TY - JOUR A1 - Chen, Yi-chun A1 - Mishra, Dushyant A1 - Gläß, Sebastian A1 - Gerber, Bertram T1 - Behavioral Evidence for Enhanced Processing of the Minor Component of Binary Odor Mixtures in Larval Drosophila JF - Frontiers in Psychology N2 - A fundamental problem in deciding between mutually exclusive options is that the decision needs to be categorical although the properties of the options often differ but in grade. We developed an experimental handle to study this aspect of behavior organization. Larval Drosophila were trained such that in one set of animals odor A was rewarded, but odor B was not (A+/B), whereas a second set of animals was trained reciprocally (A/B+). We then measured the preference of the larvae either for A, or for B, or for “morphed” mixtures of A and B, that is for mixtures differing in the ratio of the two components. As expected, the larvae showed higher preference when only the previously rewarded odor was presented than when only the previously unrewarded odor was presented. For mixtures of A and B that differed in the ratio of the two components, the major component dominated preference behavior—but it dominated less than expected from a linear relationship between mixture ratio and preference behavior. This suggests that a minor component can have an enhanced impact in a mixture, relative to such a linear expectation. The current paradigm may prove useful in understanding how nervous systems generate discrete outputs in the face of inputs that differ only gradually. KW - learning KW - memory KW - perception KW - compound conditioning KW - decision-making KW - Drosophila Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170011 VL - 8 IS - 1923 ER - TY - JOUR A1 - Grünewald, Benedikt A1 - Lange, Maren D A1 - Werner, Christian A1 - O'Leary, Aet A1 - Weishaupt, Andreas A1 - Popp, Sandy A1 - Pearce, David A A1 - Wiendl, Heinz A1 - Reif, Andreas A1 - Pape, Hans C A1 - Toyka, Klaus V A1 - Sommer, Claudia A1 - Geis, Christian T1 - Defective synaptic transmission causes disease signs in a mouse model of juvenile neuronal ceroid lipofuscinosis JF - eLife N2 - Juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease) caused by mutations in the CLN3 gene is the most prevalent inherited neurodegenerative disease in childhood resulting in widespread central nervous system dysfunction and premature death. The consequences of CLN3 mutation on the progression of the disease, on neuronal transmission, and on central nervous network dysfunction are poorly understood. We used Cln3 knockout (Cln3\(^{Δex1-6}\)) mice and found increased anxiety-related behavior and impaired aversive learning as well as markedly affected motor function including disordered coordination. Patch-clamp and loose-patch recordings revealed severely affected inhibitory and excitatory synaptic transmission in the amygdala, hippocampus, and cerebellar networks. Changes in presynaptic release properties may result from dysfunction of CLN3 protein. Furthermore, loss of calbindin, neuropeptide Y, parvalbumin, and GAD65-positive interneurons in central networks collectively support the hypothesis that degeneration of GABAergic interneurons may be the cause of supraspinal GABAergic disinhibition. KW - CLN3 KW - mutation KW - mouse model KW - synaptic transmission KW - amygdala KW - hippocampus Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170004 VL - 6 IS - e28685 ER - TY - JOUR A1 - Lapa, Constantin A1 - Kircher, Stefan A1 - Schirbel, Andreas A1 - Rosenwald, Andreas A1 - Kropf, Saskia A1 - Pelzer, Theo A1 - Walles, Thorsten A1 - Buck, Andreas K. A1 - Weber, Wolfgang A. A1 - Wester, Hans-Juergen A1 - Herrmann, Ken A1 - Lückerath, Katharina T1 - Targeting CXCR4 with [\(^{68}\)Ga]Pentixafor: a suitable theranostic approach in pleural mesothelioma? JF - Oncotarget N2 - C-X-C motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. This study investigated the feasibility of CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using [\(^{68}\)Ga]Pentixafor in malignant pleural mesothelioma. Six patients with pleural mesothelioma underwent [\(^{68}\)Ga]Pentixafor-PET/CT. 2′-[\(^{18}\)F]fluoro-2′-deoxy-D-glucose ([\(^{18}\)F]FDG)-PET/CT (4/6 patients) and immunohistochemistry obtained from biopsy or surgery (all) served as standards of reference. Additionally, 9 surgical mesothelioma samples were available for histological work-up. Whereas [\(^{18}\)F]FDG-PET depicted active lesions in all patients, [\(^{68}\)Ga]Pentixafor-PET/CT recorded physiologic tracer distribution and none of the 6 patients presented [\(^{68}\)Ga]Pentixafor-positive lesions. This finding paralleled results of immunohistochemistry which also could not identify relevant CXCR4 surface expression in the samples analyzed. In contrast to past reports, our data suggest widely absence of CXCR4 expression in pleural mesothelioma. Hence, robust cell surface expression should be confirmed prior to targeting this chemokine receptor for diagnosis and/or therapy. KW - PET KW - CXCR4 KW - [\(^{68}\)Ga] pentixafor KW - pleural mesothelioma KW - theranostics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169989 VL - 8 IS - 57 ER - TY - JOUR A1 - Köping, Maria A1 - Shehata-Dieler, Wafaa A1 - Cebulla, Mario A1 - Rak, Kristen A1 - Oder, Daniel A1 - Müntze, Jonas A1 - Nordbeck, Peter A1 - Wanner, Christoph A1 - Hagen, Rudolf A1 - Schraven, Sebastian T1 - Cardiac and renal dysfunction is associated with progressive hearing loss in patients with Fabry disease JF - PLoS ONE N2 - Background Fabry disease (FD) is an X-linked recessive hereditary lysosomal storage disorder which results in the accumulation of globotriaosylceramid (Gb3) in tissues of kidney and heart as well as central and peripheral nervous system. Besides prominent renal and cardiac organ involvement, cochlear symptoms like high-frequency hearing loss and tinnitus are frequently found with yet no comprehensive data available in the literature. Objective To examine hearing loss in patients with FD depending on cardiac and renal function. Material and methods Single-center study with 68 FD patients enrolled between 2012 and 2016 at the Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery of the University of Würzburg. Every subject underwent an oto-rhino-laryngological examination as well as behavioral, electrophysiological and electroacoustical audiological testing. High-frequency thresholds were evaluated by using a modified PTA\(_{6}\) (0.5, 1, 2, 4, 6, 8) and HF-PTA (6, 8 kHz). Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class. Results Sensorineural hearing loss was detected in 58.8% of the cohort, which occurred typically in sudden episodes and affected especially high frequencies. Hearing loss is asymmetric, beginning unilaterally and affecting the contralateral ear later. Tinnitus was reported by 41.2%. Renal and cardiac impairment influenced the severity of hearing loss (p < 0.05). Conclusions High frequency hearing loss is a common problem in patients with FD. Although not life-threatening, it can seriously reduce quality of life and should be taken into account in diagnosis and therapy. Optimized extensive hearing assessment including higher frequency thresholds should be used. KW - cardiac dysfunction KW - renal dysfunction KW - Fabry disease KW - hearing loss Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169961 VL - 12 IS - 11 ER - TY - JOUR A1 - Glaser, Kirsten A1 - Silwedel, Christine A1 - Fehrholz, Markus A1 - Waaga-Gasser, Ana M. A1 - Henrich, Birgit A1 - Claus, Heike A1 - Speer, Christian P. T1 - Ureaplasma Species Differentially Modulate Pro- and Anti-Inflammatory Cytokine Responses in Newborn and Adult Human Monocytes Pushing the State Toward Pro-Inflammation JF - Frontiers in Cellular and Infection Microbiology N2 - Background: Ureaplasma species have been associated with chorioamnionitis and preterm birth and have been implicated in the pathogenesis of neonatal short and long-term morbidity. However, being mostly commensal bacteria, controversy remains on the pro-inflammatory capacity of Ureaplasma. Discussions are ongoing on the incidence and impact of prenatal, perinatal, and postnatal infection. The present study addressed the impact of Ureaplasma isolates on monocyte-driven inflammation. Methods: Cord blood monocytes of term neonates and adult monocytes, either native or LPS-primed, were cultured with Ureaplasma urealyticum (U. urealyticum) serovar 8 (Uu8) and Ureaplasma parvum serovar 3 (Up3). Using qRT-PCR, cytokine flow cytometry, and multi-analyte immunoassay, we assessed mRNA and protein expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, IL-12p40, IL-10, and IL-1 receptor antagonist (IL-1ra) as well as Toll-like receptor (TLR) 2 and TLR4. Results: Uu8 and Up3 induced mRNA expression and protein release of TNF-α, IL-1β and IL-8 in term neonatal and adult monocytes (p < 0.01 and p < 0.05). Intracellular protein expression of TNF-α, IL-1β and IL-8 in Ureaplasma-stimulated cells paralleled those results. Ureaplasma-induced cytokine levels did not significantly differ from LPS-mediated levels except for lower intracellular IL-1β in adult monocytes (Uu8: p < 0.05). Remarkably, ureaplasmas did not induce IL-12p40 response and promoted lower amounts of anti-inflammatory IL-10 and IL-1ra than LPS, provoking a cytokine imbalance more in favor of pro-inflammation (IL-1β/IL-10, IL-8/IL-10 and IL-8/IL-1ra: p < 0.01, vs. LPS). In contrast to LPS, both isolates induced TLR2 mRNA in neonatal and adult cells (p < 0.001 and p < 0.05) and suppressed TLR4 mRNA in adult monocytes (p < 0.05). Upon co-stimulation, Uu8 and Up3 inhibited LPS-induced intracellular IL-1β (p < 0.001 and p < 0.05) and IL-8 in adult monocytes (p < 0.01), while LPS-induced neonatal cytokines were maintained or aggravated (p < 0.05). Conclusion: Our data demonstrate a considerable pro-inflammatory capacity of Ureaplasma isolates in human monocytes. Stimulating pro-inflammatory cytokine responses while hardly inducing immunomodulatory and anti-inflammatory cytokines, ureaplasmas might push monocyte immune responses toward pro-inflammation. Inhibition of LPS-induced cytokines in adult monocytes in contrast to sustained inflammation in term neonatal monocytes indicates a differential modulation of host immune responses to a second stimulus. Modification of TLR2 and TLR4 expression may shape host susceptibility to inflammation. KW - Ureaplasma KW - infection KW - inflammation KW - immunomodulation KW - chorioamnionitis KW - neonatal morbidity KW - monocytes KW - cord blood Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169958 VL - 7 IS - 484 ER - TY - JOUR A1 - Scherzad, Agmal A1 - Meyer, Till A1 - Kleinsasser, Norbert A1 - Hackenberg, Stephan T1 - Molecular Mechanisms of Zinc Oxide Nanoparticle-Induced Genotoxicity Short Running Title: Genotoxicity of ZnO NPs JF - Materials N2 - Background: Zinc oxide nanoparticles (ZnO NPs) are among the most frequently applied nanomaterials in consumer products. Evidence exists regarding the cytotoxic effects of ZnO NPs in mammalian cells; however, knowledge about the potential genotoxicity of ZnO NPs is rare, and results presented in the current literature are inconsistent. Objectives: The aim of this review is to summarize the existing data regarding the DNA damage that ZnO NPs induce, and focus on the possible molecular mechanisms underlying genotoxic events. Methods: Electronic literature databases were systematically searched for studies that report on the genotoxicity of ZnO NPs. Results: Several methods and different endpoints demonstrate the genotoxic potential of ZnO NPs. Most publications describe in vitro assessments of the oxidative DNA damage triggered by dissoluted Zn2+ ions. Most genotoxicological investigations of ZnO NPs address acute exposure situations. Conclusion: Existing evidence indicates that ZnO NPs possibly have the potential to damage DNA. However, there is a lack of long-term exposure experiments that clarify the intracellular bioaccumulation of ZnO NPs and the possible mechanisms of DNA repair and cell survival. KW - zinc oxide nanoparticles KW - genotoxicity KW - DNA damage KW - ROS KW - autophagy Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169948 VL - 10 IS - 12 ER - TY - JOUR A1 - Ickrath, Pascal A1 - Wagner, Martin A1 - Scherzad, Agmal A1 - Gehrke, Thomas A1 - Burghartz, Marc A1 - Hagen, Rudolf A1 - Radeloff, Katrin A1 - Kleinsasser, Norbert A1 - Hackenberg, Stephan T1 - Time-Dependent Toxic and Genotoxic Effects of Zinc Oxide Nanoparticles after Long-Term and Repetitive Exposure to Human Mesenchymal Stem Cells JF - International Journal of Environmental Research and Public Health N2 - Zinc oxide nanoparticles (ZnO-NP) are widely spread in consumer products. Data about the toxicological characteristics of ZnO-NP is still under controversial discussion. The human skin is the most important organ concerning ZnO-NP exposure. Intact skin was demonstrated to be a sufficient barrier against NPs; however, defect skin may allow NP contact to proliferating cells. Within these cells, stem cells are the most important toxicological target for NPs. The aim of this study was to evaluate the genotoxic and cytotoxic effects of ZnO-NP at low-dose concentrations after long-term and repetitive exposure to human mesenchymal stem cells (hMSC). Cytotoxic effects of ZnO-NP were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Furthermore, genotoxicity was evaluated by the comet assay. For long-term observation over 6 weeks, transmission electron microscopy (TEM) was applied. The results of the study indicated cytotoxic effects of ZnO-NP beginning at high concentrations of 50 μg/mL and genotoxic effects in hMSC exposed to 1 and 10 μg/mL ZnO-NP. Repetitive exposure enhanced cyto- but not genotoxicity. Intracellular NP accumulation was observed up to 6 weeks. The results suggest cytotoxic and genotoxic potential of ZnO-NP. Even low doses of ZnO-NP may induce toxic effects as a result of repetitive exposure and long-term cellular accumulation. This data should be considered before using ZnO-NP on damaged skin. KW - zinc oxide KW - ZnO KW - nanoparticles KW - cytotoxicity KW - toxicity KW - genotoxicity Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169932 VL - 14 IS - 12 ER - TY - JOUR A1 - Hellmann, Anna-Maria A1 - Lother, Jasmin A1 - Wurster, Sebastian A1 - Lutz, Manfred B. A1 - Schmitt, Anna Lena A1 - Morton, Charles Oliver A1 - Eyrich, Matthias A1 - Czakai, Kristin A1 - Einsele, Hermann A1 - Loeffler, Juergen T1 - Human and Murine Innate Immune Cell Populations Display Common and Distinct Response Patterns during Their In Vitro Interaction with the Pathogenic Mold Aspergillus fumigatus JF - Frontiers in Immunology N2 - Aspergillus fumigatus is the main cause of invasive fungal infections occurring almost exclusively in immunocompromised patients. An improved understanding of the initial innate immune response is key to the development of better diagnostic tools and new treatment options. Mice are commonly used to study immune defense mechanisms during the infection of the mammalian host with A. fumigatus. However, little is known about functional differences between the human and murine immune response against this fungal pathogen. Thus, we performed a comparative functional analysis of human and murine dendritic cells (DCs), macrophages, and polymorphonuclear cells (PMNs) using standardized and reproducible working conditions, laboratory protocols, and readout assays. A. fumigatus did not provoke identical responses in murine and human immune cells but rather initiated relatively specific responses. While human DCs showed a significantly stronger upregulation of their maturation markers and major histocompatibility complex molecules and phagocytosed A. fumigatus more efficiently compared to their murine counterparts, murine PMNs and macrophages exhibited a significantly stronger release of reactive oxygen species after exposure to A. fumigatus. For all studied cell types, human and murine samples differed in their cytokine response to conidia or germ tubes of A. fumigatus. Furthermore, Dectin-1 showed inverse expression patterns on human and murine DCs after fungal stimulation. These specific differences should be carefully considered and highlight potential limitations in the transferability of murine host–pathogen interaction studies. KW - murine model KW - humans KW - Aspergillus fumigatus KW - innate immune response KW - fungal infection Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169926 VL - 8 IS - 1716 ER - TY - JOUR A1 - Stein, Katharina A1 - Coulibaly, Drissa A1 - Stenchly, Kathrin A1 - Goetze, Dethardt A1 - Porembski, Stefan A1 - Lindner, André A1 - Konaté, Souleymane A1 - Linsenmair, Eduard K. T1 - Bee pollination increases yield quantity and quality of cash crops in Burkina Faso, West Africa JF - Scientific Reports N2 - Mutualistic biotic interactions as among flowering plants and their animal pollinators are a key component of biodiversity. Pollination, especially by insects, is a key element in ecosystem functioning, and hence constitutes an ecosystem service of global importance. Not only sexual reproduction of plants is ensured, but also yields are stabilized and genetic variability of crops is maintained, counteracting inbreeding depression and facilitating system resilience. While experiencing rapid environmental change, there is an increased demand for food and income security, especially in sub-Saharan communities, which are highly dependent on small scale agriculture. By combining exclusion experiments, pollinator surveys and field manipulations, this study for the first time quantifies the contribution of bee pollinators to smallholders’ production of the major cash crops, cotton and sesame, in Burkina Faso. Pollination by honeybees and wild bees significantly increased yield quantity and quality on average up to 62%, while exclusion of pollinators caused an average yield gap of 37% in cotton and 59% in sesame. Self-pollination revealed inbreeding depression effects on fruit set and low germination rates in the F1-generation. Our results highlight potential negative consequences of any pollinator decline, provoking risks to agriculture and compromising crop yields in sub-Saharan West Africa. KW - bees KW - pollination KW - Burkina Faso KW - cash crops KW - cotton KW - sesame Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169914 VL - 7 IS - 17691 ER - TY - JOUR A1 - Genheimer, Hannah A1 - Andreatta, Marta A1 - Asan, Esther A1 - Pauli, Paul T1 - Reinstatement of contextual conditioned anxiety in virtual reality and the effects of transcutaneous vagus nerve stimulation in humans JF - Scientific Reports N2 - Since exposure therapy for anxiety disorders incorporates extinction of contextual anxiety, relapses may be due to reinstatement processes. Animal research demonstrated more stable extinction memory and less anxiety relapse due to vagus nerve stimulation (VNS). We report a valid human three-day context conditioning, extinction and return of anxiety protocol, which we used to examine effects of transcutaneous VNS (tVNS). Seventy-five healthy participants received electric stimuli (unconditioned stimuli, US) during acquisition (Day1) when guided through one virtual office (anxiety context, CTX+) but never in another (safety context, CTX−). During extinction (Day2), participants received tVNS, sham, or no stimulation and revisited both contexts without US delivery. On Day3, participants received three USs for reinstatement followed by a test phase. Successful acquisition, i.e. startle potentiation, lower valence, higher arousal, anxiety and contingency ratings in CTX+ versus CTX−, the disappearance of these effects during extinction, and successful reinstatement indicate validity of this paradigm. Interestingly, we found generalized reinstatement in startle responses and differential reinstatement in valence ratings. Altogether, our protocol serves as valid conditioning paradigm. Reinstatement effects indicate different anxiety networks underlying physiological versus verbal responses. However, tVNS did neither affect extinction nor reinstatement, which asks for validation and improvement of the stimulation protocol. KW - psychology KW - vagus nerve stimulation KW - contextual anxiety KW - fear conditioning KW - extinction Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169892 VL - 7 IS - 17886 ER - TY - JOUR A1 - Thalhammer, Johanna T1 - L’art de bien chanter und Von der Kunst zierlich zu singen und zu spielen – Eine kontrastive Analyse von Texten der musikalischen Fachsprache im 18. Jahrhundert anhand von Auszügen aus Code de musique pratique, Rameau (1760) und Der vollkommene Capellmeister, Mattheson (1739) JF - promptus - Würzburger Beiträge zur Romanistik N2 - This article is an analysis and a comparison of German and French special language of music in the 18th century, more precisely about the terms used to describe the activity of singing. The analysis is based on two treatises about music theory. The first writing, Der Vollkommene Capellmeister, was written by Johann Mattheson in 1739 and the second, Code de musique pratique by Jean-Philippe Rameau was published in 1760. Both texts contain a chapter which gives explanations how to sing. The treatises include different types of technical words: specific terms easy identified as special language terms like names of ornaments in the music, special verbs standing for singing, and words and anaphors to describe tonality and dynamics. By having a look on the terms of music language, the influence of Italian and French words on German vocabulary of music becomes obvious. The vocabulary is often similar in both languages, but not always defined as a part of the special language of music. KW - special language of music KW - contrastive analysis of languages KW - vocabulary of singing KW - Mattheson KW - Rameau Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172958 SN - 2510-2613 VL - 3 ER - TY - JOUR A1 - Schäfer, Elena T1 - Veo veo. ¿Qué ves? Durch Hör-Seh-Verstehen zu Mehrsprachigkeitskompetenz JF - promptus - Würzburger Beiträge zur Romanistik N2 - Multilingualism is part of our everyday lives and has recently entered the medium of film. Based on the linguistic diversity of Spanish-speaking countries, the present paper explores multilingualism as a key competence of foreign language learning. Since film provides students with audiovisual access to multilingual situations, a selection of educational videos that form parts of German textbooks will be critically explored concerning the presentation of multilingual phenomena. The results will be discussed in order to contribute to the systematic acquisition of multilingual skills in the sense of language and cultural awareness during classroom learning. KW - Mehrsprachigkeit KW - Hör-Seh-Verstehen KW - Spanisch KW - Lehrwerkanalyse KW - Lernvideo Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172946 SN - 2510-2613 VL - 3 ER - TY - JOUR A1 - Rauchhaus, Moritz T1 - Topo-Analyse hin zur Ewigkeit: Catherine Pozzi zwischen Journal und Peau d’Âme JF - promptus - Würzburger Beiträge zur Romanistik N2 - Peau d’Âme has often been regarded as an enigmatic and mysterious text which prevented a broad attention and interpretation since its posthumous publication in 1935. But putting the perspective on Pozzi’s Journal, particularly during the years 1920 and 1921, allows us to discover a significant intertextuality between both of them. Catherine Pozzi’s perception of space in her every day writing does not differ from her philosophical work, since for her the concepts of center and periphery do not form a strict dichotomy. It becomes superfluous in a world without limits. The perception and philosophy of Catherine Pozzi tends to go beyond the boundaries of space which allows us, as readers of these two forms of writing, to comprehend her vision of a spatial and temporal eternity. KW - Paris KW - Catherine Pozzi KW - Peau d’Âme KW - Raumwahrnehmung KW - Montpellier Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172938 SN - 2510-2613 VL - 3 ER - TY - JOUR A1 - Bobineau, Julien A1 - Hesselbach, Robert T1 - Interview mit Prof. Dr. Elissa Pustka JF - promptus - Würzburger