TY - JOUR A1 - Alma, Harma A1 - de Jong, Corina A1 - Jelusic, Danijel A1 - Wittmann, Michael A1 - Schuler, Michael A1 - Flokstra-de Blok, Bertine A1 - Kocks, Janwillem A1 - Schultz, Konrad A1 - van der Molen, Thys T1 - Health status instruments for patients with COPD in pulmonary rehabilitation: defining a minimal clinically important difference JF - npj Primary Care Respiration Medicine N2 - The minimal clinically important difference (MCID) defines to what extent change on a health status instrument is clinically relevant, which aids scientists and physicians in measuring therapy effects. This is the first study that aimed to establish the MCID of the Clinical chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ), the COPD Assessment Test (CAT) and the St George’s Respiratory Questionnaire (SGRQ) in the same pulmonary rehabilitation population using multiple approaches. In total, 451 COPD patients participated in a 3-week Pulmonary Rehabilitation (PR) programme (58 years, 65% male, 43 pack-years, GOLD stage II/III/IV 50/39/11%). Techniques used to assess the MCID were anchor-based approaches, including patient-referencing, criterion-referencing and questionnaire-referencing, and the distribution-based methods standard error of measurement (SEM), 1.96SEM and half standard deviation (0.5s.d.). Patient- and criterion-referencing led to MCID estimates of 0.56 and 0.62 (CCQ); 3.12 and 2.96 (CAT); and 8.40 and 9.28 (SGRQ). Questionnaire-referencing suggested MCID ranges of 0.28–0.61 (CCQ), 1.46–3.08 (CAT) and 6.86–9.47 (SGRQ). The SEM, 1.96SEM and 0.5s.d. were 0.29, 0.56 and 0.46 (CCQ); 3.28, 6.43 and 2.80 (CAT); 5.20, 10.19 and 6.06 (SGRQ). Pooled estimates were 0.52 (CCQ), 3.29 (CAT) and 7.91 (SGRQ) for improvement. MCID estimates differed depending on the method used. Pooled estimates suggest clinically relevant improvements needing to exceed 0.40 on the CCQ, 3.00 on the CAT and 7.00 on the SGRQ for moderate to very severe COPD patients. The MCIDs of the CAT and SGRQ in the literature might be too low, leading to overestimation of treatment effects for patients with COPD. KW - COPD KW - rehabilitation KW - health status instruments Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166327 VL - 26 IS - 16041 ER - TY - JOUR A1 - Redlich, Christoph A1 - Lingnau, Benjamin A1 - Holzinger, Steffen A1 - Schlottmann, Elisabeth A1 - Kreinberg, Sören A1 - Schneider, Christian A1 - Kamp, Martin A1 - Höfling, Sven A1 - Wolters, Janik A1 - Reitzenstein, Stephan A1 - Lüdge, Kathy T1 - Mode-switching induced super-thermal bunching in quantum-dot microlasers JF - New Journal of Physics N2 - The super-thermal photon bunching in quantum-dot (QD) micropillar lasers is investigated both experimentally and theoretically via simulations driven by dynamic considerations. Using stochastic multi-mode rate equations we obtain very good agreement between experiment and theory in terms of intensity profiles and intensity-correlation properties of the examined QD micro-laser's emission. Further investigations of the time-dependent emission show that super-thermal photon bunching occurs due to irregular mode-switching events in the bimodal lasers. Our bifurcation analysis reveals that these switchings find their origin in an underlying bistability, such that spontaneous emission noise is able to effectively perturb the two competing modes in a small parameter region. We thus ascribe the observed high photon correlation to dynamical multistabilities rather than quantum mechanical correlations. KW - microlaser KW - nonlinear dynamics KW - correlation properties KW - photon statistics KW - noise and multimode dynamics KW - quantum dot laser Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166286 VL - 18 IS - 063011 ER - TY - JOUR A1 - Hargart, F A1 - Roy-Choudhury, K A1 - John, T A1 - Portalupi, S L A1 - Schneider, C A1 - Höfling, S A1 - Kamp, M A1 - Hughes, S A1 - Michler, P T1 - Probing different regimes of strong field light-matter interaction with semiconductor quantum dots and few cavity photons JF - New Journal of Physics N2 - In this work we present an extensive experimental and theoretical investigation of different regimes of strong field light–matter interaction for cavity-driven quantum dot (QD) cavity systems. The electric field enhancement inside a high-Q micropillar cavity facilitates exceptionally strong interaction with few cavity photons, enabling the simultaneous investigation for a wide range of QD-laser detuning. In case of a resonant drive, the formation of dressed states and a Mollow triplet sideband splitting of up to 45 μeV is measured for amean cavity photon number \(\leq\) 1. In the asymptotic limit of the linear ACStark effect we systematically investigate the power and detuning dependence of more than 400 QDs. Some QD-cavity systems exhibit an unexpected anomalous Stark shift, which can be explained by an extended dressed 4-levelQDmodel.Weprovide a detailed analysis of the QD-cavity systems properties enabling this novel effect. The experimental results are successfully reproduced using a polaron master equation approach for the QD-cavity system, which includes the driving laser field, exciton-cavity and exciton-phonon interactions KW - light–matter interaction KW - quantum dots KW - AC Stark effect KW - dressed states Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166278 VL - 18 ER - TY - JOUR A1 - van de Kerkhof, Nora WA A1 - Fekkes, Durk A1 - van der Heijden, Frank MMA A1 - Hoogendijk, Witte JG A1 - Stöber, Gerald A1 - Egger, Jos IM A1 - Verhoeven, Willem MA T1 - Cycloid psychoses in the psychosis spectrum: evidence for biochemical differences with schizophrenia JF - Neuropsychiatric Disease and Treatment N2 - Cycloid psychoses (CP) differ from schizophrenia regarding symptom profile, course, and prognosis and over many decades they were thought to be a separate entity within the psychosis spectrum. As to schizophrenia, research into the pathophysiology has focused on dopamine, brain-derived neurotrophic factor, and glutamate signaling in which, concerning the latter, the N-methyl-d-aspartate receptor plays a crucial role. The present study aims to determine whether CP can biochemically be delineated from schizophrenia. Eighty patients referred for psychotic disorders were assessed with the Comprehensive Assessment of Symptoms and History, and (both at inclusion and after 6 weeks of antipsychotic treatment) with the Positive and Negative Syndrome Scale and Clinical Global Impression. From 58 completers, 33 patients were diagnosed with schizophrenia and ten with CP according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Leonhard criteria, respectively. Fifteen patients were diagnosed with other disorders within the psychosis spectrum. At both time points, blood levels of the dopamine metabolite homovanillic acid, brain-derived neurotrophic factor, and amino acids related to glutamate neurotransmission were measured and compared with a matched control sample. Patients with CP showed a significantly better response to antipsychotic treatment as compared to patients with schizophrenia. In CP, glycine levels were elevated and tryptophan levels were lowered as compared to schizophrenia. Glutamate levels were increased in both patient groups as compared to controls. These results, showing marked differences in both treatment outcome and glutamate-related variable parameters, may point at better neuroplasticity in CP, necessitating demarcation of this subgroup within the psychosis spectrum. KW - cycloid psychoses KW - schizophrenia KW - glutamate KW - glycine KW - tryptophan KW - neuroplasticity Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166255 VL - 12 ER - TY - JOUR A1 - Stoeckel, M. Cornelia A1 - Esser, Roland W. A1 - Gamer, Matthias A1 - Büchel, Christian A1 - von Leupoldt, Andreas T1 - Brain Responses during the Anticipation of Dyspnea JF - Neural Plasticity N2 - Dyspnea is common in many cardiorespiratory diseases. Already the anticipation of this aversive symptom elicits fear in many patients resulting in unfavorable health behaviors such as activity avoidance and sedentary lifestyle. This study investigated brain mechanisms underlying these anticipatory processes. We induced dyspnea using resistive-load breathing in healthy subjects during functional magnetic resonance imaging. Blocks of severe and mild dyspnea alternated, each preceded by anticipation periods. Severe dyspnea activated a network of sensorimotor, cerebellar, and limbic areas. The left insular, parietal opercular, and cerebellar cortices showed increased activation already during dyspnea anticipation. Left insular and parietal opercular cortex showed increased connectivity with right insular and anterior cingulate cortex when severe dyspnea was anticipated, while the cerebellum showed increased connectivity with the amygdala. Notably, insular activation during dyspnea perception was positively correlated with midbrain activation during anticipation. Moreover, anticipatory fear was positively correlated with anticipatory activation in right insular and anterior cingulate cortex. The results demonstrate that dyspnea anticipation activates brain areas involved in dyspnea perception. The involvement of emotion-related areas such as insula, anterior cingulate cortex, and amygdala during dyspnea anticipation most likely reflects anticipatory fear and might underlie the development of unfavorable health behaviors in patients suffering from dyspnea. KW - brain response KW - dyspnea KW - cardiorespiratory disease KW - anticipation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166238 VL - 2016 IS - 6434987 ER - TY - JOUR A1 - Benoit, Joshua B. A1 - Adelman, Zach N. A1 - Reinhardt, Klaus A1 - Dolan, Amanda A1 - Poelchau, Monica A1 - Jennings, Emily C. A1 - Szuter, Elise M. A1 - Hagan, Richard W. A1 - Gujar, Hemant A1 - Shukla, Jayendra Nath A1 - Zhu, Fang A1 - Mohan, M. A1 - Nelson, David R. A1 - Rosendale, Andrew J. A1 - Derst, Christian A1 - Resnik, Valentina A1 - Wernig, Sebastian A1 - Menegazzi, Pamela A1 - Wegener, Christian A1 - Peschel, Nicolai A1 - Hendershot, Jacob M. A1 - Blenau, Wolfgang A1 - Predel, Reinhard A1 - Johnston, Paul R. A1 - Ioannidis, Panagiotis A1 - Waterhouse, Robert M. A1 - Nauen, Ralf A1 - Schorn, Corinna A1 - Ott, Mark-Christoph A1 - Maiwald, Frank A1 - Johnston, J. Spencer A1 - Gondhalekar, Ameya D. A1 - Scharf, Michael E. A1 - Raje, Kapil R. A1 - Hottel, Benjamin A. A1 - Armisén, David A1 - Crumière, Antonin Jean Johan A1 - Refki, Peter Nagui A1 - Santos, Maria Emilia A1 - Sghaier, Essia A1 - Viala, Sèverine A1 - Khila, Abderrahman A1 - Ahn, Seung-Joon A1 - Childers, Christopher A1 - Lee, Chien-Yueh A1 - Lin, Han A1 - Hughes, Daniel S.T. A1 - Duncan, Elizabeth J. A1 - Murali, Shwetha C. A1 - Qu, Jiaxin A1 - Dugan, Shannon A1 - Lee, Sandra L. A1 - Chao, Hsu A1 - Dinh, Huyen A1 - Han, Yi A1 - Doddapaneni, Harshavardhan A1 - Worley, Kim C. A1 - Muzny, Donna M. A1 - Wheeler, David A1 - Panfilio, Kristen A. A1 - Jentzsch, Iris M. Vargas A1 - Jentzsch, IMV A1 - Vargo, Edward L. A1 - Booth, Warren A1 - Friedrich, Markus A1 - Weirauch, Matthew T. A1 - Anderson, Michelle A.E. A1 - Jones, Jeffery W. A1 - Mittapalli, Omprakash A1 - Zhao, Chaoyang A1 - Zhou, Jing-Jiang A1 - Evans, Jay D. A1 - Attardo, Geoffrey M. A1 - Robertson, Hugh M. A1 - Zdobnov, Evgeny M. A1 - Ribeiro, Jose M.C. A1 - Gibbs, Richard A. A1 - Werren, John H. A1 - Palli, Subba R. A1 - Schal, Coby A1 - Richards, Stephen T1 - Unique features of a global human ectoparasite identified through sequencing of the bed bug genome JF - Nature Communications N2 - The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite. KW - human ectoparasite KW - bed bug KW - Cimex lectularius KW - genome Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166221 VL - 7 IS - 10165 ER - TY - JOUR A1 - Conrad, Thomas A1 - Albrecht, Anne-Susann A1 - Rodrigues de Melo Costa, Veronica A1 - Sauer, Sascha A1 - Meierhofer, David A1 - Andersson Ørom, Ulf T1 - Serial interactome capture of the human cell nucleus JF - Nature Communications