@article{Andres2013, author = {Andres, Katharina}, title = {'Fashion's Final Frontier': The Correlation of Gender Roles and Fashion in Star Trek}, series = {Culture Unbound}, volume = {5}, journal = {Culture Unbound}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128827}, pages = {639-649}, year = {2013}, abstract = {Since its creation in 1966, Star Trek has been a dominant part of popular culture and as thus served as the source for many cultural references. Star Trek's creator Gene Roddenberry wanted to realize his vision of a utopia but at the same time, he used the futuristic setting of the show to comment on the present time, on actual social and political circumstances. This means that each series can be regarded as a mirror image of the time in which it was created. The clothing of the characters in the different series is one part of that image. The uniforms of The Original Se-ries show influences of the 1960s pop art movement as well as the mini-skirt trend that experienced its peak in that decade. In the course of almost 40 years, howev-er, many things changed. In the 1990s, in Deep Space Nine and Voyager, a unisex uniform replaced the mini-dresses, with few exceptions; the colorful shirts gave way to ones that were mostly black. This trend continues into the new century. This essay interprets the evolution of the female officers' uniforms from femi-nized dresses to androgynous clothing over the development of the series as a reflection of the change of gender roles in contemporary American society. The general functions of the female characters' uniforms are the central object of its analysis while the few, but noteworthy exceptions to this pattern are given specif-ic attention. Finally, one of the most intriguing lines of enquiry is, how the pre-quel series Enterprise, supposed to be set before The Original Series, but pro-duced and aired from 2001 to 2005, fits in the picture.}, language = {en} } @phdthesis{Skiera2013, author = {Skiera, Christina}, title = {1H NMR spectroscopic determination of deterioration marker compounds in fats and oils}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-95756}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {In food and pharmaceutical analysis, the classical indices peroxide value (PV), acid value (AV) and p-anisidine value (ANV) still play an important role as quality and authenticity control parameters of fats and oils. These indices are sum parameters for certain deterioration products (PV for hydroperoxides, AV for free fatty acids, ANV for aldehydes) and are obtained using volumetric or UV/VIS spectroscopic analytical approaches. 1H NMR spectroscopy provides a fast and simple alternative to these classical approaches. In the present work, novel 1H NMR methods to determine hydroperoxides, free fatty acids and aldehydes in fats and oils were developed. Hydroperoxides: The influence of solvent, water, free fatty acids and sample weight on the hydroperoxide group proton (OOH) signal was investigated. On the basis of the obtained results, the sample preparation procedure of the new 1H NMR method was established. A rough assignment of the hydroperoxide group signals in edible fats and oils to methyl oleate, methyl linoleate and methyl linolenate was conducted. Furthermore, to gain information on how many different hydroperoxide species originate from trioleate autoxidation, a kinetic study on trioleate monohydroperoxides was performed. The evaluation of the data strongly indicates that all of the conceivable 18 trioleate monohydroperoxides were formed during trioleate autoxidation. The analytical performance of the NMR method was compared to that of the classical PV approach by means of the so-called "relative sensitivity" according to Mandel. It was shown that both methods exhibit a similar analytical performance. A total of 444 edible oil samples were analysed using both methods. For some oil varieties considerable discrepancies were found between the results. In the case of black seed oil and olive oil two substances were identified that influence the classical PV determination and thus cause positive (black seed oil) and negative (olive oil) deviations from the theoretical PV expected from the NMR values. Free fatty acids: In order to find the optimal solvent mixture to measure the carboxyl group protons (COOH) of free fatty acids in fats and oils, the effect of solvent on the COOH signal was investigated for different mixtures of CDCl3 and DMSO-d6. The comparison of the NMR method with the classical AV method by means of the relative sensitivity revealed that both methods exhibit a similar analytical performance. 420 edible oil samples were analysed by both approaches. Except for pumpkin seed oil, where slight deviations were observed, there was a good compliance between the results obtained from the two methods. Furthermore, the applicability of the 1H NMR assay to further lipids with relevance in pharmacy was tested. For hard fat, castor oil, waxes and oleyl oleate modifications of the original sample preparation procedure of the NMR method were necessary to achieve comparable results for both methods. Aldehydes: The new 1H NMR method enables the determination of the molar amounts of n-alkanals, (E)-2-alkenals and (E,E)-2,4-alkadienals. It was illustrated that the ANV can be modelled as a linear combination of the NMR integrals of these aldehyde species. A functional relationship was derived on the basis In conclusion, the new 1H NMR methods provide an excellent alternative to of calibration experiments. The suitability of the model was shown by comparing the NMR-determined ANVs with the measured classical ANVs of 79 commercially available edible oils of different oil types. In conclusion, the new 1H NMR methods provide an excellent alternative to the determination of the classical indices PV, AV and ANV. They have several advantages over the classical methods including the consumption of small solvent amounts, the ability to automatize measurement and to acquire several different parameters out of the same NMR spectrum. Especially concerning their selectivity, the 1H NMR methods are highly superior to the classical methods.}, subject = {Fett}, language = {en} } @article{KarabegGrauthoffKollertetal.2013, author = {Karabeg, Margherita M. and Grauthoff, Sandra and Kollert, Sina Y. and Weidner, Magdalena and Heiming, Rebecca S. and Jansen, Friederike and Popp, Sandy and Kaiser, Sylvia and Lesch, Klaus-Peter and Sachser, Norbert and Schmitt, Angelika G. and Lewejohann, Lars}, title = {5-HTT Deficiency Affects Neuroplasticity and Increases Stress Sensitivity Resulting in Altered Spatial Learning Performance in the Morris Water Maze but Not in the Barnes Maze}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {10}, doi = {10.1371/journal.pone.0078238}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129978}, pages = {e78238}, year = {2013}, abstract = {The purpose of this study was to evaluate whether spatial hippocampus-dependent learning is affected by the serotonergic system and stress. Therefore, 5-HTT knockout (-/-), heterozygous (+/-) and wildtype (+/+) mice were subjected to the Barnes maze (BM) and the Morris water maze (WM), the latter being discussed as more aversive. Additionally, immediate early gene (IEG) expression, hippocampal adult neurogenesis (aN), and blood plasma corticosterone were analyzed. While the performance of 5-HTT-/- mice in the BM was undistinguishable from both other genotypes, they performed worse in the WM. However, in the course of the repeated WM trials 5-HTT-/- mice advanced to wildtype level. The experience of a single trial of either the WM or the BM resulted in increased plasma corticosterone levels in all genotypes. After several trials 5-HTT-/- mice exhibited higher corticosterone concentrations compared with both other genotypes in both tests. Corticosterone levels were highest in 5-HTT-/- mice tested in the WM indicating greater aversiveness of the WM and a greater stress sensitivity of 5-HTT deficient mice. Quantitative immunohistochemistry in the hippocampus revealed increased cell counts positive for the IEG products cFos and Arc as well as for proliferation marker Ki67 and immature neuron marker NeuroD in 5-HTT-/- mice compared to 5-HTT+/+ mice, irrespective of the test. Most differences were found in the suprapyramidal blade of the dentate gyrus of the septal hippocampus. Ki67-immunohistochemistry revealed a genotype x environment interaction with 5-HTT genotype differences in na{\"i}ve controls and WM experience exclusively yielding more Ki67-positive cells in 5-HTT+/+ mice. Moreover, in 5-HTT-/- mice we demonstrate that learning performance correlates with the extent of aN. Overall, higher baseline IEG expression and increased an in the hippocampus of 5-HTT-/- mice together with increased stress sensitivity may constitute the neurobiological correlate of raised alertness, possibly impeding optimal learning performance in the more stressful WM.}, language = {en} } @article{BloemerPachelHofmannetal.2013, author = {Bl{\"o}mer, Nadja and Pachel, Christina and Hofmann, Urlich and Nordbeck, Peter and Bauer, Wolfgang and Mathes, Denise and Frey, Anna and Bayer, Barbara and Vogel, Benjamin and Ertl, Georg}, title = {5-Lipoxygenase facilitates healing after myocardial infarction}, series = {Basic Research in Cardiology}, volume = {108}, journal = {Basic Research in Cardiology}, number = {4}, doi = {10.1007/s00395-013-0367-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132602}, year = {2013}, abstract = {Early healing after myocardial infarction (MI) is characterized by a strong inflammatory reaction. Most leukotrienes are pro-inflammatory and are therefore potential mediators of healing and remodeling after myocardial ischemia. The enzyme 5-lipoxygenase (5-LOX) has a key role in the transformation of arachidonic acid in leukotrienes. Thus, we tested the effect of 5-LOX on healing after MI. After chronic coronary artery ligation, early mortality was significantly increased in 5-LOX\(^{-/-}\) when compared to matching wildtype (WT) mice due to left ventricular rupture. This effect could be reproduced in mice treated with the 5-LOX inhibitor Zileuton. A perfusion mismatch due to the vasoactive potential of leukotrienes is not responsible for left ventricular rupture since local blood flow assessed by magnetic resonance perfusion measurements was not different. However, after MI, there was an accentuation of the inflammatory reaction with an increase of pro-inflammatory macrophages. Yet, mortality was not changed in chimeric mice (WT vs. 5-LOX\(^{-/-}\) bone marrow in 5-LOX\(^{-/-}\) animals), indicating that an altered function of 5-LOX\(^{-/-}\) inflammatory cells is not responsible for the phenotype. Collagen production and accumulation of fibroblasts were significantly reduced in 5-LOX\(^{-/-}\) mice in vivo after MI. This might be due to an impaired migration of 5-LOX\(^{-/-}\) fibroblasts, as shown in vitro to serum. In conclusion, a lack or inhibition of 5-LOX increases mortality after MI because of healing defects. This is not mediated by a change in local blood flow, but through an altered inflammation and/or fibroblast function.}, language = {en} } @article{HertleinSturmJakobetal.2013, author = {Hertlein, Tobias and Sturm, Volker and Jakob, Peter and Ohlsen, Knut}, title = {\(^{19}\)F Magnetic Resonance Imaging of Perfluorocarbons for the Evaluation of Response to Antibiotic Therapy in a Staphylococcus aureus Infection Model}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0064440}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130113}, pages = {e64440}, year = {2013}, abstract = {Background The emergence of antibiotic resistant bacteria in recent decades has highlighted the importance of developing new drugs to treat infections. However, in addition to the design of new drugs, the development of accurate preclinical testing methods is essential. In vivo imaging technologies such as bioluminescence imaging (BLI) or magnetic resonance imaging (MRI) are promising approaches. In a previous study, we showed the effectiveness of \(^{19}\)F MRI using perfluorocarbon (PFC) emulsions for detecting the site of Staphylococcus aureus infection. In the present follow-up study, we investigated the use of this method for in vivo visualization of the effects of antibiotic therapy. Methods/Principal findings Mice were infected with S. aureus Xen29 and treated with 0.9\% NaCl solution, vancomycin or linezolid. Mock treatment led to the highest bioluminescence values during infection followed by vancomycin treatment. Counting the number of colony-forming units (cfu) at 7 days post-infection (p.i.) showed the highest bacterial burden for the mock group and the lowest for the linezolid group. Administration of PFCs at day 2 p.i. led to the accumulation of \(^{19}\)F at the rim of the abscess in all mice (in the shape of a hollow sphere), and antibiotic treatment decreased the \(^{19}\)F signal intensity and volume. Linezolid showed the strongest effect. The BLI, cfu, and MRI results were comparable. Conclusions \(^{19}\)F-MRI with PFCs is an effective non-invasive method for assessing the effects of antibiotic therapy in vivo. This method does not depend on pathogen specific markers and can therefore be used to estimate the efficacy of antibacterial therapy against a broad range of clinically relevant pathogens, and to localize sites of infection.}, language = {en} } @article{KuehlhornRathSchmoeckeletal.2013, author = {K{\"u}hlhorn, Franziska and Rath, Matthias and Schmoeckel, Katrin and Cziupka, Katharina and Nguyen, Huu Hung and Hildebrandt, Petra and H{\"u}nig, Thomas and Sparwasser, Tim and Huehn, Jochen and P{\"o}tschke, Christian and Br{\"o}ker, Barbara M.}, title = {\(Foxp3^+\) Regulatory T Cells Are Required for Recovery from Severe Sepsis}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0065109}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130940}, pages = {e65109}, year = {2013}, abstract = {The role of regulatory T cells (Tregs) in bacterial sepsis remains controversial because antibody-mediated depletion experiments gave conflicting results. We employed DEREG mice (DEpletion of REGulatory T cells) and a caecal ligation and puncture model to elucidate the role of \(CD4^+Foxp3^+\) Tregs in sepsis. In DEREG mice natural Tregs can be visualized easily and selectively depleted by diphtheria toxin because the animals express the diphtheria toxin receptor and enhanced green fluorescent protein as a fusion protein under the control of the foxp3 locus. We confirmed rapid Treg-activation and an increased ratio of Tregs to Teffs in sepsis. Nevertheless, 24 h after sepsis induction, Treg-depleted and control mice showed equally strong inflammation, immune cell immigration into the peritoneum and bacterial dissemination. During the first 36 h of disease survival was not influenced by Treg-depletion. Later, however, only Treg-competent animals recovered from the insult. We conclude that the suppressive capacity of Tregs is not sufficient to control overwhelming inflammation and early mortality, but is a prerequisite for the recovery from severe sepsis.}, language = {en} } @article{MayMederakeShehataDieler2013, author = {May-Mederake, Birgit and Shehata-Dieler, Wafaa}, title = {A Case Study Assessing the Auditory and Speech Development of Four Children Implanted with Cochlear Implants by the Chronological Age of 12 Months}, series = {Case Reports in Otolaryngology}, volume = {2013}, journal = {Case Reports in Otolaryngology}, number = {359218}, doi = {10.1155/2013/359218}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128750}, year = {2013}, abstract = {Children with severe hearing loss most likely receive the greatest benefit from a cochlear implant (CI) when implanted at less than 2 years of age. Children with a hearing loss may also benefit greater from binaural sensory stimulation. Four children who received their first CI under 12 months of age were included in this study. Effects on auditory development were determined using the German LittlEARS Auditory Questionnaire, closed- and open-set monosyllabic word tests, aided free-field, the Mainzer and G{\"o}ttinger speech discrimination tests, Monosyllabic-Trochee-Polysyllabic (MTP), and Listening Progress Profile (LiP). Speech production and grammar development were evaluated using a German language speech development test (SETK), reception of grammar test (TROG-D) and active vocabulary test (AWST-R). The data showed that children implanted under 12 months of age reached open-set monosyllabic word discrimination at an age of 24 months. LiP results improved over time, and children recognized 100\% of words in the MTP test after 12 months. All children performed as well as or better than their hearing peers in speech production and grammar development. SETK showed that the speech development of these children was in general age appropriate. The data suggests that early hearing loss intervention benefits speech and language development and supports the trend towards early cochlear implantation. Furthermore, the data emphasizes the potential benefits associated with bilateral implantation.}, language = {en} } @article{MarcusVogelSchubertetal.2013, author = {Marcus, U. and Vogel, U. and Schubert, A. and Claus, H. and Baetzing-Feigenbaum, J. and Hellenbrand, W. and Wichmann, O.}, title = {A cluster of invasive meningococcal disease in young men who have sex with men in Berlin, October 2012 to May 2013}, series = {Eurosurveillance}, volume = {18}, journal = {Eurosurveillance}, number = {28}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131711}, pages = {6-8}, year = {2013}, abstract = {No abstract available.}, language = {en} } @article{LudwigSaemannAlexanderetal.2013, author = {Ludwig, K. U. and S{\"a}mann, P. and Alexander, M. and Becker, J. and Bruder, J. and Moll, K. and Spieler, D. and Czisch, M. and Warnke, A. and Docherty, S. J. and Davis, O. S. P. and Plomin, R. and N{\"o}then, M. M. and Landerl, K. and M{\"u}ller-Myhsok, B. and Hoffmann, P. and Schumacher, J. and Schulte-K{\"o}rne, G. and Czamara, D.}, title = {A common variant in Myosin-18B contributes to mathematical abilities in children with dyslexia and intraparietal sulcus variability in adults}, series = {Translational Psychiatry}, volume = {3}, journal = {Translational Psychiatry}, number = {e229}, doi = {10.1038/tp.2012.148}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131513}, year = {2013}, abstract = {The ability to perform mathematical tasks is required in everyday life. Although heritability estimates suggest a genetic contribution, no previous study has conclusively identified a genetic risk variant for mathematical performance. Research has shown that the prevalence of mathematical disabilities is increased in children with dyslexia. We therefore correlated genome-wide data of 200 German children with spelling disability, with available quantitative data on mathematic ability. Replication of the top findings in additional dyslexia samples revealed that rs133885 was a genome-wide significant marker for mathematical abilities\((P_{comb}=7.71 x 10^{-10}, n=699)\), with an effect size of 4.87\%. This association was also found in a sample from the general population (P=0.048, n=1080), albeit with a lower effect size. The identified variant encodes an amino-acid substitution in MYO18B, a protein with as yet unknown functions in the brain. As areas of the parietal cortex, in particular the intraparietal sulcus (IPS), are involved in numerical processing in humans, we investigated whether rs133885 was associated with IPS morphology using structural magnetic resonance imaging data from 79 neuropsychiatrically healthy adults. Carriers of the MYO18B risk-genotype displayed a significantly lower depth of the right IPS. This validates the identified association between rs133885 and mathematical disability at the level of a specific intermediate phenotype.}, language = {en} } @article{KnorrRudolfNuernberger2013, author = {Knorr, Johannes and Rudolf, Philipp and Nuernberger, Patrick}, title = {A comparative study on chirped-pulse upconversion and direct multichannel MCT detection}, doi = {10.1364/OE.21.030693}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111334}, year = {2013}, abstract = {A comparative study is carried out on two spectroscopic techniques employed to detect ultrafast absorption changes in the mid-infrared spectral range, namely direct multichannel detection via HgCdTe (MCT) photodiode arrays and the newly established technique of chirped-pulse upconversion (CPU). Whereas both methods are meanwhile individually used in a routine manner, we directly juxtapose their applicability in femtosecond pump-probe experiments based on 1 kHz shot-to-shot data acquisition. Additionally, we examine different phase-matching conditions in the CPU scheme for a given mid-infrared spectrum, thereby simultaneously detecting signals which are separated by more than 200 cm-1.}, language = {en} } @article{BaeuerleinRiedelBakeretal.2013, author = {B{\"a}uerlein, Carina A. and Riedel, Simone S. and Baker, Jeanette and Brede, Christian and Jord{\´a}n Garrote, Ana-Laura and Chopra, Martin and Ritz, Miriam and Beilhack, Georg F. and Schulz, Stephan and Zeiser, Robert and Schlegel, Paul G. and Einsele, Hermann and Negrin, Robert S. and Beilhack, Andreas}, title = {A diagnostic window for the treatment of acute graft-versus-host disease prior to visible clinical symptoms in a murine model}, series = {BMC Medicine}, journal = {BMC Medicine}, doi = {10.1186/1741-7015-11-134}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96797}, year = {2013}, abstract = {Background Acute graft-versus-host disease (aGVHD) poses a major limitation for broader therapeutic application of allogeneic hematopoietic cell transplantation (allo-HCT). Early diagnosis of aGVHD remains difficult and is based on clinical symptoms and histopathological evaluation of tissue biopsies. Thus, current aGVHD diagnosis is limited to patients with established disease manifestation. Therefore, for improved disease prevention it is important to develop predictive assays to identify patients at risk of developing aGVHD. Here we address whether insights into the timing of the aGVHD initiation and effector phases could allow for the detection of migrating alloreactive T cells before clinical aGVHD onset to permit for efficient therapeutic intervention. Methods Murine major histocompatibility complex (MHC) mismatched and minor histocompatibility antigen (miHAg) mismatched allo-HCT models were employed to assess the spatiotemporal distribution of donor T cells with flow cytometry and in vivo bioluminescence imaging (BLI). Daily flow cytometry analysis of peripheral blood mononuclear cells allowed us to identify migrating alloreactive T cells based on homing receptor expression profiles. Results We identified a time period of 2 weeks of massive alloreactive donor T cell migration in the blood after miHAg mismatch allo-HCT before clinical aGVHD symptoms appeared. Alloreactive T cells upregulated α4β7 integrin and P-selectin ligand during this migration phase. Consequently, targeted preemptive treatment with rapamycin, starting at the earliest detection time of alloreactive donor T cells in the peripheral blood, prevented lethal aGVHD. Conclusions Based on this data we propose a critical time frame prior to the onset of aGVHD symptoms to identify alloreactive T cells in the peripheral blood for timely and effective therapeutic intervention.}, language = {en} } @article{DegenkolbeKoenigZimmeretal.2013, author = {Degenkolbe, Elisa and K{\"o}nig, Jana and Zimmer, Julia and Walther, Maria and Reißner, Carsten and Nickel, Joachim and Pl{\"o}ger, Frank and Raspopovic, Jelena and Sharpe, James and Dathe, Katharina and Hecht, Jacqueline T. and Mundlos, Stefan and Doelken, Sandra C. and Seemann, Petra}, title = {A GDF5 Point Mutation Strikes Twice - Causing BDA1 and SYNS2}, series = {PLOS Genetics}, volume = {9}, journal = {PLOS Genetics}, number = {10}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1003846}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127556}, pages = {e1003846}, year = {2013}, abstract = {Growth and Differentiation Factor 5 (GDF5) is a secreted growth factor that belongs to the Bone Morphogenetic Protein (BMP) family and plays a pivotal role during limb development. GDF5 is a susceptibility gene for osteoarthritis (OA) and mutations in GDF5 are associated with a wide variety of skeletal malformations ranging from complex syndromes such as acromesomelic chondrodysplasias to isolated forms of brachydactylies or multiple synostoses syndrome 2 (SYNS2). Here, we report on a family with an autosomal dominant inherited combination of SYNS2 and additional brachydactyly type A1 (BDA1) caused by a single point mutation in GDF5 (p.W414R). Functional studies, including chondrogenesis assays with primary mesenchymal cells, luciferase reporter gene assays and Surface Plasmon Resonance analysis, of the GDF5 W-414R variant in comparison to other GDF5 mutations associated with isolated BDA1 (p.R399C) or SYNS2 (p.E491K) revealed a dual pathomechanism characterized by a gain-and loss-of-function at the same time. On the one hand insensitivity to the main GDF5 antagonist NOGGIN (NOG) leads to a GDF5 gain of function and subsequent SYNS2 phenotype. Whereas on the other hand, a reduced signaling activity, specifically via the BMP receptor type IA (BMPR1A), is likely responsible for the BDA1 phenotype. These results demonstrate that one mutation in the overlapping interface of antagonist and receptor binding site in GDF5 can lead to a GDF5 variant with pathophysiological relevance for both, BDA1 and SYNS2 development. Consequently, our study assembles another part of the molecular puzzle of how loss and gain of function mutations in GDF5 affect bone development in hands and feet resulting in specific types of brachydactyly and SYNS2. These novel insights into the biology of GDF5 might also provide further clues on the pathophysiology of OA.}, language = {en} } @article{SchusterJohannsenRoewer2013, author = {Schuster, Frank and Johannsen, Stephan and Roewer, Norbert}, title = {A Minimal-Invasive Metabolic Test Detects Malignant Hyperthermia Susceptibility in a Patient after Sevoflurane-Induced Metabolic Crisis}, series = {Case Reports in Anesthesiology}, journal = {Case Reports in Anesthesiology}, doi = {10.1155/2013/953859}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97080}, year = {2013}, abstract = {Malignant hyperthermia is a rare but life-threatening complication of general anesthesia in predisposed patients usually triggered by potent inhalation anesthetics and/or the depolarizing muscle relaxant succinylcholine. The authors present a case of delayed sevoflurane-induced malignant hyperthermia in a 21-year-old male patient that was sufficiently treated by discontinuation of trigger agent application and dantrolene infusion. After surviving an MH episode diagnostic procedures are indicated to increase patient safety. In the presented case, the use of a novel minimal-invasive metabolic test with intramuscular injection of halothane and caffeine successfully confirmed MH susceptibility and hence might be an alternative for invasive in vitro contracture testing in selected cases.}, language = {en} } @article{GersztenSahgalSheehanetal.2013, author = {Gerszten, Peter C. and Sahgal, Arjun and Sheehan, Jason P. and Kersh, Ronald and Chen, Stephanie and Flickinger, John C. and Quader, Mubina and Fahim, Daniel and Grills, Inga and Shin, John H. and Winey, Brian and Oh, Kevin and Sweeney, Reinhart A. and Guckenberger, Matthias}, title = {A multi-national report on methods for institutional credentialing for spine radiosurgery}, series = {Radiation Oncology}, volume = {8}, journal = {Radiation Oncology}, number = {158}, doi = {10.1186/1748-717X-8-158}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131485}, year = {2013}, abstract = {Background: Stereotactic body radiotherapy and radiosurgery are rapidly emerging treatment options for both malignant and benign spine tumors. Proper institutional credentialing by physicians and medical physicists as well as other personnel is important for the safe and effective adoption of spine radiosurgery. This article describes the methods for institutional credentialing for spine radiosurgery at seven highly experienced international institutions. Methods: All institutions (n = 7) are members of the Elekta Spine Radiosurgery Research Consortium and have a dedicated research and clinical focus on image-guided spine radiosurgery. A questionnaire consisting of 24 items covering various aspects of institutional credentialing for spine radiosurgery was completed by all seven institutions. Results: Close agreement was observed in most aspects of spine radiosurgery credentialing at each institution. A formal credentialing process was believed to be important for the implementation of a new spine radiosurgery program, for patient safety and clinical outcomes. One institution has a written policy specific for spine radiosurgery credentialing, but all have an undocumented credentialing system in place. All institutions rely upon an in-house proctoring system for the training of both physicians and medical physicists. Four institutions require physicians and medical physicists to attend corporate sponsored training. Two of these 4 institutions also require attendance at a non-corporate sponsored academic society radiosurgery course. Corporate as well as non-corporate sponsored training were believed to be complimentary and both important for training. In 5 centers, all cases must be reviewed at a multidisciplinary conference prior to radiosurgery treatment. At 3 centers, neurosurgeons are not required to be involved in all cases if there is no evidence for instability or spinal cord compression. Backup physicians and physicists are required at only 1 institution, but all institutions have more than one specialist trained to perform spine radiosurgery. All centers believed that credentialing should also be device specific, and all believed that professional societies should formulate guidelines for institutions on the requirements for spine radiosurgery credentialing. Finally, in 4 institutions radiation therapists were required to attend corporate-sponsored device specific training for credentialing, and in only 1 institution were radiation therapists required to also attend academic society training for credentialing. Conclusions: This study represents the first multi-national report of the current practice of institutional credentialing for spine radiosurgery. Key methodologies for safe implementation and credentialing of spine radiosurgery have been identified. There is strong agreement among experienced centers that credentialing is an important component of the safe and effective implementation of a spine radiosurgery program.