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 - Kroll-Ludwigs, Kathrin A1 - Kaesling, Katharina T1 - Family Law and Culture in Europe: Developments, Challenges and Opportunities – Konferenz der Commission on European Family Law vom 29.-31. August 2013, Bonn JF - Zeitschrift für Europäisches Privatrecht (ZEuP) N2 - Vor dem Hintergrund zunehmender gesellschaftlicher Veränderungen bei den Lebens- und Familienformen hat es sich die Commission on European Family Law (CEFL) seit 2001 zum Ziel gesetzt, unverbindliche Regelungsvorschläge für ein europaweit einheitliches Familienrecht zu schaffen. Die Vorstellung und Diskussion dieser auf rechtsvergleichender Basis erstellten Principles erfolgt auf den regelmäßig veranstalteten Tagungen der CEFL. Die nunmehr fünfte Konferenz zum Thema „Family Law and Culture in Europe – Developments, Challenges and Opportunities“ fand erstmals in Deutschland statt. Ausgerichtet wurde die Veranstaltung, zu der ca. 200 Teilnehmerinnen und Teilnehmern aus Wissenschaft und Praxis aus insgesamt 33 Ländern angereist waren, von Nina Dethloff (Direktorin des Instituts für Deutsches, Europäisches und Internationales Familienrecht an der Universität Bonn), Katharina Boele-Woelki (Direktorin des Utrecht Centre for European Research into Family Law und Preisträgerin des Anneliese Maier-Forschungspreises der Alexander von Humboldt-Stiftung) und Werner Gephart (Direktor des Käte Hamburger Kollegs „Recht als Kultur“). Y1 - 2014 SN - 0943-3929 IS - 3 SP - 673 EP - 676 PB - Beck CY - München ER - TY - JOUR A1 - Bernecker, Andreas T1 - Do politicians shirk when reelection is certain? Evidence from the German parliament JF - European Journal of Political Economy N2 - Does stiffer electoral competition reduce political shirking? For a micro-analysis of this question, I construct a new data set spanning the years 2005 to 2012 covering biographical and political information about German Members of Parliament (MPs), including their attendance rates in voting sessions. For the parliament elected in 2009, I show that indeed opposition party MPs who expect to face a close race in their district show significantly and relevantly lower absence rates in parliament beforehand. MPs of governing parties seem not to react significantly to electoral competition. These results are confirmed by an analysis of the parliament elected in 2005, by several robustness checks, and also by employing an instrumental variable strategy exploiting convenient peculiarities of the German electoral system. The study also shows how MPs elected via party lists react to different levels of electoral competition. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.ejpoleco.2014.07.001 SN - 0176-2680 VL - 36 SP - 55 EP - 70 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Bernecker, Andreas T1 - Divided Government and the Adoption of Economic Reforms JF - CESifo DICE Report - Journal for Institutional Comparison Y1 - 2014 SN - 1612-0663 VL - 12 IS - 4 SP - 47 EP - 52 PB - Ifo Institute for Economic Research CY - München 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 - Akimbekov, N. Sh. A1 - Digel, Ilya A1 - Zhubanova, A. A. T1 - Advantages of creation of e-books in training of specialists biologists and biotechnologists JF - KazNU Bulletin. Biology series. N2 - The necessity of e-books as a primary of learning, its opportunities for realization of competence during training biologist and biotechnologist specialists are determined. Definitions and requirements to the e-books, its advantages in comparison with traditional textbooks, and the ways of creation of e-books in the SunRav BookEditor program are considered. KW - SunRav BookEditor KW - softs KW - distance learning KW - e-issues KW - e-books Y1 - 2014 SN - 1563-0218 VL - 60 IS - 1 SP - 249 EP - 252 PB - Al-Farabi Kazakh National University CY - Almaty ER - TY - JOUR A1 - Akimbekov, N.Sh. A1 - Digel, Ilya A1 - O´Heras, C. A1 - Tastambek, K.T. A1 - Savitskaya, I.S. A1 - Ualyeva, P.S. A1 - Mansurov, Z.A. A1 - Zhubanova, A.A. T1 - Adsorption of bacterial lipopolysaccharides on carbonized rice husks obtained in the batch experiments JF - Experimental Biology N2 - The scope of this study is the measurement of endotoxin adsorption rate for carbonized rice husk. It showed good adsorption properties for LPS. During the batch experiments, several techniques were used and optimized for improving the material’s adsorption behavior. Also, with the results obtained it was possible to differentiate the materials according to their adsorption capacity and kinetic characteristics. KW - surface modification KW - adsorption KW - carbonized rice husk KW - lipopolysaccharide Y1 - 2014 SN - 1563-0218 N1 - Original in russischer Sprache VL - 60 IS - 1/2 SP - 144 EP - 148 PB - Al-Farabi Kazakh National University CY - Almaty 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 - Poghossian, Arshak A1 - Schöning, Michael Josef T1 - Label-free sensing of biomolecules with field-effect devices for clinical applications JF - Electroanalysis N2 - Among the variety of transducer concepts proposed for label-free detection of biomolecules, the semiconductor field-effect device (FED) is one of the most attractive platforms. As medical techniques continue to progress towards diagnostic and therapies based on biomarkers, the ability of FEDs for a label-free, fast and real-time detection of multiple pathogenic and physiologically relevant molecules with high specificity and sensitivity offers very promising prospects for their application in point-of-care and personalized medicine for an early diagnosis and treatment of diseases. The presented paper reviews recent advances and current trends in research and development of different FEDs for label-free, direct electrical detection of charged biomolecules by their intrinsic molecular charge. The authors are mainly focusing on the detection of the DNA hybridization event, antibody-antigen affinity reaction as well as clinically relevant biomolecules such as cardiac and cancer biomarkers. Y1 - 2014 U6 - http://dx.doi.org/10.1002/elan.201400073 SN - 1521-4109 (E-Journal); 1040-0397 (Print) VL - 26 IS - 6 SP - 1197 EP - 1213 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Oberländer, Jan A1 - Kirchner, Patrick A1 - Boyen, Hans-Gerd A1 - Schöning, Michael Josef T1 - Detection of hydrogen peroxide vapor by use of manganese(IV) oxide as catalyst for calorimetric gas sensors JF - Physica status solidi A: Applications and materials science N2 - In this work, the catalyst manganese(IV) oxide (MnO2), of calorimetric gas sensors (to monitor the sterilization agent vaporized hydrogen peroxide) has been investigated in more detail. Chemical analyses by means of X-ray-induced photoelectron spectroscopy have been performed to unravel the surface chemistry prior and after exposure to hydrogen peroxide vapor at elevated temperature, as applied in the sterilization processes of beverage cartons. The surface characterization reveals a change in oxidation states of the metal oxide catalyst after exposure to hydrogen peroxide. Additionally, a cleaning effect of the catalyst, which itself is attached to the sensor surface by means of a polymer interlayer, could be observed. Y1 - 2014 U6 - http://dx.doi.org/10.1002/pssa.201330359 SN - 1521-396X (E-Journal); 1862-6319 (E-Journal); 0031-8965 (Print); 1862-6300 (Print) VL - 211 IS - 6 SP - 1372 EP - 1376 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Butenweg, Christoph A1 - Schmitt, T. A1 - Rosen, B. T1 - Seismische Einwirkungen auf erdverlegte Rohrleitungen JF - Bauingenieur N2 - Die erdbebensichere Auslegung von erdverlegten Rohrleitungssystemen ist von wesentlicher Bedeutung zur Sicherstellung der Funktionalität der Versorgungsinfrastruktur nach einem Erdbebenereignis. Zur Vermeidung von Netzausfällen ist es erforderlich, die räumlich weit ausgedehnten Leitungssysteme mit geeigneten rechnerischen Modellen seismisch zu bemessen. Der vorliegende Beitrag behandelt die Beanspruchung von Rohrleitungssystemen durch seismische Welleneinwirkung und stellt