N2 - Novel RNA-guided cellular functions are paralleled by an increasing number of RNA-binding proteins (RBPs). Here we present ‘serial RNA interactome capture’ (serIC), a multiple purification procedure of ultraviolet-crosslinked poly(A)–RNA–protein complexes that enables global RBP detection with high specificity. We apply serIC to the nuclei of proliferating K562 cells to obtain the first human nuclear RNA interactome. The domain composition of the 382 identified nuclear RBPs markedly differs from previous IC experiments, including few factors without known RNA-binding domains that are in good agreement with computationally predicted RNA binding. serIC extends the number of DNA–RNA-binding proteins (DRBPs), and reveals a network of RBPs involved in p53 signalling and double-strand break repair. serIC is an effective tool to couple global RBP capture with additional selection or labelling steps for specific detection of highly purified RBPs. KW - human cell nucleus KW - serial RNA interactome capture KW - RNA-binding proteins Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166172 VL - 7 IS - 11212 ER - TY - JOUR A1 - Jahnke, Frank A1 - Gies, Christopher A1 - Aßmann, Marc A1 - Bayer, Manfred A1 - Leymann, H.A.M. A1 - Foerster, Alexander A1 - Wiersig, Jan A1 - Schneider, Christian A1 - Kamp, Martin A1 - Höfling, Sven T1 - Giant photon bunching, superradiant pulse emission and excitation trapping in quantum-dot nanolasers JF - Nature Communications N2 - Light is often characterized only by its classical properties, like intensity or coherence. When looking at its quantum properties, described by photon correlations, new information about the state of the matter generating the radiation can be revealed. In particular the difference between independent and entangled emitters, which is at the heart of quantum mechanics, can be made visible in the photon statistics of the emitted light. The well-studied phenomenon of superradiance occurs when quantum–mechanical correlations between the emitters are present. Notwithstanding, superradiance was previously demonstrated only in terms of classical light properties. Here, we provide the missing link between quantum correlations of the active material and photon correlations in the emitted radiation. We use the superradiance of quantum dots in a cavity-quantum electrodynamics laser to show a direct connection between superradiant pulse emission and distinctive changes in the photon correlation function. This directly demonstrates the importance of quantum–mechanical correlations and their transfer between carriers and photons in novel optoelectronic devices. KW - photon bunching KW - quantum mechanics KW - superradiant pulse emission Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166144 VL - 7 IS - 11540 ER - TY - JOUR A1 - Göbel, Kerstin A1 - Pankratz, Susann A1 - Asaridou, Chloi-Magdalini A1 - Herrmann, Alexander M. A1 - Bittner, Stefan A1 - Merker, Monika A1 - Ruck, Tobias A1 - Glumm, Sarah A1 - Langhauser, Friederike A1 - Kraft, Peter A1 - Krug, Thorsten F. A1 - Breuer, Johanna A1 - Herold, Martin A1 - Gross, Catharina C. A1 - Beckmann, Denise A1 - Korb-Pap, Adelheid A1 - Schuhmann, Michael K. A1 - Kuerten, Stefanie A1 - Mitroulis, Ioannis A1 - Ruppert, Clemens A1 - Nolte, Marc W. A1 - Panousis, Con A1 - Klotz, Luisa A1 - Kehrel, Beate A1 - Korn, Thomas A1 - Langer, Harald F. A1 - Pap, Thomas A1 - Nieswandt, Bernhard A1 - Wiendl, Heinz A1 - Chavakis, Triantafyllos A1 - Kleinschnitz, Christoph A1 - Meuth, Sven G. T1 - Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells JF - Nature Communications N2 - Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein–kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders. KW - blood coagulation KW - factor XII KW - neuroinflammation KW - dendric cells Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165503 VL - 7 IS - 11626 ER - TY - JOUR A1 - Domschke, Katharina A1 - Zwanzger, Peter A1 - Rehbein, Maimu A A1 - Steinberg, Christian A1 - Knoke, Kathrin A1 - Dobel, Christian A1 - Klinkenberg, Isabelle A1 - Kugel, Harald A1 - Kersting, Anette A1 - Arolt, Volker A1 - Pantev, Christo A1 - Junghofer, Markus T1 - Magnetoencephalographic correlates of emotional processing in major depression before and after pharmacological treatment JF - International Journal of Neuropsychopharmacology N2 - Background: In major depressive disorder (MDD), electrophysiological and imaging studies suggest reduced neural activity in the parietal and dorsolateral prefrontal cortex regions. In the present study, neural correlates of emotional processing in MDD were analyzed for the first time in a pre-/post-treatment design by means of magnetoencephalography (MEG), allowing for detecting temporal dynamics of brain activation. Methods: Twenty-five medication-free Caucasian in-patients with MDD and 25 matched controls underwent a baseline MEG session with passive viewing of pleasant, unpleasant, and neutral pictures. Fifteen patients were followed-up with a second MEG session after 4 weeks of antidepressant monopharmacotherapy with mirtazapine. The corresponding controls received no intervention between the measurements. The clinical course of depression was assessed using the Hamilton Depression scale. Results: Prior to treatment, an overall neocortical hypoactivation during emotional processing, particularly at the parietal regions and areas at the right temporoparietal junction, as well as abnormal valence-specific reactions at the right parietal and bilateral dorsolateral prefrontal cortex (dlPFC) regions were observed in patients compared to controls. These effects occurred <150ms, suggesting dysfunctional processing of emotional stimuli at a preconscious level. Successful antidepressant treatment resulted in a normalization of the hypoactivation at the right parietal and right temporoparietal regions. Accordingly, both dlPFC regions revealed an increase of activity after therapy. Conclusions: The present study provides neurophysiological evidence for dysfunctional emotional processing in a fronto-parieto-temporal network, possibly contributing to the pathogenesis of MDD. These activation patterns might have the potential to serve as biomarkers of treatment success. KW - dorsolateral prefrontal cortex KW - temporoparietal junction KW - parietal hypoactivation KW - IAPS KW - EEG KW - MEG KW - MDD Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149873 VL - 19 IS - 2 ER - TY - JOUR A1 - Barbieri, Flavia L. A1 - Gardon, Jacques A1 - Ruiz-Castell, María A1 - Paco V., Pamela A1 - Muckelbauer, Rebecca A1 - Casiot, Corinne A1 - Freydier, Rémi A1 - Duprey, Jean-Louis A1 - Chen, Chih-Mei A1 - Müller-Nordhorn, Jacqueline A1 - Keil, Thomas T1 - Toxic trace elements in maternal and cord blood and social determinants in a Bolivian mining city JF - International Journal of Environmental Health Research N2 - This study assessed lead, arsenic, and antimony in maternal and cord blood, and associations between maternal concentrations and social determinants in the Bolivian mining city of Oruro using the baseline assessment of the ToxBol/Mine-Niño birth cohort. We recruited 467 pregnant women, collecting venous blood and sociodemographic information as well as placental cord blood at birth. Metallic/semimetallic trace elements were measured using inductively coupled plasma mass spectrometry. Lead medians in maternal and cord blood were significantly correlated (Spearman coefficient = 0.59; p < 0.001; 19.35 and 13.50 μg/L, respectively). Arsenic concentrations were above detection limit (3.30 μg/L) in 17.9 % of maternal and 34.6 % of cord blood samples. They were not associated (Fischer’s p = 0.72). Antimony medians in maternal and cord blood were weakly correlated (Spearman coefficient = 0.15; p < 0.03; 9.00 and 8.62 μg/L, respectively). Higher concentrations of toxic elements in maternal blood were associated with maternal smoking, low educational level, and partner involved in mining. KW - environmental exposure KW - metallic trace elements KW - maternal exposure KW - prenatal exposure KW - risk factors Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150385 VL - 26 IS - 2 ER - TY - JOUR A1 - Gratwohl, A A1 - Pfirrmann, M A1 - Zander, A A1 - Kröger, N A1 - Beelen, D A1 - Novotny, J A1 - Nerl, C A1 - Scheid, C A1 - Spiekermann, K A1 - Mayer, J A1 - Sayer, HG A1 - Falge, C A1 - Bunjes, D A1 - Döhner, H A1 - Ganser, A A1 - Schmidt-Wolf, I A1 - Schwerdtfeger, R A1 - Baurmann, H A1 - Kuse, R A1 - Schmitz, N A1 - Wehmeier, A A1 - Fischer, J Th A1 - Ho, AD A1 - Wilhelm, M A1 - Goebeler, M-E A1 - Lindemann, HW A1 - Bormann, M A1 - Hertenstein, B A1 - Schlimok, G A1 - Baerlocher, GM A1 - Aul, C A1 - Pfreundschuh, M A1 - Fabian, M A1 - Staib, P A1 - Edinger, M A1 - Schatz, M A1 - Fauser, A A1 - Arnold, R A1 - Kindler, T A1 - Wulf, G A1 - Rosselet, A A1 - Hellmann, A A1 - Schäfer, E A1 - Prümmer, O A1 - Schenk, M A1 - Hasford, J A1 - Heimpel, H A1 - Hossfeld, DK A1 - Kolb, H-J A1 - Büsche, G A1 - Haferlach, C A1 - Schnittger, S A1 - Müller, MC A1 - Reiter, A A1 - Berger, U A1 - Saußele, S A1 - Hochhaus, A A1 - Hehlmann, R T1 - Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment JF - Leukemia N2 - Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69–0.82) vs 0.69 (95% CI: 0.61–0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P = 0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered. KW - chronic myeloid leukemia KW - stem cell transplantation KW - drug treatment KW - CML KW - tyrosine kinase inhibitors KW - allogeneic hematopoietic stem cell transplantation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150368 VL - 30 ER - TY - JOUR A1 - Pritchard, Rory A. A1 - Falk, Lovissa A1 - Larsson, Mathilda A1 - Leinders, Mathias A1 - Sorkin, Linda S. T1 - Different phosphoinositide 3-kinase isoforms mediate carrageenan nociception and inflammation JF - Pain N2 - Phosphoinositide 3-kinases (PI3Ks) participate in signal transduction cascades that can directly activate and sensitize nociceptors and enhance pain transmission. They also play essential roles in chemotaxis and immune cell infiltration leading to inflammation. We wished to determine which PI3K isoforms were involved in each of these processes. Lightly anesthetized rats (isoflurane) were injected subcutaneously with carrageenan in their hind paws. This was preceded by a local injection of 1% DMSO vehicle or an isoform-specific antagonist to PI3K-α (compound 15-e), -β (TGX221), -δ (Cal-101), or -γ (AS252424). We measured changes in the mechanical pain threshold and spinal c-Fos expression (4 hours after injection) as indices of nociception. Paw volume, plasma extravasation (Evans blue, 0.3 hours after injection), and neutrophil (myeloperoxidase; 1 hour after injection) and macrophage (CD11b+; 4 hour after injection) infiltration into paw tissue were the measured inflammation endpoints. Only PI3K-γ antagonist before treatment reduced the carrageenan-induced pain behavior and spinal expression of c-Fos (P ≤ 0.01). In contrast, pretreatment with PI3K-α, -δ, and-γ antagonists reduced early indices of inflammation. Plasma extravasation PI3K-α (P ≤ 0.05), -δ (P ≤ 0.05), and -γ (P ≤ 0.01), early (0-2 hour) edema -α (P ≤ 0.05), -δ (P ≤ 0.001), and -γ (P ≤ 0.05), and neutrophil infiltration (all P ≤ 0.001) were all reduced compared to vehicle pretreatment. Later (2-4 hour), edema and macrophage infiltration (P ≤ 0.05) were reduced by only the PI3K-δ and -γ isoform antagonists, with the PI3K-δ antagonist having a greater effect on edema. PI3K-β antagonism was ineffective in all paradigms. These data indicate that pain and clinical inflammation are pharmacologically separable and may help to explain clinical conditions in which inflammation naturally wanes or goes into remission, but pain continues unabated. KW - c-Fos KW - macrophage KW - neutrophil KW - plasma extravasation KW - pain KW - edema Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150248 VL - 157 IS - 1 ER - TY - JOUR A1 - Zhu, Min A1 - Shabala, Lana A1 - Cuin, Tracey A A1 - Huang, Xin A1 - Zhou, Meixue