TY - JOUR A1 - Conrad, Christopher A1 - Schönbrodt-Stitt, Sarah A1 - Löw, Fabian A1 - Sorokin, Denis A1 - Paeth, Heiko T1 - Cropping Intensity in the Aral Sea Basin and Its Dependency from the Runoff Formation 2000–2012 JF - Remote Sensing N2 - This study is aimed at a better understanding of how upstream runoff formation affected the cropping intensity (CI: number of harvests) in the Aral Sea Basin (ASB) between 2000 and 2012. MODIS 250 m NDVI time series and knowledge-based pixel masking that included settlement layers and topography features enabled to map the irrigated cropland extent (iCE). Random forest models supported the classification of cropland vegetation phenology (CVP: winter/summer crops, double cropping, etc.). CI and the percentage of fallow cropland (PF) were derived from CVP. Spearman’s rho was selected for assessing the statistical relation of CI and PF to runoff formation in the Amu Darya and Syr Darya catchments per hydrological year. Validation in 12 reference sites using multi-annual Landsat-7 ETM+ images revealed an average overall accuracy of 0.85 for the iCE maps. MODIS maps overestimated that based on Landsat by an average factor of ~1.15 (MODIS iCE/Landsat iCE). Exceptional overestimations occurred in case of inaccurate settlement layers. The CVP and CI maps achieved overall accuracies of 0.91 and 0.96, respectively. The Amu Darya catchment disclosed significant positive (negative) relations between upstream runoff with CI (PF) and a high pressure on the river water resources in 2000–2012. Along the Syr Darya, reduced dependencies could be observed, which is potentially linked to the high number of water constructions in that catchment. Intensified double cropping after drought years occurred in Uzbekistan. However, a 10 km × 10 km grid of Spearman’s rho (CI and PF vs. upstream runoff) emphasized locations at different CI levels that are directly affected by runoff fluctuations in both river systems. The resulting maps may thus be supportive on the way to achieve long-term sustainability of crop production and to simultaneously protect the severely threatened environment in the ASB. The gained knowledge can be further used for investigating climatic impacts of irrigation in the region. KW - irrigated cropland extent KW - cropland vegetation phenology KW - land and water management KW - modis KW - landsat central asia Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147701 VL - 8 IS - 630 ER - TY - JOUR A1 - Colvill, Emma A1 - Booth, Jeremy A1 - Nill, Simeon A1 - Fast, Martin A1 - Bedford, James A1 - Oelfke, Uwe A1 - Nakamura, Mitsuhiro A1 - Poulsen, Per A1 - Worm, Esben A1 - Hansen, Rune A1 - Ravkilde, Thomas A1 - Rydhög, Jonas Scherman A1 - Pommer, Tobias A1 - af Rosenschold, Per Munck A1 - Lang, Stephanie A1 - Guckenberger, Matthias A1 - Groh, Christian A1 - Herrmann, Christian A1 - Verellen, Dirk A1 - Poels, Kenneth A1 - Wang, Lei A1 - Hadsell, Michael A1 - Sothmann, Thilo A1 - Blanck, Oliver A1 - Keall, Paul T1 - A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy: a multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking JF - Radiotherapy and Oncology N2 - Purpose: A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion. Methods and materials: Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for gamma-tests recorded. Results: For all lung traces all measurement sets show improved dose accuracy with a mean 2%/2 mm gamma-fail rate of 1.6% with adaptation and 15.2% without adaptation (p < 0.001). For all prostate the mean 2%/2 mm gamma-fail rate was 1.4% with adaptation and 17.3% without adaptation (p < 0.001). The difference between the four systems was small with an average 2%/2 mm gamma-fail rate of <3% for all systems with adaptation for lung and prostate. Conclusions: The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods. KW - Robotic tracking KW - Gimbaled tracking KW - MLC tracking KW - Couch tracking KW - Organ motion Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189605 VL - 119 IS - 1 ER - TY - JOUR A1 - Clauss, Kersten A1 - Yan, Huimin A1 - Kuenzer, Claudia T1 - Mapping Paddy Rice in China in 2002, 2005, 2010 and 2014 with MODIS Time Series JF - Remote Sensing N2 - Rice is an important food crop and a large producer of green-house relevant methane. Accurate and timely maps of paddy fields are most important in the context of food security and greenhouse gas emission modelling. During their life-cycle, rice plants undergo a phenological development that influences their interaction with waves in the visible light and infrared spectrum. Rice growth has a distinctive signature in time series of remotely-sensed data. We used time series of MODIS (Moderate Resolution Imaging Spectroradiometer) products MOD13Q1 and MYD13Q1 and a one-class support vector machine to detect these signatures and classify paddy rice areas in continental China. Based on these classifications, we present a novel product for continental China that shows rice areas for the years 2002, 2005, 2010 and 2014 at 250-m resolution. Our classification has an overall accuracy of 0.90 and a kappa coefficient of 0.77 compared to our own reference dataset for 2014 and correlates highly with rice area statistics from China’s Statistical Yearbooks (R2 of 0.92 for 2010, 0.92 for 2005 and 0.90 for 2002). Moderate resolution time series analysis allows accurate and timely mapping of rice paddies over large areas with diverse cropping schemes. KW - agriculture KW - rice KW - China KW - MODIS KW - time series KW - SVM KW - OCSVM KW - change detection Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180557 VL - 8 IS - 5 ER - TY - JOUR A1 - Citron, Francesca M. M. A1 - Abugaber, David A1 - Herbert, Cornelia T1 - Approach and Withdrawal Tendencies during Written Word Processing: Effects of Task, Emotional Valence, and Emotional Arousal JF - frontiers in Psychology N2 - The affective dimensions of emotional valence and emotional arousal affect processing of verbal and pictorial stimuli. Traditional emotional theories assume a linear relationship between these dimensions, with valence determining the direction of a behavior (approach vs. withdrawal) and arousal its intensity or strength. In contrast, according to the valence-arousal conflict theory, both dimensions are interactively related: positive valence and low arousal (PL) are associated with an implicit tendency to approach a stimulus, whereas negative valence and high arousal (NH) are associated with withdrawal. Hence, positive, high-arousal (PH) and negative, low-arousal (NL) stimuli elicit conflicting action tendencies. By extending previous research that used several tasks and methods, the present study investigated whether and how emotional valence and arousal affect subjective approach vs. withdrawal tendencies toward emotional words during two novel tasks. In Study 1, participants had to decide whether they would approach or withdraw from concepts expressed by written words. In Studies 2 and 3 participants had to respond to each word by pressing one of two keys labeled with an arrow pointing upward or downward. Across experiments, positive and negative words, high or low in arousal, were presented. In Study 1 (explicit task), in line with the valence-arousal conflict theory, PH and NL words were responded to more slowly than PL and NH words. In addition, participants decided to approach positive words more often than negative words. In Studies 2 and 3, participants responded faster to positive than negative words, irrespective of their level of arousal. Furthermore, positive words were significantly more often associated with “up” responses than negative words, thus supporting the existence of implicit associations between stimulus valence and response coding (positive is up and negative is down). Hence, in contexts in which participants' spontaneous responses are based on implicit associations between stimulus valence and response, there is no influence of arousal. In line with the valence-arousal conflict theory, arousal seems to affect participants' approach-withdrawal tendencies only when such tendencies are made explicit by the task, and a minimal degree of processing depth is required. KW - approach KW - withdrawal KW - valence KW - arousal KW - emotion KW - words KW - polarity effects Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165318 VL - 6 IS - 1935 ER - TY - JOUR A1 - Cicova, Zdenka A1 - Dejung, Mario A1 - Skalicky, Tomas A1 - Eisenhuth, Nicole A1 - Hanselmann, Steffen A1 - Morriswood, Brooke A1 - Figueiredo, Luisa M. A1 - Butter, Falk A1 - Janzen, Christian J. T1 - Two flagellar BAR domain proteins in Trypanosoma brucei with stage-specific regulation JF - Scientific Reports N2 - Trypanosomes are masters of adaptation to different host environments during their complex life cycle. Large-scale proteomic approaches provide information on changes at the cellular level, and in a systematic way. However, detailed work on single components is necessary to understand the adaptation mechanisms on a molecular level. Here, we have performed a detailed characterization of a bloodstream form (BSF) stage-specific putative flagellar host adaptation factor Tb927.11.2400, identified previously in a SILAC-based comparative proteome study. Tb927.11.2400 shares 38% amino acid identity with TbFlabarin (Tb927.11.2410), a procyclic form (PCF) stage-specific flagellar BAR domain protein. We named Tb927.11.2400 TbFlabarin-like (TbFlabarinL), and demonstrate that it originates from a gene duplication event, which occurred in the African trypanosomes. TbFlabarinL is not essential for the growth of the parasites under cell culture conditions and it is dispensable for developmental differentiation from BSF to the PCF in vitro. We generated TbFlabarinL-specific antibodies, and showed that it localizes in the flagellum. Co-immunoprecipitation experiments together with a biochemical cell fractionation suggest a dual association of TbFlabarinL with the flagellar membrane and the components of the paraflagellar rod. KW - parasite biology KW - protein translocation KW - Trypanosoma brucei Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181021 VL - 6 ER - TY - JOUR A1 - Chumak, Tetyana A1 - Rüttiger, Lukas A1 - Lee, Sze Chim A1 - Campanelli, Dario A1 - Zuccotti, Annalisa A1 - Singer, Wibke A1 - Popelář, Jiří A1 - Gutsche, Katja A1 - Geisler, Hyun-Soon A1 - Schraven, Sebastian Philipp A1 - Jaumann, Mirko A1 - Panford-Walsh, Rama A1 - Hu, Jing A1 - Schimmang, Thomas A1 - Zimmermann, Ulrike A1 - Syka, Josef A1 - Knipper, Marlies T1 - BDNF in Lower Brain Parts Modifies Auditory Fiber Activity to Gain Fidelity but Increases the Risk for Generation of Central Noise After Injury JF - Molecular Neurobiology N2 - For all sensory organs, the establishment of spatial and temporal cortical resolution is assumed to be initiated by the first sensory experience and a BDNF-dependent increase in intracortical inhibition. To address the potential of cortical BDNF for sound processing, we used mice with a conditional deletion of BDNF in which Cre expression was under the control of the Pax2 or TrkC promoter. BDNF deletion profiles between these mice differ in the organ of Corti (BDNF \(^{Pax2}\) -KO) versus the auditory cortex and hippocampus (BDNF \(^{TrkC}\) -KO). We demonstrate that BDNF \(^{Pax2}\) -KO but not BDNF \(^{TrkC}\) -KO mice exhibit reduced sound-evoked suprathreshold ABR waves at the level of the auditory nerve (wave I) and inferior colliculus (IC) (wave IV), indicating that BDNF in lower brain regions but not in the auditory cortex improves sound sensitivity during hearing onset. Extracellular recording of IC neurons of BDNF \(^{Pax2}\) mutant mice revealed that the reduced sensitivity of auditory fibers in these mice went hand in hand with elevated thresholds, reduced dynamic range, prolonged latency, and increased inhibitory strength in IC neurons. Reduced parvalbumin-positive contacts were found in the ascending auditory circuit, including the auditory cortex and hippocampus of BDNF \(^{Pax2}\) -KO, but not of BDNF \(^{TrkC}\) -KO mice. Also, BDNF \(^{Pax2}\) -WT but not BDNF \(^{Pax2}\) -KO mice did lose basal inhibitory strength in IC neurons after acoustic trauma. These findings suggest that BDNF in the lower parts of the auditory system drives auditory fidelity along the entire ascending pathway up to the cortex by increasing inhibitory strength in behaviorally relevant frequency regions. Fidelity and inhibitory strength can be lost following auditory nerve injury leading to diminished sensory outcome and increased central noise. KW - Inner hair cell KW - Neurotropathic Factor KW - Hearing-loss KW - Alzheimers-disease KW - low-threshold fibers KW - cochlear nucleus neurons KW - Frequency-response areas KW - Inferior colliculus KW - Environmental enrichment KW - Synaptic plasticity KW - Cortical plasticity KW - BDNF KW - Central hyperactivity KW - High-spontaneous rate KW - Homeostatic plasticity KW - Sound detection threshold Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187341 VL - 53 IS - 8 ER - TY - JOUR A1 - Chubanov, Vladimir A1 - Ferioli, Silvia A1 - Wisnowsky, Annika A1 - Simmons, David G. A1 - Leitzinger, Christin A1 - Einer, Claudia A1 - Jonas, Wenke A1 - Shymkiv, Yuriy A1 - Gudermann, Thomas A1 - Bartsch, Harald A1 - Braun, Attila A1 - Akdogan, Banu A1 - Mittermeier, Lorenz A1 - Sytik, Ludmila A1 - Torben, Friedrich A1 - Jurinovic, Vindi A1 - van der Vorst, Emiel P. C. A1 - Weber, Christian A1 - Yildirim, Önder A. A1 - Sotlar, Karl A1 - Schürmann, Annette A1 - Zierler, Susanna A1 - Zischka, Hans A1 - Ryazanov, Alexey G. T1 - Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival JF - eLife N2 - Mg2+ regulates many physiological processes and signalling pathways. However, little is known about the mechanisms underlying the organismal balance of Mg2+. Capitalizing on a set of newly generated mouse models, we provide an integrated mechanistic model of the regulation of organismal Mg2+ balance during prenatal development and in adult mice by the ion channel TRPM6. We show that TRPM6 activity in the placenta and yolk sac is essential for embryonic development. In adult mice, TRPM6 is required in the intestine to maintain organismal Mg2+ balance, but is dispensable in the kidney. Trpm6 inactivation in adult mice leads to a shortened lifespan, growth deficit and metabolic alterations indicative of impaired energy balance. Dietary Mg2+ supplementation not only rescues all phenotypes displayed by Trpm6-deficient adult mice, but also may extend the lifespan of wildtype mice. Hence, maintenance of organismal Mg2+ balance by TRPM6 is crucial for prenatal development and survival to adulthood. KW - signalling pathways Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164987 VL - 5 ER - TY - JOUR A1 - Chopra, Martin A1 - Biehl, Marlene A1 - Steinfatt, Tim A1 - Brandl, Andreas A1 - Kums, Juliane A1 - Amich, Jorge A1 - Vaeth, Martin A1 - Kuen, Janina A1 - Holtappels, Rafaela A1 - Podlech, Jürgen A1 - Mottok, Anja A1 - Kraus, Sabrina A1 - Jordán-Garotte, Ana-Laura A1 - Bäuerlein, Carina A. A1 - Brede, Christian A1 - Ribechini, Eliana A1 - Fick, Andrea A1 - Seher, Axel A1 - Polz, Johannes A1 - Ottmueller, Katja J. A1 - Baker, Jeannette A1 - Nishikii, Hidekazu A1 - Ritz, Miriam A1 - Mattenheimer, Katharina A1 - Schwinn, Stefanie A1 - Winter, Thorsten A1 - Schäfer, Viktoria A1 - Krappmann, Sven A1 - Einsele, Hermann A1 - Müller, Thomas D. A1 - Reddehase, Matthias J. A1 - Lutz, Manfred B. A1 - Männel, Daniela N. A1 - Berberich-Siebelt, Friederike A1 - Wajant, Harald A1 - Beilhack, Andreas T1 - Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion JF - Journal of Experimental Medicine N2 - Donor CD4\(^+\)Foxp3\(^+\) regulatory T cells (T reg cells) suppress graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HCT allo-HCT]). Current clinical study protocols rely on the ex vivo expansion of donor T reg cells and their infusion in high numbers. In this study, we present a novel strategy for inhibiting GvHD that is based on the in vivo expansion of recipient T reg cells before allo-HCT, exploiting the crucial role of tumor necrosis factor receptor 2 (TNFR2) in T reg cell biology. Expanding radiation-resistant host T reg cells in recipient mice using a mouse TNFR2-selective agonist before allo-HCT significantly prolonged survival and reduced GvHD severity in a TNFR2-and T reg cell-dependent manner. The beneficial effects of transplanted T cells against leukemia cells and infectious pathogens remained unaffected. A corresponding human TNFR2-specific agonist expanded human T reg cells in vitro. These observations indicate the potential of our strategy to protect allo-HCT patients from acute GvHD by expanding T reg cells via selective TNFR2 activation in vivo. KW - Tumor-necrosis-factor KW - Regulatory-cells KW - Bone marrow transplantantation KW - Graft-versus-leukemia KW - Rheumatoid arthritis KW - Autoimmune diseases KW - Factor receptor KW - Alpha therapy KW - Expression KW - Suppression Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187640 VL - 213 IS - 9 ER - TY - JOUR A1 - Chiorean, E. G. A1 - Von Hoff, D. D. A1 - Reni, M. A1 - Arena, F. P. A1 - Infante, J. R. A1 - Bathini, V. G. A1 - Wood, T. E. A1 - Mainwaring, P. N. A1 - Muldoon, R. T. A1 - Clingan, P. R. A1 - Kunzmann, V. A1 - Ramanathan, R. K. A1 - Tabernero, J. A1 - Goldstein, D. A1 - McGovern, D. A1 - Lu, B. A1 - Ko, A. T1 - CA19-9 decrease at 8 weeks as a predictor of overall survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic pancreatic cancer JF - Annals of Oncology N2 - Background A phase I/II study and subsequent phase III study (MPACT) reported significant correlations between CA19-9 decreases and prolonged overall survival (OS) with nab-paclitaxel plus gemcitabine (nab-P + Gem) treatment for metastatic pancreatic cancer (MPC). CA19-9 changes at week 8 and potential associations with efficacy were investigated as part of an exploratory analysis in the MPACT trial. Patients and methods Untreated patients with MPC (N = 861) received nab-P + Gem or Gem alone. CA19-9 was evaluated at baseline and every 8 weeks. Results Patients with baseline and week-8 CA19-9 measurements were analyzed (nab-P + Gem: 252; Gem: 202). In an analysis pooling the treatments, patients with any CA19-9 decline (80%) versus those without (20%) had improved OS (median 11.1 versus 8.0 months; P = 0.005). In the nab-P + Gem arm, patients with (n = 206) versus without (n = 46) any CA19-9 decrease at week 8 had a confirmed overall response rate (ORR) of 40% versus 13%, and a median OS of 13.2 versus 8.3 months (P = 0.001), respectively. In the Gem-alone arm, patients with (n = 159) versus without (n = 43) CA19-9 decrease at week 8 had a confirmed ORR of 15% versus 5%, and a median OS of 9.4 versus 7.1 months (P = 0.404), respectively. In the nab-P + Gem and Gem-alone arms, by week 8, 16% (40/252) and 6% (13/202) of patients, respectively, had an unconfirmed radiologic response (median OS 13.7 and 14.7 months, respectively), and 79% and 84% of patients, respectively, had stable disease (SD) (median OS 11.1 and 9 months, respectively). Patients with SD and any CA19-9 decrease (158/199 and 133/170) had a median OS of 13.2 and 9.4 months, respectively. Conclusion This analysis demonstrated that, in patients with MPC, any CA19-9 decrease at week 8 can be an early marker for chemotherapy efficacy, including in those patients with SD. CA19-9 decrease identified more patients with survival benefit than radiologic response by week 8. KW - CA19-9 KW - pancreatic cancer KW - chemotherapy KW - nab-paclitaxel KW - MPACT Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189659 VL - 27 IS - 4 ER - TY - JOUR A1 - Chillo, Omary A1 - Kleinert, Eike Christian A1 - Lautz, Thomas A1 - Lasch, Manuel A1 - Pagel, Judith-Irina A1 - Heun, Yvonn A1 - Troidl, Kerstin A1 - Fischer, Silvia A1 - Caballero-Martinez, Amelia A1 - Mauer, Annika A1 - Kurz, Angela R. M. A1 - Assmann, Gerald A1 - Rehberg, Markus A1 - Kanse, Sandip M. A1 - Nieswandt, Bernhard A1 - Walzog, Barbara A1 - Reichel, Christoph A. A1 - Mannell, Hanna A1 - Preissner, Klaus T. A1 - Deindl, Elisabeth T1 - Perivascular Mast Cells Govern Shear Stress-Induced Arteriogenesis by Orchestrating Leukocyte Function JF - Cell Reports N2 - The body has the capacity to compensate for an occluded artery by creating a natural bypass upon increased fluid shear stress. How this mechanical force is translated into collateral artery growth (arteriogenesis) is unresolved. We show that extravasation of neutrophils mediated by the platelet receptor GPIbα and uPA results in Nox2-derived reactive oxygen radicals, which activate perivascular mast cells. These c-kit+/CXCR-4+ cells stimulate arteriogenesis by recruiting additional neutrophils as well as growth-promoting monocytes and T cells. Additionally, mast cells may directly contribute to vascular remodeling and vascular cell proliferation through increased MMP activity and by supplying growth-promoting factors. Boosting mast cell recruitment and activation effectively promotes arteriogenesis, thereby protecting tissue from severe ischemic damage. We thus find that perivascular mast cells are central regulators of shear stress-induced arteriogenesis by orchestrating leukocyte function and growth factor/cytokine release, thus providing a therapeutic target for treatment of vascular occlusive diseases. KW - Mast cells Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164800 VL - 16 IS - 8 ER - TY - JOUR A1 - Chenari, Hossein Mahmoudi A1 - Seibel, Christoph A1 - Hauschild, Dirk A1 - Reinert, Friedrich A1 - Abdollahian, Hossein T1 - Titanium Dioxide Nanoparticles: Synthesis, X-Ray Line Analysis and Chemical Composition Study JF - Materials Research N2 - TiO2 nanoparticleshave been synthesized by the sol-gel method using titanium alkoxide and isopropanolas a precursor. The structural properties and chemical composition of the TiO2 nanoparticles were studied usingX-ray diffraction, scanning electron microscopy, and X-ray photoelectron spectroscopy.The X-ray powder diffraction pattern confirms that the particles are mainly composed of the anatase phase with the preferential orientation along [101] direction. The physical parameters such as strain, stress and energy density were investigated from the Williamson- Hall (W-H) plot assuming a uniform deformation model (UDM), and uniform deformation energy density model (UDEDM). The W-H analysis shows an anisotropic nature of the strain in nanopowders. The scanning electron microscopy image shows clear TiO2 nanoparticles with particle sizes varying from 60 to 80nm. The results of mean particle size of TiO2 nanoparticles show an inter correlation with the W-H analysis and SEM results. Our X-ray photoelectron spectroscopy spectra show that nearly a complete amount of titanium has reacted to TiO2 KW - TiO\(_2\) KW - Nanoparticles KW - X-ray analysis KW - SEM KW - XPS Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165807 VL - 19 IS - 6 ER - TY - JOUR A1 - Chen, Jiangtian A1 - Reiher, Wencke A1 - Hermann-Luibl, Christiane A1 - Sellami, Azza A1 - Cognigni, Paola A1 - Kondo, Shu A1 - Helfrich-Förster, Charlotte A1 - Veenstra, Jan A. A1 - Wegener, Christian T1 - Allatostatin A Signalling in Drosophila Regulates Feeding and Sleep and Is Modulated by PDF JF - PLoS Genetics N2 - Feeding and sleep are fundamental behaviours with significant interconnections and cross-modulations. The circadian system and peptidergic signals are important components of this modulation, but still little is known about the mechanisms and networks by which they interact to regulate feeding and sleep. We show that specific thermogenetic activation of peptidergic Allatostatin A (AstA)-expressing PLP neurons and enteroendocrine cells reduces feeding and promotes sleep in the fruit fly Drosophila. The effects of AstA cell activation are mediated by AstA peptides with receptors homolog to galanin receptors subserving similar and apparently conserved functions in vertebrates. We further identify the PLP neurons as a downstream target of the neuropeptide pigment-dispersing factor (PDF), an output factor of the circadian clock. PLP neurons are contacted by PDF-expressing clock neurons, and express a functional PDF receptor demonstrated by cAMP imaging. Silencing of AstA signalling and continuous input to AstA cells by tethered PDF changes the sleep/activity ratio in opposite directions but does not affect rhythmicity. Taken together, our results suggest that pleiotropic AstA signalling by a distinct neuronal and enteroendocrine AstA cell subset adapts the fly to a digestive energy-saving state which can be modulated by PDF. KW - neurons KW - neuroimaging KW - circadian rhythms KW - food consumption KW - sleep KW - biological locomotion KW - Drosophila melanogaster KW - signal peptides Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-178170 VL - 12 IS - 9 ER - TY - JOUR A1 - Chagtai, Tasnim A1 - Zill, Christina A1 - Dainese, Linda A1 - Wegert, Jenny A1 - Savola, Suvi A1 - Popov, Sergey A1 - Mifsud, William A1 - Vujanic, Gordan A1 - Sebire, Neil A1 - Le Bouc, Yves A1 - Ambros, Peter F. A1 - Kager, Leo A1 - O`Sullivan, Maureen J. A1 - Blaise, Annick A1 - Bergeron, Christophe A1 - Holmquist Mengelbier, Linda A1 - Gisselsson, David A1 - Kool, Marcel A1 - Tytgat, Godelieve A.M. A1 - van den Heuvel-Eibrink, Marry