}, language = {en} } @article{ScharmannThornhamGrafeetal.2013, author = {Scharmann, Mathias and Thornham, Daniel G. and Grafe, T. Ulmar and Federle, Walter}, title = {A Novel Type of Nutritional Ant-Plant Interaction: Ant Partners of Carnivorous Pitcher Plants Prevent Nutrient Export by Dipteran Pitcher Infauna}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0063556}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130952}, pages = {e63556}, year = {2013}, abstract = {Many plants combat herbivore and pathogen attack indirectly by attracting predators of their herbivores. Here we describe a novel type of insect-plant interaction where a carnivorous plant uses such an indirect defence to prevent nutrient loss to kleptoparasites. The ant Camponotus schmitzi is an obligate inhabitant of the carnivorous pitcher plant Nepenthes bicalcarata in Borneo. It has recently been suggested that this ant-plant interaction is a nutritional mutualism, but the detailed mechanisms and the origin of the ant-derived nutrient supply have remained unexplained. We confirm that N. bicalcarata host plant leaves naturally have an elevated \(^{15}N/^{14}N\) stable isotope abundance ratio (\(\delta ^{15}N\)) when colonised by C. schmitzi. This indicates that a higher proportion of the plants' nitrogen is insect-derived when C. schmitzi ants are present (ca. 100\%, vs. 77\% in uncolonised plants) and that more nitrogen is available to them. We demonstrated direct flux of nutrients from the ants to the host plant in a \(^{15}N\) pulse-chase experiment. As C. schmitzi ants only feed on nectar and pitcher contents of their host, the elevated foliar \(\delta ^{15}N\) cannot be explained by classic ant-feeding (myrmecotrophy) but must originate from a higher efficiency of the pitcher traps. We discovered that C. schmitzi ants not only increase the pitchers' capture efficiency by keeping the pitchers' trapping surfaces clean, but they also reduce nutrient loss from the pitchers by predating dipteran pitcher inhabitants (infauna). Consequently, nutrients the pitchers would have otherwise lost via emerging flies become available as ant colony waste. The plants' prey is therefore conserved by the ants. The interaction between C. schmitzi, N. bicalcarata and dipteran pitcher infauna represents a new type of mutualism where animals mitigate the damage by nutrient thieves to a plant.}, language = {en} } @article{KlementFrobelAlbersetal.2013, author = {Klement, Rainer Johannes and Frobel, Thomas and Albers, Torsten and Fikenzer, Sven and Prinzhausen, Jan and K{\"a}mmerer, Ulrike}, title = {A pilot case study on the impact of a self-prescribed ketogenic diet on biochemical parameters and running performance in healthy and physically active individuals}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78901}, year = {2013}, abstract = {Background: Ketogenic diets (KDs) have gained some popularity not only as effective weight-loss diets and treatment options for several diseases, but also among healthy and physically active individuals for various reasons. However, data on the effects of ketosis in the latter group of individuals are scarce. We therefore collected pilot data on the physiological response to a self-prescribed ketogenic diet lasting 5-7 weeks in a small cohort of healthy and physically active individuals. Methods: Twelve subjects (7 males, 5 females, age 24-60 years) who followed moderate to intensive exercise routines underwent blood testing, bioelectrical impedance analysis (BIA) and spiroergometry during an incremental treadmill test. On the next day, they went on a self-prescribed KD for a median of 38 days (range 35-50 days), after which the same tests were performed again. Ketosis was self-monitored by urinary ketone strips. Subjective feeling during the diet was assessed by a questionnaire after the intervention. Due to the small and heterogenous sample, the results are interpreted in the context of the already existing literature. Results: The KDs were tolerated well by the majority of individuals. Impaired recovery from exercise remained the most frequently reported side effect until the end of the study. Most blood parameters remained stable during the intervention. However, there were significant elevations of total and LDL cholesterol concentrations (p<0.01) and a trend towards increased HDL-cholesterol (p=0.05). The drastic reduction of carbohydrates had no statistically significant influence on running performance judged by the time to exhaustion, VO2max and respiratory compensation points. BIA measurements showed significant increases in phase angle (p=0.01) indicating improvements of body composition with an estimated decrease of 3.4 kg of fat mass (p=0.002) and gain of 1.3 kg of fat free mass. We discuss the validity of these estimates taking into account a possibly altered hydration status due to the KD. Conclusions: Active healthy individuals will probably experience no major problems during a short term KD lasting several weeks. The drastically reduced carbohydrate content of the diet seems to be no limiting factor for running performance. In addition, improvements in body composition can be expected. While most biochemical parameters are not influenced by the diet, there seems to be an impact on the blood lipid profile that could be considered problematic with respect to cardiovascular disease risk. However, the predictive role of cholesterol levels alone in individuals undergoing regular physical activity remains to be elucidated.}, subject = {Fettgehalt}, language = {en} } @article{DmochewitzFoertschZwergeretal.2013, author = {Dmochewitz, Lydia and F{\"o}rtsch, Christina and Zwerger, Christian and Vaeth, Martin and Felder, Edward and Huber-Lang, Markus and Barth, Holger}, title = {A Recombinant Fusion Toxin Based on Enzymatic Inactive C3bot1 Selectively Targets Macrophages}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {1}, doi = {10.1371/journal.pone.0054517}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131189}, pages = {e54517}, year = {2013}, abstract = {Background: The C3bot1 protein (~23 kDa) from Clostridium botulinum ADP-ribosylates and thereby inactivates Rho. C3bot1 is selectively taken up into the cytosol of monocytes/macrophages but not of other cell types such as epithelial cells or fibroblasts. Most likely, the internalization occurs by a specific endocytotic pathway via acidified endosomes. Methodology/Principal Findings: Here, we tested whether enzymatic inactive C3bot1E174Q serves as a macrophage-selective transport system for delivery of enzymatic active proteins into the cytosol of such cells. Having confirmed that C3bot1E174Q does not induce macrophage activation, we used the actin ADP-ribosylating C2I (~50 kDa) from Clostridium botulinum as a reporter enzyme for C3bot1E174Q-mediated delivery into macrophages. The recombinant C3bot1E174Q-C2I fusion toxin was cloned and expressed as GST-protein in Escherichia coli. Purified C3bot1E174Q-C2I was recognized by antibodies against C2I and C3bot and showed C2I-specific enzyme activity in vitro. When applied to cultured cells C3bot1E174Q-C2I ADP-ribosylated actin in the cytosol of macrophages including J774A.1 and RAW264.7 cell lines as well as primary cultured human macrophages but not of epithelial cells. Together with confocal fluorescence microscopy experiments, the biochemical data indicate the selective uptake of a recombinant C3-fusion toxin into the cytosol of macrophages. Conclusions/Significance: In summary, we demonstrated that C3bot1E174Q can be used as a delivery system for fast, selective and specific transport of enzymes into the cytosol of living macrophages. Therefore, C3-based fusion toxins can represent valuable molecular tools in experimental macrophage pharmacology and cell biology as well as attractive candidates to develop new therapeutic approaches against macrophage-associated diseases.}, language = {en} } @phdthesis{JosephNedumparambil2013, author = {Joseph Nedumparambil, George}, title = {A Search of the Roots of Syro-Malabar Church in Kerala}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-77747}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {A Search of the Roots of Syro-Malabar Church in Kerala}, subject = {Syro-Malabarische Kirche}, language = {en} } @article{PfeifferGoetzXiangetal.2013, author = {Pfeiffer, Verena and G{\"o}tz, Rudolf and Xiang, Chaomei and Camarero, Guadelupe and Braun, Attila and Zhang, Yina and Blum, Robert and Heinsen, Helmut and Nieswandt, Bernhard and Rapp, Ulf R.}, title = {Ablation of BRaf Impairs Neuronal Differentiation in the Postnatal Hippocampus and Cerebellum}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {3}, doi = {10.1371/journal.pone.0058259}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130304}, pages = {e58259}, year = {2013}, abstract = {This study focuses on the role of the kinase BRaf in postnatal brain development. Mice expressing truncated, non-functional BRaf in neural stem cell-derived brain tissue demonstrate alterations in the cerebellum, with decreased sizes and fuzzy borders of the glomeruli in the granule cell layer. In addition we observed reduced numbers and misplaced ectopic Purkinje cells that showed an altered structure of their dendritic arborizations in the hippocampus, while the overall cornus ammonis architecture appeared to be unchanged. In male mice lacking BRaf in the hippocampus the size of the granule cell layer was normal at postnatal day 12 (P12) but diminished at P21, as compared to control littermates. This defect was caused by a reduced ability of dentate gyrus progenitor cells to differentiate into NeuN positive granule cell neurons. In vitro cell culture of P0/P1 hippocampal cells revealed that BRaf deficient cells were impaired in their ability to form microtubule-associated protein 2 positive neurons. Together with the alterations in behaviour, such as autoaggression and loss of balance fitness, these observations indicate that in the absence of BRaf all neuronal cellular structures develop, but neuronal circuits in the cerebellum and hippocampus are partially disturbed besides impaired neuronal generation in both structures.}, language = {en} } @article{FaragFroehlerOexleetal.2013, author = {Farag, Heba Gamal and Froehler, Sebastian and Oexle, Konrad and Ravindran, Ethiraj and Schindler, Detlev and Staab, Timo and Huebner, Angela and Kraemer, Nadine and Chen, Wei and Kaindl, Angela M.}, title = {Abnormal centrosome and spindle morphology in a patient with autosomal recessive primary microcephaly type 2 due to compound heterozygous WDR62 gene mutation}, series = {Orphanet Journal of Rare Diseases}, volume = {8}, journal = {Orphanet Journal of Rare Diseases}, number = {178}, issn = {1750-1172}, doi = {10.1186/1750-1172-8-178}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123505}, year = {2013}, abstract = {Background: Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental disease with severe microcephaly at birth due to a pronounced reduction in brain volume and intellectual disability. Biallelic mutations in the WD repeat-containing protein 62 gene WDR62 are the genetic cause of MCPH2. However, the exact underlying pathomechanism of MCPH2 remains to be clarified. Methods/results: We characterized the clinical, radiological, and cellular features that add to the human MCPH2 phenotype. Exome sequencing followed by Sanger sequencing in a German family with two affected daughters with primary microcephaly revealed in the index patient the compound heterozygous mutations c. 1313G>A (p.R438H) / c.2864-2867delACAG (p.D955Afs*112) of WDR62, the second of which is novel. Radiological examination displayed small frontal lobes, corpus callosum hypoplasia, simplified hippocampal gyration, and cerebellar hypoplasia. We investigated the cellular phenotype in patient-derived lymphoblastoid cells and compared it with that of healthy female controls. WDR62 expression in the patient's immortalized lymphocytes was deranged, and mitotic spindle defects as well as abnormal centrosomal protein localization were apparent. Conclusion: We propose that a disruption of centrosome integrity and/or spindle organization may play an important role in the development of microcephaly in MCPH2.}, language = {en} } @article{RiedelMofoloAvotaetal.2013, author = {Riedel, Alice and Mofolo, Boitumelo and Avota, Elita and Schneider-Schaulies, Sibylle and Meintjes, Ayton and Mulder, Nicola and Kneitz, Susanne}, title = {Accumulation of Splice Variants and Transcripts in Response to PI3K Inhibition in T Cells}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {2}, doi = {10.1371/journal.pone.0050695}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130335}, pages = {e50695}, year = {2013}, abstract = {Background Measles virus (MV) causes T cell suppression by interference with phosphatidylinositol-3-kinase (PI3K) activation. We previously found that this interference affected the activity of splice regulatory proteins and a T cell inhibitory protein isoform was produced from an alternatively spliced pre-mRNA. Hypothesis Differentially regulated and alternatively splice variant transcripts accumulating in response to PI3K abrogation in T cells potentially encode proteins involved in T cell silencing. Methods To test this hypothesis at the cellular level, we performed a Human Exon 1.0 ST Array on RNAs isolated from T cells stimulated only or stimulated after PI3K inhibition. We developed a simple algorithm based on a splicing index to detect genes that undergo alternative splicing (AS) or are differentially regulated (RG) upon T cell suppression. Results Applying our algorithm to the data, 9\% of the genes were assigned as AS, while only 3\% were attributed to RG. Though there are overlaps, AS and RG genes differed with regard to functional regulation, and were found to be enriched in different functional groups. AS genes targeted extracellular matrix (ECM)-receptor interaction and focal adhesion pathways, while RG genes were mainly enriched in cytokine-receptor interaction and Jak-STAT. When combined, AS/RG dependent alterations targeted pathways essential for T cell receptor signaling, cytoskeletal dynamics and cell cycle entry. Conclusions PI3K abrogation interferes with key T cell activation processes through both differential expression and alternative splicing, which together actively contribute to T cell suppression.}, language = {en} } @article{RiedelMofoloAvotaetal.2013, author = {Riedel, Alice and Mofolo, Boitumelo and Avota, Elita and Schneider-Schaulies, Sibylle and Meintjes, Ayton and Mulder, Nicola and Kneitz, Susanne}, title = {Accumulation of Splice Variants and Transcripts in Response to PI3K Inhibition in T Cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-77917}, year = {2013}, abstract = {Background: Measles virus (MV) causes T cell suppression by interference with phosphatidylinositol-3-kinase (PI3K) activation. We previously found that this interference affected the activity of splice regulatory proteins and a T cell inhibitory protein isoform was produced from an alternatively spliced pre-mRNA. Hypothesis: Differentially regulated and alternatively splice variant transcripts accumulating in response to PI3K abrogation in T cells potentially encode proteins involved in T cell silencing. Methods: To test this hypothesis at the cellular level, we performed a Human Exon 1.0 ST Array on RNAs isolated from T cells stimulated only or stimulated after PI3K inhibition. We developed a simple algorithm based on a splicing index to detect genes that undergo alternative splicing (AS) or are differentially regulated (RG) upon T cell suppression. Results: Applying our algorithm to the data, 9\% of the genes were assigned as AS, while only 3\% were attributed to RG. Though there are overlaps, AS and RG genes differed with regard to functional regulation, and were found to be enriched in different functional groups. AS genes targeted extracellular matrix (ECM)-receptor interaction and focal adhesion pathways, while RG genes were mainly enriched in cytokine-receptor interaction and Jak-STAT. When combined, AS/RG dependent alterations targeted pathways essential for T cell receptor signaling, cytoskeletal dynamics and cell cycle entry. Conclusions: PI3K abrogation interferes with key T cell activation processes through both differential expression and alternative splicing, which together actively contribute to T cell suppression.}, subject = {Biologie}, language = {en} } @phdthesis{Luecking2013, author = {L{\"u}cking, Thomas}, title = {Acquisition Behavior in High-Technology Industries - The Role of Product Diversification, Technological Change, and IP Protection}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85065}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Frequent acquisition activities in high-technology industries are due to the intense competition, driven by short product life cycles, more complex products/services and prevalent network effects. This dissertation theoretically analyzes the circumstances leading to technology-driven acquisitions and empirically tests these within a clearly defined market scenario.}, subject = {Mergers and Acquisitions}, language = {en} } @article{MorschhaeuserRamirezZavalaWeyleretal.2013, author = {Morschh{\"a}user, Joachim and Ram{\´i}rez-Zavala, Bernardo and Weyler, Michael and Gildor, Tsvia and Schmauch, Christian and Kornitzer, Daniel and Arkowitz, Robert}, title = {Activation of the Cph1-Dependent MAP Kinase Signaling Pathway Induces White-Opaque Switching in Candida albicans}, series = {PLoS Pathogens}, journal = {PLoS Pathogens}, doi = {10.1371/journal.ppat.1003696}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97281}, year = {2013}, abstract = {Depending on the environmental conditions, the pathogenic yeast Candida albicans can undergo different developmental programs, which are controlled by dedicated transcription factors and upstream signaling pathways. C. albicans strains that are homozygous at the mating type locus can switch from the normal yeast form (white) to an elongated cell type (opaque), which is the mating-competent form of this fungus. Both white and opaque cells use the Ste11-Hst7-Cek1/Cek2 MAP kinase signaling pathway to react to the presence of mating pheromone. However, while opaque cells employ the transcription factor Cph1 to induce the mating response, white cells recruit a different downstream transcription factor, Tec1, to promote the formation of a biofilm that facilitates mating of opaque cells in the population. The switch from the white to the opaque cell form is itself induced by environmental signals that result in the upregulation of the transcription factor Wor1, the master regulator of white-opaque switching. To get insight into the upstream signaling pathways controlling the switch, we expressed all C. albicans protein kinases from a tetracycline-inducible promoter in a switching-competent strain. Screening of this library of strains showed that a hyperactive form of Ste11 lacking its N-terminal domain (Ste11ΔN467) efficiently stimulated white cells to switch to the opaque phase, a behavior that did not occur in response to pheromone. Ste11ΔN467-induced switching specifically required the downstream MAP kinase Cek1 and its target transcription factor Cph1, but not Cek2 and Tec1, and forced expression of Cph1 also promoted white-opaque switching in a Wor1-dependent manner. Therefore, depending on the activation mechanism, components of the pheromone-responsive MAP kinase pathway can be reconnected to stimulate an alternative developmental program, switching of white cells to the mating-competent opaque phase.}, language = {en} } @article{HolzapfelProdingerPilgeetal.2013, author = {Holzapfel, Boris Michael and Prodinger, Peter M. and Pilge, Hakan and Banke, Ingo J. and B{\"u}rklein, Dominik and Miethke, Thomas and Gradinger, Reiner}, title = {Acute Osteomyelitis of the Humerus mimicking Malignancy: Streptococcus pneumoniae as Exceptional Pathogen in an Immunocompetent Adult}, series = {BMC Infectious Diseases}, journal = {BMC Infectious Diseases}, doi = {10.1186/1471-2334-13-266}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-95790}, year = {2013}, abstract = {Background Chronic osteomyelitis due to direct bone trauma or vascular insufficiency is a frequent problem in orthopaedic surgery. In contrast, acute haematogenous osteomyelitis represents a rare entity that almost exclusively affects prepubescent children or immunodeficient adults. Case Presentation In this article, we report the case of acute pneumococcal osteomyelitis of the humerus in an immunocompetent and otherwise healthy 44-year-old male patient presenting with minor inflammation signs and misleading clinical features. Conclusions The diagnosis had to be confirmed by open biopsy which allowed the initiation of a targeted therapy. A case of pneumococcal osteomyelitis of a long bone, lacking predisposing factors or trauma, is unique in adults and has not been reported previously.}, language = {en} } @article{GunrebenGeisKleinschnitz2013, author = {Gunreben, Ignaz and Geis, Christian and Kleinschnitz, Christoph}, title = {Acute tetraparesis secondary to bilateral precentral gyral cerebral ischemia: a case report}, series = {Journal of Medical Case Reports}, journal = {Journal of Medical Case Reports}, doi = {10.1186/1752-1947-7-61}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96179}, year = {2013}, abstract = {Introduction Sudden tetraparesis represents a neurological emergency and is most often caused by traumatic spinal cord injury, spinal epidural bleeding or brainstem ischemia and less frequently by medial disc herniation or spinal ischemia. Case presentation Here we report the rare case of an 82-year-old Caucasian man who developed severe tetraparesis four days after radical cystoprostatectomy. An emergency diagnostic study for spinal cord affection was normal. Brain magnetic resonance imaging revealed acute bilateral ischemic strokes in the precentral gyri as the underlying cause. Conclusions This case report underlines the need to also consider unusual causes of tetraparesis in an emergency situation apart from spinal cord or brain stem injury in order not to leave severe symptomatology unclear and possibly miss therapeutic options.}, language = {en} } @article{QuinklerBeuschleinHahneretal.2013, author = {Quinkler, Marcus and Beuschlein, Felix and Hahner, Stefanie and Meyer, Gesine and Sch{\"o}fl, Christof and Stalla, G{\"u}nter K.}, title = {Adrenal Cortical Insufficiency-a Life Threatening Illness With Multiple Etiologies}, series = {Deutsches {\"A}rzteblatt International}, volume = {110}, journal = {Deutsches {\"A}rzteblatt International}, doi = {10.3238/arztebl.2013.0882}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131662}, pages = {51-52}, year = {2013}, abstract = {Background: The clinical signs of adrenal cortical insufficiency (incidence, ca. 25 per million per year; prevalence, ca. 400 per million) are nonspecific, and misdiagnoses are therefore common. Glucocorticoid substitution therapy has been in use for 50 years but is not a wholly adequate treatment. Our understanding of this disease remains incomplete in many ways. Methods: We selectively searched the Medline database for publications on adrenal cortical insufficiency, with particular attention to studies from the year 2000 onward (search terms: "adrenal insufficiency" or "Addison's disease" or "hypopituitarism"). Results: Hydrocortisone substitution therapy is often given in doses of 10-25 mg/day, timed according to the circadian rhythm. Gastrointestinal and other, febrile infections account for 30-50\% of life-threatening adrenocortical crises. Such crises affect 8 of 100 persons with adrenal cortical insufficiency per year and must be treated by the immediate administration of glucocorticoids and fluids. When persons with adrenal cortical insufficiency are acutely ill or are otherwise under unusual stress, they may need additional amounts of hydrocortisone, often in the range of 5-10 mg but occasionally as high as 200 mg. The sustained administration of excessive amounts of steroid can shorten patients' lives by several years. Inappropriate substitution therapy can cause other major medical conditions, such as metabolic syndrome and osteoporosis. Conclusion: Important measures for the prevention of adrenocortical crises include improved care by treating physicians, education of patients and their families, the provision of emergency identifying documents, and the prescription of glucocorticoid emergency kits.}, language = {en} } @article{EderRothermundDeHouwer2013, author = {Eder, Andreas B. and Rothermund, Klaus and De Houwer, Jan}, title = {Affective Compatibility between Stimuli and Response Goals: A Primer for a New Implicit Measure of Attitudes}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {11}, doi = {10.1371/journal.pone.0079210}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129872}, pages = {e79210}, year = {2013}, abstract = {We examined whether a voluntary response becomes associated with the (affective) meaning of intended response effects. Four experiments revealed that coupling a keypress with positive or negative consequences produces affective compatibility effects when the keypress has to be executed in response to positively or negatively evaluated stimulus categories. In Experiment 1, positive words were evaluated faster with a keypress that turned the words ON (versus OFF), whereas negative words were evaluated faster with a keypress that turned the words OFF (versus ON). Experiment 2 showed that this compatibility effect is reversed if an aversive tone is turned ON and OFF with keypresses. Experiment 3 revealed that keypresses acquire an affective meaning even when the association between the responses and their effects is variable and intentionally reconfigured before each trial. Experiment 4 used affective response effects to assess implicit ingroup favoritism, showing that the measure is sensitive to the valence of categories and not to the valence of exemplars. Results support the hypothesis that behavioral reactions become associated with the affective meaning of the intended response goal, which has important implications for the understanding and construction of implicit attitude measures.