@article{KonteTerpitzPlemenitaš2016, author = {Konte, Tilen and Terpitz, Ulrich and Plemenitaš, Ana}, title = {Reconstruction of the High-Osmolarity Glycerol (HOG) Signaling Pathway from the Halophilic Fungus Wallemia ichthyophaga in Saccharomyces cerevisiae}, series = {Frontiers in Microbiology}, journal = {Frontiers in Microbiology}, doi = {10.3389/fmicb.2016.00901}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165214}, year = {2016}, abstract = {The basidiomycetous fungus Wallemia ichthyophaga grows between 1.7 and 5.1 M NaCl and is the most halophilic eukaryote described to date. Like other fungi, W. ichthyophaga detects changes in environmental salinity mainly by the evolutionarily conserved high-osmolarity glycerol (HOG) signaling pathway. In Saccharomyces cerevisiae, the HOG pathway has been extensively studied in connection to osmotic regulation, with a valuable knock-out strain collection established. In the present study, we reconstructed the architecture of the HOG pathway of W. ichthyophaga in suitable S. cerevisiae knock-out strains, through heterologous expression of the W. ichthyophaga HOG pathway proteins. Compared to S. cerevisiae, where the Pbs2 (ScPbs2) kinase of the HOG pathway is activated via the SHO1 and SLN1 branches, the interactions between the W. ichthyophaga Pbs2 (WiPbs2) kinase and the W. ichthyophaga SHO1 branch orthologs are not conserved: as well as evidence of poor interactions between the WiSho1 Src-homology 3 (SH3) domain and the WiPbs2 proline-rich motif, the absence of a considerable part of the osmosensing apparatus in the genome of W. ichthyophaga suggests that the SHO1 branch components are not involved in HOG signaling in this halophilic fungus. In contrast, the conserved activation of WiPbs2 by the S. cerevisiae ScSsk2/ScSsk22 kinase and the sensitivity of W. ichthyophaga cells to fludioxonil, emphasize the significance of two-component (SLN1-like) signaling via Group III histidine kinase. Combined with protein modeling data, our study reveals conserved and non-conserved protein interactions in the HOG signaling pathway of W. ichthyophaga and therefore significantly improves the knowledge of hyperosmotic signal processing in this halophilic fungus.}, language = {en} } @article{ContarinoSmitvandenDooletal.2016, author = {Contarino, Maria Fiorella and Smit, Marenka and van den Dool, Joost and Volkmann, Jens and Tijssen, Marina A. J.}, title = {Unmet Needs in the Management of Cervical Dystonia}, series = {Frontiers in Neurology}, volume = {7}, journal = {Frontiers in Neurology}, number = {165}, doi = {10.3389/fneur.2016.00165}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165225}, year = {2016}, abstract = {Cervical dystonia (CD) is a movement disorder which affects daily living of many patients. In clinical practice, several unmet treatment needs remain open. This article focuses on the four main aspects of treatment. We describe existing and emerging treatment approaches for CD, including botulinum toxin injections, surgical therapy, management of non-motor symptoms, and rehabilitation strategies. The unsolved issues regarding each of these treatments are identified and discussed, and possible future approaches and research lines are proposed.}, language = {en} } @article{ArimanyNardiMinuesaPastorAngladaetal.2016, author = {Arimany-Nardi, Cristina and Minuesa, Gerard and Pastor-Anglada, Mar{\c{c}}al and Keller, Thorsten and Erkizia, Itziar and Koepsell, Hermann and Martinez-Picado, Javier}, title = {Role of Human Organic Cation Transporter 1 (hOCT1) Polymorphisms in Lamivudine (3TC) Uptake and Drug-Drug Interactions}, series = {Frontiers in Pharmacology}, volume = {7}, journal = {Frontiers in Pharmacology}, number = {175}, doi = {10.3389/fphar.2016.00175}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165236}, year = {2016}, abstract = {Lamivudine (3TC), a drug used in the treatment of HIV infection, needs to cross the plasma membrane to exert its therapeutic action. Human Organic cation transporter 1 (hOCT1), encoded by the SLC22A1 gene, is the transporter responsible for its uptake into target cells. As SLC22A1 is a highly polymorphic gene, the aim of this study was to determine how SNPs in the OCT1-encoding gene affected 3TC internalization and its interaction with other co-administered drugs. HEK293 cells stably transfected with either the wild type form or the polymorphic variants of hOCT1 were used to perform kinetic and drug-drug interaction studies. Protein co-immunoprecipitation was used to assess the impact of selected polymorphic cysteines on the oligomerization of the transporter. Results showed that 3TC transport efficiency was reduced in all polymorphic variants tested (R61C, C88R, S189L, M420del, and G465R). This was not caused by lack of oligomerization in case of variants located at the transporter extracellular loop (R61C and C88R). Drug-drug interaction measurements showed that co-administered drugs [abacavir (ABC), zidovudine (AZT), emtricitabine (FTC), tenofovir diproxil fumarate (TDF), efavirenz (EFV) and raltegravir (RAL)], differently inhibited 3TC uptake depending upon the polymorphic variant analyzed. These data highlight the need for accurate analysis of drug transporter polymorphic variants of clinical relevance, because polymorphisms can impact on substrate (3TC) translocation but even more importantly they can differentially affect drug-drug interactions at the transporter level.