M. A1 - Graf, Norbert A1 - van Tinteren, Harm A1 - Coulomb, Aurore A1 - Gessler, Manfred A1 - Williams, Richard Dafydd A1 - Pritchard-Jones, Kathy T1 - Gain of 1q As a Prognostic Biomarker in Wilms Tumors (WTs) Treated With Preoperative Chemotherapy in the International Society of Paediatric Oncology (SIOP) WT 2001 Trial: a SIOP Renal Tumours Biology Consortium Study JF - Journal of Clinical Oncology N2 - Purpose Wilms tumor (WT) is the most common pediatric renal tumor. Treatment planning under International Society of Paediatric Oncology (SIOP) protocols is based on staging and histologic assessment of response to preoperative chemotherapy. Despite high overall survival (OS), many relapses occur in patients without specific risk factors, and many successfully treated patients are exposed to treatments with significant risks of late effects. To investigate whether molecular biomarkers could improve risk stratification, we assessed 1q status and other potential copy number biomarkers in a large WT series. Materials and Methods WT nephrectomy samples from 586 SIOP WT 2001 patients were analyzed using a multiplex ligation-dependent probe amplification (MLPA) assay that measured the copy number of 1q and other regions of interest. Results One hundred sixty-seven (28%) of 586 WTs had 1q gain. Five-year event-free survival (EFS) was 75.0% in patients with 1q gain (95% CI, 68.5% to 82.0%) and 88.2% in patients without gain (95% CI, 85.0% to 91.4%). OS was 88.4% with gain (95% CI, 83.5% to 93.6%) and 94.4% without gain (95% CI, 92.1% to 96.7%). In univariable analysis, 1q gain was associated with poorer EFS (P<.001; hazard ratio, 2.33) and OS (P=.01; hazard ratio, 2.16). The association of 1q gain with poorer EFS retained significance in multivariable analysis adjusted for 1p and 16q loss, sex, stage, age, and histologic risk group. Gain of 1q remained associated with poorer EFS in tumor subsets limited to either intermediate-risk localized disease or nonanaplastic localized disease. Other notable aberrations associated with poorer EFS included MYCN gain and TP53 loss. Conclusion Gain of 1q is a potentially valuable prognostic biomarker in WT, in addition to histologic response to preoperative chemotherapy and tumor stage. KW - Poor-prognosis KW - Mutations KW - Gene KW - Drosha KW - MYCN KW - Mechanisms KW - Reveals KW - Event KW - Relapse KW - Locus Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187478 VL - 34 IS - 26 ER - TY - JOUR A1 - Ceyman, Harald A1 - Rosspeintner, Arnulf A1 - Schreck, Maximilian H. A1 - Mützel, Carina A1 - Stoy, Andreas A1 - Vauthey, Eric A1 - Lambert, Christoph T1 - Cooperative enhancement versus additivity of two-photon-absorption cross sections in linear and branched squaraine superchromophores JF - Physical Chemistry Chemical Physics N2 - The linear and nonlinear optical properties of a series of oligomeric squaraine dyes were investigated by one-photon absorption spectroscopy (1PA) and two-photon absorption (2PA) induced fluorescence spectroscopy. The superchromophores are based on two indolenine squaraine dyes with transoid (SQA) and cisoid configuration (SQB). Using these monomers, linear dimers and trimers as well as star-shaped trimers and hexamers with benzene or triphenylamine cores were synthesised and investigated. The red-shifted and intensified 1PA spectra of all superchromophores could well be explained by exciton coupling theory. In the linear chromophore arrangements we also found superradiance of fluorescence but not in the branched systems. Furthermore, the 2PA showed enhanced cross sections for the linear oligomers but only additivity for the branched systems. This emphasizes that the enhancement of the 2PA cross section in the linear arrangements is probably caused by orbital interactions of higher excited configurations. KW - 2-photon absorption KW - Vibronic contributions KW - One-photon KW - Molecules KW - Intensity KW - Multibranched structures KW - Optical properties KW - Dyes KW - Chromophores KW - Design Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188299 VL - 18 IS - 24 ER - TY - JOUR A1 - Cate, Marie-Sophie A1 - Gajendra, Sangeetha A1 - Alsbury, Samantha A1 - Raabe, Thomas A1 - Tear, Guy A1 - Mitchell, Kevin J. T1 - Mushroom body defect is required in parallel to Netrin for midline axon guidance in Drosophila JF - Development N2 - The outgrowth of many neurons within the central nervous system is initially directed towards or away from the cells lying at the midline. Recent genetic evidence suggests that a simple model of differential sensitivity to the conserved Netrin attractants and Slit repellents is insufficient to explain the guidance of all axons at the midline. In the Drosophila embryonic ventral nerve cord, many axons still cross the midline in the absence of the Netrin genes (NetA and NetB) or their receptor frazzled. Here we show that mutation of mushroom body defect (mud) dramatically enhances the phenotype of Netrin or frazzled mutants, resulting in many more axons failing to cross the midline, although mutations in mud alone have little effect. This suggests that mud, which encodes a microtubule-binding coiled-coil protein homologous to NuMA and LIN-5, is an essential component of a Netrin-independent pathway that acts in parallel to promote midline crossing. We demonstrate that this novel role of Mud in axon guidance is independent of its previously described role in neural precursor development. These studies identify a parallel pathway controlling midline guidance in Drosophila and highlight a novel role for Mud potentially acting downstream of Frizzled to aid axon guidance. KW - Drosophila KW - Axon guidance KW - Midline KW - Mud KW - NuMA KW - LIN-5 KW - Netrin Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189770 VL - 143 IS - 6 ER - TY - JOUR A1 - Canessa, Andrea A1 - Pozzi, Nicolò G. A1 - Arnulfo, Gabriele A1 - Brumberg, Joachim A1 - Reich, Martin M. A1 - Pezzoli, Gianni A1 - Ghilardi, Maria F. A1 - Matthies, Cordula A1 - Steigerwald, Frank A1 - Volkmann, Jens A1 - Isaias, Ioannis U. T1 - Striatal Dopaminergic Innervation Regulates Subthalamic Beta-Oscillations and Cortical-Subcortical Coupling during Movements: Preliminary Evidence in Subjects with Parkinson's Disease JF - Frontiers in Human Neuroscience N2 - Activation of the basal ganglia has been shown during the preparation and execution of movement. However, the functional interaction of cortical and subcortical brain areas during movement and the relative contribution of dopaminergic striatal innervation remains unclear. We recorded local field potential (LFP) activity from the subthalamic nucleus (STN) and high-density electroencephalography (EEG) signals in four patients with Parkinson’s disease (PD) off dopaminergic medication during a multi-joint motor task performed with their dominant and non-dominant hand. Recordings were performed by means of a fully-implantable deep brain stimulation (DBS) device at 4 months after surgery. Three patients also performed a single-photon computed tomography (SPECT) with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT) to assess striatal dopaminergic innervation. Unilateral movement execution led to event-related desynchronization (ERD) followed by a rebound after movement termination event-related synchronization (ERS) of oscillatory beta activity in the STN and primary sensorimotor cortex of both hemispheres. Dopamine deficiency directly influenced movement-related beta-modulation, with greater beta-suppression in the most dopamine-depleted hemisphere for both ipsi- and contralateral hand movements. Cortical-subcortical, but not interhemispheric subcortical coherencies were modulated by movement and influenced by striatal dopaminergic innervation, being stronger in the most dopamine-depleted hemisphere. The data are consistent with a role of dopamine in shielding subcortical structures from an excessive cortical entrapment and cross-hemispheric coupling, thus allowing fine-tuning of movement. KW - beta oscillations KW - Parkinson’s disease KW - motor control KW - movement disorders KW - imaging KW - subthalamic nucleus KW - coherence analysis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164061 VL - 10 IS - 611 ER - TY - JOUR A1 - Canesi, Margherita A1 - Giordano, Rosaria A1 - Lazzari, Lorenza A1 - Isalberti, Maurizio A1 - Isaias, Ioannis Ugo A1 - Benti, Riccardo A1 - Rampini, Paolo A1 - Marotta, Giorgio A1 - Colombo, Aurora A1 - Cereda, Emanuele A1 - Dipaola, Mariangela A1 - Montemurro, Tiziana A1 - Vigano, Mariele A1 - Budelli, Silvia A1 - Montelatici, Elisa A1 - Lavazza, Cristiana A1 - Cortelezzi, Agostino A1 - Pezzoli, Gianni T1 - Finding a new therapeutic approach for no-option Parkinsonisms: mesenchymal stromal cells for progressive supranuclear palsy JF - Journal of Translational Medicine N2 - Background: The trophic, anti-apoptotic and regenerative effects of bone marrow mesenchymal stromal cells (MSC) may reduce neuronal cell loss in neurodegenerative disorders. Methods: We used MSC as a novel candidate therapeutic tool in a pilot phase-I study for patients affected by progressive supranuclear palsy (PSP), a rare, severe and no-option form of Parkinsonism. Five patients received the cells by infusion into the cerebral arteries. Effects were assessed using the best available motor function rating scales (UPDRS, Hoehn and Yahr, PSP rating scale), as well as neuropsychological assessments, gait analysis and brain imaging before and after cell administration. Results: One year after cell infusion, all treated patients were alive, except one, who died 9 months after the infusion for reasons not related to cell administration or to disease progression (accidental fall). In all treated patients motor function rating scales remained stable for at least six-months during the one-year follow-up. Conclusions: We have demonstrated for the first time that MSC administration is feasible in subjects with PSP. In these patients, in whom deterioration of motor function is invariably rapid, we recorded clinical stabilization for at least 6 months. These encouraging results pave the way to the next randomized, placebo-controlled phase-II study that will definitively provide information on the efficacy of this innovative approach. KW - Progressive supranuclear palsy KW - Mesenchymal stem/stromal cells KW - Cell therapy KW - Regenerative medicine Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165725 VL - 14 IS - 127 ER - TY - JOUR A1 - Będkowski, Janusz A1 - Majek, Karol A1 - Majek, Piotr A1 - Musialik, Paweł A1 - Pełka, Michał A1 - Nüchter, Andreas T1 - Intelligent mobile system for improving spatial design support and security inside buildings JF - Mobile Networks and Applications N2 - This paper concerns the an intelligent mobile application for spatial design support and security domain. Mobility has two aspects in our research: The first one is the usage of mobile robots for 3D mapping of urban areas and for performing some specific tasks. The second mobility aspect is related with a novel Software as a Service system that allows access to robotic functionalities and data over the Ethernet, thus we demonstrate the use of the novel NVIDIA GRID technology allowing to virtualize the graphic processing unit. We introduce Complex Shape Histogram, a core component of our artificial intelligence engine, used for classifying 3D point clouds with a Support Vector Machine. We use Complex Shape Histograms also for loop closing detection in the simultaneous localization and mapping algorithm. Our intelligent mobile system is built on top of the Qualitative Spatio-Temporal Representation and Reasoning framework. This framework defines an ontology and a semantic model, which are used for building the intelligent mobile user interfaces. We show experiments demonstrating advantages of our approach. In addition, we test our prototypes in the field after the end-user case studies demonstrating a relevant contribution for future intelligent mobile systems that merge mobile robots with novel data centers. KW - Intelligent mobile system KW - 3D object recognition KW - Qualitative representation and reasoning KW - 3D mapping Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189597 VL - 21 IS - 2 ER - TY - JOUR A1 - Böttcher, S. A1 - Prifert, C. A1 - Weißbrich, B. A1 - Adams, O. A1 - Aldabbagh, S. A1 - Eis-Hübinger, A. M. A1 - Diedrich, S. T1 - Detection of enterovirus D68 in patients hospitalised in three tertiary university hospitals in Germany, 2013 to 2014 JF - Eurosurveillance N2 - Enterovirus D68 (EV-D68) has been recognised as a worldwide emerging pathogen associated with severe respiratory symptoms since 2009. We