@phdthesis{Rothe2015, author = {Rothe, Dietrich Gernot}, title = {Spin Transport in Topological Insulators and Geometrical Spin Control}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125628}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {In the field of spintronics, spin manipulation and spin transport are the main principles that need to be implemented. The main focus of this thesis is to analyse semiconductor systems where high fidelity in these principles can be achieved. To this end, we use numerical methods for precise results, supplemented by simpler analytical models for interpretation. The material system of 2D topological insulators, HgTe/CdTe quantum wells, is interesting not only because it provides a topologically distinct phase of matter, physically manifested in its protected transport properties, but also since within this system, ballistic transport of high quality can be realized, with Rashba spin-orbit coupling and electron densities that are tunable by electrical gating. Extending the Bernvevig-Hughes-Zhang model for 2D topological insulators, we derive an effective four-band model including Rashba spin-orbit terms due to an applied potential that breaks the spatial inversion symmetry of the quantum well. Spin transport in this system shows interesting physics because the effects of Rashba spin-orbit terms and the intrinsic Dirac-like spin-orbit terms compete. We show that the resulting spin Hall signal can be dominated by the effect of Rashba spin-orbit coupling. Based on spin splitting due to the latter, we propose a beam splitter setup for all-electrical generation and detection of spin currents. Its working principle is similar to optical birefringence. In this setup, we analyse spin current and spin polarization signals of different spin vector components and show that large in-plane spin polarization of the current can be obtained. Since spin is not a conserved quantity of the model, we first analyse the transport of helicity, a conserved quantity even in presence of Rashba spin-orbit terms. The polarization defined in terms of helicity is related to in-plane polarization of the physical spin. Further, we analyse thermoelectric transport in a setup showing the spin Hall effect. Due to spin-orbit coupling, an applied temperature gradient generates a transverse spin current, i.e. a spin Nernst effect, which is related to the spin Hall effect by a Mott-like relation. In the metallic energy regimes, the signals are qualitatively explained by simple analytic models. In the insulating regime, we observe a spin Nernst signal that originates from the finite-size induced overlap of edge states. In the part on methods, we discuss two complementary methods for construction of effective semiconductor models, the envelope function theory and the method of invariants. Further, we present elements of transport theory, with some emphasis on spin-dependent signals. We show the connections of the adiabatic theorem of quantum mechanics to the semiclassical theory of electronic transport and to the characterization of topological phases. Further, as application of the adiabatic theorem to a control problem, we show that universal control of a single spin in a heavy-hole quantum dot is experimentally realizable without breaking time reversal invariance, but using a quadrupole field which is adiabatically changed as control knob. For experimental realization, we propose a GaAs/GaAlAs quantum well system.}, subject = {Elektronischer Transport}, language = {en} } @article{RottlaenderKuerten2015, author = {Rottlaender, Andrea and Kuerten, Stefanie}, title = {Stepchild or prodigy? Neuroprotection in multiple sclerosis (MS) research}, series = {International Journal of Molecular Sciences}, volume = {16}, journal = {International Journal of Molecular Sciences}, doi = {10.3390/ijms160714850}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148416}, pages = {14850-14865}, year = {2015}, abstract = {Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS) and characterized by the infiltration of immune cells, demyelination and axonal loss. Loss of axons and nerve fiber pathology are widely accepted as correlates of neurological disability. Hence, it is surprising that the development of neuroprotective therapies has been neglected for a long time. A reason for this could be the diversity of the underlying mechanisms, complex changes in nerve fiber pathology and the absence of biomarkers and tools to quantify neuroregenerative processes. Present therapeutic strategies are aimed at modulating or suppressing the immune response, but do not primarily attenuate axonal pathology. Yet, target-oriented neuroprotective strategies are essential for the treatment of MS, especially as severe damage of nerve fibers mostly occurs in the course of disease progression and cannot be impeded by immune modulatory drugs. This review shall depict the need for neuroprotective strategies and elucidate difficulties and opportunities.}, language = {en} } @article{ElMajdoubHunscheIgressaetal.2015, author = {El Majdoub, Faycal and Hunsche, Stefan and Igressa, Alhadi and Kocher, Martin and Sturm, Volker and Maarouf, Mohammad}, title = {Stereotactic LINAC-Radiosurgery for Glomus Jugulare Tumors: A Long-Term Follow-Up of 27 Patients}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0129057}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151717}, pages = {e0129057}, year = {2015}, abstract = {Background The optimal treatment of glomus jugulare tumors (GJTs) remains controversial. Due to the critical location, microsurgery still provides high treatment-related morbidity and a decreased quality of life. Thus, we performed stereotactical radiosurgery (SRS) for the treatment of GJTs and evaluated the long-term outcome. Methods Between 1991 and 2011, 32 patients with GJTs underwent SRS using a linear accelerator (LINAC) either as primary or salvage therapy. Twenty-seven patients (median age 59.9 years, range 28.7-79.9 years) with a follow-up greater than five years (median 11 years, range 5.3-22.1 years) were selected for retrospective analysis. The median therapeutic single dose applied to the tumor surface was 15 Gy (range 11-20 Gy) and the median tumor volume was 9.5 ml (range 2.8-51 ml). Results Following LINAC-SRS, 10 of 27 patients showed a significant improvement of their previous neurological complaints, whereas 12 patients remained unchanged. Five patients died during follow-up due to old age or other, not treatment-related reasons. MR-imaging showed a partial remission in 12 and a stable disease in 15 patients. No tumor progression was observed. The actuarial overall survival rates after five, ten and 20 years were 100\%, 95.2\% and 79.4\%, respectively. Conclusions Stereotactic LINAC-Radiosurgery can achieve an excellent long-term tumor control beside a low rate of morbidity in the treatment of GJTs. It should be considered as an alternative therapy regime to surgical resection or fractionated external beam radiation either as primary, adjuvant or salvage therapy.}, language = {en} } @article{HoffmannEtzrodtWillkommetal.2015, author = {Hoffmann, Linda S. and Etzrodt, Jennifer and Willkomm, Lena and Sanyal, Abhishek and Scheja, Ludger and Fischer, Alexander W. C. and Stasch, Johannes-Peter and Bloch, Wilhelm and Friebe, Andreas and Heeren, Joerg and Pfeifer, Alexander}, title = {Stimulation of soluble guanylyl cyclase protects against obesity by recruiting brown adipose tissue}, series = {Nature Communications}, volume = {6}, journal = {Nature Communications}, number = {7235}, doi = {10.1038/ncomms8235}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143127}, year = {2015}, abstract = {Obesity is characterized by a positive energy balance and expansion of white adipose tissue (WAT). In contrast, brown adipose tissue (BAT) combusts energy to produce heat. Here we show that a small molecule stimulator (BAY 41-8543) of soluble guanylyl cyclase (sGC), which produces the second messenger cyclic GMP (cGMP), protects against diet-induced weight gain, induces weight loss in established obesity, and also improves the diabetic phenotype. Mechanistically, the haeme-dependent sGC stimulator BAY 41-8543 enhances lipid uptake into BAT and increases whole-body energy expenditure, whereas ablation of the haeme-containing \(\beta\)\(_{1}\)-subunit of sGC severely impairs BAT function. Notably, the sGC stimulator enhances differentiation of human brown adipocytes as well as induces 'browning' of primary white adipocytes. Taken together, our data suggest that sGC is a potential pharmacological target for the treatment of obesity and its comorbidities.}, language = {en} } @article{ZinnerSperlichKruegeretal.2015, author = {Zinner, Christoph and Sperlich, Billy and Krueger, Malte and Focke, Tim and Reed, Jennifer and Mester, Joachim}, title = {Strength, Endurance, Throwing Velocity and in-Water Jump Performance of Elite German Water Polo Players}, series = {Journal of Human Kinetics}, volume = {45}, journal = {Journal of Human Kinetics}, doi = {10.1515/hukin-2015-0015}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148812}, pages = {149-156}, year = {2015}, abstract = {The purpose of this study was threefold: 1) to assess the eggbeater kick and throwing performance using a number of water polo specific tests, 2) to explore the relation between the eggbeater kick and throwing performance, and 3) to investigate the relation between the eggbeater kick in the water and strength tests performed in a controlled laboratory setting in elite water polo players. Fifteen male water polo players of the German National Team completed dynamic and isometric strength tests for muscle groups (adductor, abductor, abdominal, pectoralis) frequently used during water polo. After these laboratory strength tests, six water polo specific in-water tests were conducted. The eggbeater kick assessed leg endurance and agility, maximal throwing velocity and jump height. A 400 m test and a sprint test examined aerobic and anaerobic performance. The strongest correlation was found between jump height and arm length (p < 0.001, r = 0.89). The laboratory diagnostics of important muscles showed positive correlations with the results of the in-water tests (p < 0.05, r = 0.52-0.70). Muscular strength of the adductor, abdominal and pectoralis muscles was positively related to in-water endurance agility as assessed by the eggbeater kick (p < 0.05; r = 0.53-0.66). Findings from the current study emphasize the need to assess indices of water polo performance both in and out of the water as well as the relation among these parameters to best assess the complex profile of water polo players.}, language = {en} } @article{LukasczikGerlichSchuleretal.2015, author = {Lukasczik, Matthias and Gerlich, Christian and Schuler, Michael and Neuderth, Silke and Dlugosch, Gabriele and Faller, Hermann}, title = {Stress and resources in women attending an inpatient prevention/rehabilitation measure for parents: Secondary analysis of quality assurance data}, series = {Open Journal of Medical Psychology}, volume = {4}, journal = {Open Journal of Medical Psychology}, doi = {10.4236/ojmp.2015.42003}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125316}, pages = {23-34}, year = {2015}, abstract = {Questionnaire data from two projects on the development of quality assurance instruments for an inpatient rehabilitation/prevention program for parents were used for a secondary analysis. In this analysis, the associations of gains in a psychosocial resource (parenting self-efficacy) and two types of stressors experienced by mothers at the start of treatment (parenting hassles, depressive symptoms) with general life satisfaction and satisfaction with health at the end of treatment were explored. Structural equation modeling was applied to data from N = 1724 female patients. Potential resource-stressor interactions were tested using the Latent Moderated Structural Equations approach. Results showed that parenting hassles were negatively associated with general life satisfaction and satisfaction with health while self-efficacy gains were weakly positively correlated with both variables. No interaction of parenting hassles and self-efficacy gains was found. Depressive symptoms were negatively associated with both satisfaction measures. In these models, self-efficacy gains were not substantially correlated with life satisfaction, but showed a small association with satisfaction with health. There was no significant interaction of depressive symptoms and self-efficacy gains. The findings imply that interventions for distressed mothers—as exemplarily illustrated by this inpatient setting—should focus on identifying and reducing initial stressors as these may continue to impair mothers' subjective health despite gains in parenting-related resources.}, language = {en} } @article{SalvadorBurekFoerster2015, author = {Salvador, Ellaine and Burek, Malgorzata and F{\"o}rster, Carola Y.}, title = {Stretch and/or oxygen glucose deprivation (OGD) in an in vitro traumatic brain injury (TBI) model induces calcium alteration and inflammatory cascade}, series = {Frontiers in Cellular Neuroscience}, volume = {9}, journal = {Frontiers in Cellular Neuroscience}, number = {323}, doi = {10.3389/fncel.2015.00323}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148255}, year = {2015}, abstract = {The blood-brain barrier (BBB), made up of endothelial cells of capillaries in the brain, maintains the microenvironment of the central nervous system. During ischemia and traumatic brain injury (TBI), cellular disruption leading to mechanical insult results to the BBB being compromised. Oxygen glucose deprivation (OGD) is the most commonly used in vitro model for ischemia. On the other hand, stretch injury is currently being used to model TBI in vitro. In this paper, the two methods are used alone or in combination, to assess their effects on cerebrovascular endothelial cells cEND in the presence or absence of astrocytic factors. Applying severe stretch and/or OGD to cEND cells in our experiments resulted to cell swelling and distortion. Damage to the cells induced release of lactate dehydrogenase enzyme (LDH) and nitric oxide (NO) into the cell culture medium. In addition, mRNA expression of inflammatory markers interleukin (I L)-6, IL-1\(\alpha\) chemokine (C-C motif) ligand 2 (CCL2) and tumor necrosis factor (TNF)-\(\alpha\) also increased. These events could lead to the opening of calcium ion channels resulting to excitotoxicity. This could be demonstrated by increased calcium level in OGD-subjected cEND cells incubated with astrocyte-conditioned medium. Furthermore, reduction of cell membrane integrity decreased tight junction proteins claudin-5 and occludin expression. In addition, permeability of the endothelial cell monolayer increased. Also, since cell damage requires an increased uptake of glucose, expression of glucose transporter glut1 was found to increase at the mRNA level after OGD. Overall, the effects of OGD on cEND cells appear to be more prominent than that of stretch with regards to TJ proteins, NO, glutl expression, and calcium level. Astrocytes potentiate these effects on calcium level in cEND cells. Combining both methods to model TBI in vitro shows a promising improvement to currently available models.