Beiträge zur Romanistik N2 - Interview mit Prof. Dr. Elissa Pustka KW - Interview KW - Karriere KW - Wissenschaftlicher Nachwuchs Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172927 SN - 2510-2613 VL - 3 ER - TY - JOUR A1 - Mounga, Bauvarie T1 - Stratégies narratives et violence dans le roman post-colonial africain : le cas de la technique du fragmentaire dans Le Pleurer-rire d’Henri Lopès JF - promptus - Würzburger Beiträge zur Romanistik N2 - After independence, in the sixties, sub-Saharan Africa including Francophone, saw moving to the head of his governments, dictatorial powers. Henri Lopès translated this in his work by a formal violence. We will study in this paper, the violence employed by the Congolese novelist in Le Pleurer-rire (1982): the technique of fragmentary. Our work is structured in three parts: the presentation of formal violence in Le Pleurer-rire, manifestations of postcolonial political system in this novel and the operation of the technique of fragmentary. KW - postcolonial novel KW - narration KW - technique of fragmentary KW - dictatorship KW - violence Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172916 SN - 2510-2613 VL - 3 ER - TY - JOUR A1 - Ibrahim, Amira T1 - L’orientalisme français : définition et histoire JF - promptus - Würzburger Beiträge zur Romanistik N2 - The history of intellectual and cultural contact between West and East is very complicated and contradictory. A long time ago, eastern culture attracted the attention of many writers, orientalists and researchers, who headed east not only to study and describe the fascinating eastern civilizations, but also to analyze their different literary, historical and scientific aspects. The new mysterious but exciting environment inspired the orientalists to record and describe what they experienced regarding the architecture, the nature and the people. The attractive eastern natural views which are distinguishable from the monotonous western environment – especially after the industrial revolution – helped them to find new prospects. The East has been coming into focus since the middle ages, when the church campaigns started to study Islam as the prevalent religion in this area. The orientalist motivations were not only religious, but also followed economic, colonial and scientific agenda, which lead to a plethora of specialized research, stories, novels and analytical studies. A close look at the orientalists’ works will provide us with an overview of eastern civilization. Therefore, their works are considered as a mirror reflecting their point of view to the east and the north of Africa, especially to pharaonic Egypt. The orientalists who travelled to the east and expressed their passion to this old civilization in their writings influenced the literary movement deeply. But what do we mean by the term orientalism? Edward Saïd has defined this term in different ways. Saïd presented and interpreted it as a way of thinking, a historical phenomenon. Defining orientalism has become a problem indeed, and now it is carrying a number of meanings which do not match. Therefore, the aim of the study is to bring into focus the most important definitions of the term orientalism from the late 17th to the mid-20th century. KW - orientalisme KW - les Turqueries KW - la campagne d’Égypte KW - Edward Saïd Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172899 SN - 2510-2613 VL - 3 ER - TY - JOUR A1 - Hennemann, Anja T1 - «ainda é nova a música, i think» Zur Code-Alternation in portugiesischen online-Diskursen JF - promptus - Würzburger Beiträge zur Romanistik N2 - The present paper is concerned with the use of English cognitive verbs like think, mean and guess as well as with fixed expressions that contain these verbs like guess what (?) or think about it in Portuguese online discourses. In the qualitative analysis of examples retrieved from the Corpus do Português (Web/Dialects) I mainly focus on the syntactic behavior of the expressions under survey, also comparing their use and function in the English language. In the final part of the paper I reflect about possible reasons of the employment of English elements in Portuguese conversation. KW - Code-switching KW - Portugiesisch KW - Englisch KW - online-Kommunikation KW - (nonce) borrowing Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172882 SN - 2510-2613 VL - 3 ER - TY - JOUR A1 - Dürner, Benedikt T1 - Der lyrische Triebtäter André Pieyre de Mandiargues Gewalt und Erotik im Gedichtband L’Âge de craie JF - promptus - Würzburger Beiträge zur Romanistik N2 - The surrealists are not the only influence on the literary efforts of André Pieyre de Mandiargues – but it’s this influence that makes his oeuvre capable for an analysis based on Freudian theories. This way of an analysis is even more appropriate knowing that two of Mandiargues’ main and favourite themes – the eroticism and the violence – coincide with the Freudian life and destruction drive. Analysing the two poems Les filles des gobes and Les ruines de l’amour from the volume of poems L’Âge de craie, it’s these two paradigms that are clearly recognizable: Mandiargues’ symbolism reveals the duality of the domination by desires. KW - Gewalt KW - Bataille KW - Trieb KW - Freud KW - Erotik Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172876 SN - 2510-2613 VL - 3 ER - TY - JOUR A1 - Book, Bettina T1 - Komplementsätze im Spanischen JF - promptus - Würzburger Beiträge zur Romanistik N2 - This paper discusses complementation strategies in Spanish, focusing on a specific construction most speakers are not aware of: the complementation clause preceded by the verb conocer. Not being a typical complement-taking verb, conocer surprises with a stable and persistent presence throughout the centuries, from Old Spanish to Modern Spanish. After giving an introduction into the field of complementation clauses and one of its main focus of study, grammatical mood, this study uses empirical data from the corpus programs CORDE, CREA and CORPES XXI to show the usage and prevalence of the construction in question. In doing so, this analysis gives a quantitative insight, exemplifying the results with several examples from all ages. KW - Syntax KW - Komplementsatz KW - Korpus KW - quantitativ KW - conocer Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172869 SN - 2510-2613 VL - 3 ER - TY - JOUR A1 - Berneiser, Tobias T1 - Lissabonner Navigationen. Literarische Nautik und heterotopischer Stadtdiskurs in José Cardoso Pires’ Lisboa – Livro de Bordo JF - promptus - Würzburger Beiträge zur Romanistik N2 - This article seeks to analyse urban representation in José Cardoso Pires’s Lisboa – Livro de Bordo (1997), a book dedicated to the author’s home city Lisbon, by focusing on its prevailing nautical and maritime imagery. This imagery as well as its tendency to design Lisbon as a city-ship shall be examined with regard to spatial construction in the Livro de Bordo. Urban sailing as well as the recurrent representations of the Portuguese capital’s spaces as heterotopias will be interpreted as approaches to subvert institutional and homogenic discourses on Lisbon. KW - José Cardoso Pires, Lisbon KW - heterotopia KW - urban discourse KW - urban semiotics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172859 SN - 2510-2613 VL - 3 ER - TY - JOUR A1 - Apostolidis -Gkarpousis, Alexandros A1 - Koch, Christian T1 - Convergences et divergences dans les articles «Langage» de Louis de Jaucourt et «Langue» de Nicolas Beauzée. Une comparaison de deux articles de l’Encyclopédie de Diderot et D’Alembert JF - promptus - Würzburger Beiträge zur Romanistik N2 - The two articles of «Langage» and «Langue», published in 1765 in the 9th volume of the great French Encyclopédie by Diderot and D’Alembert, treat some essential philosophical questions on the human ability of communication with linguistic signs. Nevertheless, as the two authors Jaucourt and Beauzée did not share completely identic points of view, the comparative lecture of both articles reveals a complementary perspective, particularly relating to the origin of language as a divine gift or humans’ creation for communicative needs. A further aspect of divergence concerns the textual composition of the article « Langage » as a structured informative text, and the article « Langue » as a long and freely composed writing including personal remarks by the author. The following article deals with the potential of approaches to the Encyclopédie in modern linguistics, concretely demonstrated in the comparative analysis of these two articles. KW - Encyclopédie KW - Lumières KW - philosophie du langage KW - Beauzée KW - Jaucourt Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172843 SN - 2510-2613 VL - 3 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Sheikhbahaei, Sara A1 - Jones, Krystyna M. A1 - Javadi, Mehrbod S. A1 - Solnes, Lilja B. A1 - Ross, Ashley E. A1 - Allaf, Mohamad E. A1 - Pienta, Kenneth J. A1 - Lapa, Constantin A1 - Buck, Andreas K. A1 - Higuchi, Takahiro A1 - Pomper, Martin G. A1 - Gorin, Micheal A. A1 - Rowe, Steven P. T1 - Patterns of uptake of prostate-specific membrane antigen (PSMA)-targeted \(^{18}\)F-DCFPyL in peripheral ganglia JF - Annals of Nuclear Medicine N2 - Objective: Radiotracers targeting prostate-specific membrane antigen (PSMA) have increasingly been recognized as showing uptake in a number of normal structures, anatomic variants, and non-prostate-cancer pathologies. We aimed to explore the frequency and degree of uptake in peripheral ganglia in patients undergoing PET with the PSMA-targeted agent \(^{18}\)F-DCFPyL. Methods: A total of 98 patients who underwent \(^{18}\)F-DCFPyL PET/CT imaging were retrospectively analyzed. This included 76 men with prostate cancer (PCa) and 22 patients with renal cell carcinoma (RCC; 13 men, 9 women). Scans were evaluated for uptake in the cervical, stellate, celiac, lumbar and sacral ganglia. Maximum standardized uptake value corrected to body weight (SUV\(_{max}\)), and maximum standardized uptake value corrected to lean body mass (SUL\(_{max}\)) were recorded for all ganglia with visible uptake above background. Ganglia-to-background ratios were calculated by dividing the SUV\(_{max}\) and SUL\(_{max}\) values by the mean uptake in the ascending aorta (Aortamean) and the right gluteus muscle (Gluteusmean). Results: Overall, 95 of 98 (96.9%) patients demonstrated uptake in at least one of the evaluated peripheral ganglia. With regard to the PCa cohort, the most frequent sites of radiotracer accumulation were lumbar ganglia (55/76, 72.4%), followed by the cervical ganglia (51/76, 67.1%). Bilateral uptake was found in the majority of cases [lumbar 44/55 (80%) and cervical 30/51 (58.8%)]. Additionally, discernible radiotracer uptake was recorded in 50/76 (65.8%) of the analyzed stellate ganglia and in 45/76 (59.2%) of the celiac ganglia, whereas only 5/76 (6.6%) of the sacral ganglia demonstrated \(^{18}\)F-DCFPyL accumulation. Similar findings were observed for patients with RCC, with the most frequent locations of radiotracer uptake in both the lumbar (20/22, 90.9%) and cervical ganglia (19/ 22, 86.4%). No laterality preference was found in mean PSMA-ligand uptake for either the PCa or RCC cohorts. Conclusion: As PSMA-targeted agents become more widely disseminated, the patterns of uptake in structures that are not directly relevant to patients’ cancers must be understood. This is the first systematic evaluation of the uptake of \(^{18}\)F-DCFPyL in ganglia demonstrating a general trend with a descending frequency of radiotracer accumulation in lumbar, cervical, stellate, celiac, and sacral ganglia. The underlying biology that leads to variability of PSMA-targeted radiotracers in peripheral ganglia is not currently understood, but may provide opportunities for future research. KW - 18F-DCFPL KW - Positronen-Emissions-Tomografie KW - Prostata KW - PSMA KW - Ganglia KW - Pitfall KW - PET KW - Tracer KW - Radiotracer KW - Imaging pitfalls KW - Prostate Cancer Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166971 SN - 0914-7187 VL - 31 IS - 9 ER - TY - JOUR A1 - Schindler, Julia A1 - Richter, Tobias A1 - Eyßer, Carolin T1 - Mood moderates the effect of self-generation during learning JF - Frontline Learning Research N2 - Generating information, compared to reading, improves learning and enhances long-term retention of the learned content. This so-called generation effect has been demonstrated repeatedly for recall and recognition of single words. However, before adopting generating as a learning strategy in educational contexts, conditions moderating the effect need to be identified. This study investigated the impact of positive and negative mood states on the generation effect with short expository texts. According to the dual-force framework (Fiedler, Nickel, Asbeck, & Pagel, 2003), positive mood should facilitate generation by enhancing creative knowledge-based top-down processing (assimilation). Negative mood, however, should facilitate learning in the read-condition by enhancing critical stimulus-driven bottom-up processing (accommodation). In contrast to our expectations, we found no general generation effect but an overall learning advantage of read compared to generated texts. However, a significant interaction of learning condition and mood indicates that learners in a better mood recall generated texts better than learners in a more negative mood, whereas no mood effect was found when the texts were read. The results of the present study partially support the predictions of the dual-force framework and are discussed in the context of recent theoretical approaches to the generation effect. KW - mood states KW - generation effect KW - learning with expository texts Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159282 VL - 5 IS - 4 ER - TY - JOUR A1 - Koessler, Juergen A1 - Schwarz, Michaela A1 - Weber, Katja A1 - Etzel, Julia A1 - Koessler, Angela A1 - Boeck, Markus A1 - Kobsar, Anna T1 - The role of adenosine diphosphate mediated platelet responsiveness for the stability of platelet integrity in citrated whole blood under ex vivo conditions JF - PLoS ONE N2 - Background: Platelets are important for effective hemostasis and considered to be involved in pathophysiological processes, e.g. in cardiovascular diseases. Platelets provided for research or for therapeutic use are frequently separated from citrated whole blood (WB) stored for different periods of time. Although functionally intact platelets are required, the stability of platelet integrity, e.g. adenosine diphosphate (ADP) mediated responsiveness, has never been thoroughly investigated in citrated WB under ex vivo conditions. Objectives: Platelet integrity was evaluated at different time points in citrated WB units, collected from healthy donors and stored for 5 days at ambient temperature. The analysis included the measurement of activation markers, of induced light transmission aggregometry and of purinergic receptor expression or function. Inhibitory pathways were explored by determination of basal vasodilator-stimulated phosphoprotein (VASP)-phosphorylation, intracellular cyclic nucleotide levels and the content of phosphodiesterase 5A. Fresh peripheral blood (PB) samples served as controls. Results: On day 5 of storage, thrombin receptor activating peptide-6 (TRAP-6) stimulated CD62P expression and fibrinogen binding were comparable to PB samples. ADP induced aggregation continuously decreased during storage. Purinergic receptor expression remained unchanged, whereas the P2Y1 activity progressively declined in contrast to preserved P2Y12 and P2X1 function. Inhibitory pathways were unaffected except for a slight elevation of VASP phosphorylation at Ser\(^{239}\) on day 5. Conclusion: After 5 days of storage in citrated WB, platelet responsiveness to TRAP-6 is sufficiently maintained. However, ADP-mediated platelet integrity is more sensitive to deterioration, especially after storage for more than 2 days. Decreasing ADP-induced aggregation is particularly caused by the impairment of the purinergic receptor P2Y1 activity. These characteristics should be considered in the use of platelets from stored citrated WB for experimental or therapeutic issues. KW - fibrinogen KW - phosphorylation KW - platelets KW - blood KW - specimen storage KW - flow cytometry Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159879 VL - 12 IS - 11 ER - TY - JOUR A1 - Mülek, Melanie A1 - Seefried, Lothar A1 - Genest, Franca A1 - Högger, Petra T1 - Distribution of constituents and metabolites of maritime pine bark extract (Pycnogenol\(^{®}\)) into serum, blood cells, and synovial fluid of patients with severe osteoarthritis: a randomized controlled trial JF - Nutrients N2 - The present randomized controlled study aimed to investigate the in vivo distribution of constituents or metabolites of the standardized maritime pine bark extract Pycnogenol\(^{®}\). Thirty-three patients with severe osteoarthritis scheduled for a knee arthroplasty were randomized to receive either 200 mg per day Pycnogenol\(^{®}\) (P+) or no treatment (Co) over three weeks before surgery. Serum, blood cells, and synovial fluid samples were analyzed using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization (LC-ESI/MS/MS). Considerable interindividual differences were observed indicating pronounced variability of the polyphenol pharmacokinetics. Notably, the highest polyphenol concentrations were not detected in serum. Catechin and taxifolin primarily resided within the blood cells while the microbial catechin metabolite δ-(3,4-dihydroxy-phenyl)-γ-valerolactone, ferulic, and caffeic acid were mainly present in synovial fluid samples. Taxifolin was detected in serum and synovial fluid exclusively in the P+ group. Likewise, no ferulic acid was found in serum samples of the Co group. Calculating ratios of analyte distribution in individual patients revealed a simultaneous presence of some polyphenols in serum, blood cells, and/or synovial fluid only in the P+ group. This is the first evidence that polyphenols distribute into the synovial fluid of patients with osteoarthritis which supports rationalizing the results of clinical efficacy studies. KW - osteoarthritis KW - randomized controlled study KW - LC-ESI/MS/MS KW - human KW - pine bark extract KW - polyphenols Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159862 VL - 9 IS - 5 ER - TY - JOUR A1 - Schuhmann, Michael K. A1 - Fluri, Felix T1 - Effects of fullerenols on mouse brain microvascular endothelial cells JF - International Journal of Molecular Sciences N2 - Fullerenols, water-soluble C60-fullerene derivatives, have been shown to exert neuroprotective effects in vitro and in vivo, most likely due to their capability to scavenge free radicals. However, little is known about the effects of fullerenols on the blood–brain barrier (BBB), especially on cerebral endothelial cells under inflammatory conditions. Here, we investigated whether the treatment of primary mouse brain microvascular endothelial cells with fullerenols impacts basal and inflammatory blood–brain barrier (BBB) properties in vitro. While fullerenols (1, 10, and 100 µg/mL) did not change transendothelial electrical resistance under basal and inflammatory conditions, 100 µg/mL of fullerenol significantly reduced erk1/2 activation and resulted in an activation of NFκB in an inflammatory milieu. Our findings suggest that fullerenols might counteract oxidative stress via the erk1/2 and NFκB pathways, and thus are able to protect microvascular endothelial cells under inflammatory conditions. KW - mouse brain microvascular endothelial cell cultur KW - adhesion molecules KW - fullerenes KW - blood-brain barrier KW - inflammation KW - tight junctions Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158072 SN - 1422-0067 VL - 18 IS - 8 ER - TY - JOUR A1 - Born, Dennis-Peter A1 - Zinner, Christoph A1 - Sperlich, Billy T1 - The mucosal immune function is not compromised during a period of high-intensity interval training. Is it time to reconsider an old assumption? JF - Frontiers in Physiology N2 - Purpose: The aim of the study was to evaluate the mucosal immune function and circadian variation of salivary cortisol, Immunoglobin-A (sIgA) secretion rate and mood during a period of high-intensity interval training (HIIT) compared to long-slow distance training (LSD). Methods: Recreational male runners (n = 28) completed nine sessions of either HIIT or LSD within 3 weeks. The HIIT involved 4 × 4 min of running at 90–95% of maximum heart rate interspersed with 3 min of active recovery while the LSD comprised of continuous running at 70–75% of maximum heart rate for 60–80 min. The psycho-immunological stress-response was investigated with a full daily profile of salivary cortisol and immunoglobin-A (sIgA) secretion rate along with the mood state on a baseline day, the first and last day of training and at follow-up 4 days after the last day of training. Before and after the training period, each athlete's running performance and peak oxygen uptake (V·O\(_{2peak}\)) was determined with an incremental exercise test. Results: The HIIT resulted in a longer time-to-exhaustion (P = 0.02) and increased V·O\(_{2peak}\) compared to LSD (P = 0.01). The circadian variation of sIgA secretion rate showed highest values in the morning immediately after waking up followed by a decrease throughout the day in both groups (P < 0.05). With HIIT, the wake-up response of sIgA secretion rate was higher on the last day of training (P < 0.01) as well as the area under the curve (AUC\(_{G}\)) higher on the first and last day of training and follow-up compared to the LSD (P = 0.01). Also the AUC\(_{G}\) for the sIgA secretion rate correlated with the increase in V·O\(_{2peak}\) and running performance. The AUC\(_{G}\) for cortisol remained unaffected on the first and last day of training but increased on the follow-up day with both, HIIT and LSD (P < 0.01). Conclusion: The increased sIgA secretion rate with the HIIT indicates no compromised mucosal immune function compared to LSD and shows the functional adaptation of the mucosal immune system in response to the increased stress and training load of nine sessions of HIIT. KW - high-volume training KW - periodization KW - circadian rhythm KW - cortisol KW - diurnal profile KW - endurance KW - immunoglobin-A Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158025 VL - 8 IS - 485 ER - TY - JOUR A1 - Wallmann-Sperlich, Birgit A1 - Bipp, Tanja A1 - Bucksch, Jens A1 - Froboese, Ingo T1 - Who uses height-adjustable desks? - Sociodemographic, health-related, and psycho-social variables of regular users JF - International Journal of Behavioral Nutrition and Physical Activity N2 - Background: Sit-to-stand height-adjustable desks (HAD) may promote workplace standing, as long as workers use them on a regular basis. The aim of this study was to investigate (i) how common HAD in German desk-based workers are, and how frequently HADs are used, (ii) to identify sociodemographic, health-related, and psycho-social variables of workday sitting including having a HAD, and (iii) to analyse sociodemographic, health-related, and psycho-social variables of users and non-users of HADs. Methods: A cross-sectional sample of 680 participants (51.9% men; 41.0 ± 13.1 years) in a desk-based occupation was interviewed by telephone about their occupational sitting and standing proportions, having and usage of a HAD, and answered questions concerning psycho-social variables of occupational sitting. The proportion of workday sitting was calculated for participants having an HAD (n = 108) and not-having an HAD (n = 573), as well as for regular users of HAD (n = 54), and irregular/non-users of HAD (n = 54). Linear regressions were conducted to calculate associations between socio-demographic, health-related, psychosocial variables and having/not having an HAD, and the proportion of workday sitting. Logistic regressions were executed to examine the association of mentioned variables and participants’ usage of HADs. Results: Sixteen percent report that they have an HAD, and 50% of these report regular use of HAD. Having an HAD is not a correlate of