here report EV-D68 detection in hospitalised patients with acute respiratory infection admitted to three tertiary hospitals in Germany between January 2013 and December 2014. From a total of 14,838 respiratory samples obtained during the study period, 246 (1.7%) tested enterovirus-positive and, among these, 39 (15.9%) were identified as EV-D68. Infection was observed in children and teenagers (0–19 years; n=31), the majority (n=22) being under five years-old, as well as in adults > 50 years of age (n=8). No significant difference in prevalence was observed between the 2013 and 2014 seasons. Phylogenetic analyses based on viral protein 1 (VP1) sequences showed co-circulation of different EV-D68 lineages in Germany. Sequence data encompassing the entire capsid region of the genome were analysed to gain information on amino acid changes possibly relevant for immunogenicity and revealed mutations in two recently described pleconaril binding sites. KW - Enterovirus Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165068 VL - 21 IS - 19 ER - TY - JOUR A1 - Böhm, Jennifer A1 - Scherzer, Sönke A1 - Krol, Elzbieta A1 - Kreuzer, Ines A1 - von Meyer, Katharina A1 - Lorey, Christian A1 - Mueller, Thomas D. A1 - Shabala, Lana A1 - Monte, Isabel A1 - Solano, Roberto A1 - Al-Rasheid, Khaled A. S. A1 - Rennenberg, Heinz A1 - Shabala, Sergey A1 - Neher, Erwin A1 - Hedrich, Rainer T1 - The Venus flytrap Dionaea muscipula counts prey-induced action potentials to induce sodium uptake JF - Current Biology N2 - Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na\(^+\)-rich animal and nutrition for the plant. KW - jasmonic acid biosynthesis KW - gene expression KW - signal transduction KW - transporters KW - Arabidopsis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190870 VL - 26 IS - 3 ER - TY - JOUR A1 - Böhm, Jennifer A1 - Scherzer, Sönke A1 - Krol, Elzbieta A1 - Kreuzer, Ines A1 - von Meyer, Katharina A1 - Lorey, Christian A1 - Mueller, Thomas D. A1 - Shabala, Lana A1 - Monte, Isabel A1 - Salano, Roberto A1 - Al-Rasheid, Khaled A. S. A1 - Rennenberg, Heinz A1 - Shabala, Sergey A1 - Neher, Erwin A1 - Hedrich, Rainer T1 - The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake JF - Current Biology N2 - Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na+-rich animal and nutrition for the plant. KW - Venusfliegenfalle KW - Dionaea muscipula Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128054 VL - 26 IS - 3 ER - TY - JOUR A1 - Böhm, J. A1 - Scherzer, S. A1 - Shabala, S. A1 - Krol, E. A1 - Neher, E. A1 - Mueller, T. D. A1 - Hedrich, R. T1 - Venus flytrap HKT1-type channel provides for prey sodium uptake into carnivorous plant without conflicting with electrical excitability JF - Molecular Plant N2 - The animal diet of the carnivorous Venus flytrap, Dionaea muscipula, contains a sodium load that enters the capture organ via an HKT1-type sodium channel, expressed in special epithelia cells on the inner trap lobe surface. DmHKT1 expression and sodium uptake activity is induced upon prey contact. Here, we analyzed the HKT1 properties required for prey sodium osmolyte management of carnivorous Dionaea. Analyses were based on homology modeling, generation of model-derived point mutants, and their functional testing in Xenopus oocytes. We showed that the wild-type HKT1 and its Na\(^+\)- and K\(^+\)-permeable mutants function as ion channels rather than K\(^+\) transporters driven by proton or sodium gradients. These structural and biophysical features of a high-capacity, Na\(^+\)-selective ion channel enable Dionaea glands to manage prey-derived sodium loads without confounding the action potential-based information management of the flytrap. KW - sodium channel KW - HKT1 KW - Dionaea muscipula KW - action potential KW - glands KW - sodium uptake Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189803 VL - 9 IS - 3 ER - TY - JOUR A1 - Buttmann, Mathias A1 - Seuffert, Linda A1 - Mäder, Uwe A1 - Toyka, Klaus V. T1 - Malignancies after mitoxantrone for multiple sclerosis: a retrospective cohort study JF - Neurology N2 - Objective: To assess the therapy-related risk of malignancies in mitoxantrone-treated patients with multiple sclerosis. Methods: This retrospective observational cohort study included all mitoxantrone-treated patients with multiple sclerosis seen at our department between 1994 and 2007. We collected follow-up information on medically confirmed malignancies, life status, and cause of death, as of 2010. Malignancy rates were compared to the German national cancer registry matched for sex, age, and year of occurrence. Results: Follow-up was completed in 676 of 677 identified patients. Median follow-up time was 8.7 years (interquartile range 6.8-11.2), corresponding to 6,220 person-years. Median cumulative mitoxantrone dose was 79.0 mg/m(2) (interquartile range 50.8-102.4). Thirty-seven patients (5.5%) were diagnosed with a malignancy after mitoxantrone initiation, revealing a standardized incidence ratio of 1.50 (95% confidence interval CI] 1.05-2.08). Entities included breast cancer (n = 9), colorectal cancer (n = 7), acute myeloid leukemia (n = 4, 0.6%), and others (each entity n = 1 or 2). The standardized incidence ratio of colorectal cancer was 2.98 (95% CI 1.20-6.14) and of acute myeloid leukemia 10.44 (95% CI 3.39-24.36). It was not increased for other entities including breast cancer. Multivariate Cox regression identified higher age at treatment initiation but neither cumulative mitoxantrone dose (>75 vs 75 mg/m(2)) nor treatment with other immunosuppressive drugs or sex as a risk factor. Fifty-five patients had died, among them 12 of a malignancy and 43 reportedly of other causes. Conclusions: While the overall incidence of malignancies was only mildly increased, the risk of leukemia and colorectal cancer was heightened. If confirmed, posttherapy colonoscopy could become advisable. KW - multiple sclerosis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188300 VL - 86 ER - TY - JOUR A1 - Busch, Martin A1 - Nadal, Jennifer A1 - Schmid, Matthias A1 - Paul, Katharina A1 - Titze, Stephanie A1 - Hübner, Silvia A1 - Köttgen, Anna A1 - Schultheiss, Ulla T. A1 - Baid-Agrawal, Seema A1 - Lorenzen, Johan A1 - Schlieper, Georg A1 - Sommerer, Claudia A1 - Krane, Vera A1 - Hilge, Robert A1 - Kielstein, Jan T. A1 - Kronenberg, Florian A1 - Wanner, Christoph A1 - Eckardt, Kai-Uwe A1 - Wolf, Gunter T1 - Glycaemic control and antidiabetic therapy in patients with diabetes mellitus and chronic kidney disease - cross-sectional data from the German Chronic Kidney Disease (GCKD) cohort JF - BMC Nephrology N2 - Background Diabetes mellitus (DM) is the leading cause of end-stage renal disease. Little is known about practice patterns of anti-diabetic therapy in the presence of chronic kidney disease (CKD) and correlates with glycaemic control. We therefore aimed to analyze current antidiabetic treatment and correlates of metabolic control in a large contemporary prospective cohort of patients with diabetes and CKD. Methods The German Chronic Kidney Disease (GCKD) study enrolled 5217 patients aged 18–74 years with an estimated glomerular filtration rate (eGFR) between 30–60 mL/min/1.73 m2 or proteinuria >0.5 g/d. The use of diet prescription, oral anti-diabetic medication, and insulin was assessed at baseline. HbA1c, measured centrally, was the main outcome measure. Results At baseline, DM was present in 1842 patients (35 %) and the median HbA1C was 7.0 % (25th–75th percentile: 6.8–7.9 %), equalling 53 mmol/mol (51, 63); 24.2 % of patients received dietary treatment only, 25.5 % oral antidiabetic drugs but not insulin, 8.4 % oral antidiabetic drugs with insulin, and 41.8 % insulin alone. Metformin was used by 18.8 %. Factors associated with an HbA1C level >7.0 % (53 mmol/mol) were higher BMI (OR = 1.04 per increase of 1 kg/m2, 95 % CI 1.02–1.06), hemoglobin (OR = 1.11 per increase of 1 g/dL, 95 % CI 1.04–1.18), treatment with insulin alone (OR = 5.63, 95 % CI 4.26–7.45) or in combination with oral antidiabetic agents (OR = 4.23, 95 % CI 2.77–6.46) but not monotherapy with metformin, DPP-4 inhibitors, or glinides. Conclusions Within the GCKD cohort of patients with CKD stage 3 or overt proteinuria, antidiabetic treatment patterns were highly variable with a remarkably high proportion of more than 50 % receiving insulin-based therapies. Metabolic control was overall satisfactory, but insulin use was associated with higher HbA1C levels. KW - Chronic kidney disease KW - Glycaemic control KW - Hemoglobin A1C KW - Insulin therapy KW - Oral antidiabetic drugs KW - Diabetes mellitus Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164687 VL - 17 IS - 59 ER - TY - JOUR A1 - Busch, Albert A1 - Hoffjan, Sabine A1 - Bergmann, Frauke A1 - Hartung, Birgit A1 - Jung, Helena A1 - Hanel, Daniela A1 - Tzschach, Andeas A1 - Kadar, Janos A1 - von Kodolitsch, Yskert A1 - Germer, Christoph-Thomas A1 - Trobisch, Heiner A1 - Strasser, Erwin A1 - Wildenauer, René T1 - Vascular type Ehlers-Danlos syndrome is associated with platelet dysfunction and low vitamin D serum concentration JF - Orphanet Journal of Rare Diseases N2 - Background The vascular type represents a very rare, yet the clinically most fatal entity of Ehlers-Danlos syndrome (EDS). Patients are often admitted due to arterial bleedings and the friable tissue and the altered coagulation contribute to the challenge in treatment strategies. Until now there is little information about clotting characteristics that might influence hemostasis decisively and eventually worsen emergency situations. Results 22 vascular type EDS patients were studied for hemoglobin, platelet volume and count, Quick and activated partial thromboplastin time, fibrinogen, factor XIII, von Willebrand disease, vitamin D and platelet aggregation by modern standard laboratory methods. Results show a high prevalence of over 50 % for platelet aggregation disorders in vascular type EDS patients, especially for collagen and epinephrine induced tests, whereas the plasmatic cascade did not show any alterations. Additionally, more than half of the tested subjects showed low vitamin D serum levels, which might additionally affect vascular wall integrity. Conclusion The presented data underline the importance of detailed laboratory screening methods in vascular type EDS patients in order to allow for targeted application of platelet-interacting substances that might be of decisive benefit in the emergency setting. KW - vascular type KW - vitamin D KW - Ehlers-Danlos syndrome KW - EDS KW - platelet dysfunction Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147757 VL - 11 IS - 111 ER - TY - JOUR A1 - Busch, Albert A1 - Busch, Martin A1 - Scholz, Claus-Jürgen A1 - Kellersmann, Richard A1 - Otto, Christoph A1 - Chernogubova, Ekaterina A1 - Maegdefessel, Lars A1 - Zernecke, Alma A1 - Lorenz, Udo T1 - Aneurysm miRNA Signature Differs, Depending on Disease Localization and Morphology JF - International Journal of Molecular Science N2 - Limited comprehension of aneurysm pathology has led to inconclusive results from clinical trials. miRNAs are key regulators of post-translational gene modification and are useful tools in elucidating key features of aneurysm pathogenesis in distinct entities of abdominal and popliteal aneurysms. Here, surgically harvested specimens from 19 abdominal aortic aneurysm (AAA) and 8 popliteal artery aneurysm (PAA) patients were analyzed for miRNA expression and histologically classified regarding extracellular matrix (ECM) remodeling and inflammation. DIANA-based computational target prediction and pathway enrichment analysis verified our results, as well as previous ones. miRNA-362, -19b-1, -194, -769, -21 and -550 were significantly down-regulated in AAA samples depending on degree of inflammation. Similar or inverse regulation was found for miR-769, 19b-1 and miR-550, -21, whereas miR-194 and -362 were unaltered in PAA. In situ hybridization verified higher expression of miR-550 and -21 in PAA compared to AAA and computational analysis for target genes and pathway enrichment affirmed signal transduction, cell-cell-interaction and cell degradation pathways, in line with previous results. Despite the vague role of miRNAs for potential diagnostic and treatment purposes, the number of candidates from tissue signature studies is increasing. Tissue morphology influences subsequent research, yet comparison of distinct entities of aneurysm disease can unravel core pathways. KW - AAA KW - miRNA expression KW - pathway analysis KW - histologic diversity KW - popliteal aneurysm Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146422 SN - International Journal of Molecular Science