}, language = {en} } @article{LaineAlbeckavandeLindeetal.2015, author = {Laine, Romain F. and Albecka, Anna and van de Linde, Sebastian and Rees, Eric J. and Crump, Colin M. and Kaminski, Clemens F.}, title = {Structural analysis of herpes simplex virus by optical super-resolution imaging}, series = {Nature Communications}, volume = {6}, journal = {Nature Communications}, number = {5980}, doi = {10.1038/ncomms6980}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144623}, year = {2015}, abstract = {Herpes simplex virus type-1 (HSV-1) is one of the most widespread pathogens among humans. Although the structure of HSV-1 has been extensively investigated, the precise organization of tegument and envelope proteins remains elusive. Here we use super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) in combination with a model-based analysis of single-molecule localization data, to determine the position of protein layers within virus particles. We resolve different protein layers within individual HSV-1 particles using multi-colour dSTORM imaging and discriminate envelope-anchored glycoproteins from tegument proteins, both in purified virions and in virions present in infected cells. Precise characterization of HSV-1 structure was achieved by particle averaging of purified viruses and model-based analysis of the radial distribution of the tegument proteins VP16, VP1/2 and pUL37, and envelope protein gD. From this data, we propose a model of the protein organization inside the tegument.}, language = {en} } @phdthesis{Delto2015, author = {Delto, Carolyn Francesca}, title = {Structural and Biochemical Characterization of the GABA(A) Receptor Interacting Protein Muskelin}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115922}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {In a study from 2011, the protein muskelin was described as a central coordinator of the retrograde transport of GABA(A) receptors in neurons. As muskelin governs the transport along actin filaments as well as microtubules, it might be the first representative of a novel class of regulators, which coordinate cargo transport across the borders of these two independent systems of transport paths and their associated motorproteins. To establish a basis for understanding the mode of operation of muskelin, the aim of this thesis was an in-depth biochemical and structural characterization of muskelin and its interaction with the GABA(A) receptor. One focus of the work was the analysis of the oligomerization of muskelin. As could be demonstrated, the oligomerization is based on two independent interactions mediated by different domains of the protein: a known interaction of the N-terminal discoidin domain with the C-terminal portion, termed head-to-tail interaction, and a dimerization of the LisH motif in muskelin that was so far neglected in the literature. For the detailed studies of both binding events, the solution of a crystal structure of a fragment of muskelin, comprising the Discoidin domain and the LisH motif, was an important basis. The fragment crystallized as a dimer, with dimerization being mediated solely by the LisH motif. Biochemical analysis corroborated that the LisH motif in muskelin serves as a dimerization element, and, moreover, showed that the C-terminal domain of the protein substantially stabilizes this dimerization. In addition, the crystal structure revealed the molecular composition of the surface of the head in the head-to-tail interaction, namely the discoidin domain. This information enabled to map the amino acids contributing to binding, which showed that the binding site of the head-to-tail interaction coincides with the generic ligand binding site of the discoidin domain. As part of the analyses, residues that are critical for LisH-dimerization and the head-to-tail binding, respectively, were identified, whose mutation specifically interfered with each of the interactions separately. These mutations allowed to investigate the interplay of these interactions during oligomerization. It could be shown that recombinant muskelin assembles into a tetramer to which both interactions, the LisH-dimerization and the head-to-tail binding, contribute independently. When one of the two interactions was disturbed, only a dimer mediated via the respective other interaction could be formed; when both interactions were disturbed, the protein was present as monomer. Furthermore, Frank Heisler in the group of Matthias Kneussel was able to show the drastic impact of an impaired LisH-dimerization on muskelin in cells using these mutations. Disturbing the LisH-dimerization led to a complete redistribution of the originally cytoplasmic muskelin to the nucleus which was accompanied by a severe impairment of its function during GABA(A) receptor transport. Following up on these results in an analysis of muskelin variants, for which alterations of the subcellular localization had been published earlier, the crucial influence of LisH-dimerization to the subcellular localization and thereby the role of muskelin in the cell was confirmed. The biochemical studies of the interaction of muskelin and the alpha1 subunit of the GABA(A) receptor demonstrated a direct binding with an affinity in the low micromolar range, which is mediated primarily by the kelch repeat domain in muskelin. For the binding site on the GABA(A) receptor, it was confirmed that the thirteen most C-terminal residues of the intracellular domain are critical for the binding of muskelin. In accordance with the strong conservation of these residues among the alpha subunits of the GABA(A) receptor, it could be shown that an interaction with muskelin in vitro is also possible for the alpha2 and alpha5 subunits. Based on the comparison of the binding sites between the homologous subunits, tentative conclusions can be drawn about the details of the binding, which may serve as a starting point for follow-up studies. This thesis thereby makes valuable contributions to the understanding of muskelin, in particular the significance of its oligomerization. It furthermore provides an experimental framework for future studies that address related topics, such as the characterization of other muskelin interaction partners, or the questions raised in this work.}, subject = {Oligomerisation}, language = {en} } @article{LeeSongHanetal.2015, author = {Lee, Eun-Hye and Song, Jin-Dong and Han, Il-Ki and Chang, Soo-Kyung and Langer, Fabian and H{\"o}fling, Sven and Forchel, Alfred and Kamp, Martin and Kim, Jong-Su}, title = {Structural and optical properties of position-retrievable low-density GaAs droplet epitaxial quantum dots for application to single photon sources with plasmonic optical coupling}, series = {Nanoscale Research Letters}, volume = {10}, journal = {Nanoscale Research Letters}, number = {114}, doi = {10.1186/s11671-015-0826-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143692}, year = {2015}, abstract = {The position of a single GaAs quantum dot (QD), which is optically active, grown by low-density droplet epitaxy (DE) (approximately 4 QDs/μm\(^{2}\)), was directly observed on the surface of a 45-nm-thick Al\(_{0.3}\)Ga\(_{0.7}\)As capping layer. The thin thickness of AlGaAs capping layer is useful for single photon sources with plasmonic optical coupling. A micro-photoluminescence for GaAs DE QDs has shown exciton/biexciton behavior in the range of 1.654 to 1.657 eV. The direct observation of positions of low-density GaAs DE QDs would be advantageous for mass fabrication of devices that use a single QD, such as single photon sources.}, language = {en} } @article{DyksikMotykaSęketal.2015, author = {Dyksik, Mateusz and Motyka, Marcin and Sęk, Grzegorz and Misiewicz, Jan and Dallner, Matthias and Weih, Robert and Kamp, Martin and H{\"o}fling, Sven}, title = {Submonolayer Uniformity of Type II InAs/GaInSb W-shaped Quantum Wells Probed by Full-Wafer Photoluminescence Mapping in the Mid-infrared Spectral Range}, series = {Nanoscale Research Letters}, volume = {10}, journal = {Nanoscale Research Letters}, number = {402}, doi = {10.1186/s11671-015-1104-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139733}, year = {2015}, abstract = {The spatial uniformity of GaSb- and InAs substrate-based structures containing type II quantum wells was probed by means of large-scale photoluminescence (PL) mapping realized utilizing a Fourier transform infrared spectrometer. The active region was designed and grown in a form of a W-shaped structure with InAs and GaInSb layers for confinement of electrons and holes, respectively. The PL spectra were recorded over the entire 2-in. wafers, and the parameters extracted from each spectrum, such as PL peak energy position, its linewidth and integrated intensity, were collected in a form of two-dimensional spatial maps. Throughout the analysis of these maps, the wafers' homogeneity and precision of the growth procedure were investigated. A very small variation of PL peak energy over the wafer indicates InAs quantum well width fluctuation of only a fraction of a monolayer and hence extraordinary thickness accuracy, a conclusion further supported by high uniformity of both the emission intensity and PL linewidth.}, language = {en} } @article{DrubeWeberLoschinskietal.2015, author = {Drube, Sebastian and Weber, Franziska and Loschinski, Romy and Beyer, Mandy and Rothe, Mandy and Rabenhorst, Anja and G{\"o}pfert, Christiane and Meininger, Isabel and Diamanti, Michaela A. and Stegner, David and H{\"a}fner, Norman and B{\"o}ttcher, Martin and Reinecke, Kirstin and Herdegen, Thomas and Greten, Florian R. and Nieswandt, Bernhard and Hartmann, Karin and Kr{\"a}mer, Oliver H. and Kamradt, Thomas}, title = {Subthreshold IKK activation modulates the effector functions of primary mast cells and allows specific targeting of transformed mast cells}, series = {Oncotarget}, volume = {6}, journal = {Oncotarget}, number = {7}, doi = {10.18632/oncotarget.3022}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143681}, pages = {5354-5368}, year = {2015}, abstract = {Mast cell differentiation and proliferation depends on IL-3. IL-3 induces the activation of MAP-kinases and STATs and consequently induces proliferation and survival. Dysregulation of IL-3 signaling pathways also contribute to inflammation and tumorigenesis. We show here that IL-3 induces a SFK- and Ca2\(^{+}\)-dependent activation of the inhibitor of κB kinases 2 (IKK2) which results in mast cell proliferation and survival but does not induce IκBα-degradation and NFκB activation. Therefore we propose the term "subthreshold IKK activation". This subthreshold IKK activation also primes mast cells for enhanced responsiveness to IL-33R signaling. Consequently, co-stimulation with IL-3 and IL-33 increases IKK activation and massively enhances cytokine production induced by IL-33. We further reveal that in neoplastic mast cells expressing constitutively active Ras, subthreshold IKK activation is associated with uncontrolled proliferation. Consequently, pharmacological IKK inhibition reduces tumor growth selectively by inducing apoptosis in vivo. Together, subthreshold IKK activation is crucial to mediate the full IL-33-induced effector functions in primary mast cells and to mediate uncontrolled proliferation of neoplastic mast cells. Thus, IKK2 is a new molecularly defined target structure.