the proportion of workday sitting. Further analysis restricted to participants having available a HAD highlights that only the ‘perceived advantages of sitting less’ was significantly associated with HAD use in the fully adjusted model (OR 1.75 [1.09; 2.81], p < 0.05). Conclusions: The present findings indicate that accompanying behavioral action while providing an HAD is promising to increase the regular usage of HAD. Hence, future research needs to address the specificity of behavioral actions in order to enhance regular HAD use, and needs to give more fundamental insights into these associations. KW - cross-sectional KW - office-workers KW - desk-based KW - height-adjustable desk KW - occupational sitting and physical activity questionnaire KW - sitting time KW - correlates KW - natural approach Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157888 VL - 14 IS - 26 ER - TY - JOUR A1 - Wang Ip, Chi A1 - Klaus, Laura-Christin A1 - Karikari, Akua A. A1 - Visanji, Naomi P. A1 - Brotchie, Jonathan M. A1 - Lang, Anthony E. A1 - Volkmann, Jens A1 - Koprich, James B. T1 - AAV1/2-induced overexpression of A53T-α-synuclein in the substantia nigra results in degeneration of the nigrostriatal system with Lewy-like pathology and motor impairment: a new mouse model for Parkinson’s disease JF - Acta Neuropathologica Communications N2 - α-Synuclein is a protein implicated in the etiopathogenesis of Parkinson’s disease (PD). AAV1/2-driven overexpression of human mutated A53T-α-synuclein in rat and monkey substantia nigra (SN) induces degeneration of nigral dopaminergic neurons and decreases striatal dopamine and tyrosine hydroxylase (TH). Given certain advantages of the mouse, especially it being amendable to genetic manipulation, translating the AAV1/2-A53T α-synuclein model to mice would be of significant value. AAV1/2-A53T α-synuclein or AAV1/2 empty vector (EV) at a concentration of 5.16 x 10\(^{12}\) gp/ml were unilaterally injected into the right SN of male adult C57BL/6 mice. Post-mortem examinations included immunohistochemistry to analyze nigral α-synuclein, Ser129 phosphorylated α-synuclein and TH expression, striatal dopamine transporter (DAT) levels by autoradiography and dopamine levels by high performance liquid chromatography. At 10 weeks, in AAV1/2-A53T α-synuclein mice there was a 33% reduction in TH+ dopaminergic nigral neurons (P < 0.001), 29% deficit in striatal DAT binding (P < 0.05), 38% and 33% reductions in dopamine (P < 0.001) and DOPAC (P < 0.01) levels and a 60% increase in dopamine turnover (homovanilic acid/dopamine ratio; P < 0.001). Immunofluorescence showed that the AAV1/2-A53T α-synuclein injected mice had widespread nigral and striatal expression of vector-delivered A53T-α-synuclein. Concurrent staining with human PD SN samples using gold standard histological methodology for Lewy pathology detection by proteinase K digestion and application of specific antibody raised against human Lewy body α-synuclein (LB509) and Ser129 phosphorylated α-synuclein (81A) revealed insoluble α-synuclein aggregates in AAV1/2-A53T α-synuclein mice resembling Lewy-like neurites and bodies. In the cylinder test, we observed significant paw use asymmetry in the AAV1/2-A53T α-synuclein group when compared to EV controls at 5 and 9 weeks post injection (P < 0.001; P < 0.05). These data show that unilateral injection of AAV1/2-A53T α-synuclein into the mouse SN leads to persistent motor deficits, neurodegeneration of the nigrostriatal dopaminergic system and development of Lewy-like pathology, thereby reflecting clinical and pathological hallmarks of human PD. KW - Lewy-like pathology KW - Parkinson’s disease KW - α-synuclein KW - A53T KW - mutation KW - mouse model Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159429 VL - 5 IS - 11 ER - TY - JOUR A1 - Römer, Daniela A1 - Bollazzi, Martin A1 - Roces, Flavio T1 - Carbon dioxide sensing in an obligate insect-fungus symbiosis: CO\(_{2}\) preferences of leaf-cutting ants to rear their mutualistic fungus JF - PLoS ONE N2 - Defense against biotic or abiotic stresses is one of the benefits of living in symbiosis. Leaf-cutting ants, which live in an obligate mutualism with a fungus, attenuate thermal and desiccation stress of their partner through behavioral responses, by choosing suitable places for fungus-rearing across the soil profile. The underground environment also presents hypoxic (low oxygen) and hypercapnic (high carbon dioxide) conditions, which can negatively influence the symbiont. Here, we investigated whether workers of the leaf-cutting ant Acromyrmex lundii use the CO\(_{2}\) concentration as an orientation cue when selecting a place to locate their fungus garden, and whether they show preferences for specific CO\(_{2}\) concentrations. We also evaluated whether levels preferred by workers for fungus-rearing differ from those selected for themselves. In the laboratory, CO\(_{2}\) preferences were assessed in binary choices between chambers with different CO\(_{2}\) concentrations, by quantifying number of workers in each chamber and amount of relocated fungus. Leaf-cutting ants used the CO\(_{2}\) concentration as a spatial cue when selecting places for fungus-rearing. A. lundii preferred intermediate CO\(_{2}\) levels, between 1 and 3%, as they would encounter at soil depths where their nest chambers are located. In addition, workers avoided both atmospheric and high CO\(_{2}\) levels as they would occur outside the nest and at deeper soil layers, respectively. In order to prevent fungus desiccation, however, workers relocated fungus to high CO\(_{2}\) levels, which were otherwise avoided. Workers’ CO\(_{2}\) preferences for themselves showed no clear-cut pattern. We suggest that workers avoid both atmospheric and high CO\(_{2}\) concentrations not because they are detrimental for themselves, but because of their consequences for the symbiotic partner. Whether the preferred CO\(_{2}\) concentrations are beneficial for symbiont growth remains to be investigated, as well as whether the observed preferences for fungus-rearing influences the ants’ decisions where to excavate new chambers across the soil profile. KW - fungi KW - nesting habits KW - carbon dioxide KW - ants KW - social systems KW - humidity KW - symbiosis KW - fungal physiology Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159561 VL - 12 IS - 4 ER - TY - JOUR A1 - Hergovits, Sabine A1 - Mais, Christine A1 - Haan, Claude A1 - Costa-Pereira, Ana P. A1 - Hermanns, Heike M. T1 - Oncostatin M induces RIG-I and MDA5 expression and enhances the double-stranded RNA response in fibroblasts JF - Journal of Cellular and Molecular Medicine N2 - Interleukin (IL)-6-type cytokines have no direct antiviral activity; nevertheless, they display immune-modulatory functions. Oncostatin M (OSM), a member of the IL-6 family, has recently been shown to induce a distinct number of classical interferon stimulated genes (ISG). Most of them are involved in antigen processing and presentation. However, induction of retinoic acid-inducible gene (RIG)-I-like receptors (RLR) has not been investigated. Here we report that OSM has the capability to induce the expression of the DExD/H-Box RNA helicases RIG-I and melanoma differentiation antigen 5 (MDA5) as well as of the transcription factors interferon regulatory factor (IRF)1, IRF7 and IRF9 in primary fibroblasts. Induction of the helicases depends on tyrosine as well as serine phosphorylation of STAT1. Moreover, we could show that the OSM-induced STAT1 phosphorylation is predominantly counter-regulated by a strong STAT3-dependent SOCS3 induction, as Stat3 as well as Socs3 knock-down results in an enhanced and prolonged helicase and IRF expression. Other factors involved in regulation of STAT1 or IRF1 activity, like protein tyrosine phosphatase, non-receptor type 2 (PTPN2), promyelocytic leukaemia protein (PML) or small ubiquitin-related modifier 1 (SUMO1), play a minor role in OSM-mediated induction of RLR. Remarkably, OSM and interferon-γ (IFN-γ) synergize to mediate transcription of RLR and pre-treatment of fibroblasts with OSM fosters the type I interferon production in response to a subsequent encounter with double-stranded RNA. Together, these findings suggest that the OSM-induced JAK/STAT1 signalling is implicated in virus protection of non-professional immune cells and may cooperate with interferons to enhance RLR expression in these cells. KW - oncostatin M KW - DExD/H-Box RNA helicase KW - RIG-I KW - STAT1 KW - innate immunity Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159558 VL - 21 IS - 11 ER - TY - JOUR A1 - Klughammer, Johanna A1 - Dittrich, Marcus A1 - Blom, Jochen A1 - Mitesser, Vera A1 - Vogel, Ulrich A1 - Frosch, Matthias A1 - Goesmann, Alexander A1 - Müller, Tobias A1 - Schoen, Christoph T1 - Comparative genome sequencing reveals within-host genetic changes in Neisseria meningitidis during invasive disease JF - PLoS ONE N2 - Some members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanism called phase variation. In line with the hypothesis that phase variation evolved as an adaptation to colonize diverse hosts, computational comparisons of all 27 to date completely sequenced and annotated meningococcal genomes retrieved from public databases showed that contingency genes are indeed enriched for genes involved in host interactions. To assess within-host genetic changes in meningococci, we further used ultra-deep whole-genome sequencing of throat-blood strain pairs isolated from four patients suffering from invasive meningococcal disease. We detected up to three mutations per strain pair, affecting predominantly contingency genes involved in type IV pilus biogenesis. However, there was not a single (set) of mutation(s) that could invariably be found in all four pairs of strains. Phenotypic assays further showed that these genetic changes were generally not associated with increased serum resistance, higher fitness in human blood ex vivo or differences in the interaction with human epithelial and endothelial cells in vitro. In conclusion, we hypothesize that virulence of meningococci results from accidental emergence of invasive variants during carriage and without within host evolution of invasive phenotypes during disease progression in vivo. KW - blood KW - comparative genomics KW - throat KW - genetic loci KW - Neisseria meningitidis KW - genomic libraries KW - genome sequencing KW - sequence assembly tools Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159547 VL - 12 IS - 1 ER - TY - JOUR A1 - Jessberger, Steffen A1 - Högger, Petra A1 - Genest, Franca A1 - Salter, Donald M. A1 - Seefried, Lothar T1 - Cellular pharmacodynamic effects of Pycnogenol\(^{®}\) in patients with severe osteoarthritis: a randomized controlled pilot study JF - BMC Complementary and Alternative Medicine N2 - Background: The standardized maritime pine bark extract (Pycnogenol\(^{®}\)) has previously shown symptom alleviating effects in patients suffering from moderate forms of knee osteoarthritis (OA). The cellular mechanisms for this positive impact are so far unknown. The purpose of the present randomized pilot controlled study was to span the knowledge gap between the reported clinical effects of Pycnogenol\(^{®}\) and its in vivo mechanism of action in OA patients. Methods: Thirty three patients with severe OA scheduled for a knee arthroplasty either received 100 mg of Pycnogenol\(^{®}\) twice daily or no treatment (control group) three weeks before surgery. Cartilage, synovial fluid and serum samples were collected during surgical intervention. Relative gene expression of cartilage homeostasis markers were analyzed in the patients' chondrocytes. Inflammatory and cartilage metabolism mediators were investigated in serum and synovial fluid samples. Results: The oral intake of Pycnogenol\(^{®}\) downregulated the gene expression of various cartilage degradation markers in the patients' chondrocytes, the decrease of MMP3, MMP13 and the pro-inflammatory cytokine IL1B were statistically significant (p ≤ 0.05). Additionally, protein concentrations of ADAMTS-5 in serum were reduced