geeignete Näherungsansätze und ein detailliertes Rechenmodell für seismische Leitungsanalysen vor. Mit den Ansätzen wird in Berechnungsbeispielen der Einfluss wesentlicher Parameter auf die seismisch induzierten Dehnungen in Rohrleitungssystemen untersucht. Y1 - 2014 SN - 0005-6650 N1 - gedruckt in der Bereichsbibliothek Bayernallee unter der Signatur 13 Z 049 vorhanden VL - 89 SP - 316 EP - 324 PB - VDI Fachmedien CY - Düsseldorf ER - TY - JOUR A1 - Altherr, Lena A1 - Ederer, Thorsten A1 - Lorenz, Ulf A1 - Pelz, Peter F. A1 - Pöttgen, Philipp ED - Lübbecke, Marco ED - Koster, Arie ED - Letmathe, Peter ED - Madlener, Reihard ED - Peis, Britta ED - Walther, Grit T1 - Experimental validation of an enhanced system synthesis approach JF - Operations Research Proceedings 2014 N2 - Planning the layout and operation of a technical system is a common task for an engineer. Typically, the workflow is divided into consecutive stages: First, the engineer designs the layout of the system, with the help of his experience or of heuristic methods. Secondly, he finds a control strategy which is often optimized by simulation. This usually results in a good operating of an unquestioned sys- tem topology. In contrast, we apply Operations Research (OR) methods to find a cost-optimal solution for both stages simultaneously via mixed integer program- ming (MILP). Technical Operations Research (TOR) allows one to find a provable global optimal solution within the model formulation. However, the modeling error due to the abstraction of physical reality remains unknown. We address this ubiq- uitous problem of OR methods by comparing our computational results with mea- surements in a test rig. For a practical test case we compute a topology and control strategy via MILP and verify that the objectives are met up to a deviation of 8.7%. Y1 - 2014 SN - 978-3-319-28695-2 U6 - http://dx.doi.org/10.1007/978-3-319-28697-6_1 PB - Springer CY - Basel ER - TY - JOUR A1 - Golland, Alexander T1 - Datenschutz durch modulare Zertifizierung: Trusted Cloud-Pilotprojekt bringt neuen Ansatz JF - DSB Datenschutz-Berater Y1 - 2014 SN - 0170-7256 VL - 38 IS - 10 SP - 213 EP - 215 PB - dfv Mediengruppe CY - Frankfurt a.M. ER - TY - JOUR A1 - Golland, Alexander A1 - Engling, Christoph T1 - a-i3/BSI Symposium 2014: Sicherheit von Daten und Identitäten angesichts NSA und Big Data JF - DSB Datenschutz-Berater Y1 - 2014 SN - 0170-7256 VL - 38 IS - 7-8 SP - 165 EP - 166 PB - dfv Mediengruppe CY - Frankfurt a.M. ER - TY - JOUR A1 - Yang, Peng-Fei A1 - Kriechbaumer, Andreas A1 - Albracht, Kirsten A1 - Sanno, Maximilian A1 - Ganse, Bergita A1 - Koy, Timmo A1 - Shang, Peng A1 - brüggemann, Gert-Peter A1 - Müller, Lars Peter A1 - Rittweger, Jörn T1 - A novel optical approach for assessing in vivo bone segment deformation and its application in muscle-bone relationship studies in humans JF - Journal of Orthopaedic Translation Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.jot.2014.07.078 SN - 2214-0328 SN - 2214-031X VL - 2 IS - 4 SP - 238 EP - 238 PB - Elsevier CY - Singapore ER - TY - JOUR A1 - Finkenberger, Isabel Maria A1 - Schlaich, Christoph T1 - Mehr als Wohnen. Vom Zusammenleben in integrierten Nachbarschaften JF - APuZ - Aus Politik und Zeitgeschichte N2 - Neue Dörfer braucht das Land! Dörfer in der Stadt und Dörfer auf dem Land (…). Die Planung und Gestaltung nachhaltiger Raumsysteme, die durch ein neues Verständnis des gemeinschaftlichen Besitzes (und dessen Nutzung) ressourcenfressende Individualisierungstendenzen unserer Gesellschaft überwinden, aber zugleich größtmöglichen Freiraum für eine individuelle Persönlichkeitsentfaltung zur Verfügung stellen." Dieses Zitat der Hamburger Initiative "Wir sind Dorf" beschreibt eine aktuelle Diskussion in unserer Gesellschaft, die sowohl in der Forschung und forschungsgeleiteten Initiativen, in Politik und Planung als auch in der Bürger-schaft stattfindet. Sie wird nicht nur auf wissenschaftlichen Veranstaltungen geführt, sondern auch in konkreten Projekten für integrative