}, language = {en} } @article{ProppingLorenzMicheletal.2016, author = {Propping, Stefan and Lorenz, Kristina and Michel, Martin C. and Wirth, Manfred P. and Ravens, Ursula}, title = {beta-Adrenoceptor-mediated Relaxation of Urinary Bladder Muscle in beta 2-Adrenoceptor Knockout Mice}, series = {Frontiers in Pharmacology}, volume = {7}, journal = {Frontiers in Pharmacology}, number = {118}, doi = {10.3389/fphar.2016.00118}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165245}, year = {2016}, abstract = {Background and Objective: In order to characterize the β-adrenoceptor (AR) subtypes involved in agonist-stimulated relaxation of murine urinary bladder we studied the effects of (-)-isoprenaline and CL 316,243 on tonic contraction and spontaneous contractions in detrusor strips of wild-type (WT) and β2-AR knockout (β2-AR KO) mice. Materials and Methods: Urinary bladders were isolated from male WT and β2-AR KO mice. β-AR subtype expression was determined with quantitative real-time PCR. Intact muscle strips pre-contracted with KCl (40 mM) were exposed to cumulatively increasing concentrations of (-)-isoprenaline or β3-AR agonist CL 316,243 in the presence and absence of the subtype-selective β-AR blockers CGP 20712A (β1-ARs), ICI 118,551 (β2-ARs), and L748,337 (β3-ARs). Results: Quantitative real-time PCR confirmed lack of β2-AR expression in bladder tissue from β2-AR KO mice. In isolated detrusor strips, pre-contraction with KCl increased basal tone and enhanced spontaneous activity significantly more in β2-AR KO than in WT. (-)-Isoprenaline relaxed tonic tension and attenuated spontaneous activity with similar potency, but the concentrations required were two orders of magnitude higher in β2-AR KO than WT. The concentration-response curves (CRCs) for relaxation were not affected by CGP 20712A (300 nM), but were shifted to the right by ICI 118,551 (50 nM) and L748,337 (10 μM). The -logEC50 values for (-)-isoprenaline in WT and β2-AR KO tissue were 7.98 and 6.00, respectively, suggesting a large receptor reserve of β2-AR. (-)-CL 316,243 relaxed detrusor and attenuated spontaneous contractions from WT and β2-AR KO mice with a potency corresponding to the drug's affinity for β3-AR. L743,337 shifted the CRCs to the right. Conclusion: Our findings in β2-AR KO mice suggest that there is a large receptor reserve for β2-AR in WT mice so that this β-AR subtype will mediate relaxation of tone and attenuation of spontaneous activity under physiological conditions. Nevertheless, upon removal of this reserve, β3-AR can also mediate murine detrusor relaxation.}, language = {en} } @article{ZinnerMoralesAlamoOrtenbladetal.2016, author = {Zinner, Christoph and Morales-Alamo, David and {\O}rtenblad, Niels and Larsen, Filip J. and Schiffer, Tomas A. and Willis, Sarah J. and Gelabert-Rebato, Miriam and Perez-Valera, Mario and Boushel, Robert and Calbet, Jose A. L. and Holmberg, Hans-Christer}, title = {The Physiological Mechanisms of Performance Enhancement with Sprint Interval Training Differ between the Upper and Lower Extremities in Humans}, series = {Frontiers in Physiology}, volume = {7}, journal = {Frontiers in Physiology}, number = {426}, doi = {10.3389/fphys.2016.00426}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165257}, year = {2016}, abstract = {To elucidate the mechanisms underlying the differences in adaptation of arm and leg muscles to sprint training, over a period of 11 days 16 untrained men performed six sessions of 4-6 × 30-s all-out sprints (SIT) with the legs and arms, separately, with a 1-h interval of recovery. Limb-specific VO2peak, sprint performance (two 30-s Wingate tests with 4-min recovery), muscle efficiency and time-trial performance (TT, 5-min all-out) were assessed and biopsies from the m. vastus lateralis and m. triceps brachii taken before and after training. VO2peak and Wmax increased 3-11\% after training, with a more pronounced change in the arms (P < 0.05). Gross efficiency improved for the arms (+8.8\%, P < 0.05), but not the legs (-0.6\%). Wingate peak and mean power outputs improved similarly for the arms and legs, as did TT performance. After training, VO2 during the two Wingate tests was increased by 52 and 6\% for the arms and legs, respectively (P < 0.001). In the case of the arms, VO2 was higher during the first than second Wingate test (64 vs. 44\%, P < 0.05). During the TT, relative exercise intensity, HR, VO2, VCO2, VE, and Vt were all lower during arm-cranking than leg-pedaling, and oxidation of fat was minimal, remaining so after training. Despite the higher relative intensity, fat oxidation was 70\% greater during leg-pedaling (P = 0.017). The aerobic energy contribution in the legs was larger than for the arms during the Wingate tests, although VO2 for the arms was enhanced more by training, reducing the O2 deficit after SIT. The levels of muscle glycogen, as well as the myosin heavy chain composition were unchanged in both cases, while the activities of 3-hydroxyacyl-CoA-dehydrogenase and citrate synthase were elevated only in the legs and capillarization enhanced in both limbs. Multiple regression analysis demonstrated that the variables that predict TT performance differ for the arms and legs. The primary mechanism of adaptation to SIT by both the arms and legs is enhancement of aerobic energy production. However, with their higher proportion of fast muscle fibers, the arms exhibit greater plasticity.