TY - JOUR A1 - Andres, Katharina T1 - 'Fashion's Final Frontier': The Correlation of Gender Roles and Fashion in Star Trek JF - Culture Unbound N2 - 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. KW - Star Trek KW - science fiction KW - fashion KW - women KW - 1960s KW - backlash Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128827 VL - 5 ER - TY - THES A1 - Skiera, Christina T1 - 1H NMR spectroscopic determination of deterioration marker compounds in fats and oils T1 - 1H-NMR spektroskopische Bestimmung von Fettverderbsmarkern in Fetten und Ölen N2 - 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. N2 - Im Bereich der Lebensmittel- und pharmazeutischen Analytik besitzen die klassischen Fettkennzahlen Peroxidzahl (POZ), Säurezahl (SZ) und p-Anisidinzahl (AnZ) bis heute eine große Bedeutung in der Qualitäts- und Authentizitätskontrolle von Fetten und Ölen. Diese Kennzahlen sind Summenparameter für bestimmte Verderbsprodukte (POZ für Hydroperoxide, SZ für freie Fettsäuren, AnZ für Aldehyde) und werden mittels volumetrischer oder UV/VIS-spektroskopischer Verfahren ermittelt. 1H-NMR Spektroskopie bietet eine einfache und schnelle Alternative zu den klassischen Fettkennzahlen. In der vorliegenden Arbeit wurden neue 1H-NMR Methoden zur Bestimmung von Hydroperoxiden, freien Fettsäuren und Aldehyden in Fetten und Ölen entwickelt. Hydroperoxide: Der Einfluss des Lösungsmittels, von Wasser, freien Fettsäuren und der Probeneinwaage auf das Hydroperoxidgruppensignal wurde untersucht. Anhand der Ergebnisse wurde die Probenaufarbeitungsprozedur für die neue 1H-NMR Methode erarbeitet. Es wurde eine grobe Zuordnung der Hydroperoxidgruppensignale in Fetten und Ölen zu Methyloleat, Methyllinoleat und Methylinolenat vorgenommen. Weiterhin wurde eine kinetische Studie für Trioleat-Monohydroperoxide durchgeführt, um Informationen darüber zu erhalten, wieviel verschiedene Hydroperoxidspezies bei der Autoxidation von Trioleat gebildet werden. Das Ergebnis weist stark darauf hin, dass alle 18 möglichen Monohydroperoxide entstehen. Die analytische Leistungsfähigkeit der NMR-Methode und der klassischen POZ-Methode wurde mit Hilfe der sog. „relative sensitivity“ nach Mandel verglichen. Es wurde gezeigt, dass beide Methoden eine vergleichbare analytische Leistungsfähigkeit besitzen. Insgesamt wurden 444 Speiseölproben mit beiden Methoden untersucht. Für einige Ölarten wurden beträchtliche Diskrepanzen zwischen der POZ und den NMR-Ergebnissen beobachtet. Im Fall von Schwarzkümmelöl und Olivenöl wurden zwei Substanzen identifiziert, die bei der klassischen POZ-Bestimmung miterfasst werden und dadurch für die positiven (Schwarzkümmelöl) und negativen (Olivenöl) Abweichungen von den aufgrund der NMR-Ergebnisse theoretisch zu erwartenden POZ-Werten verantwortlich sind. Freie Fettsäuren: Zur Optimierung der Messbedingungen wurde der Einfluss des Lösungsmittels auf das Carboxylgruppensignal von freien Fettsäuren für verschiedene Mischungen von CDCl3 und DMSO-d6 untersucht. Die NMR-Methode wurde mit der klassischen SZ-Methode mit Hilfe der „relative sensitivity“ verglichen. Dabei wurde eine vergleichbare analytische Leistungsfähigkeit für beide Methoden festgestellt. 420 Speiseöle wurden mit beiden Methoden analysiert. Mit Ausnahme der Analysenergebnisse von Kürbiskernölen, die geringe Abweichungen zeigten, wurde eine gute Übereinstimmung der Ergebnisse beider Methoden beobachtet. Weiterhin wurde die Anwendbarkeit der 1H-NMR-Methode für weitere Lipide mit Bedeutung in der Pharmazie getestet. Durch Modifikation der ursprünglichen Analysenvorschrift der NMR-Methode wurden für Hartfett, Rizinusöl, Wachse und Oleyloleat mit beiden Methoden vergleichbare Ergebnisse erhalten. Aldehyde: Mit der neuen 1H-NMR Methode können die molaren Gehalte von n-Alkanalen, (E)-2-Alkenalen und (E,E)-2,4-Alkadienalen bestimmt werden. Die vorliegende Arbeit zeigt, dass die AnZ als eine Linearkombination der normalisierten NMR-Integrale der Aldehyde modelliert werden kann. Ein funktionaler Zusammenhang wurde auf Grundlage von Kalibrationsexperimenten abgeleitet. Die Eignung des Modells wurde durch den Vergleich der mittels NMR bestimmten AnZ mit der klassischen AnZ von 79 kommerziell erhältlichen Speiseölen verschiedener Ölarten gezeigt. Abschließend lässt sich sagen, dass die neuen 1H-NMR-Methoden eine sehr gute Alternative zu der Bestimmung der klassischen Fettkennzahlen POZ, SZ and AnZ darstellen. Sie besitzen mehrer Vorteile gegenüber den klassischen Methoden wie beispielsweise der geringe Lösungsmittelverbrauch, die Automatisierbarkeit der Messung und die Möglichkeit mehrere unterschiedliche Parameter aus demselben NMR-Spektrum bestimmen zu können. Es hat sich gezeigt, dass die 1H-NMR-Methoden den klassischen Methoden insbesondere hinsichtlich ihrer Selektivität weit überlegen sind und damit fehlerhafte Befunde, wie sie z. B. bei der POZ-Bestimmung auftreten können, vermieden werden. KW - Fett KW - Öl KW - Verderb KW - NMR-Spektroskopie KW - Fettkennzahlen KW - lipid deterioration markers KW - hydroperoxides KW - free fatty acids KW - aldehydes KW - lipid deterioration KW - Protonen-NMR-Spektroskopie KW - Lipide KW - Hydroperoxide KW - Aldehyde Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-95756 ER - TY - JOUR A1 - Karabeg, Margherita M. A1 - Grauthoff, Sandra A1 - Kollert, Sina Y. A1 - Weidner, Magdalena A1 - Heiming, Rebecca S. A1 - Jansen, Friederike A1 - Popp, Sandy A1 - Kaiser, Sylvia A1 - Lesch, Klaus-Peter A1 - Sachser, Norbert A1 - Schmitt, Angelika G. A1 - Lewejohann, Lars T1 - 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 JF - PLoS ONE N2 - 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 naïve 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. KW - immediate early genes KW - learning curves KW - animal performance KW - animal behavior KW - serotonin KW - learning KW - mice KW - hippocampus Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129978 VL - 8 IS - 10 ER - TY - JOUR A1 - Blömer, Nadja A1 - Pachel, Christina A1 - Hofmann, Urlich A1 - Nordbeck, Peter A1 - Bauer, Wolfgang A1 - Mathes, Denise A1 - Frey, Anna A1 - Bayer, Barbara A1 - Vogel, Benjamin A1 - Ertl, Georg T1 - 5-Lipoxygenase facilitates healing after myocardial infarction JF - Basic Research in Cardiology N2 - 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. KW - lipoxygenase KW - myocardial infarction KW - extracellular matrix remodeling KW - inflammation Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132602 VL - 108 IS - 4 ER - TY - JOUR A1 - Hertlein, Tobias A1 - Sturm, Volker A1 - Jakob, Peter A1 - Ohlsen, Knut T1 - \(^{19}\)F Magnetic Resonance Imaging of Perfluorocarbons for the Evaluation of Response to Antibiotic Therapy in a Staphylococcus aureus Infection Model JF - PLoS ONE N2 - 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. KW - staphylococcus aureus KW - abscesses KW - vancomycin KW - antibiotics KW - magnetic resonance imaging KW - emulsions KW - bioluminescence imaging KW - in vivo imaging Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130113 VL - 8 IS - 5 ER - TY - JOUR A1 - Kühlhorn, Franziska A1 - Rath, Matthias A1 - Schmoeckel, Katrin A1 - Cziupka, Katharina A1 - Nguyen, Huu Hung A1 - Hildebrandt, Petra A1 - Hünig, Thomas A1 - Sparwasser, Tim A1 - Huehn, Jochen A1 - Pötschke, Christian A1 - Bröker, Barbara M. T1 - \(Foxp3^+\) Regulatory T Cells Are Required for Recovery from Severe Sepsis JF - PLoS ONE N2 - 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. KW - CD4(+)CD25(+) KW - toll-like receptors KW - TGF-BETA KW - mediated suppression KW - polymicrobial sepsis KW - improves survival KW - adoptive transfer KW - infected mice KW - in-vivo KW - CD4(+) Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130940 VL - 8 IS - 5 ER - TY - JOUR A1 - May-Mederake, Birgit A1 - Shehata-Dieler, Wafaa T1 - A Case Study Assessing the Auditory and Speech Development of Four Children Implanted with Cochlear Implants by the Chronological Age of 12 Months JF - Case Reports in Otolaryngology N2 - 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 Göttinger 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. KW - Otolaryngolgy Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128750 VL - 2013 IS - 359218 ER - TY - JOUR A1 - Marcus, U. A1 - Vogel, U. A1 - Schubert, A. A1 - Claus, H. A1 - Baetzing-Feigenbaum, J. A1 - Hellenbrand, W. A1 - Wichmann, O. T1 - A cluster of invasive meningococcal disease in young men who have sex with men in Berlin, October 2012 to May 2013 JF - Eurosurveillance N2 - No abstract available. KW - meningococcal disease Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131711 VL - 18 IS - 28 ER - TY - JOUR A1 - Ludwig, K. U. A1 - Sämann, P. A1 - Alexander, M. A1 - Becker, J. A1 - Bruder, J. A1 - Moll, K. A1 - Spieler, D. A1 - Czisch, M. A1 - Warnke, A. A1 - Docherty, S. J. A1 - Davis, O. S. P. A1 - Plomin, R. A1 - Nöthen, M. M. A1 - Landerl, K. A1 - Müller-Myhsok, B. A1 - Hoffmann, P. A1 - Schumacher, J. A1 - Schulte-Körne, G. A1 - Czamara, D. T1 - A common variant in Myosin-18B contributes to mathematical abilities in children with dyslexia and intraparietal sulcus variability in adults JF - Translational Psychiatry N2 - 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. KW - disability KW - sulcal morphology KW - prelevance KW - identification KW - brain KW - cancer KW - association KW - developmental dyscalculia KW - tumor-suppressor gene KW - correlate KW - disorders KW - dyscalculia KW - dyslexia KW - genomic imaging KW - mathematics KW - quantitative trait Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131513 N1 - Supplementary Information accompanies the paper on the Translational Psychiatry website (http://www.nature.com/tp). VL - 3 IS - e229 ER - TY - JOUR A1 - Knorr, Johannes A1 - Rudolf, Philipp A1 - Nuernberger, Patrick T1 - A comparative study on chirped-pulse upconversion and direct multichannel MCT detection N2 - 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. KW - Ultrafast spectroscopy KW - Upconversion KW - infrared spectroscopy KW - Lithium niobate KW - CCD, charge-coupled device Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111334 ER - TY - JOUR A1 - Bäuerlein, Carina A. A1 - Riedel, Simone S. A1 - Baker, Jeanette A1 - Brede, Christian A1 - Jordán Garrote, Ana-Laura A1 - Chopra, Martin A1 - Ritz, Miriam A1 - Beilhack, Georg F. A1 - Schulz, Stephan A1 - Zeiser, Robert A1 - Schlegel, Paul G. A1 - Einsele, Hermann A1 - Negrin, Robert S. A1 - Beilhack, Andreas T1 - A diagnostic window for the treatment of acute graft-versus-host disease prior to visible clinical symptoms in a murine model JF - BMC Medicine N2 - 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. KW - Allogeneic stem cell transplantation KW - Graft-versus-host disease KW - Minor histocompatibility antigen mismatch transplantation Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96797 UR - http://www.biomedcentral.com/1741-7015/11/134 ER - TY - JOUR A1 - Degenkolbe, Elisa A1 - König, Jana A1 - Zimmer, Julia A1 - Walther, Maria A1 - Reißner, Carsten A1 - Nickel, Joachim A1 - Plöger, Frank A1 - Raspopovic, Jelena A1 - Sharpe, James A1 - Dathe, Katharina A1 - Hecht, Jacqueline T. A1 - Mundlos, Stefan A1 - Doelken, Sandra C. A1 - Seemann, Petra T1 - A GDF5 Point Mutation Strikes Twice - Causing BDA1 and SYNS2 JF - PLOS Genetics N2 - 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. KW - dominant-negative mutatio KW - morphogenetic protein receptors KW - brachtydacyly type A2 KW - BMP KW - gene encoding noggin KW - growth factor beta KW - signal tranduction KW - molecular mechanism KW - crystal-structure KW - differentiation Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127556 SN - 1553-7404 VL - 9 IS - 10 ER - TY - JOUR A1 - Schuster, Frank A1 - Johannsen, Stephan A1 - Roewer, Norbert T1 - A Minimal-Invasive Metabolic Test Detects Malignant Hyperthermia Susceptibility in a Patient after Sevoflurane-Induced Metabolic Crisis JF - Case Reports in Anesthesiology N2 - 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. KW - Medizin Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97080 ER - TY - JOUR A1 - Gerszten, Peter C. A1 - Sahgal, Arjun A1 - Sheehan, Jason P. A1 - Kersh, Ronald A1 - Chen, Stephanie A1 - Flickinger, John C. A1 - Quader, Mubina A1 - Fahim, Daniel A1 - Grills, Inga A1 - Shin, John H. A1 - Winey, Brian A1 - Oh, Kevin A1 - Sweeney, Reinhart A. A1 - Guckenberger, Matthias T1 - A multi-national report on methods for institutional credentialing for spine radiosurgery JF - Radiation Oncology N2 - 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. KW - cyberknife radiosurgery KW - advanced technology KW - conformal radiotherapy KW - clinical trials KW - quality assurance KW - credentialing KW - spine tumors KW - stereotactic body radiotherapy KW - spine Radiosurgery KW - paraspinal tumors KW - intensity modulated radiotherapy KW - ACR practice guidelines KW - radiation therapy Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131485 VL - 8 IS - 158 ER - TY - JOUR A1 - Scharmann, Mathias A1 - Thornham, Daniel G. A1 - Grafe, T. Ulmar A1 - Federle, Walter T1 - A Novel Type of Nutritional Ant-Plant Interaction: Ant Partners of Carnivorous Pitcher Plants Prevent Nutrient Export by Dipteran Pitcher Infauna JF - PLoS ONE N2 - 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. KW - community KW - alternative trapping strategies KW - leaf-litter utilization KW - nepenthes bicalcarata KW - camponotus schmitzi KW - food web KW - epiphytic fern KW - nitrogen KW - prey KW - rafflesiana Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130952 VL - 8 IS - 5 ER - TY - JOUR A1 - Klement, Rainer Johannes A1 - Frobel, Thomas A1 - Albers, Torsten A1 - Fikenzer, Sven A1 - Prinzhausen, Jan A1 - Kämmerer, Ulrike T1 - 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 N2 - 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. KW - Fettgehalt KW - Blut KW - Ketogene Kost KW - High fat diet KW - exercise KW - bioimpedance analysis KW - blood lipids; fat loss; running performance Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-78901 ER - TY - JOUR A1 - Dmochewitz, Lydia A1 - Förtsch, Christina A1 - Zwerger, Christian A1 - Vaeth, Martin A1 - Felder, Edward A1 - Huber-Lang, Markus A1 - Barth, Holger T1 - A Recombinant Fusion Toxin Based on Enzymatic Inactive C3bot1 Selectively Targets Macrophages JF - PLoS ONE N2 - 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. KW - C3 KW - mammalian cells KW - clostridium botulinum KW - ADP-ribosylation toxins KW - botulinum C2 toxin KW - membrane translocation KW - bacterial toxins KW - actin filaments KW - cellular uptake KW - ribosyltransferase Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131189 VL - 8 IS - 1 ER - TY - THES A1 - Joseph Nedumparambil, George T1 - A Search of the Roots of Syro-Malabar Church in Kerala T1 - Die Suche nach den Wurzeln der syro-malabarischen Kirche in Kerala N2 - A Search of the Roots of Syro-Malabar Church in Kerala N2 - Die Suche nach den Wurzeln der syro-malabarischen Kirche in Kerala KW - Syro-Malabarische Kirche KW - Kerala KW - Syro-Malabarische Kirche KW - Kerala KW - Syro-Malabar Church in Kerala Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-77747 ER - TY - JOUR A1 - Pfeiffer, Verena A1 - Götz, Rudolf A1 - Xiang, Chaomei A1 - Camarero, Guadelupe A1 - Braun, Attila A1 - Zhang, Yina A1 - Blum, Robert A1 - Heinsen, Helmut A1 - Nieswandt, Bernhard A1 - Rapp, Ulf R. T1 - Ablation of BRaf Impairs Neuronal Differentiation in the Postnatal Hippocampus and Cerebellum JF - PLoS ONE N2 - 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. KW - granule cells KW - hippocampus KW - neurons KW - neuronal dendrites KW - embryos KW - dentate gyrus KW - neuronal differentiation KW - cerebellum Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130304 VL - 8 IS - 3 ER - TY - JOUR A1 - Farag, Heba Gamal A1 - Froehler, Sebastian A1 - Oexle, Konrad A1 - Ravindran, Ethiraj A1 - Schindler, Detlev A1 - Staab, Timo A1 - Huebner, Angela A1 - Kraemer, Nadine A1 - Chen, Wei A1 - Kaindl, Angela M. T1 - Abnormal centrosome and spindle morphology in a patient with autosomal recessive primary microcephaly type 2 due to compound heterozygous WDR62 gene mutation JF - Orphanet Journal of Rare Diseases N2 - 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. KW - cell division KW - intellectual disability KW - missense mutations KW - protein KW - malformations KW - establishment KW - cytokinesis KW - genome KW - midbody KW - database KW - maintenance KW - families KW - microcephaly KW - WDR62 mutation Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123505 SN - 1750-1172 VL - 8 IS - 178 ER - TY - JOUR A1 - Riedel, Alice A1 - Mofolo, Boitumelo A1 - Avota, Elita A1 - Schneider-Schaulies, Sibylle A1 - Meintjes, Ayton A1 - Mulder, Nicola A1 - Kneitz, Susanne T1 - Accumulation of Splice Variants and Transcripts in Response to PI3K Inhibition in T Cells JF - PLoS ONE N2 - 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. KW - T cells KW - gene regulation KW - alternative splicing KW - measles virus KW - T cell receptors KW - reverse transcriptase-polymerase chain reaction KW - cell cycle and cell division KW - TCR signaling cascade Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130335 VL - 8 IS - 2 ER - TY - JOUR A1 - Riedel, Alice A1 - Mofolo, Boitumelo A1 - Avota, Elita A1 - Schneider-Schaulies, Sibylle A1 - Meintjes, Ayton A1 - Mulder, Nicola A1 - Kneitz, Susanne T1 - Accumulation of Splice Variants and Transcripts in Response to PI3K Inhibition in T Cells N2 - 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. KW - Biologie Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-77917 ER - TY - THES A1 - Lücking, Thomas T1 - Acquisition Behavior in High-Technology Industries – The Role of Product Diversification, Technological Change, and IP Protection T1 - Akquisitionsverhalten in Hochtechnologiebranchen – Die Rolle von Produktdiversifikation, technologischem Wandel und dem Schutz von geistigem Eigentum N2 - 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. N2 - Die zahlreichen Unternehmensakquisitionen in Hochtechnologiebranchen sind einem intensiven Wettbewerb geschuldet, der durch immer kürzere Produktlebenszyklen, komplexere Produktdesigns und extreme Netzwerkeffekte geprägt ist. Die vorliegende Forschungsarbeit hat zum Ziel, die genauen Umstände, die zu technologiegetriebenen Akquisitionen führen, in Form von relevanten erklärenden Einflussfaktoren theoretisch herzuleiten und empirisch zu untersuchen. KW - Mergers and Acquisitions KW - Technologieunternehmen KW - Hochtechnologie KW - Unternehmensakquisition KW - Produktdiversifikation KW - High-technology KW - acquisition behavior KW - product diversification KW - strategic management KW - organizational science KW - Spitzentechnologie KW - Strategisches Management KW - Organisationstheorie Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85065 ER - TY - JOUR A1 - Morschhäuser, Joachim A1 - Ramírez-Zavala, Bernardo A1 - Weyler, Michael A1 - Gildor, Tsvia A1 - Schmauch, Christian A1 - Kornitzer, Daniel A1 - Arkowitz, Robert T1 - Activation of the Cph1-Dependent MAP Kinase Signaling Pathway Induces White-Opaque Switching in Candida albicans JF - PLoS Pathogens N2 - 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. KW - biofilms KW - candida albicans KW - library screening KW - pheromones KW - protein expressions KW - protein kinase signaling cascade KW - regulator genes KW - transcription factors Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97281 ER - TY - JOUR A1 - Holzapfel, Boris Michael A1 - Prodinger, Peter M. A1 - Pilge, Hakan A1 - Banke, Ingo J. A1 - Bürklein, Dominik A1 - Miethke, Thomas A1 - Gradinger, Reiner T1 - Acute Osteomyelitis of the Humerus mimicking Malignancy: Streptococcus pneumoniae as Exceptional Pathogen in an Immunocompetent Adult JF - BMC Infectious Diseases N2 - 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. KW - Acute osteomyelitis KW - Haematogenous KW - Long bones KW - Immunodeficiency KW - Osteomyelitis of the humerus Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-95790 ER - TY - JOUR A1 - Gunreben, Ignaz A1 - Geis, Christian A1 - Kleinschnitz, Christoph T1 - Acute tetraparesis secondary to bilateral precentral gyral cerebral ischemia: a case report JF - Journal of Medical Case Reports N2 - 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. KW - Medizin Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96179 UR - http://www.jmedicalcasereports.com/content/7/1/61 ER - TY - JOUR A1 - Quinkler, Marcus A1 - Beuschlein, Felix A1 - Hahner, Stefanie A1 - Meyer, Gesine A1 - Schöfl, Christof A1 - Stalla, Günter K. T1 - Adrenal Cortical Insufficiency-a Life Threatening Illness With Multiple Etiologies JF - Deutsches Ärzteblatt International N2 - 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. KW - short term KW - subjective health-status KW - modified-release hydrocortisone KW - glucocorticoid replacement regimens KW - Addisons disease KW - therapeutic management KW - hypopituitary patients KW - premature mortality KW - circadian therapy KW - adult patients Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131662 VL - 110 ER - TY - JOUR A1 - Eder, Andreas B. A1 - Rothermund, Klaus A1 - De Houwer, Jan T1 - Affective Compatibility between Stimuli and Response Goals: A Primer for a New Implicit Measure of Attitudes JF - PLoS ONE N2 - 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. KW - German people KW - reaction time KW - non-verbal communication KW - social psychology KW - cognitive psychology KW - hands KW - priming (psychology) KW - social research Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129872 VL - 8 IS - 11 ER - TY - THES A1 - Löw, Fabian T1 - Agricultural crop mapping from multi-scale remote sensing data - Concepts and applications in heterogeneous Middle Asian agricultural landscapes T1 - Kartierung von Agrarflächen mit multiskaligen Fernerkundungsdaten - Konzepte und Anwendung in heterogenen Agrarlandschaften Mittelasiens N2 - 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. N2 - Landwirtschaftlicher Ackerbau spielt heute eine Schlüsselrolle bei der Nahrungsmittelversorgung der Menschheit. Eine der zukünftigen Herausforderungen wird die Ernährung der stetig wachsenden Erdbevölkerung sein, welche bis zum Jahr 2050 auf neun Milliarden Menschen anwachsen wird. Das Potential zur Ausdehnung von Ackerland ist jedoch begrenzt, so dass die Steigerung der landwirtschaftlichen Produktionseffizienz ein wichtiges Mittel ist, um den künftigen Nahrungsmittelbedarf zu decken. Daher gibt es einen zunehmenden Bedarf an belastbaren, genauen und umfassenden Informationen über die Agrarproduktion. Der Nutzen der Satellitenbild-Fernerkundung ist in diesem Kontext mittlerweile anerkannt. Eine wichtige Voraussetzung für das Agrarmonitoring sind aktuelle Informationen über die Fläche sowie die räumliche Verteilung von Anbaukulturen. Durch die technologische Entwicklung steht heute eine Vielfalt an Satellitenbildsystemen mit immer höherer räumlicher und zeitlicher Auflösung zur Verfügung. Die Klassifikation solcher hochaufgelösten, multi-temporalen Datensätze stellt eine bewährte Methode dar, um Karten der agrarischen Landnutzung zu erstellen und die benötigten Informationen zu erhalten. Jedoch müssen die dabei verwendeten Methoden auf die sehr komplexen Eingangsdaten anwendbar sein. Zudem benötigt