Lebenswelten, die Fragestellungen von Ernährung und Energieversorgung, von Arbeit und Ökonomie, aber auch eines neuen räumlichen und sozialen Miteinanders einbeziehen. Anders als bei den weit verbreiteten Baugruppen geht es nicht ausschließlich um die Schaffung von Wohnraum. Die Nachbarschaftsidee verbindet das Bedürfnis nach gemeinschaftlichem Wohnen und Wirtschaften mit einer neuen Werteorientierung, die auf persönlicher Verantwortungsübernahme beruht. Y1 - 2024 SN - 2194-3621 VL - 2014 IS - 20-21 SP - 46 EP - 52 PB - Bundeszentrale für politische Bildung - bpb CY - Bonn ER - TY - JOUR A1 - Finkenberger, Isabel Maria T1 - Vox populi. (Transformations-)potenziale nachkriegsmoderner Freiraumressourcen JF - Stadt+Grün N2 - Heute wie damals werden die großzügigen und offenen Siedlungsstrukturen der ersten Nachkriegsjahrzehnte mit ihrem hohen Anteil an "Grün" vielfach geschätzt und als solche nicht grundlegend hinterfragt. "Grün" verheißt im Allgemeinen Licht, Luft und Sonne, Freizeit und Erholung und gilt als etwas Wünschenswertes im städtischen Kontext. Unbeachtet bleibt, dass dem Begriff "Grün" zunächst keine Eigenschaften oder Qualitäten zugewiesen sind - er sagt noch lange nichts über dessen räumliche Qualität, dessen Nutzbarkeit, Erreichbarkeit und Zugänglichkeit aus. Abstandsgrün und Straßenbegleitgrün ist eben auch "Grün". Neben einer quantitativen Argumentation, welche ökologischen Aspekte wie Biotopvernetzung, Stadt- und Mikroklima berücksichtigt, sollten wir verstärkt qualitativ denken und damit die Grundlage für einen erweiterten und wesentlich differenzierteren Diskurs über urbane Freiräume ebnen. Y1 - 2024 SN - 0948-9770 VL - 2014 IS - 1 SP - 31 EP - 35 PB - Patzer CY - Berlin ER - TY - JOUR A1 - Theysohn, Jens M. A1 - Kraff, Oliver A1 - Eilers, Kristina A1 - Andrade, Dorian A1 - Gerwig, Marcus A1 - Timmann, Dagmar A1 - Schmitt, Franz A1 - Ladd, Mark E. A1 - Ladd, Susanne C. A1 - Bitz, Andreas T1 - Vestibular effects of a 7 Tesla MRI examination compared to 1.5 T and 0 T in healthy volunteers JF - PLoS one N2 - Ultra-high-field MRI (7 Tesla (T) and above) elicits more temporary side-effects compared to 1.5 T and 3 T, e.g. dizziness or “postural instability” even after exiting the scanner. The current study aims to assess quantitatively vestibular performance before and after exposure to different MRI scenarios at 7 T, 1.5 T and 0 T. Sway path and body axis rotation (Unterberger's stepping test) were quantitatively recorded in a total of 46 volunteers before, 2 minutes after, and 15 minutes after different exposure scenarios: 7 T head MRI (n = 27), 7 T no RF (n = 22), 7 T only B₀ (n = 20), 7 T in & out B₀ (n = 20), 1.5 T no RF (n = 20), 0 T (n = 15). All exposure scenarios lasted 30 minutes except for brief one minute exposure in 7 T in & out B₀. Both measures were documented utilizing a 3D ultrasound system. During sway path evaluation, the experiment was repeated with eyes both open and closed. Sway paths for all long-lasting 7 T scenarios (normal, no RF, only B₀) with eyes closed were significantly prolonged 2 minutes after exiting the scanner, normalizing after 15 minutes. Brief exposure to 7 T B₀ or 30 minutes exposure to 1.5 T or 0 T did not show significant changes. End positions after Unterberger's stepping test were significantly changed counter-clockwise after all 7 T scenarios, including the brief in & out B₀ exposure. Shorter exposure resulted in a smaller alteration angle. In contrast to sway path, reversal of changes in body axis rotation was incomplete after 15 minutes. 1.5 T caused no rotational changes. The results show that exposure to the 7 Tesla static magnetic field causes only a temporary dysfunction or “over-compensation” of the vestibular system not measurable at 1.5 or 0 Tesla. Radiofrequency fields, gradient switching, and orthostatic dysregulation do not seem to play a role. Y1 - 2014 U6 - http://dx.doi.org/10.1371/journal.pone.0092104 SN - 1932-6203 VL - 9 IS - 3 PB - PLOS CY - San Francisco 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 -