}, language = {en} } @article{NyssenVanNieulandVandenbergheetal.2016, author = {Nyssen, Jan and Van Nieuland, Jasper and Vandenberghe, Dimitri and Juilleret, J{\´e}r{\^o}me and Terhorst, Birgit}, title = {Gr{\`e}zes lit{\´e}es and their genesis: the site of Enscherange in the Rhenish-Ardennes Massif as a case study}, series = {Die Erde : Journal of the Geographical Society of Berlin}, volume = {147}, journal = {Die Erde : Journal of the Geographical Society of Berlin}, number = {1}, doi = {10.12854/erde-147-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165032}, year = {2016}, abstract = {The freeze-thaw cycles in periglacial areas during the Quaternary glacials increased frost weathering, leading to a disintegration of rock formations. Transported downslope, clasts allowed in some areas the formation of stratified slope deposits known as "gr{\`e}zes lit{\´e}es". This study reviews the existing theories and investigates the gr{\`e}zes lit{\´e}es deposits of Enscherange and Rodershausen in Luxembourg. This process was reinforced by the lithostructural control of the parent material expressed by the dip of schistosity (66°) and its orientation parallel to the main slopes in the area. This gave opportunities to activate the frost-weathering process on top of the ridge where the parent material outcropped. As the stratified slope deposits have a dip of 23° and as there is no significant lateral variation in rock fragment size, slope processes that involve only gravity are excluded and transportation in solifluction lobes with significant slopewash and sorting processes is hypothesized. The Enscherange formation, the biggest known outcrop of gr{\`e}zes lit{\´e}es in north-western Europe, shows evidence of clear layering over the whole profile depth. A palaeolandscape reconstruction shows that ridges must have been tens of metres higher than presently. The investigation of the matrix composition shows Laacher See tephra in the overlying periglacial cover bed with infiltrations of the minerals in the reworked upper layer of the gr{\`e}zes lit{\´e}es deposit. Chronostratigraphic approaches using the underlying cryoturbation zone and Laacher See heavy minerals in the overlying topsoil place the formation of gr{\`e}zes lit{\´e}es deposits in the Late Pleistocene.}, language = {en} } @article{BechtleCamargoMolinaDeschetal.2016, author = {Bechtle, Philip and Camargo-Molina, Jos{\´e} Eliel and Desch, Klaus and Dreiner, Herbert K. and Hamer, Matthias and Kr{\"a}mer, Michael and O'Leary, Ben and Porod, Werner and Sarrazin, Bj{\"o}rn and Stefaniak, Tim and Uhlenbrock, Mathias and Wienemann, Peter}, title = {Killing the cMSSM softly}, series = {The European Physical Journal C}, volume = {76}, journal = {The European Physical Journal C}, number = {96}, doi = {10.1140/epjc/s10052-015-3864-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165045}, year = {2016}, abstract = {We investigate the constrained Minimal Supersymmetric Standard Model (cMSSM) in the light of constraining experimental and observational data from precision measurements, astrophysics, direct supersymmetry searches at the LHC and measurements of the properties of the Higgs boson, by means of a global fit using the program Fittino. As in previous studies, we find rather poor agreement of the best fit point with the global data. We also investigate the stability of the electro-weak vacuum in the preferred region of parameter space around the best fit point. We find that the vacuum is metastable, with a lifetime significantly longer than the age of the Universe. For the first time in a global fit of supersymmetry, we employ a consistent methodology to evaluate the goodness-of-fit of the cMSSM in a frequentist approach by deriving p values from large sets of toy experiments. We analyse analytically and quantitatively the impact of the choice of the observable set on the p value, and in particular its dilution when confronting the model with a large number of barely constraining measurements. Finally, for the preferred sets of observables, we obtain p values for the cMSSM below 10 \%, i.e. we exclude the cMSSM as a model at the 90 \% confidence level.}, language = {en} } @article{BoettcherPrifertWeissbrichetal.2016, author = {B{\"o}ttcher, S. and Prifert, C. and Weißbrich, B. and Adams, O. and Aldabbagh, S. and Eis-H{\"u}binger, A. M. and Diedrich, S.