feed, etc. As a new method, the reutilization of the by-product SBE for the microbiologic formation of acetone, butanol, and ethanol (ABE) is presented as proof-of-concept. The SBE was taken from a palm oil cleaning process. The recycling concept is based on the application of lipolytic clostridia strains. Due to considerably long fermentation times, co-fermentation with Candida rugosa and enzymatic hydrolyses of the bound oil with a subsequent clostridia fermentation are shown as alternative routes. Anaerobic fermentations under comparison of different clostridia strains were performed with glycerol media, enzymatically hydrolyzed palm oil and SBE. Solutes, side product compositions and productivities were quantified via HPLC. A successful production of ABE solutes from SBE has been done with a yield of 0.15 g butanol per gram of bound glycerol. Thus, the biotechnological recycling of the waste stream is possible in principle. Inhibition of the substrate suspension has been observed. A chromatographic ion-exchange of substrates increased the biomass concentration. Y1 - 2014 U6 - http://dx.doi.org/10.1002/elsc.201300113 SN - 1618-2863 VL - 14 IS - 4 SP - 425 EP - 432 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Al-Kaidy, Huschyar A1 - Duwe, Anna A1 - Huster, Manuel A1 - Muffler, Kai A1 - Schlegel, Christin A1 - Sieker, Tim A1 - Stadtmüller, Ralf A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Biotechnologie und Bioverfahrenstechnik – Vom ersten Ullmanns Artikel bis hin zu aktuellen Forschungsthemen JF - Chemie Ingenieur Technik N2 - Biotechnologie und die mit ihr verbundenen technischen Prozesse prägen seit Jahrtausenden die Entwicklung der Menschheit. Ausgehend von empirischen Verfahren, insbesondere zur Herstellung von Lebensmitteln und täglichen Gebrauchsgütern, haben sich diese Disziplinen zu einem der innovativsten Zukunftsfelder entwickelt. Durch das immer detailliertere Verständnis zellulärer Vorgänge können mittlerweile Produktionsstämme gezielt optimiert werden. Im Zusammenspiel mit moderner Prozesstechnik können so eine Vielzahl von Bulk- und Feinchemikalien sowie Pharmazeutika effizient hergestellt werden. In diesem Artikel werden exemplarisch einige der aktuellen Trends vorgestellt. Y1 - 2014 U6 - http://dx.doi.org/10.1002/cite.201400083 SN - 0009-286X VL - 86 IS - 12 SP - 2215 EP - 2225 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Wiesen, Sebastian A1 - Tippkötter, Nils A1 - Muffler, Kai A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Ruf, Nils A1 - Ulber, Roland T1 - Adsorptive Vorbehandlung von Rohglycerin für die 1,3-Propandiol Fermentation mit Clostridium diolis JF - Chemie Ingenieur Technik N2 - Bei der Gewinnung von Fettsäuren aus Pflanzenölen, z. B. zur Herstellung von Biopolymeren, oder bei der Biodiesel- und Seifenproduktion, fällt Glycerin als Nebenprodukt an. Bei der Biokonversion dieses Rohstoffes zu 1,3-Propandiol wird der Produktionsorganismus Clostridium diolis durch Verunreinigungen im Rohglycerin gehemmt. Als inhibierende Substanzen konnten freie Fettsäuren identifiziert werden. Mithilfe eines adsorptiven Aufarbeitungsverfahrens ist es gelungen, die Fettsäuren zu entfernen und die Konversionseffizienz zu 1,3-Propandiol zu erhöhen. Y1 - 2014 U6 - http://dx.doi.org/10.1002/cite.201300080 N1 - Englischer Titel: Adsorptive Pretreatment of Crude Glycerol Prior to Fermentation to 1,3-Propanediole by Clostridium Diolis VL - 86 IS - 1-2 SP - 129 EP - 135 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Tippkötter, Nils A1 - Duwe, Anna-Maria A1 - Wiesen, Sebastian A1 - Sieker, Tim A1 - Ulber, Roland T1 - Enzymatic hydrolysis of beech wood lignocellulose at high solid contents and its utilization as substrate for the production of biobutanol and dicarboxylic acids JF - Bioresource Technology N2 - The development of a cost-effective hydrolysis for crude cellulose is