}, language = {en} } @phdthesis{Loew2013, author = {L{\"o}w, Fabian}, title = {Agricultural crop mapping from multi-scale remote sensing data - Concepts and applications in heterogeneous Middle Asian agricultural landscapes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-102093}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Agriculture is mankind's primary source of food production and plays the key role for cereal supply to humanity. One of the future challenges will be to feed a constantly growing population, which is expected to reach more than nine billion by 2050. The potential to expand cropland is limited, and enhancing agricultural production efficiency is one important means to meet the future food demand. Hence, there is an increasing demand for dependable, accurate and comprehensive agricultural intelligence on crop production. The value of satellite earth observation (EO) data for agricultural monitoring is well recognized. One fundamental requirement for agricultural monitoring is routinely updated information on crop acreage and the spatial distribution of crops. With the technical advancement of satellite sensor systems, imagery with higher temporal and finer spatial resolution became available. The classification of such multi-temporal data sets is an effective and accurate means to produce crop maps, but methods must be developed that can handle such large and complex data sets. Furthermore, to properly use satellite EO for agricultural production monitoring a high temporal revisit frequency over vast geographic areas is often necessary. However, this often limits the spatial resolution that can be used. The challenge of discriminating pixels that correspond to a particular crop type, a prerequisite for crop specific agricultural monitoring, remains daunting when the signal encoded in pixels stems from several land uses (mixed pixels), e.g. over heterogeneous landscapes where individual fields are often smaller than individual pixels. The main purposes of the presented study were (i) to assess the influence of input dimensionality and feature selection on classification accuracy and uncertainty in object-based crop classification, (ii) to evaluate if combining classifier algorithms can improve the quality of crop maps (e.g. classification accuracy), (iii) to assess the spatial resolution requirements for crop identification via image classification. Reporting on the map quality is traditionally done with measures that stem from the confusion matrix based on the hard classification result. Yet, these measures do not consider the spatial variation of errors in maps. Measures of classification uncertainty can be used for this purpose, but they have attained only little attention in remote sensing studies. Classifier algorithms like the support vector machine (SVM) can estimate class memberships (the so called soft output) for each classified pixel or object. Based on these estimations, measures of classification uncertainty can be calculated, but it has not been analysed in detail, yet, if these are reliable in predicting the spatial distribution of errors in maps. In this study, SVM was applied for the classification of agricultural crops in irrigated landscapes in Middle Asia at the object-level. Five different categories of features were calculated from RapidEye time series data as classification input. The reliability of classification uncertainty measures like entropy, derived from the soft output of SVM, with regard to predicting the spatial distribution of error was evaluated. Further, the impact of the type and dimensionality of the input data on classification uncertainty was analysed. The results revealed that SMVs applied to the five feature categories separately performed different in classifying different types of crops. Incorporating all five categories of features by concatenating them into one stacked vector did not lead to an increase in accuracy, and partly reduced the model performance most obviously because of the Hughes phenomena. Yet, applying the random forest (RF) algorithm to select a subset of features led to an increase of classification accuracy of the SVM. The feature group with red edge-based indices was the most important for general crop classification, and the red edge NDVI had an outstanding importance for classifying crops. Two measures of uncertainty were calculated based on the soft output from SVM: maximum a-posteriori probability and alpha quadratic entropy. Irrespective of the measure used, the results indicate a decline in classification uncertainty when a dimensionality reduction was performed. The two uncertainty measures were found to be reliable indicators to predict errors in maps. Correctly classified test cases were associated with low uncertainty, whilst incorrectly test cases tended to be associated with higher uncertainty. The issue of combining the results of different classifier algorithms in order to increase classification accuracy was addressed. First, the SVM was compared with two other non-parametric classifier algorithms: multilayer perceptron neural network (MLP) and RF. Despite their comparatively high classification performance, each of the tested classifier algorithms tended to make errors in different parts of the input space, e.g. performed different in classifying crops. Hence, a combination of the complementary outputs was envisaged. To this end, a classifier combination scheme was proposed, which is based on existing algebraic operators. It combines the outputs of different classifier algorithms at the per-case (e.g. pixel or object) basis. The per-case class membership estimations of each classifier algorithm were compared, and the reliability of each classifier algorithm with respect to classifying a specific crop class was assessed based on the confusion matrix. In doing so, less reliable classifier algorithms were excluded at the per-class basis before the final combination. Emphasis was put on evaluating the selected classification algorithms under limiting conditions by applying them to small input datasets and to reduced training sample sets, respectively. Further, the applicability to datasets from another year was demonstrated to assess temporal transferability. Although the single classifier algorithms performed well in all test sites, the classifier combination scheme provided consistently higher classification accuracies over all test sites and in different years, respectively. This makes this approach distinct from the single classifier algorithms, which performed different and showed a higher variability in class-wise accuracies. Further, the proposed classifier combination scheme performed better when using small training set sizes or when applied to small input datasets, respectively. A framework was proposed to quantitatively define pixel size requirements for crop identification via image classification. That framework is based on simulating how agricultural landscapes, and more specifically the fields covered by one crop of interest, are seen by instruments with increasingly coarser resolving power. The concept of crop specific pixel purity, defined as the degree of homogeneity of the signal encoded in a pixel with respect to the target crop type, is used to analyse how mixed the pixels can be (as they become coarser) without undermining their capacity to describe the desired surface properties (e.g. to distinguish crop classes via supervised or unsupervised image classification). This tool can be modulated using different parameterizations to explore trade-offs between pixel size and pixel purity when addressing the question of crop identification. Inputs to the experiments were eight multi-temporal images from the RapidEye sensor. Simulated pixel sizes ranged from 13 m to 747.5 m, in increments of 6.5 m. Constraining parameters for crop identification were defined by setting thresholds for classification accuracy and uncertainty. Results over irrigated agricultural landscapes in Middle Asia demonstrate that the task of finding the optimum pixel size did not have a "one-size-fits-all" solution. The resulting values for pixel size and purity that were suitable for crop identification proved to be specific to a given landscape, and for each crop they differed across different landscapes. Over the same time series, different crops were not identifiable simultaneously in the season and these requirements further changed over the years, reflecting the different agro-ecological conditions the investigated crops were growing in. Results further indicate that map quality (e.g. classification accuracy) was not homogeneously distributed in a landscape, but that it depended on the spatial structures and the pixel size, respectively. The proposed framework is generic and can be applied to any agricultural landscape, thereby potentially serving to guide recommendations for designing dedicated EO missions that can satisfy the requirements in terms of pixel size to identify and discriminate crop types. Regarding the operationalization of EO-based techniques for agricultural monitoring and its application to a broader range of agricultural landscapes, it can be noted that, despite the high performance of existing methods (e.g. classifier algorithms), transferability and stability of such methods remain one important research issue. This means that methods developed and tested in one place might not necessarily be portable to another place or over several years, respectively. Specifically in Middle Asia, which was selected as study region in this thesis, classifier combination makes sense due to its easy implementation and because it enhanced classification accuracy for classes with insufficient training samples. This observation makes it interesting for operational contexts and when field reference data availability is limited. Similar to the transferability of methods, the application of only one certain kind of EO data (e.g. with one specific pixel size) over different landscapes needs to be revisited and the synergistic use of multi-scale data, e.g. combining remote sensing imagery of both fine and coarse spatial resolution, should be fostered. The necessity to predict and control the effects of spatial and temporal scale on crop classification is recognized here as a major goal to achieve in EO-based agricultural monitoring.}, subject = {Fernerkundung}, language = {en} } @article{DrechslerRitzTomaschitzetal.2013, author = {Drechsler, Christiane and Ritz, Eberhard and Tomaschitz, Andreas and Pilz, Stefan and Sch{\"o}nfeld, Stephan and Blouin, Katja and Bidlingmaier, Martin and Hammer, Fabian and Krane, Vera and M{\"a}rz, Winfried and Allolio, Bruno and Fassnacht, Martin and Wanner, Christoph}, title = {Aldosterone and cortisol affect the risk of sudden cardiac death in haemodialysis patients}, series = {European Heart Journal}, volume = {34}, journal = {European Heart Journal}, doi = {10.1093/eurheartj/ehs361}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132562}, pages = {578-585}, year = {2013}, abstract = {Background: Sudden cardiac death is common and accounts largely for the excess mortality of patients on maintenance dialysis. It is unknown whether aldosterone and cortisol increase the incidence of sudden cardiac death in dialysis patients. Methods and results: We analysed data from 1255 diabetic haemodialysis patients participating in the German Diabetes and Dialysis Study (4D Study). Categories of aldosterone and cortisol were determined at baseline and patients were followed for a median of 4 years. By Cox regression analyses, hazard ratios (HRs) were determined for the effect of aldosterone, cortisol, and their combination on sudden death and other adjudicated cardiovascular outcomes. The mean age of the patients was 66 ± 8 years (54\% male). Median aldosterone was <15 pg/mL (detection limit) and cortisol 16.8 µg/dL. Patients with aldosterone levels >200 pg/mL had a significantly higher risk of sudden death (HR: 1.69; 95\% CI: 1.06-2.69) compared with those with an aldosterone <15 pg/mL. The combined presence of high aldosterone (>200 pg/mL) and high cortisol (>21.1 µg/dL) levels increased the risk of sudden death in striking contrast to patients with low aldosterone (<15 pg/mL) and low cortisol (<13.2 µg/dL) levels (HR: 2.86, 95\% CI: 1.32-6.21). Furthermore, all-cause mortality was significantly increased in the patients with high levels of both hormones (HR: 1.62, 95\% CI: 1.01-2.62). Conclusions: The joint presence of high aldosterone and high cortisol levels is strongly associated with sudden cardiac death as well as all-cause mortality in haemodialysed type 2 diabetic patients. Whether a blockade of the mineralocorticoid receptor decreases the risk of sudden death in these patients must be examined in future trials.}, language = {en} } @article{ElsebergBorrmannNuechter2013, author = {Elseberg, Jan and Borrmann, Dorit and N{\"u}chter, Andreas}, title = {Algorithmic Solutions for Computing Precise Maximum Likelihood 3D Point Clouds from Mobile Laser Scanning Platforms}, series = {Remote Sensing}, volume = {5}, journal = {Remote Sensing}, number = {11}, doi = {10.3390/rs5115871}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130478}, pages = {5871-5906}, year = {2013}, abstract = {Mobile laser scanning puts high requirements on the accuracy of the positioning systems and the calibration of the measurement system. We present a novel algorithmic approach for calibration with the goal of improving the measurement accuracy of mobile laser scanners. We describe a general framework for calibrating mobile sensor platforms that estimates all configuration parameters for any arrangement of positioning sensors, including odometry. In addition, we present a novel semi-rigid Simultaneous Localization and Mapping (SLAM) algorithm that corrects the vehicle position at every point in time along its trajectory, while simultaneously improving the quality and precision of the entire acquired point cloud. Using this algorithm, the temporary failure of accurate external positioning systems or the lack thereof can be compensated for. We demonstrate the capabilities of the two newly proposed algorithms on a wide variety of datasets.}, language = {en} } @article{AndersTrautmann2013, author = {Anders, Diana and Trautmann, Axel}, title = {Allergic anaphylaxis due to subcutaneously injected heparin}, series = {Allergy, Asthma \& Clinical Immunology}, journal = {Allergy, Asthma \& Clinical Immunology}, doi = {10.1186/1710-1492-9-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96214}, year = {2013}, abstract = {Heparins are one of the most used class of anticoagulants in daily clinical practice. Despite their widespread application immune-mediated hypersensitivity reactions to heparins are rare. Among these, the delayed-type reactions to s.c. injected heparins are well-known usually presenting as circumscribed eczematous plaques at the injection sites. In contrast, potentially life-threatening systemic immediate-type anaphylactic reactions to heparins are extremely rare. Recently, some cases of non-allergic anaphylaxis could be attributed to undesirable heparin contaminants. A 43-year-old patient developed severe anaphylaxis symptoms within 5-10 minutes after s.c. injection of enoxaparin. Titrated skin prick testing with wheal and flare responses up to an enoxaparin dilution of 1:10.000 indicated a probable allergic mechanism of the enoxaparin-induced anaphylaxis. The basophil activation test as an additional in-vitro test method was negative. Furthermore, skin prick testing showed rather broad cross-reactivity among different heparin preparations tested. In the presented case, history, symptoms, and results of skin testing strongly suggested an IgE-mediated allergic hypersensitivity against different heparins. Therefore, as safe alternative anticoagulants the patient could receive beneath coumarins the hirudins or direct thrombin inhibitors. Because these compounds have a completely different molecular structure compared with the heparin-polysaccharides.}, language = {en} } @article{FujiKappEinsele2013, author = {Fuji, Shigeo and Kapp, Markus and Einsele, Hermann}, title = {Alloreactivity of virus-specific T cells: possible implication of graft-versus-host disease and graft-versus-leukemia effects}, series = {Frontiers in Immunology}, volume = {4}, journal = {Frontiers in Immunology}, number = {330}, doi = {10.3389/fimmu.2013.00330}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129260}, year = {2013}, abstract = {Immune reconstitution of functional virus-specific T cells after allogeneic hematopoietic stem cell transplantation (HSCT) has been intensively investigated. However, the possible role of crossreactivity of these virus-specific T cells against allogeneic targets is still unclear. Theoretically, as in the field of organ transplantation, virus-specific T cells possess crossreactivity potential after allogeneic HSCT. Such crossreactivity is assumed to play a role in graft-versus-host disease and graft-versus-leukemia effects. In this article, we aim to give a comprehensive overview of current understanding about crossreactivity of virus-specific T cells.}, language = {en} } @article{BoehmVasliMaureretal.2013, author = {B{\"o}hm, Johann and Vasli, Nasim and Maurer, Marie and Cowling, Belinda and Shelton, G. Diane and Kress, Wolfram and Toussaint, Anne and Prokic, Ivana and Schara, Ulrike and Anderson, Thomas James and Weis, Joachim and Tiret, Laurent and Laporte, Jocelyn}, title = {Altered Splicing of the BIN1 Muscle-Specific Exon in Humans and Dogs with Highly Progressive Centronuclear Myopathy}, series = {PLOS Genetics}, volume = {9}, journal = {PLOS Genetics}, number = {6}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1003430}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127590}, pages = {e1003430}, year = {2013}, abstract = {Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies.}, language = {en} } @article{AtanasovBenkertThelenetal.2013, author = {Atanasov, Georgi and Benkert, Christoph and Thelen, Armin and Tappe, Dennis and Frosch, Matthias and Teichmann, Dieter and Barth, Thomas F. E. and Wittekind, Christian and Schubert, Stefan and Jonas, Sven}, title = {Alveolar echinococcosis-spreading disease challenging clinicians: A case report and literature review}, series = {World Journal of Gastroenterology}, volume = {19}, journal = {World Journal of Gastroenterology}, number = {26}, doi = {10.3748/wjg.v19.i26.4257}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131525}, pages = {4257-4261}, year = {2013}, abstract = {Human alveolar echinococcosis (AE) is a potentially deadly disease; recent studies have shown that the endemic area of Echinococcus multilocularis, its causative agent, is larger than previously known. This disease has low prevalence and remains underreported in Europe. Emerging clinical data show that diagnostic difficulties are still common. We report on a 76-year old patient suffering from AE lesions restricted to the left lobe of the liver who underwent a curative extended left hemihepatectomy. Prior to the resection a liver biopsy under the suspicion of an atypical malignancy was performed. After the intervention he developed a pseudoaneurysm of the hepatic artery that was successfully coiled. Surprisingly, during surgery, the macroscopic appearance of the tumour revealed a growth pattern that was rather typical for cystic echinococcosis (CE), i.e., a gross tumour composed of multiple large vesicles with several centimeters in diameter. In addition, there were neither extensive adhesions nor infiltrations of the neighboring pancreas and diaphragm as was expected from previous imaging results. The unexpected diagnosis of AE was confirmed by definite histopathology, specific polymerase chain reaction and serology results. This is a rare case of unusual macroscopic presentation of AE that posed immense diagnostic challenges and had an eventful course. To our knowledge this is the first case of an autochthonous infection in this particular geographic area of Germany, the federal state of Saxony. This report may provide new hints for an expanding area of risk for AE and emphasizes the risk of complications in the scope of diagnostic procedures and the limitations of modern radiological imaging.}, language = {en} } @phdthesis{Zancolli2013, author = {Zancolli, Giulia}, title = {Amphibian diversity along the slope of Mount Kilimanjaro: from species to genes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-91792}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {1. Since the early nineteenth century describing (and understanding) patterns of distribution of biodiversity across the Earth has represented one of the most significant intellectual challenges to ecologists and biogeographers. Among the most striking patterns of species richness are: the latitudinal and elevational gradients, with peaks in number of species at low latitudes and somewhere at mid altitudes, although other patterns, e.g. declines with increasing elevation, are often observed. Even in highly diverse tropical regions, species richness is not evenly distributed but there are "hotspots" of biodiversity where an exceptional number of species, especially endemics, are concentrated. Unfortunately, such areas are also experiencing dramatic loss of habitat. Among vertebrate taxa, amphibians are facing the most alarming number of extinctions. Habitat destruction, pollution and emergence of infectious diseases such as chytridiomycosis, are causing worldwide population declines. Responses to these drivers can be multidirectional and subtle, i.e. they may not be captured at the species but at the genetic level. Moreover, present patterns of diversity can result from the influence of past geological, climatic and environmental changes. In this study, I used a multidisciplinary and multilevel approach to understand how and to which extent the landscape influences amphibian diversity. Mount Kilimanjaro is an exceptional tropical region where the landscape is rapidly evolving due to land use changes; additionally, there is a broad lack of knowledge of its amphibian fauna. During two rainy seasons in 2011, I recorded anurans from the foothills to 3500 m altitude; in addition, I focused on two river frog species and collected tissue samples for genetic analysis and swabs for detection of chytridiomycosis, the deadly disease caused by Batrachochytrium dendrobatidis (Bd). 2. I analyzed how species richness and composition change with increasing elevation and anthropogenic disturbance. In order to disentangle the observed patterns of species diversity and distribution, I incorporated inferences from historical biogeography and compared the assemblage of Mt. Kilimanjaro and Mt. Meru (both recent volcanoes) with those of the older Eastern Arc Mountains. Species richness decreased with elevation and locally increased in presence of water bodies, but I did not detect effects of either anthropogenic disturbance or vegetation structure on species richness and composition. Moreover, I found a surprisingly low number of forest species. Historical events seem to underlie the current pattern of species distribution; the young age of Mt. Kilimanjaro and the complex biogeographic processes which occurred in East Africa during the last 20 million years prevented montane forest frogs from colonizing the volcano. 3. I focused on the genetic level of biodiversity and investigated how the landscape, i.e. elevation, topographic relief and land cover, influence genetic variation, population structure and gene flow of two ecologically similar and closely related river frog species, namely Amietia angolensis and Amietia wittei. I detected greater genetic differentiation among populations in the highland species (A. wittei) and higher genetic variation in the lowland species (A. angolensis), although genetic diversity was not significantly correlated with elevation. Importantly, human settlements seemed to restrict gene flow in A. angolensis, whereas steep slopes were positively correlated with gene flow in A. wittei. This results show that even ecologically similar species can respond differently to landscape processes and that the spatial configuration of topographic features combined with species-specific biological attributes can affect dispersal and gene flow in disparate ways. 4. River frogs of the genus Amietia seem to be particularly susceptible to chytridiomycosis, showing the highest pathogen load in Kenya and other African countries. In the last study, I collected swab samples from larvae of A. angolensis and A. wittei for Bd detection. Both species resulted Bd-positive. The presence of Bd on Mt. Kilimanjaro has serious implication. For instance, Bd can be transported by footwear of hikers from contaminated water and soil. Tourists visiting Mt. Kilimanjaro may translocate Bd zoospores to other areas such as the nearby Eastern Arc Mts. where endemic and vulnerable species may still be na{\"i}ve to the fungus and thus suffer of population declines. 5. My study significantly contributed to the knowledge of the amphibian fauna of Mt. Kilimanjaro and of East Africa in general, and it represents a valuable tool for future conservation actions and measures. Finally, it highlights the importance of using a multidisciplinary (i.e. community ecology, historical biogeography, landscape genetics, disease ecology) and multilevel (i.e. community, species, population, gene) approach to disentangle patterns of biodiversity.}, subject = {Kilimandscharo}, language = {en} } @unpublished{GeiselhartGielenLazaretal.2013, author = {Geiselhart, Roman and Gielen, Rob H. and Lazar, Mircea and Wirth, Fabian R.}, title = {An Alternative Converse Lyapunov Theorem for Discrete-Time Systems}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78512}, year = {2013}, abstract = {This paper presents an alternative approach for obtaining a converse Lyapunov theorem for discrete-time systems. The proposed approach is constructive, as it provides an explicit Lyapunov function. The developed converse theorem establishes existence of global Lyapunov functions for globally exponentially stable (GES) systems and semi-global practical Lyapunov functions for globally asymptotically stable systems. Furthermore, for specific classes of sys- tems, the developed converse theorem can be used to establish non-conservatism of a particular type of Lyapunov functions. Most notably, a proof that conewise linear Lyapunov functions are non-conservative for GES conewise linear systems is given and, as a by-product, tractable construction of polyhedral Lyapunov functions for linear systems is attained.}, subject = {Ljapunov-Funktion}, language = {en} } @article{GageikStrohmeierMontenegro2013, author = {Gageik, Nils and Strohmeier, Michael and Montenegro, Sergio}, title = {An Autonomous UAV with an Optical Flow Sensor for Positioning and Navigation}, series = {International Journal of Advanced Robotic Systems}, journal = {International Journal of Advanced Robotic Systems}, doi = {10.5772/56813}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96368}, year = {2013}, abstract = {A procedure to control all six DOF (degrees of freedom) of a UAV (unmanned aerial vehicle) without an external reference system and to enable fully autonomous flight is presented here. For 2D positioning the principle of optical flow is used. Together with the output of height estimation, fusing ultrasonic, infrared and inertial and pressure sensor data, the 3D position of the UAV can be computed, controlled and steered. All data processing is done on the UAV. An external computer with a pathway planning interface is for commanding purposes only. The presented system is part of the AQopterI8 project, which aims to develop an autonomous flying quadrocopter for indoor application. The focus of this paper is 2D positioning using an optical flow sensor. As a result of the performed evaluation, it can be concluded that for position hold, the standard deviation of the position error is 10cm and after landing the position error is about 30cm.}, language = {en} } @article{SirenStetterHirschbergetal.2013, author = {Sir{\´e}n, Anna-Leena and Stetter, Christian and Hirschberg, Markus and Nieswandt, Bernhard and Ernestus, Ralf-Ingo and Heckmann, Manfred}, title = {An experimental protocol for in vivo imaging of neuronal structural plasticity with 2-photon microscopy in mice}, series = {Experimental \& Translational Stroke Medicine}, journal = {Experimental \& Translational Stroke Medicine}, doi = {10.1186/2040-7378-5-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96908}, year = {2013}, abstract = {Introduction Structural plasticity with synapse formation and elimination is a key component of memory capacity and may be critical for functional recovery after brain injury. Here we describe in detail two surgical techniques to create a cranial window in mice and show crucial points in the procedure for long-term repeated in vivo imaging of synaptic structural plasticity in the mouse neocortex. Methods Transgenic Thy1-YFP(H) mice expressing yellow-fluorescent protein (YFP) in layer-5 pyramidal neurons were prepared under anesthesia for in vivo imaging of dendritic spines in the parietal cortex either with an open-skull glass or thinned skull window. After a recovery period of 14 days, imaging sessions of 45-60 min in duration were started under fluothane anesthesia. To reduce respiration-induced movement artifacts, the skull was glued to a stainless steel plate fixed to metal base. The animals were set under a two-photon microscope with multifocal scanhead splitter (TriMScope, LaVision BioTec) and the Ti-sapphire laser was tuned to the optimal excitation wavelength for YFP (890 nm). Images were acquired by using a 20×, 0.95 NA, water-immersion objective (Olympus) in imaging depth of 100-200 μm from the pial surface. Two-dimensional projections of three-dimensional image stacks containing dendritic segments of interest were saved for further analysis. At the end of the last imaging session, the mice were decapitated and the brains removed for histological analysis. Results Repeated in vivo imaging of dendritic spines of the layer-5 pyramidal neurons was successful using both open-skull glass and thinned skull windows. Both window techniques were associated with low phototoxicity after repeated sessions of imaging. Conclusions Repeated imaging of dendritic spines in vivo allows monitoring of long-term structural dynamics of synapses. When carefully controlled for influence of repeated anesthesia and phototoxicity, the method will be suitable to study changes in synaptic structural plasticity after brain injury.