}, language = {en} } @phdthesis{Kuhlmann2015, author = {Kuhlmann, Matthias}, title = {Sulfur-functional polymers for biomedical applications}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119832}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Aim of this thesis was to combine the versatility of sulfur-chemistry, regarding redox-sensitivity as well as chemo- and site-specific conjugation, with multifunctionality of poly(glycidol)s as an alternative to poly(ethylene glycol). First the homo- and copolymerizations of EEGE and AGE were performed with respect to molar-mass distribution and reaction kinetics. A detailed study was given, varying the polymerization parameters such as DP, counter ion, solvent and monomer influence. It can be concluded that in general the rates for all polymerizations are higher using K+, in contrast to Cs+, as counter ion for the active alkoxide species. Unfortunately, K+ as counter ion commonly leads to a reduced control over polymer dispersity. In this thesis it was shown that the broad molar-mass distributions might be reduced by adding the monomer in a step-wise manner. In experiments with a syringe pump, for continuously adding the monomer, a significant reduction of the dispersities could be found using K+ as counter ion. In analogy to the oxyanionic polymerization of epoxides, the polymerization of episulfides via a thioanionic mechanism with various DPs was successful with thiols/DBU as initiator. In most experiments bimodality could be observed due to the dimerization, caused by oxidation processes by introduced oxygen during synthesis. Reducing this was successful by modifying the degassing procedure, e.g. repeated degassing cycles after each step, i.e. initiation, monomer addition and quenching. Unfortunately, it was not always possible to completely avoid the dimerization due to oxidation. Thiophenol, butanethiol, mercaptoethanol and dithiothreitol were used as thiol initiators, all being capable to initiate the polymerization. With the prediction and the narrow molar-mass distributions, the living character of the polymerization is therefore indicated. Homo- and copolymers of poly(glycidol) were used to functionalize these polymers with side-chains bearing amines, thiols, carboxylic acids and cysteines. The cysteine side-chains were obtained using a newly synthesized thiol-functional thiazolidine. For this, cysteine was protected using a condensation reaction with acetone yielding a dimethyl-substituted thiazolidine. Protection of the ring-amine was obtained via a mixed-anhydride route using formic acid and acetic anhydride. The carboxylic acid of 2,2-dimethylthiazolidine-4-carboxylic acid was activated with CDI and cysteamine attached. The obtained crystalline mercaptothiazolidine was subjected to thiol-ene click chemistry with allyl-functional poly(glycidol). A systematic comparison of thermal- versus photo-initiation showed a much higher yield and reaction rate for the UV-light mediated thiol-ene synthesis with DMPA as photo-initiator. Hydrolysis of the protected thiazolidine-functionalities was obtained upon heating the samples for 5 d at 70 °C in 0.1 M HCl. Dialysis against acetic acid lead to cysteine-functional poly(glycidol)s, storable as the acetate salt even under non-inert atmosphere. An oxidative TNBSA assay was developed to quantify the cysteine-content without the influence of the thiol-functionality. A cooperation partner coupled C-terminal thioester peptides with the cysteine-functional poly(glycidol)s and showed the good accessibility and reactivity of the cysteines along the backbone. SDS-PAGE, HPLC and MALDI-ToF measurements confirmed the successful coupling.}, subject = {Polymer}, language = {en} } @article{EhmannSauerKittel2015, author = {Ehmann, Nadine and Sauer, Markus and Kittel, Robert J.}, title = {Super-resolution microscopy of the synaptic active zone}, series = {Frontiers in Cellular Neuroscience}, volume = {9}, journal = {Frontiers in Cellular Neuroscience}, number = {7}, doi = {10.3389/fncel.2015.00007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148997}, year = {2015}, abstract = {Brain function relies on accurate information transfer at chemical synapses. At the presynaptic active zone (AZ) a variety of specialized proteins are assembled to complex architectures, which set the basis for speed, precision and plasticity of synaptic transmission. Calcium channels are pivotal for the initiation of excitation-secretion coupling and, correspondingly, capture a central position at the AZ. Combining quantitative functional studies with modeling approaches has provided predictions of channel properties, numbers and even positions on the nanometer scale. However, elucidating the nanoscopic organization of the surrounding protein network requires direct ultrastructural access. Without this information, knowledge of molecular synaptic structure-function relationships remains incomplete. Recently, super-resolution microscopy (SRM) techniques have begun to enter the neurosciences. These approaches combine high spatial resolution with the molecular specificity of fluorescence microscopy. Here, we discuss how SRM can be used to obtain information on the organization of AZ proteins}, language = {en} } @article{GoerlZhangStepanenkoetal.2015, author = {G{\"o}rl, Daniel and Zhang, Xin and Stepanenko, Vladimir and W{\"u}rthner, Frank}, title = {Supramolecular block copolymers by kinetically controlled co-self-assembly of planar and core-twisted perylene bisimides}, series = {Nature Communications}, volume = {6}, journal = {Nature Communications}, number = {7009}, doi = {10.1038/ncomms8009}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148657}, year = {2015}, abstract = {New synthetic methodologies for the formation of block copolymers have revolutionized polymer science within the last two decades. However, the formation of supramolecular block copolymers composed of alternating sequences of larger block segments has not been realized yet. Here we show by transmission electron microscopy (TEM), 2D NMR and optical spectroscopy that two different perylene bisimide dyes bearing either a flat (A) or a twisted (B) core self-assemble in water into supramolecular block copolymers with an alternating sequence of (A\(_{m}\)BB)\(_{n}\). The highly defined ultralong nanowire structure of these supramolecular copolymers is entirely different from those formed upon self-assembly of the individual counterparts, that is, stiff nanorods (A) and irregular nanoworms (B), respectively. Our studies further reveal that the as-formed supramolecular block copolymer constitutes a kinetic self-assembly product that transforms into thermodynamically more stable self-sorted homopolymers upon heating.}, language = {en} } @phdthesis{Holz2015, author = {Holz, Elisa Mira}, title = {Systematic evaluation of non-invasive brain-computer interfaces as assistive devices for persons with severe motor impairment based on a user-centred approach - in controlled settings and independent use}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126334}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Brain-computer interfaces (BCIs) are devices that translate signals from the brain into control commands for applications. Within the last twenty years, BCI applications have been developed for communication, environmental control, entertainment, and substitution of motor functions. Since BCIs provide muscle independent communication and control of the environment by circumventing motor pathways, they are considered as assistive technologies for persons with neurological and neurodegenerative diseases leading to motor paralysis, such as amyotrophic lateral sclerosis (ALS), muscular dystrophy, spinal muscular atrophy and stroke (K{\"u}bler, Kotchoubey, Kaiser, Wolpaw, \& Birbaumer, 2001). Although most researcher mention persons with severe motor impairment as target group for their BCI systems, most studies include healthy participants and studies including potential BCI end-users are sparse. Thus, there is a substantial lack of studies that investigate whether results obtained in healthy participants can be transferred to patients with neurodegenerative diseases. This clearly shows that BCI research faces a translational gap between intense BCI research and bringing BCI applications to end-users outside the lab (K{\"u}bler, Mattia, Rupp, \& Tangermann, 2013). Translational studies are needed that investigate whether BCIs can be successfully used by severely disabled end-users and whether those end-users would accept BCIs as assistive devices. Another obvious discrepancy exists between a plethora of short-term studies and a sparse number of long-term studies. BCI research thus also faces a reliability gap (K{\"u}bler, Mattia, et al., 2013). Most studies present only one BCI session, however the few studies that include several testing sessions indicate high inter- and intra-individual variance in the end-users' performance due to non-stationarity of signals. Long-term studies, however, are needed to demonstrate whether a BCI can be reliably used as assistive device over a longer period of time in the daily-life of a person. Therefore there is also a great need for reliability studies. The purpose of the present thesis was to address these research gaps and to bring BCIs closer to end-users in need, especially into their daily-lives, following a user-centred design (UCD). The UCD was suggested as theoretical framework for bringing BCIs to end-users by K{\"u}bler and colleagues (K{\"u}bler et al., 2014; Zickler et al., 2011). This approach aims at the close and iterative interaction between BCI developers and end-users with the final goal to develop BCI systems that are accepted as assistive devices by end-users. The UCD focuses on usability, that is, how well a BCI technology matches the purpose and meets the needs and requirements of the targeted end-users and was standardized with the ISO 9241-210. Within the UCD framework, usability of a device can be defined with regard to its effectiveness, efficiency and satisfaction. These aspects were operationalized by K{\"u}bler and colleagues to evaluate BCI-controlled applications. As suggested by Vaughan and colleagues, the number of BCI sessions, the total usage duration and the impact of the BCI on the life of the person can be considered as indicators of usefulness of the BCI in long-term daily-life use (Vaughan, Sellers, \& Wolpaw, 2012). These definitions and metrics for usability and usefulness were applied for evaluating BCI applications as assistive devices in controlled settings and independent use. Three different BCI applications were tested and evaluated by in total N=10 end-users: In study 1 a motor-imagery (MI) based BCI for gaming was tested by four end-users with severe motor impairment. In study 2, a hybrid P300 event-related (ERP) based BCI for communication was tested by four severely motor restricted end-users with severe motor impairment. Study 1 and 2 are short-term studies conducted in a controlled-setting. In study 3 a P300-ERP BCI for creative expression was installed for long-term independent use at the homes of two end-users in the locked-in state. Both end-users are artists who had gradually lost the ability to paint after being diagnosed with ALS. Results reveal that BCI controlled devices are accepted as assistive devices. Main obstacles for daily-life use were the not very aesthetic design of the EEG-cap and electrodes (cap is eye-catching and looks medical), low comfort (cables disturb, immobility, electrodes press against head if lying on a head cushion), complicated and time-consuming adjustment, low efficiency and low effectiveness, and not very high reliability (many influencing factors). While effectiveness and efficiency in the MI based BCI were lower compared to applications using the P300-ERP as input channel, the MI controlled gaming application was nevertheless better accepted by the end-users and end-users would rather like to use it compared to the communication applications. Thus, malfunctioning and errors, low speed, and the EEG cap are rather tolerated in gaming applications, compared to communication devices. Since communication is essential for daily-life, it has to be fast and reliable. BCIs for communication, at the current state of the art, are not considered competitive with other assistive devices, if other devices, such as eye-gaze, are still an option. However BCIs might be an option when controlling an application for entertainment in daily-life, if communication is still available. Results demonstrate that BCI is adopted in daily-life if it matches the end-users needs and requirements. Brain Painting serves as best representative, as it matches the artists' need for creative expression. Caveats such as uncomfortable cap, dependence on others for set-up, and experienced low control are tolerated and do not prevent BCI use on a daily basis. Also end-users in real need of means for communication, such as persons in the locked-in state with unreliable eye-movement or no means for independent communication, do accept obstacles of the BCI, as it is the last or only solution to communicate or control devices. Thus, these aspects are "no real obstacles" but rather "challenges" that do not prevent end-users to use the BCI in their daily-lives. For instance, one end-user, who uses a BCI in her daily-life, stated: "I don't care about aesthetic design of EEG cap and electrodes nor amplifier". Thus, the question is not which system is superior to the other, but which system is best for an individual user with specific symptoms, needs, requirements, existing assistive solutions, support by caregivers/family etc.; it is thereby a question of indication. These factors seem to be better "predictors" for adoption of a BCI in daily-life, than common usability criterions such as effectiveness or efficiency. The face valid measures of daily-life demonstrate that BCI-controlled applications can be used in daily-life for more than 3 years, with high satisfaction for the end-users, without experts being present and despite a decrease in the amplitude of the P300 signal. Brain Painting re-enabled both artists to be creatively active in their home environment and thus improved their feelings of happiness, usefulness, self-esteem, well-being, and consequently quality of life and supports social inclusion. This thesis suggests that BCIs are valuable tools for people in the locked-in state.