}, title = {Detection of enterovirus D68 in patients hospitalised in three tertiary university hospitals in Germany, 2013 to 2014}, series = {Eurosurveillance}, volume = {21}, journal = {Eurosurveillance}, number = {19}, doi = {10.2807/1560-7917.ES.2016.21.19.30227}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165068}, pages = {pii=30227}, year = {2016}, abstract = {Enterovirus D68 (EV-D68) has been recognised as a worldwide emerging pathogen associated with severe respiratory symptoms since 2009. We here report EV-D68 detection in hospitalised patients with acute respiratory infection admitted to three tertiary hospitals in Germany between January 2013 and December 2014. From a total of 14,838 respiratory samples obtained during the study period, 246 (1.7\%) tested enterovirus-positive and, among these, 39 (15.9\%) were identified as EV-D68. Infection was observed in children and teenagers (0-19 years; n=31), the majority (n=22) being under five years-old, as well as in adults > 50 years of age (n=8). No significant difference in prevalence was observed between the 2013 and 2014 seasons. Phylogenetic analyses based on viral protein 1 (VP1) sequences showed co-circulation of different EV-D68 lineages in Germany. Sequence data encompassing the entire capsid region of the genome were analysed to gain information on amino acid changes possibly relevant for immunogenicity and revealed mutations in two recently described pleconaril binding sites.}, language = {en} } @article{HeldBerzHensgenetal.2016, author = {Held, Martina and Berz, Annuska and Hensgen, Ronja and Muenz, Thomas S. and Scholl, Christina and R{\"o}ssler, Wolfgang and Homberg, Uwe and Pfeiffer, Keram}, title = {Microglomerular Synaptic Complexes in the Sky-Compass Network of the Honeybee Connect Parallel Pathways from the Anterior Optic Tubercle to the Central Complex}, series = {Frontiers in Behavioral Neuroscience}, volume = {10}, journal = {Frontiers in Behavioral Neuroscience}, number = {186}, doi = {10.3389/fnbeh.2016.00186}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165080}, year = {2016}, abstract = {While the ability of honeybees to navigate relying on sky-compass information has been investigated in a large number of behavioral studies, the underlying neuronal system has so far received less attention. The sky-compass pathway has recently been described from its input region, the dorsal rim area (DRA) of the compound eye, to the anterior optic tubercle (AOTU). The aim of this study is to reveal the connection from the AOTU to the central complex (CX). For this purpose, we investigated the anatomy of large microglomerular synaptic complexes in the medial and lateral bulbs (MBUs/LBUs) of the lateral complex (LX). The synaptic complexes are formed by tubercle-lateral accessory lobe neuron 1 (TuLAL1) neurons of the AOTU and GABAergic tangential neurons of the central body's (CB) lower division (TL neurons). Both TuLAL1 and TL neurons strongly resemble neurons forming these complexes in other insect species. We further investigated the ultrastructure of these synaptic complexes using transmission electron microscopy. We found that single large presynaptic terminals of TuLAL1 neurons enclose many small profiles (SPs) of TL neurons. The synaptic connections between these neurons are established by two types of synapses: divergent dyads and divergent tetrads. Our data support the assumption that these complexes are a highly conserved feature in the insect brain and play an important role in reliable signal transmission within the sky-compass pathway.}, language = {en} } @article{MeyerRichterSchreiberetal.2016, author = {Meyer, Neele and Richter, S. Helene and Schreiber, Rebecca S. and Kloke, Vanessa and Kaiser, Sylvia and Lesch, Klaus-Peter and Sachser, Norbert}, title = {The Unexpected Effects of Beneficial and Adverse Social Experiences during Adolescence on Anxiety and Aggression and Their Modulation by Genotype}, series = {Frontiers in Behavioral Neuroscience}, volume = {10}, journal = {Frontiers in Behavioral Neuroscience}, number = {97}, doi = {10.3389/fnbeh.2016.00097}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165090}, year = {2016}, abstract = {Anxiety and aggression are part of the behavioral repertoire of humans and animals. However, in their exaggerated form both can become maladaptive and result in psychiatric disorders. On the one hand, genetic predisposition has been shown to play a crucial modulatory role in anxiety and aggression. On the other hand, social experiences have been implicated in the modulation of these traits. However, so far, mainly experiences in early life phases have been considered crucial for shaping anxiety-like and aggressive behavior, while the phase of adolescence has largely been neglected. Therefore, the aim of the present study was to elucidate how levels of anxiety-like and aggressive behavior are shaped by social experiences during adolescence and serotonin transporter (5-HTT) genotype. For this purpose, male mice of a 5-HTT knockout mouse model including all three genotypes (wildtype, heterozygous and homozygous 5-HTT knockout mice) were either exposed to an adverse social situation or a beneficial social environment during adolescence. This was accomplished in a custom-made cage system where mice experiencing the adverse environment were repeatedly introduced to the territory of a dominant opponent but had the possibility to escape to a refuge cage. Mice encountering beneficial social conditions had free access to a female mating partner. Afterwards, anxiety-like and aggressive behavior was assessed in a battery of tests. Surprisingly, unfavorable conditions during adolescence led to a decrease in anxiety-like behavior and an increase in exploratory locomotion. Additionally, aggressive behavior was augmented in animals that experienced social adversity. Concerning genotype, homozygous 5-HTT knockout mice were more anxious and less aggressive than heterozygous 5-HTT knockout and wildtype mice. In summary, adolescence is clearly an important phase in which anxiety-like and aggressive behavior can be shaped. Furthermore, it seems that having to cope with challenge during adolescence instead of experiencing throughout beneficial social conditions leads to reduced levels of anxiety-like behavior.