A1 - Munns, Rana A1 - Shabala, Sergey T1 - Nax loci affect SOS1-like Na\(^{+}\)/H\(^{+}\) exchanger expression and activity in wheat JF - Journal of Experimental Botany N2 - Salinity stress tolerance in durum wheat is strongly associated with a plant’s ability to control Na\(^{+}\) delivery to the shoot. Two loci, termed Nax1 and Nax2, were recently identified as being critical for this process and the sodium transporters HKT1;4 and HKT1;5 were identified as the respective candidate genes. These transporters retrieve Na\(^{+}\) from the xylem, thus limiting the rates of Na\(^{+}\) transport from the root to the shoot. In this work, we show that the Nax loci also affect activity and expression levels of the SOS1-like Na\(^{+}\)/H\(^{+}\) exchanger in both root cortical and stelar tissues. Net Na\(^{+}\) efflux measured in isolated steles from salt-treated plants, using the non-invasive ion flux measuring MIFE technique, decreased in the sequence: Tamaroi (parental line)>Nax1=Nax2>Nax1:Nax2 lines. This efflux was sensitive to amiloride (a known inhibitor of the Na\(^{+}\)/H\(^{+}\) exchanger) and was mirrored by net H\(^{+}\) flux changes. TdSOS1 relative transcript levels were 6–10-fold lower in Nax lines compared with Tamaroi. Thus, it appears that Nax loci confer two highly complementary mechanisms, both of which contribute towards reducing the xylem Na\(^{+}\) content. One enhances the retrieval of Na\(^{+}\) back into the root stele via HKT1;4 or HKT1;5, whilst the other reduces the rate of Na\(^{+}\) loading into the xylem via SOS1. It is suggested that such duality plays an important adaptive role with greater versatility for responding to a changing environment and controlling Na\(^{+}\) delivery to the shoot. KW - HKT transporter KW - potassium KW - salinity stress KW - sequestration KW - sodium KW - xylem loading Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150236 VL - 67 IS - 3 ER - TY - JOUR A1 - Wandrey, Georg A1 - Wurzel, Joel A1 - Hoffmann, Kyra A1 - Ladner, Tobias A1 - Büchs, Jochen A1 - Meinel, Lorenz A1 - Lühmann, Tessa T1 - Probing unnatural amino acid integration into enhanced green fluorescent protein by genetic code expansion with a high-throughput screening platform JF - Journal of Biological Engineering N2 - Background Genetic code expansion has developed into an elegant tool to incorporate unnatural amino acids (uAA) at predefined sites in the protein backbone in response to an amber codon. However, recombinant production and yield of uAA comprising proteins are challenged due to the additional translation machinery required for uAA incorporation. Results We developed a microtiter plate-based high-throughput monitoring system (HTMS) to study and optimize uAA integration in the model protein enhanced green fluorescence protein (eGFP). Two uAA, propargyl-L-lysine (Plk) and (S)-2-amino-6-((2-azidoethoxy) carbonylamino) hexanoic acid (Alk), were incorporated at the same site into eGFP co-expressing the native PylRS/tRNAPyl CUA pair originating from Methanosarcina barkeri in E. coli. The site-specific uAA functionalization was confirmed by LC-MS/MS analysis. uAA-eGFP production and biomass growth in parallelized E. coli cultivations was correlated to (i) uAA concentration and the (ii) time of uAA addition to the expression medium as well as to induction parameters including the (iii) time and (iv) amount of IPTG supplementation. The online measurements of the HTMS were consolidated by end point-detection using standard enzyme-linked immunosorbent procedures. Conclusion The developed HTMS is powerful tool for parallelized and rapid screening. In light of uAA integration, future applications may include parallelized screening of different PylRS/tRNAPyl CUA pairs as well as further optimization of culture conditions. KW - protein engineering KW - amber codon suppression KW - online monitoring system KW - high-throughput screening KW - unnatural amino acid KW - bio-orthogonal chemistry Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166304 VL - 10 IS - 11 ER - TY - JOUR A1 - Asthana, Manish Kumar A1 - Brunhuber, Bettina A1 - Mühlberger, Andreas A1 - Reif, Andreas A1 - Schneider, Simone A1 - Herrmann, Martin J. T1 - Preventing the Return of Fear Using Reconsolidation Update Mechanisms Depends on the Met-Allele of the Brain Derived Neurotrophic Factor Val66Met Polymorphism JF - International Journal of Neuropsychopharmacology N2 - Background: Memory reconsolidation is the direct effect of memory reactivation followed by stabilization of newly synthesized proteins. It has been well proven that neural encoding of both newly and reactivated memories requires synaptic plasticity. Brain derived neurotrophic factor (BDNF) has been extensively investigated regarding its role in the formation of synaptic plasticity and in the alteration of fear memories. However, its role in fear reconsolidation is still unclear; hence, the current study has been designed to investigate the role of the BDNF val66met polymorphism (rs6265) in fear memory reconsolidation in humans. Methods: An auditory fear-conditioning paradigm was conducted, which comprised of three stages (acquisition, reactivation, and spontaneous recovery). One day after fear acquisition, the experimental group underwent reactivation of fear memory followed by the extinction training (reminder group), whereas the control group (non-reminder group) underwent only extinction training. On day 3, both groups were subjected to spontaneous recovery of earlier learned fearful memories. The treat-elicited defensive response due to conditioned threat was measured by assessing the skin conductance response to the conditioned stimulus. All participants were genotyped for rs6265. Results: The results indicate a diminishing effect of reminder on the persistence of fear memory only in the Met-allele carriers, suggesting a moderating effect of the BDNF polymorphism in fear memory reconsolidation. Conclusions: Our findings suggest a new role for BDNF gene variation in fear memory reconsolidation in humans. KW - BDNF KW - brain derived neurotrophic factor KW - fear conditioning KW - genetics memory KW - reconsolidation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166217 VL - 19 IS - 6 ER - TY - JOUR A1 - Schuhmann, Michael K. A1 - Gunreben, Ignaz A1 - Kleinschnitz, Christoph A1 - Kraft, Peter T1 - Immunohistochemical Analysis of Cerebral Thrombi Retrieved by Mechanical Thrombectomy from Patients with Acute Ischemic Stroke JF - International Journal of Molecular Sciences N2 - Mechanical thrombectomy is a novel treatment option for patients with acute ischemic stroke (AIS). Only a few studies have previously suggested strategies to categorize retrieved clots according to their histologic composition. However, these reports did not analyze potential biomarkers that are of importance in stroke-related inflammation. We therefore histopathologically investigated 37 intracerebral thrombi mechanically retrieved from patients with AIS, and focused on the composition of immune cells and platelets. We also conducted correlation analyses of distinctive morphologic patterns (erythrocytic, serpentine, layered, red, white, mixed appearance) with clinical parameters. Most T cells and monocytes were detected in erythrocytic and red clots, in which the distribution of these cells was random. In contrast, von Willebrand factor (vWF)-positive areas co-localized with regions of fibrin and collagen. While clots with huge amounts of vWF seem to be associated with a high National Institute of Health Stroke Scale score at admission, histologic findings could not predict the clinical outcome at discharge. In summary, we provide the first histologic description of mechanically retrieved intracerebral thrombi regarding biomarkers relevant for inflammation in ischemic stroke. KW - thrombus formation KW - immune cells KW - lymphocytes KW - mechanical thrombectomy KW - ischemic stroke KW - inflammation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166206 VL - 17 IS - 3 ER - TY - JOUR A1 - Grünewald, Benedikt A1 - Bennett, Jeffrey L. A1 - Toyka, Klaus V. A1 - Sommer, Claudia A1 - Geis, Christian T1 - Efficacy of Polyvalent Human Immunoglobulins in an Animal Model of Neuromyelitis Optica Evoked by Intrathecal Anti-Aquaporin 4 Antibodies JF - International Journal of Molecular Sciences N2 - Neuromyelitis Optica Spectrum Disorders (NMOSD) are associated with autoantibodies (ABs) targeting the astrocytic aquaporin-4 water channels (AQP4-ABs). These ABs have a direct pathogenic role by initiating a variety of immunological and inflammatory processes in the course of disease. In a recently-established animal model, chronic intrathecal passive-transfer of immunoglobulin G from NMOSD patients (NMO-IgG), or of recombinant human AQP4-ABs (rAB-AQP4), provided evidence for complementary and immune-cell independent effects of AQP4-ABs. Utilizing this animal model, we here tested the effects of systemically and intrathecally applied pooled human immunoglobulins (IVIg) using a preventive and a therapeutic paradigm. In NMO-IgG animals, prophylactic application of systemic IVIg led to a reduced median disease score of 2.4 on a 0–10 scale, in comparison to 4.1 with sham treatment. Therapeutic IVIg, applied systemically after the 10th intrathecal NMO-IgG injection, significantly reduced the disease score by 0.8. Intrathecal IVIg application induced a beneficial effect in animals with NMO-IgG (median score IVIg 1.6 vs. sham 3.7) or with rAB-AQP4 (median score IVIg 2.0 vs. sham 3.7). We here provide evidence that treatment with IVIg ameliorates disease symptoms in this passive-transfer model, in analogy to former studies investigating passive-transfer animal models of other antibody-mediated disorders. KW - intrathecal application KW - NMOSD KW - aquaporin 4 KW - autoantibody KW - IVIg Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166000 VL - 17 IS - 9 ER - TY - JOUR A1 - Grimmig, Tanja A1 - Moench, Romana A1 - Kreckel, Jennifer A1 - Haack, Stephanie A1 - Rueckert, Felix A1 - Rehder, Roberta A1 - Tripathi, Sudipta A1 - Ribas, Carmen A1 - Chandraker, Anil A1 - Germer, Christoph T. A1 - Gasser, Martin A1 - Waaga-Gasser, Ana Maria T1 - Toll Like Receptor 2, 4, and 9 Signaling Promotes Autoregulative Tumor Cell Growth and VEGF/PDGF Expression in Human Pancreatic Cancer JF - International Journal of Molecular Sciences N2 - Toll like receptor (TLR) signaling has been suggested to play an important role in the inflammatory microenvironment of solid tumors and through this inflammation-mediated tumor growth. Here, we studied the role of tumor cells in their process of self-maintaining TLR expression independent of inflammatory cells and cytokine milieu for autoregulative tumor growth signaling in pancreatic cancer. We analyzed the expression of TLR2, -4, and -9 in primary human cancers and their impact on tumor growth via induced activation in several established pancreatic cancers. TLR-stimulated pancreatic cancer cells were specifically investigated for activated signaling pathways of VEGF/PDGF and anti-apoptotic Bcl-xL expression as well as tumor cell growth. The primary pancreatic cancers and cell lines expressed TLR2, -4, and -9. TLR-specific stimulation resulted in activated MAP-kinase signaling, most likely via autoregulative stimulation of demonstrated TLR-induced VEGF and PDGF expression. Moreover, TLR activation prompted the expression of Bcl-xL and has been demonstrated for the first time to induce tumor cell proliferation in pancreatic cancer. These findings strongly suggest that pancreatic cancer cells use specific Toll like receptor signaling to promote tumor cell proliferation and emphasize the particular role of TLR2, -4, and -9 in this autoregulative process of tumor cell activation and proliferation in pancreatic cancer. KW - tumor growth KW - TLR2 KW - TLR4 KW - TLR9 KW - pancreatic cancer KW - inflammation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165743 VL - 17 IS - 12 ER - TY - JOUR A1 - Düking, Peter A1 - Hotho, Andreas A1 - Holmberg, Hans-Christer A1 - Fuss, Franz Konstantin A1 - Sperlich, Billy T1 - Comparison of Non-Invasive Individual Monitoring of the Training and Health of Athletes with Commercially Available Wearable Technologies JF - Frontiers in Physiology N2 - Athletes adapt their training daily to optimize performance, as well as avoid fatigue, overtraining and other undesirable effects on their health. To optimize training load, each athlete must take his/her own personal objective and subjective characteristics into consideration and an increasing number of wearable technologies (wearables) provide convenient monitoring of various parameters. Accordingly, it is important to help athletes decide which parameters are of primary interest and which wearables can monitor these parameters most effectively. Here, we discuss the wearable technologies available for non-invasive monitoring of various parameters concerning an athlete's training and health. On the basis of these considerations, we suggest directions for future development. Furthermore, we propose that a combination of several wearables is most effective for accessing all relevant parameters, disturbing the athlete as little as possible, and optimizing performance and promoting health. KW - sports technology KW - wearable technologies KW - performance parameters KW - health monitoring KW - performance monitoring Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165516 VL - 7 IS - 71 ER - TY - JOUR A1 - Halder, Sebastian A1 - Takano, Kouji A1 - Ora, Hiroki A1 - Onishi, Akinari A1 - Utsumi, Kota A1 - Kansaku, Kenji T1 - An Evaluation of Training with an Auditory P300 Brain-Computer Interface for the Japanese Hiragana Syllabary JF - Frontiers in Neuroscience N2 - Gaze-independent brain-computer interfaces (BCIs) are a possible communication channel for persons with paralysis. We investigated if it is possible to use auditory stimuli to create a BCI for the Japanese Hiragana syllabary, which has 46 Hiragana characters. Additionally, we investigated if training has an effect on accuracy despite the high amount of different stimuli involved. Able-bodied participants (N = 6) were asked to select 25 syllables (out of fifty possible choices) using a two step procedure: First the consonant (ten choices) and then the vowel (five choices). This was repeated on 3 separate days. Additionally, a person with spinal cord injury (SCI) participated in the experiment. Four out of six healthy participants reached Hiragana syllable accuracies above 70% and the information transfer rate increased from 1.7 bits/min in the first session to 3.2 bits/min in the third session. The accuracy of the participant with SCI increased from 12% (0.2 bits/min) to 56% (2 bits/min) in session three. Reliable selections from a 10 × 5 matrix using auditory stimuli were possible and performance is increased by training. We were able to show that auditory P300 BCIs can be used for communication with up to fifty symbols. This enables the use of the technology of auditory P300 BCIs with a variety of applications. KW - gaze independence KW - assistive technology KW - electroencephalography KW - event-related potentials KW - P300 KW - auditory stimulation KW - brain-computer interface Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165465 VL - 10 IS - 446 ER - TY - JOUR A1 - Langlhofer, Georg A1 - Villmann, Carmen T1 - The Intracellular Loop of the Glycine Receptor: It's not all about the Size JF - Frontiers in Molecular Neuroscience N2 - The family of Cys-loop receptors (CLRs) shares a high degree of homology and sequence identity. The overall structural elements are highly conserved with a large extracellular domain (ECD) harboring an α-helix and 10 β-sheets. Following the ECD, four transmembrane domains (TMD) are connected by intracellular and extracellular loop structures. Except the TM3–4 loop, their length comprises 7–14 residues. The TM3–4 loop forms the largest part of the intracellular domain (ICD) and exhibits the most variable region between all CLRs. The ICD is defined by the TM3–4 loop together with the TM1–2 loop preceding the ion channel pore. During the last decade, crystallization approaches were successful for some members of the CLR family. To allow crystallization, the intracellular loop was in most structures replaced by a short linker present in prokaryotic CLRs. Therefore, no structural information about the large TM3–4 loop of CLRs including the glycine receptors (GlyRs) is available except for some basic stretches close to TM3 and TM4. The intracellular loop has been intensively studied with regard to functional aspects including desensitization, modulation of channel physiology by pharmacological substances, posttranslational modifications, and motifs important for trafficking. Furthermore, the ICD interacts with scaffold proteins enabling inhibitory synapse formation. This review focuses on attempts to define structural and functional elements within the ICD of GlyRs discussed with the background of protein-protein interactions and functional channel formation in the absence of the TM3–4 loop. KW - posttranslational modifications KW - GlyR receptors KW - synaptic inhibition KW - intracellular domain KW - interaction partners Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165394 IS - 9 ER - TY - JOUR A1 - Dix, Andreas A1 - Czakai, Kristin A1 - Springer, Jan A1 - Fliesser, Mirjam A1 - Bonin, Michael A1 - Guthke, Reinhard A1 - Schmitt, Anna L. A1 - Einsele, Hermann A1 - Linde, Jörg A1 - Löffler, Jürgen T1 - Genome-Wide Expression Profiling Reveals S100B as Biomarker for Invasive Aspergillosis JF - Frontiers in Microbiology N2 - Invasive aspergillosis (IA) is a devastating opportunistic infection and its treatment constitutes a considerable burden for the health care system. Immunocompromised patients are at an increased risk for IA, which is mainly caused by the species Aspergillus fumigatus. An early and reliable diagnosis is required to initiate the appropriate antifungal therapy. However, diagnostic sensitivity and accuracy still needs to be improved, which can be achieved at least partly by the definition of new biomarkers. Besides the direct detection of the pathogen by the current diagnostic methods, the analysis of the host response is a promising strategy toward this aim. Following this approach, we sought to identify new biomarkers for IA. For this purpose, we analyzed gene expression profiles of hematological patients and compared profiles of patients suffering from IA with non-IA patients. Based on microarray data, we applied a comprehensive feature selection using a random forest classifier. We identified the transcript coding for the S100 calcium-binding protein B (S100B) as a potential new biomarker for the diagnosis of IA. Considering the expression of this gene, we were able to classify samples from patients with IA with 82.3% sensitivity and 74.6% specificity. Moreover, we validated the expression of S100B in a real-time reverse transcription polymerase chain reaction (RT-PCR) assay and we also found a down-regulation of S100B in A. fumigatus stimulated DCs. An influence on the IL1B and CXCL1 downstream levels was demonstrated by this S100B knockdown. In conclusion, this study covers an effective feature selection revealing a key regulator of the human immune response during IA. S100B may represent an additional diagnostic marker that in combination with the established techniques may improve the accuracy of IA diagnosis. KW - human biomarker KW - invasive aspergillosis KW - allogeneic stem cell transplantation KW - gene expression data KW - fungal infection Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165386 IS - 7 ER - TY - JOUR A1 - Kalleda, Natarajaswamy A1 - Amich, Jorge A1 - Arslan, Berkan A1 - Poreddy, Spoorthi A1 - Mattenheimer, Katharina A1 - Mokhtari, Zeinab A1 - Einsele, Hermann A1 - Brock, Matthias A1 - Heinze, Katrin Gertrud A1 - Beilhack, Andreas T1 - Dynamic Immune Cell Recruitment After Murine Pulmonary Aspergillus fumigatus Infection under Different Immunosuppressive Regimens JF - Frontiers in Microbiology N2 - Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonary immune response after A. fumigatus infection to reveal basic immunological events that fail to effectively control invasive fungal disease. In different immunocompromised murine models, myeloid, notably neutrophils, and macrophages, but not lymphoid cells were strongly recruited to the lungs upon infection. Other myeloid cells, particularly dendritic cells and monocytes, were only recruited to lungs of corticosteroid treated mice, which developed a strong pulmonary inflammation after infection. Lymphoid cells, particularly CD4\(^+\) or CD8\(^+\) T-cells and NK cells were highly reduced upon immunosuppression and not recruited after A. fumigatus infection. Moreover, adoptive CD11b\(^+\) myeloid cell transfer rescued cyclophosphamide immunosuppressed mice from lethal A. fumigatus infection but not cortisone and cyclophosphamide immunosuppressed mice. Our findings illustrate that CD11b\(^+\) myeloid cells are critical for anti-A. fumigatus defense under cyclophosphamide immunosuppressed conditions. KW - corticosteroids and cyclophosphamide KW - aspergillus fumigatus KW - CD11b+ myeloid cells KW - immune cell recruitment Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165368 VL - 7 IS - 1107 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 - Isaias, Ioannis U. A1 - Trujillo, Paula A1 - Summers, Paul A1 - Marotta, Giorgio A1 - Mainardi, Luca A1 - Pezzoli, Gianni A1 - Zecca, Luigi A1 - Costa, Antonella T1 - Neuromelanin Imaging and Dopaminergic Loss in Parkinson's Disease JF - Frontiers in Aging Neuroscience N2 - Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the major pathologic substrate is a loss of dopaminergic neurons from the substantia nigra. Our main objective was to determine the correspondence between changes in the substantia nigra, evident in neuromelanin and iron sensitive magnetic resonance imaging (MRI), and dopaminergic striatal innervation loss in patients with PD. Eighteen patients and 18 healthy control subjects were included in the study. Using neuromelanin-MRI, we measured the volume of the substantia nigra and the contrast-to-noise-ratio between substantia nigra and a background region. The apparent transverse relaxation rate and magnetic susceptibility of the substantia nigra were calculated from dual-echo MRI. Striatal dopaminergic innervation was measured as density of dopamine transporter (DAT) by means of single-photon emission computed tomography and [123I] N-ω-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) tropane. Patients showed a reduced volume of the substantia nigra and contrast-to-noise-ratio and both positively correlated with the corresponding striatal DAT density. The apparent transverse relaxation rate and magnetic susceptibility values of the substantia nigra did not differ between patients and healthy controls. The best predictor of DAT reduction was the volume of the substantia nigra. Clinical and imaging correlations were also investigated for the locus coeruleus. Our results suggest that neuromelanin-MRI can be used for quantifying substantia nigra pathology in PD where it closely correlates with dopaminergic striatal innervation loss. Longitudinal studies should further explore the role of Neuromelanin-MRI as an imaging biomarker of PD, especially for subjects at risk of developing the disease. KW - MRI KW - neuromelanin KW - dopamine KW - Parkinson's disease KW - FP-CIT SPECT Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164046 VL - 8 IS - 196 ER - TY - JOUR A1 - Hennighausen, Christine A1 - Hudders, Liselot A1 - Lange, Benjamin P. A1 - Fink, Hanna T1 - What If the Rival Drives a Porsche? Luxury Car Spending as a Costly Signal in Male Intrasexual Competition JF - Evolutionary Psychology N2 - Previous research found that men conspicuously consume luxury products to attract a mate and to signal their mate value. However, these studies have yet neglected to investigate the function