}, language = {en} } @phdthesis{Audretsch2013, author = {Audretsch, Christof}, title = {Analysing Quorum Sensing and Biofilm formation in Staphylococcus aureus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-92189}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Staphylococcus aureus (SA) causes nosocomial infections including life threatening sepsis by multi-resistant strains (MRSA). It has the ability to form biofilms to protect it from the host immune system and from anti staphylococcal drugs. Biofilm and planctonic life style is regulated by a complex Quorum-Sensing (QS) system with agr as a central regulator. To study biofilm formation and QS mechanisms in SA a Boolean network was build (94 nodes, 184 edges) including two different component systems such as agr, sae and arl. Important proteins such as Sar, Rot and SigB were included as further nodes in the model. System analysis showed there are only two stable states biofilm forming versus planctonic with clearly different subnetworks turned on. Validation according to gene expression data confirmed this. Network consistency was tested first according to previous knowledge and literature. Furthermore, the predicted node activity of different in silico knock-out strains agreed well with corresponding micro array experiments and data sets. Additional validation included the expression of further nodes (Northern blots) and biofilm production compared in different knock-out strains in biofilm adherence assays. The model faithfully reproduces the behaviour of QS signalling mutants. The integrated model allows also prediction of various other network mutations and is supported by experimental data from different strains. Furthermore, the well connected hub proteins elucidate how integration of different inputs is achieved by the QS network. For in silico as well as in vitro experiments it was found that the sae-locus is also a central modulator of biofilm production. Sae knock-out strains showed stronger biofilms. Wild type phenotype was rescued by sae complementation. To elucidate the way in which sae takes influence on biofilm formation the network was used and Venn-diagrams were made, revealing nodes regulated by sae and changed in biofilms. In these Venn-diagrams nucleases and extracellular proteins were found to be promising nodes. The network revealed DNAse to be of great importance. Therefore qualitatively the DNAse amount, produced by different SA mutants was measured, it was tried to dissolve biofilms with according amounts of DNAse and the concentration of nucleic acids, proteins and polysaccharides were measured in biofilms of different SA mutants. With its thorough validation the network model provides a powerful tool to study QS and biofilm formation in SA, including successful predictions for different knock-out mutant behaviour, QS signalling and biofilm formation. This includes implications for the behaviour of MRSA strains and mutants. Key regulatory mutation combinations (agr-, sae-, sae-/agr-, sigB+, sigB+/sae-) were directly tested in the model but also in experiments. High connectivity was a good guide to identify master regulators, whose detailed behaviour was studied both in vitro and in the model. Together, both lines of evidence support in particular a refined regulatory role for sae and agr with involvement in biofilm repression and/or SA dissemination. With examination of the composition of different mutant biofilms as well as with the examination of the reaction cascade that connects sae to the biofilm forming ability of SA and also by postulating that nucleases might play an important role in that, first steps were taken in proving and explaining regulatory links leading from sae to biofilms. Furthermore differences in biofilms of different mutant SA strains were found leading us in perspective towards a new understanding of biofilms including knowledge how to better regulate, fight and use its different properties.}, subject = {Staphylococcus aureus}, language = {en} } @phdthesis{DasGupta2013, author = {Das Gupta, Mithun}, title = {Analyse von MicroRNA-Profilen in humanen dendritischen Zellen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-108326}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {The field of microRNA research has gained enormous significance during recent years. Current studies have shown that microRNAs play an important role in many biological processes via posttranscriptional gene regulation. This also applies for the TLR-mediated recognition of pathogens by immune cells. Among others, the microRNAs miR-132, miR-146a and miR-155 have been characterized by various authors. However, the specific role of microRNAs in the defense against fungal infections by Aspergillus fumigatus has not been investigated so far, although this ubiquitous mold causes severe infections in immuno-compromised patients. As dendritic cells play a pivotal part in the in vivo recognition of A. fumigatus, the present study investigates the reaction of these cells to A. fumigatus and other pathogens on the microRNA level. For this purpose, dendritic cells were incubated with different forms of A. fumigatus and other pathogens for up to twelve hours. Subsequently, the expression of miR-132, miR-146a and miR-155 was quantified by real-time PCR. Levels of miR-132 in dendritic cells were significantly increased after stimulation with living germ tubes of A. fum, but showed no change after treatment with LPS. Relative expression level of miR-146a was moderately elevated upon stimulation with LPS, but did not respond to co-cultivation with living germ tubes. MiR-155 was highly induced by both stimuli. These results show, that dependent on the stimulus, microRNAs are differentially regulated in dendritic cells. Among the tested microRNAs, miR-155 showed the strongest and most stable expression values. Therefore, further experiments focused on this mircoRNA. It was shown, that the up-regulation of miR-155 is dependent on the germination stage of the fungus. Induction of miR-155 was low with conidia, moderate with hyphae and high with germ tubes. The extent of miR-155 induction also corresponded with the multiplicity of infection (MOI), with higher MOIs triggering a stronger miR-155 response. These results suggest that miR-132 and miR-155 play an important role in the immunologic reaction of DCs against A. fumigatus and that a further characterization of these microRNA, especially with respect to their specific function in DCs, could contribute to the understanding of the biological mechanisms of Aspergillosis.}, subject = {Aspergillus fumigatus}, language = {en} } @article{BrehmKoziolKrohne2013, author = {Brehm, Klaus and Koziol, Uriel and Krohne, Georg}, title = {Anatomy and development of the larval nervous system in Echinococcus multilocularis}, series = {Frontiers in Zoology}, journal = {Frontiers in Zoology}, doi = {10.1186/1742-9994-10-24}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96504}, year = {2013}, abstract = {Background The metacestode larva of Echinococcus multilocularis (Cestoda: Taeniidae) develops in the liver of intermediate hosts (typically rodents, or accidentally in humans) as a labyrinth of interconnected cysts that infiltrate the host tissue, causing the disease alveolar echinococcosis. Within the cysts, protoscoleces (the infective stage for the definitive canid host) arise by asexual multiplication. These consist of a scolex similar to that of the adult, invaginated within a small posterior body. Despite the importance of alveolar echinococcosis for human health, relatively little is known about the basic biology, anatomy and development of E. multilocularis larvae, particularly with regard to their nervous system. Results We describe the existence of a subtegumental nerve net in the metacestode cysts, which is immunoreactive for acetylated tubulin-α and contains small populations of nerve cells that are labeled by antibodies raised against several invertebrate neuropeptides. However, no evidence was found for the existence of cholinergic or serotoninergic elements in the cyst wall. Muscle fibers occur without any specific arrangement in the subtegumental layer, and accumulate during the invaginations of the cyst wall that form brood capsules, where protoscoleces develop. The nervous system of the protoscolex develops independently of that of the metacestode cyst, with an antero-posterior developmental gradient. The combination of antibodies against several nervous system markers resulted in a detailed description of the protoscolex nervous system, which is remarkably complex and already similar to that of the adult worm. Conclusions We provide evidence for the first time of the existence of a nervous system in the metacestode cyst wall, which is remarkable given the lack of motility of this larval stage, and the lack of serotoninergic and cholinergic elements. We propose that it could function as a neuroendocrine system, derived from the nervous system present in the bladder tissue of other taeniids. The detailed description of the development and anatomy of the protoscolex neuromuscular system is a necessary first step toward the understanding of the developmental mechanisms operating in these peculiar larval stages.}, language = {en} } @article{HuangBelharazemLietal.2013, author = {Huang, Bei and Belharazem, Djeda and Li, Li and Kneitz, Susanne and Schnabel, Philipp A. and Rieker, Ralf J. and K{\"o}rner, Daniel and Nix, Wilfried and Schalke, Berthold and M{\"u}ller-Hermelink, Hans Konrad and Ott, German and Rosenwald, Andreas and Str{\"o}bel, Philipp and Marx, Alexander}, title = {Anti-apoptotic signature in thymic squamous cell carcinomas - functional relevance of anti-apoptotic BIRC3 expression in the thymic carcinoma cell line 1889c}, series = {Frontiers in Oncology}, volume = {3}, journal = {Frontiers in Oncology}, number = {316}, doi = {10.3389/fonc.2013.00316}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132214}, year = {2013}, abstract = {The molecular pathogenesis of thymomas and thymic arcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and TCs, suggesting that other oncogenic principles might be important.This made us re-analyze historic expression data obtained in a spectrumof thymomas and thymic squamous cell carcinomas (TSCCs) with a custom-made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC.}, language = {en} } @article{vanDintherZhangWeidaueretal.2013, author = {van Dinther, Maarten and Zhang, Juan and Weidauer, Stella E. and Boschert, Verena and Muth, Eva-Maria and Knappik, Achim and de Gorter, David J. J. and van Kasteren, Puck B. and Frisch, Christian and M{\"u}ller, Thomas D. and ten Dijke, Peter}, title = {Anti-Sclerostin Antibody Inhibits Internalization of Sclerostin and Sclerostin-Mediated Antagonism of Wnt/LRP6 Signaling}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0062295}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130981}, pages = {e62295}, year = {2013}, abstract = {Sclerosteosis is a rare high bone mass disease that is caused by inactivating mutations in the SOST gene. Its gene product, Sclerostin, is a key negative regulator of bone formation and might therefore serve as a target for the anabolic treatment of osteoporosis. The exact molecular mechanism by which Sclerostin exerts its antagonistic effects on Wnt signaling in bone forming osteoblasts remains unclear. Here we show that Wnt3a-induced transcriptional responses and induction of alkaline phosphatase activity, an early marker of osteoblast differentiation, require the Wnt co-receptors LRP5 and LRP6. Unlike Dickkopf1 (DKK1), Sclerostin does not inhibit Wnt-3a-induced phosphorylation of LRP5 at serine 1503 or LRP6 at serine 1490. Affinity labeling of cell surface proteins with \([^{125} I]\) Sclerostin identified LRP6 as the main specific Sclerostin receptor in multiple mesenchymal cell lines. When cells were challenged with Sclerostin fused to recombinant green fluorescent protein (GFP) this was internalized, likely via a Clathrin-dependent process, and subsequently degraded in a temperature and proteasome-dependent manner. Ectopic expression of LRP6 greatly enhanced binding and cellular uptake of Sclerostin-GFP, which was reduced by the addition of an excess of non-GFP-fused Sclerostin. Finally, an anti-Sclerostin antibody inhibited the internalization of Sclerostin-GFP and binding of Sclerostin to LRP6. Moreover, this antibody attenuated the antagonistic activity of Sclerostin on canonical Wnt-induced responses.}, language = {en} } @article{BeierGaetschenbergerAzzamietal.2013, author = {Beier, Hildburg and G{\"a}tschenberger, Heike and Azzami, Klara and Tautz, J{\"u}rgen}, title = {Antibacterial Immune Competence of Honey Bees (Apis mellifera) Is Adapted to Different Life Stages and Environmental Risks}, series = {PLoS ONE}, journal = {PLoS ONE}, doi = {10.1371/journal.pone.0066415}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96895}, year = {2013}, abstract = {The development of all honey bee castes proceeds through three different life stages all of which encounter microbial infections to a various extent. We have examined the immune strength of honey bees across all developmental stages with emphasis on the temporal expression of cellular and humoral immune responses upon artificial challenge with viable Escherichia coli bacteria. We employed a broad array of methods to investigate defence strategies of infected individuals: (a) fate of bacteria in the haemocoel; (b) nodule formation and (c) induction of antimicrobial peptides (AMPs). Newly emerged adult worker bees and drones were able to activate efficiently all examined immune reactions. The number of viable bacteria circulating in the haemocoel of infected bees declined rapidly by more than two orders of magnitude within the first 4-6 h post-injection (p.i.), coinciding with the occurrence of melanised nodules. Antimicrobial activity, on the other hand, became detectable only after the initial bacterial clearance. These two temporal patterns of defence reactions very likely represent the constitutive cellular and the induced humoral immune response. A unique feature of honey bees is that a fraction of worker bees survives the winter season in a cluster mostly engaged in thermoregulation. We show here that the overall immune strength of winter bees matches that of young summer bees although nodulation reactions are not initiated at all. As expected, high doses of injected viable E.coli bacteria caused no mortality in larvae or adults of each age. However, drone and worker pupae succumbed to challenge with E.coli even at low doses, accompanied by a premature darkening of the pupal body. In contrast to larvae and adults, we observed no fast clearance of viable bacteria and no induction of AMPs but a rapid proliferation of E.coli bacteria in the haemocoel of bee pupae ultimately leading to their death.}, language = {en} } @phdthesis{Busch2013, author = {Busch, Martin}, title = {Aortic Dendritic Cell Subsets in Healthy and Atherosclerotic Mice and The Role of the miR-17~92 Cluster in Dendritic Cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-71683}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Atherosclerosis is accepted to be a chronic inflammatory disease of the arterial vessel wall. Several cellular subsets of the immune system are involved in its initiation and progression, such as monocytes, macrophages, T and B cells. Recent research has demonstrated that dendritic cells (DCs) contribute to atherosclerosis, too. DCs are defined by their ability to sense and phagocyte antigens, to migrate and to prime other immune cells, such as T cells. Although all DCs share these functional characteristics, they are heterogeneous with respect to phenotype and origin. Several markers have been used to describe DCs in different lymphoid and non-lymphoid organs; however, none of them has proven to be unambiguous. The expression of surface molecules is highly variable depending on the state of activation and the surrounding tissue. Furthermore, DCs in the aorta or the atherosclerotic plaque can be derived from designated precursor cells or from monocytes. In addition, DCs share both their marker expression and their functional characteristics with other myeloid cells like monocytes and macrophages. The repertoire of aortic DCs in healthy and atherosclerotic mice has just recently started to be explored, but yet there is no systemic study available, which describes the aortic DC compartment. Because it is conceivable that distinct aortic DC subsets exert dedicated functions, a detailed description of vascular DCs is required. The first part of this thesis characterizes DC subsets in healthy and atherosclerotic mice. It describes a previously unrecognized DC subset and also sheds light on the origin of vascular DCs. In recent years, microRNAs (miRNAs) have been demonstrated to regulate several cellular functions, such as apoptosis, differentiation, development or proliferation. Although several cell types have been characterized extensively with regard to the miRNAs involved in their regulation, only few studies are available that focus on the role of miRNAs in DCs. Because an improved understanding of the regulation of DC functions would allow for new therapeutic options, research on miRNAs in DCs is required. The second part of this thesis focuses on the role of the miRNA cluster miR- 17~92 in DCs by exploring its functions in healthy and atherosclerotic mice. This thesis clearly demonstrates for the first time an anti-inflammatory and atheroprotective role for the miR17-92 cluster. A model for its mechanism is suggested.}, subject = {Aorta}, language = {en} } @article{RestMayoralFernandez2013, author = {Rest, Christina and Mayoral, Mar{\´i}a Jos{\´e} and Fern{\´a}ndez, Gustavo}, title = {Aqueous Self-Sorting in Extended Supramolecular Aggregates}, series = {International Journal of Molecular Sciences}, volume = {14}, journal = {International Journal of Molecular Sciences}, number = {1}, doi = {10.3390/ijms14011541}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129435}, pages = {1541-1565}, year = {2013}, abstract = {Self-organization and self-sorting processes are responsible for the regulation and control of the vast majority of biological processes that eventually sustain life on our planet. Attempts to unveil the complexity of these systems have been devoted to the investigation of the binding processes between artificial molecules, complexes or aggregates within multicomponent mixtures, which has facilitated the emergence of the field of self-sorting in the last decade. Since, artificial systems involving discrete supramolecular structures, extended supramolecular aggregates or gel-phase materials in organic solvents or—to a lesser extent—in water have been investigated. In this review, we have collected diverse strategies employed in recent years to construct extended supramolecular aggregates in water upon self-sorting of small synthetic molecules. We have made particular emphasis on co-assembly processes in binary mixtures leading to supramolecular structures of remarkable complexity and the influence of different external variables such as solvent and concentration to direct recognition or discrimination processes between these species. The comprehension of such recognition phenomena will be crucial for the organization and evolution of complex matter.}, language = {en} } @article{TappeHaeuplerSchaeferetal.2013, author = {Tappe, Dennis and Haeupler, Alexandra and Sch{\"a}fer, Hansj{\"o}rg and Racz, Paul and Cramer, Jakob P. and Poppert, Sven}, title = {Armillifer armillatus Pentastomiasis in African Immigrant, Germany}, series = {Emerging Infectious Diseases}, volume = {19}, journal = {Emerging Infectious Diseases}, number = {3}, doi = {10.3201/eid1903.121508}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129054}, pages = {507-508}, year = {2013}, abstract = {No abstract available.}, language = {en} } @article{ManchiaAdliAkulaetal.2013, author = {Manchia, Mirko and Adli, Mazda and Akula, Nirmala and Arda, Raffaella and Aubry, Jean-Michel and Backlund, Lena and Banzato, Claudio E. M. and Baune, Bernhard T. and Bellivier, Frank and Bengesser, Susanne and Biernacka, Joanna M. and Brichant-Petitjean, Clara and Bui, Elise and Calkin, Cynthia V. and Cheng, Andrew Tai Ann and Chillotti, Caterina and Cichon, Sven and Clark, Scott and Czerski, Piotr M. and Dantas, Clarissa and Del Zompo, Maria and DePaulo, J. Raymond and Detera-Wadleigh, Sevilla D. and Etain, Bruno and Falkai, Peter and Fris{\´e}n, Louise and Frye, Mark A. and Fullerton, Jan and Gard, S{\´e}bastien and Garnham, Julie and Goes, Fernando S. and Grof, Paul and Gruber, Oliver and Hashimoto, Ryota and Hauser, Joanna and Heilbronner, Urs and Hoban, Rebecca and Hou, Liping and Jamain, St{\´e}phane and Kahn, Jean-Pierre and Kassem, Layla and Kato, Tadafumi and Kelsoe, John R. and Kittel-Schneider, Sarah and Kliwicki, Sebastian and Kuo, Po-Hsiu and Kusumi, Ichiro and Laje, Gonzalo and Lavebratt, Catharina and Leboyer, Marion and Leckband, Susan G. and L{\´o}pez Jaramillo, Carlos A. and Maj, Mario and Malafosse, Alain and Martinsson, Lina and Masui, Takuya and Mitchell, Philip B. and Mondimore, Frank and Monteleone, Palmiero and Nallet, Audrey and Neuner, Maria and Nov{\´a}k, Tom{\´a}s and O'Donovan, Claire and {\"O}sby, Urban and Ozaki, Norio and Perlis, Roy H. and Pfennig, Andrea and Potash, James B. and Reich-Erkelenz, Daniela and Reif, Andreas and Reininghaus, Eva and Richardson, Sara and Rouleau, Guy A. and Rybakowski, Janusz K. and Schalling, Martin and Schofield, Peter R. and Schubert, Oliver K. and Schweizer, Barbara and Seem{\"u}ller, Florian and Grigoroiu-Serbanescu, Maria and Severino, Giovanni and Seymour, Lisa R. and Slaney, Claire and Smoller, Jordan W. and Squassina, Alessio and Stamm, Thomas and Steele, Jo and Stopkova, Pavla and Tighe, Sarah K. and Tortorella, Alfonso and Turecki, Gustavo and Wray, Naomi R. and Wright, Adam and Zandi, Peter P. and Zilles, David and Bauer, Michael and Rietschel, Marcella and McMahon, Francis J. and Schulze, Thomas G. and Alda, Martin}, title = {Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0065636}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130938}, pages = {e65636}, year = {2013}, abstract = {Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (\(\kappa\))] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (\(\kappa\) = 0.66 and \(\kappa\) = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (\(ICC_1 = 0.71\) and \(ICC_2 = 0.75\), respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.}, language = {en} } @phdthesis{Niederlechner2013, author = {Niederlechner, Stefanie}, title = {Assessment of the basic molecular mechanisms underlying L-glutamine's cytoprotective effects after intestinal injury}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-77399}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Critical illness like sepsis, shock, and intestinal bowel disease are one of the leading causes of morbidity and mortality in the US and around the world. At present, studies to define new therapeutic interventions that can protect tissues and cells against injury and attenuate inflammation are fields of intense investigation. While research over the past decade has clearly identified GLN as a vital stress substrate facilitating cellular survival following injury, the initiation steps in GLN's cytoprotective molecular mechanism still remain elusive. Previously published work suggested that stabilization of ECM proteins and activation of ECM receptor osmosignaling may play a central role in the orchestration of many cellular pathways following stress. Thus, I hypothesized that preservation of ECM protein and EGFR levels as well as ECM receptor signaling play key roles in the molecular mechanisms underlying GLN's protection against thermal injury in the intestine. I was able to confirm via Western blotting and by using silencing RNA against FN, Ntn-1, EGFR, and their negative controls, that GLN-mediated preservation of FN, Ntn-1, and EGFR levels is critical in GLN's protection against hyperthermia in IEC-6 cells. By using a selective FN-Integrin interaction inhibitor GRGDSP, its negative control peptide GRGESP, and Src-kinase inhibitor PP2, I showed that FN-Integrin signaling and Src-kinase activation are essential in GLN-mediated protection in the intestine. This applied to EGFR signaling as demonstrated using the EGFR tyrosine kinase inhibitor AG1478. In addition to GRGDSP and AG1478, ERK1/2 inhibitors PD98059 and UO126 as well as the p38MAPK inhibitor SB203580 revealed that GLN is protective by activating ERK1/2 and dephosphorylating p38MAPK via FN-Integrin and EGFR signaling. However, GLN-mediated PI3-K/Akt/Hsp70 activation seems to occur independently of FN-Integrin and EGFR signaling as indicated by Western blots as well as experiments using the PI3-K inhibitor LY294002, GRGDSP, and AG1478. The results showed that GLN activates cell survival signaling pathways via integrins as well as EGFRs after hyperthermia. Moreover, I found that GLN-mediated preservation of FN expression after HS is regulated via PI3-K signaling. Whether GLN-mediated PI3-K signaling happens simultaneously to FN-Integrin and EGFR signaling or whether PI3-K signaling coordinates FN-Integrin and EGFR signaling needs to be investigated in future studies. Further, experiments with PD98059 and GRGDSP revealed that ERK1/2 assists in mediating transactivation of HSF-1 following HS. This leads to increases in Hsp70 expression via FN-Integrin signaling, which is known to attenuate apoptosis after thermal injury. Fluorescence microscopy results indicated that HS and GLN regulate cell are size changes and the morphology of F-actin via FN-Integrin signaling. Experiments using GRGDSP and GRGESP showed that GLN enhances cellular survival via FN-Integrin signaling in a manner that does not require increased intracellular GLN concentrations (as quantified using LC-MS/MS). In summary, my thesis work gives new and potentially clinically relevant mechanistic insights into GLN-mediated molecular cell survival pathways. These results warrant clinical translation to assess if clinical outcome of critically ill patients suffering from gastrointestinal diseases can be improved by GLN treatment and/or by targeting the molecular pathways found in my studies.}, subject = {Glutamin}, language = {en} } @phdthesis{Asthana2013, author = {Asthana, Manish}, title = {Associative learning - Genetic modulation of extinction and reconsolidation and the effects of transcranial Direct Current Stimulation (tDCS)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-84158}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Scientific surveys provide sufficient evidence that anxiety disorders are one of the most common psy-chiatric disorders in the world. The lifetime prevalence rate of anxiety disorder is 28.8\% (Kessler, et al., 2005). The most widely studied anxiety disorders are as follows panic disorder (PD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), social phobia (or social anxiety disorder), specific phobias, and generalized anxiety disorder (GAD). (NIMH Article, 2009). Classical conditioning is the stable paradigm used from the last one century to understand the neurobi-ology of fear learning. Neurobiological mechanism of fear learning is well documented with the condi-tioning studies. In the therapy of anxiety disorders, exposure based therapies are known to be the most effective approaches. Flooding is a form of exposure therapy in which a participant is exposed to the fear situation and kept in that situation until their fear dissipates. The exposure therapy is based on the phenomena of extinction; this means that a conditioned response diminishes if the conditioned stimulus (CS) is repeatedly presented without an unconditioned stimulus (UCS). One problem with extinction as well as with exposure-based therapy is the problem of fear return (for e.g. renewal, spontaneous recov-ery and reinstatement) after successful extinction. Therefore, extinction does not delete the fear memory trace. It has been well documented that memory processes can be modulated or disrupted using several sci-entific paradigms such as behavioral (for e.g. exposure therapy), pharmacological (for e.g. drug manipu-lation), non-invasive stimulation (for e.g. non-invasive stimulation such as electroconvulsive shock (ECS), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), etc. However, modulation of memory processes after reactivation or via non-invasive stimulation is still not clear, which is the focus of the current study. In addition, study of genetic variant suggests that genetic differences play a vital role in the psychiatric disorder especially in fear learning. Hence, it is also one of the concerns of the current dissertation to investigate the interaction between gene and reconsolidation of memory. With respect to fear-conditioning, there are three findings in the current dissertation, which are as fol-lows: (i) In the first study we investigated that non-invasive weak electrical stimulation interferes with the consolidation process and disrupts the fear consolidation to attain stable form. This might offer an effective treatment in the pathological memories, for e.g. PTSD, PD, etc. (ii) In the second study we demonstrated whether a brief single presentation of the CS will inhibit the fear recovery. Like earlier studies we also found that reactivation followed by reconsolidation douses fear return. Attenuation of fear recovery was observed in the reminder group compared to the no-reminder group. (iii) Finally, in our third study we found a statistically significant role of brain derived neurotrophic factor (BDNF) polymorphism in reconsolidation. Results of the third study affirm the involvement of BDNF variants (Met vs. Val) in the modulation of conditioned fear memory after its reactivation. In summary, we were able to show in the current thesis modulation of associative learning and recon-solidation via transcranial direct current stimulation and genetic polymorphism.