TY - JOUR A1 - Gebeshuber, Christoph A. A1 - Kornauth, Christoph A1 - Dong, Lihua A1 - Sierig, Ralph A1 - Seibler, Jost A1 - Reiss, Martina A1 - Tauber, Stefanie A1 - Bilban, Martin A1 - Wang, Shijun A1 - Kain, Renate A1 - Böhmig, Georg A. A1 - Moeller, Marcus J. A1 - Gröne, Hermann-Josef A1 - Englert, Christoph A1 - Martinez, Javier A1 - Kerjaschki, Dontscho T1 - Focal segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1 JF - Nature Medicine Y1 - 2013 U6 - http://dx.doi.org/10.1038/nm.3142 SN - 1078-8956 VL - 19 IS - 4 SP - 481 EP - 487 ER - TY - JOUR A1 - Kornfeld, Jan-Wilhelm A1 - Baitzel, Catherina A1 - Könner, A. Christine A1 - Nicholls, Hayley T. A1 - Vogt, Merly C. A1 - Herrmanns, Karolin A1 - Scheja, Ludger A1 - Haumaitre, Cécile A1 - Wolf, Anna M. A1 - Knippschild, Uwe A1 - Seibler, Jost A1 - Cereghini, Silvia A1 - Heeren, Joerg A1 - Stoffel, Markus A1 - Brüning, Jens C. T1 - Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b JF - Nature Y1 - 2013 SN - 0028-0836 U6 - http://dx.doi.org/10.1038/nature11793 VL - 494 IS - 7435 SP - 111 EP - 115 PB - Springer Nature CY - Cham ER - TY - JOUR A1 - Wiegand, Sandra A1 - Voigt, Birgit A1 - Albrecht, Dirk A1 - Bongaerts, Johannes A1 - Evers, Stefan A1 - Hecker, Michael A1 - Daniel, Rolf A1 - Liesegang, Heiko T1 - Fermentation stage-dependent adaptations of Bacillus licheniformis during enzyme production JF - Microbial Cell Factories Y1 - 2013 U6 - http://dx.doi.org/10.1186/1475-2859-12-120 SN - 1475-2859 VL - 12 SP - 120 PB - Biomed Central CY - London ER - TY - JOUR A1 - Thiel, Alexander A1 - Tippkötter, Nils A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Ruf, Friedrich A1 - Ulber, Roland T1 - New zeolite adsorbents for downstream processing of polyphenols from renewable resources JF - Engineering in Life Sciences N2 - Commercial materials with polyvinylpolypyrrolidone and polymeric amberlites (XAD7HP, XAD16) are commonly used for the adsorptive downstream processing of polyphenols from renewable resources. In this study, beta-zeolite-based adsorbent systems were examined, and their properties were compared to organic resins. Batch adsorption experiments were conducted with synthetic solutions of major polyphenols. Adsorption isotherms and desorption characteristics of individual adsorbent were determined based on these results. Maximum adsorption capacities were calculated using the Langmuir model. For example, the zeolites had capacities up to 203.2 mg/g for ferulic acid. To extend these results to a complex system, additional experiments were performed on rapeseed meal and wheat seed extracts as representative renewable resources. HPLC analysis showed that with 7.5% w/v, which is regarded as the optimum amount of zeolites, zeolites A and B could bind 100% of the major polyphenols as well as release polyphenols at high yields. Additionally, regeneration experiments were performed with isopropyl alcohol at 99°C to evaluate how zeolites regenerate under mild conditions. The results showed only a negligible loss of adsorption capacity and no loss of desorption capacity. In summary, it was concluded that beta-zeolites were promising adsorbents for developing new processes to isolate polyphenols from renewable resources. Y1 - 2013 U6 - http://dx.doi.org/10.1002/elsc.201200188 VL - 13 IS - 3 SP - 239 EP - 246 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Tippkötter, Nils A1 - Al-Kaidy, Huschyar A1 - Wollny, Steffen A1 - Ulber, Roland T1 - Functionalized magnetizable particles for downstream processing in single-use systems JF - Chemie Ingenieur Technik N2 - Biotechnological downstream processing is usually an elaborate procedure, requiring a multitude of unit operations to isolate the target component. Besides the disadvantageous space-time yield, the risks of cross-contaminations and product loss grow fast with the complexity of the isolation procedure. A significant reduction of unit operations can be achieved by application of magnetic particles, especially if these are functionalized with affinity ligands. As magnetic susceptible materials are highly uncommon in biotechnological processes, target binding and selective separation of such particles from fermentation or reactions broths can be done in a single step. Since the magnetizable particles can be produced from iron salts and low priced polymers, a single-use implementation of these systems is highly conceivable. In this article, the principles of magnetizable particles, their synthesis and functionalization are explained. Furthermore, applications in the area of reaction engineering, microfluidics and downstream processing are discussed focusing on established single-use technologies and development potential. Y1 - 2013 U6 - http://dx.doi.org/10.1002/cite.201200130 VL - 85 IS - 1-2: Special Issue: Single-Use Technology SP - 76 EP - 86 PB - Wiley CY - Weinheim ER - TY - PAT A1 - Al-Kaidy, Huschyar A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - A system and a method for the implementation of chemical, biological or physical reactions [Europäische Patentanmeldung] N2 - The invention relates to a system for the implementation of chemical, biological or physical reactions, consisting of - one or more magnetic micro-reactors, each comprising a shell made of hydrophobic magnetic nanoparticles encapsulating an aqueous core, - a plane platform comprising a surface to receive the