VL - 17 IS - 1 ER - TY - JOUR A1 - Burns, Alan J. A1 - Goldstein, Allan M. A1 - Newgreen, Donald F. A1 - Stamp, Lincon A1 - Schäfer, Karl-Herbert A1 - Metzger, Marco A1 - Hotta, Ryo A1 - Young, Heather M. A1 - Andrews, Peter W. A1 - Thapar, Nikhil A1 - Belkind-Gerson, Jaime A1 - Bondurand, Nadege A1 - Bornstein, Joel C. A1 - Chan, Wood Yee A1 - Cheah, Kathryn A1 - Gershon, Michael D. A1 - Heuckeroth, Robert O. A1 - Hofstra, Robert M.W. A1 - Just, Lothar A1 - Kapur, Raj P. A1 - King, Sebastian K. A1 - McCann, Conor J. A1 - Nagy, Nandor A1 - Ngan, Elly A1 - Obermayr, Florian A1 - Pachnis, Vassilis A1 - Pasricha, Pankaj J. A1 - Sham, Mai Har A1 - Tam, Paul A1 - Vanden Berghe, Pieter T1 - White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies JF - Developmental Biology N2 - Over the last 20 years, there has been increasing focus on the development of novel stem cell based therapies for the treatment of disorders and diseases affecting the enteric nervous system (ENS) of the gastrointestinal tract (so-called enteric neuropathies). Here, the idea is that ENS progenitor/stem cells could be transplanted into the gut wall to replace the damaged or absent neurons and glia of the ENS. This White Paper sets out experts' views on the commonly used methods and approaches to identify, isolate, purify, expand and optimize ENS stem cells, transplant them into the bowel, and assess transplant success, including restoration of gut function. We also highlight obstacles that must be overcome in order to progress from successful preclinical studies in animal models to ENS stem cell therapies in the clinic. KW - Neural crest cells KW - Rat mynteric plexus KW - Intestinal pseudoobstruction KW - Hypertrophic pyloric-stenosis KW - Hirschsprung disease liability KW - Slow-transit constipation KW - Oxide synthase gene KW - Term follow-up KW - Nitric-oxide KW - In-vivo KW - Enteric nervous system KW - Enteric neuropathies KW - Stem cells KW - Cell replacement therapy KW - Hirschsprung disease Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187415 VL - 417 IS - 2 ER - TY - JOUR A1 - Buck, Andreas A1 - Decristoforo, Clemens T1 - Highlights lecture EANM 2015: the search for nuclear medicine's superheroes JF - European Journal of Nuclear Medicine and Molecular Imaging N2 - The EANM 2015 Annual Congress, held from October 10th to 14th in Hamburg, Germany, was outstanding in many respects. With 5550 participants, this was by far the largest European congress concerning nuclear medicine. More than 1750 scientific presentations were submitted, with more than 250 abstracts from young scientists, indicating that the future success of our discipline is fuelled by a high number of young individuals becoming involved in a multitude of scientific activities. Significant improvements have been made in molecular imaging of cancer, particularly in prostate cancer. PSMA-directed PET/CT appears to become a new gold standard for staging and restaging purposes. Novel tumour specific compounds have shown their potential for target identification also in other solid neoplasms and further our understanding of tumour biology and heterogeneity. In addition, a variety of nuclear imaging techniques guiding surgical interventions have been introduced. A particular focus of the congress was put on targeted, radionuclide based therapies. Novel theranostic concepts addressing also tumour entities with high incidence rates such as prostate cancer, melanoma, and lymphoma, have shown effective anti-tumour activity. Strategies have been presented to improve further already established therapeutic regimens such as somatostatin receptor based radio receptor therapy for treating advanced neuroendocrine tumours. Significant contributions were presented also in the neurosciences track. An increasing number of target structures of high interest in neurology and psychiatry are now available for PET and SPECT imaging, facilitating specific imaging of different subtypes of dementia and movement disorders as well as neuroinflammation. Major contributions in the cardiovascular track focused on further optimization of cardiac perfusion imaging by reducing radiation exposure, reducing scanning time, and improving motion correction. Besides coronary artery disease, many contributions focused on cardiac inflammation, cardiac sarcoidosis, and specific imaging of large vessel vasculitis. The physics and instrumentation track included many highlights such as novel, high resolution scanners. The most noteworthy news and developments of this meeting were summarized in the highlights lecture. Only 55 scientific contributions were mentioned, and hence they represent only a brief summary, which is outlined in this article. For a more detailed view, all presentations can be accessed by the online version of the European Journal of Nuclear Medicine and Molecular Imaging (Volume 42, Supplement 1). KW - Conjugate arc therapy KW - Phase-II KW - 18F-FDG PET/CT KW - Highlights Lecture KW - Molecular Imaging KW - Prostate-cancer KW - Radionuclide therapy KW - Myocardial perfusion KW - Preclinical evaluation KW - Targeted therapy KW - Thyroid cancer KW - SPECT KW - 2015 KW - EANM KW - Hamburg KW - Physics and instrumentation KW - Radiopharmacy KW - Oncology KW - Radionuclide Therapy KW - Cardiology KW - Neurosciences Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187613 VL - 43 IS - 10 ER - TY - JOUR A1 - Buch, Marina-Rafaela T1 - Madame Chrysanthème (1887) et Japoneries d’automne (1889) de Pierre Loti entre japonisme et exotisme désenchanté JF - promptus - Würzburger Beiträge zur Romanistik N2 - The novel Madame Chrysanthème (1887) and the essays collected in Japoneries d’automne (1889) written by French travel author Pierre Loti offer a paradoxical view of Japan during the Meiji period. In both travel writings, the author is torn between aesthetic japonism – which spread all over Europe at the end of the 19th century – and exotic expectations, i.e. the picturesque fascination of the Other. The latter, however, remains unsatisfied throughout his stay. In both writings, Pierre Loti provides an insight into Japan that entirely reflects the spirit of his time. Thereby, he contributes to an image of Japan, which will long remain vivid in the Occident. Contemporaries perceive Loti’s representation of Japan as a realistic testimony, tinged with both sensory impressions and his highly ambiguous feelings towards the distant country, which in the end remained incomprehensible to him. KW - Madame Chrysanthème KW - Japoneries d’automne KW - Pierre Loti KW - Loti, Pierre KW - Japan KW - Meiji-Periode Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161603 SN - 2510-2613 VL - 2 ER - TY - JOUR A1 - Brüning, Christoph A1 - Wehner, Johannes A1 - Hausner, Julian A1 - Wenzel, Michael A1 - Engel, Volker T1 - Exciton dynamics in perturbed vibronic molecular aggregates JF - Structural Dynamics N2 - A site specific perturbation of a photo-excited molecular aggregate can lead to a localization of excitonic energy. We investigate this localization dynamics for laser-prepared excited states. Changing the parameters of the electric field significantly influences the exciton localization which offers the possibility for a selective control of this process. This is demonstrated for aggregates possessing a single vibrational degree of freedom per monomer unit. It is shown that the effects identified for the molecular dimer can be generalized to larger aggregates with a high density of vibronic states. KW - absorption spectra KW - excited states KW - polymers KW - excitons KW - wave functions Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126085 VL - 3 ER - TY - JOUR A1 - Brunke, Dirk T1 - Der nationalepische Pionier Esteban Echeverría. Ein Beitrag zur Entstehungsgeschichte des romantischen epischen Gedichts in Hispanoamerika JF - promptus - Würzburger Beiträge zur Romanistik N2 - This article concentrates on the Argentine author Esteban Echeverría who is known as the founding father of Romanticism in the River Plate region. The author of this article intends to show that the importance of Echeverría for the development of Argentine national literature goes beyond the spreading of Romanticist aesthetics. Especially his poem La cautiva (1837) has been regarded as the national epic poem of Argentina because it represents national landscape and the early days of national history. However, as the classification of this narrative poem as the national epic poem already indicates, Echeverría also contributed to the presence of this prestigious genre at the River Plate region. By investigating Echeverría‘s less known verse texts – namely the texts which were read by all Romantics but which have been neglected by literary studies so far – this article illustrates that Echeverría gave decisive impulses for the presence of the epic poem at the River Plate. KW - episches Gedicht KW - romantisches Gedicht KW - Hispanoamerika KW - Entstehungsgeschichte KW - Echeverría, Esteban KW - Hispanoamerika KW - Literatur KW - Gedicht Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161592 SN - 2510-2613 VL - 2 ER - TY - JOUR A1 - Brunet, Frédéric G. A1 - Volff, Jean-Nicolas A1 - Schartl, Manfred T1 - Whole Genome Duplications Shaped the Receptor Tyrosine Kinase Repertoire of Jawed Vertebrates JF - Genome Biology Evolution N2 - The receptor tyrosine kinase (RTK) gene family, involved primarily in cell growth and differentiation, comprises proteins with a common enzymatic tyrosine kinase intracellular domain adjacent to a transmembrane region. The amino-terminal portion of RTKs is extracellular and made of different domains, the combination of which characterizes each of the 20 RTK subfamilies among mammals. We analyzed a total of 7,376 RTK sequences among 143 vertebrate species to provide here the first comprehensive census of the jawed vertebrate repertoire. We ascertained the 58 genes previously described in the human and mouse genomes and established their phylogenetic relationships. We also identified five additional RTKs amounting to a total of 63 genes in jawed vertebrates. We found that the vertebrate RTK gene family has been shaped by the two successive rounds of whole genome duplications (WGD) called 1R and 2R (1R/2R) that occurred at the base of the vertebrates. In addition, the Vegfr and Ephrin receptor subfamilies were expanded by single gene duplications. In teleost fish, 23 additional RTK genes have been retained after another expansion through the fish-specific third round (3R) of WGD. Several lineage-specific gene losses were observed. For instance, birds have lost three RTKs, and different genes are missing in several fish sublineages. The RTK gene family presents an unusual high gene retention rate from the vertebrate WGDs (58.75% after 1R/2R, 64.4% after 3R), resulting in an expansion that might be correlated with the evolution of complexity of vertebrate cellular communication and intracellular signaling. KW - receptor tyrosine kinase KW - vertebrates KW - deuterostomes KW - whole genome duplications Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146988 VL - 8 IS - 15 ER - TY - JOUR A1 - Brevik, Erlend J A1 - van Donkelaar, Marjolein M. J. A1 - Weber, Heike A1 - Sánchez-Mora, Cristina A1 - Jacob, Christian A1 - Rivero, Olga A1 - Kittel-Schneider, Sarah A1 - Garcia-martinez, Iris A1 - Aebi, Marcel A1 - van Hulzen, Kimm A1 - Cormand, Bru A1 - Ramos-Quiroga, Josep A A1 - Lesch, Klaus-Peter A1 - Reif, Andreas A1 - Ribases, Marta A1 - Franke, Barbara A1 - Posserud, Maj-Britt A1 - Johansson, Stefan A1 - Lundervold, Astri J. A1 - Haavik, Jan A1 - Zayats, Tetyana T1 - Genome-wide analyses of aggressiveness in attention-deficit hyperactivity disorder JF - American Journal of Medical Genetics Part B-Neuropsychiatric Genetics N2 - Aggressiveness is a behavioral trait that has the potential to be harmful to individuals and society. With an estimated heritability of about 40%, genetics is important in its development. We performed an exploratory genome-wide association (GWA) analysis of childhood aggressiveness in attention deficit hyperactivity disorder (ADHD) to gain insight into the underlying biological processes associated with this trait. Our primary sample consisted of 1,060 adult ADHD patients (aADHD). To further explore the genetic architecture of childhood aggressiveness, we performed enrichment analyses of suggestive genome-wide associations observed in aADHD among GWA signals of dimensions of oppositionality (defiant/vindictive and irritable dimensions) in childhood ADHD (cADHD). No single polymorphism reached genome-wide significance (P<5.00E-08). The strongest signal in aADHD was observed at