}, language = {en} } @article{ZhouAllisonKuebleretal.2016, author = {Zhou, Sijie and Allison, Brendan Z. and K{\"u}bler, Andrea and Cichocki, Andrzej and Wang, Xingyu and Jin, Jing}, title = {Effects of Background Music on Objective and Subjective Performance Measures in an Auditory BCI}, series = {Frontiers in Computational Neuroscience}, volume = {10}, journal = {Frontiers in Computational Neuroscience}, number = {105}, doi = {10.3389/fncom.2016.00105}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165101}, year = {2016}, abstract = {Several studies have explored brain computer interface (BCI) systems based on auditory stimuli, which could help patients with visual impairments. Usability and user satisfaction are important considerations in any BCI. Although background music can influence emotion and performance in other task environments, and many users may wish to listen to music while using a BCI, auditory, and other BCIs are typically studied without background music. Some work has explored the possibility of using polyphonic music in auditory BCI systems. However, this approach requires users with good musical skills, and has not been explored in online experiments. Our hypothesis was that an auditory BCI with background music would be preferred by subjects over a similar BCI without background music, without any difference in BCI performance. We introduce a simple paradigm (which does not require musical skill) using percussion instrument sound stimuli and background music, and evaluated it in both offline and online experiments. The result showed that subjects preferred the auditory BCI with background music. Different performance measures did not reveal any significant performance effect when comparing background music vs. no background. Since the addition of background music does not impair BCI performance but is preferred by users, auditory (and perhaps other) BCIs should consider including it. Our study also indicates that auditory BCIs can be effective even if the auditory channel is simultaneously otherwise engaged.}, language = {en} } @article{WiedenmannBocquillonDeaconetal.2016, author = {Wiedenmann, J. and Bocquillon, E. and Deacon, R.S. and Hartinger, S. and Herrmann, O. and Klapwijk, T.M. and Maier, L. and Ames, C. and Br{\"u}ne, C. and Gould, C. and Oiwa, A. and Ishibashi, K. and Tarucha, S. and Buhmann, H. and Molenkamp, L.W.}, title = {4π-periodic Josephson supercurrent in HgTe-based topological Josephson junctions}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, doi = {10.1038/ncomms10303}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175353}, year = {2016}, abstract = {The Josephson effect describes the generic appearance of a supercurrent in a weak link between two superconductors. Its exact physical nature deeply influences the properties of the supercurrent. In recent years, considerable efforts have focused on the coupling of superconductors to the surface states of a three-dimensional topological insulator. In such a material, an unconventional induced p-wave superconductivity should occur, with a doublet of topologically protected gapless Andreev bound states, whose energies vary 4π-periodically with the superconducting phase difference across the junction. In this article, we report the observation of an anomalous response to rf irradiation in a Josephson junction made of a HgTe weak link. The response is understood as due to a 4π-periodic contribution to the supercurrent, and its amplitude is compatible with the expected contribution of a gapless Andreev doublet. Our work opens the way to more elaborate experiments to investigate the induced superconductivity in a three-dimensional insulator.}, language = {en} } @article{FroehlichHanekePapenfortetal.2016, author = {Fr{\"o}hlich, Kathrin S. and Haneke, Katharina and Papenfort, Kai and Vogel, J{\"o}rg}, title = {The target spectrum of SdsR small RNA in Salmonella}, series = {Nucleic Acids Research}, volume = {44}, journal = {Nucleic Acids Research}, number = {21}, doi = {10.1093/nar/gkw632}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175365}, pages = {10406-10422}, year = {2016}, abstract = {Model enteric bacteria such as Escherichia coli and Salmonella enterica express hundreds of small non-coding RNAs (sRNAs), targets for most of which are yet unknown. Some sRNAs are remarkably well conserved, indicating that they serve cellular functions that go beyond the necessities of a single species. One of these 'core sRNAs' of largely unknown function is the abundant ∼100-nucleotide SdsR sRNA which is transcribed by the general stress σ-factor, σ\(^{S}\) and accumulates in stationary phase. In Salmonella, SdsR was known to inhibit the synthesis of the species-specific porin, OmpD. However, sdsR genes are present in almost all enterobacterial genomes, suggesting that additional, conserved targets of this sRNA must exist. Here, we have combined SdsR pulse-expression with whole genome transcriptomics to discover 20 previously unknown candidate targets of SdsR which include mRNAs coding for physiologically important regulators such as the carbon utilization regulator, CRP, the nucleoid-associated chaperone, StpA and the antibiotic resistance transporter, TolC. Processing of SdsR by RNase E results in two cellular SdsR variants with distinct target spectra. While the overall physiological role of this orphan core sRNA remains to be fully understood, the new SdsR targets present valuable leads to determine sRNA functions in resting bacteria.