of male conspicuous consumption in same-sex competition. Given that intersexual selection and intrasexual selection are closely related processes, it stands to reason that a further function of male conspicuous consumption could be to impress and deter same-sex rivals. An 2 (intrasexual competition context vs. control) × 2 (conspicuous luxury vs. inconspicuous nonluxury) between-subjects experimental study conducted with an Amazon Mechanical Turk sample (N = 160) revealed that men reported both higher liking of and an intent to purchase a conspicuous luxury car compared to an inconspicuous nonluxury car due to increased feelings of social status. This effect was stronger in the intrasexual competition than in the control context. An additional perception study using a single-factor between-subjects design (conspicuous luxury vs. inconspicuous nonluxury car) among German men (N = 405) indicated that male participants rated a man who displayed a conspicuous luxury car more as a rival and mate poacher and less as a friend. They further perceived him to be superior on various mate value characteristics (i.e., attractiveness, intelligence, ambition, and status) and rated him as more oriented toward short-term mating. In sum, our findings add to previous research in the field of evolutionary consumer psychology by suggesting that male conspicuous consumption of luxuries may also serve a function in male–male competition. KW - costly KW - dual function KW - intrasexual competition KW - men KW - luxury brands KW - conspicuous consumption KW - signaling KW - evolutionary consumer psychology Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-163481 VL - 14 IS - 4 ER - TY - JOUR A1 - Kümmel, Reiner T1 - The Impact of Entropy Production and Emission Mitigation on Economic Growth JF - Entropy N2 - Entropy production in industrial economies involves heat currents, driven by gradients of temperature, and particle currents, driven by specific external forces and gradients of temperature and chemical potentials. Pollution functions are constructed for the associated emissions. They reduce the output elasticities of the production factors capital, labor, and energy in the growth equation of the capital-labor-energy-creativity model, when the emissions approach their critical limits. These are drawn by, e.g., health hazards or threats to ecological and climate stability. By definition, the limits oblige the economic actors to dedicate shares of the available production factors to emission mitigation, or to adjustments to the emission-induced changes in the biosphere. Since these shares are missing for the production of the quantity of goods and services that would be available to consumers and investors without emission mitigation, the “conventional” output of the economy shrinks. The resulting losses of conventional output are estimated for two classes of scenarios: (1) energy conservation; and (2) nuclear exit and subsidies to photovoltaics. The data of the scenarios refer to Germany in the 1980s and after 11 March 2011. For the energy-conservation scenarios, a method of computing the reduction of output elasticities by emission abatement is proposed. KW - economic growth KW - entropy production KW - emissions KW - critical limits KW - pollution functions KW - output elasticities Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-163185 VL - 18 IS - 3 ER - TY - JOUR A1 - Weismann, Dirk A1 - Schneider, Andreas A1 - Höybye, Charlotte T1 - Clinical aspects of symptomatic hyponatremia JF - Endocrine Connections N2 - Hyponatremia (HN) is a common condition, with a large number of etiologies and a complicated treatment. Although chronic HN has been shown to be a predictor of poor outcome, sodium-increasing treatments in chronic stable and asymptomatic HN have not proven to increase life expectancy. For symptomatic HN, in contrast, the necessity for urgent treatment has broadly been accepted to avoid the development of fatal cerebral edema. On the other hand, a too rapid increase of serum sodium in chronic HN may result in cerebral damage due to osmotic demyelinisation. Recently, administration of hypertonic saline bolus has been recommended as first-line treatment in patients with moderate-to-severe symptomatic HN. This approach is easy to memorize and holds the potential to greatly facilitate the initial treatment of symptomatic HN. First-line treatment of chronic HN is fluid restriction and if ineffective treatment with tolvaptan or in some patients other agents should be considered. A number of recommendations and guidelines have been published on HN. In the present review, the management of patients with HN in relation to everyday clinical practice is summarized with focus on the acute management. KW - hyponatremia KW - clinical Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162936 VL - 5 IS - 5 ER - TY - JOUR A1 - Lorenzin, Francesca A1 - Benary, Uwe A1 - Baluapuri, Apoorva A1 - Walz, Susanne A1 - Jung, Lisa Anna A1 - von Eyss, Björn A1 - Kisker, Caroline A1 - Wolf, Jana A1 - Eilers, Martin A1 - Wolf, Elmar T1 - Different promoter affinities account for specificity in MYC-dependent gene regulation JF - eLife N2 - Enhanced expression of the MYC transcription factor is observed in the majority of tumors. Two seemingly conflicting models have been proposed for its function: one proposes that MYC enhances expression of all genes, while the other model suggests gene-specific regulation. Here, we have explored the hypothesis that specific gene expression profiles arise since promoters differ in affinity for MYC and high-affinity promoters are fully occupied by physiological levels of MYC. We determined cellular MYC levels and used RNA- and ChIP-sequencing to correlate promoter occupancy with gene expression at different concentrations of MYC. Mathematical modeling showed that binding affinities for interactions of MYC with DNA and with core promoter-bound factors, such as WDR5, are sufficient to explain promoter occupancies observed in vivo. Importantly, promoter affinity stratifies different biological processes that are regulated by MYC, explaining why tumor-specific MYC levels induce specific gene expression programs and alter defined biological properties of cells. KW - MYC KW - promoter affinity KW - human KW - mathematical modeling KW - mouse KW - ChIP-sequencing KW - MIZ1 KW - cancer biology KW - cell biology KW - WDR5 Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162913 VL - 5 ER - TY - JOUR A1 - Kaluza, Benjamin F. A1 - Wallace, Helen A1 - Heard, Tim A. A1 - Klein, Aelxandra-Maria A1 - Leonhardt, Sara D. T1 - Urban gardens promote bee foraging over natural habitats and plantations JF - Ecology and Evolution N2 - Increasing human land use for agriculture and housing leads to the loss of natural habitat and to widespread declines in wild bees. Bee foraging dynamics and fitness depend on the availability of resources in the surrounding landscape, but how precisely landscape related resource differences affect bee foraging patterns remains unclear. To investigate how landscape and its interaction with season and weather drive foraging and resource intake in social bees, we experimentally compared foraging activity, the allocation of foragers to different resources (pollen, nectar, and resin) and overall resource intake in the Australian stingless bee Tetragonula carbonaria (Apidae, Meliponini). Bee colonies were monitored in different seasons over two years. We compared foraging patterns and resource intake between the bees' natural habitat (forests) and two landscapes differently altered by humans (suburban gardens and agricultural macadamia plantations). We found foraging activity as well as pollen and nectar forager numbers to be highest in suburban gardens, intermediate in forests and low in plantations. Foraging patterns further differed between seasons, but seasonal variations strongly differed between landscapes. Sugar and pollen intake was low in plantations, but contrary with our predictions, it was even higher in gardens than in forests. In contrast, resin intake was similar across landscapes. Consequently, differences in resource availability between natural and altered landscapes strongly affect foraging patterns and thus resource intake in social bees. While agricultural monocultures largely reduce foraging success, suburban gardens can increase resource intake well above rates found in natural habitats of bees, indicating that human activities can both decrease and increase the availability of resources in a landscape and thus reduce or enhance bee fitness. KW - urbanization KW - anthropogenic activities KW - climate factors KW - meliponines KW - resource availability Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162713 VL - 6 IS - 5 ER - TY - JOUR A1 - Ahmed, Zeeshan A1 - Zeeshan, Saman A1 - Dandekar, Thomas T1 - Mining biomedical images towards valuable information retrieval in biomedical and life sciences JF - Database - The Journal of Biological Databases and Curation N2 - Biomedical images are helpful sources for the scientists and practitioners in drawing significant hypotheses, exemplifying approaches and describing experimental results in published biomedical literature. In last decades, there has been an enormous increase in the amount of heterogeneous biomedical image production and publication, which results in a need for bioimaging platforms for feature extraction and analysis of text and content in biomedical images to take advantage in implementing effective information retrieval systems. In this review, we summarize technologies related to data mining of figures. We describe and compare the potential of different approaches in terms of their developmental aspects, used methodologies, produced results, achieved accuracies and limitations. Our comparative conclusions include current challenges for bioimaging software with selective image mining, embedded text extraction and processing of complex natural language queries. KW - humans KW - software KW - image processing KW - animals KW - computer-assisted KW - data mining/methods KW - natural language processing Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162697 VL - 2016 ER - TY - JOUR A1 - Tiede, Jennifer A1 - Grafe, Silke T1 - Media Pedagogy in German and US Teacher Education JF - Communicar N2 - Varios estudios de investigación y de práctica llegan a la conclusión de que la pedagogía de los medios debe integrarse en la formación de profesores para que estos futuros docentes puedan utilizar los medios de comunicación en sus clases con eficacia y éxito. Sin embargo, estos resultados no se reflejan en los programas universitarios vigentes, de manera que en algunas instituciones los profesores en formación pueden llegar al término de sus estudios sin haber abordado cuestiones de educación en medios. Para comprender, evaluar y más adelante mejorar la situación actual de la formación del profesorado en el ámbito de la pedagogía de los medios se necesitan extensas investigaciones. Teniendo en cuenta esta situación, el siguiente artículo presenta un resumen del «statu quo» de las competencias en pedagogía de los medios de los futuros profesores, centrándose en los ejemplos de Alemania y EEUU. Para crear una base presentamos diferentes modelos de competencias pedagógicas mediáticas de ambos países e intentaremos responder a la pregunta si estas competencias son promovidas por los programas de formación del profesorado. Después, se describirán el método y resultados seleccionados de un estudio que midió las competencias en pedagogía de los medios de estudiantes de ambos países, estudio basado en un modelo generalizador de competencias pedagógicas mediáticas que conectan la investigación alemana e internacional en este campo. La perspectiva internacional comparada ayuda a extender perspectivas y comprender diferencias y similitudes. Los datos de este estudio sirven para identificar diferentes formas de integrar la pedagogía de los medios de comunicación en la formación del profesorado. Además, se