}, subject = {Gehirn-Computer-Schnittstelle}, language = {en} } @phdthesis{Richard2015, author = {Richard, Annika}, title = {Systematic Review of Measles, Mumps and Rubella Vaccination Programs in Selected European Countries and the Influence of Migration Movements}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-138033}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Masern, Mumps und R{\"o}teln sind virale Infektionskrankheiten, die schwere und verheerenden Komplikationen bei den erkrankten Personen verursachen k{\"o}nnen. Die weltweite Krankheitslast dieser Infektionskrankheiten ist hoch und k{\"o}nnte durch erfolgreiche Impfstrategien merkenswert reduziert werden. Die WHO hat daher das Ziel der globalen Eliminierung von Masern und R{\"o}teln sowie der Kontrolle der oft simultan geimpften Mumps Erkrankung gesetzt. Im Jahr 2010 einigten sich die WHO-Mitgliedstaaten der europ{\"a}ischen Region, gezielte Strategien zu verfolgen, um Masern und R{\"o}teln bis Ende des Jahres 2015 in Europa zu eliminieren. Analysen bez{\"u}glich des aktuellen Fortschrittes werden daher zunehmend relevanter. Als Teil dieser systematischen Literaturrecherche wurden die Immunisierungsstrategien, Impfraten und Krankheitsinzidenzen von elf europ{\"a}ischen L{\"a}ndern untersucht und ihre Fortschritte im Hinblick auf die Krankheitseliminierung bewertet. Eine erfolgreiche Pr{\"a}vention der endemischen {\"U}bertragung von Masern, Mumps oder R{\"o}teln Viren konnte in mehreren L{\"a}ndern erreicht werden, darunter Schweden, Kroatien, Griechenland und Spanien. Den L{\"a}ndern {\"O}sterreich, Frankreich, Deutschland, Italien, Polen, T{\"u}rkei und dem Vereinigten K{\"o}nigreich von Großbritannien und Nordirland ist es trotz verbesserter Immunisierungsraten bisher nicht gelungen, die Eliminierungsziele zu erreichen. In der T{\"u}rkei, Italien und Polen, kam es in den letzten Jahren zu starken Anstiegen der Fallzahlen, welche die Masern, Mumps und R{\"o}teln Kontrolle in Europa deutlich erschweren und das zeitnahe Erreichen der Eliminationsziele gef{\"a}hrden. Unzureichend immunisierte Bev{\"o}lkerungsgruppen, die zu einer Aufrechterhaltung der Infektionserkrankungen im europ{\"a}ischen Raum beitragen k{\"o}nnen, wurden identifiziert. Dazu z{\"a}hlen S{\"a}uglinge und Kleinkinder, Jugendliche und junge Erwachsene, M{\"a}nner, k{\"u}rzlich eingewanderte Personen und Fl{\"u}chtlinge, sowie reisende ethnischer Minderheiten. Die Gr{\"u}nde f{\"u}r das erh{\"o}hte Risiko einer Masern, Mumps oder R{\"o}teln Infektion unter diesen Personengruppen sind vielf{\"a}ltig und ein Ergebnis von verschiedenen historischen und aktuellen Impfstrategien, kulturellen, politischen und religi{\"o}sen Unterschieden, sowie pers{\"o}nlichem Glauben und Ansichten. Das Reisen und die Migration von infizierten Personen nach und zwischen den verschiedenen europ{\"a}ischen L{\"a}ndern spielt auch eine wesentliche Rolle bei der kontinuierlichen {\"U}bertragung der Erkrankungen in Europa. Nur durch eine ausreichend hohe Immunit{\"a}t der Bev{\"o}lkerung kann das Auftreten von gr{\"o}ßeren Ausbr{\"u}chen trotz der Einfuhr viraler Erreger verhindert werden. Bestrebungen sollte daher die Immunisierung aller impff{\"a}higen Personen umfassen, sowie die Erweiterung spezifischer Impfstrategien f{\"u}r unzureichend immunisierte Bev{\"o}lkerungsgruppen, die nur schwer durch Routineimpfungen zu erreichen sind. Europ{\"a}ische L{\"a}nder, in denen die WHO Eliminierungsziele bisher nicht erreicht wurden, k{\"o}nnten m{\"o}glicherweise von alternativen Impfstrategien profitieren. Ein einheitlicher, europaweiter MMR-Impfplan basierend auf den erfolgreichen Immunisierungsverfahren der L{\"a}nder, die Masern, Mumps und R{\"o}teln erfolgreich bek{\"a}mpft haben, stellt ein wirksames Instrument zur Verbesserung der allgemeinen Bev{\"o}lkerungsimmunit{\"a}t und Kontrolle der drei Infektionskrankheiten dar. Ein Entwurf solch eines Impfplanes wurde im Rahmen dieser Dissertation erstellt und enth{\"a}lt Strategien f{\"u}r das Erreichen ungesch{\"u}tzter Bev{\"o}lkerungsgruppen, unabh{\"a}ngig von Alter, Geschlecht oder Migrationshintergrund. Die Umsetzung einheitlicher Impfempfehlungen bringt mehrere Herausforderungen mit sich. Die vielen Vorteile im Hinblick auf die verbesserte Immunisierung, {\"U}berwachung und Bek{\"a}mpfung der Erkrankungen lassen die Aufw{\"a}nde jedoch als berechtigt erscheinen. Die endemische Eliminierung von Masern, Mumps und R{\"o}teln Viren innerhalb der europ{\"a}ischen Region ist durchaus erzielbar. Die aktuelle epidemiologische Situation deutet jedoch darauf hin, dass das Ziel nicht bis zum Ende des Jahres 2015 erreicht wird, sondern weitere Bestrebungen auf internationaler Ebene notwendig sind, um eine wirksame Krankheitsbek{\"a}mpfung in der n{\"a}heren Zukunft zu erreichen. Durch nationale und internationale Verbesserungen der Immunisierungsstrategien und gezielten Impfkampagnen sowie Erkrankungs-Meldesystemen und laborchemischen Erregerbest{\"a}tigungen kann eine weitgef{\"a}cherte Bev{\"o}lkerungsimmunit{\"a}t erzielt und Krankheitseliminierung unter ad{\"a}quatem Monitoring des Fortschritts im gesamten europ{\"a}ischen Raum erreicht werden.}, subject = {Masern}, language = {en} } @article{BahnikStuchlik2015, author = {Bahn{\´i}k, Štěp{\´a}n and Stuchl{\´i}k, Aleš}, title = {Temporal and spatial strategies in an active place avoidance task on Carousel: a study of effects of stability of arena rotation speed in rats}, series = {PeerJ}, volume = {3}, journal = {PeerJ}, number = {e1257}, doi = {10.7717/peerj.1257}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141931}, year = {2015}, abstract = {The active place avoidance task is a dry-arena task used to assess spatial navigation and memory in rodents. In this task, a subject is put on a rotating circular arena and avoids an invisible sector that is stable in relation to the room. Rotation of the arena means that the subject's avoidancemust be active, otherwise the subject will be moved in the to-be-avoided sector by the rotation of the arena and a slight electric shock will be administered. The present experiment explored the effect of variable arena rotation speed on the ability to avoid the to-be-avoided sector. Subjects in a group with variable arena rotation speed learned to avoid the sector with the same speed and attained the same avoidance ability as rats in a group with a stable arena rotation speed. Only a slight difference in preferred position within the room was found between the two groups. No difference was found between the two groups in the dark phase, where subjects could not use orientation cues in the room. Only one rat was able to learn the avoidance of the to-be-avoided sector in this phase. The results of the experiment suggest that idiothetic orientation and interval timing are not crucial for learning avoidance of the to-be-avoided sector. However, idiothetic orientation might be sufficient for avoiding the sector in the dark.}, language = {en} } @article{HillmannWiedmannFraseretal.2015, author = {Hillmann, Steffi and Wiedmann, Silke and Fraser, Alec and Baeza, Juan and Rudd, Anthony and Norrving, Bo and Asplund, Kjell and Niewada, Maciej and Dennis, Martin and Hermanek, Peter and Wolfe, Charles D. A. and Heuschmann, Peter U.}, title = {Temporal changes in the quality of acute stroke care in five national audits across Europe}, series = {BioMed Research International}, volume = {2015}, journal = {BioMed Research International}, number = {432497}, doi = {10.1155/2015/432497}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149059}, year = {2015}, abstract = {Background. Data on potential variations in delivery of appropriate stroke care over time are scarce. We investigated temporal changes in the quality of acute hospital stroke care across five national audits in Europe over a period of six years. Methods. Data were derived from national stroke audits in Germany, Poland, Scotland, Sweden, and England/Wales/Northern Ireland participating within the European Implementation Score (EIS) collaboration. Temporal changes in predefined quality indicators with comparable information between the audits were investigated. Multivariable logistic regression analyses were performed to estimate adherence to quality indicators over time. Results. Between 2004 and 2009, individual data from 542,112 patients treated in 538 centers participating continuously over the study period were included. In most audits, the proportions of patients who were treated on a SU, were screened for dysphagia, and received thrombolytic treatment increased over time and ranged from 2-fold to almost 4-fold increase in patients receiving thrombolytic therapy in 2009 compared to 2004. Conclusions. A general trend towards a better quality of stroke care defined by standardized quality indicators was observed over time. The association between introducing a specific measure and higher adherence over time might indicate that monitoring of stroke care performance contributes to improving quality of care.}, language = {en} } @article{ScholzGehringGuanetal.2015, author = {Scholz, Nicole and Gehring, Jennifer and Guan, Chonglin and Ljaschenko, Dmitrij and Fischer, Robin and Lakshmanan, Vetrivel and Kittel, Robert J. and Langenhan, Tobias}, title = {The adhesion GPCR Latrophilin/CIRL shapes mechanosensation}, series = {Cell Reports}, volume = {11}, journal = {Cell Reports}, doi = {10.1016/j.celrep.2015.04.008}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148626}, pages = {866-874}, year = {2015}, abstract = {G-protein-coupled receptors (GPCRs) are typically regarded as chemosensors that control cellular states in response to soluble extracellular cues. However, the modality of stimuli recognized through adhesion GPCR (aGPCR), the second largest class of the GPCR superfamily, is unresolved. Our study characterizes the Drosophila aGPCR Latrophilin/dCirl, a prototype member of this enigmatic receptor class. We show that dCirl shapes the perception of tactile, proprioceptive, and auditory stimuli through chordotonal neurons, the principal mechanosensors of Drosophila. dCirl sensitizes these neurons for the detection of mechanical stimulation by amplifying their input-output function. Our results indicate that aGPCR may generally process and modulate the perception of mechanical signals, linking these important stimuli to the sensory canon of the GPCR superfamily.}, language = {en} } @article{RovitusoDuffySchroeteretal.2015, author = {Rovituso, Damiano M. and Duffy, Catharina E. and Schroeter, Michael and Kaiser, Claudia C. and Kleinschnitz, Christoph and Bayas, Antonios and Elsner, Rebecca and Kuerten, Stefanie}, title = {The brain antigen-specific B cell response correlates with glatiramer acetate responsiveness in relapsing-remitting multiple sclerosis patients}, series = {Scientific Reports}, volume = {5}, journal = {Scientific Reports}, number = {14265}, doi = {10.1038/srep14265}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148172}, year = {2015}, abstract = {B cells have only recently begun to attract attention in the immunopathology of multiple sclerosis (MS). Suitable markers for the prediction of treatment success with immunomodulatory drugs are still missing. Here we evaluated the B cell response to brain antigens in n = 34 relapsing-remitting MS (RRMS) patients treated with glatiramer acetate (GA) using the enzyme-linked immunospot technique (ELISPOT). Our data demonstrate that patients can be subdivided into responders that show brain-specific B cell reactivity in the blood and patients without this reactivity. Only in patients that classified as B cell responders, there was a significant positive correlation between treatment duration and the time since last relapse in our study. This correlation was GA-specific because it was absent in a control group that consisted of interferon-\(\beta\) (IFN-\(\beta\))-treated RRMS patients (n = 23). These data suggest that GA has an effect on brain-reactive B cells in a subset of patients and that only this subset benefits from treatment. The detection of brain-reactive B cells is likely to be a suitable tool to identify drug responders.}, language = {en} } @article{GarciaMartinezBrunkAvalosetal.2015, author = {Garc{\´i}a-Mart{\´i}nez, Jorge and Brunk, Michael and Avalos, Javier and Terpitz, Ulrich}, title = {The CarO rhodopsin of the fungus Fusarium fujikuroi is a light-driven proton pump that retards spore germination}, series = {Scientific Reports}, volume = {5}, journal = {Scientific Reports}, number = {7798}, doi = {10.1038/srep07798}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149049}, year = {2015}, abstract = {Rhodopsins are membrane-embedded photoreceptors found in all major taxonomic kingdoms using retinal as their chromophore. They play well-known functions in different biological systems, but their roles in fungi remain unknown. The filamentous fungus Fusarium fujikuroi contains two putative rhodopsins, CarO and OpsA. The gene carO is light-regulated, and the predicted polypeptide contains all conserved residues required for proton pumping. We aimed to elucidate the expression and cellular location of the fungal rhodopsin CarO, its presumed proton-pumping activity and the possible effect of such function on F. fujikuroi growth. In electrophysiology experiments we confirmed that CarO is a green-light driven proton pump. Visualization of fluorescent CarO-YFP expressed in F. fujikuroi under control of its native promoter revealed higher accumulation in spores (conidia) produced by light-exposed mycelia. Germination analyses of conidia from carO\(^{-}\) mutant and carO\(^{+}\) control strains showed a faster development of light-exposed carO-germlings. In conclusion, CarO is an active proton pump, abundant in light-formed conidia, whose activity slows down early hyphal development under light. Interestingly, CarO-related rhodopsins are typically found in plant-associated fungi, where green light dominates the phyllosphere. Our data provide the first reliable clue on a possible biological role of a fungal rhodopsin.}, language = {en} } @phdthesis{Zuern2015, author = {Z{\"u}rn, Michael}, title = {The Dual Nature of Utility - Categorical and Comparative Evaluations in Economic Decisions}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120141}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Utility is perhaps the most central concept in modern economic theorizing. However, the behaviorist reduction to Revealed Preference not only removed the psychological content of utility but experimental investigations also exposed numerous anomalies in this theory. This program of research focused on the psychological processes by which utility judgments are generated. For this purpose, the standard assumption of a homogeneous concept is substituted by the Utilitarian Duality Hypothesis. In particular, judgments concerning categorical utility (uCat) infer an object's category based on its attributes which may subsequently allow the transfer of evaluative information like feelings or attitudes. In contrast, comparative utility (uCom) depends on the distance to a reference value on a specific dimension of comparison. Importantly, dimensions of comparison are manifold and context dependent. In a series of experiments, we show that the resulting Dual Utility Model is able to explain several known anomalies in a parsimonious fashion. Moreover, we identify central factors determining the relative weight assigned to both utility components. Finally, we discuss the implications of the Utilitarian Duality for both, the experimental practice in economics as well as the consequences for economic theorizing. In sum, we propose that the Dual Utility Model can serve as an integrative framework for both the rational model and its anomalies.