}, language = {en} } @phdthesis{Forster2016, author = {Forster, Johannes}, title = {Variational Approach to the Modeling and Analysis of Magnetoelastic Materials}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147226}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2016}, abstract = {This doctoral thesis is concerned with the mathematical modeling of magnetoelastic materials and the analysis of PDE systems describing these materials and obtained from a variational approach. The purpose is to capture the behavior of elastic particles that are not only magnetic but exhibit a magnetic domain structure which is well described by the micromagnetic energy and the Landau-Lifshitz-Gilbert equation of the magnetization. The equation of motion for the material's velocity is derived in a continuum mechanical setting from an energy ansatz. In the modeling process, the focus is on the interplay between Lagrangian and Eulerian coordinate systems to combine elasticity and magnetism in one model without the assumption of small deformations. The resulting general PDE system is simplified using special assumptions. Existence of weak solutions is proved for two variants of the PDE system, one including gradient flow dynamics on the magnetization, and the other featuring the Landau-Lifshitz-Gilbert equation. The proof is based on a Galerkin method and a fixed point argument. The analysis of the PDE system with the Landau-Lifshitz-Gilbert equation uses a more involved approach to obtain weak solutions based on G. Carbou and P. Fabrie 2001.}, subject = {Magnetoelastizit{\"a}t}, language = {en} } @article{KunzLiangNillaetal.2016, author = {Kunz, Meik and Liang, Chunguang and Nilla, Santosh and Cecil, Alexander and Dandekar, Thomas}, title = {The drug-minded protein interaction database (DrumPID) for efficient target analysis and drug development}, series = {Database}, volume = {2016}, journal = {Database}, doi = {10.1093/database/baw041}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147369}, pages = {baw041}, year = {2016}, abstract = {The drug-minded protein interaction database (DrumPID) has been designed to provide fast, tailored information on drugs and their protein networks including indications, protein targets and side-targets. Starting queries include compound, target and protein interactions and organism-specific protein families. Furthermore, drug name, chemical structures and their SMILES notation, affected proteins (potential drug targets), organisms as well as diseases can be queried including various combinations and refinement of searches. Drugs and protein interactions are analyzed in detail with reference to protein structures and catalytic domains, related compound structures as well as potential targets in other organisms. DrumPID considers drug functionality, compound similarity, target structure, interactome analysis and organismic range for a compound, useful for drug development, predicting drug side-effects and structure-activity relationships.}, language = {en} } @article{StrekalovaMarkovaShevtsovaetal.2016, author = {Strekalova, Tatyana and Markova, Nataliia and Shevtsova, Elena and Zubareva, Olga and Bakhmet, Anastassia and Steinbusch, Harry M. and Bachurin, Sergey and Lesch, Klaus-Peter}, title = {Individual Differences in Behavioural Despair Predict Brain GSK-3beta Expression in Mice: The Power of a Modified Swim Test}, series = {Neural Plasticity}, volume = {2016}, journal = {Neural Plasticity}, doi = {10.1155/2016/5098591}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147379}, pages = {5098591}, year = {2016}, abstract = {While deficient brain plasticity is a well-established pathophysiologic feature of depression, little is known about disorder-associated enhanced cognitive processing. Here, we studied a novel mouse paradigm that potentially models augmented learning of adverse memories during development of a depressive-like state. We used a modification of the classic two-day protocol of a mouse Porsolt test with an additional session occurring on Day 5 following the initial exposure. Unexpectedly, floating behaviour and brain glycogen synthase kinase-3 beta (GSK-3beta) mRNA levels, a factor of synaptic plasticity as well as a marker of distress and depression, were increased during the additional swimming session that was prevented by imipramine. Observed increases of GSK-3beta mRNA in prefrontal cortex during delayed testing session correlated with individual parameters of behavioural despair that was not found in the classic Porsolt test. Repeated swim exposure was accompanied by a lower pGSK-3beta/GSK-3beta ratio. A replacement of the second or the final swim sessions with exposure to the context of testing resulted in increased GSK-3beta mRNA level similar to the effects of swimming, while exclusion of the second testing prevented these changes. Together, our findings implicate the activation of brain GSK-3beta expression in enhanced contextual conditioning of adverse memories, which is associated with an individual susceptibility to a depressive syndrome.