pueden sacar conclusiones sobre las consecuencias que implican estos procesos para profesores en formación y sus competencias mediáticas. N2 - Various research works and practitioners conclude that media pedagogy should be integrated in teacher education in order to enable future teachers to use media for their lessons effectively and successfully. However, this realization is not necessarily reflected in actual university curricula, as preservice teachers at some places can still finish their studies without ever dealing with media pedagogical issues. To understand, assess and eventually improve the status of media pedagogical teacher education, comprehensive research is required. Against this background, the following article seeks to present a theory-based and empirical overview of the status quo of preservice teachers’ pedagogical media competencies focusing Germany and the USA exemplarily. To form a basis, different models of pedagogical media competencies from both countries will be introduced and the extent to which these competencies have become part of teacher education programs and related studies will be summarised. Afterwards, method and selected results of a study will be described where the skills in question were measured with students from both countries, based on a comprehensive model of pedagogical media competencies that connects German and international research in this field. The international comparative perspective will help broaden the viewpoint and understand differences, but also similarities. These data serve to identify different ways of integrating media pedagogy into teacher training and draw conclusions on the consequences these processes entail for preservice teachers and their pedagogical media competencies. T2 - Pedagogía mediática en la formación de profesores de Alemania y EEUU KW - enseñanzapor por competencias KW - currículum KW - análisis transnacional KW - investigación de currículo universitario KW - currículo de la educación en medios KW - alfabetización mediática KW - educación en medios KW - pedagogía KW - formación de profesorado KW - investigación KW - media literacy KW - media education KW - pedagogy KW - preservice teacher education KW - competency based teaching KW - curricula KW - research KW - crossnational analysis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162600 VL - XXIV IS - 49 ER - TY - JOUR A1 - Han, Yanshuo A1 - Tanios, Fadwa A1 - Reeps, Christian A1 - Zhang, Jian A1 - Schwamborn, Kristina A1 - Eckstein, Hans-Henning A1 - Zernecke, Alma A1 - Pelisek, Jaroslav T1 - Histone acetylation and histone acetyltransferases show significant alterations in human abdominal aortic aneurysm JF - Clinical Epigenetics N2 - Background Epigenetic modifications may play a relevant role in the pathogenesis of human abdominal aortic aneurysm (AAA). The aim of the study was therefore to investigate histone acetylation and expression of corresponding lysine [K] histone acetyltransferases (KATs) in AAA. Results A comparative study of AAA tissue samples (n = 37, open surgical intervention) and healthy aortae (n = 12, trauma surgery) was performed using quantitative PCR, immunohistochemistry (IHC), and Western blot. Expression of the KAT families GNAT (KAT2A, KAT2B), p300/CBP (KAT3A, KAT3B), and MYST (KAT5, KAT6A, KAT6B, KAT7, KAT8) was significantly higher in AAA than in controls (P ≤ 0.019). Highest expression was observed for KAT2B, KAT3A, KAT3B, and KAT6B (P ≤ 0.007). Expression of KAT2B significantly correlated with KAT3A, KAT3B, and KAT6B (r = 0.705, 0.564, and 0.528, respectively, P < 0.001), and KAT6B with KAT3A, KAT3B, and KAT6A (r = 0.407, 0.500, and 0.531, respectively, P < 0.05). Localization of highly expressed KAT2B, KAT3B, and KAT6B was further characterized by immunostaining. Significant correlations were observed between KAT2B with endothelial cells (ECs) (r = 0.486, P < 0.01), KAT3B with T cells and macrophages, (r = 0.421 and r = 0.351, respectively, P < 0.05), KAT6A with intramural ECs (r = 0.541, P < 0.001) and with a contractile phenotype of smooth muscle cells (SMCs) (r = 0.425, P < 0.01), and KAT6B with T cells (r = 0.553, P < 0.001). Furthermore, KAT2B was associated with AAA diameter (r = 0.382, P < 0.05), and KAT3B, KAT6A, and KAT6B correlated negatively with blood urea nitrogen (r = −0.403, −0.408, −0.478, P < 0.05). In addtion, acetylation of the histone substrates H3K9, H3K18 and H3K14 was increased in AAA compared to control aortae. Conclusions Our results demonstrate that aberrant epigenetic modifications such as changes in the expression of KATs and acetylation of corresponding histones are present in AAA. These findings may provide new insight in the pathomechanism of AAA. KW - acetyltransferases KW - epigenetics KW - AAA KW - histone acetylation KW - KAT/HAT Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162557 VL - 8 IS - 3 ER - TY - JOUR A1 - Görl, Daniel A1 - Soberats, Bartolome A1 - Herbst, Stefanie A1 - Stepanenko, Vladimir A1 - Würthner, Frank T1 - Perylene bisimide hydrogels and lyotropic liquid crystals with temperature-responsive color change JF - Chemical Science N2 - The self-assembly of perylene bisimide (PBI) dyes bearing oligo ethylene glycol (OEG) units in water affords responsive functional nanostructures characterized by their lower critical solution temperature (LCST). Tuning of the LCST is realized by a supramolecular approach that relies on two structurally closely related PBI–OEG molecules. The two PBIs socially co-assemble in water and the resulting nanostructures exhibit a single LCST in between the transition temperatures of the aggregates formed by single components. This permits to precisely tune the transition from a hydrogel to a lyotropic liquid crystal state at temperatures between 26 and 51 °C by adjusting the molar fraction of the two PBIs. Owing to concomitant changes in PBI–PBI interactions this phase transition affords a pronounced color change with “fluorescence-on” response that can be utilized as a smart temperature sensory system. KW - perylene bisimide hydrogels Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162459 VL - 7 IS - 11 ER - TY - JOUR A1 - Paknia, Elham A1 - Chari, Ashwin A1 - Stark, Holger A1 - Fischer, Utz T1 - The Ribosome Cooperates with the Assembly Chaperone pICln to Initiate Formation of snRNPs JF - Cell Reports N2 - The formation of macromolecular complexes within the crowded environment of cells often requires aid from assembly chaperones. PRMT5 and SMN complexes mediate this task for the assembly of the common core of pre-mRNA processing small nuclear ribonucleoprotein particles (snRNPs). Core formation is initiated by the PRMT5-complex subunit pICln, which pre-arranges the core proteins into spatial positions occupied in the assembled snRNP. The SMN complex then accepts these pICln-bound proteins and unites them with small nuclear RNA (snRNA). Here, we have analyzed how newly synthesized snRNP proteins are channeled into the assembly pathway to evade mis-assembly. We show that they initially remain bound to the ribosome near the polypeptide exit tunnel and dissociate upon association with pICln. Coincident with its release activity, pICln ensures the formation of cognate heterooligomers and their chaperoned guidance into the assembly pathway. Our study identifies the ribosomal quality control hub as a site where chaperone-mediated assembly of macromolecular complexes can be initiated. KW - ribosome KW - snRNPs KW - assembly chaperone KW - pICln Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162420 VL - 16 IS - 12 ER - TY - JOUR A1 - Maiellaro, Isabella A1 - Lohse, Martin J. A1 - Kitte, Robert J. A1 - Calebiro, Davide T1 - cAMP Signals in Drosophila Motor Neurons Are Confined to Single Synaptic Boutons JF - Cell Reports N2 - The second messenger cyclic AMP (cAMP) plays an important role in synaptic plasticity. Although there is evidence for local control of synaptic transmission and plasticity, it is less clear whether a similar spatial confinement of cAMP signaling exists. Here, we suggest a possible biophysical basis for the site-specific regulation of synaptic plasticity by cAMP, a highly diffusible small molecule that transforms the physiology of synapses in a local and specific manner. By exploiting the octopaminergic system of Drosophila, which mediates structural synaptic plasticity via a cAMP-dependent pathway, we demonstrate the existence of local cAMP signaling compartments of micrometer dimensions within single motor neurons. In addition, we provide evidence that heterogeneous octopamine receptor localization, coupled with local differences in phosphodiesterase activity, underlies the observed differences in cAMP signaling in the axon, cell body, and boutons. KW - cAMP KW - synaptic plasticity KW - PDE KW - octopamine KW - FRET KW - active zone KW - dunce KW - GPCR Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162324 VL - 17 IS - 5 ER - TY - JOUR A1 - Siegmund, Daniela A1 - Kums, Juliane A1 - Ehrenschwender, Martin A1 - Wajant, Harald T1 - Activation of TNFR2 sensitizes macrophages for TNFR1-mediated necroptosis JF - Cell Death & Disease N2 - Macrophages express TNFR1 as well as TNFR2 and are also major producers of tumor necrosis factor (TNF), especially upon contact with pathogen-associated molecular patterns. Consequently, TNF not only acts as a macrophage-derived effector molecule but also regulates the activity and viability of macrophages. Here, we investigated the individual contribution of TNFR1 and TNFR2 to TNF-induced cell death in macrophages. Exclusive stimulation of TNFR1 showed no cytotoxic effect whereas selective stimulation of TNFR2 displayed mild cytotoxicity. Intriguingly, the latter was strongly enhanced by the caspase inhibitor zVAD-fmk. The strong cytotoxic activity of TNFR2 in the presence of zVAD-fmk was reversed by necrostatin-1, indicating necroptotic cell death. TNFR1- and TNF-deficient macrophages turned out to be resistant against TNFR2-induced cell death. In addition, the cIAP-depleting SMAC mimetic BV6 also enforced TNF/TNFR1-mediated necroptotic cell death in the presence of zVAD-fmk. In sum, our data suggest a model in which TNFR2 sensitizes macrophages for endogenous TNF-induced TNFR1-mediated necroptosis by the known ability of TNFR2 to interfere with the survival activity of TRAF2-cIAP1/2 complexes. KW - TNFR2 Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162317 VL - 7 ER - TY - JOUR A1 - Gambaryan, Stepan A1 - Subramanian, Hariharan A1 - Kehrer, Linda A1 - Mindukshev, Igor A1 - Sudnitsyna, Julia A1 - Reiss, Cora A1 - Rukoyatkina, Natalia A1 - Friebe, Andreas A1 - Sharina, Iraida A1 - Martin, Emil A1 - Walter, Ulrich T1 - Erythrocytes do not activate purified and platelet soluble guanylate cyclases even in conditions favourable for NO synthesis JF - Cell Communication and Signaling N2 - Background Direct interaction between Red blood cells (RBCs) and platelets is known for a long time. The bleeding time is prolonged in anemic patients independent of their platelet count and could be corrected by transfusion of RBCs, which indicates that RBCs play an important role in hemostasis and platelet activation. However, in the last few years, opposing mechanisms of platelet inhibition by RBCs derived nitric oxide (NO) were proposed. The aim of our study was to identify whether RBCs could produce NO and activate soluble guanylate cyclase (sGC) in platelets. Methods To test whether RBCs could activate sGC under different conditions (whole blood, under hypoxia, or even loaded with NO), we used our well-established and highly sensitive models of NO-dependent sGC activation in platelets and activation of purified sGC. The activation of sGC was monitored by detecting the phosphorylation of Vasodilator Stimulated Phosphoprotein (VASPS239) by flow cytometry and Western blot. ANOVA followed by Bonferroni’s test and Student’s t-test were used as appropriate. Results We show that in the whole blood, RBCs prevent NO-mediated inhibition of ADP and TRAP6-induced platelet