}, subject = {Nutzen}, language = {en} } @article{WieserMoscovitch2015, author = {Wieser, Matthias J. and Moscovitch, David A.}, title = {The effect of affective context on visuocortical processing of neutral faces in social anxiety - An ERP study}, series = {Frontiers in Psychology}, volume = {6}, journal = {Frontiers in Psychology}, doi = {10.3389/fpsyg.2015.01824}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125148}, pages = {1824}, year = {2015}, abstract = {It has been demonstrated that verbal context information alters the neural processing of ambiguous faces such as faces with no apparent facial expression. In social anxiety, neutral faces may be implicitly threatening for socially anxious individuals due to their ambiguous nature, but even more so if these neutral faces are put in self-referential negative contexts. Therefore, we measured event-related brain potentials (ERPs) in response to neutral faces which were preceded by affective verbal information (negative, neutral, positive). Participants with low social anxiety (LSA; n = 23) and high social anxiety (HSA; n = 21) were asked to watch and rate valence and arousal of the respective faces while continuous EEG was recorded. ERP analysis revealed that HSA showed elevated P100 amplitudes in response to faces, but reduced structural encoding of faces as indexed by reduced N170 amplitudes. In general, affective context led to an enhanced early posterior negativity (EPN) for negative compared to neutral facial expressions. Moreover, HSA compared to LSA showed enhanced late positive potentials (LPP) to negatively contextualized faces, whereas in LSA this effect was found for faces in positive contexts. Also, HSA rated faces in negative contexts as more negative compared to LSA. These results point at enhanced vigilance for neutral faces regardless of context in HSA, while structural encoding seems to be diminished (avoidance). Interestingly, later components of sustained processing (LPP) indicate that LSA show enhanced visuocortical processing for faces in positive contexts (happy bias), whereas this seems to be the case for negatively contextualized faces in HSA (threat bias). Finally, our results add further new evidence that top-down information in interaction with individual anxiety levels can influence early-stage aspects of visual perception.}, language = {en} } @article{ZusanGiesekingZersonetal.2015, author = {Zusan, Andreas and Gieseking, Bj{\"o}rn and Zerson, Mario and Dyakonov, Vladimir and Magerle, Robert and Deibel, Carsten}, title = {The Effect of Diiodooctane on the Charge Carrier Generation in Organic Solar Cells Based on the Copolymer PBDTTT-C}, series = {Scientific Reports}, volume = {5}, journal = {Scientific Reports}, doi = {10.1038/srep08286}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125022}, pages = {8286}, year = {2015}, abstract = {Microstructural changes and the understanding of their effect on photocurrent generation are key aspects for improving the efficiency of organic photovoltaic devices. We analyze the impact of a systematically increased amount of the solvent additive diiodooctane (DIO) on the morphology of PBDTTT-C:PC71BM blends and related changes in free carrier formation and recombination by combining surface imaging, photophysical and charge extraction techniques. We identify agglomerates visible in AFM images of the 0\% DIO blend as PC71BM domains embedded in an intermixed matrix phase. With the addition of DIO, a decrease in the size of fullerene domains along with a demixing of the matrix phase appears for 0.6\% and 1\% DIO. Surprisingly, transient absorption spectroscopy reveals an efficient photogeneration already for the smallest amount of DIO, although the largest efficiency is found for 3\% DIO. It is ascribed to a fine-tuning of the blend morphology in terms of the formation of interpenetrating donor and acceptor phases minimizing geminate and nongeminate recombination as indicated by charge extraction experiments. An increase in the DIO content to 10\% adversely affects the photovoltaic performance, most probably due to an inefficient free carrier formation and trapping in a less interconnected donor-acceptor network.}, language = {en} } @article{NeumannOhlsenDonatetal.2015, author = {Neumann, Yvonne and Ohlsen, Knut and Donat, Stefanie and Engelmann, Susanne and Kusch, Harald and Albrecht, Dirk and Cartron, Michael and Hurd, Alexander and Foster, Simon J.}, title = {The effect of skin fatty acids on Staphylococcus aureus}, series = {Archives of Microbiology}, volume = {197}, journal = {Archives of Microbiology}, doi = {10.1007/s00203-014-1048-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121657}, pages = {245-67}, year = {2015}, abstract = {Staphylococcus aureus is a commensal of the human nose and skin. Human skin fatty acids, in particular cis-6-hexadecenoic acid (C-6-H), have high antistaphylococcal activity and can inhibit virulence determinant production. Here, we show that sub-MIC levels of C-6-H result in induction of increased resistance. The mechanism(s) of C-6-H activity was investigated by combined transcriptome and proteome analyses. Proteome analysis demonstrated a pleiotropic effect of C-6-H on virulence determinant production. In response to C-6-H, transcriptomics revealed altered expression of over 500 genes, involved in many aspects of virulence and cellular physiology. The expression of toxins (hla, hlb, hlgBC) was reduced, whereas that of host defence evasion components (cap, sspAB, katA) was increased. In particular, members of the SaeRS regulon had highly reduced expression, and the use of specific mutants revealed that the effect on toxin production is likely mediated via SaeRS}, language = {en} } @phdthesis{Erlbeck2015, author = {Erlbeck, Helena}, title = {The event-related potentials Mismatch Negativity, P300, and N400: Effects of attentional modulation and application in patients with disorders of consciousness}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121041}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {The present work comprises four studies dealing with the investigation of the auditory event-related potentials (ERP) Mismatch Negativity (MMN), P300, and N400 under different attentional instructions, and with their application in patients with disorders of consciousness (DOC) to assess residual cognitive functioning. In guided interviews (study 1), practitioners working with DOC patients stated their general interest in and an objective need for the complementation of current diagnostic procedures by reliable and valid ERP-based methods. Subsequently, in study 2, simple oddball and semantic paradigms were applied to 19 behaviorally non-responsive DOC patients revealing the presence of at least one ERP in eight patients investigated. In the third and fourth study, specific attentional effects on ERPs were investigated in healthy participants to define optimal instructions and stimulus parameters. In study 3, MMN and N400 amplitudes were assessed in 18 participants, and in study 4, MMN and P300 amplitudes were assessed in 32 participants. Both studies included an ignore task (attention on simultaneous visual stimuli), a passive task, and a focused task and revealed distinct attentional effects on P300 and N400 with largest amplitudes in the focused task, smaller ones in the passive task and no ERP in the ignore task. An MMN was elicited in all tasks, but still, amplitudes differed as a function of task. In addition, study 4 included oddball paradigms comprising several deviants in different dimensions. Higher amplitudes were found in this multifeature paradigm compared to traditional oddball paradigms and larger amplitudes were elicited by deviants highly different from standards. It is concluded that ERPs represent a promising tool to complement clinical assessment of DOC patients. Application of ERP paradigms should include focused instructions, especially when using semantic material. Furthermore, multifeature paradigms have been proven especially useful eliciting large amplitudes and allowing for the investigation of several dimensions of deviants at the same time.}, subject = {Bewusstseinsst{\"o}rung}, language = {en} } @article{LeonhardtSpielbergWeberetal.2015, author = {Leonhardt, Ines and Spielberg, Steffi and Weber, Michael and Albrecht-Eckardt, Daniela and Bl{\"a}ss, Markus and Claus, Ralf and Barz, Dagmar and Scherlach, Kirstin and Hertweck, Christian and L{\"o}ffler, J{\"u}rgen and H{\"u}nniger, Kerstin and Kurzai, Oliver}, title = {The fungal quorum-sensing molecule farnesol activates innate immune cells but suppresses cellular adaptive immunity}, series = {mBio}, volume = {6}, journal = {mBio}, number = {2}, doi = {10.1128/mBio.00143-15}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143756}, pages = {e00143-15}, year = {2015}, abstract = {Farnesol, produced by the polymorphic fungus Candida albicans, is the first quorum-sensing molecule discovered in eukaryotes. Its main function is control of C. albicans filamentation, a process closely linked to pathogenesis. In this study, we analyzed the effects of farnesol on innate immune cells known to be important for fungal clearance and protective immunity. Farnesol enhanced the expression of activation markers on monocytes (CD86 and HLA-DR) and neutrophils (CD66b and CD11b) and promoted oxidative burst and the release of proinflammatory cytokines (tumor necrosis factor alpha [TNF-\(\alpha\)] and macrophage inflammatory protein 1 alpha [MIP-1 \(\alpha\)]). However, this activation did not result in enhanced fungal uptake or killing. Furthermore, the differentiation of monocytes to immature dendritic cells (iDC) was significantly affected by farnesol. Several markers important for maturation and antigen presentation like CD1a, CD83, CD86, and CD80 were significantly reduced in the presence of farnesol. Furthermore, farnesol modulated migrational behavior and cytokine release and impaired the ability of DC to induce T cell proliferation. Of major importance was the absence of interleukin 12 (IL-12) induction in iDC generated in the presence of farnesol. Transcriptome analyses revealed a farnesol-induced shift in effector molecule expression and a down-regulation of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor during monocytes to iDC differentiation. Taken together, our data unveil the ability of farnesol to act as a virulence factor of C. albicans by influencing innate immune cells to promote inflammation and mitigating the Th1 response, which is essential for fungal clearance.}, language = {en} } @article{WehrleLiedertHeilmannetal.2015, author = {Wehrle, Esther and Liedert, Astrid and Heilmann, Aline and Wehner, Tim and Bindl, Ronny and Fischer, Lena and Haffner-Luntzer, Melanie and Jakob, Franz and Schinke, Thorsten and Amling, Michael and Ignatius, Anita}, title = {The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice}, series = {Disease Models \& Mechanisms}, volume = {8}, journal = {Disease Models \& Mechanisms}, doi = {10.1242/dmm.018622}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144700}, pages = {93-104}, year = {2015}, abstract = {Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV). We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96) were either ovariectomised (OVX) or sham operated (non-OVX) at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day) with 0.3 g peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, micro-computed tomography (mu CT), histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (-81\%) and bone formation (-80\%) in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2) and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+ 1398\%) and bone formation (+637\%), which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet). On a molecular level, we found an upregulation of ER alpha in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERa might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and effective in confined target populations.}, language = {en} } @article{WehrleLiedertHeilmannetal.2015, author = {Wehrle, Esther and Liedert, Astrid and Heilmann, Aline and Wehner, Tim and Bindl, Ronny and Fischer, Lena and Haffner-Luntzer, Melanie and Jakob, Franz and Schinke, Thorsten and Amling, Michael and Ignatius, Anita}, title = {The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice}, series = {Disease Models \& Mechanisms}, volume = {8}, journal = {Disease Models \& Mechanisms}, doi = {10.1242/dmm.018622}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121109}, pages = {93-104}, year = {2015}, abstract = {Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV). We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96) were either ovariectomised (OVX) or sham operated (non-OVX) at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day) with 0.3 G: peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, micro-computed tomography (μCT), histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (-81\%) and bone formation (-80\%) in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2) and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+1398\%) and bone formation (+637\%), which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet). On a molecular level, we found an upregulation of ERα in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERα might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and effective in confined target populations.