rs10826548, within a long noncoding RNA gene (beta = -1.66, standard error (SE) = 0.34, P = 1.07E-06), closely followed by rs35974940 in the neurotrimin gene (beta = 3.23, SE = 0.67, P = 1.26E-06). The top GWA SNPs observed in aADHD showed significant enrichment of signals from both the defiant/vindictive dimension (Fisher's P-value = 2.28E-06) and the irritable dimension in cADHD (Fisher's P-value = 0.0061). In sum, our results identify a number of biologically interesting markers possibly underlying childhood aggressiveness and provide targets for further genetic exploration of aggressiveness across psychiatric disorders. KW - Large multicenter ADHD KW - Antisocial behavior KW - Diagnostic approach KW - Rating scale KW - Gene KW - Deficit/hyperactivity disorder KW - Susceptibility loci KW - Conduct disorder KW - Association KW - Adult KW - ADHD KW - Aggression KW - GWAS Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188116 VL - 171B IS - 5 ER - TY - JOUR A1 - Brendtke, Rico A1 - Wiehl, Michael A1 - Groeber, Florian A1 - Schwarz, Thomas A1 - Walles, Heike A1 - Hansmann, Jan T1 - Feasibility Study on a Microwave-Based Sensor for Measuring Hydration Level Using Human Skin Models JF - PLoS ONE N2 - Tissue dehydration results in three major types of exsiccosis—hyper-, hypo-, or isonatraemia. All three types entail alterations of salt concentrations leading to impaired biochemical processes, and can finally cause severe morbidity. The aim of our study was to demonstrate the feasibility of a microwave-based sensor technology for the non-invasive measurement of the hydration status. Electromagnetic waves at high frequencies interact with molecules, especially water. Hence, if a sample contains free water molecules, this can be detected in a reflected microwave signal. To develop the sensor system, human three-dimensional skin equivalents were instituted as a standardized test platform mimicking reproducible exsiccosis scenarios. Therefore, skin equivalents with a specific hydration and density of matrix components were generated and microwave measurements were performed. Hydration-specific spectra allowed deriving the hydration state of the skin models. A further advantage of the skin equivalents was the characterization of the impact of distinct skin components on the measured signals to investigate mechanisms of signal generation. The results demonstrate the feasibility of a non-invasive microwave-based hydration sensor technology. The sensor bears potential to be integrated in a wearable medical device for personal health monitoring. KW - gels KW - microwave radiation KW - collagens KW - skin physiology KW - reflection KW - skin anatomy KW - epidermis KW - antennas Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-179934 VL - 11 IS - 4 ER - TY - JOUR A1 - Braunschweig, Holger A1 - Krummenacher, Ivo A1 - Mailänder, Lisa A1 - Pentecost, Leanne A1 - Vargas, Alfredo T1 - Formation of a stable radical by oxidation of a tetraorganoborate JF - Chemical Communications N2 - Herein, we describe the selective formation of a stable neutral spiroborate radical by one-electron oxidation of the corresponding tetraorganoborate salt Li[B(C\(_4\)Ph\(_4\))\(_2\)], formally containing a tetrahedral borate centre and a s-cis-butadiene radical cation as the spin-bearing site. Spectroscopic and computational methods have been used to determine the spin distribution and the chromism observed in the solid state. KW - tetraorganoborate salt KW - spiroborates KW - one-electron oxidation KW - spin distribution KW - chromism Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191321 VL - 52 IS - 43 ER - TY - JOUR A1 - Braunschweig, Holger A1 - Ewing, William C. A1 - Ghosh, Sundargopal A1 - Kramer, Thomas A1 - Mattock, James D. A1 - Östreicher, Sebastian A1 - Vargas, Alfredo A1 - Werner, Christine T1 - Trimetallaborides as starting points for the syntheses of large metal-rich molecular borides and clusters JF - Chemical Science N2 - Treatment of an anionic dimanganaborylene complex ([{Cp(CO)\(_2\)Mn}\(_2\)B]\(^-\)) with coinage metal cations stabilized by a very weakly coordinating Lewis base (SMe\(_2\)) led to the coordination of the incoming metal and subsequent displacement of dimethylsulfide in the formation of hexametalladiborides featuring planar four-membered M\(_2\)B\(_2\) cores (M = Cu, Au) comparable to transition metal clusters constructed around four-membered rings composed solely of coinage metals. The analogies between compounds consisting of B\(_2\)M\(_2\) units and M\(_4\) (M = Cu, Au) units speak to the often overlooked metalloid nature of boron. Treatment of one of these compounds (M = Cu) with a Lewis-basic metal fragment (Pt(PCy\(_3\))\(_2\)) led to the formation of a tetrametallaboride featuring two manganese, one copper and one platinum atom, all bound to boron in a geometry not yet seen for this kind of compound. Computational examination suggests that this geometry is the result of d\(^{10}\)-d\(^{10}\) dispersion interactions between the copper and platinum fragments. KW - anionic dimetalloborylene complexes KW - trimetallaborides KW - tetrametallaborides KW - Boron KW - metallaboranes KW - crystal structure KW - metal borylene complexes Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191511 VL - 7 IS - 1 ER - TY - JOUR A1 - Braunschweig, Holger A1 - Constantinidis, Philipp A1 - Dellermann, Theresa A1 - Ewing, William A1 - Fischer, Ingo A1 - Hess, Merlin A1 - Knight, Fergus A1 - Rempel, Anna A1 - Schneider, Christoph A1 - Ullrich, Stefan A1 - Vargas, Alfredo A1 - Woolins, Derek T1 - Highly Strained Heterocycles Constructed from Boron–Boron Multiple Bonds and Heavy Chalcogens JF - Angewandte Chemie, International Edition N2 - The reactions of a diborene with elemental selenium or tellurium are shown to afford a diboraselenirane or diboratellurirane, respectively. These reactions are reminiscent of the sequestration of subvalent oxygen and nitrogen in the formation of oxiranes and aziridines; however, such reactivity is not known between alkenes and the heavy chalcogens. Although carbon is too electronegative to affect the reduction of elements with lower relative electronegativity, the highly reducing nature of the B B double bond enables reactions with Se0 and Te0. The capacity of multiple bonds between boron atoms to donate electron density is highlighted in reactions where diborynes behave as nucleophiles, attacking one of the two Te atoms of diaryltellurides, forming salts consisting of diboratellurenium cations and aryltelluride anions. KW - Boron KW - Heterocycles KW - Multiple bonds KW - Selenium KW - Tellurium KW - Bor KW - Heterocyclische Verbindungen KW - Selen KW - Tellur Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-138237 N1 - This is the peer reviewed version of the following article: Angew. Chem. Int. Ed. 2016, 55, 5606–5609, which has been published in final form at 10.1002/anie.201601691. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. N1 - Accepted Version VL - 55 IS - 18 SP - 5606 EP - 5609 ER - TY - JOUR A1 - Bratengeier, Klaus A1 - Holubyev, Kostyantyn T1 - Anisotropy of dose contributions-an instrument to upgrade real time IMRT and VMAT adaptation? JF - Medical Physics N2 - Purpose: To suggest a definition of dose deposition anisotropy for the purpose of ad hoc adaptation of intensity modulated arc therapy (IMRT) and volumetric arc therapy (VMAT), particularly in the vicinity of important organs at risk (OAR), also for large deformations. Methods: Beam's-eye-view (BEV) based fluence warping is a standard adaptation method with disadvantages for strongly varying OAR shapes. 2-Step-adaptation overcomes these difficulties by a deeper analysis of the 3D properties of adaptation processes, but requires separate arcs for every OAR to spare, which makes it impractical for cases with multiple OARs. The authors aim to extend the 2-Step method to arbitrary intensity modulated plan by analyzing the anisotropy of dose contributions. Anisotropy was defined as a second term of Fourier transformation of gantry angle dependent dose contributions. For a cylindrical planning target volume (PTV) surrounding an OAR of varying diameter, the anisotropy and the dose-normalized anisotropy were analyzed for several scenarios of optimized fluence distributions. 2-Step adaptation to decreasing and increasing OAR diameter was performed, and compared to a usual fluence based adaptation method. For two clinical cases, prostate and neck, the VMAT was generated and the behavior of anisotropy was qualitatively explored for deformed organs at risk. # Results: Dose contribution anisotropy in the PTV peaks around nearby OARs. The thickness of the "anisotropy wall" around OAR increases for increasing OAR radius, as also does the width of 2-Step dose saturating fluence peak adjacent to the OAR K. Bratengeier et al., "A comparison between 2-Step IMRT and conventional IMRT planning," Radiother. Oncol. 84, 298-306 (2007)]. Different optimized beam fluence profiles resulted in comparable radial dependence of normalized anisotropy. As predicted, even for patient cases, anisotropy was inflated even more than increasing diameters of OAR. Conclusions: For cylindrically symmetric cases, the dose distribution anisotropy defined in the present work implicitly contains adaptation-relevant information about 3D relationships between PTV and OAR and degree of OAR sparing. For more complex realistic cases, it shows the predicted behavior qualitatively. The authors claim to have found a first component for advancing a 2-Step adaptation to a universal adaptation algorithm based on the BEV projection of the dose anisotropy. Further planning studies to explore the potential of anisotropy for adaptation algorithms using phantoms and clinical cases of differing complexity will follow. KW - modulated arc therapy KW - 2-step IMRT KW - radiation-therapy KW - online adaption KW - prostate-cancer KW - plans KW - IMAT KW - tracking KW - radiotherapy KW - adaption KW - IMRT KW - VMAT Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186833 VL - 43 IS - 11 ER - TY - JOUR A1 - Bousquet, J. A1 - Farrell, J. A1 - Crooks, G. A1 - Hellings, P. A1 - Bel, E. H. A1 - Bewick, M. A1 - Chavannes, N. H. A1 - Correia de Sousa, J. A1 - Cruz, A. A. A1 - Haahtela, T. A1 - Joos, G. A1 - Khaltaev, N. A1 - Malva, J. A1 - Muraro, A. A1 - Nogues, M. A1 - Palkonen, S. A1 - Pedersen, S. A1 - Robalo-Cordeiro, C. A1 - Samolinski, B. A1 - Strandberg, T. A1 - Valiulis, A. A1 - Yorgancioglu, A. A1 - Zuberbier, T. A1 - Bedbrook, A. A1 - Aberer, W. A1 - Adachi, M. A1 - Agusti, A. A1 - Akdis, C. A. A1 - Akdis, M. A1 - Ankri, J. A1 - Alonso, A. A1 - Annesi-Maesano, I. A1 - Ansotegui, I. J. A1 - Anto, J. M. A1 - Arnavielhe, S. A1 - Arshad, H. A1 - Bai, C. A1 - Baiardini, I. A1 - Bachert, C. A1 - Baigenzhin, A. K. A1 - Barbara, C. A1 - Bateman, E. D. A1 - Beghé, B. A1 - Ben Kheder, A. A1 - Bennoor, K. S. A1 - Benson, M. A1 - Bergmann, K. C. A1 - Bieber, T. A1 - Bindslev-Jensen, C. A1 - Bjermer, L. A1 - Blain, H. A1 - Blasi, F. A1 - Boner, A. L. A1 - Bonini, M. A1 - Bonini, S. A1 - Bosnic-Anticevitch, S. A1 - Boulet, L. P. A1 - Bourret, R. A1 - Bousquet, P. J. A1 - Braido, F. A1 - Briggs, A. H. A1 - Brightling, C. E. A1 - Brozek, J. A1 - Buhl, R. A1 - Burney, P. G. A1 - Bush, A. A1 - Caballero-Fonseca, F. A1 - Caimmi, D. A1 - Calderon, M. A. A1 - Calverley, P. M. A1 - Camargos, P. A. M. A1 - Canonica, G. W. A1 - Camuzat, T. A1 - Carlsen, K. H. A1 - Carr, W. A1 - Carriazo, A. A1 - Casale, T. A1 - Cepeda Sarabia, A. M. A1 - Chatzi, L. A1 - Chen, Y. Z. A1 - Chiron, R. A1 - Chkhartishvili, E. A1 - Chuchalin, A. G. A1 - Chung, K. F. A1 - Ciprandi, G. A1 - Cirule, I. A1 - Cox, L. A1 - Costa, D. J. A1 - Custovic, A. A1 - Dahl, R. A1 - Dahlen, S. E. A1 - Darsow, U. A1 - De Carlo, G. A1 - De Blay, F. A1 - Dedeu, T. A1 - Deleanu, D. A1 - De Manuel Keenoy, E. A1 - Demoly, P. A1 - Denburg, J. A. A1 - Devillier, P. A1 - Didier, A. A1 - Dinh-Xuan, A. T. A1 - Djukanovic, R. A1 - Dokic, D. A1 - Douagui, H. A1 - Dray, G. A1 - Dubakiene, R. A1 - Durham, S. R. A1 - Dykewicz, M. S. A1 - El-Gamal, Y. A1 - Emuzyte, R. A1 - Fabbri, L. M. A1 - Fletcher, M. A1 - Fiocchi, A. A1 - Fink Wagner, A. A1 - Fonseca, J. A1 - Fokkens, W. J. A1 - Forastiere, F. A1 - Frith, P. A1 - Gaga, M. A1 - Gamkrelidze, A. A1 - Garces, J. A1 - Garcia-Aymerich, J. A1 - Gemicioğlu, B. A1 - Gereda, J. E. A1 - González Diaz, S. A1 - Gotua, M. A1 - Grisle, I. A1 - Grouse, L. A1 - Gutter, Z. A1 - Guzmán, M. A. A1 - Heaney, L. G. A1 - Hellquist-Dahl, B. A1 - Henderson, D. A1 - Hendry, A. A1 - Heinrich, J. A1 - Heve, D. A1 - Horak, F. A1 - Hourihane, J. O’. B. A1 - Howarth, P. A1 - Humbert, M. A1 - Hyland, M. E. A1 - Illario, M. A1 - Ivancevich, J. C. A1 - Jardim, J. R. A1 - Jares, E. J. A1 - Jeandel, C. A1 - Jenkins, C. A1 - Johnston, S. L. A1 - Jonquet, O. A1 - Julge, K. A1 - Jung, K. S. A1 - Just, J. A1 - Kaidashev, I. A1 - Kaitov, M. R. A1 - Kalayci, O. A1 - Kalyoncu, A. F. A1 - Keil, T. A1 - Keith, P. K. A1 - Klimek, L. A1 - Koffi N’Goran, B. A1 - Kolek, V. A1 - Koppelman, G. H. A1 - Kowalski, M. L. A1 - Kull, I. A1 - Kuna, P. A1 - Kvedariene, V. A1 - Lambrecht, B. A1 - Lau, S. A1 - Larenas‑Linnemann, D. A1 - Laune, D. A1 - Le, L. T. T. A1 - Lieberman, P. A1 - Lipworth, B. A1 - Li, J. A1 - Lodrup Carlsen, K. A1 - Louis, R. A1 - MacNee, W. A1 - Magard, Y. A1 - Magnan, A. A1 - Mahboub, B. A1 - Mair, A. A1 - Majer, I. A1 - Makela, M. J. A1 - Manning, P. A1 - Mara, S. A1 - Marshall, G. D. A1 - Masjedi, M. R. A1 - Matignon, P. A1 - Maurer, M. A1 - Mavale‑Manuel, S. A1 - Melén, E. A1 - Melo‑Gomes, E. A1 - Meltzer, E. O. A1 - Menzies‑Gow, A. A1 - Merk, H. A1 - Michel, J. P. A1 - Miculinic, N. A1 - Mihaltan, F. A1 - Milenkovic, B. A1 - Mohammad, G. M. Y. A1 - Molimard, M. A1 - Momas, I. A1 - Montilla‑Santana, A. A1 - Morais‑Almeida, M. A1 - Morgan, M. A1 - Mösges, R. A1 - Mullol, J. A1 - Nafti, S. A1 - Namazova‑Baranova, L. A1 - Naclerio, R. A1 - Neou, A. A1 - Neffen, H. A1 - Nekam, K. A1 - Niggemann, B. A1 - Ninot, G. A1 - Nyembue, T. D. A1 - O’Hehir, R. E. A1 - Ohta, K. A1 - Okamoto, Y. A1 - Okubo, K. A1 - Ouedraogo, S. A1 - Paggiaro, P. A1 - Pali‑Schöll, I. A1 - Panzner, P. A1 - Papadopoulos, N. A1 - Papi, A. A1 - Park, H. S. A1 - Passalacqua, G. A1 - Pavord, I. A1 - Pawankar, R. A1 - Pengelly, R. A1 - Pfaar, O. A1 - Picard, R. A1 - Pigearias, B. A1 - Pin, I. A1 - Plavec, D. A1 - Poethig, D. A1 - Pohl, W. A1 - Popov, T. A. A1 - Portejoie, F. A1 - Potter, P. A1 - Postma, D. A1 - Price, D. A1 - Rabe, K. F. A1 - Raciborski, F. A1 - Radier Pontal, F. A1 - Repka‑Ramirez, S. A1 - Reitamo, S. A1 - Rennard, S. A1 - Rodenas, F. A1 - Roberts, J. A1 - Roca, J. A1 - Rodriguez Mañas, L. A1 - et al, T1 - Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5) JF - Clinical and Translational Allergy N2 - Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing. KW - EIP on AHA KW - European Innovation Partnership on Active and Healthy Ageing KW - AIRWAYS ICPs KW - MACVIA KW - Scaling up KW - Chronic respiratory diseases KW - ARIA Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166874 VL - 6 IS - 29 ER - TY - JOUR A1 - Bousquet, J. A1 - Anto, J. M. A1 - Akdis, M. A1 - Auffray, C. A1 - Keil, T. A1 - Momas, I. A1 - Postma, D. S. A1 - Valenta, R. A1 - Wickman, M. A1 - Cambon-Thomsen, A. A1 - Haahtela, T. A1 - Lambrecht, B. N. A1 - Lodrup Carlsen, K. C. A1 - Koppelman, G. H. A1 - Sunyer, J. A1 - Zuberbier, T. A1 - Annesi-Maesano, I. A1 - Arno, A. A1 - Bindslev-Jensen, C. A1 - De Carlo, G. A1 - Forastiere, F. A1 - Heinrich, J. A1 - Kowalski, M. L. A1 - Maier, D. A1 - Melen, E. A1 - Palkonen, S. A1 - Smit, H. A. A1 - Standl, M. A1 - Wright, J. A1 - Asarnoj, A. A1 - Benet, M. A1 - Ballardini, N. A1 - Garcia-Aymerich, J. A1 - Gehring, U. A1 - Guerra, S. A1 - Hohman, C. A1 - Kull, I. A1 - Lupinek, C. A1 - Pinart, M. A1 - Skrindo, I. A1 - Westman, M. A1 - Smagghe, D. A1 - Akdis, C. A1 - Albang, R. A1 - Anastasova, V. A1 - Anderson, N. A1 - Bachert, C. A1 - Ballereau, S. A1 - Ballester, F. A1 - Basagana, X. A1 - Bedbrook, A. A1 - Bergstrom, A. A1 - von Berg, A. A1 - Brunekreef, B. A1 - Burte, E. A1 - Carlsen, K.H. A1 - Chatzi, L. A1 - Coquet, J.M. A1 - Curin, M. A1 - Demoly, P. A1 - Eller, E. A1 - Fantini, M.P. A1 - Gerhard, B. A1 - Hammad, H. A1 - von Hertzen, L. A1 - Hovland, V. A1 - Jacquemin, B. A1 - Just, J. A1 - Keller, T. A1 - Kerkhof, M. A1 - Kiss, R. A1 - Kogevinas, M. A1 - Koletzko, S. A1 - Lau, S. A1 - Lehmann, I. A1 - Lemonnier, N. A1 - McEachan, R. A1 - Makela, M. A1 - Mestres, J. A1 - Minina, E. A1 - Mowinckel, P. A1 - Nadif, R. A1 - Nawijn, M. A1 - Oddie, S. A1 - Pellet, J. A1 - Pin, I. A1 - Porta, D. A1 - Rancière, F. A1 - Rial-Sebbag, A. A1 - Schuijs, M.J. A1 - Siroux, V. A1 - Tischer, C.G. A1 - Torrent, M. A1 - Varraso, R. A1 - De Vocht, J. A1 - Wenger, K. A1 - Wieser, S. A1 - Xu, C. T1 - Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story Mechanisms of the Development of ALLergy; EUFP7-CP-IP; Project No: 261357; 2010-2015 JF - Allergy N2 - MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda. KW - asthma KW - birth cohort KW - atopic-dermatitis KW - immune-responses KW - IgE KW - multimorbidity KW - polysensitization KW - rhinitis KW - chronic respiratory-diseases KW - childhood asthma KW - immunological reactivity KW - IgE sensitazion KW - immunoglobulin-e KW - integraed care Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186858 VL - 71 IS - 11 ER - TY - JOUR A1 - Bossert, Nelli A1 - de Bruin, Donny A1 - Götz, Maria A1 - Bouwmeester, Dirk A1 - Heinrich, Doris T1 - Fluorescence-tunable Ag-DNA biosensor with tailored cytotoxicity for live-cell applications JF - Scientific Reports N2 - DNA-stabilized silver clusters (Ag-DNA) show excellent promise as a multi-functional nanoagent for molecular investigations in living cells. The unique properties of these fluorescent nanomaterials allow for intracellular optical sensors with tunable cytotoxicity based on simple modifications of the DNA sequences. Three Ag-DNA nanoagent designs are investigated, exhibiting optical responses to the intracellular environments and sensing-capability of ions, functional inside living cells. Their sequence-dependent fluorescence responses inside living cells include (1) a strong splitting of the fluorescence peak for a DNA hairpin construct, (2) an excitation and emission shift of up to 120 nm for a single-stranded DNA construct, and (3) a sequence robust in fluorescence properties. Additionally, the cytotoxicity of these Ag-DNA constructs is tunable, ranging from highly cytotoxic to biocompatible Ag-DNA, independent of their optical sensing capability. Thus, Ag-DNA represents a versatile live-cell nanoagent addressable towards anti-cancer, patient-specific and anti-bacterial applications. KW - Ag-DNA KW - DNA-encapsulated silver nanoclusters KW - nanoagent KW - fluorescence Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167482 VL - 6 IS - 37897 ER - TY - JOUR A1 - Boschert, V. A1 - Frisch, C. A1 - Back, J. W. A1 - van Pee,, K. A1 - Weidauer, S. E. A1 - Muth, E.-M. A1 - Schmieder, P. A1 - Beerbaum, M. A1 - Knappik, A. A1 - Timmerman, P. A1 - Mueller, T. D. T1 - The sclerostin-neutralizing antibody AbD09097 recognizes an epitope adjacent to sclerostin's binding site for the Wnt co-receptor LRP6 JF - Open Biology N2 - The glycoprotein sclerostin has been identified as a negative regulator of bone growth. It exerts its function by interacting with the Wnt co-receptor LRP5/6, blocks the binding of Wnt factors and thereby inhibits Wnt signalling. Neutralizing anti-sclerostin antibodies are able to restore Wnt activity and enhance bone growth thereby presenting a new osteoanabolic therapy approach for diseases such as osteoporosis. We have generated various Fab antibodies against human and murine sclerostin using a phage display set-up. Biochemical analyses have identified one Fab developed against murine sclerostin, AbD09097 that efficiently neutralizes sclerostin's Wnt inhibitory activity. In vitro interaction analysis using sclerostin variants revealed that this neutralizing Fab binds to sclerostin's flexible second loop, which has been shown to harbour the LRP5/6 binding motif. Affinity maturation was then applied to AbD09097, providing a set of improved neutralizing Fab antibodies which particularly bind human sclerostin with enhanced affinity. Determining the crystal structure of AbD09097 provides first insights into how this antibody might recognize and neutralize sclerostin. Together with the structure–function relationship derived from affinity maturation these new data will foster the rational design of new and highly efficient anti-sclerostin antibodies for the therapy of bone loss diseases such as osteoporosis. KW - phage display KW - Wnt signalling KW - sclerostin KW - neutralizing antibody KW - osteoporosis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177925 VL - 6 ER - TY - JOUR A1 - Bornstein, Stefan R. A1 - Allolio, Bruno A1 - Arlt, Wiebke A1 - Barthel, Andreas A1 - Don-Wauchope, Andrew A1 - Hammer, Gary D. A1 - Husebye, Eystein S. A1 - Merke, Deborah P. A1 - Murad, M. Hassan A1 - Stratakis, Constantine A. A1 - Torpy, David J. T1 - Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society Clinical Practice Guideline JF - Journal of Clinical Endocrinology & Metabolism N2 - Objective: This clinical practice guideline addresses the diagnosis and treatment of primary adrenal insufficiency. Participants: The Task Force included a chair, selected by The Clinical Guidelines Subcommittee of the Endocrine Society, eight additional clinicians experienced with the disease, a methodologist, and a medical writer. The co-sponsoring associations (European Society of Endocrinology and the American Association for Clinical Chemistry) had participating members. The Task Force received no corporate funding or remuneration in connection with this review. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to determine the strength of recommendations and the quality of evidence. Consensus Process: The evidence used to formulate recommendations was derived from two commissioned systematic reviews as well as other published systematic reviews and studies identified by the Task Force. The guideline was reviewed and approved sequentially by the Endocrine Society's Clinical Guidelines Subcommittee and Clinical Affairs Core Committee, members responding to a web posting, and the Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. Conclusions: We recommend diagnostic tests for the exclusion of primary adrenal insufficiency in all patients with indicative clinical symptoms or signs. In particular, we suggest a low diagnostic (and therapeutic) threshold in acutely ill patients, as well as in patients with predisposing factors. This is also recommended for pregnant women with unexplained persistent nausea, fatigue, and hypotension. We recommend a short corticotropin test (250 mu g) as the "gold standard" diagnostic tool to establish the diagnosis. If a short corticotropin test is not possible in the first instance, we recommend an initial screening procedure comprising the measurement of morning plasma ACTH and cortisol levels. Diagnosis of the underlying cause should include a validated assay of autoantibodies against 21-hydroxylase. In autoantibody-negative individuals, other causes should be sought. We recommend once-daily fludrocortisone (median, 0.1 mg) and hydrocortisone (15-25 mg/d) or cortisone acetate replacement (20-35 mg/d) applied in two to three daily doses in adults. In children, hydrocortisone (similar to 8 mg/m\(^2\)/d) is recommended. Patients should be educated about stress dosing and equipped with a steroid card and glucocorticoid preparation for parenteral emergency administration. Follow-up should aim at monitoring appropriate dosing of corticosteroids and associated autoimmune diseases, particularly autoimmune thyroid disease. KW - glucocorticoid replacement therapy KW - Addison's disease KW - short Synacthen test KW - insulin tolerance test Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190893 VL - 101 IS - 2 ER - TY - JOUR A1 - Born, Dennis-Peter A1 - Zinner, Christoph A1 - Düking, Peter A1 - Sperlich, Billy T1 - Multi-Directional Sprint Training Improves Change-Of-Direction Speed and Reactive Agility in Young Highly Trained Soccer Players JF - Journal of Sports Science and Medicine N2 - The aim of this study was to evaluate the effect of a repeated sprint training with multi-directional change-of-direction (COD) movements (RSmulti) compared to repeated shuttle sprints (RSS) on variables related to COD speed and reactive agility. Nineteen highly-trained male U15 soccer players were assigned into two groups performing either RSmulti or RSS. For both groups, each training session involved 20 repeated 15 s sprints interspersed with 30 s recovery. With RSmulti the COD movements were randomized and performed in response to a visual stimulus, while the RSS involved predefined 180° COD movements. Before and following the six training sessions, performance in the Illinois agility test (IAT), COD speed in response to a visual stimulus, 20 m linear sprint time and vertical jumping height were assessed. Both groups improved their performance in the IAT (p < 0.01, ES = 1.13; p = 0.01, ES = 0.55). The COD speed in response to a visual stimulus improved with the RSmulti (p < 0.01, ES = 1.03), but not the RSS (p = 0.46, ES = 0.28). No differences were found for 20 m sprint time (P=0.73, ES = 0.07; p = 0.14, ES = 0.28) or vertical jumping height (p = 0.46, ES = 0.11; p = 0.29, ES = 0.12) for the RSmulti and RSS, respectively. In conclusion, performance in the IAT improved with the RSmulti as well as RSS. With the RSmulti however, the COD movements are performed in response to a visual stimulus, which may result in specific adaptations that improve COD speed and reactive agility in young highly trained soccer players. KW - team sport KW - COD movements KW - repeated shuttle sprints KW - speed KW - Speedcourt Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146866 UR - http://www.jssm.org/researchjssm-15-314.xml.xml VL - 15 ER - TY - JOUR A1 - Borkert, Franziska T1 - BibScout – der mobile Auskunftsdienst an der UB Würzburg JF - BuB. Forum Bibliothek und Information N2 - Seit dem Wintersemester 2014/15 setzt die Universitätsbibliothek (UB) Würzburg in der Zentralbibliothek sogenannte BibScouts ein. Das sind studentische Hilfskräfte, die die Nutzerinnen und Nutzer der Bibliothek – hauptsächlich Studierende – beim Kopieren, Drucken, Scannen und beim Auffinden von Büchern unterstützen. Die BibScouts haben keinen festen Standort, sondern helfen direkt vor Ort, an den Kopierern, Computern, Scan-Stationen und in den Lesesälen. Erkennbar sind sie an blauen Westen mit dem Logo der UB Würzburg sowie dem Hinweis »Fragen? Ich helfe weiter!