activation. Likewise, coincubation of RBCs with platelets results in strong inhibition of NO-induced sGC activation. Under hypoxic conditions, incubation of RBCs with NO donor leads to Hb-NO formation which inhibits sGC activation in platelets. Similarly, RBCs inhibit activation of purified sGC, even under conditions optimal for RBC-mediated generation of NO from nitrite. Conclusions All our experiments demonstrate that RBCs act as strong NO scavengers and prevent NO-mediated inhibition of activated platelets. In all tested conditions, RBCs were not able to activate platelet or purified sGC. KW - hemoglobin KW - erythrocytes KW - nitric oxide KW - soluble guanylate cyclase KW - platelets Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161223 VL - 14 IS - 16 ER - TY - JOUR A1 - Oder, Daniel A1 - Üceyler, Nurcan A1 - Liu, Dan A1 - Hu, Kai A1 - Petritsch, Bernhard A1 - Sommer, Claudia A1 - Ertl, Georg A1 - Wanner, Christoph A1 - Nordbeck, Peter T1 - Organ manifestations and long-term outcome of Fabry disease in patients with the GLA haplotype D313Y JF - BMJ Open N2 - Objectives: The severity of Fabry disease is dependent on the type of mutation in the α-galactosidase A (AgalA) encoding gene (GLA). This study focused on the impact of the GLA haplotype D313Y on long-term organ involvement and function. Setting and participants: In this monocentric study, all participants presenting with the D313Y haplotype between 2001 and 2015 were comprehensively clinically investigated at baseline and during a 4-year follow-up if available. Five females and one male were included. Primary and secondary outcome measures: Cardiac, nephrological, neurological, laboratory and quality of life data. Results: AgalA enzyme activity in leucocytes (0.3±0.9 nmol/min/mg protein (mean±SD)) and serum lyso-Gb3 (0.6±0.3 ng/mL at baseline) were in normal range in all patients. Cardiac morphology and function were normal (left-ventricular (LV) ejection fraction 66±8%; interventricular septum 7.7±1.4 mm; LV posterior wall 7.5±1.4 mm; normalised LV mass in MRI 52±9 g/m2; LV global longitudinal strain −21.6±1.9%) and there were no signs of myocardial fibrosis in cardiac MRI. Cardiospecific biomarkers were also in normal range. Renal function was not impaired (estimated glomerular filtration rate MDRD 103±15 mL/min; serum-creatinine 0.75±0.07 mg/dL; cystatin-c 0.71±0.12 mg/L). One female patient (also carrying a Factor V Leiden mutation) had a transitory ischaemic attack. One patient showed white matter lesions in brain MRI, but none had Fabry-associated pain attacks, pain crises, evoked pain or permanent pain. Health-related quality of life analysis revealed a reduction in individual well-being. At long-term follow-up after 4 years, no significant change was seen in any parameter. Conclusions: The results of the current study suggest that the D313Y genotype does not lead to severe organ manifestations as seen in genotypes known to be causal for classical FD." KW - inherited metabolic disorders KW - Anderson-Fabry Disease KW - D313Y genotype KW - Fabry cardiomyopathy KW - Fabry nephropathy KW - Fabry-associated pain Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161210 VL - 6 ER - TY - JOUR A1 - Jordan, Martin C. A1 - Zimmermann, Christina A1 - Gho, Sheridan A. A1 - Frey, Sönke P. A1 - Blunk, Torsten A1 - Meffert, Rainer H. A1 - Hoelscher-Doht, Stefanie T1 - Biomechanical analysis of different osteosyntheses and the combination with bone substitute in tibial head depression fractures JF - BMC Musculoskeletal Disorders N2 - Background Tibial head depression fractures demand a high level of fracture stabilization to prevent a secondary loss of reduction after surgery. Elderly individuals are at an increased risk of developing these fractures, and biomechanical investigations of the fractures are rare. Therefore, the aim of this study was to systematically analyze different types of osteosyntheses in combination with two commonly used bone substitutes. Methods Lateral tibial head depression fractures were created in synthetic bones. After reduction, the fractures were stabilized with eight different treatment options of osteosynthesis alone or in combination with a bone substitute. Two screws, 4 screws and a lateral buttress plate were investigated. As a bone substitute, two common clinically used calcium phosphate cements, Norian® Drillable and ChronOS™ Inject, were applied. Displacement of the articular fracture fragment (mm) during cyclic loading, stiffness (N/mm) and maximum load (N) in Load-to-Failure tests were measured. Results The three different osteosyntheses (Group 1: 2 screws, group 2: 4 screws, group 3: plate) alone revealed a significantly higher displacement compared to the control group (Group 7: ChronOS™ Inject only) (Group 1, 7 [p < 0.01]; group 2, 7 [p = 0.04]; group 3, 7 [p < 0.01]). However, the osteosyntheses in combination with bone substitute exhibited no differences in displacement compared to the control group. The buttress plate demonstrated a higher normalized maximum load than the 2 and 4 screw osteosynthesis. Comparing the two different bone substitutes to each other, ChronOS™ inject had a significantly higher stiffness and lower displacement than Norian® Drillable. Conclusions The highest biomechanical stability under maximal loading was provided by a buttress plate osteosynthesis. A bone substitute, such as the biomechanically favorable ChronOS™ Inject, is essential to reduce the displacement under lower loading. KW - tibial fracture fixation KW - tibial head fracture KW - biomechanical test KW - static test KW - cyclic test Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161201 VL - 17 IS - 287 ER - TY - JOUR A1 - Moremi, Nyambura A1 - Claus, Heike A1 - Mshana, Stephen E. T1 - Antimicrobial resistance pattern: a report of microbiological cultures at a tertiary hospital in Tanzania JF - BMC Infectious Diseases N2 - Background Antimicrobial resistance has been declared by the World Health Organization as a threat to the public health. The aim of this study was to analyze antimicrobial resistance patterns of the common pathogens occurring at the Bugando Medical Centre (BMC), Mwanza, Tanzania to provide data for antimicrobial stewardship programmes. Methods A total of 3330 microbiological culture results scripts representing non-repetitive specimens reported between June 2013 and May 2015 were retrieved and analyzed for pathogens and their susceptibility patterns using STATA-11 software. Results Out of 3330 specimens, 439 (13.2%) had positive culture. Staphylococcus aureus (n = 100; 22.8%), Klebsiella pneumoniae (n = 65; 14.8%) and Escherichia coli (n = 41; 9.3%) were the most frequently isolated bacteria. Of 78 Staphylococcus aureus tested, 27 (34.6%) were found to be methicillin resistant Staphylococcus aureus (MRSA). Rates of resistance of Klebsiella pneumoniae and Escherichia coli isolates to third generation cephalosporins were 38.5% (25/65) and 29.3% (12/41) respectively. Staphylococcus aureus and Klesbiella pneumoniae were commonly isolated from bloodstream infections while Escherichia coli and Pseudomonas aeruginosa were the predominant isolates from urinary tract and wounds infections respectively. Of 23 Salmonella species isolated, 22 (95%) were recovered from the blood. Nine of the 23 Salmonella species isolates (39%) were found to be resistant to third generation cephalosporins. The resistance rate of gram-negative bacteria to third generation cephalosporins increased from 26.5% in 2014 to 57.9% in 2015 (p = 0.004) while the rate of MRSA decreased from 41.2% in 2013 to 9.5% in 2015 (p = 0.016). Multidrug-resistant gram-negative isolates were commonly isolated from Intensive Care Units and it was noted that, the majority of invasive infections were due to gram-negative bacteria. Conclusion There is an increase in proportion of gram-negative isolates resistant to third generation cephalosporins. The diversity of potential pathogens resistant to commonly prescribed antibiotics underscores the importance of sustained and standardized antimicrobial resistance surveillance and antibiotic stewardship programmes in developing countries. KW - Tanzania KW - antimicrobial resistance KW - cephalosporin-resistant gram-negative bacteria KW - MRSA Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161185 VL - 16 IS - 756 ER - TY - JOUR A1 - Diessner, Joachim A1 - Wischnewsky, Manfred A1 - Stüber, Tanja A1 - Stein, Roland A1 - Krockenberger, Mathias A1 - Häusler, Sebastian A1 - Janni, Wolfgang A1 - Kreienberg, Rolf A1 - Blettner, Maria A1 - Schwentner, Lukas A1 - Wöckel, Achim A1 - Bartmann, Catharina T1 - Evaluation of clinical parameters influencing the development of bone metastasis in breast cancer JF - BMC Cancer N2 - Background The development of metastases is a negative prognostic parameter for the clinical outcome of breast cancer. Bone constitutes the first site of distant metastases for many affected women. The purpose of this retrospective multicentre study was to evaluate if and how different variables such as primary tumour stage, biological and histological subtype, age at primary diagnosis, tumour size, the number of affected lymph nodes as well as grading influence the development of bone-only metastases. Methods This retrospective German multicentre study is based on the BRENDA collective and included 9625 patients with primary breast cancer recruited from 1992 to 2008. In this analysis, we investigated a subgroup of 226 patients with bone-only metastases. Association between bone-only relapse and clinico-pathological risk factors was assessed in multivariate models using the tree-building algorithms “exhausted CHAID (Chi-square Automatic Interaction Detectors)” and CART(Classification and Regression Tree), as well as radial basis function networks (RBF-net), feedforward multilayer perceptron networks (MLP) and logistic regression. Results Multivariate analysis demonstrated that breast cancer subtypes have the strongest influence on the development of bone-only metastases (χ2 = 28). 29.9 % of patients with luminal A or luminal B (ABC-patients) and 11.4 % with triple negative BC (TNBC) or HER2-overexpressing tumours had bone-only metastases (p < 0.001). Five different mathematical models confirmed this correlation. The second important risk factor is the age at primary diagnosis. Moreover, BC subcategories influence the overall survival from date of metastatic disease of patients with bone-only metastases. Patients with bone-only metastases and TNBC (p < 0.001; HR = 7.47 (95 % CI: 3.52–15.87) or HER2 overexpressing BC (p = 0.007; HR = 3.04 (95 % CI: 1.36–6.80) have the worst outcome compared to patients with luminal A or luminal B tumours and bone-only metastases. Conclusion The bottom line of different mathematical models is the prior importance of subcategories of breast cancer and the age at primary diagnosis for the appearance of osseous metastases. The primary tumour stage, histological subtype, tumour size, the number of affected lymph nodes, grading and NPI seem to have only a minor influence on the development of bone-only metastases. KW - BRENDA KW - breast cancer KW - bone metastases KW - skeleton KW - breast cancer subtypes Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161173 VL - 16 IS - 307 ER - TY - JOUR A1 - Stein, Roland Gregor A1 - Wollschläger, Daniel A1 - Kreienberg, Rolf A1 - Janni, Wolfgang A1 - Wischnewsky, Manfred A1 - Diessner, Joachim A1 - Stüber, Tanja A1 - Bartmann, Catharina A1 - Krockenberger, Mathias A1 - Wischhusen, Jörg A1 - Wöckel, Achim A1 - Blettner, Maria A1 - Schwentner, Lukas T1 - The impact of breast cancer biological subtyping on tumor size assessment by ultrasound and mammography - a retrospective multicenter cohort study of 6543 primary breast cancer patients JF - BMC Cancer N2 - Background Mammography and ultrasound are the gold standard imaging techniques for preoperative assessment and for monitoring the efficacy of neoadjuvant chemotherapy in breast cancer. Maximum accuracy in predicting pathological tumor size non-invasively