an essential part of biorefinery developments. To establish such high solid hydrolysis, a new solid state reactor with static mixing is used. However, concentrations >10% (w/w) cause a rate and yield reduction of enzymatic hydrolysis. By optimizing the synergetic activity of cellulolytic enzymes at solid concentrations of 9%, 17% and 23% (w/w) of crude Organosolv cellulose, glucose concentrations of 57, 113 and 152 g L⁻¹ are reached. However, the glucose yield decreases from 0.81 to 0.72gg⁻¹ at 17% (w/w). Optimal conditions for hydrolysis scale-up under minimal enzyme addition are identified. As result, at 23% (w/w) crude cellulose the glucose yield increases from 0.29 to 0.49gg⁻¹. As proof of its applicability, biobutanol, succinic and itaconic acid are produced with the crude hydrolysate. The potential of the substrate is proven e.g. by a high butanol yield of 0.33gg⁻¹. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.biortech.2014.06.052 VL - 167 SP - 447 EP - 455 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Hoehr, Cornelia A1 - Paulßen, Elisabeth A1 - Benard, Francois A1 - Lee, Chris Jaeil A1 - Hou, Xinchi A1 - Badesso, Brian A1 - Ferguson, Simon A1 - Miao, Qing A1 - Yang, Hua A1 - Buckley, Ken A1 - Hanemaayer, Victoire A1 - Zeisler, Stefan A1 - Ruth, Thomas A1 - Celler, Anna A1 - Schaffer, Paul T1 - ⁴⁴ᶢSc production using a water target on a 13 MeV cyclotron JF - Nuclear medicine and biology N2 - Access to promising radiometals as isotopes for novel molecular imaging agents requires that they are routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for the metal of interest is necessary, both of which can introduce significant hurdles in development of less common isotopes. Herein, we describe the production of ⁴⁴Sc (t₁⸝₂ = 3.97 h, Eavg,β⁺ = 1.47 MeV, branching ratio = 94.27%) in a solution target and an automated loading system which allows a quick turn-around between different radiometallic isotopes and therefore greatly improves their availability for tracer development. Experimental yields are compared to theoretical calculations. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.nucmedbio.2013.12.016 SN - 1872-9614 VL - 41 IS - 5 SP - 401 EP - 406 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Luisier, Raphaëlle A1 - Lempiäinen, Harri A1 - Scherbichler, Nina A1 - Braeuning, Albert A1 - Geissler, Miriam A1 - Dubost, Valerie A1 - Müller, Arne A1 - Scheer, Nico A1 - Chibout, Salah-Dine A1 - Hara, Hisanori A1 - Picard, Frank A1 - Theil, Diethilde A1 - Couttet, Philippe A1 - Vitobello, Antonio A1 - Grenet, Olivier A1 - Grasl-Kraupp, Bettina A1 - Ellinger-Ziegelbauer, Heidrung A1 - Thomson, John P. A1 - Meehan, Richard R. A1 - Elcombe, Clifford R. A1 - Henderson, Colin J. A1 - Wolf, C. Roland A1 - Schwarz, Michael A1 - Moulin, Pierre A1 - Terranova, Remi A1 - Moggs, Jonathan G. T1 - Phenobarbital Induces Cell Cycle Transcriptional Responses in Mouse Liver Humanized for Constitutive Androstane and Pregnane X Receptors JF - Toxicological Sciences N2 - The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARᴷᴼ-PXRᴷᴼ), double humanized CAR and PXR (CARʰ-PXRʰ), and wild-type C57BL/6 mice. Wild-type and CARʰ-PXRʰ mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CARᴷᴼ-PXRᴷᴼ mouse livers and largely reversible in wild-type and CARʰ-PXRʰ mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARʰ-PXRʰ mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB. Y1 - 2014 U6 - http://dx.doi.org/https://doi.org/10.1093/toxsci/kfu038 SN - 1094-2025 VL - 139 IS - 2 SP - 501 EP - 511 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Salpati, Laurent A1 - Chu, Xiaoyan A1 - Chen, Liangfu A1 - Prasad, Bhagwat A1 - Dallas, Shannon A1 - Evers, Raymond A1 - Mamaril-Fishman, Donna A1 - Geier, Ethan G. A1 - Kehler, Jonathan A1 - Kunta, Jeevan A1 - Mezler, Mario A1 - Laplanche, Loic A1 - Pang, Jodie A1 - Soars, Matthew G. A1 - Unadkat, Jashvant D. A1 - van Waterschoot, Robert A.B. A1 - Yabut, Jocelyn A1 - Schinkel, Alfred H. A1 - Scheer, Nico A1 - Rode, Anja T1 - Evaluation of organic anion transporting polypeptide 1B1 and 1B3 humanized mice as a translational model to study the pharmacokinetics of statins JF - Drug Metabolism and Disposition N2 - Organic anion transporting polypeptide (Oatp) 1a/1b knockout and OATP1B1 and -1B3 humanized mouse models are promising tools for studying the roles of these transporters in drug disposition. Detailed characterization of these models will help to better understand their utility for predicting clinical outcomes. To advance this approach, we carried out a comprehensive analysis of these mouse lines by evaluating the compensatory changes in mRNA expression, quantifying the amounts of OATP1B1 and -1B3 protein by liquid chromatography–tandem mass spectrometry, and studying the active uptake in isolated hepatocytes and the pharmacokinetics of some prototypical substrates including statins. Major outcomes from these studies were 1) mostly moderate compensatory changes in only a few genes involved in drug metabolism and disposition, 2) a robust hepatic expression of OATP1B1 and -1B3 proteins in the respective humanized mouse models, and 3) functional activities of the human transporters in hepatocytes isolated from the humanized models with several substrates tested in vitro and with pravastatin in vivo. However, the expression of OATP1B1 and -1B3 in the humanized models did not significantly alter liver or plasma concentrations of rosuvastatin and pitavastatin compared with Oatp1a/1b knockout controls under the conditions used in our studies. Hence, although the humanized OATP1B1 and -1B3 mice showed in vitro and/or in vivo functional activity with some statins, further characterization of these models is required to define their potential use and limitations in the prediction of drug disposition and drug-drug interactions in humans. Y1 - 2014 U6 - http://dx.doi.org/10.1124/dmd.114.057976 SN - 1521-009X VL - 42 IS - 8 SP - 1301 EP - 1313 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Scheer, Nico A1 - Mclaughlin, Lesley A. A1 - Rode, Anja A1 - MacLeod, Alastair Kenneth A1 - Henderson, Colin J. A1 - Wolf, Roland C. T1 - Deletion of thirty murine cytochrome P450 genes results in viable mice with compromised drug metabolism JF - Drug Metabolism and Disposition N2 - 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. Y1 - 2014 U6 - http://dx.doi.org/10.1124/dmd.114.057885 SN - 1521-009X VL - 42 IS - 6 SP - 1022 EP - 1030 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications JF - Xenobiotica N2 - 1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug–drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described. 2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created. 3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug–drug interactions as well as in human metabolite testing and risk assessment. 4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed. KW - transporters KW - human metabolites KW - drug metabolising enzymes KW - drug–drug interactions KW - bioavailability Y1 - 2014 U6 - http://dx.doi.org/10.3109/00498254.2013.815831 SN - 1366-5928 VL - 44 IS - 2 SP - 96 EP - 108 PB - Taylor & Francis CY - Abingdon ER - TY - JOUR A1 - Hentschke, Reinhard A1 - Hager, Jonathan A1 - Hojdis, Nils T1 - Molecular Modeling Approach to the Prediction of Mechanical Properties of Silica-Reinforced Rubbers JF - Journal of Applied Polymer Science N2 - 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. KW - theory and modeling KW - supramolecular structures KW - rubber KW - mechanical properties KW - elastomers Y1 - 2014 U6 - http://dx.doi.org/10.1002/app.40806 SN - 1097-4628 VL - 131 IS - 18 SP - 1 EP - 9 PB - Wiley CY - New York, NY ER - TY - JOUR A1 - Schroeter, Rebecca