}, language = {en} } @article{RieplMusselOsinskyetal.2016, author = {Riepl, Korbinian and Mussel, Patrick and Osinsky, Roman and Hewig, Johannes}, title = {Influences of State and Trait Affect on Behavior, Feedback-Related Negativity, and P3b in the Ultimatum Game}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {11}, doi = {10.1371/journal.pone.0146358}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147386}, pages = {e0146358}, year = {2016}, abstract = {The present study investigates how different emotions can alter social bargaining behavior. An important paradigm to study social bargaining is the Ultimatum Game. There, a proposer gets a pot of money and has to offer part of it to a responder. If the responder accepts, both players get the money as proposed by the proposer. If he rejects, none of the players gets anything. Rational choice models would predict that responders accept all offers above 0. However, evidence shows that responders typically reject a large proportion of all unfair offers. We analyzed participants' behavior when they played the Ultimatum Game as responders and simultaneously collected electroencephalogram data in order to quantify the feedback-related negativity and P3b components. We induced state affect (momentarily emotions unrelated to the task) via short movie clips and measured trait affect (longer-lasting emotional dispositions) via questionnaires. State happiness led to increased acceptance rates of very unfair offers. Regarding neurophysiology, we found that unfair offers elicited larger feedback-related negativity amplitudes than fair offers. Additionally, an interaction of state and trait affect occurred: high trait negative affect (subsuming a variety of aversive mood states) led to increased feedback-related negativity amplitudes when participants were in an angry mood, but not if they currently experienced fear or happiness. We discuss that increased rumination might be responsible for this result, which might not occur, however, when people experience happiness or fear. Apart from that, we found that fair offers elicited larger P3b components than unfair offers, which might reflect increased pleasure in response to fair offers. Moreover, high trait negative affect was associated with decreased P3b amplitudes, potentially reflecting decreased motivation to engage in activities. We discuss implications of our results in the light of theories and research on depression and anxiety.}, language = {en} } @article{KoesslerHermannWeberetal.2016, author = {Koessler, Juergen and Hermann, Stephanie and Weber, Katja and Koessler, Angela and Kuhn, Sabine and Boeck, Markus and Kobsar, Anna}, title = {Role of Purinergic Receptor Expression and Function for Reduced Responsiveness to Adenosine Diphosphate in Washed Human Platelets}, series = {PLoS One}, volume = {11}, journal = {PLoS One}, number = {1}, doi = {10.1371/journal.pone.0147370}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146400}, pages = {e0147370}, year = {2016}, abstract = {Background Washing of platelets is an important procedure commonly used for experimental studies, e.g. in cardiovascular research. As a known phenomenon, responsiveness to adenosine diphosphate (ADP) is reduced in washed platelets, although underlying molecular mechanisms—potentially interfering with experimental results—have not been thoroughly studied. Objectives Since ADP mediates its effects via three purinergic receptors P2Y1, P2X1 and P2Y12, their surface expression and function were investigated in washed platelets and, for comparison, in platelet-rich-plasma (PRP) at different time points for up to 2 hours after preparation. Results In contrast to PRP, flow cytometric analysis of surface expression in washed platelets revealed an increase of all receptors during the first 60 minutes after preparation followed by a significant reduction, which points to an initial preactivation of platelets and consecutive degeneration. The activity of the P2X1 receptor (measured by selectively induced calcium flux) was substantially maintained in both PRP and washed platelets. P2Y12 function (determined by flow cytometry as platelet reactivity index) was partially reduced after platelet washing compared to PRP, but remained stable in course of ongoing storage. However, the function of the P2Y1 receptor (measured by selectively induced calcium flux) continuously declined after preparation of washed platelets. Conclusion In conclusion, decreasing ADP responsiveness in washed platelets is particularly caused by impaired activity of the P2Y1 receptor associated with disturbed calcium regulation, which has to be considered in the design of experimental studies addressing ADP mediated platelet function.