micro-reactors, - a source that generates a magnetic field above or underneath the platform for manipulating the one or more hydrophobic magnetic micro-reactors, or for moving them along the surface of the platform from one position to another position, characterized in that the aqueous core of the one or more magnetic micro-reactors contains a reaction solution or buffer, and wherein the magnetic field generated by the source correlates to a defined position on the surface of the platform. Y1 - 2013 PB - Europäisches Patentamt CY - Den Hague ER - TY - PAT A1 - Stadtmüller, Ralf A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - A method for production of single-stranded nucleic acids [Europäische Patentanmeldung] Y1 - 2013 PB - Europäisches Patentamt CY - Den Hague ER - TY - JOUR A1 - Pellegrini, Paul A. A1 - Howell, Nicholas R. A1 - Shepherd, Rachael K. A1 - Lengkeek, Nigel A. A1 - Paulßen, Elisabeth A1 - Katsifis, Andrew G. A1 - Greguric, Ivan T1 - Synthesis and Radiolabelling of DOTA-Linked Glutamine Analogues with 67,68Ga as Markers for Increased Glutamine Metabolism in Tumour Cells JF - Molecules Y1 - 2013 U6 - http://dx.doi.org/10.3390/molecules18067160 SN - 1420-3049 VL - 18 IS - 6 SP - 7160 EP - 7178 PB - MDPI CY - Basel ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Le, Van So A1 - Lengkeek, Nigel A1 - Pellegrini, Paul A1 - Jackson, Tim A1 - Greguric, Ivan A1 - Weiner, Ron T1 - Influence of Metal Ions on the 68Ga-labeling of DOTATATE JF - Applied Radiation and Isotopes Y1 - 2013 U6 - http://dx.doi.org/10.1016/j.apradiso.2013.08.010 SN - 1872-9800 VL - 82 SP - 232 EP - 238 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Xenobiotic receptor humanized mice and their utility JF - Drug Metabolism Reviews Y1 - 2013 U6 - http://dx.doi.org/10.3109/03602532.2012.738687 SN - 1097-9883 IS - 1 SP - 110 EP - 121 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Huck, Christina A1 - Schiffels, Johannes A1 - Herrera, Cony N. A1 - Schelden, Maximilian A1 - Selmer, Thorsten A1 - Poghossian, Arshak A1 - Baumann, Marcus A1 - Wagner, Patrick A1 - Schöning, Michael Josef T1 - Metabolic responses of Escherichia coli upon glucose pulses captured by a capacitive field-effect sensor JF - Physica Status Solidi (A) N2 - Living cells are complex biological systems transforming metabolites taken up from the surrounding medium. Monitoring the responses of such cells to certain substrate concentrations is a challenging task and offers possibilities to gain insight into the vitality of a community influenced by the growth environment. Cell-based sensors represent a promising platform for monitoring the metabolic activity and thus, the “welfare” of relevant organisms. In the present study, metabolic responses of the model bacterium Escherichia coli in suspension, layered onto a capacitive field-effect structure, were examined to pulses of glucose in the concentration range between 0.05 and 2 mM. It was found that acidification of the surrounding medium takes place immediately after glucose addition and follows Michaelis–Menten kinetic behavior as a function of the glucose concentration. In future, the presented setup can, therefore, be used to study substrate specificities on the enzymatic level and may as well be used to perform investigations of more complex metabolic responses. Conclusions and perspectives highlighting this system are discussed. Y1 - 2013 U6 - http://dx.doi.org/10.1002/pssa.201200900 SN - 0031-8965 VL - 210 IS - 5 SP - 926 EP - 931 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Bäcker, Matthias A1 - Rakowski, D. A1 - Poghossian, Arshak A1 - Biselli, Manfred A1 - Wagner, Patrick A1 - Schöning, Michael Josef T1 - Chip-based amperometric enzyme sensor system for monitoring of bioprocesses by flow-injection analysis JF - Journal of Biotechnology N2 - A microfluidic chip integrating amperometric enzyme sensors for the detection of glucose, glutamate and glutamine in cell-culture fermentation processes has been developed. The enzymes glucose oxidase, glutamate oxidase and glutaminase were immobilized by means of cross-linking with glutaraldehyde on platinum thin-film electrodes integrated within a microfluidic channel. The biosensor chip was coupled to a flow-injection analysis system for electrochemical characterization of the sensors. The sensors have been characterized in terms of sensitivity, linear working range and detection limit. The sensitivity evaluated from the respective peak areas was 1.47, 3.68 and 0.28 μAs/mM for the glucose, glutamate and glutamine sensor, respectively. The calibration curves were linear up to a concentration of 20 mM glucose and glutamine and up to 10 mM for glutamate. The lower detection limit amounted to be 0.05 mM for the glucose and glutamate sensor, respectively, and 0.1 mM for the glutamine sensor. Experiments in cell-culture medium have demonstrated a good correlation between the glutamate, glutamine and glucose concentrations measured with the chip-based biosensors in a differential-mode and the commercially available instrumentation. The obtained results demonstrate the feasibility of the realized microfluidic biosensor chip for monitoring of bioprocesses. Y1 - 2013 U6 - http://dx.doi.org/10.1016/j.jbiotec.2012.03.014 SN - 0168-1656 VL - 163 IS - 4 SP - 371 EP - 376 PB - Elsevier CY - Amsterdam 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 -