man zur Modellierung der Agrarproduktion oft eine hohe Aufnahmefrequenz bei gleichzeitig großer räumlicher Abdeckung. Diese Voraussetzungen schränken jedoch aus technischen Gründen oftmals die zur Verfügung stehenden Pixelgrößen ein, da Sensoren, welche diese Voraussetzungen erfüllen, in der Regel eine gröbere räumliche Auflösung haben. Die Unterscheidung von Pixeln unterschiedlicher Landnutzung als eine Voraussetzung für feldfrucht-spezifisches Agrarmonitoring kann dann erschwert sein, wenn Satellitenbilder über heterogenen Landschaften aufgezeichnet werden. In solchen Fällen kann das im Pixel kodierte Signal von mehreren Nutzungstypen stammen (Mischpixel), was zur Zunahme von Klassifikationsfehlern führen kann. Hauptgegenstände dieser Studie sind: (i) die Untersuchung des Einflusses der Größe sowie der Art der Eingangsdaten auf die Klassifikationsgenauigkeit und die Klassifikationsunsicherheit in der objekt-basierten Landnutzungsklassifikation; (ii) die Kombination von Klassifikationsalgorithmen zur Steigerung der Klassifikationsgenauigkeit; (iii) die Untersuchung des Einflusses der Pixelgröße auf die agrarische Landnutzungsklassifikation. Die Genauigkeit einer Klassifikation wird im Allgemeinen mit Hilfe von Gütemaßen ermittelt, welche auf der Konfusionsmatrix basieren. Jedoch berücksichtigen diese Maße nicht die räumliche Variabilität von Klassifikationsfehlern in einer Karte. Maße der Klassifikationsunsicherheit können für diesen Zweck verwendet werden, allerdings ist deren Anwendung in der Fernerkundung bislang nur selten untersucht worden. Klassifikationsalgorithmen wie das Stützvektorverfahren können für jedes Pixel oder Objekt klassenweise Abschätzungen der Klassenzugehörigkeit berechnen, aus welchen dann Maße der Klassifikationsunsicherheit (z.B. Entropie) berechnet werden können. Jedoch wurde noch nicht hinreichend untersucht, ob die damit gewonnenen Informationen zur Abschätzung der räumlichen Verteilung von Klassifikationsfehlern in Karten zuverlässig sind. In dieser Studie wurde das Stützvektorverfahren verwendet, um die agrarische Landnutzung in bewässerten Agrarlandschaften Zentralasiens zu klassifizieren. Fünf Kategorien von Eingangsdaten wurden aus Aufnahmen des RapidEye Systems berechnet und als Grundlage für die agrarische Landnutzungsklassifikation verwendet. Es wurde untersucht, ob Maße der Klassifikationsunsicherheit, welche auf den pixel- bzw. objektweisen Abschätzungen der Klassenzugehörigkeit durch das Stützvektorverfahren basieren, die räumliche Verteilung von Klassifikationsfehlern in Landnutzungskarten zuverlässig schätzen können. Weiterhin wurde der Einfluss sowohl der Art als auch der Größe der Eingangsdaten auf die Klassifikationsunsicherheit untersucht. Die Ergebnisse der Untersuchung weisen darauf hin, dass sich sowohl die getrennte als auch die kombinierte Verwendung der fünf Eingangsdatenkategorien unterschiedlich zur Klassifikation verschiedener Landnutzungsklassen eignen. Die kombinierte Verwendung aller fünf Kategorien führte zum Teil zu einer Reduktion der Klassifikationsgenauigkeit, was wahrscheinlich auf das Hughes-Phänomen zurückzuführen ist. Durch die Verwendung des „Random Forest“ Verfahrens zur Selektion geeigneter Eingangsdaten konnte die Klassifikationsgenauigkeit des Stützvektorverfahrens gesteigert werden. Eingangsdaten basierend auf dem sogenannten „Red Edge“ Kanal des RapidEye Systems waren zur Klassifikation von Feldfrüchten am wichtigsten, insbesondere der „Red Edge NDVI“. Zwei Maße der Klassifikationsunsicherheit wurden berechnet: die maximale a-posteriori Klassifikationswahrscheinlichkeit und die Alpha-Quadrat Entropie. Die Ergebnisse weisen darauf hin, dass diese beiden Maße verlässliche Prädiktoren für die räumliche Verteilung von Klassifikationsfehlern sind. Korrekt klassifizierte Testfelder waren durch geringe Klassifikationsunsicherheit und inkorrekt klassifizierte Testfelder in der Regel durch hohe Klassifikationsunsicherheit charakterisiert. Es wurde untersucht, ob die Kombination mehrerer Klassifikationsalgorithmen zu einer Steigerung der Klassifikationsgenauigkeit führt. Zunächst wurde das Stützvektorverfahren mit anderen nicht-parametrischen Verfahren (neuronalen Netzwerken und Random Forest) verglichen. Obwohl die getesteten Klassifikationsalgorithmen gute Gesamt-Klassifikationsgenauigkeiten erzielten, bestanden große Unterschiede in den klassenweisen Genauigkeiten. Daher wurde ein Verfahren entwickelt, um die teilweise komplementären Ergebnisse unterschiedlicher Klassifikationsalgorithmen zu kombinieren. Dieses Verfahren basiert auf der Erweiterung algebraischer Kombinationsoperatoren und kombiniert die Ergebnisse verschiedener Klassifikationsalgorithmen basierend auf den pixel- bzw. objektweisen Abschätzungen der Klassenzugehörigkeit. Zudem wurde jeder Klassifikationsalgorithmus klassenweise bewertet, basierend auf Maßen der Konfusionsmatrix. So konnten Klassifikationsalgorithmen für diejenigen Klassen von der Kombination ausgeschlossen werden, für deren klassenweisen Genauigkeiten bestimmte Kriterien nicht erfüllt wurden. Das vorgestellte Verfahren wurde mit den Ergebnissen der einzelnen Klassifikationsalgorithmen verglichen. Zudem wurde auf räumliche und zeitliche Übertragbarkeit hin getestet und der Einfluss der Auswahl von Trainingsdaten wurde untersucht. Obwohl die einzelnen Klassifikationsalgorithmen genaue Ergebnisse erzielten, konnte das vorgestellte Kombinationsverfahren in allen Gebieten und über mehrere Jahre bessere Ergebnisse mit geringerer Variabilität erzielen. Zudem konnte das Verfahren auch dann genauere Ergebnisse liefern, wenn nur wenige Trainingsdaten oder Eingangsdaten zur Verfügung standen. In dieser Studie wurde eine Methodik entwickelt, um quantitativ die maximal tolerierbaren Pixelgrößen für die agrarische Landnutzungsklassifikation zu bestimmen. Diese Methodik kann verwendet werden, um den kombinierten Effekt von Pixelgröße und Pixelreinheit im Kontext der Feldfruchtidentifikation mittels überwachter Klassifikation zu untersuchen. Die feldfruchtspezifische Pixelreinheit (definiert als der Grad der Homogenität des in Pixeln kodierten Signals) wurde verwendet um zu untersuchen, wie inhomogen die in gröberen Bildpixeln gespeicherte Information sein darf, um unterschiedliche Anbaukulturen mittels überwachter und unüberwachter Klassifikation unterscheiden zu können. Als Eingangsdaten für die Untersuchung wurden Bilder des RapidEye Systems verwendet. Es wurden Bildgrößen zwischen 13 m und 747.5 m in Schritten von 6.5 m simuliert. Als limitierende Faktoren für die Klassifikation wurden unterschiedliche Schwellenwerte für Maße der Klassifikationsgenauigkeit und Klassifikationsunsicherheit berücksichtigt. Die Ergebnisse zeigen, dass die Werte für tolerierbare Pixelgrößen und Pixelreinheiten sowohl landschafts- als auch feldfruchtspezifisch waren. Zudem konnten Feldfrüchte nicht simultan innerhalb der Wachstumsperiode identifiziert werden und die Voraussetzungen änderten sich in verschiedenen Jahren, was wahrscheinlich auf die unterschiedlichen agro-ökologischen Bedingungen in den untersuchten Landschaften zurückgeführt werden kann. Die Ergebnisse zeigen, dass Klassifikationsgüte in Karten räumlich ungleich verteilt war und von den räumlichen Strukturen bzw. von der Wahl der räumlichen Auflösung abhing. Die vorgestellte Methodik kann auch in anderen Agrarlandschaften getestet werden. Des Weiteren kann die Eignung bestehender bzw. die Entwicklung künftiger Satellitenbildmissionen unterstützt werden. In Hinblick auf die Nutzung von Satellitenbild-Fernerkundung für Agrarmonitoring und deren Anwendung in einer Vielfalt von Agrarlandschaften kann festgestellt werden, dass die räumliche Übertragbarkeit von Methoden und die Stabilität der Ergebnisse (z.B. gleichbleibend hohe Klassifikationsgenauigkeiten) weiterhin