significantly (p ≤ 0.05) after three weeks intake of the pine bark extract. Conclusions: This is the first report about positive cellular effects of a dietary supplement on key catabolic and inflammatory markers in patients with severe OA. The results provide a rational basis for understanding previously reported clinical effects of Pycnogenol\(^{®}\) on symptom scores of patients suffering from OA. KW - maritime pine bark extract KW - qPCR KW - ADAMTS KW - cartilage KW - clinical study KW - osteoarthritis KW - Pycnogenol KW - serum KW - synovial fluid Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159532 VL - 17 IS - 537 ER - TY - JOUR A1 - Haertle, Larissa A1 - El Hajj, Nady A1 - Dittrich, Marcus A1 - Müller, Tobias A1 - Nanda, Indrajit A1 - Lehnen, Harald A1 - Haaf, Thomas T1 - Epigenetic signatures of gestational diabetes mellitus on cord blood methylation JF - Clinical Epigenetics N2 - Background: Intrauterine exposure to gestational diabetes mellitus (GDM) confers a lifelong increased risk for metabolic and other complex disorders to the offspring. GDM-induced epigenetic modifications modulating gene regulation and persisting into later life are generally assumed to mediate these elevated disease susceptibilities. To identify candidate genes for fetal programming, we compared genome-wide methylation patterns of fetal cord bloods (FCBs) from GDM and control pregnancies. Methods and results: Using Illumina’s 450K methylation arrays and following correction for multiple testing, 65 CpG sites (52 associated with genes) displayed significant methylation differences between GDM and control samples. Four candidate genes, ATP5A1, MFAP4, PRKCH, and SLC17A4, from our methylation screen and one, HIF3A, from the literature were validated by bisulfite pyrosequencing. The effects remained significant after adjustment for the confounding factors maternal BMI, gestational week, and fetal sex in a multivariate regression model. In general, GDM effects on FCB methylation were more pronounced in women with insulin-dependent GDM who had a more severe metabolic phenotype than women with dietetically treated GDM. Conclusions: Our study supports an association between maternal GDM and the epigenetic status of the exposed offspring. Consistent with a multifactorial disease model, the observed FCB methylation changes are of small effect size but affect multiple genes/loci. The identified genes are primary candidates for transmitting GDM effects to the next generation. They also may provide useful biomarkers for the diagnosis, prognosis, and treatment of adverse prenatal exposures. KW - fetal programming KW - insulin treatment KW - DNA methylation KW - fetal cord blood KW - gestational diabetes mellitus Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159459 VL - 9 IS - 28 ER - TY - JOUR A1 - Hillmann, Steffi A1 - Wiedmann, Silke A1 - Rücker, Viktoria A1 - Berger, Klaus A1 - Nabavi, Darius A1 - Bruder, Ingo A1 - Koennecke, Hans-Christian A1 - Seidel, Günter A1 - Misselwitz, Björn A1 - Janssen, Alfred A1 - Burmeister, Christoph A1 - Matthis, Christine A1 - Busse, Otto A1 - Hermanek, Peter A1 - Heuschmann, Peter Ulrich T1 - Stroke unit care in Germany: the German stroke registers study group (ADSR) JF - BMC Neurology N2 - Background: Factors influencing access to stroke unit (SU) care and data on quality of SU care in Germany are scarce. We investigated characteristics of patients directly admitted to a SU as well as patient-related and structural factors influencing adherence to predefined indicators of quality of acute stroke care across hospitals providing SU care. Methods: Data were derived from the German Stroke Registers Study Group (ADSR), a voluntary network of 9 regional registers for monitoring quality of acute stroke care in Germany. Multivariable logistic regression analyses were performed to investigate characteristics influencing direct admission to SU. Generalized Linear Mixed Models (GLMM) were used to estimate the influence of structural hospital characteristics (percentage of patients admitted to SU, year of SU-certification, and number of stroke and TIA patients treated per year) on adherence to predefined quality indicators. Results: In 2012 180,887 patients were treated in 255 hospitals providing certified SU care participating within the ADSR were included in the analysis; of those 82.4% were directly admitted to a SU. Ischemic stroke patients without disturbances of consciousness (p < .0001), an interval onset to admission time ≤3 h (p < .0001), and weekend admission (p < .0001) were more likely to be directly admitted to a SU. A higher proportion of quality indicators within predefined target ranges were achieved in hospitals with a higher proportion of SU admission (p = 0.0002). Quality of stroke care could be maintained even if certification was several years ago. Conclusions: Differences in demographical and clinical characteristics regarding the probability of SU admission were observed. The influence of structural characteristics on adherence to evidence-based quality indicators was low. KW - stroke register KW - stroke unit care KW - quality of health care KW - quality indicators Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159447 VL - 17 IS - 49 ER - TY - JOUR A1 - Bening, Constanze A1 - Hamouda, Khaled A1 - Oezkur, Mehmet A1 - Schimmer, Christoph A1 - Schade, Ina A1 - Gorski, Armin A1 - Aleksic, Ivan A1 - Leyh, Rainer T1 - Rapid deployment valve system shortens operative times for aortic valve replacement through right anterior minithoracotomy JF - Journal of Cardiothoracic Surgery N2 - Background: There is growing evidence from the literature that right anterior minithoracotomy aortic valve replacement (RAT-AVR) improves clinical outcome. However, increased cross clamp time is the strongest argument for surgeons not performing RAT-AVR. Rapid deployment aortic valve systems have the potential to decrease cross-clamp time and ease this procedure. We assessed clinical outcome of rapid deployment and conventional valves through RAT. Methods: Sixty-eight patients (mean age 76 ± 6 years, 32% females) underwent RAT-AVR between 9/2013 and 7/2015. According to the valve type implanted the patients were divided into two groups. In 43 patients (R-group; mean age 74.1 ± 6.6 years) a rapid deployment valve system (Edwards Intuity, Edwards Lifesciences Corp; Irvine, Calif) and in 25 patients (C-group; mean age 74.2 ± 6.6 years) a conventional stented biological aortic valve was implanted. Results: Aortic cross-clamp (42.1 ± 12 min vs. 68.3 ± 20.3 min; p < 0.001) and bypass time (80.4 ± 39.3 min vs. 106.6 ± 23.2 min; p = 0.001) were shorter in the rapid deployment group (R-group). We observed no differences in clinical outcome. Postoperative gradients (R-group: max gradient, 14.3 ± 8 mmHg vs. 15.5 ± 5 mmHg (C-group), mean gradient, 9.2 ± 1.7 mmHg (R-group) vs. 9.1 ± 2.3 mmHg (C-group) revealed no differences. However, larger prostheses were implanted in C-group (25 mm; IQR 23–27 mm vs. 23 mm; IQR 21–25; p = 0.009). Conclusions: Our data suggest that the rapid deployment aortic valve system reduced cross clamp and bypass time in patients undergoing RAT-AVR with similar hemodynamics as with larger size stented prosthesis. However, larger studies and long-term follow-up are mandatory to confirm our findings. KW - aortic valve replacement KW - minimally invasive surgery KW - heart valve prosthesis KW - biological rapid deployment aortic valve Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159439 VL - 12 IS - 27 ER - TY - JOUR A1 - Gilbert, Fabian A1 - Klein, Detlef A1 - Weng, Andreas Max A1 - Köstler, Herbert A1 - Schmitz, Benedikt A1 - Schmalzl, Jonas A1 - Böhm, Dirk T1 - Supraspinatus muscle elasticity measured with real time shear wave ultrasound elastography correlates with MRI spectroscopic measured amount of fatty degeneration JF - BMC Muscoskeletal Disorders N2 - Background: Fatty Degeneration (FD) of the rotator cuff muscles influences functional and anatomical outcome after rotator cuff repair. The MRI based estimation of fatty degeneration is the gold standard. There is some evidence that Ultrasound elastography (EUS) can detect local differences of tissue stiffness in muscles and tendons. Shear-wave elastography (SWE) was evaluated to determine the extent to which shear wave velocity was associated with measures of fatty degeneration. MRI-spectroscopic fat measurement was used as a reference to quantify the amount of fat in the muscle belly. Methods: Forty-two patients underwent SWE of the supraspinatus muscles at its thickest diameter. After ultrasound evaluation an MRI-spectroscopic fat measurement of the supraspinatus muscle was performed using the SPLASH-technique. A gel filled capsule was used to locate the measured area in the MRI. The values of shear wave velocity (SWV) measured with SWE and spectroscopic fat measurement were correlated statistically using Pearson’s correlation test. Results: Correlation of the fat amount measured with MRI-spectroscopy and the SWV measured with SWE was ρ =0.82. Spectroscopic measured fat ratio of the supraspinatus muscle ranged from 0% to 77.41% and SWV from 1.59 m/s to 5.32 m/s. In 4 patients no sufficient SWE could be performed, these individuals showed a larger diameter of the overlying soft tissue. SWV measured with SWE showed a good correlation with MRI spectroscopic fat amount of the supraspinatus muscle. Conclusion: These preliminary data suggest that SWE may be a sufficient tool in detecting and estimating the amount of fatty degeneration in the supraspinatus muscle in real time. Large overlying soft tissue may be a limitation in performing sufficient EUS. KW - shoulder surgery KW - rotator cuff KW - MRI KW - ultrasound KW - fatty degeneration Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159378 VL - 18 IS - 549 ER - TY - JOUR A1 - Becam, Jérôme A1 - Walter, Tim A1 - Burgert, Anne A1 - Schlegel, Jan A1 - Sauer, Markus A1 - Seibel, Jürgen A1 - Schubert-Unkmeir, Alexandra T1 - Antibacterial activity of ceramide and ceramide analogs against pathogenic Neisseria JF - Scientific Reports N2 - Certain fatty acids and sphingoid bases found at mucosal surfaces are known to have antibacterial activity and are thought to play a more direct role in innate immunity against bacterial infections. Herein, we analysed the antibacterial activity of sphingolipids, including the sphingoid base sphingosine as well as short-chain C\(_{6}\) and long-chain C\(_{16}\)-ceramides and azido-functionalized ceramide analogs against pathogenic Neisseriae. Determination of the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) demonstrated that short-chain ceramides and a ω-azido-functionalized C\(_{6}\)-ceramide were active against Neisseria meningitidis and N. gonorrhoeae, whereas they were inactive against Escherichia coli and Staphylococcus aureus. Kinetic assays showed that killing of N. meningitidis occurred within 2 h with ω–azido-C\(_{6}\)-ceramide at 1 X the MIC. Of note, at a bactericidal concentration, ω–azido-C\(_{6}\)-ceramide had no significant toxic effect on host cells. Moreover, lipid uptake and localization was studied by flow cytometry and confocal laser scanning microscopy (CLSM) and revealed a rapid uptake by bacteria within 5 min. CLSM and super-resolution fluorescence imaging by direct stochastic optical reconstruction microscopy demonstrated homogeneous distribution of ceramide analogs in the bacterial membrane. Taken together, these data demonstrate the potent bactericidal activity of sphingosine and synthetic short-chain ceramide analogs against pathogenic Neisseriae. KW - ceramide analogs KW - Neisseria KW - ceramide Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159367 VL - 7 ER - TY - JOUR A1 - Rodrigues, Johannes A1 - Ulrich, Natalie A1 - Mussel, Patrick A1 - Carlo, Gustavo A1 - Hewig, Johannes T1 - Measuring prosocial tendencies in Germany: sources of validity and reliablity of the revised prosocial tendency measure JF - Frontiers in Psychology N2 - The prosocial tendencies measure (PTM; Carlo and Randall, 2002) is a widely used measurement for