}, language = {en} } @article{DiemerAlpersPeperkornetal.2015, author = {Diemer, Julia and Alpers, Georg W. and Peperkorn, Henrik M. and Shiban, Youssef and M{\"u}hlberger, Andreas}, title = {The impact of perception and presence on emotional reactions: a review of research in virtual reality}, series = {Frontiers in Psychology}, volume = {6}, journal = {Frontiers in Psychology}, number = {26}, doi = {10.3389/fpsyg.2015.00026}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144200}, year = {2015}, abstract = {Virtual reality (VR) has made its way into mainstream psychological research in the last two decades. This technology, with its unique ability to simulate complex, real situations and contexts, offers researchers unprecedented opportunities to investigate human behavior in well controlled designs in the laboratory. One important application of VR is the investigation of pathological processes in mental disorders, especially anxiety disorders. Research on the processes underlying threat perception, fear, and exposure therapy has shed light on more general aspects of the relation between perception and emotion. Being by its nature virtual, i.e., simulation of reality, VR strongly relies on the adequate selection of specific perceptual cues to activate emotions. Emotional experiences in turn are related to presence, another important concept in VR, which describes the user's sense of being in a VR environment. This paper summarizes current research into perception of fear cues, emotion, and presence, aiming at the identification of the most relevant aspects of emotional experience in VR and their mutual relations. A special focus lies on a series of recent experiments designed to test the relative contribution of perception and conceptual information on fear in VR. This strand of research capitalizes on the dissociation between perception (bottom up input) and conceptual information (top-down input) that is possible in VR. Further, we review the factors that have so far been recognized to influence presence, with emotions (e.g., fear) being the most relevant in the context of clinical psychology. Recent research has highlighted the mutual influence of presence and fear in VR, but has also traced the limits of our current understanding of this relationship. In this paper, the crucial role of perception on eliciting emotional reactions is highlighted, and the role of arousal as a basic dimension of emotional experience is discussed. An interoceptive attribution model of presence is suggested as a first step toward an integrative framework for emotion research in VR. Gaps in the current literature and future directions are outlined.}, language = {en} } @article{FedericoRedentiSturleseetal.2015, author = {Federico, Stephanie and Redenti, Sara and Sturlese, Mattia and Ciancetta, Antonella and Kachler, Sonja and Klotz, Karl-Norbert and Cacciari, Barbara and Moro, Stefano and Spalluto, Giampiero}, title = {The Influence of the 1-(3-Trifluoromethyl-Benzyl)-1H-Pyrazole-4-yl Moiety on the Adenosine Receptors Affinity Profile of Pyrazolo[4,3-e][1,2,4]Triazolo[1,5-c]Pyrimidine Derivatives}, series = {PLoS One}, volume = {10}, journal = {PLoS One}, number = {12}, doi = {10.1371/journal.pone.0143504}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137133}, pages = {e0143504}, year = {2015}, abstract = {A new series of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine (PTP) derivatives has been developed in order to explore their affinity and selectivity profile at the four adenosine receptor subtypes. In particular, the PTP scaffold was conjugated at the C2 position with the 1-(3-trifluoromethyl-benzyl)-1H-pyrazole, a group believed to confer potency and selectivity toward the human (h) A\(_{2B}\) adenosine receptor (AR) to the xanthine ligand 8-(1-(3-(trifluoromethyl) benzyl)-1H-pyrazol-4-yl)-1,3-dimethyl-1H-purine-2,6(3H, 7H)-dione (CVT 6975). Interestingly, the synthesized compounds turned out to be inactive at the hA\(_{2B}\) AR but they displayed affinity at the hA\(_3\) AR in the nanomolar range. The best compound of the series (6) shows both high affinity (hA\(_3\) AR K\(_i\) = 11 nM) and selectivity (A\(_1\)/A\(_3\) and A\(_{2A}\)/A\(_3\) > 9090; A\(_{2B}\)/A\(_3\) > 909) at the hA\(_3\) AR. To better rationalize these results, a molecular docking study on the four AR subtypes was performed for all the synthesized compounds. In addition, CTV 6975 and two close analogues have been subjected to the same molecular docking protocol to investigate the role of the 1-(3-trifluoromethyl-benzyl)-1H-pyrazole on the binding at the four ARs.}, language = {en} } @article{BiernackaSangkuhlJenkinsetal.2015, author = {Biernacka, J. M. and Sangkuhl, K. and Jenkins, G. and Whaley, R. M. and Barman, P. and Batzler, A. and Altman, R. B. and Arolt, V. and Brockm{\"o}ller, J. and Chen, C. H. and Domschke, K. and Hall-Flavin, D. K. and Hong, C. J. and Illi, A. and Ji, Y. and Kampman, O. and Kinoshita, T. and Leinonen, E. and Liou, Y. J. and Mushiroda, T. and Nonen, S. and Skime, M. K. and Wang, L. and Baune, B. T. and Kato, M. and Liu, Y. L. and Praphanphoj, V. and Stingl, J. C. and Tsai, S. J. and Kubo, M. and Klein, T. E. and Weinshilboum, R.}, title = {The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response}, series = {Translational Psychiatry}, volume = {5}, journal = {Translational Psychiatry}, number = {e553}, doi = {10.1038/tp.2015.47}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143223}, year = {2015}, abstract = {Response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably between patients. The International SSRI Pharmacogenomics Consortium (ISPC) was formed with the primary goal of identifying genetic variation that may contribute to response to SSRI treatment of major depressive disorder. A genome-wide association study of 4-week treatment outcomes, measured using the 17-item Hamilton Rating Scale for Depression (HRSD-17), was performed using data from 865 subjects from seven sites. The primary outcomes were percent change in HRSD-17 score and response, defined as at least 50\% reduction in HRSD-17. Data from two prior studies, the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study (PGRN-AMPS) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, were used for replication, and a meta-analysis of the three studies was performed (N = 2394). Although many top association signals in the ISPC analysis map to interesting candidate genes, none were significant at the genome-wide level and the associations were not replicated using PGRN-AMPS and STAR*D data. Top association results in the meta-analysis of response included single-nucleotide polymorphisms (SNPs) in the HPRTP4 (hypoxanthine phosphoribosyltransferase pseudogene 4)/VSTM5 (V-set and transmembrane domain containing 5) region, which approached genome-wide significance (P = 5.03E - 08) and SNPs 5' upstream of the neuregulin-1 gene, NRG1 (P = 1.20E - 06). NRG1 is involved in many aspects of brain development, including neuronal maturation and variations in this gene have been shown to be associated with increased risk for mental disorders, particularly schizophrenia. Replication and functional studies of these findings are warranted.}, language = {en} } @article{HoppAlbertWeissenberger2015, author = {Hopp, Sarah and Albert-Weissenberger, Christiane}, title = {The kallikrein-kinin system: a promising therapeutic target for traumatic brain injury}, series = {Neural Regeneration Research}, volume = {10}, journal = {Neural Regeneration Research}, number = {6}, doi = {10.4103/1673-5374.158339}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149416}, pages = {885-886}, year = {2015}, abstract = {No abstract available.}, language = {en} } @article{PaschLinkBecketal.2015, author = {Pasch, Elisabeth and Link, Jana and Beck, Carolin and Scheuerle, Stefanie and Alsheimer, Manfred}, title = {The LINC complex component Sun4 plays a crucial role in sperm head formation and fertility}, series = {Biology Open}, volume = {4}, journal = {Biology Open}, doi = {10.1242/bio.015768}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125212}, pages = {1792-1802}, year = {2015}, abstract = {LINC complexes are evolutionarily conserved nuclear envelope bridges, physically connecting the nucleus to the peripheral cytoskeleton. They are pivotal for dynamic cellular and developmental processes, like nuclear migration, anchoring and positioning, meiotic chromosome movements and maintenance of cell polarity and nuclear shape. Active nuclear reshaping is a hallmark of mammalian sperm development and, by transducing cytoskeletal forces to the nuclear envelope, LINC complexes could be vital for sperm head formation as well. We here analyzed in detail the behavior and function of Sun4, a bona fide testis-specific LINC component. We demonstrate that Sun4 is solely expressed in spermatids and there localizes to the posterior nuclear envelope, likely interacting with Sun3/Nesprin1 LINC components. Our study revealed that Sun4 deficiency severely impacts the nucleocytoplasmic junction, leads to mislocalization of other LINC components and interferes with the formation of the microtubule manchette, which finally culminates in a globozoospermia-like phenotype. Together, our study provides direct evidence for a critical role of LINC complexes in mammalian sperm head formation and male fertility.}, language = {en} } @techreport{Lauth2015, type = {Working Paper}, author = {Lauth, Hans-Joachim}, title = {The Matrix of Democracy: A Three-Dimensional Approach to Measuring the Quality of Democracy and Regime Transformations}, doi = {10.25972/OPUS-10966}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-109665}, pages = {29}, year = {2015}, abstract = {The article presents a proposal for the assessment of the quality of democracy. After elaborating on the methodological strategy, a definition of democracy is proposed, which entails the construction of the matrix of democracy based on three dimensions (political freedom, political equality, and political and judicial control) and five institutions. The methodological application of this measuring tool is then explained. This conception guarantees an appropriate measurement in different cultural contexts, enables the characterization of democratic profiles, and allows for the identification of deficiencies in democracies. Before the conclusion, three examples of the measurement (USA, Russia, and Italy) illustrate how the matrix works.}, subject = {Vergleichende politische Wissenschaft}, language = {en} } @article{RuckBittnerAfzalietal.2015, author = {Ruck, Tobias and Bittner, Stefan and Afzali, Ali Maisam and G{\"o}bel, Kerstin and Glumm, Sarah and Kraft, Peter and Sommer, Claudia and Kleinschnitz, Christoph and Preusse, Corinna and Stenzel, Werner and Wiendl, Heinz and Meuth, Sven G.}, title = {The NKG2D-IL-15 signaling pathway contributes to T-cell mediated pathology in inflammatory myopathies}, series = {Oncotarget}, volume = {6}, journal = {Oncotarget}, number = {41}, doi = {10.18632/oncotarget.6462}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136047}, year = {2015}, abstract = {NKG2D is an activating receptor on T cells, which has been implicated in the pathogenesis of autoimmune diseases. T cells are critically involved in idiopathic inflammatory myopathies (IIM) and have been proposed as specific therapeutic targets. However, the mechanisms underlying T cell-mediated progressive muscle destruction in IIM remain to be elucidated. We here determined the involvement of the NKG2D - IL-15 signaling pathway. Primary human myoblasts expressed NKG2D ligands, which were further upregulated upon inflammatory stimuli. In parallel, shedding of the soluble NKG2D ligand MICA (sMICA) decreased upon inflammation potentially diminishing inhibition of NKG2D signaling. Membrane-related expression of IL-15 by myoblasts induced differentiation of naive CD8\(^+\) T cells into highly activated, cytotoxic \(CD8^+NKG2D^{high}\) T cells demonstrating NKG2D-dependent lysis of myoblasts in vitro. \(CD8^+NKG2D^{high}\) T cell frequencies were increased in the peripheral blood of polymyositis (PM) patients and correlated with serum creatinine kinase concentrations, while serum sMICA levels were not significantly changed. In muscle biopsy specimens from PM patients expression of the NKG2D ligand MICA/B was upregulated, IL-15 was expressed by muscle cells, CD68\(^+\) macrophages as well as CD4\(^+\) T cells, and \(CD8^+NKG2D^+\) cells were frequently detected within inflammatory infiltrates arguing for a local signaling circuit in the inflammatory muscle milieu. In conclusion, the NKG2D - IL-15 signaling pathway contributes to progressive muscle destruction in IIM potentially opening new therapeutic avenues.}, language = {en} } @article{Schulze2015, author = {Schulze, Daniel}, title = {The Passive Gaze and Hyper-Immunised Spectators: The Politics of Theatrical Live-Broadcasting}, series = {Journal of Contemporary Drama in English}, volume = {3}, journal = {Journal of Contemporary Drama in English}, number = {2}, issn = {2195-0164}, doi = {10.1515/jcde-2015-0024}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195091}, pages = {315-326}, year = {2015}, abstract = {No abstract available.}, language = {en} } @phdthesis{Klein2015, author = {Klein, Dennis}, title = {The pathogenic role of endogenous antibodies in a mouse model for Charcot-Marie-Tooth 1B neuropathy}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121941}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Charcot-Marie-Tooth (CMT) type 1 neuropathies are a genetically heterogeneous group of non-treatable inherited disorders affecting the peripheral nervous system that lead to sensory and motor dysfunction. Secondary low grade inflammation, implicating the innate and adaptive immune system, could previously be identified as a substantial disease modifier in two mouse models for CMT1, CMT1B and 1X, respectively. However, the exact mechanism how the adaptive immune system contributes to disease pathogenesis is not completely understood. Based on observations that the accumulation of endogenous antibodies to myelin components is important for rapid myelin clearance after nerve injury during Wallerian degeneration, a possibly similar mechanism was considered for endogenous antibodies as disease amplifier in mice heterozygously deficient for P0 (P0het), mimicking some typical features of CMT1B. In this study an increased antibody deposition was detected in the affected peripheral nerves of P0het myelin mutant mice. By crossbreeding P0het mutants with mice specifically lacking B-lymphocytes, and therefore antibodies (JHD-/-), a decline of endoneurial macrophages together with a substantially ameliorated demyelination could be demonstrated in 6-month-old mutant mice. Moreover, reconstitution with murine IgGs reverted the neuropathic phenotype, substantiating that endogenous antibodies are potentially pathogenic at this early stage of disease. Unexpectedly, in 12-months-old P0het mutants, JHD deficiency resulted in disease aggravation accompanied by an increased inflammatory reaction and M2-polarized macrophage response. These observations suggest that in a mouse model for CMT1B, the lack of endogenous antibodies has a dichotomous effect: ameliorating early macrophage-mediated demyelination, as opposed to increasing inflammatory reactions leading to disease aggravation at older ages.