is critical for individualized therapy and surgical planning. We therefore aimed to assess the accuracy of tumor size measurement by ultrasound and mammography in a multicentered health services research study. Methods We retrospectively analyzed data from 6543 patients with unifocal, unilateral primary breast cancer. The maximum tumor diameter was measured by ultrasound and/or mammographic imaging. All measurements were compared to final tumor diameter determined by postoperative histopathological examination. We compared the precision of each imaging method across different patient subgroups as well as the method-specific accuracy in each patient subgroup. Results Overall, the correlation with histology was 0.61 for mammography and 0.60 for ultrasound. Both correlations were higher in pT2 cancers than in pT1 and pT3. Ultrasound as well as mammography revealed a significantly higher correlation with histology in invasive ductal compared to lobular cancers (p < 0.01). For invasive lobular cancers, the mammography showed better correlation with histology than ultrasound (p = 0.01), whereas there was no such advantage for invasive ductal cancers. Ultrasound was significantly superior for HR negative cancers (p < 0.001). HER2/neu positive cancers were also more precisely assessed by ultrasound (p < 0.001). The size of HER2/neu negative cancers could be more accurately predicted by mammography (p < 0.001). Conclusion This multicentered health services research approach demonstrates that predicting tumor size by mammography and ultrasound provides accurate results. Biological tumor features do, however, affect the diagnostic precision. KW - histopathology KW - breast cancer KW - ultrasound KW - mammography KW - tumor size Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161050 VL - 16 IS - 549 ER - TY - JOUR A1 - Joukhadar, R. A1 - Wöckel, A. A1 - Herr, D. A1 - Paulus, V. A1 - Radosa, J. A1 - Hamza, A. A1 - Solomayer, E. A1 - Baum, S. T1 - Challenges of Longevity: Safety of Vaginal and Laparoscopic Urogynecological Procedures in Septuagenarians and Older Patients JF - BioMed Research International N2 - Introduction. Pelvic organ prolapse (POP) and urinary incontinence (UI) have increasing prevalence in the elderly population. The aim of this study was to compare the comorbidities of these procedures between <70 y/o and ≥70 y/o patients. Materials and Methods. In our retrospective study over a period of 2.5 years, 407 patients had received an urogynecological procedure. All patients with POP were treated by reconstructive surgery. Complications were reported using the standardized classification of Clavien-Dindo (CD). The study can be assigned to stage 2b Exploration IDEAL (Idea, Development, Exploration, Assessment, Long-term study)-system of surgical innovation. Results. Operation time, blood loss, and intraoperative complications have not been more frequent in the elderly, whereas hospital stay was significantly longer in ≥70 y/o patients. Regarding postoperative complications, we noticed that ≥70 y/o patients had an almost threefold risk to develop mild early postoperative complications compared to younger patients (OR: 2.86; 95% CI: 1.76–4.66). On the contrary, major complications were not more frequent. No case of life-threatening complication or the need for blood transfusion was reported. Conclusion. After urogynecological procedures, septuagenarians and older patients are more likely to develop mild postoperative complications but not more intraoperative or severe postoperative complications compared to younger patients. KW - gynecologic surgical procedures/methods KW - postoperative complications/epidemiology KW - vagina/surgery KW - pelvic organ prolapse/surgery KW - middle Aged KW - laparoscopy/methods KW - uterine prolapse/surgery KW - urinary incontinence/surgery KW - surgical Mesh KW - retrospective Studies KW - age factors KW - aged KW - aged 80 and over KW - female KW - reconstructive surgical procedures/methods Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161005 VL - 2016 IS - Article ID 5184595 ER - TY - JOUR A1 - Zinner, C. A1 - Krueger, M. A1 - Reed, J. L. A1 - Kohl-Bareis, M. A1 - Holmberg, H. C. A1 - Sperlich, B. T1 - Exposure to a combination of heat and hyperoxia during cycling at submaximal intensity does not alter thermoregulatory responses JF - Biology of Sport N2 - In this study, we tested the hypothesis that breathing hyperoxic air (F\(_{in}\)O\(_2\) = 0.40) while exercising in a hot environment exerts negative effects on the total tissue level of haemoglobin concentration (tHb); core (T\(_{core}\)) and skin (T\(_{skin}\)) temperatures; muscle activity; heart rate; blood concentration of lactate; pH; partial pressure of oxygen (P\(_a\)O\(_2\)) and carbon dioxide; arterial oxygen saturation (S\(_a\)O\(_2\)); and perceptual responses. Ten well-trained male athletes cycled at submaximal intensity at 21°C or 33°C in randomized order: first for 20 min while breathing normal air (FinO\(_2\) = 0.21) and then 10 min with F\(_{in}\)O\(_2\) = 0.40 (HOX). At both temperatures, S\(_a\)O\(_2\) and P\(_a\)O\(_2\), but not tHb, were increased by HOX. Tskin and perception of exertion and thermal discomfort were higher at 33°C than 21°C (p < 0.01), but independent of F\(_{in}\)O\(_2\). T\(_{core}\) and muscle activity were the same under all conditions (p > 0.07). Blood lactate and heart rate were higher at 33°C than 21°C. In conclusion, during 30 min of submaximal cycling at 21°C or 33°C, T\(_{core}\), T\(_{skin}\) and T\(_{body}\), tHb, muscle activity and ratings of perceived exertion and thermal discomfort were the same under normoxic and hyperoxic conditions. Accordingly, breathing hyperoxic air (F\(_{in}\)O\(_2\) = 0.40) did not affect thermoregulation under these conditions. KW - heat stress KW - hyperthermia KW - skin blood flow KW - thermoregulation KW - vasoconstriction Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-160993 VL - 33 IS - 1 ER - TY - JOUR A1 - Huang, Guozheng A1 - Schramm, Simon A1 - Heilmann, Jörg A1 - Biedermann, David A1 - Kren, Vladimír A1 - Decker, Michael T1 - Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins JF - Beilstein Journal of Organic Chemistry N2 - Various Mitsunobu conditions were investigated for a series of flavonolignans (silybin A, silybin B, isosilybin A, and silychristin A) to achieve either selective esterification in position C-23 or dehydration in a one-pot reaction yielding the biologically important enantiomers of hydnocarpin D, hydnocarpin and isohydnocarpin, respectively. This represents the only one-pot semi-synthetic method to access these flavonolignans in high yields. KW - Mitsunobu KW - dehydration KW - flavonoid KW - hydnocarpin KW - silybin Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-160986 VL - 12 ER - TY - JOUR A1 - Sawatzky, Edgar A1 - Drakopoulos, Antonios A1 - Rölz, Martin A1 - Sotriffer, Christoph A1 - Engels, Bernd A1 - Decker, Michael T1 - Experimental and theoretical investigations into the stability of cyclic aminals JF - Beilstein Journal of Organic Chemistry N2 - Background: Cyclic aminals are core features of natural products, drug molecules and important synthetic intermediates. Despite their relevance, systematic investigations into their stability towards hydrolysis depending on the pH value are lacking. Results: A set of cyclic aminals was synthesized and their stability quantified by kinetic measurements. Steric and electronic effects were investigated by choosing appropriate groups. Both molecular mechanics (MM) and density functional theory (DFT) based studies were applied to support and explain the results obtained. Rapid decomposition is observed in acidic aqueous media for all cyclic aminals which occurs as a reversible reaction. Electronic effects do not seem relevant with regard to stability, but the magnitude of the conformational energy of the ring system and pK a values of the N-3 nitrogen atom. Conclusion: Cyclic aminals are stable compounds when not exposed to acidic media and their stability is mainly dependent on the conformational energy of the ring system. Therefore, for the preparation and work-up of these valuable synthetic intermediates and natural products, appropriate conditions have to be chosen and for application as drug molecules their sensitivity towards hydrolysis has to be taken into account. KW - quantum mechanics KW - hydrolysis KW - kinetics KW - molecular mechanics KW - natural products Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-160976 VL - 12 ER - TY - JOUR A1 - Schuster, Ann-Christin A1 - Burghardt, Markus A1 - Alfarhan, Ahmed A1 - Bueno, Amauri A1 - Hedrich, Rainer A1 - Leide, Jana A1 - Thomas, Jacob A1 - Riederer, Markus T1 - Effectiveness of cuticular transpiration barriers in a desert plant at controlling water loss at high temperatures JF - AoB Plants N2 - Maintaining the integrity of the cuticular transpiration barrier even at elevated temperatures is of vital importance especially for hot-desert plants. Currently, the temperature dependence of the leaf cuticular water permeability and its relationship with the chemistry of the cuticles are not known for a single desert plant. This study investigates whether (i) the cuticular permeability of a desert plant is lower than that of species from non-desert habitats, (ii) the temperature-dependent increase of permeability is less pronounced than in those species and (iii) whether the susceptibility of the cuticular permeability barrier to high temperatures is related to the amounts or properties of the cutin or the cuticular waxes. We test these questions with Rhazya stricta using the minimum leaf water vapour conductance (gmin) as a proxy for cuticular water permeability. gmin of R. stricta (5.41 × 10\(^{-5}\) m s\(^{-1}\) at 25 °C) is in the upper range of all existing data for woody species from various non-desert habitats. At the same time, in R. stricta, the effect of temperature (15-50 °C) on gmin (2.4-fold) is lower than in all other species (up to 12-fold). Rhazya stricta is also special since the temperature dependence of gmin does not become steeper above a certain transition temperature. For identifying the chemical and physical foundation of this phenomenon, the amounts and the compositions of cuticular waxes and cutin were determined. The leaf cuticular wax (251.4 μg cm\(^{-2}\)) is mainly composed of pentacyclic triterpenoids (85.2% of total wax) while long-chain aliphatics contribute only 3.4%. In comparison with many other species, the triterpenoid-to-cutin ratio of R. stricta (0.63) is high. We propose that the triterpenoids deposited within the cutin matrix restrict the thermal expansion of the polymer and, thus, prevent thermal damage to the highly ordered aliphatic wax barrier even at high temperatures. KW - conductance KW - triterpenoids KW - aliphatic compounds KW - cuticular transpiration KW - cuticular wax KW - cutin KW - desert KW - minimum KW - plant cuticle KW - temperature KW - transition temperature Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-160963 VL - 8 ER - TY - JOUR A1 - Goldmann, Julius A1 - Hornung, Christoph T1 - Interview mit Prof. (em.) Dr. Frank-Rutger Hausmann JF - promptus - Würzburger Beiträge zur Romanistik N2 - Frank-Rutger Hausmann war Professor für Romanische Philologie (Schwerpunkt französische und italienische Literatur) in Freiburg, Aachen und wiederum Freiburg. Hausmann hat sich zudem intensiv mit der Fachgeschichte der deutschen Romanistik und der Geisteswissenschaften allgemein beschäftigt. Für die zweite Ausgabe der promptus-Interviewreihe durften wir ihn nach seiner Perspektive auf die historische und aktuelle Situation der Romanistik befragen. Er arbeitet momentan u.a. an einem Romanistenlexikon, das online veröffentlicht wird, und hat das Romanistenarchiv in Augsburg gegründet. KW - Romanistik KW - Interview KW - aktuelle Situation KW - historische Situation KW - Romansitik KW - Biographisches Interview KW - Perspektive Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161586 SN - 2510-2613 VL - 2 ER -