prosocial tendencies in English speaking participants. This instrument distinguishes between six different types of prosocial tendencies that partly share some common basis, but also can be opposed to each other. To examine these constructs in Germany, a study with 1067 participants was conducted. The study investigated the structure of this German version of the PTM-R via exploratory factor analysis, confirmatory factor analysis, correlations with similar constructs in subsamples as well as via measurement invariance test concerning the original English version. The German translation showed a similar factor structure to the English version in exploratory factor analysis and in confirmatory factor analysis. Measurement invariance was found between the English and German language versions of the PTM and support for the proposed six-factor structure (altruistic, anonymous, compliant, dire, emotional and public prosocial behavior) was also found in confirmatory factor analysis. Furthermore, the expected interrelations of these factors of prosocial behavior tendencies were obtained. Finally, correlations of the prosocial behavior tendencies with validating constructs and behaviors were found. Thus, the findings stress the importance of seeing prosocial behavior not as a single dimension construct, but as a factored construct which now can also be assessed in German speaking participants. KW - measurement invariance KW - prosocial tendency measure KW - prosocial behavior KW - altruism KW - validation KW - German translation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159351 VL - 8 ER - TY - JOUR A1 - Zinner, Christoph A1 - Born, Dennis-Peter A1 - Sperlich, Billy T1 - Ischemic preconditioning does not alter performance in multidirectional high-intensity intermittent exercise JF - Frontiers in Physiology N2 - Purpose: Research dealing with ischemic preconditioning (IPC) has primarily focused on variables associated to endurance performance with little research about the acute responses of IPC on repeated multidirectional running sprint performance. Here we aimed to investigate the effects of IPC of the arms and the legs on repeated running sprint performance with changes-of-direction (COD) movements. Methods: Thirteen moderately-to-well-trained team-sport athletes (7 males; 6 females; age: 24 ± 2 years, size: 175 ± 8 cm, body mass: 67.9 ± 8.1 kg) performed 16 × 30 m all-out sprints (15 s rest) with multidirectional COD movements on a Speedcourt\(^{©}\) with IPC (3 × 5 min) of the legs (IPC\(_{leg}\); 240 mm Hg) or of the arms (remote IPC: IPC\(_{remote}\); 180–190 mm Hg) 45 min before the sprints and a control trial (CON; 20 mm Hg). Results: The mean (±SD) time for the 16 × 30 m multidirectional COD sprints was similar between IPC\(_{leg}\) (Mean t: 16.0 ± 1.8 s), IPC\(_{remote}\) (16.2 ± 1.7 s), and CON (16.0 ± 1.6 s; p = 0.50). No statistical differences in oxygen uptake (mean difference: 0%), heart rate (1.1%) nor muscle oxygen saturation of the vastus lateralis (4.7%) and biceps brachii (7.8%) between the three conditions were evident (all p > 0.05). Conclusions: IPC (3 × 5 min) of the legs (220 mm Hg) or arms (180–190 mm Hg; remote IPC) applied 45 min before 16 × 30 m repeated multidirectional running sprint exercise does not improve sprint performance, oxygen uptake, heart rate nor muscle oxygen saturation of the vastus lateralis muscle when compared to a control trial. KW - team sport KW - agility KW - change of direction KW - muscle oxygen saturation KW - near-infrared spectroscopy Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159348 VL - 8 ER - TY - JOUR A1 - Kelm, M. A1 - Seyfried, F. A1 - Reimer, S. A1 - Krajinovic, K. A1 - Miras, A. D. A1 - Jurowich, C. A1 - Germer, C. T. A1 - Brand, M. T1 - Proximal jejunal stoma as ultima ratio in case of traumatic distal duodenal perforation facilitating successful EndoVAC\(^{®}\) treatment: a case report JF - International Journal of Surgery Case Reports N2 - Introduction: During damage control surgery for blunt abdominal traumata simultaneous duodenal perforations can be missed making secondary sufficient surgical treatment challenging. Endoluminal vacuum (EndoVAC™) therapy has been shown to be a revolutionary option but has anatomical and technical limits. Presentation of the case: A 59-year old man with hemorrhagic shock due to rupture of the mesenteric root after blunt abdominal trauma received damage control treatment. Within a scheduled second-look, perforation of the posterior duodenal wall was identified. Due to local and systemic conditions, further surgical treatment was limited. Decision for endoscopic treatment was made but proved to be difficult due to the distal location. Finally, double-barreled jejunal stoma was created for transstomal EndoVAC™ treatment. Complete leakage healing was achieved and jejunostomy reversal followed subsequently. Discussion: During damage control surgery simultaneous bowel injuries can be missed leading to life-threatening complications with limited surgical options. EndoVAC™ treatment is an option for gastrointestinal perforations but has anatomical limitations that can be sufficiently shifted by a transstomal approach for intestinal leakage. Conclusion: In trauma related laparotomy complete mobilization of the duodenum is crucial. As ultima ratio, transstomal EndoVAC™ is a safe and feasible option and can be considered for similar cases. KW - transstomal endoluminal vacuum therapy KW - EndoVAC and small bowel KW - duodenal trauma KW - duodenal perforation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159292 VL - 41 ER - TY - JOUR A1 - Heiby, Julia C. A1 - Rajab, Suhaila A1 - Rat, Charlotte A1 - Johnson, Christopher M. A1 - Neuweiler, Hannes T1 - Conservation of folding and association within a family of spidroin N-terminal domains JF - Scientific Reports N2 - Web spiders synthesize silk fibres, nature’s toughest biomaterial, through the controlled assembly of fibroin proteins, so-called spidroins. The highly conserved spidroin N-terminal domain (NTD) is a pH-driven self-assembly device that connects spidroins to super-molecules in fibres. The degree to which forces of self-assembly is conserved across spider glands and species is currently unknown because quantitative measures are missing. Here, we report the comparative investigation of spidroin NTDs originating from the major ampullate glands of the spider species Euprosthenops australis, Nephila clavipes, Latrodectus hesperus, and Latrodectus geometricus. We characterized equilibrium thermodynamics and kinetics of folding and self-association using dynamic light scattering, stopped-flow fluorescence and circular dichroism spectroscopy in combination with thermal and chemical denaturation experiments. We found cooperative two-state folding on a sub-millisecond time scale through a late transition state of all four domains. Stability was compromised by repulsive electrostatic forces originating from clustering of point charges on the NTD surface required for function. pH-driven dimerization proceeded with characteristic fast kinetics yielding high affinities. Results showed that energetics and kinetics of NTD self-assembly are highly conserved across spider species despite the different silk mechanical properties and web geometries they produce. KW - spider KW - N-terminal domain KW - spidroin Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159272 VL - 7 ER - TY - JOUR A1 - Awad, Eman A1 - Othman, Eman M. A1 - Stopper, Helga T1 - Effects of resveratrol, lovastatin and the mTOR-inhibitor RAD-001 on insulin-induced genomic damage in vitro JF - Molecules N2 - Diabetes mellitus (DM) is one of the major current health problems due to lifestyle changes. Before diagnosis and in the early years of disease, insulin blood levels are elevated. However, insulin generates low levels of reactive oxygen species (ROS) which are integral to the regulation of a variety of intracellular signaling pathways, but excess levels of insulin may also lead to DNA oxidation and DNA damage. Three pharmaceutical compounds, resveratrol, lovastatin and the mTOR-inhibitor RAD-001, were investigated due to their known beneficial effects. They showed protective properties against genotoxic damage and significantly reduced ROS after in vitro treatment of cultured cells with insulin. Therefore, the selected pharmaceuticals may be attractive candidates to be considered for support of DM therapy. KW - genomic damage KW - insulin KW - resveratrol KW - lovastatin KW - mTOR-inhibitor RAD-001 Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159260 VL - 22 IS - 12 ER - TY - JOUR A1 - Kohlmorgen, Britta A1 - Elias, Johannes A1 - Schoen, Christoph T1 - Improved performance of the artus Mycobacterium tuberculosis RG PCR kit in a low incidence setting: a retrospective monocentric study JF - Scientific Reports N2 - Tuberculosis (TB) and the spread of Mycobacterium tuberculosis complex (MTBC) strains resistant against rifampin (RIF) and isoniazid (INH) pose a serious threat to global health. However, rapid and reliable MTBC detection along with RIF/INH susceptibility testing are challenging in low prevalence countries due to the higher rate of false positives. Here, we provide the first performance data for the artus MTBC PCR assay in a low prevalence setting. We analyze 1323 respiratory and 311 non-respiratory samples with the artus MTBC PCR assay as well as by mycobacterial culture and microscopy. We propose retesting of specimens in duplicate and consideration of a determined cycle-threshold value cut-off greater than 34, as this significantly increases accuracy, specificity, and negative predictive value without affecting sensitivity. Furthermore, we tested fourteen MTBC positive samples with the GenoType MTBDRplus test and demonstrate that using an identical DNA extraction protocol for both assays does not impair downstream genotypic testing for RIF and INH susceptibility. In conclusion, our procedure optimizes the use of the artus MTB assay with workload efficient methods in a low incidence setting. Combining the modified artus MTB with the GenoType MTBDRplus assays allows rapid and accurate detection of MTBC and RIF/INH resistance. KW - laboratory techniques and procedures KW - Tuberculosis Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159248 VL - 7 IS - 14127 ER - TY - JOUR A1 - Grob, Robin A1 - Fleischmann, Pauline N. A1 - Grübel, Kornelia A1 - Wehner, Rüdiger A1 - Rössler, Wolfgang T1 - The role of celestial compass information in Cataglyphis ants during learning walks and for neuroplasticity in the central complex and mushroom bodies JF - Frontiers in Behavioral Neuroscience N2 - Central place foragers are faced with the challenge to learn the position of their nest entrance in its surroundings, in order to find their way back home every time they go out to search for food. To acquire navigational information at the beginning of their foraging career, Cataglyphis noda performs learning walks during the transition from interior worker to forager. These small loops around the nest entrance are repeatedly interrupted by strikingly accurate back turns during which the ants stop and precisely gaze back to the nest entrance—presumably to learn the landmark panorama of the nest surroundings. However, as at this point the complete navigational toolkit is not yet available, the ants are in need of a reference system for the compass component of the path integrator to align their nest entrance-directed gazes. In order to find this directional reference system, we systematically manipulated the skylight information received by ants during learning walks in their natural habitat, as it has been previously suggested that the celestial compass, as part of the path integrator, might provide such a reference system. High-speed video analyses of distinct learning walk elements revealed that even exclusion from the skylight polarization pattern, UV-light spectrum and the position of the sun did not alter the accuracy of the look back to the nest behavior. We therefore conclude that C. noda uses a different reference system to