}, language = {en} } @article{FehrholzGlaserSeidenspinneretal.2016, author = {Fehrholz, Markus and Glaser, Kirsten and Seidenspinner, Silvia and Ottensmeier, Barbara and Curstedt, Tore and Speer, Christian P. and Kunzmann, Steffen}, title = {Impact of the New Generation Reconstituted Surfactant CHF5633 on Human CD4\(^+\) Lymphocytes}, series = {PLoS One}, volume = {11}, journal = {PLoS One}, number = {4}, doi = {10.1371/journal.pone.0153578}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146419}, pages = {e0153578}, year = {2016}, abstract = {Background Natural surfactant preparations, commonly isolated from porcine or bovine lungs, are used to treat respiratory distress syndrome in preterm infants. Besides biophysical effectiveness, several studies have documented additional immunomodulatory properties. Within the near future, synthetic surfactant preparations may be a promising alternative. CHF5633 is a new generation reconstituted synthetic surfactant preparation with defined composition, containing dipalmitoyl-phosphatidylcholine, palmitoyl-oleoyl-phosphatidylglycerol and synthetic analogs of surfactant protein (SP-) B and SP-C. While its biophysical effectiveness has been demonstrated in vitro and in vivo, possible immunomodulatory abilities are currently unknown. Aim The aim of the current study was to define a potential impact of CHF5633 and its single components on pro- and anti-inflammatory cytokine responses in human CD4\(^+\) lymphocytes. Methods Purified human CD4\(^+\) T cells were activated using anti CD3/CD28 antibodies and exposed to CHF5633, its components, or to the well-known animal-derived surfactant Poractant alfa (Curosurf®). Proliferative response and cell viability were assessed using flow cytometry and a methylthiazolyldiphenyltetrazolium bromide colorimetric assay. The mRNA expression of IFNγ, IL-2, IL-17A, IL-22, IL-4, and IL-10 was measured by quantitative PCR, while intracellular protein expression was assessed by means of flow cytometry. Results Neither CHF5633 nor any of its phospholipid components with or without SP-B or SP-C analogs had any influence on proliferative ability and viability of CD4\(^+\) lymphocytes under the given conditions. IFNγ, IL-2, IL-17A, IL-22, IL-4, and IL-10 mRNA as well as IFNγ, IL-2, IL-4 and IL-10 protein levels were unaffected in both non-activated and activated CD4+ lymphocytes after exposure to CHF5633 or its constituents compared to non-exposed controls. However, in comparison to Curosurf®, expression levels of anti-inflammatory IL-4 and IL-10 mRNA were significantly increased in CHF5633 exposed CD4\(^+\) lymphocytes. Conclusion For the first time, the immunomodulatory capacity of CHF5633 on CD4\(^+\) lymphocytes was evaluated. CHF5633 did not show any cytotoxicity on CD4\(^+\) cells. Moreover, our in vitro data indicate that CHF5633 does not exert unintended pro-inflammatory effects on non-activated and activated CD4+ T cells. As far as anti-inflammatory cytokines are concerned, it might lack an overall reductive ability in comparison to animal-derived surfactants, potentially leaving pro- and anti-inflammatory cytokine response in balance.}, language = {en} } @article{BuschBuschScholzetal.2016, author = {Busch, Albert and Busch, Martin and Scholz, Claus-J{\"u}rgen and Kellersmann, Richard and Otto, Christoph and Chernogubova, Ekaterina and Maegdefessel, Lars and Zernecke, Alma and Lorenz, Udo}, title = {Aneurysm miRNA Signature Differs, Depending on Disease Localization and Morphology}, series = {International Journal of Molecular Science}, volume = {17}, journal = {International Journal of Molecular Science}, number = {1}, issn = {International Journal of Molecular Science}, doi = {10.3390/ijms17010081}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146422}, pages = {81}, year = {2016}, abstract = {Limited comprehension of aneurysm pathology has led to inconclusive results from clinical trials. miRNAs are key regulators of post-translational gene modification and are useful tools in elucidating key features of aneurysm pathogenesis in distinct entities of abdominal and popliteal aneurysms. Here, surgically harvested specimens from 19 abdominal aortic aneurysm (AAA) and 8 popliteal artery aneurysm (PAA) patients were analyzed for miRNA expression and histologically classified regarding extracellular matrix (ECM) remodeling and inflammation. DIANA-based computational target prediction and pathway enrichment analysis verified our results, as well as previous ones. miRNA-362, -19b-1, -194, -769, -21 and -550 were significantly down-regulated in AAA samples depending on degree of inflammation. Similar or inverse regulation was found for miR-769, 19b-1 and miR-550, -21, whereas miR-194 and -362 were unaltered in PAA. In situ hybridization verified higher expression of miR-550 and -21 in PAA compared to AAA and computational analysis for target genes and pathway enrichment affirmed signal transduction, cell-cell-interaction and cell degradation pathways, in line with previous results. Despite the vague role of miRNAs for potential diagnostic and treatment purposes, the number of candidates from tissue signature studies is increasing. Tissue morphology influences subsequent research, yet comparison of distinct entities of aneurysm disease can unravel core pathways.}, language = {en} }