}, subject = {Konditionierung}, language = {en} } @phdthesis{Shiban2013, author = {Shiban, Youssef}, title = {Attenuating Renewal following Exposure Therapy : Mechanisms of Exposure in Multiple Contexts and its Influence on the Renewal of Fear: Studies in Virtual Reality}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76673}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {„Renewal" bezeichnet das Wiederauftreten von Angst nach erfolgreicher Expositionstherapie in Folge einer erneuten Konfrontation mit dem phobischen Stimulus in einem neuen, sich vom Expositionskontext unterscheidenden Kontext. Bouton (1994) zufolge deutet diese Angstr{\"u}ckkehr durch einen Kontextwechsel darauf hin, dass die Angst nicht gel{\"o}scht wurde. Stattdessen wurde w{\"a}hrend der Expositionssitzung eine neue Assoziation gelernt, die das gef{\"u}rchtete Objekt mit „keiner Angst", also den konditionierten Reiz (conditioned stimulus, CS) mit „keinem unkonditionierten Reiz" (no unconditioned stimulus, no US), verbindet. Bouton argumentiert weiter, dass diese Assoziation kontextabh{\"a}ngig ist, wodurch Effekte wie Angst-Renewal erkl{\"a}rt werden k{\"o}nnen. Da in einem neuen Kontext die CS-no US-Assoziation nicht aktiviert wird, wird die Angst auch nicht gehemmt. Die Kontextabh{\"a}ngigkeit der CS-no US-Assoziation wurde in mehreren Studien belegt (Balooch \& Neumann, 2011; Siavash Bandarian Balooch, Neumann, \& Boschen, 2012; Culver, Stoyanova, \& Craske, 2011; Kim \& Richardson, 2009; Neumann \& Kitlertsirivatana, 2010). Aktuell konzentriert sich die Forschung zur Therapie von Angstst{\"o}rungen auf die Frage, wie Angst reduziert und gleichzeitig ein R{\"u}ckfall verhindert werden kann. Hierzu werden verschiedene Expositionsprotokolle untersucht, wie zum Beispiel (1) Exposition in mehreren Kontexten (multiple contexts exposure, MCE), um Renewal zu reduzieren (z.B. Balooch \& Neumann, 2011); (2) verl{\"a}ngerte Exposition (prolonged exposure, PE), um die hemmende Assoziation w{\"a}hrend des Extinktionslernes zu st{\"a}rken (z.B. Thomas, Vurbic, \& Novak, 2009) und (3) Rekonsolidierungs-Updates (reconsolidation update, RU), die den Rekonsolidierungsprozess durch eine kurze Exposition des CS+ vor der eigentlichen Exposition aktualisieren sollen (Schiller et al., 2010). Bisher liegen jedoch nur sehr wenige Studien vor, die diese neuen Expositionsprotokolle an klinischen Stichproben untersucht haben, und - soweit bekannt - keine Studie, welche die Wirkmechanismen dieser Protokolle an einer klinischen Stichprobe erforscht. Die vorliegende Dissertation hat drei Ziele. Das erste Ziel besteht darin zu pr{\"u}fen, ob Expositionstherapie in multiplen Kontexten die Wahrscheinlichkeit von Renewal reduziert. Das zweite Ziel ist die Untersuchung der Mechanismen, die dem Effekt der Exposition in multiplen Kontexten zugrunde liegen und das dritte ist den Kontext im Zusammenhang mit Konditionierung und Extinktion zu konzeptualisieren. Insgesamt wurden drei Studien durchgef{\"u}hrt. Die erste Studie untersuchte den Effekt von Exposition in multiplen Kontexten auf Renewal, die zweite und dritte Studie die Wirkmechanismen von MCE. In der ersten Studie wurden spinnenphobische Probanden (N = 30) viermal mit einer virtuellen Spinne konfrontiert. Die Expositionstrials wurden entweder in einem gleichbleibenden Kontext oder in vier verschiedenen Kontexten durchgef{\"u}hrt. Am Ende der Sitzung absolvierten alle Teilnehmer einen virtuellen Renewaltest, bei dem die virtuelle Spinne in einem neuen Kontext gezeigt wurde, und einen in vivo Verhaltensvermeidungstest (behavioral avoidance test, BAT) mit einer echten Spinne. Die Ergebnisse zeigten, dass Probanden, welche die vier Expositionstrials in unterschiedlichen Kontexten erfuhren, weniger Angst, sowohl im virtuellen Renewaltest als auch im BAT, erlebten. In dieser Studie konnte die Wirksamkeit von MCE f{\"u}r die Reduktion von Renewal erfolgreich nachgewiesen werden. Studie 2 (N = 35) untersuchte die Wirkmechanismen von MCE in einem differentiellen Konditionierungsparadigma. Die Extinktion wurde in multiplen Kontexten durchgef{\"u}hrt. Hierbei war das Ziel, eine {\"a}hnliche Verminderung von Renewal wie in Studie 1 nachzuweisen. Der Extinktion folgten zwei Tests, mit dem Ziel m{\"o}gliche hemmende Effekte des Kontexts, die w{\"a}hrend der Extinktionsphase erworben wurden, aufzudecken. Bez{\"u}glich des Effektes von MCE wurden drei Hypothesen aufgestellt: (1) Der Extinktionskontext wird mit der Exposition assoziiert, fungiert folglich w{\"a}hrend der Extinktion als Sicherheitssignal und konkurriert daher mit dem Sicherheitslernen des CS. Dies f{\"u}hrt zu einem verminderten Extinktionseffekt auf den CS, wenn die Extinktion nur in einem Kontext durchgef{\"u}hrt wird. (2) Die Elemente im Extinktionskontext (z.B. Raumfarbe, M{\"o}bel) stehen im Zusammenhang mit der CS-no US-Assoziation und erinnern daher an die Extinktion, was zu einer gr{\"o}ßeren Angsthemmung f{\"u}hrt, wenn sie w{\"a}hrend eines Tests gezeigt werden. (3) Nach der emotionalen Prozesstheorie (emotional process theory; Bouton, 1994; Foa et al., 1996) bestimmen die Therapieprozessfaktoren die St{\"a}rke des Renewals. Beispielsweise korrelieren initiale Angstaktivierung, Aktivierung in und zwischen den Sitzungen mit der St{\"a}rke des Renewals. Jedoch waren in dieser Studie keine Unterschiede zwischen den Gruppen im Renewaltest zu beobachten, weswegen die Ergebnisse der zwei Nachtests nicht zu interpretieren sind. Das Ziel von Studie 3 (N = 61) war es, das Konzept des Kontexts im Rahmen von Konditionierung und Exposition zu definieren. In Studie 3 wurde das Auftreten der Generalisierungsabnahme (generalization decrement) genutzt, bei der eine konditionierte Reaktion infolge eines Kontextwechsels nur reduziert auftritt. Auf diesem Weg kann Kontext{\"a}hnlichkeit quantifiziert werden. Nach einer Akquisitonsphase in einem Kontext wurden die Teilnehmer in einem von drei verschiedenen Kontexten getestet. Zwei dieser Kontexte unterschieden sich nur in einer Dimension (Anordnung der Objekte vs. Objekteigenschaften). Die dritte Gruppe wurde im Akquisitonskontext getestet und diente als Kontrollgruppe. Es fanden sich jedoch keine Unteschiede zwischen den Gruppen in den Testphasen. Eine m{\"o}gliche Erkl{\"a}rung ist die Neuartigkeit des Testkontextes. Teilnehmer, die nach der Extinktion einem neuen Kontext ausgesetzt waren, erwarteten in einem anderen Kontext eine zweite Extinktionsphase und zeigten daher mehr statt weniger Angst als erwartet.}, subject = {Angst}, language = {en} } @article{MatthiesBrillKagaetal.2013, author = {Matthies, Cordula and Brill, Stefan and Kaga, Kimitaka and Morita, Akio and Kumakawa, Kozo and Skarzynski, Henryk and Claassen, Andre and Hui, Yau and Chiong, Charlotte and M{\"u}ller, Joachim and Behr, Robert}, title = {Auditory Brainstem Implantation Improves Speech Recognition in Neurofibromatosis Type II Patients}, series = {ORL}, volume = {75}, journal = {ORL}, number = {5}, issn = {0301-1569}, doi = {10.1159/000350568}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196383}, pages = {282-295}, year = {2013}, abstract = {This prospective study aimed to determine speech understanding in neurofibromatosis type II (NF2) patients following implantation of a MED-EL COMBI 40+ auditory brainstem implant (ABI). Patients (n = 32) were enrolled postsurgically. Nonauditory side effects were evaluated at fitting and audiological performance was determined using the Sound Effects Recognition Test (SERT), Monosyllable-Trochee-Polysyllable (MTP) test and open-set sentence tests. Subjective benefits were determined by questionnaire. ABI activation was documented in 27 patients, 2 patients were too ill for testing and 3 patients were without any auditory perception. SERT and MTP outcomes under auditory-only conditions improved significantly between first fitting and 12-month follow-up. Open-set sentence recognition improved from 5\% at first fitting to 37\% after 12 months. The number of active electrodes had no significant effect on performance. All questionnaire respondents were 'satisfied' to 'very satisfied' with their ABI. An ABI is an effective treatment option in NF2 patients with the potential to provide open-set speech recognition and subjective benefits. To our knowledge, the data presented herein is exceptional in terms of the open-set speech perception achieved in NF2 patients.}, language = {en} } @article{LatifHeoRazuinetal.2013, author = {Latif, Baha and Heo, Chong Chin and Razuin, Rahimi and Shamalaa, Devi V.}, title = {Autochthonous Human Schistosomiasis, Malaysia}, series = {Emerging Infectious Diseases}, volume = {19}, journal = {Emerging Infectious Diseases}, number = {8}, doi = {10.3201/eid1908.121710}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131692}, pages = {1340-1341}, year = {2013}, abstract = {No abstract available.}, language = {en} } @article{KoutsilieriLutzScheller2013, author = {Koutsilieri, E. and Lutz, M. B. and Scheller, C.}, title = {Autoimmunity, dendritic cells and relevance for Parkinson's disease}, series = {Journal of Neural Transmission}, volume = {120}, journal = {Journal of Neural Transmission}, doi = {10.1007/s00702-012-0842-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132308}, pages = {75-81}, year = {2013}, abstract = {Innate and adaptive immune responses in neurodegenerative diseases have become recently a focus of research and discussions. Parkinson's disease (PD) is a neurodegenerative disorder without known etiopathogenesis. The past decade has generated evidence for an involvement of the immune system in PD pathogenesis. Both inflammatory and autoimmune mechanisms have been recognized and studies have emphasized the role of activated microglia and T-cell infiltration. In this short review, we focus on dendritic cells, on their role in initiation of autoimmune responses, we discuss aspects of neuroinflammation and autoimmunity in PD, and we report new evidence for the involvement of neuromelanin in these processes.}, language = {en} } @article{HedrichHofmannPabliketal.2013, author = {Hedrich, Christian M. and Hofmann, Sigrun R. and Pablik, Jessica and Morbach, Henner and Girschick, Hermann J.}, title = {Autoinflammatory bone disorders with special focus on chronic recurrent multifocal osteomyelitis (CRMO)}, series = {Pediatric Rheumatology}, volume = {11}, journal = {Pediatric Rheumatology}, number = {47}, issn = {1546-0096}, doi = {10.1186/1546-0096-11-47}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125694}, year = {2013}, abstract = {Sterile bone inflammation is the hallmark of autoinflammatory bone disorders, including chronic nonbacterial osteomyelitis (CNO) with its most severe form chronic recurrent multifocal osteomyelitis (CRMO). Autoinflammatory osteopathies are the result of a dysregulated innate immune system, resulting in immune cell infiltration of the bone and subsequent osteoclast differentiation and activation. Interestingly, autoinflammatory bone disorders are associated with inflammation of the skin and/or the intestine. In several monogenic autoinflammatory bone disorders mutations in disease-causing genes have been reported. However, regardless of recent developments, the molecular pathogenesis of CNO/CRMO remains unclear. Here, we discuss the clinical presentation and molecular pathophysiology of human autoinflammatory osteopathies and animal models with special focus on CNO/CRMO. Treatment options in monogenic autoinflammatory bone disorders and CRMO will be illustrated.}, language = {en} } @article{HedrichHofmannPabliketal.2013, author = {Hedrich, Christian M. and Hofmann, Sigrun R. and Pablik, Jessica and Morbach, Henner and Girschick, Hermann J.}, title = {Autoinflammatory bone disorders with special focus on chronic recurrent multifocal osteomyelitis (CRMO)}, series = {Pediatric Rheumatology}, volume = {11}, journal = {Pediatric Rheumatology}, number = {47}, doi = {10.1186/1546-0096-11-47}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132456}, year = {2013}, abstract = {Sterile bone inflammation is the hallmark of autoinflammatory bone disorders, including chronic nonbacterial osteomyelitis (CNO) with its most severe form chronic recurrent multifocal osteomyelitis (CRMO). Autoinflammatory osteopathies are the result of a dysregulated innate immune system, resulting in immune cell infiltration of the bone and subsequent osteoclast differentiation and activation. Interestingly, autoinflammatory bone disorders are associated with inflammation of the skin and/or the intestine. In several monogenic autoinflammatory bone disorders mutations in disease-causing genes have been reported. However, regardless of recent developments, the molecular pathogenesis of CNO/CRMO remains unclear. Here, we discuss the clinical presentation and molecular pathophysiology of human autoinflammatory osteopathies and animal models with special focus on CNO/CRMO. Treatment options in monogenic autoinflammatory bone disorders and CRMO will be illustrated.}, language = {en} } @article{BeckerCaminitiFiorellaetal.2013, author = {Becker, Martin and Caminiti, Saverio and Fiorella, Donato and Francis, Louise and Gravino, Pietro and Haklay, Mordechai (Muki) and Hotho, Andreas and Loreto, Virrorio and Mueller, Juergen and Ricchiuti, Ferdinando and Servedio, Vito D. P. and Sirbu, Alina and Tria, Franesca}, title = {Awareness and Learning in Participatory Noise Sensing}, series = {PLOS ONE}, volume = {8}, journal = {PLOS ONE}, number = {12}, issn = {1932-6203}, doi = {10.1371/journal.pone.0081638}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127675}, pages = {e81638}, year = {2013}, abstract = {The development of ICT infrastructures has facilitated the emergence of new paradigms for looking at society and the environment over the last few years. Participatory environmental sensing, i.e. directly involving citizens in environmental monitoring, is one example, which is hoped to encourage learning and enhance awareness of environmental issues. In this paper, an analysis of the behaviour of individuals involved in noise sensing is presented. Citizens have been involved in noise measuring activities through the WideNoise smartphone application. This application has been designed to record both objective (noise samples) and subjective (opinions, feelings) data. The application has been open to be used freely by anyone and has been widely employed worldwide. In addition, several test cases have been organised in European countries. Based on the information submitted by users, an analysis of emerging awareness and learning is performed. The data show that changes in the way the environment is perceived after repeated usage of the application do appear. Specifically, users learn how to recognise different noise levels they are exposed to. Additionally, the subjective data collected indicate an increased user involvement in time and a categorisation effect between pleasant and less pleasant environments.}, language = {en} } @phdthesis{Vidal2013, author = {Vidal, Marie}, title = {b-adrenergic receptors and Erk1/2-mediated cardiac hypertrophy}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-83671}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Chronische Aktivierung von b-Adrenorezeptoren (b-ARs) durch Katecholamine ist ein Stimulus f{\"u}r kardiale Hypertrophie und Herzinsuffizienz. Ebenso f{\"u}hrt die Expression von b1-ARs oder Gas-Proteinen in genetisch modifizierten M{\"a}usen zu Hypertrophie und Herzinsuffizienz. Allerdings f{\"u}hrt die direkte Aktivierung dem Gas nachgeschalteten Komponenten des b-adrenergen Signalwegs wie z.B. die Aktivierung der Adenylylcyclase (AC) oder der Proteinkinase A (PKA) nicht im signifikanten Ausmaß zur Herzhypertrophie. Diese Ergebnisse deuten darauf hin, dass zus{\"a}tzlich zu dem klassischen Signalweg, auch weitere durch Gas-Proteine aktivierte Komponenten in die b-adrenerg vermittelte Hypertrophieentwicklung involviert sind. Interessanterweise wurde vor kurzem ein hypertropher Signalweg beschrieben, der eine direkte Involvierung von Gbg-Untereinheiten bei der Induktion von Herzhypertrophie durch die extrazellul{\"a}r-regulierten Kinasen 1 und 2 (ERK1/2) zeigt: Nach Aktivierung Gaq-gekoppelter Rezeptoren binden Gbg-Untereinheiten an die aktivierte Raf/Mek/Erk Kaskade. Die Bindung der freigesetzten Gbg-Untereinheiten an Erk1/2 f{\"u}hrt zu einer Autophosphorylierung von Erk1/2 an Threonin 188 (bzw. Thr208 in Erk1; im folgenden ErkThr188-Phosphorylierung genannt), welche f{\"u}r die Vermittlung kardialer Hypertrophie verantwortlich ist. In dieser Arbeit konnte nun gezeigt werden, dass auch die Aktivierung von b-ARs in M{\"a}usen sowie von isolierten Kardiomyozyten zur Induktion von ErkThr188-Phosphorylierung f{\"u}hrt. Dar{\"u}berhinaus f{\"u}hrte die {\"U}berexpression von Erk2 Mutanten (Erk2T188S und Erk2T188A), die nicht an Threonin 188 phosphoryliert werden k{\"o}nnen, zu einer deutlich reduzierten Hypertrophieantwort von Kardiomyozyten auf Isoproterenol. Auch die kardiale Expression der Erk2T188S Mutante im M{\"a}usen verminderte die Hypertrophieantwort auf eine 2-w{\"o}chige Isoproterenol-Behandlung deutlich: Die linksventrikul{\"a}re Wanddicke, aber auch interstitielle Fibrose und Herzinsuffizienzmarker wie z.B. BNP waren signifikant reduziert. Weiterhin konnte in dieser Arbeit gezeigt werden, dass tats{\"a}chlich ein Zusammenspiel von Ga und Gbg-vermittelten Signalen zur Induktion von ErkThr188-Phosphorylierung und damit zur Induktion von b-adrenerg vermittelter Hypertrophie notwendig ist. W{\"a}hrend die Hemmung von Gbg-Signalen mit dem C-Terminus der GRK2 oder die Hemmung von Adenylylzyklase eine ErkThr188-Phosphorylierung und eine Hypertrophieantwort nach Isoprenalingabe effektiv reduzierten, f{\"u}hrt die alleinige Aktivierung von Adenylylzyklase nicht zu einer Hypertrophieantwort. Diese Ergebnisse k{\"o}nnten bei der Entwicklung neuer m{\"o}glicher therapeutischen Strategien zur Therapie b-adrenerg induzierter Herzhypertrophie und Herzinsuffizienz helfen.}, subject = {Adrenerger Rezeptor}, language = {en} } @article{BeckerOelschlaegerWullaertetal.2013, author = {Becker, Svetlana and Oelschlaeger, Tobias A. and Wullaert, Andy and Pasparakis, Manolis and Wehkamp, Jan and Stange, Eduard F. and Gersemann, Michael}, title = {Bacteria Regulate Intestinal Epithelial Cell Differentiation Factors Both In Vitro and In Vivo}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {2}, doi = {10.1371/journal.pone.0055620}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131168}, pages = {e55620}, year = {2013}, abstract = {Background: The human colon harbours a plethora of bacteria known to broadly impact on mucosal metabolism and function and thought to be involved in inflammatory bowel disease pathogenesis and colon cancer development. In this report, we investigated the effect of colonic bacteria on epithelial cell differentiation factors in vitro and in vivo. As key transcription factors we focused on Hes1, known to direct towards an absorptive cell fate, Hath1 and KLF4, which govern goblet cell. Methods: Expression of the transcription factors Hes1, Hath1 and KLF4, the mucins Muc1 and Muc2 and the defensin HBD2 were measured by real-time PCR in LS174T cells following incubation with several heat-inactivated E. coli strains, including the probiotic E. coli Nissle 1917+/- flagellin, Lactobacilli and Bifidobacteria. For protein detection Western blot experiments and chamber-slide immunostaining were performed. Finally, mRNA and protein expression of these factors was evaluated in the colon of germfree vs. specific pathogen free vs. conventionalized mice and colonic goblet cells were counted. Results: Expression of Hes1 and Hath1, and to a minor degree also of KLF4, was reduced by E. coli K-12 and E. coli Nissle 1917. In contrast, Muc1 and HBD2 expression were significantly enhanced, independent of the Notch signalling pathway. Probiotic E. coli Nissle 1917 regulated Hes1, Hath1, Muc1 and HBD2 through flagellin. In vivo experiments confirmed the observed in vitro effects of bacteria by a diminished colonic expression of Hath1 and KLF4 in specific pathogen free and conventionalized mice as compared to germ free mice whereas the number of goblet cells was unchanged in these mice. Conclusions: Intestinal bacteria influence the intestinal epithelial differentiation factors Hes1, Hath1 and KLF4, as well as Muc1 and HBD2, in vitro and in vivo. The induction of Muc1 and HBD2 seems to be triggered directly by bacteria and not by Notch.}, language = {en} } @article{WippelMaurerFortschetal.2013, author = {Wippel, Carolin and Maurer, Jana and Fortsch, Christina and Hupp, Sabrina and Bohl, Alexandra and Ma, Jiangtao and Mitchell, Timothy J. and Bunkowski, Stephanie and Br{\"u}ck, Wolfgang and Nau, Roland and Iliev, Asparouh I.}, title = {Bacterial Cytolysin during Meningitis Disrupts the Regulation of Glutamate in the Brain, Leading to Synaptic Damage}, series = {PLoS Pathogens}, volume = {9}, journal = {PLoS Pathogens}, number = {6}, doi = {10.1371/journal.ppat.1003380}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130462}, pages = {e1003380}, year = {2013}, abstract = {Abstract Streptococcus pneumoniae (pneumococcal) meningitis is a common bacterial infection of the brain. The cholesterol-dependent cytolysin pneumolysin represents a key factor, determining the neuropathogenic potential of the pneumococci. Here, we demonstrate selective synaptic loss within the superficial layers of the frontal neocortex of post-mortem brain samples from individuals with pneumococcal meningitis. A similar effect was observed in mice with pneumococcal meningitis only when the bacteria expressed the pore-forming cholesterol-dependent cytolysin pneumolysin. Exposure of acute mouse brain slices to only pore-competent pneumolysin at disease-relevant, non-lytic concentrations caused permanent dendritic swelling, dendritic spine elimination and synaptic loss. The NMDA glutamate receptor antagonists MK801 and D-AP5 reduced this pathology. Pneumolysin increased glutamate levels within the mouse brain slices. In mouse astrocytes, pneumolysin initiated the release of glutamate in a calcium-dependent manner. We propose that pneumolysin plays a significant synapto- and dendritotoxic role in pneumococcal meningitis by initiating glutamate release from astrocytes, leading to subsequent glutamate-dependent synaptic damage. We outline for the first time the occurrence of synaptic pathology in pneumococcal meningitis and demonstrate that a bacterial cytolysin can dysregulate the control of glutamate in the brain, inducing excitotoxic damage. Author Summary Bacterial meningitis is one of the most devastating brain diseases. Among the bacteria that cause meningitis, Streptococcus pneumoniae is the most common. Meningitis predominantly affects children, especially in the Third World, and most of them do not survive. Those that do survive often suffer permanent brain damage and hearing problems. The exact morphological substrates of brain damage in Streptococcus pneumoniae meningitis remain largely unknown. In our experiments, we found that the brain cortex of patients with meningitis demonstrated a loss of synapses (the contact points among neurons, responsible for the processes of learning and memory), and we identified the major pneumococcal neurotoxin pneumolysin as a sufficient cause of this loss. The effect was not direct but was mediated by the brain neurotransmitter glutamate, which was released upon toxin binding by one of the non-neuronal cell types of the brain - the astrocytes. Pneumolysin initiated calcium influx in astrocytes and subsequent glutamate release. Glutamate damaged the synapses via NMDA-receptors - a mechanism similar to the damage occurring in brain ischemia. Thus, we show that synaptic loss is present in pneumococcal meningitis, and we identify the toxic bacterial protein pneumolysin as the major factor in this process. These findings alter our understanding of bacterial meningitis and establish new therapeutic strategies for this fatal disease.}, language = {en} } @phdthesis{Fronhofer2013, author = {Fronhofer, Emanuel Alexis}, title = {Beyond classical metapopulations: trade-offs and information use in dispersal ecology}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85816}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {All animal and plant species must disperse in order to survive. Although this fact may seem trivial, and the importance of the dispersal process is generally accepted, the eco-evolutionary forces influencing dispersal, and the underlying movement elements, are far from being comprehensively understood. Beginning in the 1950s scientists became aware of the central role of dispersal behaviour and landscape connectivity for population viability and species diversity. Subsequently, dispersal has mainly been studied in the context of metapopulations. This has allowed researchers to take into account the landscape level, e.g. for determining conservation measures. However, a majority of theses studies classically did not include dispersal evolution. Yet, it is well known that dispersal is subject to evolution and that this process may occur (very) rapidly, i.e. over short ecological time-scales. Studies that do take dispersal evolution into account, mostly focus on eco-evolutionary forces arising at the level of populations - intra-specific competition or Allee effects, for example - and at the level of landscapes - e.g. connectivity, patch area and fragmentation. Yet, relevant ecological and evolutionary forces can emerge at all levels of biological complexity, from genes and individuals to populations, communities and landscapes. Here, I focus on eco-evolutionary forces arising at the gene- and especially at the individual level. Combining individual-based modelling and empirical field work, I explicitly analyse the influence of mobility trade-offs and information use for dispersal decisions - i.e. individual level factors - during the three phases of dispersal - emigration, transfer and immigration. I additionally take into account gene level factors such as ploidy, sexual reproduction (recombination) and dominance. Mobility-fertility trade-offs may shape evolutionarily stable dispersal strategies and lead to the coexistence of two or more dispersal strategies, i.e. polymorphisms and polyphenisms. This holds true for both dispersal distances (chapter 3) and emigration rates (chapter 4). In sessile organisms - such as trees or corals - maternal investment, i.e. transgenerational trade-offs between maternal fertility and propagule dispersiveness, can be the cause of bimodal and fat-tailed dispersal kernels. However, the coexistence of two or more dispersal strategies may be critically dependent on gene level factors, such as ploidy or dominance (chapter 4). Passively dispersing individuals may realize such multimodal dispersal kernels by mixing different dispersal vectors. Active choice of these vectors allows to optimize the kernel. As most animals have evolved some kind of memory and sensory apparatus - chemical, acoustic or optical sensors - it is obvious that these capacities should be used for dispersal decisions. Chapter 5 explores the use of chemical cues for vector choice in passively dispersed animals. I find that the neotropical phoretic flower mites Spadiseius calyptrogynae non-randomly mix different dispersal vectors, i.e. one short- and one long-distance disperser, in order to achieve fat-tailed dispersal kernels. Such kernels allow an optimal exploitation of patchily distributed habitats. In addition, this strategy increases the probability of successful immigration as the short-distance dispersal vectors show directed dispersal towards suitable habitats. Results from individual-based simulations support and explain my empirical findings. The use of memory and sensory apparatus in dispersal is also the main topic of chapter 6 which strives to bridge the gap between dispersal and movement ecology. In this part of my thesis I develop a model of non-random, memory-based animal movement strategies. Extending the movement ecology paradigm of Nathan (2008a) I postulate that four elements may be relevant for the emergence of efficient movement strategies: perception, memory, inference and anticipation. Movement strategies including these four elements optimize search efficiency at two scales: within patches and between patches. This leads to a significantly increased search efficiency over a comparable area restricted search strategy. These four chapters are completed by a general analysis of metapopulation dynamics (chapter 2). I find that although the metapopulation concept is very popular in theoretical ecology, classical metapopulations can be predicted to be rare in nature, as suggested by lacking empirical evidence. This is especially the case when gene level factors, such as ploidy and sex, are taken into account. In summary, my work analyses the effects of ecological and evolutionary forces arising at the gene- and individual level on the evolution of dispersal and movement strategies. I highlight the importance of including these limiting factors, mechanisms and processes and show how they impact the evolution of dispersal in spatially structured populations. All chapters demonstrate that these forces may have dramatic effects on resulting ecological and evolutionary dynamics. If we intend to understand animal and plant dispersal or movement, it is crucial to include eco-evolutionary forces emerging at all levels of complexity, from genes to communities and landscapes. This endeavour is certainly not purely academic. Particularly nowadays, with rapidly changing landscape structures and anticipated drastic shifts of climatic zones due to global change, dispersal is a factor that cannot be overestimated.}, subject = {Metapopulation}, language = {en} } @article{Schoech2013, author = {Sch{\"o}ch, Christof}, title = {Big? Smart? Clean? Messy? Data in the Humanities?