initially align their gaze directions. However, a comparison of neuroanatomical changes in the central complex and the mushroom bodies before and after learning walks revealed that exposure to UV light together with a naturally changing polarization pattern was essential to induce neuroplasticity in these high-order sensory integration centers of the ant brain. This suggests a crucial role of celestial information, in particular a changing polarization pattern, in initially calibrating the celestial compass system. KW - sky-compass pathway KW - visual orientation KW - look-back behavior KW - desert ants KW - vector navigation KW - memory KW - central complex KW - mushroom body Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159235 VL - 11 IS - 226 ER - TY - JOUR A1 - Halboth, Florian A1 - Roces, Flavio T1 - The construction of ventilation turrets in Atta vollenweideri leaf-cutting ants: Carbon dioxide levels in the nest tunnels, but not airflow or air humidity, influence turret structure JF - PLoS ONE N2 - Nest ventilation in the leaf-cutting ant Atta vollenweideri is driven via a wind-induced mechanism. On their nests, workers construct small turrets that are expected to facilitate nest ventilation. We hypothesized that the construction and structural features of the turrets would depend on the colony’s current demands for ventilation and thus might be influenced by the prevailing environmental conditions inside the nest. Therefore, we tested whether climate-related parameters, namely airflow, air humidity and CO\(_{2}\) levels in the outflowing nest air influenced turret construction in Atta vollenweideri. In the laboratory, we simulated a semi-natural nest arrangement with fungus chambers, a central ventilation tunnel providing outflow of air and an aboveground building arena for turret construction. In independent series, different climatic conditions inside the ventilation tunnel were experimentally generated, and after 24 hours, several features of the built turret were quantified, i.e., mass, height, number and surface area (aperture) of turret openings. Turret mass and height were similar in all experiments even when no airflow was provided in the ventilation tunnel. However, elevated CO\(_{2}\) levels led to the construction of a turret with several minor openings and a larger total aperture. This effect was statistically significant at higher CO\(_{2}\) levels of 5% and 10% but not at 1% CO\(_{2}\). The construction of a turret with several minor openings did not depend on the strong differences in CO\(_{2}\) levels between the outflowing and the outside air, since workers also built permeated turrets even when the CO\(_{2}\) levels inside and outside were both similarly high. We propose that the construction of turrets with several openings and larger opening surface area might facilitate the removal of CO\(_{2}\) from the underground nest structure and could therefore be involved in the control of nest climate in leaf-cutting ants. KW - carbon dioxide KW - animal sociality KW - ants KW - fungi KW - humidity KW - social systems KW - nesting habits KW - fungal structure Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159133 VL - 12 IS - 11 ER - TY - JOUR A1 - Böhm, Lena A1 - Torsin, Sanda A1 - Tint, Su Hlaing A1 - Eckstein, Marie Therese A1 - Ludwig, Tobias A1 - Pérez, J. Christian T1 - The yeast form of the fungus Candida albicans promotes persistence in the gut of gnotobiotic mice JF - PLoS Pathogens N2 - Many microorganisms that cause systemic, life-threatening infections in humans reside as harmless commensals in our digestive tract. Yet little is known about the biology of these microbes in the gut. Here, we visualize the interface between the human commensal and pathogenic fungus Candida albicans and the intestine of mice, a surrogate host. Because the indigenous mouse microbiota restricts C. albicans settlement, we compared the patterns of colonization in the gut of germ free and antibiotic-treated conventionally raised mice. In contrast to the heterogeneous morphologies found in the latter, we establish that in germ free animals the fungus almost uniformly adopts the yeast cell form, a proxy of its commensal state. By screening a collection of C. albicans transcription regulator deletion mutants in gnotobiotic mice, we identify several genes previously unknown to contribute to in vivo fitness. We investigate three of these regulators—ZCF8, ZFU2 and TRY4—and show that indeed they favor the yeast form over other morphologies. Consistent with this finding, we demonstrate that genetically inducing non-yeast cell morphologies is detrimental to the fitness of C. albicans in the gut. Furthermore, the identified regulators promote adherence of the fungus to a surface covered with mucin and to mucus-producing intestinal epithelial cells. In agreement with this result, histology sections indicate that C. albicans dwells in the murine gut in close proximity to the mucus layer. Thus, our findings reveal a set of regulators that endows C. albicans with the ability to endure in the intestine through multiple mechanisms. KW - Candida albicans KW - deletion mutagenesis KW - gastrointestinal tract KW - fungi KW - regulator genes KW - gene regulation KW - mouse models KW - fungal genetics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159120 VL - 13 IS - 10 ER - TY - JOUR A1 - Radakovic, D. A1 - Reboredo, J. A1 - Helm, M. A1 - Weigel, T. A1 - Schürlein, S. A1 - Kupczyk, E. A1 - Leyh, R. G. A1 - Walles, H. A1 - Hansmann, J. T1 - A multilayered electrospun graft as vascular access for hemodialysis JF - PLoS ONE N2 - Despite medical achievements, the number of patients with end-stage kidney disease keeps steadily raising, thereby entailing a high number of surgical and interventional procedures to establish and maintain arteriovenous vascular access for hemodialysis. Due to vascular disease, aneurysms or infection, the preferred access—an autogenous arteriovenous fistula—is not always available and appropriate. Moreover, when replacing small diameter blood vessels, synthetic vascular grafts possess well-known disadvantages. A continuous multilayered gradient electrospinning was used to produce vascular grafts made of collagen type I nanofibers on luminal and adventitial graft side, and poly-ɛ-caprolactone as medial layer. Therefore, a custom-made electrospinner with robust environmental control was developed. The morphology of electrospun grafts was characterized by scanning electron microscopy and measurement of mechanical properties. Human microvascular endothelial cells were cultured in the graft under static culture conditions and compared to cultures obtained from dynamic continuous flow bioreactors. Immunofluorescent analysis showed that endothelial cells form a continuous luminal layer and functional characteristics were confirmed by uptake of acetylated low-density-lipoprotein. Incorporation of vancomycin and gentamicin to the medial graft layer allowed antimicrobial inhibition without exhibiting an adverse impact on cell viability. Most striking a physiological hemocompatibility was achieved for the multilayered grafts. KW - collagens KW - polymers KW - vascular surgery KW - endothelial cells KW - cell cultures KW - blood KW - antibiotics KW - scanning electron microscopy Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159102 VL - 12 IS - 10 ER - TY - JOUR A1 - Dombert, Benjamin A1 - Balk, Stefanie A1 - Lüningschrör, Patrick A1 - Moradi, Mehri A1 - Sivadasan, Rajeeve A1 - Saal-Bauernschubert, Lena A1 - Jablonka, Sibylle T1 - BDNF/trkB induction of calcium transients through Ca\(_{v}\)2.2 calcium channels in motoneurons corresponds to F-actin assembly and growth cone formation on β2-chain laminin (221) JF - Frontiers in Molecular Neuroscience N2 - Spontaneous Ca\(^{2+}\) transients and actin dynamics in primary motoneurons correspond to cellular differentiation such as axon elongation and growth cone formation. Brain-derived neurotrophic factor (BDNF) and its receptor trkB support both motoneuron survival and synaptic differentiation. However, in motoneurons effects of BDNF/trkB signaling on spontaneous Ca\(^{2+}\) influx and actin dynamics at axonal growth cones are not fully unraveled. In our study we addressed the question how neurotrophic factor signaling corresponds to cell autonomous excitability and growth cone formation. Primary motoneurons from mouse embryos were cultured on the synapse specific, β2-chain containing laminin isoform (221) regulating axon elongation through spontaneous Ca\(^{2+}\) transients that are in turn induced by enhanced clustering of N-type specific voltage-gated Ca\(^{2+}\) channels (Ca\(_{v}\)2.2) in axonal growth cones. TrkB-deficient (trkBTK\(^{-/-}\)) mouse motoneurons which express no full-length trkB receptor and wildtype motoneurons cultured without BDNF exhibited reduced spontaneous Ca\(^{2+}\) transients that corresponded to altered axon elongation and defects in growth cone morphology which was accompanied by changes in the local actin cytoskeleton. Vice versa, the acute application of BDNF resulted in the induction of spontaneous Ca\(^{2+}\) transients and Ca\(_{v}\)2.2 clustering in motor growth cones, as well as the activation of trkB downstream signaling cascades which promoted the stabilization of β-actin via the LIM kinase pathway and phosphorylation of profilin at Tyr129. Finally, we identified a mutual regulation of neuronal excitability and actin dynamics in axonal growth cones of embryonic motoneurons cultured on laminin-221/211. Impaired excitability resulted in dysregulated axon extension and local actin cytoskeleton, whereas upon β-actin knockdown Ca\(_{v}\)2.2 clustering was affected. We conclude from our data that in embryonic motoneurons BDNF/trkB signaling contributes to axon elongation and growth cone formation through changes in the local actin cytoskeleton accompanied by increased Ca\(_{v}\)2.2 clustering and local calcium transients. These findings may help to explore cellular mechanisms which might be dysregulated during maturation of embryonic motoneurons leading to motoneuron disease. KW - growth cone KW - BDNF KW - trkB KW - Ca\(_{v}\)2.2 KW - F-actin KW - motor axon Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159094 VL - 10 IS - 346 ER - TY - JOUR A1 - Lapa, Constantin A1 - Arias-Loza, Paula A1 - Hayakawa, Nobuyuki A1 - Wakabayashi, Hiroshi A1 - Werner, Rudolf A. A1 - Chen, Xinyu A1 - Shinaji, Tetsuya A1 - Herrmann, Ken A1 - Pelzer, Theo A1 - Higuchi, Takahiro T1 - Whitening and impaired glucose utilization of brown adipose tissue in a rat model of type 2 diabetes mellitus JF - Scientific Reports N2 - Brown adipose tissue (BAT) is an attractive therapeutic target to combat diabetes and obesity due to its ability to increase glucose expenditure. In a genetic rat model (ZDF fa/fa) of type-2 diabetes and obesity, we aimed to investigate glucose utilization of BAT by \(^{18}\)F-FDG PET imaging. Male Zucker diabetic fatty (ZDF) and Male Zucker lean (ZL) control rats were studied at 13 weeks. Three weeks prior to imaging, ZDF rats were randomized into a no-restriction (ZDF-ND) and a mild calorie restriction (ZDF-CR) group. Dynamic \(^{18}\)F-FDG PET using a dedicated small animal PET system was performed under hyperinsulinemic-euglycemic clamp. \(^{18}\)F-FDG PET identified intense inter-scapular BAT glucose uptake in all ZL control rats, while no focally increased \(^{18}\)F-FDG uptake was detected in all ZDF-ND rats. Mild but significant improved BAT tracer uptake was identified after calorie restriction in diabetic rats (ZDF-CR). The weight of BAT tissue and fat deposits were significantly increased in ZDF-CR and ZDF-ND rats as compared to ZL controls, while UCP-1 and mitochondrial concentrations were significantly decreased. Whitening and severely impaired insulin-stimulated glucose uptake in BAT was confirmed in a rat model of type-2 diabetes. Additionally, calorie restriction partially restored the impaired BAT glucose uptake. KW - molecular medicine KW - endocrinology Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159066 VL - 7 ER -