« auf dem Rücken. Die BibScouts, die nur während der Vorlesungszeit eingesetzt werden, entlasten durch ihre Anwesenheit das bibliothekarische Personal an der Informationstheke. KW - mobiler Auskunftsdienst KW - peer-to-peer Auskunftsdienst KW - roving reference KW - roaming reference KW - Auskunftsdienst KW - Universitätsbibliothek Würzburg Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148145 UR - http://b-u-b.de/archiv/ VL - 68 IS - 12 ER - TY - JOUR A1 - Boll, Sabine A1 - Bartholomaeus, Marie A1 - Peter, Ulrike A1 - Lupke, Ulrike A1 - Gamer, Matthias T1 - Attentional mechanisms of social perception are biased in social phobia JF - Journal of Anxiety Disorders N2 - Previous studies of social phobia have reported an increased vigilance to social threat cues but also an avoidance of socially relevant stimuli such as eye gaze. The primary aim of this study was to examine attentional mechanisms relevant for perceiving social cues by means of abnormalities in scanning of facial features in patients with social phobia. In two novel experimental paradigms, patients with social phobia and healthy controls matched on age, gender and education were compared regarding their gazing behavior towards facial cues. The first experiment was an emotion classification paradigm which allowed for differentiating reflexive attentional shifts from sustained attention towards diagnostically relevant facial features. In the second experiment, attentional orienting by gaze direction was assessed in a gaze-cueing paradigm in which non-predictive gaze cues shifted attention towards or away from subsequently presented targets. We found that patients as compared to controls reflexively oriented their attention more frequently towards the eyes of emotional faces in the emotion classification paradigm. This initial hypervigilance for the eye region was observed at very early attentional stages when faces were presented for 150 ms, and persisted when facial stimuli were shown for 3 s. Moreover, a delayed attentional orienting into the direction of eye gaze was observed in individuals with social phobia suggesting a differential time course of eye gaze processing in patients and controls. Our findings suggest that basic mechanisms of early attentional exploration of social cues are biased in social phobia and might contribute to the development and maintenance of the disorder. KW - Social anxiety KW - Eye gaze KW - Vigilance KW - Amygdala KW - Emotional expression KW - Gaze perception Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189046 VL - 40 ER - TY - JOUR A1 - Blättner, Sebastian A1 - Das, Sudip A1 - Paprotka, Kerstin A1 - Eilers, Ursula A1 - Krischke, Markus A1 - Kretschmer, Dorothee A1 - Remmele, Christian W. A1 - Dittrich, Marcus A1 - Müller, Tobias A1 - Schuelein-Voelk, Christina A1 - Hertlein, Tobias A1 - Mueller, Martin J. A1 - Huettel, Bruno A1 - Reinhardt, Richard A1 - Ohlsen, Knut A1 - Rudel, Thomas A1 - Fraunholz, Martin J. T1 - Staphylococcus aureus Exploits a Non-ribosomal Cyclic Dipeptide to Modulate Survival within Epithelial Cells and Phagocytes JF - PLoS Pathogens N2 - Community-acquired (CA) Staphylococcus aureus cause various diseases even in healthy individuals. Enhanced virulence of CA-strains is partly attributed to increased production of toxins such as phenol-soluble modulins (PSM). The pathogen is internalized efficiently by mammalian host cells and intracellular S. aureus has recently been shown to contribute to disease. Upon internalization, cytotoxic S. aureus strains can disrupt phagosomal membranes and kill host cells in a PSM-dependent manner. However, PSM are not sufficient for these processes. Here we screened for factors required for intracellular S. aureus virulence. We infected escape reporter host cells with strains from an established transposon mutant library and detected phagosomal escape rates using automated microscopy. We thereby, among other factors, identified a non-ribosomal peptide synthetase (NRPS) to be required for efficient phagosomal escape and intracellular survival of S. aureus as well as induction of host cell death. By genetic complementation as well as supplementation with the synthetic NRPS product, the cyclic dipeptide phevalin, wild-type phenotypes were restored. We further demonstrate that the NRPS is contributing to virulence in a mouse pneumonia model. Together, our data illustrate a hitherto unrecognized function of the S. aureus NRPS and its dipeptide product during S. aureus infection. KW - cell death KW - cytotoxicity KW - Staphylococcus aureus KW - host cells KW - neutrophils KW - macrophages KW - transposable elements KW - epithelial cells Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180380 VL - 12 IS - 9 ER - TY - JOUR A1 - Bluemel, Christina A1 - Linke, Fraenze A1 - Herrmann, Ken A1 - Simunovic, Iva A1 - Eiber, Matthias A1 - Kestler, Christian A1 - Buck, Andreas K. A1 - Schirbel, Andreas A1 - Bley, Thorsten A. A1 - Wester, Hans-Juergen A1 - Vergho, Daniel A1 - Becker, Axel T1 - Impact of \(^{68}\)Ga-PSMA PET/CT on salvage radiotherapy planning in patients with prostate cancer and persisting PSA values or biochemical relapse after prostatectomy JF - EJNMMI Research N2 - Background Salvage radiotherapy (SRT) is clinically established in prostate cancer (PC) patients with PSA persistence or biochemical relapse (BCR) after prior radical surgery. PET/CT imaging prior to SRT may be performed to localize disease recurrence. The recently introduced \(^{68}\)Ga-PSMA outperforms other PET tracers for detection of recurrence and is therefore expected also to impact radiation planning. Forty-five patients with PSA persistence (16 pts) or BCR (29 pts) after prior prostatectomy, scheduled to undergo SRT of the prostate bed, underwent \(^{68}\)Ga-PSMA PET/CT. The median PSA level was 0.67 ng/ml. The impact of \(^{68}\)Ga-PSMA PET/CT on the treatment decision was assessed. Patients with oligometastatic (≤5 lesions) PC underwent radiotherapy (RT), with the extent of the RT area and dose escalation being based on PET positivity. Results Suspicious lesions were detected in 24/45 (53.3 %) patients. In 62.5 % of patients, lesions were only detected by 68Ga-PSMA PET. Treatment was changed in 19/45 (42.2 %) patients, e.g., extending SRT to metastases (9/19), administering dose escalation in patients with morphological local recurrence (6/19), or replacing SRT by systemic therapy (2/19). 38/45 (84.4 %) followed the treatment recommendation, with data on clinical follow-up being available in 21 patients treated with SRT. All but one showed biochemical response (mean PSA decline 78 ± 19 %) within a mean follow-up of 8.12 ± 5.23 months. Conclusions \(^{68}\)Ga-PSMA PET/CT impacts treatment planning in more than 40 % of patients scheduled to undergo SRT. Future prospective studies are needed to confirm this significant therapeutic impact on patients prior to SRT. KW - prostate cancer KW - salvage radiotherapy KW - PSMA KW - PET/CT KW - recurrence Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147798 VL - 6 IS - 78 ER - TY - JOUR A1 - Biscotti, Maria Assunta A1 - Gerdol, Marco A1 - Canapa, Adriana A1 - Forconi, Mariko A1 - Olmo, Ettore A1 - Pallavicini, Alberto A1 - Barucca, Marco A1 - Schartl, Manfred T1 - The Lungfish Transcriptome: A Glimpse into Molecular Evolution Events at the Transition from Water to Land JF - Scientific Reports N2 - Lungfish and coelacanths are the only living sarcopterygian fish. The phylogenetic relationship of lungfish to the last common ancestor of tetrapods and their close morphological similarity to their fossil ancestors make this species uniquely interesting. However their genome size, the largest among vertebrates, is hampering the generation of a whole genome sequence. To provide a partial solution to the problem, a high-coverage lungfish reference transcriptome was generated and assembled. The present findings indicate that lungfish, not coelacanths, are the closest relatives to land-adapted vertebrates. Whereas protein-coding genes evolve at a very slow rate, possibly reflecting a “living fossil” status, transposable elements appear to be active and show high diversity, suggesting a role for them in the remarkable expansion of the lungfish genome. Analyses of single genes and gene families documented changes connected to the water to land transition and demonstrated the value of the lungfish reference transcriptome for comparative studies of vertebrate evolution. KW - lungfish KW - transcriptome KW - genome KW - sarcopterygian fish Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167753 VL - 6 IS - 21571 ER - TY - JOUR A1 - Biehl, Stefanie C. A1 - Merz, Christian J. A1 - Dresler, Thomas A1 - Heupel, Julia A1 - Reichert, Susanne A1 - Jacob, Christian P. A1 - Deckert, Jürgen A1 - Herrmann, Martin J. T1 - Increase or Decrease of fMRI Activity in Adult Attention Deficit/ Hyperactivity Disorder: Does It Depend on Task Difficulty? JF - International Journal of Neuropsychopharmacology N2 - Background: Attention deficit/hyperactivity disorder has been shown to affect working memory, and fMRI studies in children and adolescents with attention deficit/hyperactivity disorder report hypoactivation in task-related attentional networks. However, studies with adult attention deficit/hyperactivity disorder patients addressing this issue as well as the effects of clinically valid methylphenidate treatment are scarce. This study contributes to closing this gap. Methods: Thirty-five adult patients were randomized to 6 weeks of double-blind placebo or methylphenidate treatment. Patients completed an fMRI n-back working memory task both before and after the assigned treatment, and matched healthy controls were tested and compared to the untreated patients. Results: There were no whole-brain differences between any of the groups. However, when specified regions of interest were investigated, the patient group showed enhanced BOLD responses in dorsal and ventral areas before treatment. This increase was correlated with performance across all participants and with attention deficit/hyperactivity disorder symptoms in the patient group. Furthermore, we found an effect of treatment in the right superior frontal gyrus, with methylphenidate-treated patients exhibiting increased activation, which was absent in the placebo-treated patients. Conclusions: Our results indicate distinct activation differences between untreated adult attention deficit/hyperactivity disorder patients and matched healthy controls during a working memory task. These differences might reflect compensatory efforts by the patients, who are performing at the same level as the healthy controls. We furthermore found a positive effect of methylphenidate on the activation of a frontal region of interest. These observations contribute to a more thorough understanding of adult attention deficit/hyperactivity disorder and provide impulses for the evaluation of therapy-related changes. KW - working memory KW - clinical trial KW - child memory KW - short-term methylphenidate brain KW - methylphenidate KW - adult attention deficit/hyperactivity disorder KW - fMRI KW - functional magnetic resonance imaging Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147551 VL - 19 IS - 10 ER -