A1 - Hoffmann, Tamara A1 - Voigt, Birgit A1 - Meyer, Hanna A1 - Bleisteiner, Monika A1 - Muntel, Jan A1 - Jürgen, Britta A1 - Albrecht, Dirk A1 - Becher, Dörte A1 - Lalk, Michael A1 - Evers, Stefan A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Putzer, Harald A1 - Hecker, Michael A1 - Schweder, Thomas A1 - Bremer, Erhard T1 - Stress responses of the industrial workhorse Bacillus licheniformis to osmotic challenges JF - PLoS ONE N2 - 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. Y1 - 2014 U6 - http://dx.doi.org/10.1371/journal.pone.0080956 SN - 1932-6203 VL - 8 IS - 11 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Handtke, Stefan A1 - Schroeter, Rebecca A1 - Jürgen, Britta A1 - Methling, Karen A1 - Schlüter, Rabea A1 - Albrecht, Dirk A1 - Hijum, Sacha A. F. T. van A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Lalk, Michael A1 - Schweder, Thomas A1 - Hecker, Michael A1 - Voigt, Birgit T1 - Bacillus pumilus reveals a remarkably high resistance to hydrogen peroxide provoked oxidative stress JF - PLOS one N2 - Bacillus pumilus is characterized by a higher oxidative stress resistance than other comparable industrially relevant Bacilli such as B. subtilis or B. licheniformis. In this study the response of B. pumilus to oxidative stress was investigated during a treatment with high concentrations of hydrogen peroxide at the proteome, transcriptome and metabolome level. Genes/proteins belonging to regulons, which are known to have important functions in the oxidative stress response of other organisms, were found to be upregulated, such as the Fur, Spx, SOS or CtsR regulon. Strikingly, parts of the fundamental PerR regulon responding to peroxide stress in B. subtilis are not encoded in the B. pumilus genome. Thus, B. pumilus misses the catalase KatA, the DNA-protection protein MrgA or the alkyl hydroperoxide reductase AhpCF. Data of this study suggests that the catalase KatX2 takes over the function of the missing KatA in the oxidative stress response of B. pumilus. The genome-wide expression analysis revealed an induction of bacillithiol (Cys-GlcN-malate, BSH) relevant genes. An analysis of the intracellular metabolites detected high intracellular levels of this protective metabolite, which indicates the importance of bacillithiol in the peroxide stress resistance of B. pumilus. Y1 - 2014 U6 - http://dx.doi.org/10.1371/journal.pone.0085625 SN - 1932-6203 VL - 9 IS - 1 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Schiffels, Johannes A1 - Pinkenburg, Olaf A1 - Schelden, Maximilian A1 - Aboulnaga, El-Hussiny A. A. A1 - Baumann, Marcus A1 - Selmer, Thorsten T1 - An innovative cloning platform enables large-scale production and maturation of an oxygen-tolerant [NiFe]-hydrogenase from cupriavidus necator in Escherichia coli JF - PLOS one. 2013 Y1 - 2013 U6 - http://dx.doi.org/10.1371/journal.pone.0068812 SN - 1932-6203 PB - Public Library of Science CY - San Francisco, California ER - TY - JOUR A1 - Abulnaga, El-Hussiny A1 - Pinkenburg, Olaf A1 - Schiffels, Johannes A1 - E-Refai, Ahmed A1 - Buckel, Wolfgang A1 - Selmer, Thorsten T1 - Effect of an Oxygen-Tolerant Bifurcating Butyryl Coenzyme A Dehydrogenase/Electron-Transferring Flavoprotein Complex from Clostridium difficile on Butyrate Production in Escherichia coli JF - Journal of bacteriology Y1 - 2013 SN - 1098-5530 [E-Journal] SN - 0021-9193 [Print] VL - 195 IS - 16 SP - 3704 EP - 3713 ER - TY - JOUR A1 - Aboulnaga, E. H. A1 - Pinkenburg, O. A1 - Schiffels, Johannes A1 - El-Refai, A. A1 - Buckel, W. A1 - Selmer, Thorsten T1 - Butyrate production in Escherichia coli: Exploitation of an oxygen tolerant bifurcating butyryl-CoA dehydrogenase/electron transferring flavoprotein complex from Clostridium difficile JF - Journal of bacteriology. June 14, 2013 Y1 - 2013 SN - 1098-5530 (E-Journal) ; 0021-9193 (Print) SP - Epub ahead of print ER -