}, series = {Journal of the Digital Humanities}, volume = {2}, journal = {Journal of the Digital Humanities}, number = {3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129492}, pages = {2-13}, year = {2013}, abstract = {No abstract available.}, language = {en} } @phdthesis{Schmidt2013, author = {Schmidt, Tobias}, title = {Biotransformation of trans-1-chloro-3,3,3-trifluoropropene and 2,3,3,3-tetrafluoropropene}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78579}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {The novel refrigerant 2,3,3,3-tetrafluoropropene (HFO-1234yf) as well as the novel foam blowing and precision cleaning agent trans-1-chloro-3,3,3-trifluoropropene (trans-HCFO-1233zd) are both chlorofluorocarbon replacements with low GWPs and a short atmospheric life time. Whereas the hydrofluoroolefin HFO-1234yf has no negative effect on stratospheric ozone due to the lack of chlorine in its structure, the hydrochlorofluoroolefine trans-HCFO-1233zd exhibits a very low potential for ozone depletion (ODP). This is approximately 100 times lower than the ozone depletion potential of precursor compounds such as 1,1,2-trichloro-1,2,2-trifluoroethane (CFC-113). Principle aims of this thesis were to investigate the unknown metabolism of the new solvent trans-HCFO-1233zd and to further investigate a possible biotransformation based toxicity of HFO-1234yf observed in rabbits. Therefore study specimens of different in vitro and in vivo studies with trans-HCFO-1233zd and HFO-1234yf were analyzed for metabolites using 19FNMR spectroscopy, LC-MS/MS spectrometry and GC/MS spectrometry. Metabolites were identified by comparison with purchased or synthesized standard substances. Excretion kinetics of the predominant metabolites were determined by LC-MS/MS quantification,inorganic fluoride was determined by potentiometry. Moreover cytochrome P-450 2E1 and 3A4 liver enzyme activities were measured in a multi-exposure study with HFO-1234yf. ...}, subject = {Propenderivate}, language = {en} } @article{KunathKrauseWullichetal.2013, author = {Kunath, Frank and Krause, Steffen F. and Wullich, Bernd and Goebell, Peter J. and Engehausen, Dirk G. and Burger, Maximilian and Meerpohl, Joerg J. and Keck, Bastian}, title = {Bladder cancer - the neglected tumor: a descriptive analysis of publications referenced in MEDLINE and data from the register clinicaltrials.gov}, series = {BMC Urology}, volume = {13}, journal = {BMC Urology}, number = {56}, doi = {10.1186/1471-2490-13-56}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122133}, year = {2013}, abstract = {Background: Uro-oncological neoplasms have both a high incidence and mortality rate and are therefore a major public health problem. The aim of this study was to evaluate research activity in uro-oncology over the last decade. Methods: We searched MEDLINE and ClinicalTrials.gov systematically for studies on prostatic, urinary bladder, kidney, and testicular neoplasms. The increase in newly published reports per year was analyzed using linear regression. The results are presented with 95\% confidence intervals, and a p value <0.05 was considered statistically significant. Results: The number of new publications per year increased significantly for prostatic, kidney and urinary bladder neoplasms (all <0.0001). We identified 1,885 randomized controlled trials (RCTs); also for RCTs, the number of newly published reports increased significantly for prostatic (p = 0.001) and kidney cancer (p = 0.005), but not for bladder (p = 0.09) or testicular (p = 0.44) neoplasms. We identified 3,114 registered uro-oncological studies in ClinicalTrials.gov. However, 85\% of these studies are focusing on prostatic (45\%) and kidney neoplasms (40\%), whereas only 11\% were registered for bladder cancers. Conclusions: While the number of publications on uro-oncologic research rises yearly for prostatic and kidney neoplasms, urothelial carcinomas of the bladder seem to be neglected despite their important clinical role. Clinical research on neoplasms of the urothelial bladder must be explicitly addressed and supported.}, language = {en} } @article{LinsenmannMonoranuKessleretal.2013, author = {Linsenmann, Thomas and Monoranu, Camelia M. and Kessler, Almuth F. and Ernestus, Ralf I. and Westermaier, Thomas}, title = {Bone chips, fibrin glue, and osteogeneration following lateral suboccipital craniectomy: a case report}, series = {BMC Research Notes}, journal = {BMC Research Notes}, doi = {10.1186/1756-0500-6-523}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97346}, year = {2013}, abstract = {Background Suboccipital craniectomy is a conventional approach for exploring cerebellopontine angle lesions. A variety of techniques have been successfully employed to reconstruct a craniectomy. This is the first report about the histological findings after performing a cranioplasty by using a mixture of autologous bone chips and human allogenic fibrin glue. Case presentation A 53-year-old German woman underwent left lateral suboccipital retrosigmoidal craniectomy for treatment of trigeminal neuralgia in 2008. Cranioplasty was perfomed by using a mixture of autologous bone chips and human allogenic fibrin glue. Due to recurrent neuralgia, a second left lateral suboccipital craniectomy was performed in 2012. The intraoperative findings revealed a complete ossification of the former craniotomy including widely mature trabecular bone tissue in the histological examination. Conclusion A mixture of autologous bone chips and human allogenic fibrin glue seems to provide sufficient bone-regeneration revealed by histological and neuroradiological examinations.}, language = {en} } @article{ZellerMuellerGutberletetal.2013, author = {Zeller, Mario and M{\"u}ller, Alexander and Gutberlet, Marcel and Nichols, Thomas and Hahn, Dietbert and K{\"o}stler, Herbert and Bartsch, Andreas J.}, title = {Boosting BOLD fMRI by K-Space Density Weighted Echo Planar Imaging}, series = {PLoS ONE}, journal = {PLoS ONE}, doi = {10.1371/journal.pone.0074501}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97233}, year = {2013}, abstract = {Functional magnetic resonance imaging (fMRI) has become a powerful and influential method to non-invasively study neuronal brain activity. For this purpose, the blood oxygenation level-dependent (BOLD) effect is most widely used. T2* weighted echo planar imaging (EPI) is BOLD sensitive and the prevailing fMRI acquisition technique. Here, we present an alternative to its standard Cartesian recordings, i.e. k-space density weighted EPI, which is expected to increase the signal-to-noise ratio in fMRI data. Based on in vitro and in vivo pilot measurements, we show that fMRI by k-space density weighted EPI is feasible and that this new acquisition technique in fact boosted spatial and temporal SNR as well as the detection of local fMRI activations. Spatial resolution, spatial response function and echo time were identical for density weighted and conventional Cartesian EPI. The signal-to-noise ratio gain of density weighting can improve activation detection and has the potential to further increase the sensitivity of fMRI investigations.}, language = {en} } @phdthesis{Kaufmann2013, author = {Kaufmann, Tobias}, title = {Brain-computer interfaces based on event-related potentials: toward fast, reliable and easy-to-use communication systems for people with neurodegenerative disease}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-83441}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Objective: Brain Computer Interfaces (BCI) provide a muscle independent interaction channel making them particularly valuable for individuals with severe motor impairment. Thus, different BCI systems and applications have been proposed as assistive technology (AT) solutions for such patients. The most prominent system for communication utilizes event-related potentials (ERP) obtained from the electroencephalogram (EEG) to allow for communication on a character-by-character basis. Yet in their current state of technology, daily life use cases of such systems are rare. In addition to the high EEG preparation effort, one of the main reasons is the low information throughput compared to other existing AT solutions. Furthermore, when testing BCI systems in patients, a performance drop is usually observed compared to healthy users. Patients often display a low signal-to-noise ratio of the recorded EEG and detection of brain responses may be aggravated due to internally (e.g. spasm) or externally induced artifacts (e.g. from ventilation devices). Consequently, practical BCI systems need to cope with mani-fold inter-individual differences. Whilst these high demands lead to increasing complexity of the technology, daily life use of BCI systems requires straightforward setup including an easy-to-use graphical user interface that nonprofessionals can handle without expert support. Research questions of this thesis: This dissertation project aimed at bringing forward BCI technology toward a possible integration into end-users' daily life. Four basic research questions were addressed: (1) Can we identify performance predictors so that we can provide users with individual BCI solutions without the need of multiple, demanding testing sessions? (2) Can we provide complex BCI technology in an automated, user-friendly and easy-to-use manner, so that BCIs can be used without expert support at end-users' homes? (3) How can we account for and improve the low information transfer rates as compared to other existing assistive technology solutions? (4) How can we prevent the performance drop often seen when bringing BCI technology that was tested in healthy users to those with severe motor impairment? Results and discussion: (1) Heart rate variability (HRV) as an index of inhibitory control (i.e. the ability to allocate attention resources and inhibit distracting stimuli) was significantly related to ERP-BCI performance and accounted for almost 26\% of variance. HRV is easy to assess from short heartbeat recordings and may thus serve as a performance predictor for ERP-BCIs. Due to missing software solutions for appropriate processing of artifacts in heartbeat data (electrocardiogram and inter-beat interval data), our own tool was developed that is available free of charge. To date, more than 100 researchers worldwide have requested the tool. Recently, a new version was developed and released together with a website (www.artiifact.de). (2) Furthermore, a study of this thesis demonstrated that BCI technology can be incorporated into easy-to-use software, including auto-calibration and predictive text entry. Na{\"i}ve, healthy nonprofessionals were able to control the software without expert support and successfully spelled words using the auto-calibrated BCI. They reported that software handling was straightforward and that they would be able to explain the system to others. However, future research is required to study transfer of the results to patient samples. (3) The commonly used ERP-BCI paradigm was significantly improved. Instead of simply highlighting visually displayed characters as is usually done, pictures of famous faces were used as stimulus material. As a result, specific brain potentials involved in face recognition and face processing were elicited. The event-related EEG thus displayed an increased signal-to-noise ratio, which facilitated the detection of ERPs extremely well. Consequently, BCI performance was significantly increased. (4) The good results of this new face-flashing paradigm achieved with healthy participants transferred well to users with neurodegenerative disease. Using a face paradigm boosted information throughput. Importantly, two users who were highly inefficient with the commonly used paradigm displayed high accuracy when exposed to the face paradigm. The increased signal-to-noise ratio of the recorded EEG thus helped them to overcome their BCI inefficiency. Significance: The presented work at hand (1) successfully identified a physiological predictor of ERP-BCI performance, (2) proved the technology ready to be operated by na{\"i}ve nonprofessionals without expert support, (3) significantly improved the commonly used spelling paradigm and (4) thereby displayed a way to effectively prevent BCI inefficiency in patients with neurodegenerative disease. Additionally, missing software solutions for appropriate handling of artifacts in heartbeat data encouraged development of our own software tool that is available to the research community free of charge. In sum, this thesis significantly improved current BCI technology and enhanced our understanding of physiological correlates of BCI performance.}, subject = {Gehirn-Computer-Schnittstelle}, language = {en} } @article{SchulSchmittRegnerietal.2013, author = {Schul, Daniela and Schmitt, Alexandra and Regneri, Janine and Schartl, Manfred and Wagner, Toni Ulrich}, title = {Bursted BMP Triggered Receptor Kinase Activity Drives Smad1 Mediated Long-Term Target Gene Oscillation in c2c12 Cells}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0059442}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130131}, pages = {e59442}, year = {2013}, abstract = {Bone Morphogenetic Proteins (BMPs) are important growth factors that regulate many cellular processes. During embryogenesis they act as morphogens and play a critical role during organ development. They influence cell fates via concentration-gradients in the embryos where cells transduce this extracellular information into gene expression profiles and cell fate decisions. How receiving cells decode and quantify BMP2/4 signals is hardly understood. There is little data on the quantitative relationships between signal input, transducing molecules, their states and location, and ultimately their ability to integrate graded systemic inputs and generate qualitative responses. Understanding this signaling network on a quantitative level should be considered a prerequisite for efficient pathway modulation, as the BMP pathway is a prime target for therapeutic invention. Hence, we quantified the spatial distribution of the main signal transducer of the BMP2/4 pathway in response to different types and levels of stimuli in c2c12 cells. We found that the subcellular localization of Smad1 is independent of ligand concentration. In contrast, Smad1 phosphorylation levels relate proportionally to BMP2 ligand concentrations and they are entirely located in the nucleus. Interestingly, we found that BMP2 stimulates target gene expression in non-linear, wave-like forms. Amplitudes showed a clear concentration-dependency, for sustained and transient stimulation. We found that even burst-stimulation triggers gene-expression wave-like modulations that are detectable for at least 30 h. Finally, we show here that target gene expression oscillations depend on receptor kinase activity, as the kinase drives further expression pulses without receptor reactivation and the target gene expression breaks off after inhibitor treatment in c2c12 cells.}, language = {en} } @article{HolzapfelChhayaMelchelsetal.2013, author = {Holzapfel, Boris Michael and Chhaya, Mohit Prashant and Melchels, Ferry Petrus Wilhelmus and Holzapfel, Nina Pauline and Prodinger, Peter Michael and von Eisenhart-Rothe, R{\"u}diger and Griensven, Martijn van and Schantz, Jan-Thorsten and Rudert, Maximilian and Hutmacher, Dietmar Werner}, title = {Can Bone Tissue Engineering Contribute to Therapy Concepts after Resection of Musculoskeletal Sarcoma?}, series = {Sarcoma}, volume = {2013}, journal = {Sarcoma}, number = {Article ID 153640}, doi = {10.1155/2013/153640}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132465}, pages = {10 p.}, year = {2013}, abstract = {Resection of musculoskeletal sarcoma can result in large bone defects where regeneration is needed in a quantity far beyond the normal potential of self-healing. In many cases, these defects exhibit a limited intrinsic regenerative potential due to an adjuvant therapeutic regimen, seroma, or infection. Therefore, reconstruction of these defects is still one of the most demanding procedures in orthopaedic surgery. The constraints of common treatment strategies have triggered a need for new therapeutic concepts to design and engineer unparalleled structural and functioning bone grafts. To satisfy the need for long-term repair and good clinical outcome, a paradigm shift is needed from methods to replace tissues with inert medical devices to more biological approaches that focus on the repair and reconstruction of tissue structure and function. It is within this context that the field of bone tissue engineering can offer solutions to be implemented into surgical therapy concepts after resection of bone and soft tissue sarcoma. In this paper we will discuss the implementation of tissue engineering concepts into the clinical field of orthopaedic oncology.}, language = {en} } @article{KristDimeoKeil2013, author = {Krist, Lilian and Dimeo, Fernando and Keil, Thomas}, title = {Can progressive resistance training twice a week improve mobility, muscle strength, and quality of life in very elderly nursing-home residents with impaired mobility? A pilot study}, series = {Clinical Interventions in Aging}, volume = {8}, journal = {Clinical Interventions in Aging}, doi = {10.2147/CIA.S42136}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122176}, pages = {443-448}, year = {2013}, abstract = {Purpose: To determine the effects of progressive resistance training on mobility, muscle strength, and quality of life in nursing-home residents with impaired mobility. Methods: Nursing-home residents aged 77 years and older with impaired mobility were recruited in Berlin, Germany. The eight-week exercise program consisted of progressive resistance training twice a week. Mobility (primary outcome) was assessed with the Elderly Mobility Scale (zero = worst, 20 = best) at baseline and after 8 weeks. Muscle strength (secondary outcome) was determined by the eight-repetition maximum. The Short Form-36 Health Survey was used to assess quality of life. Results: Of the 15 participants (mean age 84 years, range 77-97 years), ten completed the 8-week program. Mobility (Elderly Mobility Scale mean +/- standard deviation pre 14.1 +/- 3.2 and post 17.5 +/- 3.6; P = 0.005) as well as muscle strength of upper and lower limbs improved (from 62\% at chest press up to 108\% at leg extension machine), whereas most quality of life subscales did not show considerable change. Conclusion: Resistance training twice a week over 2 months seemed to considerably improve mobility and muscle strength in persons aged 77-97 years with impaired mobility.}, language = {en} } @article{HaringLengRobinsonetal.2013, author = {Haring, Bernhard and Leng, Xiaoyan and Robinson, Jennifer and Johnson, Karen C. and Jackson, Rebecca D. and Beyth, Rebecca and Wactawski-Wende, Jean and Wyler von Ballmoos, Moritz and Goveas, Joseph S. and Kuller, Lewis H. and Wassertheil-Smoller, Sylvia}, title = {Cardiovascular Disease and Cognitive Decline in Postmenopausal Women: Results From the Women's Health Initiative Memory Study}, series = {Journal of the American Heart Association}, volume = {2}, journal = {Journal of the American Heart Association}, number = {e000369}, doi = {10.1161/JAHA.113.000369}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129487}, year = {2013}, abstract = {Background-—Data on cardiovascular diseases (CVD) and cognitive decline are conflicting. Our objective was to investigate if CVD is associated with an increased risk for cognitive decline and to examine whether hypertension, diabetes, or adiposity modify the effect of CVD on cognitive functioning. Methods and Results-—Prospective follow-up of 6455 cognitively intact, postmenopausal women aged 65 to 79 years old enrolled in the Women's Health Initiative Memory Study (WHIMS). CVD was determined by self-report. For cognitive decline, we assessed the incidence of mild cognitive impairment (MCI) or probable dementia (PD) via modified mini-mental state examination (3 MS) score, neurocognitive, and neuropsychiatric examinations. The median follow-up was 8.4 years. Women with CVD tended to be at increased risk for cognitive decline compared with those free of CVD (hazard ratio [HR], 1.29; 95\% CI: 1.00, 1.67). Women with myocardial infarction or other vascular disease were at highest risk (HR, 2.10; 95\% CI: 1.40, 3.15 or HR, 1.97; 95\% CI: 1.34, 2.87). Angina pectoris was moderately associated with cognitive decline (HR 1.45; 95\% CI: 1.05, 2.01) whereas no significant relationships were found for atrial fibrillation or heart failure. Hypertension and diabetes increased the risk for cognitive decline in women without CVD. Diabetes tended to elevate the risk for MCI/PD in women with CVD. No significant trend was seen for adiposity. Conclusions-—CVD is associated with cognitive decline in elderly postmenopausal women. Hypertension and diabetes, but not adiposity, are associated with a higher risk for cognitive decline. More research is warranted on the potential of CVD prevention for preserving cognitive functioning.}, language = {en} } @article{HaringLengRobinsonetal.2013, author = {Haring, Bernhard and Leng, Xiaoyan and Robinson, Jennifer and Johnson, Karen C. and Jackson, Rebecca D. and Beyth, Rebecca and Wactawski-Wende, Jean and Wyler von Ballmoos, Moritz and Goveas, Joseph S. and Kuller, Lewis H. and Wassertheil-Smoller, Sylvia}, title = {Cardiovascular Disease and Cognitive Decline in Postmenopausal Women: Results From the Women's Health Initiative Memory Study}, doi = {10.1161/JAHA.113.000369)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111376}, year = {2013}, abstract = {Background Data on cardiovascular diseases (CVD) and cognitive decline are conflicting. Our objective was to investigate if CVD is associated with an increased risk for cognitive decline and to examine whether hypertension, diabetes, or adiposity modify the effect of CVD on cognitive functioning. Methods and Results: Prospective follow-up of 6455 cognitively intact, postmenopausal women aged 65 to 79 years old enrolled in the Women's Health Initiative Memory Study (WHIMS). CVD was determined by self-report. For cognitive decline, we assessed the incidence of mild cognitive impairment (MCI) or probable dementia (PD) via modified mini-mental state examination (3 MS) score, neurocognitive, and neuropsychiatric examinations. The median follow-up was 8.4 years. Women with CVD tended to be at increased risk for cognitive decline compared with those free of CVD (hazard ratio [HR], 1.29; 95\% CI: 1.00, 1.67). Women with myocardial infarction or other vascular disease were at highest risk (HR, 2.10; 95\% CI: 1.40, 3.15 or HR, 1.97; 95\% CI: 1.34, 2.87). Angina pectoris was moderately associated with cognitive decline (HR 1.45; 95\% CI: 1.05, 2.01) whereas no significant relationships were found for atrial fibrillation or heart failure. Hypertension and diabetes increased the risk for cognitive decline in women without CVD. Diabetes tended to elevate the risk for MCI/PD in women with CVD. No significant trend was seen for adiposity. Conclusions: CVD is associated with cognitive decline in elderly postmenopausal women. Hypertension and diabetes, but not adiposity, are associated with a higher risk for cognitive decline. More research is warranted on the potential of CVD prevention for preserving cognitive functioning.}, language = {en} } @article{ElMeseryTrebingSchaferetal.2013, author = {El-Mesery, M. and Trebing, J. and Schafer, V. and Weisenberger, D. and Siegmund, D. and Wajant, H.}, title = {CD40-directed scFv-TRAIL fusion proteins induce CD40-restricted tumor cell death and activate dendritic cells}, series = {Cell Death \& Disease}, volume = {4}, journal = {Cell Death \& Disease}, number = {e916}, doi = {10.1038/cddis.2013.402}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128777}, year = {2013}, abstract = {Targeted cancer therapy concepts often aim at the induction of adjuvant antitumor immunity or stimulation of tumor cell apoptosis. There is further evidence that combined application of immune stimulating and tumor apoptosis-inducing compounds elicits a synergistic antitumor effect. Here, we describe the development and characterization of bifunctional fusion proteins consisting of a single-chain variable fragment (scFv) domain derived from the CD40-specific monoclonal antibody G28-5 that is fused to the N-terminus of stabilized trimeric soluble variants of the death ligand TNF-related apoptosis-inducing ligand (TRAIL). As shown before by us and others for other cell surface antigen-targeted scFv-TRAIL fusion proteins, scFv:G28-TRAIL displayed an enhanced capacity to induce apoptosis upon CD40 binding. Studies with scFv:G28 fusion proteins of TRAIL mutants that discriminate between the two TRAIL death receptors, TRAILR1 and TRAILR2, further revealed that the CD40 binding-dependent mode of apoptosis induction of scFv:G28-TRAIL is operable with each of the two TRAIL death receptors. Binding of scFv:G28-TRAIL fusion proteins to CD40 not only result in enhanced TRAIL death receptor signaling but also in activation of the targeted CD40 molecule. In accordance with the latter, the scFv:G28-TRAIL fusion proteins triggered strong CD40-mediated maturation of dendritic cells. The CD40-targeted TRAIL fusion proteins described in this study therefore represent a novel type of bifunctional fusion proteins that couple stimulation of antigen presenting cells and apoptosis induction.}, language = {en} } @article{WetzelJablonkaBlum2013, author = {Wetzel, Andrea and Jablonka, Sibylle and Blum, Robert}, title = {Cell-autonomous axon growth of young motoneurons is triggered by a voltage-gated sodium channel}, series = {Channels (Austin)}, volume = {7}, journal = {Channels (Austin)}, number = {1}, doi = {10.4161/chan.23153}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132586}, pages = {51-56}, year = {2013}, abstract = {Spontaneous electrical activity preceding synapse formation contributes to the precise regulation of neuronal development. Examining the origins of spontaneous activity revealed roles for neurotransmitters that depolarize neurons and activate ion channels. Recently, we identified a new molecular mechanism underlying fluctuations in spontaneous neuronal excitability. We found that embryonic motoneurons with a genetic loss of the low-threshold sodium channel Na\(_V\)1.9 show fewer fluctuations in intracellular calcium in axonal compartments and growth cones than wild-type littermates. As a consequence, axon growth of Na\(_V\)1.9-deficient motoneurons in cell culture is drastically reduced while dendritic growth and cell survival are not affected. Interestingly, Na\(_V\)1.9 function is observed under conditions that would hardly allow a ligand- or neurotransmitter-dependent depolarization. Thus, Na\(_V\)1.9 may serve as a cell-autonomous trigger for neuronal excitation. In this addendum, we discuss a model for the interplay between cell-autonomous local neuronal activity and local cytoskeleton dynamics in growth cone function.}, language = {en} } @article{BingShiTanKressCastroetal.2013, author = {Bing-Shi Tan, Ariel and Kress, Sebastian and Castro, Leticia and Sheppard, Allan and Raghunath, Michael}, title = {Cellular re- and de-programming by microenvironmental memory: why short TGF-β1 pulses can have long effects}, series = {Fibrogenesis Tissue Repair}, volume = {6}, journal = {Fibrogenesis Tissue Repair}, number = {12}, doi = {10.1186/1755-1536-6-12}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131898}, year = {2013}, abstract = {Background Fibrosis poses a substantial setback in regenerative medicine. Histopathologically, fibrosis is an excessive accumulation of collagen affected by myofibroblasts and this can occur in any tissue that is exposed to chronic injury or insult. Transforming growth factor (TGF)-β1, a crucial mediator of fibrosis, drives differentiation of fibroblasts into myofibroblasts. These cells exhibit α-smooth muscle actin (α-SMA) and synthesize high amounts of collagen I, the major extracellular matrix (ECM) component of fibrosis. While hormones stimulate cells in a pulsatile manner, little is known about cellular response kinetics upon growth factor impact. We therefore studied the effects of short TGF-β1 pulses in terms of the induction and maintenance of the myofibroblast phenotype. Results Twenty-four hours after a single 30 min TGF-β1 pulse, transcription of fibrogenic genes was upregulated, but subsided 7 days later. In parallel, collagen I secretion rate and α-SMA presence were elevated for 7 days. A second pulse 24 h later extended the duration of effects to 14 days. We could not establish epigenetic changes on fibrogenic target genes to explain the long-lasting effects. However, ECM deposited under singly pulsed TGF-β1 was able to induce myofibroblast features in previously untreated fibroblasts. Dependent on the age of the ECM (1 day versus 7 days' formation time), this property was diminished. Vice versa, myofibroblasts were cultured on fibroblast ECM and cells observed to express reduced (in comparison with myofibroblasts) levels of collagen I. Conclusions We demonstrated that short TGF-β1 pulses can exert long-lasting effects on fibroblasts by changing their microenvironment, thus leaving an imprint and creating a reciprocal feed-back loop. Therefore, the ECM might act as mid-term memory for pathobiochemical events. We would expect this microenvironmental memory to be dependent on matrix turnover and, as such, to be erasable. Our findings contribute to the current understanding of fibroblast induction and maintenance, and have bearing on the development of antifibrotic drugs.