}, subject = {Maus}, language = {en} } @article{PhillipsChanPaeschkeetal.2015, author = {Phillips, Jane A. and Chan, Angela and Paeschke, Katrin and Zakian, Virginia A.}, title = {The Pif1 helicase, a negative regulator of telomerase, acts preferentially at long telomeres}, series = {PLoS Genetics}, volume = {11}, journal = {PLoS Genetics}, number = {4}, doi = {10.1371/journal.pgen.1005186}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148722}, pages = {e1005186}, year = {2015}, abstract = {Telomerase, the enzyme that maintains telomeres, preferentially lengthens short telomeres. The S. cerevisiae Pif1 DNA helicase inhibits both telomerase-mediated telomere lengthening and de novo telomere addition at double strand breaks (DSB). Here, we report that the association of the telomerase subunits Est2 and Est1 at a DSB was increased in the absence of Pif1, as it is at telomeres, suggesting that Pif1 suppresses de novo telomere addition by removing telomerase from the break. To determine how the absence of Pif1 results in telomere lengthening, we used the single telomere extension assay (STEX), which monitors lengthening of individual telomeres in a single cell cycle. In the absence of Pif1, telomerase added significantly more telomeric DNA, an average of 72 nucleotides per telomere compared to the 45 nucleotides in wild type cells, and the fraction of telomeres lengthened increased almost four-fold. Using an inducible short telomere assay, Est2 and Est1 no longer bound preferentially to a short telomere in pif1 mutant cells while binding of Yku80, a telomere structural protein, was unaffected by the status of the PIF1 locus. Two experiments demonstrate that Pif1 binding is affected by telomere length: Pif1 (but not Yku80) -associated telomeres were 70 bps longer than bulk telomeres, and in the inducible short telomere assay, Pif1 bound better to wild type length telomeres than to short telomeres. Thus, preferential lengthening of short yeast telomeres is achieved in part by targeting the negative regulator Pif1 to long telomeres.}, language = {en} } @phdthesis{Masis2015, author = {Mas{\´i}s, Jethro}, title = {The Primacy of Phenomenology Over Cognitivism. Towards a Critique of the Computational Theory of Mind}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136404}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {This investigation deals with the history of the reception of phenomenological philosophy in cognitive science and how this reception has altered and continues to shape the traditional view of cognition inspired by the computer metaphor of mind. The claim will be espoused that cognitive science is not devoid of a philosophical perspective and cognitivism will be characterized precisely as the philosophy behind much work in cognitive science. In conclusion, the irreducibility of philosophical questioning to cognitive science will be defended and reasons will be given as to why it matters to mount such defense.}, subject = {Subjektive Theorie}, language = {en} } @article{FrankDengjelWilflingetal.2015, author = {Frank, Daniel O. and Dengjel, J{\"o}rn and Wilfling, Florian and Kozjak-Pavlovic, Vera and H{\"a}cker, Georg and Weber, Arnim}, title = {The Pro-Apoptotic BH3-Only Protein Bim Interacts with Components of the Translocase of the Outer Mitochondrial Membrane (TOM)}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0123341}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143301}, pages = {e0123341}, year = {2015}, abstract = {The pro-apoptotic Bcl-2-family protein Bim belongs to the BH3-only proteins known as initiators of apoptosis. Recent data show that Bim is constitutively inserted in the outer mitochondrial membrane via a C-terminal transmembrane anchor from where it can activate the effector of cytochrome c-release, Bax. To identify regulators of Bim-activity, we conducted a search for proteins interacting with Bim at mitochondria. We found an interaction of Bim with Tom70, Tom20 and more weakly with Tom40, all components of the Translocase of the Outer Membrane (TOM). In vitro import assays performed on tryptically digested yeast mitochondria showed reduced Bim insertion into the outer mitochondrial membrane (OMM) indicating that protein receptors may be involved in the import process. However, RNAi against components of TOM (Tom40, Tom70, Tom22 or Tom20) by siRNA, individually or in combination, did not consistently change the amount of Bim on HeLa mitochondria, either at steady state or upon de novo-induction. In support of this, the individual or combined knockdowns of TOM receptors also failed to alter the susceptibility of HeLa cells to Bim-induced apoptosis. In isolated yeast mitochondria, lack of Tom70 or the TOM-components Tom20 or Tom22 alone did not affect the import of Bim into the outer mitochondrial membrane. In yeast, expression of Bim can sensitize the cells to Bax-dependent killing. This sensitization was unaffected by the absence of Tom70 or by an experimental reduction in Tom40. Although thus the physiological role of the Bim-TOM-interaction remains unclear, TOM complex components do not seem to be essential for Bim insertion into the OMM. Nevertheless, this association should be noted and considered when the regulation of Bim in other cells and situations is investigated.}, language = {en} } @article{WilleSchuemannWreeetal.2015, author = {Wille, Michael and Sch{\"u}mann, Antje and Wree, Andreas and Kreutzer, Michael and Glocker, Michael O. and Mutzbauer, Grit and Schmitt, Oliver}, title = {The Proteome Profiles of the Cerebellum of Juvenile, Adult and Aged Rats-An Ontogenetic Study}, series = {International Journal of Molecular Sciences}, volume = {16}, journal = {International Journal of Molecular Sciences}, doi = {10.3390/ijms160921454}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151347}, pages = {21454 -- 21485}, year = {2015}, abstract = {In this study, we searched for proteins that change their expression in the cerebellum (Ce) of rats during ontogenesis. This study focuses on the question of whether specific proteins exist which are differentially expressed with regard to postnatal stages of development. A better characterization of the microenvironment and its development may result from these study findings. A differential two-dimensional polyacrylamide gel electrophoresis (2DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis of the samples revealed that the number of proteins of the functional classes differed depending on the developmental stages. Especially members of the functional classes of biosynthesis, regulatory proteins, chaperones and structural proteins show the highest differential expression within the analyzed stages of development. Therefore, members of these functional protein groups seem to be involved in the development and differentiation of the Ce within the analyzed development stages. In this study, changes in the expression of proteins in the Ce at different postnatal developmental stages (postnatal days (P) 7, 90, and 637) could be observed. At the same time, an identification of proteins which are involved in cell migration and differentiation was possible. Especially proteins involved in processes of the biosynthesis and regulation, the dynamic organization of the cytoskeleton as well as chaperones showed a high amount of differentially expressed proteins between the analyzed dates.}, language = {en} } @article{WilleSchuemannKreutzeretal.2015, author = {Wille, Michael and Sch{\"u}mann, Antje and Kreutzer, Michael and Glocker, Michael O and Wree, Andreas and Mutzbauer, Grit and Schmitt, Oliver}, title = {The proteome profiles of the olfactory bulb of juvenile, adult and aged rats - an ontogenetic study}, series = {Proteome Science}, volume = {13}, journal = {Proteome Science}, number = {8}, doi = {10.1186/s12953-014-0058-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144073}, year = {2015}, abstract = {Background: In this study, we searched for proteins that change their expression in the olfactory bulb (oB) of rats during ontogenesis. Up to now, protein expression differences in the developing animal are not fully understood. Our investigation focused on the question whether specific proteins exist which are only expressed during different development stages. This might lead to a better characterization of the microenvironment and to a better determination of factors and candidates that influence the differentiation of neuronal progenitor cells. Results: After analyzing the samples by two-dimensional polyacrylamide gel electrophoresis (2DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), it could be shown that the number of expressed proteins differs depending on the developmental stages. Especially members of the functional classes, like proteins of biosynthesis, regulatory proteins and structural proteins, show the highest differential expression in the stages of development analyzed. Conclusion: In this study, quantitative changes in the expression of proteins in the oB at different developmental stages (postnatal days (P) 7, 90 and 637) could be observed. Furthermore, the expression of many proteins was found at specific developmental stages. It was possible to identify these proteins which are involved in processes like support of cell migration and differentiation.}, language = {en} } @phdthesis{Bakhtiari2015, author = {Bakhtiari, Giti}, title = {The Role of Fluency in Oral Approach and Avoidance}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118666}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Names of, for instance, children or companies are often chosen very carefully. They should sound and feel good. Therefore, many companies try to choose artificially created names that can easily be pronounced in various languages. A wide range of psychological research has demonstrated that easy processing (high processing fluency) is intrinsically experienced as positive. Due to this positive feeling, easy processing can have profound influences on preferences for names. Topolinski, Maschmann, Pecher, and Winkielman (2014) have introduced a different mechanism that influences the perception of words. Across several experiments they found that words featuring consonantal inward wanderings (inward words) were preferred over words featuring consonantal outward wanderings (outward words). They argued that this was due to the fact that approach and avoidance motivations are activated by articulating inward and outward words, because the pronunciation resembles approach and avoidance behaviors of swallowing and spitting, respectively. They suggested this close link as an underlying mechanism for the so-called in-out effect, but did not test this assumption directly. In the current work, I tested an alternative fluency account of the in-out effect. Specifically, I hypothesized that processing fluency might play a critical role instead of motivational states of approach and avoidance being necessarily activated. In Chapter 1, I introduce the general topic of my dissertation, followed by a detailed introduction of the research area of approach and avoidance motivations in Chapter 2. In Chapter 3, I narrow the topic down to orally induced approach and avoidance motivations, which is the main topic of my dissertation. In Chapter 4, I introduce the research area of ecological influences on psychological processes. This chapter builds the base for the idea that human language might serve as a source of processing fluency in the in-out effect. In the following Chapter 5, I elaborate the research area of processing fluency, for which I examined whether it plays a role in the in-out effect. After an overview of my empirical work in Chapter 6, the empirical part starts with Study 1a and Study 1b (Chapter 7) that aimed to show that two languages (Eng. \& Ger.) in which the in-out effect has originally been found might feature a source of higher processing fluency for inward over outward words. The results showed that higher frequencies of inward dynamics compared to outward dynamics were found in both languages. This can lead to higher pronunciation fluency for inward compared to outward words which might in turn lay the ground for higher preferences found for inward over outward words. In Chapter 8, the assumption that inward compared to outward dynamics might be more efficient to process was tested directly in experiments that examined objective as well as subjective processing fluency of artificially constructed non-words featuring pure inward or outward dynamics. Studies 2a-4b found an objective as well as subjective processing advantage for inward over outward words. In Chapter 9, the causal role of objective and subjective pronunciation fluency in the in-out effect was examined. In Study 5 mediational analyses on item-level and across studies were conducted using objective and subjective fluency as possible mediating variables. In Study 6 mediation analyses were conducted with data on subject- and trial-level from a within-subject design. Overall, the data of the item-based, subject-based and trial-based mediation analyses provide rather mixed results. Therefore, an experimental manipulation of fluency was implemented in the last two studies. In Chapter 10, Study 7 and Study 8 demonstrate that manipulating fluency experimentally does indeed modulate the attitudinal impact of consonantal articulation direction. Articulation ease was induced by letting participants train inward or outward kinematics before the actual evaluation phase. Additionally, the simulation training was intensified in Study 8 in order to examine whether a stronger modulation of the in-out effect could be found. Training outward words led to an attenuation and, after more extensive training, even to a reversal of the in-out effect, whereas training inward words led to an enhancement of the in-out effect. This hints at my overall hypothesis that the explicit preferences of inward and outward words are, at least partially, driven by processing fluency. Almost all studies of my dissertation, except for one analysis of the item-based mediation study, speak in favor of the hypothesis that inward words compared to outward words are objectively and subjectively easier to articulate. This possibly contributes partially to a higher preference of inward over outward words. The results are discussed in Chapter 11 with respect to processing fluency and to the role of language as an ecological factor. Finally, future research ideas are elaborated.