einen wichtigen Forschungsgegenstand darstellen. So konnte in dieser Studie gezeigt werden, dass herkömmliche Methoden zur Landnutzungsklassifikation bzw. Aussagen zu optimalen Pixelgrößen nicht in allen Fällen auf andere Regionen oder über mehrere Jahre übertragbar sind. In Zentralasien, welches die Fokusregion dieser Studie ist, zeigte sich, dass die Kombination verschiedener Klassifikationsalgorithmen sinnvoll ist, da die Klassifikationsgenauigkeit bei Klassen mit nur einer geringen Anzahl von Trainingsgebieten gesteigert werden konnte. Dies macht die Anwendung dieses Verfahrens im operationellen Kontext interessant. Die Eignung eines einzigen Satellitenbildsystems (mit einer bestimmten Pixelgröße) für die agrarische Landnutzungsklassifikation in mehreren Agrarlandschaften muss in Frage gestellt werden und die synergistische Nutzung von Daten unterschiedlicher räumlicher Auflösung sollte vorangetrieben werden. Dabei ist die Untersuchung des kombinierten Einflusses der räumlichen und zeitlichen Auflösung auf die agrarische Landnutzungsklassifikation von großer Bedeutung für das erdbeobachtungsgestützte Agrarmonitoring. KW - Fernerkundung KW - Remote Sensing KW - Agriculture KW - Landwirtschaft KW - Zentralasien KW - Agrarlandschaft KW - Landnutzung Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-102093 ER - TY - JOUR A1 - Drechsler, Christiane A1 - Ritz, Eberhard A1 - Tomaschitz, Andreas A1 - Pilz, Stefan A1 - Schönfeld, Stephan A1 - Blouin, Katja A1 - Bidlingmaier, Martin A1 - Hammer, Fabian A1 - Krane, Vera A1 - März, Winfried A1 - Allolio, Bruno A1 - Fassnacht, Martin A1 - Wanner, Christoph T1 - Aldosterone and cortisol affect the risk of sudden cardiac death in haemodialysis patients JF - European Heart Journal N2 - 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. KW - mortality KW - kidney disease KW - cardiovascular events KW - sudden cardiac death KW - cortisol KW - aldosterone Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132562 VL - 34 ER - TY - JOUR A1 - Elseberg, Jan A1 - Borrmann, Dorit A1 - Nüchter, Andreas T1 - Algorithmic Solutions for Computing Precise Maximum Likelihood 3D Point Clouds from Mobile Laser Scanning Platforms JF - Remote Sensing N2 - 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. KW - mapping KW - calibration KW - non-rigid registration KW - mobile laser scanning KW - algorithms Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130478 VL - 5 IS - 11 ER - TY - JOUR A1 - Anders, Diana A1 - Trautmann, Axel T1 - Allergic anaphylaxis due to subcutaneously injected heparin JF - Allergy, Asthma & Clinical Immunology N2 - 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. KW - Anaphylaxis KW - Allergy KW - Basophil activation test KW - Enoxaparin KW - Heparin KW - Hypersensitivity KW - Immunoglobulin E KW - Immediate-type Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96214 UR - http://www.aacijournal.com/content/9/1/1 ER - TY - JOUR A1 - Fuji, Shigeo A1 - Kapp, Markus A1 - Einsele, Hermann T1 - Alloreactivity of virus-specific T cells: possible implication of graft-versus-host disease and graft-versus-leukemia effects JF - Frontiers in Immunology N2 - 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. KW - mismatch KW - allogeneic stem cell transplantation KW - GVHD KW - HLA antigens KW - GVL KW - virus-specific T-cell Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129260 VL - 4 IS - 330 ER - TY - JOUR A1 - Böhm, Johann A1 - Vasli, Nasim A1 - Maurer, Marie A1 - Cowling, Belinda A1 - Shelton, G. Diane A1 - Kress, Wolfram A1 - Toussaint, Anne A1 - Prokic, Ivana A1 - Schara, Ulrike A1 - Anderson, Thomas James A1 - Weis, Joachim A1 - Tiret, Laurent A1 - Laporte, Jocelyn T1 - Altered Splicing of the BIN1 Muscle-Specific Exon in Humans and Dogs with Highly Progressive Centronuclear Myopathy JF - PLOS Genetics N2 - 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. KW - linked myotubular myopathy KW - skeletal muscle KW - inherited myopathy KW - SH3 domain KW - amphiphysin-2 BIN1 KW - membrane curvature KW - tumor-suppressor KW - great dane KW - mutation KW - gene Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127590 SN - 1553-7404 VL - 9 IS - 6 ER - TY - JOUR A1 - Atanasov, Georgi A1 - Benkert, Christoph A1 - Thelen, Armin A1 - Tappe, Dennis A1 - Frosch, Matthias A1 - Teichmann, Dieter A1 - Barth, Thomas F. E. A1 - Wittekind, Christian A1 - Schubert, Stefan A1 - Jonas, Sven T1 - Alveolar echinococcosis-spreading disease challenging clinicians: A case report and literature review JF - World Journal of Gastroenterology N2 - 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. KW - hemihepatectomy KW - multilocularis KW - Germany KW - Europe KW - liver KW - alveolar echinococcosis KW - echinococcus multilocularis KW - autochthonous infection KW - liver resection Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131525 VL - 19 IS - 26 ER - TY - THES A1 - Zancolli, Giulia T1 - Amphibian diversity along the slope of Mount Kilimanjaro: from species to genes T1 - Diversität von Amphibien im Höhengradienten des Mount Kilimanjaro: von Arten zu Genen N2 - 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 naïve 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. N2 - Seit Ende des 19. Jahrhunderts ist es eine der größten intellektuellen Herausforderungen für Ökologen und Biogeographen, die Verteilungsmuster der Biodiversität auf der Erde zu beschreiben und letztlich zu verstehen. Zu den auffälligsten Mustern des Artenreichtums gehören die Gradienten, die sich in Abhängigkeit von der geographischer Breite und der Höhe über dem Meeresspiegel ergeben. Dabei treten Maxima der Artenzahl in den niederen Breiten und stellenweise in mittleren Höhenregionen auf; es lassen sich aber auch andere Muster beobachten, z.B. eine Abnahme der Artenzahl mit zunehmender Höhe. Selbst in den hochdiversen Tropen sind Arten nicht gleichmäßig verteilt. So gibt es sog. „hotspots“ der Biodiversität mit einer außergewöhnlich großen Zahl von Arten (meist Endemiten). Gerade diese Regionen sind es, die heute dramatische 1. Seit Ende des 19. Jahrhunderts ist es eine der größten intellektuellen Herausforderungen für Ökologen und Biogeographen, die Verteilungsmuster der Biodiversität auf der Erde zu beschreiben und letztlich zu verstehen. Zu den auffälligsten Mustern des Artenreichtums gehören die Gradienten, die sich in Abhängigkeit von der geographischer Breite und der Höhe über dem Meeresspiegel ergeben. Dabei treten Maxima der Artenzahl in den niederen Breiten und stellenweise in mittleren Höhenregionen auf; es lassen sich aber auch andere Muster beobachten, z.B. eine Abnahme der Artenzahl mit zunehmender Höhe. Selbst in den hochdiversen Tropen sind Arten nicht gleichmäßig verteilt. So gibt es sog. „hotspots“ der Biodiversität mit einer außergewöhnlich großen Zahl von Arten (meist Endemiten). Gerade diese Regionen sind es, die heute dramatische Habitatverluste verzeichnen. Unter den Wirbeltieren sind es die Amphibien, die dabei die höchsten Aussterberaten aufweisen. Ihre Populationen gehen weltweit zurück, wofür neben Lebensraumzerstörung auch Umweltverschmutzung und die Ausbreitung von Infektionskrankheiten, z.B. Chytridiomykose, verantwortlich sind. Reaktionen auf solche Faktoren können vielschichtig sein und fast unmerklich bleiben, was bedeutet, dass sie nicht auf Artniveau, sondern nur auf genetischer Ebene erfasst werden können. Hinzu kommt, dass die aktuellen Muster der Biodiversität auf den Einfluss vergangener Veränderungen hinsichtlich Geologie, Klima und Umwelt zurückgeführt werden können ... KW - Kilimandscharo KW - biodiversity KW - Amphibien KW - Lurche KW - Biodiversität KW - Vielfalt Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-91792 ER - TY - INPR A1 - Geiselhart, Roman A1 - Gielen, Rob H. A1 - Lazar, Mircea A1 - Wirth, Fabian R. T1 - An Alternative Converse Lyapunov Theorem for Discrete-Time Systems N2 - 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. KW - Ljapunov-Funktion KW - stability analysis KW - conewise linear systems KW - discrete-time systems KW - converse Lyapunov theorems Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-78512 ER - TY - JOUR A1 - Gageik, Nils A1 - Strohmeier, Michael A1 - Montenegro, Sergio T1 - An Autonomous UAV with an Optical Flow Sensor for Positioning and Navigation JF - International Journal of Advanced Robotic Systems N2 - 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. KW - Autonomous UAV KW - Quadrocopter KW - Quadrotor KW - Optical Flow KW - positioning KW - navigation Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96368 ER - TY - JOUR A1 - Sirén, Anna-Leena A1 - Stetter, Christian A1 - Hirschberg, Markus A1 - Nieswandt, Bernhard A1 - Ernestus, Ralf-Ingo A1 - Heckmann, Manfred T1 - An experimental protocol for in vivo imaging of neuronal structural plasticity with 2-photon microscopy in mice JF - Experimental & Translational Stroke Medicine N2 - 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. KW - 2-photon microscopy KW - Fluorescence KW - In vivo imaging KW - Neurons KW - Cranial window KW - Mouse model Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96908 UR - http://www.etsmjournal.com/content/5/1/9 ER - TY - THES A1 - Audretsch, Christof T1 - Analysing Quorum Sensing and Biofilm formation in Staphylococcus aureus T1 - Untersuchungen des Quorum-Sensing und der Biofilm-Bildung in Staphylokokkus aureus N2 - 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. N2 - Staphylococcus aureus (SA) ist Auslöser nosocomialer Infektionen, darunter auch die, durch multiresistente Stämme (MRSA) verursachte, lebensbedrohliche Sepsis. Er hat die Fähigkeit Biofilme zu bilden, um sich vor dem Immunsystem des Wirtes und vor Antibiotika zu schützen. Biofilm und planktonische Lebensweise werden durch ein komplexes Quorum-Sensing (QS) System mit agr als zentralem Regulator gesteuert. Um die Biofilm Bildung und QS Mechanismen in SA zu untersuchen, wurde ein Boole´sches Netzwerk erstellt (94 Knoten, 184 Kanten) das verschiedene Zwei-Komponenten-Systeme wie agr, sae und arl mit einschließt. Wichtige Proteine wie Sar, Rot und SigB wurden als weitere Knoten im Modell eingefügt. Die Systemanalyse zeigte, dass es nur zwei stabile Zustände gibt, Biofilm bildend versus planktonisch, in denen deutlich unterschiedliche Subnetzwerke angeschaltet sind. Überprüfungen anhand von Gen-Expressions-Daten bestätigten dies. Die Netzwerkstabilität wurde zuerst an Hand von bestehendem Wissen und Literatur getestet. Zudem stimmte die vorhergesagte Aktivität der Knoten in verschiedenen in silico Knock-out Stämmen sehr gut mit den zugehörigen Micro-array Experimenten und Daten überein. Zusätzliche Validierungen schlossen die Expression weiterer Knoten (Northern Blots) und die Biofilm Produktion, verglichen durch Biofilm adherence assays, in verschiedenen Knock-out Stämmen mit ein. Das Modell spiegelt zuverlässig das Verhalten von QS-Signal Mutanten wieder. Das integrierte Modell erlaubt auch Vorhersagen von diversen anderen Netzwerk Mutationen und wird durch experimentelle Daten unterschiedlicher Stämme gestützt. Außerdem zeigen die gut vernetzten Hubproteine im Detail auf, wie die Verarbeitung unterschiedlicher Eingangssignale durch das QS-Netzwerk erreicht wird. Sowohl für in silico als auch für in vitro Experimente konnte gezeigt werden, dass der sae-Locus auch einen zentralen Modulator der Biofilm Produktion darstellt, sae Knock-out Stämme zeigten stärkere Biofilme. Der Wildtyp Phänotyp wurde durch sae Komplementierung wiederhergestellt. Um die Art und Weise, mit der sae Einfluss auf die Biofilm Bildung nimmt, aufzuklären wurde das Netzwerk genutzt und Venn-Diagramme angefertigt, welche Knoten aufzeigten, die durch sae reguliert- und in Biofilmen verändert sind. In den Venn-Diagrammen wurden Nucleasen und extrazelluläre Proteine als vielversprechende Knoten gefunden. Das Netzwerk zeigte, dass DNAse von großer Bedeutung ist. Deswegen wurde qualitativ die, durch unterschiedliche SA Mutanten produzierte, DNAse-Menge gemessen, es wurde versucht den Biofilm mit vergleichbaren DNAse-Mengen aufzulösen und die Konzentration von Nukleinsäuren, Proteinen und Polysacchariden wurde in Biofilmen unterschiedlicher SA Mutanten gemessen. Aufgrund seiner sorgfältigen Überprüfung stellt das Netzwerk-Modell ein mächtiges Werkzeug zur Untersuchung von QS und Biofilm Bildung in SA dar, erfolgreiche Vorhersagen über das Verhalten unterschiedlicher Knock-out Mutanten, QS Signale und Biofilm Bildung eingeschlossen. Dies beinhaltet Prognosen für das Verhalten von MRSA Stämmen und Mutanten. Zentrale regulatorische Mutationskombinationen (agr–, sae–, sae–/agr–, sigB+, sigB+/sae–) wurden direkt im Model aber auch in Experimenten getestet. Hohe Konektivität war ein guter Anhaltspunkt, um Hauptregulatoren zu identifizieren, deren Verhalten in vitro und im Modell untersucht wurde. Zusammen unterstützen beide Beweisführungen im Besonderen eine präzise regulatorische Rolle von sae und agr in Bezug auf Biofilm Unterdrückung und/oder SA Ausbreitung. Mit der Untersuchung der Zusammensetzung von Biofilmen unterschiedlicher Mutanten, ebenso wie mit der Untersuchung der Reaktionskaskade die sae mit der Biofilm Bildungsfähigkeit von SA verbindet und auch dem Überprüfen der Annahme, dass Nukleasen eine bedeutende Rolle hierin spielen könnten, wurden erste Schritte unternommen, um regulatoische Interaktionen zwischen sae und Biofilmen zu belegen und zu untersuchen. Des Weiteren wurden Unterschiede in Biofilmen verschiedener mutierter SA Stämme gefunden, die uns voraussichtlich zu einem neuem Verständnis von Biofilmen und damit zu Wissen führen, wie ihre Eigenschaften reguliert, bekämpft und genutzt werden können. KW - Staphylococcus aureus KW - Biofilm KW - Simulation KW - Staphylococcus aureus KW - Quorum-Sensing KW - Simulation KW - Biofilm KW - sae KW - agr KW - sar KW - DNAse Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-92189 ER - TY - THES A1 - Das Gupta, Mithun T1 - Analyse von MicroRNA-Profilen in humanen dendritischen Zellen T1 - Analysis of microRNA-profiles in human dendritic cells N2 - 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. N2 - Die Erforschung von MicroRNAs gewinnt zunehmend an Bedeutung. Aktuelle Arbeiten zeigen, dass MicroRNAs an der Regulation vieler biologischer Prozesse beteiligt sind, indem sie in die posttranskriptionelle Genregulation eingreifen. Dies betrifft auch die TLR-vermittelte Erkennung von Pathogenen durch Immunzellen. Hierbei wurden u.a. die MikroRNAs miR-132, miR-146a und miR-155 von verschiedenen Autoren charakterisiert. Die spezielle Rolle von MikroRNAs bei der Abwehr von Pilzinfektionen durch Aspergillus fumigatus ist bisher allerdings kaum untersucht, obwohl dieser ubiquitär vorkommende Schimmelpilz häufig schwere Infektionen bei immunsupprimierten Patienten auslöst. Da in vivo den dendritischen Zellen eine entscheidende Rolle bei der Erkennung von A. fumigatus zukommt, wurde in der vorliegenden Arbeit die Reaktion dieser Zellen auf A. fumigatus und andere Pathogene auf MikroRNA Ebene untersucht. Dazu wurden dendritische Zellen mit verschiedenen Formen von A. fumigatus und LPS über Zeiträume von bis zu zwölf Stunden stimuliert. Anschließend wurde die Expression von miR-132, miR-146a und miR-155 mittels Real-Time PCR bestimmt. Dabei zeigte sich, dass nach Stimulation mit A. fumigatus die miR-132 Level in dendritischen Zellen deutlich anstiegen, wohingegen eine Inkubation mit LPS keinen Einfluss auf diese MicroRNA hatte. Die relative Expression von miR-146a war nach Stimulation mit LPS leicht erhöht, zeigte allerdings keine Veränderung nach Ko-Kultur