}, language = {en} } @phdthesis{Dietz2013, author = {Dietz, Andreas}, title = {Central Asian Snow Cover Characteristics between 1986 and 2012 derived from Time Series of Medium Resolution Remote Sensing Data}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-101221}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {The eminent importance of snow cover for climatic, hydrologic, anthropogenic, and economic reasons has been widely discussed in scientific literature. Up to 50\% of the Northern Hemisphere is covered by snow at least temporarily, turning snow to the most prevalent land cover types at all. Depending on regular precipitation and temperatures below freezing point it is obvious that a changing climate effects snow cover characteristics fundamentally. Such changes can have severe impacts on local, national, and even global scale. The region of Central Asia is not an exception from this general rule, but are the consequences accompanying past, present, and possible future changes in snow cover parameters of particular importance. Being characterized by continental climate with hot and dry summers most precipitation accumulates during winter and spring months in the form of snow. The population in this 4,000,000 km² vast area is strongly depending on irrigation to facilitate agriculture. Additionally, electricity is often generated by hydroelectric power stations. A large proportion of the employed water originates from snow melt during spring months, implying that changes in snow cover characteristics will automatically affect both the total amount of obtainable water and the time when this water becomes available. The presented thesis explores the question how the spatial extent of snow covered surface has evolved since the year 1986. This investigation is based on the processing of medium resolution remote sensing data originating from daily MODIS and AVHRR sensors, thus forming a unique approach of snow cover analysis in terms of temporal and spatial resolution. Not only duration but also onset and melt of snow coverage are tracked over time, analyzing for systematic changes within this 26 years lasting time span. AVHRR data are processed from raw Level 1B orbit data to Level 3 thematic snow cover products. Both, AVHRR and MODIS snow maps undergo a further post-processing, producing daily full-area mosaics while completely eliminating inherent cloud cover. Snow cover parameters are derived based on these daily and cloud-free time series, allowing for a detailed analysis of current status and changes. The results confirm the predictions made by coarse resolution predictions from climate models: Central Asian snow cover is changing, posing new challenges for the ecosystem and future water supply. The changes, however, are not aimed at only one direction. Regions with decreasing snow cover exist as well as those where the duration of snow cover increases. A shift towards earlier snow cover start and melt can be observed, posing a serious challenge to water management authorities due to a changed runoff regime.}, subject = {Zentralasien}, language = {en} } @article{NtoukasTappePfuetzeetal.2013, author = {Ntoukas, Vasileios and Tappe, Dennis and Pf{\"u}tze, Daniel and Simon, Michaela and Holzmann, Thomas}, title = {Cerebellar Cysticercosis Caused by Larval Taenia crassiceps Tapeworm in Immunocompetent Woman, Germany}, series = {Emerging Infectious Diseases}, volume = {19}, journal = {Emerging Infectious Diseases}, number = {12}, doi = {10.3201/eid1912.130284}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131686}, pages = {2008-2011}, year = {2013}, abstract = {Human cysticercosis caused by Taenia crassiceps tapeworm larvae involves the muscles and subcutis mostly in immunocompromised patients and the eye in immunocompetent persons. We report a successfully treated cerebellar infection in an immunocompetent woman. We developed serologic tests, and the parasite was identified by histologic examination and 12s rDNA PCR and sequencing.}, language = {en} } @article{PanayotovaDimitrovaFeoktistovaPloesseretal.2013, author = {Panayotova-Dimitrova, Diana and Feoktistova, Maria and Ploesser, Michaela and Kellert, Beate and Hupe, Mike and Horn, Sebastian and Makarov, Roman and Jensen, Federico and Porubsky, Stefan and Schmieder, Astrid and Zenclussen, Ana Claudia and Marx, Alexander and Kerstan, Andreas and Geserick, Peter and He, You-Wen and Leverkus, Martin}, title = {cFLIP Regulates Skin Homeostasis and Protects against TNF-Induced Keratinocyte Apoptosis}, series = {Cell Reports}, volume = {5}, journal = {Cell Reports}, doi = {10.1016/j.celrep.2013.09.035}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122155}, pages = {397-408}, year = {2013}, abstract = {FADD, caspase-8, and cFLIP regulate the outcome of cell death signaling. Mice that constitutively lack these molecules die at an early embryonic age, whereas tissue-specific constitutive deletion of FADD or caspase-8 results in inflammatory skin disease caused by increased necroptosis. The function of cFLIP in the skin in vivo is unknown. In contrast to tissue-specific caspase-8 knockout, we show that mice constitutively lacking cFLIP in the epidermis die around embryonic days 10 and 11. When cFLIP expression was abrogated in adult skin of cFLIP(fl/fl)-K14CreER(tam) mice, severe inflammation of the skin with concomitant caspase activation and apoptotic, but not necroptotic, cell death developed. Apoptosis was dependent of autocrine tumor necrosis factor production triggered by loss of cFLIP. In addition, epidermal cFLIP protein was lost in patients with severe drug reactions associated with epidermal apoptosis. Our data demonstrate the importance of cFLIP for the integrity of the epidermis and for silencing of spontaneous skin inflammation.}, language = {en} } @article{NgwaScheuermayerMairetal.2013, author = {Ngwa, Che Julius and Scheuermayer, Matthias and Mair, Gunnar Rudolf and Kern, Selina and Br{\"u}gl, Thomas and Wirth, Christine Clara and Aminake, Makoah Nigel and Wiesner, Jochen and Fischer, Rainer and Vilcinskas, Andreas and Pradel, Gabriele}, title = {Changes in the transcriptome of the malaria parasite Plasmodium falciparum during the initial phase of transmission from the human to the mosquito}, series = {BMC Genomics}, volume = {14}, journal = {BMC Genomics}, number = {256}, issn = {1471-2164}, doi = {10.1186/1471-2164-14-256}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121905}, year = {2013}, abstract = {Background: The transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is mediated by dormant sexual precursor cells, the gametocytes, which become activated in the mosquito midgut. Because gametocytes are the only parasite stages able to establish an infection in the mosquito, they play a crucial role in spreading the tropical disease. The human-to-mosquito transmission triggers important molecular changes in the gametocytes, which initiate gametogenesis and prepare the parasite for life-cycle progression in the insect vector. Results: To better understand gene regulations during the initial phase of malaria parasite transmission, we focused on the transcriptome changes that occur within the first half hour of parasite development in the mosquito. Comparison of mRNA levels of P. falciparum gametocytes before and 30 min following activation using suppression subtractive hybridization (SSH) identified 126 genes, which changed in expression during gametogenesis. Among these, 17.5\% had putative functions in signaling, 14.3\% were assigned to cell cycle and gene expression, 8.7\% were linked to the cytoskeleton or inner membrane complex, 7.9\% were involved in proteostasis and 6.4\% in metabolism, 12.7\% were cell surface-associated proteins, 11.9\% were assigned to other functions, and 20.6\% represented genes of unknown function. For 40\% of the identified genes there has as yet not been any protein evidence. For a subset of 27 genes, transcript changes during gametogenesis were studied in detail by real-time RT-PCR. Of these, 22 genes were expressed in gametocytes, and for 15 genes transcript expression in gametocytes was increased compared to asexual blood stage parasites. Transcript levels of seven genes were particularly high in activated gametocytes, pointing at functions downstream of gametocyte transmission to the mosquito. For selected genes, a regulated expression during gametogenesis was confirmed on the protein level, using quantitative confocal microscopy. Conclusions: The obtained transcriptome data demonstrate the regulations of gene expression immediately following malaria parasite transmission to the mosquito. Our findings support the identification of proteins important for sexual reproduction and further development of the mosquito midgut stages and provide insights into the genetic basis of the rapid adaption of Plasmodium to the insect vector.}, language = {en} } @phdthesis{Zeeb2013, author = {Zeeb, Steffen}, title = {Chaos Synchronization in Time-Delayed Coupled Networks}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78966}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Die vorliegende Arbeit befasst sich mit der Untersuchung verschiedener Aspekte der Chaos Synchronisation von Netzwerken mit zeitverz{\"o}gerten Kopplungen. Ein Netzwerk aus identischen chaotischen Einheiten kann vollst{\"a}ndig und isochron synchronisieren, auch wenn der Signalaustausch einer starken Zeitverz{\"o}gerung unterliegt. Im ersten Teil der Arbeit werden Systeme mit mehreren Zeitverz{\"o}gerungen betrachtet. Dabei erstrecken sich die verschiedenen Zeitverz{\"o}gerungen jeweils {\"u}ber einen weiten Bereich an Gr{\"o}ßenordnungen. Es wird gezeigt, dass diese Zeitverz{\"o}gerungen im Lyapunov Spektrum des Systems auftreten; verschiedene Teile des Spektrums skalieren jeweils mit einer der Zeitverz{\"o}gerungen. Anhand des Skalierungsverhaltens des maximalen Lyapunov Exponenten k{\"o}nnen verschiedene Arten von Chaos definiert werden. Diese bestimmen die Synchronisationseigenschaften eines Netzwerkes und werden insbesondere wichtig bei hierarchischen Netzwerken, d.h. bei Netzwerken bestehend aus Unternetzwerken, bei welchen Signale innerhalb des Unternetzwerkes auf einer anderen Zeitskala ausgetauscht werden als zwischen verschiedenen Unternetzwerken. F{\"u}r ein solches System kann sowohl vollst{\"a}ndige als auch Unternetzwerksynchronisation auftreten. Skaliert der maximale Lyapunov Exponent mit der k{\"u}rzeren Zeitverz{\"o}gerung des Unternetzwerkes dann k{\"o}nnen nur die Elemente des Unternetzwerkes synchronisieren. Skaliert der maximale Lyapunov Exponent allerdings mit der l{\"a}ngeren Zeitverz{\"o}gerung kann das komplette Netzwerk vollst{\"a}ndig synchronisieren. Dies wird analytisch f{\"u}r die Bernoulli Abbildung und numerisch f{\"u}r die Zelt Abbildung gezeigt. Der zweite Teil befasst sich mit der Attraktordimension und ihrer {\"A}nderung am {\"U}bergang zur vollst{\"a}ndiger Chaos Synchronisation. Aus dem Lyapunov Spektrum des Systems wird die Kaplan-Yorke Dimension berechnet und es wird gezeigt, dass diese am Synchronisations{\"u}bergang aus physikalischen Gr{\"u}nden einen Sprung haben muss. Aus der Zeitreihe der Dynamik des Systems wird die Korrelationsdimension bestimmt und anschließend mit der Kaplan-Yorke Dimension verglichen. F{\"u}r Bernoulli Systeme finden wir in der Tat eine Diskontinuit{\"a}t in der Korrelationsdimension. Die St{\"a}rke des Sprungs der Kaplan-Yorke Dimension wird f{\"u}r ein Netzwerk aus Bernoulli Einheiten als Funktion der Netzwerkgr{\"o}ße berechnet. Desweiteren wird das Skalierungsverhalten der Kaplan-Yorke Dimension sowie der Kolmogoroventropie in Abh{\"a}ngigkeit der Systemgr{\"o}ße und der Zeitverz{\"o}gerung untersucht. Zu guter Letzt wird eine Verstimmung der Einheiten, d.h., ein "parameter mismatch", eingef{\"u}hrt und analysiert wie diese das Verhalten der Attraktordimension {\"a}ndert. Im dritten und letzten Teil wird die lineare Antwort eines synchronisierten chaotischen Systems auf eine kleine externe St{\"o}rung untersucht. Diese St{\"o}rung bewirkt eine Abweichung der Einheiten vom perfekt synchronisierten Zustand. Die Verteilung der Abst{\"a}nde zwischen zwei Einheiten dient als Maß f{\"u}r die lineare Antwort des Systems. Diese Verteilung sowie ihre Momente werden numerisch und f{\"u}r Spezialf{\"a}lle auch analytisch berechnet. Wir finden, dass im synchronisierten Zustand, in Abh{\"a}ngigkeit der Parameter des Systems, Verteilungen auftreten k{\"o}nnen die einem Potenzgesetz gehorchen und dessen Momente divergieren. Als weiteres Maß f{\"u}r die lineare Antwort wird die Bit Error Rate einer {\"u}bermittelten bin{\"a}ren Nachricht verwendet. The Bit Error Rate ist durch ein Integral {\"u}ber die Verteilung der Abst{\"a}nde gegeben. In dieser Arbeit wird sie vorwiegend numerisch untersucht und wir finden ein komplexes, nicht monotones Verhalten als Funktion der Kopplungsst{\"a}rke. F{\"u}r Spezialf{\"a}lle weist die Bit Error Rate eine "devil's staircase" auf, welche mit einer fraktalen Struktur in der Verteilung der Abst{\"a}nde verkn{\"u}pft ist. Die lineare Antwort des Systems auf eine harmonische St{\"o}rung wird ebenfalls untersucht. Es treten Resonanzen auf, welche in Abh{\"a}ngigkeit von der Zeitverz{\"o}gerung unterdr{\"u}ckt oder verst{\"a}rkt werden. Eine bi-direktional gekoppelte Kette aus drei Einheiten kann eine St{\"o}rung vollst{\"a}ndig heraus filtern, so dass die Bit Error Rate und auch das zweite Moment verschwinden.}, subject = {Chaostheorie}, language = {en} } @phdthesis{Sen2013, author = {Sen, Surath}, title = {Character Analysis and Numerical Computations of Standard M.I. Probability Distributions}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78623}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Development and character analysis of software programs, which compute minimum information probability distributions.}, subject = {Newton-Verfahren}, language = {en} } @phdthesis{Constantino2013, author = {Constantino, Jennifer Anne}, title = {Characterization of Novel Magnetic Materials: Ultra-Thin (Ga,Mn)As and Epitaxial-Growth MnSi Thin Films}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-90578}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {The study of magnetic phases in spintronic materials is crucial to both our fundamental understanding of magnetic interactions and for finding new effects for future applications. In this thesis, we study the basic electrical and magnetic transport properties of both epitaxially-grown MnSi thin films, a helimagnetic metal only starting to be developed within our group, and parabolic-doped ultra-thin (Ga,Mn)As layers for future studies and applications.}, subject = {Galliumarsenid}, language = {en} } @article{ForconiCanapaBaruccaetal.2013, author = {Forconi, Mariko and Canapa, Adriana and Barucca, Marco and Biscotti, Maria A. and Capriglione, Teresa and Buonocore, Francesco and Fausto, Anna M. and Makapedua, Daisy M. and Pallavicini, Alberto and Gerdol, Marco and De Moro, Gianluca and Scapigliati, Giuseppe and Olmo, Ettore and Schartl, Manfred}, title = {Characterization of Sex Determination and Sex Differentiation Genes in Latimeria}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0056006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130995}, pages = {e56006}, year = {2013}, abstract = {Genes involved in sex determination and differentiation have been identified in mice, humans, chickens, reptiles, amphibians and teleost fishes. However, little is known of their functional conservation, and it is unclear whether there is a common set of genes shared by all vertebrates. Coelacanths, basal Sarcopterygians and unique "living fossils", could help establish an inventory of the ancestral genes involved in these important developmental processes and provide insights into their components. In this study 33 genes from the genome of Latimeria chalumnae and from the liver and testis transcriptomes of Latimeria menadoensis, implicated in sex determination and differentiation, were identified and characterized and their expression levels measured. Interesting findings were obtained for GSDF, previously identified only in teleosts and now characterized for the first time in the sarcopterygian lineage; FGF9, which is not found in teleosts; and DMRT1, whose expression in adult gonads has recently been related to maintenance of sexual identity. The gene repertoire and testis-specific gene expression documented in coelacanths demonstrate a greater similarity to modern fishes and point to unexpected changes in the gene regulatory network governing sexual development.}, language = {en} } @phdthesis{Riedel2013, author = {Riedel, Simone Stefanie}, title = {Characterization of the fluorescence protein FP635 for in vivo imaging and establishment of a murine multiple myeloma model for non-invasive imaging of disease progression and response to therapy}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-77894}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Optical in vivo imaging methods have advanced the fields of stem cell transplantation, graft-versus-host disease and graft-versus-tumor responses. Two well known optical methods, based on the transmission of light through the test animal are bioluminescence imaging (BLI) and fluorescence imaging (FLI). Both methods allow whole body in vivo imaging of the same animal over an extended time span where the cell distribution and proliferation can be visualized. BLI has the advantages of producing almost no unspecific background signals and no necessity for external excitation light. Hence, BLI is a highly sensitive and reliable detection method. Yet, the BLI reporter luciferase is not applicable with common microscopy techniques, therefore abolishing this method for cellular resolution imaging. FLI in turn, presents the appealing possibility to use one fluorescent reporter for whole body imaging as well as cellular resolution applying microscopy techniques. The absorption of light occurs mainly due to melanin and hemoglobin in wavelengths up to 650 nm. Therefore, the wavelength range beyond 650 nm may allow sensitive optical imaging even in deep tissues. For this reason, significant efforts are undertaken to isolate or develop genetically enhanced fluorescent proteins (FP) in this spectral range. "Katushka" also called FP635 has an emission close to this favorable spectrum and is reported as one of the brightest far-red FPs. Our experiments also clearly showed the superiority of BLI for whole body imaging over FLI. Based on these results we applied the superior BLI technique for the establishment of a pre-clinical multiple myeloma (MM) mouse model. MM is a B-cell disease, where malignant plasma cells clonally expand in the bone marrow (BM) of older people, causing significant morbidity and mortality. Chromosomal abnormalities, considered a hallmark of MM, are present in nearly all patients and may accumulate or change during disease progression. The diagnosis of MM is based on clinical symptoms, including the CRAB criteria: increased serum calcium levels, renal insufficiency, anemia, and bone lesions (osteolytic lesions or osteoporosis with compression fractures). Other clinical symptoms include hyperviscosity, amyloidosis, and recurrent bacterial infections. Additionally, patients commonly exhibit more than 30\% clonal BM plasma cells and the presence of monoclonal protein is detected in serum and/or urine. With current standard therapies, MM remains incurable and patients diagnosed with MM between 2001 and 2007 had a 5-year relative survival rate of only 41\%. Therefore, the development of new drugs or immune cell-based therapies is desirable and necessary. To this end we developed the MOPC-315 cell line based syngeneic MM mouse model. MOPC-315 cells were labeled with luciferase for in vivo detection by BLI. We validated the non-invasively obtained BLI data with histopathology, measurement of idiotype IgA serum levels and flow cytometry. All methods affirmed the reliability of the in vivo BLI data for this model. We found that this orthotopic MM model reflects several key features of the human disease. MOPC-315 cells homed efficiently to the BM compartment including subsequent proliferation. Additionally, cells disseminated to distant skeletal parts, leading to the typical multifocal MM growth. Osteolytic lesions and bone remodeling was also detected. We found evidence that the cell line had retained plasticity seen by dynamic receptor expression regulation in different compartments such as the BM and the spleen.}, subject = {Fluoreszenzproteine}, language = {en} } @article{SchlerethHeylKrampitzetal.2013, author = {Schlereth, Katharina and Heyl, Charlotte and Krampitz, Anna-Maria and Mernberger, Marco and Finkernagel, Florian and Scharfe, Maren and Jarek, Michael and Leich, Ellen and Rosenwald, Andreas and Stiewe, Thorsten}, title = {Characterization of the p53 Cistrome - DNA Binding Cooperativity Dissects p53's Tumor Suppressor Functions}, series = {PLOS Genetics}, volume = {9}, journal = {PLOS Genetics}, number = {8}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1003726}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127579}, pages = {e1003726}, year = {2013}, abstract = {p53 protects us from cancer by transcriptionally regulating tumor suppressive programs designed to either prevent the development or clonal expansion of malignant cells. How p53 selects target genes in the genome in a context-and tissue-specific manner remains largely obscure. There is growing evidence that the ability of p53 to bind DNA in a cooperative manner prominently influences target gene selection with activation of the apoptosis program being completely dependent on DNA binding cooperativity. Here, we used ChIP-seq to comprehensively profile the cistrome of p53 mutants with reduced or increased cooperativity. The analysis highlighted a particular relevance of cooperativity for extending the p53 cistrome to non-canonical binding sequences characterized by deletions, spacer insertions and base mismatches. Furthermore, it revealed a striking functional separation of the cistrome on the basis of cooperativity; with low cooperativity genes being significantly enriched for cell cycle and high cooperativity genes for apoptotic functions. Importantly, expression of high but not low cooperativity genes was correlated with superior survival in breast cancer patients. Interestingly, in contrast to most p53-activated genes, p53-repressed genes did not commonly contain p53 binding elements. Nevertheless, both the degree of gene activation and repression were cooperativity-dependent, suggesting that p53-mediated gene repression is largely indirect and mediated by cooperativity-dependently transactivated gene products such as CDKN1A, E2F7 and non-coding RNAs. Since both activation of apoptosis genes with non-canonical response elements and repression of pro-survival genes are crucial for p53's apoptotic activity, the cistrome analysis comprehensively explains why p53-induced apoptosis, but not cell cycle arrest, strongly depends on the intermolecular cooperation of p53 molecules as a possible safeguard mechanism protecting from accidental cell killing.}, language = {en} } @phdthesis{Bach2013, author = {Bach, Fabian}, title = {Charged Current Top Quark Couplings at the LHC}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-82358}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {The top quark plays an important role in current particle physics, from a theoretical point of view because of its uniquely large mass, but also experimentally because of the large number of top events recorded by the LHC experiments ATLAS and CMS, which makes it possible to directly measure the properties of this particle, for example its couplings to the other particles of the standard model (SM), with previously unknown precision. In this thesis, an effective field theory approach is employed to introduce a minimal and consistent parametrization of all anomalous top couplings to the SM gauge bosons and fermions which are compatible with the SM symmetries. In addition, several aspects and consequences of the underlying effective operator relations for these couplings are discussed. The resulting set of couplings has been implemented in the parton level Monte Carlo event generator WHIZARD in order to provide a tool for the quantitative assessment of the phenomenological implications at present and future colliders such as the LHC or a planned international linear collider. The phenomenological part of this thesis is focused on the charged current couplings of the top quark, namely anomalous contributions to the trilinear tbW coupling as well as quartic four-fermion contact interactions of the form tbff, both affecting single top production as well as top decays at the LHC. The study includes various aspects of inclusive cross section measurements as well as differential distributions of single tops produced in the t channel, bq → tq', and in the s channel, ud → tb. We discuss the parton level modelling of these processes as well as detector effects, and finally present the prospected LHC reach for setting limits on these couplings with 10 resp. 100 fb-1 of data recorded at √s = 14 TeV.}, subject = {LHC}, language = {en} } @article{RoedelBredeHirschfeldetal.2013, author = {R{\"o}del, Mark-Oliver and Brede, Christian and Hirschfeld, Mareike and Schmitt, Thomas and Favreau, Philippe and St{\"o}cklin, Reto and Wunder, Cora and Mebs, Dietrich}, title = {Chemical Camouflage - A Frog's Strategy to Co-Exist with Aggressive Ants}, series = {PLOS ONE}, volume = {8}, journal = {PLOS ONE}, number = {12}, issn = {1932-6203}, doi = {10.1371/journal.pone.0081950}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128181}, pages = {e81950}, year = {2013}, abstract = {Whereas interspecific associations receive considerable attention in evolutionary, behavioural and ecological literature, the proximate bases for these associations are usually unknown. This in particular applies to associations between vertebrates with invertebrates. The West-African savanna frog Phrynomantis microps lives in the underground nest of ponerine ants (Paltothyreus tarsatus). The ants usually react highly aggressively when disturbed by fiercely stinging, but the frog is not attacked and lives unharmed among the ants. Herein we examined the proximate mechanisms for this unusual association. Experiments with termites and mealworms covered with the skin secretion of the frog revealed that specific chemical compounds seem to prevent the ants from stinging. By HPLC-fractionation of an aqueous solution of the frogs' skin secretion, two peptides of 1,029 and 1,143 Da were isolated and found to inhibit the aggressive behaviour of the ants. By de novo sequencing using tandem mass spectrometry, the amino acid sequence of both peptides consisting of a chain of 9 and 11 residues, respectively, was elucidated. Both peptides were synthesized and tested, and exhibited the same inhibitory properties as the original frog secretions. These novel peptides most likely act as an appeasement allomone and may serve as models for taming insect aggression.}, language = {en} } @article{RudelPrustySiegletal.2013, author = {Rudel, Thomas and Prusty, Bhupesh K. and Siegl, Christine and Hauck, Petra and Hain, Johannes and Korhonen, Suvi J. and Hiltunen-Back, Eija and Poulakkainen, Mirja}, title = {Chlamydia trachomatis Infection Induces Replication of Latent HHV-6}, series = {PLoS ONE}, journal = {PLoS ONE}, doi = {10.1371/journal.pone.0061400}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96731}, year = {2013}, abstract = {Human herpesvirus-6 (HHV-6) exists in latent form either as a nuclear episome or integrated into human chromosomes in more than 90\% of healthy individuals without causing clinical symptoms. Immunosuppression and stress conditions can reactivate HHV-6 replication, associated with clinical complications and even death. We have previously shown that co-infection of Chlamydia trachomatis and HHV-6 promotes chlamydial persistence and increases viral uptake in an in vitro cell culture model. Here we investigated C. trachomatis-induced HHV-6 activation in cell lines and fresh blood samples from patients having Chromosomally integrated HHV-6 (CiHHV-6). We observed activation of latent HHV-6 DNA replication in CiHHV-6 cell lines and fresh blood cells without formation of viral particles. Interestingly, we detected HHV-6 DNA in blood as well as cervical swabs from C. trachomatis-infected women. Low virus titers correlated with high C. trachomatis load and vice versa, demonstrating a potentially significant interaction of these pathogens in blood cells and in the cervix of infected patients. Our data suggest a thus far underestimated interference of HHV-6 and C. trachomatis with a likely impact on the disease outcome as consequence of co-infection.