}, subject = {Sozialpsychologie}, language = {en} } @phdthesis{Subbarayal2015, author = {Subbarayal, Prema}, title = {The role of human Ephrin receptor tyrosine kinase A2 (EphA2) in Chlamydia trachomatis infection}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114778}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Chlamydia trachomatis (Ctr), an obligate intracellular gram negative human pathogen, causes sexually transmitted diseases and acquired blindness in developing countries. The infectious elementary bodies (EB) of Ctr involved in adherence and invasion processes are critical for chlamydial infectivity and subsequent pathogenesis which requires cooperative interaction of several host cell factors. Few receptors have been known for this early event, yet the molecular mechanism of these receptors involvement throughout Ctr infection is not known. Chlamydial inclusion membrane serves as a signaling platform that coordinates Chlamydia-host cell interaction which encouraged me to look for host cell factors that associates with the inclusion membrane, using proteome analysis. The role of these factors in chlamydial replication was analyzed by RNA interference (RNAi) (in collaboration with AG Thomas Meyer). Interestingly, EphrinA2 receptor (EphA2), a cell surface tyrosine kinase receptor, implicated in many cancers, was identified as one of the potential candidates. Due to the presence of EphA2 in the Ctr inclusion proteome data, I investigated the role of EphA2 in Ctr infection. EphA2 was identified as a direct interacting receptor for adherence and entry of C. trachomatis. Pre-incubation of Ctr-EB with recombinant human EphA2, knockdown of EphA2 by siRNA, pretreatment of cells with anti-EphA2 antibodies or the tyrosine kinase inhibitor dasatinib significantly reduced Ctr infection. This marked reduction of Ctr infection was seen with both epithelial and endothelial cells used in this study. Ctr activates EphA2 upon infection and invades the cell together with the activated EphA2 receptor that interacts and activates PI3K survival signal, promoting chlamydial replication. EphA2 upregulation during infection is associated with Ctr inclusion membrane inside the cell and are prevented being translocated to the cell surface. Ephrins are natural ligands for Ephrin receptors that repress the activation of the PI3K/Akt pathway in a process called reverse signaling. Purified Ephrin-A1, a ligand of EphA2, strongly interferes with chlamydial infection and normal development, supporting the central role of these receptors in Chlamydia infection. Overexpression of full length EphA2, but not the mutant form lacking the intracellular cytoplasmic domain, enhanced PI3K activation and Ctr infection. Ctr infection induces EphA2 upregulation and is mediated by activation of ERK signaling pathway. Interfering with EphA2 upregulation sensitizes Ctr-infected cells to apoptosis induced by tumor necrosis factor-alpha (TNF-α) suggesting the importance of intracellular EphA2 signaling. Collectively, these results revealed the first Ephrin receptor "EphA2" that functions in promoting chlamydial infection. In addition, the engagement of a cell surface receptor at the inclusion membrane is a new mechanism how Chlamydia subverts the host cell and induces apoptosis resistance. By applying the natural ligand Ephrin-A1 and targeting EphA2 offers a promising new approach to interfere with Chlamydia infection. Thus, the work provides the evidence for a host cell surface tyrosine kinase receptor that is exploited for invasion as well as for receptor-mediated intracellular signaling to facilitate the chlamydial replication.}, subject = {Chlamydia trachomatis}, language = {en} } @article{AlavipanahWegmannQureshietal.2015, author = {Alavipanah, Sadroddin and Wegmann, Martin and Qureshi, Salman and Weng, Qihao and Koellner, Thomas}, title = {The role of vegetation in mitigating urban land surface temperatures: a case study of Munich, Germany during the warm season}, series = {Sustainability}, volume = {7}, journal = {Sustainability}, doi = {10.3390/su7044689}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143447}, pages = {4689-4706}, year = {2015}, abstract = {The Urban Heat Island (UHI) is the phenomenon of altered increased temperatures in urban areas compared to their rural surroundings. UHIs grow and intensify under extreme hot periods, such as during heat waves, which can affect human health and also increase the demand for energy for cooling. This study applies remote sensing and land use/land cover (LULC) data to assess the cooling effect of varying urban vegetation cover, especially during extreme warm periods, in the city of Munich, Germany. To compute the relationship between Land Surface Temperature (LST) and Land Use Land Cover (LULC), MODIS eight-day interval LST data for the months of June, July and August from 2002 to 2012 and the Corine Land Cover (CLC) database were used. Due to similarities in the behavior of surface temperature of different CLCs, some classes were reclassified and combined to form two major, rather simplified, homogenized classes: one of built-up area and one of urban vegetation. The homogenized map was merged with the MODIS eight-day interval LST data to compute the relationship between them. The results revealed that (i) the cooling effect accrued from urban vegetation tended to be non-linear; and (ii) a remarkable and stronger cooling effect in terms of LST was identified in regions where the proportion of vegetation cover was between seventy and almost eighty percent per square kilometer. The results also demonstrated that LST within urban vegetation was affected by the temperature of the surrounding built-up and that during the well-known European 2003 heat wave, suburb areas were cooler from the core of the urbanized region. This study concluded that the optimum green space for obtaining the lowest temperature is a non-linear trend. This could support urban planning strategies to facilitate appropriate applications to mitigate heat-stress in urban area.}, language = {en} } @article{StoegglSperlich2015, author = {St{\"o}ggl, Thomas L. and Sperlich, Billy}, title = {The training intensity distribution among well-trained and elite endurance athletes}, series = {Frontiers in Physiology}, volume = {6}, journal = {Frontiers in Physiology}, number = {295}, doi = {10.3389/fphys.2015.00295}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-138883}, year = {2015}, abstract = {Researchers have retrospectively analyzed the training intensity distribution (TID) of nationally and internationally competitive athletes in different endurance disciplines to determine the optimal volume and intensity for maximal adaptation. The majority of studies present a "pyramidal" TID with a high proportion of high volume, low intensity training (HVLIT). Some world-class athletes appear to adopt a so-called "polarized" TID (i.e., significant \% of HVLIT and high intensity training) during certain phases of the season. However, emerging prospective randomized controlled studies have demonstrated superior responses of variables related to endurance when applying a polarized TID in well-trained and recreational individuals when compared with a TID that emphasizes HVLIT or threshold training. The aims of the present review are to: (1) summarize the main responses of retrospective and prospective studies exploring TID; (2) provide a systematic overview on TIDs during preparation, pre-competition, and competition phases in different endurance disciplines and performance levels; (3) address whether one TID has demonstrated greater efficacy than another; and (4) highlight research gaps in an effort to direct future scientific studies.}, language = {en} } @phdthesis{Pusch2015, author = {Pusch, Tobias}, title = {The transcription factor NFATc1 mediates cytotoxic T cell function in vitro and in vivo}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123690}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {While numerous experiments on NFAT were already performed with CD4+ T cells showing defective cytokine release and a reduced T helper cell development, no detailed studies existed for CD8+ T cells. From this point, we wanted to examine the impact of NFATc1 and c2 on the physiological functions of CD8+ T cells in vitro and in vivo. Therefore, we used a murine infection model with the bacteria Listeria monocytogenes and mice in which NFATc1 was specifically depleted in the T cell compartment. Our first in vitro studies showed a typical NFATc1 and c2 nuclear translocation and changes on mRNA levels upon T cell activation similarly in CD4+ as well as in CD8+ T cells extracted from wild type mice. NFAT nuclear translocation is important for target gene activation and generation of effector functions. Stimulated T cell populations lacking NFATc1 and/or NFATc2 showed a markedly decreased expression of Th1/Tc1 cytokines, as e.g. IL 2 and IFNγ being important for the clearance of intracellular pathogens. From our in vitro model for the generation of allogenically reactive cytotoxic CD8+ T cells, we revealed a decreased killing and lytic granule-release capacity in Nfatc1 inactivated CD8+ T cells whereas NFATc2-/- cytotoxic T cells did not show an altered cytotoxic response compared to wild type cells. Interestingly, we found lytic granules accumulated and mitochondria not getting translocated to the immunological synapse upon re-stimulation in NFATc1-deficient CD8+ T cells. Together with results showing the CsA insensitivity of the CTL killing/degranulation capacities, we assume that some major cellular processes are affected by NFATc1 which are not directly linked to the TCR-induced signal transduction cascade. We also showed the importance of NFATc1 in T cells during intracellular infections with the bacteria Listeria monocytogenes in an in vivo mouse model. After five days, only few bacteria were detected in wt mice whereas high amounts of Listeria particles were extracted from livers of Nfatc1fl/fl x Cd4 cre mice. Although the reactivity towards the pathogen was similar in both groups, a decreased cytokine expression in NFATc1-/- CD8+ T cells was observed together with an altered memory cell generation. Our results show the importance of NFATc1 in CD8+ T cells and give some clue for a possible connection to other basal cellular functions, as e.g. the formation of an immunological synapse.}, subject = {Transkriptionsfaktor}, language = {en} } @article{PaschkeLinckeMuelleretal.2015, author = {Paschke, Ralf and Lincke, Thomas and M{\"u}ller, Stefan P. and Kreissl, Michael C. and Dralle, Henning and Fassnacht, Martin}, title = {The Treatment of Well-Differentiated Thyroid Carcinoma}, series = {Deutsches {\"A}rzteblatt International}, volume = {112}, journal = {Deutsches {\"A}rzteblatt International}, doi = {10.3238/arztebl.2015.0452}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151636}, pages = {452 -- 458}, year = {2015}, abstract = {Background: Recent decades have seen a rise in the incidence of well-differentiated (mainly papillary) thyroid carcinoma around the world. In Germany, the age-adjusted incidence of well-differentiated thyroid carcinoma in 2010 was 3.5 per 100 000 men and 8.7 per 100 000 women per year. Method: This review is based on randomized, controlled trials and multicenter trials on the treatment of well-differentiated thyroid carcinoma that were retrieved by a selective literature search, as well as on three updated guidelines issued in the past two years. Results: The recommended extent of surgical resection depends on whether the tumor is classified as low-risk or high-risk, so that papillary microcar cinomas, which carry a highly favorable prognosis, will not be overtreated. More than 90\% of localized, well-differentiated thyroid carcinomas can be cured with a combination of surgery and radioactive iodine therapy. Radio active iodine therapy is also effective in the treatment of well-differentiated thyroid carcinomas with distant metastases, yielding a 10-year survival rate of 90\%, as long as there is good iodine uptake and the tumor goes into remission after treatment; otherwise, the 10-year survival rate is only 10\%. In the past two years, better treatment options have become available for radioactive-iodine-resistant thyroid carcinoma. Phase 3 studies of two different tyrosine kinase inhibitors have shown that either one can markedly prolong progression-free survival, but not overall survival. Their more common clinically significant side effects are hand-foot syndrome, hypertension, diarrhea, proteinuria, and weight loss. Conclusion: Slow tumor growth, good resectability, and susceptibility to radioactive iodine therapy lend a favorable prognosis to most cases of well-differentiated thyroid carcinoma. The treatment should be risk-adjusted and interdisciplinary, in accordance with the current treatment guidelines. Even metastatic thyroid carcinoma has a favorable prognosis as long as there is good iodine uptake. The newly available medical treatment options for radioactive-iodine-resistant disease need to be further studied.}, language = {en} }