mit A. fumigatus. Die Expression von miR-155 wurde durch beide Stimuli stark induziert. Diese Ergebnisse zeigen, dass abhängig vom Stimulus eine differentielle Expression von MicroRNAs in dendritischen Zellen stattfindet. Unter den drei untersuchten MicroRNAs, zeigte miR-155 die höchsten und stabilsten Expressionswerte. Daher wurde der Schwerpunkt weiterer Experimente auf diese MicroRNA gesetzt. Dabei ergab sich, dass das Ausmaß der miR-155 Induktion vom Entwicklungsstadium des Pilzes abhängig ist. Konidien von A. fumigatus führten lediglich zu einer schwachen Hochregulation von miR-155, wohingegen Hyphen und insbesondere Keimschläuche ein starke Induktion von miR-155 verursachten. Die Dynamik der miR-155 Hochregulation korrelierte außerdem mit der multiplicity of infection (MOI), wobei eine höhere MOI mit einer stärkeren miR-155 Antwort einherging. Die dargestellten Ergebnisse legen nahe, dass miR-132 und miR-155 eine wichtige Rolle bei der Immunreaktion von DCs gegen A. fumigatus spielen und eine weitere Charakterisierung dieser MicroRNAs v.a. im Hinblick auf ihre spezielle Funktion in DCs einen wichtigen Beitrag zum Verständnis der biologischen Grundlagen der Aspergillosen erbringen könnte. KW - Aspergillus fumigatus KW - microRNA KW - Dendritische Zelle KW - miR-132 KW - miR-155 KW - miR-146 KW - A. fumigatus KW - dendritic cell Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-108326 ER - TY - JOUR A1 - Brehm, Klaus A1 - Koziol, Uriel A1 - Krohne, Georg T1 - Anatomy and development of the larval nervous system in Echinococcus multilocularis JF - Frontiers in Zoology N2 - 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. KW - Echinococcus KW - Metacestode KW - Protoscolex KW - Nervous system KW - Neuropeptide KW - Serotonin KW - Acetylated tubulin Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96504 UR - http://www.frontiersinzoology.com/content/10/1/24 ER - TY - JOUR A1 - Huang, Bei A1 - Belharazem, Djeda A1 - Li, Li A1 - Kneitz, Susanne A1 - Schnabel, Philipp A. A1 - Rieker, Ralf J. A1 - Körner, Daniel A1 - Nix, Wilfried A1 - Schalke, Berthold A1 - Müller-Hermelink, Hans Konrad A1 - Ott, German A1 - Rosenwald, Andreas A1 - Ströbel, Philipp A1 - Marx, Alexander T1 - Anti-apoptotic signature in thymic squamous cell carcinomas – functional relevance of anti-apoptotic BIRC3 expression in the thymic carcinoma cell line 1889c JF - Frontiers in Oncology N2 - 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. KW - gene expression KW - MTCH2 KW - targeted KW - myasthenia gravis KW - apoptosis KW - thymus KW - thymoma KW - thymic carcinoma Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132214 VL - 3 IS - 316 ER - TY - JOUR A1 - van Dinther, Maarten A1 - Zhang, Juan A1 - Weidauer, Stella E. A1 - Boschert, Verena A1 - Muth, Eva-Maria A1 - Knappik, Achim A1 - de Gorter, David J. J. A1 - van Kasteren, Puck B. A1 - Frisch, Christian A1 - Müller, Thomas D. A1 - ten Dijke, Peter T1 - Anti-Sclerostin Antibody Inhibits Internalization of Sclerostin and Sclerostin-Mediated Antagonism of Wnt/LRP6 Signaling JF - PLoS ONE N2 - 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. KW - gene KW - rat model KW - Dickkopf proteins KW - postmenopausal osteoporosis KW - increases bone-formation KW - WNT KW - LRP6 KW - density KW - receptor KW - ligand Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130981 VL - 8 IS - 4 ER - TY - JOUR A1 - Beier, Hildburg A1 - Gätschenberger, Heike A1 - Azzami, Klara A1 - Tautz, Jürgen T1 - Antibacterial Immune Competence of Honey Bees (Apis mellifera) Is Adapted to Different Life Stages and Environmental Risks JF - PLoS ONE N2 - 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. KW - escherichia coli infections KW - honey bees KW - bees KW - antimicrobials KW - bacterial pathogens KW - larvae KW - pupae KW - winter Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96895 ER - TY - THES A1 - Busch, Martin T1 - Aortic Dendritic Cell Subsets in Healthy and Atherosclerotic Mice and The Role of the miR-17~92 Cluster in Dendritic Cells T1 - Subsets dendritischer Zellen in der Aorta gesunder und atherosklerotischerMäuse und die Rolle des miR-17~92 Clusters in dendritischen Zellen N2 - 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. N2 - Atherosklerose ist eine chronisch-entzündliche Erkrankung der arteriellen Gefäßwand und zahlreiche Zellen des Immunsystems, wie zum Beispiel Monozyten, Makrophagen, T und B Zellen sind an der Entstehung und Entwicklung beteiligt. Aktuelle Forschungsergebnisse haben gezeigt, dass auch dendritische Zellen (DCs) zur Atherosklerose beitragen. DCs sind durch ihre Fähigkeit gekennzeichnet, Antigene zu erkennen, aufzunehmen, zu migrieren und andere Immunzellen, wie zum Beispiel T Zellen, zu aktivieren. Auch wenn alle DCs diese funktionellen Merkmale teilen, so sind sie in Bezug auf ihren Phänotyp oder Ursprung eine eher heterogene Gruppe. Zahlreiche Oberflächenmoleküle wurden in der Vergangenheit genutzt, um DCs in lymphatischen und nicht-lymphatischen Geweben zu beschreiben. Allerdings hat sich keines dieser Moleküle als spezifisch und unverwechselbar erwiesen. Die Expression von Oberflächenmolekülen ist sehr variabel und hängt nicht nur vom Aktivierungszustand der DCs, sondern auch vom umliegenden Gewebe ab. Dazu kommt, dass DCs in der Aorta, beziehungsweise im atherosklerotischen Plaque, von designierten Vorläuferzellen, aber auch von Monozyten abstammen können und DCs das Profil ihrer Oberflächenmoleküle, sowie ihre funktionellen Eigenschaften, mit anderen myeloiden Zellen wie Monozyten und Makrophagen teilen. Neuere Arbeiten haben damit begonnen das Repertoire an DCs in der Aorta von gesunden und atherosklerotischen Mäusen zu untersuchen. Da es naheliegt, dass verschiedene DC Untergruppen ganz bestimmte Funktionen ausüben, wird eine detaillierte Beschreibung vaskulärer DCs in der Forschung benötigt. Weil es hierzu allerdings bislang kaum Studien gibt, untersucht der erste Teil dieser Arbeit zum ersten Mal systematisch die in gesunden und atherosklerotischen Mäusen vorkommenden Gruppen an DCs. Sie beschreibt außerdem eine zuvor nicht beachtete DC-Untergruppe und gibt Aufschluss über den Ursprung vaskulärer DCs. In den letzten Jahren wurde gezeigt, dass microRNAs (mirRNAs) zahlreiche zelluläre Vorgänge wie Apoptose, Differenzierung, Entwicklung und Proliferation regulieren. Obwohl viele Zelltypen in Bezug auf die in ihrer Regulation eingebundenen mirRNAs charakterisiert wurden, gibt es nur wenige Studien, die sich mit der Rolle von mirRNAs in DCs beschäftigen. Der zweite Teil dieser Arbeit konzentriert sich auf die Rolle der miRNA Gruppe miR-17~92 in DCs und untersucht deren Rolle in gesunden und atherosklerotischen Mäusen. Diese Arbeit zeigt erstmals eine deutliche anti-inflammatorische und protektive Rolle dieser miRNA und schlägt ein Modell für die entdeckten Mechanismen vor. KW - Aorta KW - Maus KW - Zelle KW - Cluster KW - miRNS KW - Dendritische Zelle KW - Arteriosklerose KW - miR-17~92 KW - dendritic cells KW - atherosclerosis KW - mice KW - murine Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-71683 ER - TY - JOUR A1 - Rest, Christina A1 - Mayoral, María José A1 - Fernández, Gustavo T1 - Aqueous Self-Sorting in Extended Supramolecular Aggregates JF - International Journal of Molecular Sciences N2 - 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. KW - co-aggregation KW - self-sorting KW - supramolecular chemistry KW - self-assembly Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129435 VL - 14 IS - 1 ER - TY - JOUR A1 - Tappe, Dennis A1 - Haeupler, Alexandra A1 - Schäfer, Hansjörg A1 - Racz, Paul A1 - Cramer, Jakob P. A1 - Poppert, Sven T1 - Armillifer armillatus Pentastomiasis in African Immigrant, Germany JF - Emerging Infectious Diseases N2 - No abstract available. Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129054 N1 - Public Domain (Source: http://wwwnc.cdc.gov/eid/page/copyright-and-disclaimers) VL - 19 IS - 3 ER - TY - JOUR A1 - Manchia, Mirko A1 - Adli, Mazda A1 - Akula, Nirmala A1 - Arda, Raffaella A1 - Aubry, Jean-Michel A1 - Backlund, Lena A1 - Banzato, Claudio E. M. A1 - Baune, Bernhard T. A1 - Bellivier, Frank A1 - Bengesser, Susanne A1 - Biernacka, Joanna M. A1 - Brichant-Petitjean, Clara A1 - Bui, Elise A1 - Calkin, Cynthia V. A1 - Cheng, Andrew Tai Ann A1 - Chillotti, Caterina A1 - Cichon, Sven A1 - Clark, Scott A1 - Czerski, Piotr M. A1 - Dantas, Clarissa A1 - Del Zompo, Maria A1 - DePaulo, J. Raymond A1 - Detera-Wadleigh, Sevilla D. A1 - Etain, Bruno A1 - Falkai, Peter A1 - Frisén, Louise A1 - Frye, Mark A. A1 - Fullerton, Jan A1 - Gard, Sébastien A1 - Garnham, Julie A1 - Goes, Fernando S. A1 - Grof, Paul A1 - Gruber, Oliver A1 - Hashimoto, Ryota A1 - Hauser, Joanna A1 - Heilbronner, Urs A1 - Hoban, Rebecca A1 - Hou, Liping A1 - Jamain, Stéphane A1 - Kahn, Jean-Pierre A1 - Kassem, Layla A1 - Kato, Tadafumi A1 - Kelsoe, John R. A1 - Kittel-Schneider, Sarah A1 - Kliwicki, Sebastian A1 - Kuo, Po-Hsiu A1 - Kusumi, Ichiro A1 - Laje, Gonzalo A1 - Lavebratt, Catharina A1 - Leboyer, Marion A1 - Leckband, Susan G. A1 - López Jaramillo, Carlos A. A1 - Maj, Mario A1 - Malafosse, Alain A1 - Martinsson, Lina A1 - Masui, Takuya A1 - Mitchell, Philip B. A1 - Mondimore, Frank A1 - Monteleone, Palmiero A1 - Nallet, Audrey A1 - Neuner, Maria A1 - Novák, Tomás A1 - O'Donovan, Claire A1 - Ösby, Urban A1 - Ozaki, Norio A1 - Perlis, Roy H. A1 - Pfennig, Andrea A1 - Potash, James B. A1 - Reich-Erkelenz, Daniela A1 - Reif, Andreas A1 - Reininghaus, Eva A1 - Richardson, Sara A1 - Rouleau, Guy A. A1 - Rybakowski, Janusz K. A1 - Schalling, Martin A1 - Schofield, Peter R. A1 - Schubert, Oliver K. A1 - Schweizer, Barbara A1 - Seemüller, Florian A1 - Grigoroiu-Serbanescu, Maria A1 - Severino, Giovanni A1 - Seymour, Lisa R. A1 - Slaney, Claire A1 - Smoller, Jordan W. A1 - Squassina, Alessio A1 - Stamm, Thomas A1 - Steele, Jo A1 - Stopkova, Pavla A1 - Tighe, Sarah K. A1 - Tortorella, Alfonso A1 - Turecki, Gustavo A1 - Wray, Naomi R. A1 - Wright, Adam A1 - Zandi, Peter P. A1 - Zilles, David A1 - Bauer, Michael A1 - Rietschel, Marcella A1 - McMahon, Francis J. A1 - Schulze, Thomas G. A1 - Alda, Martin T1 - Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report JF - PLoS ONE N2 - 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. KW - age KW - observer agreement KW - prophylactic lithium KW - mapping susceptibility genes KW - mood disorders KW - onset KW - association KW - reliability KW - morality KW - illness Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130938 VL - 8 IS - 6 ER - TY - THES A1 - Niederlechner, Stefanie T1 - Assessment of the basic molecular mechanisms underlying L-glutamine's cytoprotective effects after intestinal injury T1 - Untersuchung und Auswertung der molekularen Mechanismen, die L-Glutamin's protektivem Zellmechanismus nach Intestinaler Verletzung zugrunde liegen N2 - 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. N2 - Kritische Erkrankungen wie Sepsis, Schock und entzündliche Darmerkrankungen sind eine der häufigsten Todesursachen in den Vereinigten Staaten und dem Rest der Welt. Von großer Bedeutung sind deshalb Studien, die darauf abzielen, neue therapeutische Ansätze zu finden, die Gewebe und Zellen vor Verletzungen schützen und Entzündungen verhindern. Im letzten Jahrzehnt hat sich herausgestellt, dass Glutamin Schutz gegen die pathophysiologischen und pathobiochemischen Entgleisungen während solcher Erkrankungen vermitteln kann. Trotzdem ist es bisher nur sehr unvollständig gelungen, die zugrundeliegenden molekularen Mechanismen, die für diese zellulären Schutzfunktionen von Glutamin verantwortlich sind, aufzuklären. In diesem Zusammenhang gab es erste Hinweise darauf, dass die Stabilisierung von extrazellulären Matrixproteinen und die Aktivierung der Signalwege extrazellulärer Matrixproteinrezeptoren eine wichtige Rolle spielen könnten. Hierauf basierend habe ich die Hypothesen aufgestellt, dass die Expression von extrazellulären Matrixproteingehalten und von epidermalen Wachstumsfaktorrezeptoren (EGFR), sowie die Aktivierung von Integrin- und EGFR-Signalwegen Schlüsselrollen in den protektiven Mechanismen von Glutamin spielen. Meine Arbeiten zeigten anhand von Western Blots und durch den Einsatz von Silencing RNA (gegen Fibronektin, Netrin-1, EGFR und deren Negativkontrollen), dass Glutamin extrazelluläre Matrixproteingehalte, wie Fibronektin und Netrin-1, und EGFR-Levels vor Hitzestress in Darmepithelzellen bewahrt, wodurch Apoptose verhindert wird. Außerdem konnte ich mit Hilfe des selektiven Inhibitors GRGDSP, seiner Negativkontrolle GRGESP und des Src-Kinase-Inhibitors PP2 nachweisen, dass auch die Aktivierung von Fibronektin-Integrin-Signalwegen und von Src-Kinasen an den Schutzmechanismen von Glutamin im Darm beteiligt sind. Wie mit Hilfe des spezifischen EGFR-Tyrosinkinase-Inhibitors AG1478 nachgewiesen werden konnte, trifft dies auch für die EGFR-Signalwege zu. Zusätzlich zu GRGDSP und AG1478 wurden auch die ERK1/2-Kinase-Inhibitoren PD98059 und UO126 und der p38MAPK-Inhibitor verwendet, um zu zeigen, dass Glutamin Darmepithelzellen durch die Aktivität von Fibronektin-Integrin- und EGFR-Signalwegen vor Hitzestress schützt, indem es EKR1/2 phosphoryliert und p38MAPK dephosphoryliert. PI-3K/Akt/Hsp70-Signalwege werden ebenfalls von Glutamin aktiviert, jedoch unabhängig von Fibronektin-Integrin- und EGFR-Signalwegen. Dies konnte anhand von Western Blot Experimenten und mit Hilfe von LY294002 (PI-3K-Inhibitor), GRGDSP und AG1478 bewiesen werden. Glutamin scheint die gleichen Signalwege sowohl mit Hilfe von Integrinen als auch von EGFR zu beeinflussen, um so den Zelltod in Darmepithelzellen nach Hitzestress zu verhindern. Desweiteren konnte gezeigt werden, dass Glutamin die Erhaltung von Fibronektinkonzentrationen nach Hitzestress durch den PI-3K-Signalweg reguliert. Ob Glutamin den PI-3K-Signalweg parallel zu den Integrin- und EGFR-Signalwegen aktiviert oder ob der von Glutamin ausgelöste PI-3K-Signalweg die Integrin- und EGFR-Signalwege steuert, muss noch weiter untersucht werden. Experimente mit PD98059 und GRGDSP zeigten, dass ERK1/2 in der Gegenwart von Glutamin den Transkriptionsfaktor HSF-1 durch den Fibronektin-Integrin-Signalweg nach Hitzestress transaktiviert. Dadurch nimmt die Expression von Hsp70, welches den Zelltod nach Hitzeschock verhindert, zu. Mit Hilfe der Fluoreszenzmikroskopie konnte gezeigt werden, dass Hitzestress und Glutamin die Zellgröße und die Aktinmorphologie von Darmepithelzellen durch Fibronektin-Integrin-Signalwege steuern können. Außerdem ergaben Versuche mit GRGDSP und GRGESP, dass Glutamin unabhänging von seinen intrazellulären Konzentrationen das Überleben von Darmepithelzellen durch die Aktivierung von Fibronektin-Integrin-Signalwegen erhöhen kann. Hierbei wurden die Glutaminkonzentrationen mit LC-MS/MS gemessen. Die Versuche im Rahmen meiner Dissertation konnten neue und potentiell klinisch relevante Signalwege der molekularen Schutzmechanismen von Glutamin aufdecken. Diese Ergebnisse können die Grundlage für translationale Studien darstellen, die weiter untersuchen, ob die Überlebensrate von Patienten mit entzündlichen Darmerkrankungen durch die Behandlung mit Glutamin oder durch gezielte Beeinflussung der hier untersuchten molekularen Mechanismen verbessert werden kann. KW - Glutamin KW - Integrine KW - Epidermaler Wachstumsfaktor-Rezeptor KW - Apoptosis KW - glutamine KW - integrins KW - epidermal growth factor receptor KW - cell death KW - cell survival KW - EGFR KW - ERK1/2 KW - p38MAPK KW - PI3-K KW - Akt KW - Apoptose Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-77399 ER -