}, language = {en} } @article{WiegeringPfannUtheetal.2013, author = {Wiegering, Armin and Pfann, Christina and Uthe, Friedrich Wilhelm and Otto, Christoph and Rycak, Lukas and M{\"a}der, Uwe and Gasser, Martin and Waaga-Gasser, Anna-Maria and Eilers, Martin and Germer, Christoph-Thomas}, title = {CIP2A Influences Survival in Colon Cancer and Is Critical for Maintaining Myc Expression}, series = {PLoS ONE}, journal = {PLoS ONE}, doi = {10.1371/journal.pone.0075292}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97252}, year = {2013}, abstract = {The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogenic factor that stabilises the c-Myc protein. CIP2A is overexpressed in several tumours, and expression levels are an independent marker for long-term outcome. To determine whether CIP2A expression is elevated in colon cancer and whether it might serve as a prognostic marker for survival, we analysed CIP2A mRNA expression by real-time PCR in 104 colon cancer samples. CIP2A mRNA was overexpressed in colon cancer samples and CIP2A expression levels correlated significantly with tumour stage. We found that CIP2A serves as an independent prognostic marker for disease-free and overall survival. Further, we investigated CIP2A-dependent effects on levels of c-Myc, Akt and on cell proliferation in three colon cancer cell lines by silencing CIP2A using small interfering (si) and short hairpin (sh) RNAs. Depletion of CIP2A substantially inhibited growth of colon cell lines and reduced c-Myc levels without affecting expression or function of the upstream regulatory kinase, Akt. Expression of CIP2A was found to be dependent on MAPK activity, linking elevated c-Myc expression to deregulated signal transduction in colon cancer.}, language = {en} } @article{RinawatiSteinLindner2013, author = {Rinawati, Fitria and Stein, Katharina and Lindner, Andr{\´e}}, title = {Climate change impacts on biodiversity-the setting of a lingering global crisis}, series = {Diversity}, volume = {5}, journal = {Diversity}, number = {1}, doi = {10.3390/d50100114}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131866}, pages = {114-123}, year = {2013}, abstract = {Climate change has created potential major threats to global biodiversity. The multiple components of climate change are projected to affect all pillars of biodiversity, from genes over species to biome level. Of particular concerns are "tipping points" where the exceedance of ecosystem thresholds will possibly lead to irreversible shifts of ecosystems and their functioning. As biodiversity underlies all goods and services provided by ecosystems that are crucial for human survival and wellbeing, this paper presents potential effects of climate change on biodiversity, its plausible impacts on human society as well as the setting in addressing a global crisis. Species affected by climate change may respond in three ways: change, move or die. Local species extinctions or a rapidly affected ecosystem as a whole respectively might move toward its particular "tipping point", thereby probably depriving its services to human society and ending up in a global crisis. Urgent and appropriate actions within various scenarios of climate change impacts on biodiversity, especially in tropical regions, are needed to be considered. Foremost a multisectoral approach on biodiversity issues with broader policies, stringent strategies and programs at international, national and local levels is essential to meet the challenges of climate change impacts on biodiversity.}, language = {en} } @phdthesis{Reicherts2013, author = {Reicherts, Philipp}, title = {Cognitive and Emotional Influences on Placebo Analgesia and Nocebo Hyperalgesia}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-106455}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {The perception of pain can be modulated by a variety of factors such as biological/pharmacological treatments as well as potent cognitive and emotional manipulations. Placebo and nocebo effects are among the most prominent examples for such manipulations. Placebo and nocebo manipulations cause reliable psychological and physiological changes, although the administered agent or treatment is inert. The present dissertation aimed at investigating the role of cognitive and emotional influences in the generation of placebo and nocebo effects on pain perception. In addition, the feasibility of solely psychological placebo manipulations to alter the perception of pain was tested. Two commonly discussed preconditions for the generation of placebo and nocebo effects are prior experiences (i.e., past encounter of drug effects) and expectations (i.e., positive or negative attitudes towards an intervention). So far, research on placebo and nocebo effects relied on the administration of sham interventions, which resembled medical treatments like inert pills, creams or injections. However, such experimental procedures deal with confounds due to earlier experiences and expectations resulting from the individual's history with medical interventions. Accordingly, the implementation of a placebo manipulation that is completely new to an individual, seems necessary to disentangle the contribution of experience and expectation for the induction of placebo and nocebo effects. To this end, in Experiment 1 the level of experience and expectation regarding a placebo-nocebo treatment was stepwise manipulated across three different experimental groups. To avoid any resemblances to earlier experiences and individual expectations, a mere psychological placebo-nocebo treatment was chosen that was new to all participants. They were instructed that visual black and white stripe patterns had been found to reliably alter the perception of pain. One group of participants received only the placebo-nocebo instruction (expectation), a second group experienced a placebo-nocebo treatment within a conditioning phase (experience) but no instruction, and a third group received the combination of both that is a placebo-nocebo instruction and a placebo-nocebo conditioning (experience + expectation). It was shown that only the experience + expectation group revealed significantly higher pain ratings and physiological responses during nocebo, compared to placebo trials of the succeeding test phase. These findings demonstrate that the induction of a mere psychological placebo-nocebo effect on pain is in principle possible. Most important, results indicate that such effects most likely rely on both, a positive treatment experience, due to the encounter of an effective intervention (placebo conditioning), and a positive expectation about the intervention (placebo instruction).Besides experience and expectation, the current mood state has been shown to modulate pain and to impact the induction of placebo and nocebo effects. In this vein it has been demonstrated that placebo effects come along with positive affect, while nocebo effects often occur together with elevated feelings of anxiety. To clarify the interaction of emotions and placebo-nocebo manipulations on pain perception, in Experiment 2 the paradigm of Experiment 1 was modified. Instead of black and white stripe patterns, positive and negative emotional pictures were presented, which either cued pain increase (nocebo) or pain decrease (placebo). Two experimental groups were compared, which differed with regard to the instructed contingency of positive pictures serving as placebo and negative pictures serving as nocebo cues or vice versa (congruent vs. incongruent). Results indicate that the differentiation of placebo and nocebo trials (behaviorally and physiologically) was more pronounced for the congruent compared to the incongruent group. However, in the incongruent group, affective pain ratings were also significantly higher for nocebo (positive pictures) than placebo (negative pictures) trials, similar to the congruent group. These findings demonstrate that a placebo-nocebo manipulation is capable to dampen and even reverse the originally pain augmenting effect of negative emotions. The results of Experiment 2 were further corroborated in Experiment 3, when the design was adapted to the fMRI scanner, and again a congruent and an incongruent experimental group were compared. Behavioral, physiological and neurophysiological markers of pain processing revealed a differentiation between nocebo and placebo conditions that was present irrespective of the experimental group. In addition, the fMRI analysis revealed an increased engagement of prefrontal areas for the incongruent group only, supposedly reflecting the reinterpretation or appraisal process when positive pictures were cueing negative outcomes. Taken together, the results of the present studies showed (a) that it is possible to induce a placebo-nocebo effect on pain solely by a psychological manipulation, (b) that both, prior experiences and positive expectation, are necessary preconditions for this placebo-nocebo effect, (c) that the impact of negative emotion on pain can be dampened and even reversed by placebo-nocebo manipulations, and (d) that most likely a cognitive top-down process is crucial for the induction of (psychological) placebo-nocebo effects. These results significantly enhance our understanding of psychological mechanisms involved in the induction of placebo-nocebo effects. Further, a fruitful foundation for future studies is provided, which will need to determine the contributions of primarily nocebo or placebo responses mediating the effects as demonstrated in the present studies. In a long-term perspective, the present findings may also help to exploit placebo effects and prevent from nocebo effect in clinical contexts by further elucidating crucial psychological factors that contribute to the placebo and nocebo response.}, subject = {Placebo}, language = {en} } @article{KasprzakSivalertpornAlbertetal.2013, author = {Kasprzak, J. and Sivalertporn, K. and Albert, F. and Schneider, C. and H{\"o}fling, S. and Kamp, M. and Forchel, A. and Muljarov, E. A. and Langbein, W.}, title = {Coherence dynamics and quantum-to-classical crossover in an exciton-cavity system in the quantum strong coupling regime}, series = {New Journal of Physics}, volume = {15}, journal = {New Journal of Physics}, number = {045013}, issn = {1367-2630}, doi = {10.1088/1367-2630/15/4/045013}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123005}, year = {2013}, abstract = {Interaction between light and matter generates optical nonlinearities, which are particularly pronounced in the quantum strong coupling regime. When a single bosonic mode couples to a single fermionic mode, a Jaynes-Cummings (JC) ladder is formed, which we realize here using cavity photons and quantum dot excitons. We measure and model the coherent anharmonic response of this strongly coupled exciton-cavity system at resonance. Injecting two photons into the cavity, we demonstrate a \(\sqrt 2\) larger polariton splitting with respect to the vacuum Rabi splitting. This is achieved using coherent nonlinear spectroscopy, specifically four-wave mixing, where the coherence between the ground state and the first (second) rung of the JC ladder can be interrogated for positive (negative) delays. With increasing excitation intensity and thus rising average number of injected photons, we observe spectral signatures of the quantum-to-classical crossover of the strong coupling regime.}, language = {en} } @article{BrixnerAeschlimannFischeretal.2013, author = {Brixner, T. and Aeschlimann, M. and Fischer, A. and Geisler, P. and Goetz, S. and Hecht, B. and Huang, J. S. and Keitzl, T. and Kramer, C. and Melchior, P. and Pfeiffer, W. and Razinskas, G. and Rewitz, C. and Schneider, C. and Str{\"u}ber, C. and Tuchscherer, P. and Voronine, D. V.}, title = {Coherent spectroscopies on ultrashort time and length scales}, series = {EPJ Web of Conferences}, volume = {41}, journal = {EPJ Web of Conferences}, doi = {10.1051/epjconf/20134109017}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129073}, pages = {09017}, year = {2013}, abstract = {Three spectroscopic techniques are presented that provide simultaneous spatial and temporal resolution: modified confocal microscopy with heterodyne detection, space-time-resolved spectroscopy using coherent control concepts, and coherent two-dimensional nano-spectroscopy. Latest experimental results are discussed.}, language = {en} } @article{BrixnerKochKullmannetal.2013, author = {Brixner, Tobias and Koch, Federico and Kullmann, Martin and Selig, Ulrike and Nuernberger, Patrick and G{\"o}tz, Daniel C. G. and Bringmann, Gerhard}, title = {Coherent two-dimensional electronic spectroscopy in the Soret band of a chiral porphyrin dimer}, series = {New Journal of Physics}, journal = {New Journal of Physics}, doi = {10.1088/1367-2630/15/2/025006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96139}, year = {2013}, abstract = {Using coherent two-dimensional (2D) electronic spectroscopy in fully noncollinear geometry, we observe the excitonic coupling of β,β'-linked bis[tetraphenylporphyrinato-zinc(II)] on an ultrafast timescale in the excited state. The results for two states in the Soret band originating from an excitonic splitting are explained by population transfer with approximately 100 fs from the energetically higher to the lower excitonic state. This interpretation is consistent with exemplary calculations of 2D spectra for a model four-level system with coupling.}, language = {en} } @phdthesis{Leingaertner2013, author = {Leing{\"a}rtner, Annette}, title = {Combined effects of climate change and extreme events on plants, arthropods and their interactions}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87758}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {I. Global climate change directly and indirectly influences biotic and abiotic components of ecosystems. Changes in abiotic ecosystem components caused by climate change comprise temperature increases, precipitation changes and more frequently occurring extreme events. Mediated by these abiotic changes, biotic ecosystem components including all living organisms will also change. Expected changes of plants and animals are advanced phenologies and range shifts towards higher latitudes and altitudes which presumably induce changes in species interactions and composition. Altitudinal gradients provide an optimal opportunity for climate change studies, because they serve as natural experiments due to fast changing climatic conditions within short distances. In this dissertation two different approaches were conducted to reveal species and community responses to climate change. First, species richness and community trait analyses along an altitudinal gradient in the Bavarian Alps (chapters II, III) and second, climate change manipulation experiments under different climatic contexts (chapters IV, V, IV). II. We performed biodiversity surveys of butterfly and diurnal moth species on 34 grassland sites along an altitudinal gradient in the National Park Berchtesgaden. Additionally, we analysed the dominance structure of life-history traits in butterfly assemblages along altitude. Species richness of butterflies and diurnal moths decreased with increasing altitude. The dominance of certain life-history-traits changed along the altitudinal gradient with a higher proportion of larger-winged species and species with higher egg numbers towards higher altitudes. However, the mean egg maturation time, population density and geographic distribution within butterfly assemblages decreased with increasing altitude. Our results indicate that butterfly assemblages were mainly shaped by environmental filtering. We conclude that butterfly assemblages at higher altitudes will presumably lack adaptive capacity to future climatic conditions, because of specific trait combinations. III. In addition to butterfly and diurnal moth species richness we also studied plant species richness in combination with pollination type analyses along the altitudinal gradient. The management type of the alpine grasslands was also integrated in the analyses to detect combined effects of climate and management on plant diversity and pollination type. Plant species richness was highest at intermediate altitudes, whereby the management type influenced the plant diversity with more plant species at grazed compared to mown or non-managed grasslands. The pollination type was affected by both the changing climate along the gradient and the management type. These results suggest that extensive grazing can maintain high plant diversity along the whole altitudinal gradient. With ongoing climate change the diversity peak of plants may shift upwards, which can cause a decrease in biodiversity due to reduced grassland area but also changes in species composition and adaptive potential of pollination types. IV. We set up manipulation experiments on 15 grassland sites along the altitudinal gradient in order to determine the combined effects of extreme climatic events (extreme drought, advanced and delayed snowmelt) and elevation on the nutritional quality and herbivory rates of alpine plants. The leaf CN (carbon to nitrogen) ratio and the plant damage through herbivores were not significantly affected by the simulated extreme events. However, elevation influenced the CN ratios and herbivory rates of alpine plants with contrasting responses between plant guilds. Furthermore, we found differences in nitrogen concentrations and herbivory rates between grasses, legumes and forbs, whereas legumes had the highest nitrogen concentrations and were damaged most. Additionally, CN ratios and herbivory rates increased during the growing season, indicating a decrease of food plant quality during the growing season. Contrasting altitudinal responses of grasses, legumes and forbs presumably can change the dominance structure among these plant guilds with ongoing climate change. V. In this study we analysed the phenological responses of grassland species to an extreme drought event, advanced and delayed snowmelt along the altitudinal gradient. Advanced snowmelt caused an advanced beginning of flowering, whereas this effect was more pronounced at higher than at lower altitudes. Extreme drought and delayed snowmelt had rather low effects on the flower phenology and the responses did not differ between higher and lower sites. The strongest effect influencing flower phenology was altitude, with a declining effect through the season. The length of flowering duration was not significantly influenced by treatments. Our data suggest that plant species at higher altitudes may be more affected by changes in snowmelt timing in contrast to lowland species, as at higher altitudes more severe changes are expected. However, the risk of extreme drought events on flowering phenology seems to be low. VI. We established soil-emergence traps on the advanced snowmelt and control treatment plots in order to detect possible changes in abundances and emergence phenologies of five arthropod orders due to elevation and treatment. Additionally, we analysed the responses of Coleoptera species richness to elevation and treatment. We found that the abundance and species richness of Coleoptera increased with elevation as well as the abundance of Diptera. However, the abundance of Hemiptera decreased with elevation and the abundances of Araneae and Hymenoptera showed no elevational patterns. The advanced snowmelt treatment increased the abundances of Araneae and Hymenoptera. The emergence of soil-hibernating arthropods was delayed up to seven weeks at higher elevations, whereas advanced snowmelt did not influence the emergence phenology of arthropods immediately after snowmelt. With climate change earlier snowmelt will occur more often, which especially will affect soil-hibernating arthropods in alpine regions and may cause desynchronisations between species interactions. VII. In conclusion, we showed that alpine ecosystems are sensitive towards changing climate conditions and extreme events and that many alpine species in the Bavarian Alps are endangered. Many alpine species could exist under warmer climatic conditions, however they are expected to be outcompeted by more competitive lowland species. Furthermore, host-parasite or predator-prey interactions can be disrupted due to different responses of certain guilds to climate change. Understanding and predicting the complex dynamics and potential risks of future climate change remains a great challenge and therefore further studies analysing species and community responses to climate change are needed.}, subject = {Insekten}, language = {en} } @phdthesis{Nube2013, author = {Nube, Jacqueline Sui Lin}, title = {Comparative Analysis of Vaccinia Virus-Encoded Markers Reflecting Actual Viral Titres in Oncolytic Virotherapy}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85689}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Using viruses to treat cancer is a novel approach to an age-old disease. Oncolytic viruses are native or recombinant viruses that have the innate or enhanced capability to infect tumour cells, replicate within the tumour microenvironment and subsequently lyse those cells. One representative, the vaccinia virus (VACV), belongs to the orthopoxvirus genus of the Poxviridae family. GLV-1h68, a recombinant and attenuated vaccinia virus devel- oped by the Genelux Corporation, is a member of this family currently being tested in various phase I/II clinical trials under the name GL-ONC1. It has been shown to specif- ically replicate in tumour cells while sparing healthy tissue and to metabolise prodrug at or transport immunological payloads to the site of affliction. Since imaging modalities offer little insight into viral replication deep within the body, and because oncolytic virotherapy is dependent on replication within the target tissue, the need for a monitoring system is evident. Pharmacokinetic analysis of this oncolytic agent was to give insight into the dynamics present in tumours during treatment. This, in turn, would give clinicians the opportunity to monitor the efficacy as early as possible after the onset of treatment, to observe treatment progression and possibly to gauge prognosis, without resorting to invasive procedures, e.g. biopsies. A criteria for viable biomarkers was that it had to be directly dependent on viral replica- tion. Ideally, a marker for treatment efficacy would be specific to the treatment modality, not necessarily the treatment type. Such a marker would be highly detectable (high sen- sitivity), specific for the treatment (high specificity), and present in an easily obtained specimen (blood). Taking this into consideration, the biomarkers were chosen for their potential to be indicators of viral replication. Thus, the biomarkers analysed in this thesis are: the native proteins expressed by the viral genes A27L and B5R, the virally encoded recombinant proteins β-galactosidase, β-glucuronidase, green fluorescent protein (GFP), carboxypeptidase G2 (CPG2) and carcinoembryonic antigen (CEA). Each marker is under the control of one of five different promoters present. All recombinant viruses used in this thesis express A27L, B5R, GFP and β-glucuronidase and all are derived from the parental virus GLV-1h68. In addition to these markers, GLV-1h68 expresses β-galactosidase; GLV-1h181 expresses CPG2. [...]}, subject = {Onkolyse}, language = {en} } @article{MatlachFreibergLeippietal.2013, author = {Matlach, Juliane and Freiberg, Florentina Joyce and Leippi, Swetlana and Grehn, Franz and Klink, Thomas}, title = {Comparison of phacotrabeculectomy versus phacocanaloplasty in the treatment of patients with concomitant cataract and glaucoma}, series = {BMC Ophthalmology}, journal = {BMC Ophthalmology}, doi = {10.1186/1471-2415-13-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-95948}, year = {2013}, abstract = {Background Cataract and glaucoma are both common comorbidities among older patients. Combining glaucoma surgery with minimal invasive phacoemulsification (phaco) is a considerable option to treat both conditions at the same time, although the combination with filtration surgery can produce a strong inflammatory response. Combined non-penetrating procedures like canaloplasty have shown to reduce intraocular pressure (IOP) comparable to trabeculectomy without the risk of serious bleb-related complications. The purpose of this retrospective study was to compare the outcomes of phacotrabeculectomy and phacocanaloplasty. Methods Thirty-nine eyes with concomitant cataract and glaucoma who underwent phacotrabeculectomy (n = 20; 51.3\%) or phacocanaloplasty (n = 19; 48.7\%) were included into this trial on reduction of IOP, use of medication, success rate, incidence of complications and postsurgical interventions. Complete success was defined as IOP reduction by 30\% or more and to 21 mmHg or less (definition 1a) or IOP to less than 18 mmHg (definition 2a) without glaucoma medication. Results Over a 12-month follow-up, baseline IOP significantly decreased from 30.0 ± 5.3 mmHg with a mean of 2.5 ± 1.2 glaucoma medications to 11.7 ± 3.5 mmHg with a mean of 0.2 ± 0.4 medications in eyes with phacotrabeculectomy (P < .0001). Eyes with phacocanaloplasty had a preoperative IOP of 28.3 ± 4.1 mmHg and were on 2.8 ± 1.1 IOP-lowering drugs. At 12 months, IOP significantly decreased to 12.6 ± 2.1 mmHg and less glaucoma medications were necessary (mean 1.0 ± 1.5 topical medications; P < .05). 15 patients (78.9\%) with phacotrabeculectomy and 9 patients (60.0\%) in the phacocanaloplasty group showed complete success according to definition 1 and 2 after 1 year (P = .276). Postsurgical complications were seen in 7 patients (36.8\%) of the phacocanaloplasty group which included intraoperative macroperforation of the trabeculo-Descemet membrane (5.3\%), hyphema (21.1\%) and bleb formation (10.5\%). Although more complications were observed in the phacotrabeculectomy group, no statistically significant difference was found. Conclusions Phacocanaloplasty offers a new alternative to phacotrabeculectomy for treatment of concomitant glaucoma and cataract, although phacotrabeculectomy yielded in better results in terms of IOP maintained without glaucoma medications.}, subject = {Augenkrankheit}, language = {en} } @article{KaufmannHolzKuebler2013, author = {Kaufmann, Tobias and Holz, Elisa M. and K{\"u}bler, Andrea}, title = {Comparison of tactile, auditory, and visual modality for brain-computer interface use: a case study with a patient in the locked-in state}, series = {Frontiers in Human Neuroscience}, journal = {Frontiers in Human Neuroscience}, doi = {10.3389/fnins.2013.00129}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97079}, year = {2013}, abstract = {This paper describes a case study with a patient in the classic locked-in state, who currently has no means of independent communication. Following a user-centered approach, we investigated event-related potentials (ERP) elicited in different modalities for use in brain-computer interface (BCI) systems. Such systems could provide her with an alternative communication channel. To investigate the most viable modality for achieving BCI based communication, classic oddball paradigms (1 rare and 1 frequent stimulus, ratio 1:5) in the visual, auditory and tactile modality were conducted (2 runs per modality). Classifiers were built on one run and tested offline on another run (and vice versa). In these paradigms, the tactile modality was clearly superior to other modalities, displaying high offline accuracy even when classification was performed on single trials only. Consequently, we tested the tactile paradigm online and the patient successfully selected targets without any error. Furthermore, we investigated use of the visual or tactile modality for different BCI systems with more than two selection options. In the visual modality, several BCI paradigms were tested offline. Neither matrix-based nor so-called gaze-independent paradigms constituted a means of control. These results may thus question the gaze-independence of current gaze-independent approaches to BCI. A tactile four-choice BCI resulted in high offline classification accuracies. Yet, online use raised various issues. Although performance was clearly above chance, practical daily life use appeared unlikely when compared to other communication approaches (e.g., partner scanning). Our results emphasize the need for user-centered design in BCI development including identification of the best stimulus modality for a particular user. Finally, the paper discusses feasibility of EEG-based BCI systems for patients in classic locked-in state and compares BCI to other AT solutions that we also tested during the study.}, language = {en} } @article{WolfChenSongetal.2013, author = {Wolf, Matthias and Chen, Shilin and Song, Jingyuan and Ankenbrand, Markus and M{\"u}ller, Tobias}, title = {Compensatory Base Changes in ITS2 Secondary Structures Correlate with the Biological Species Concept Despite Intragenomic Variability in ITS2 Sequences - A Proof of Concept}, series = {PLoS ONE}, journal = {PLoS ONE}, doi = {10.1371/journal.pone.0066726}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96450}, year = {2013}, abstract = {Compensatory base changes (CBCs) in internal transcribed spacer 2 (ITS2) rDNA secondary structures correlate with Ernst Mayr's biological species concept. This hypothesis also referred to as the CBC species concept recently was subjected to large-scale testing, indicating two distinct probabilities. (1) If there is a CBC then there are two different species with a probability of ~0.93. (2) If there is no CBC then there is the same species with a probability of ~0.76. In ITS2 research, however, the main problem is the multicopy nature of ITS2 sequences. Most recently, 454 pyrosequencing data have been used to characterize more than 5000 intragenomic variations of ITS2 regions from 178 plant species, demonstrating that mutation of ITS2 is frequent, with a mean of 35 variants per species, respectively per individual organism. In this study, using those 454 data, the CBC criterion is reconsidered in the light of intragenomic variability, a proof of concept, a necessary criterion, expecting no intragenomic CBCs in variant ITS2 copies. In accordance with the CBC species concept, we could demonstrate that the probability that there is no intragenomic CBC is ~0.99.}, language = {en} }