TY - JOUR A1 - Sharan, Malvika A1 - Förstner, Konrad U. A1 - Eulalio, Ana A1 - Vogel, Jörg T1 - APRICOT: an integrated computational pipeline for the sequence-based identification and characterization of RNA-binding proteins JF - Nucleic Acids Research N2 - RNA-binding proteins (RBPs) have been established as core components of several post-transcriptional gene regulation mechanisms. Experimental techniques such as cross-linking and co-immunoprecipitation have enabled the identification of RBPs, RNA-binding domains (RBDs) and their regulatory roles in the eukaryotic species such as human and yeast in large-scale. In contrast, our knowledge of the number and potential diversity of RBPs in bacteria is poorer due to the technical challenges associated with the existing global screening approaches. We introduce APRICOT, a computational pipeline for the sequence-based identification and characterization of proteins using RBDs known from experimental studies. The pipeline identifies functional motifs in protein sequences using position-specific scoring matrices and Hidden Markov Models of the functional domains and statistically scores them based on a series of sequence-based features. Subsequently, APRICOT identifies putative RBPs and characterizes them by several biological properties. Here we demonstrate the application and adaptability of the pipeline on large-scale protein sets, including the bacterial proteome of Escherichia coli. APRICOT showed better performance on various datasets compared to other existing tools for the sequence-based prediction of RBPs by achieving an average sensitivity and specificity of 0.90 and 0.91 respectively. The command-line tool and its documentation are available at https://pypi.python.org/pypi/bio-apricot. KW - RNA-binding proteins KW - identification KW - characterization Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157963 VL - 45 IS - 11 ER - TY - JOUR A1 - Shamim, Saquib A1 - Mahapatra, S. A1 - Scappucci, G. A1 - Klesse, W. M. A1 - Simmons, M. Y. A1 - Ghosh, Arindam T1 - Dephasing rates for weak localization and universal conductance fluctuations in two dimensional Si: P and Ge: P δ-layers JF - Scientific Reports N2 - We report quantum transport measurements on two dimensional (2D) Si:P and Ge:P δ-layers and compare the inelastic scattering rates relevant for weak localization (WL) and universal conductance fluctuations (UCF) for devices of various doping densities (0.3–2.5 × 10\(^{18}\)m\(^{−2}\)) at low temperatures (0.3–4.2 K). The phase breaking rate extracted experimentally from measurements of WL correction to conductivity and UCF agree well with each other within the entire temperature range. This establishes that WL and UCF, being the outcome of quantum interference phenomena, are governed by the same dephasing rate. KW - two-dimensional materials KW - quantum information KW - electronic properties and materials Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170934 VL - 7 IS - 46670 ER - TY - JOUR A1 - Shady, Nourhan Hisham A1 - El-Hossary, Ebaa M. A1 - Fouad, Mostafa A. A1 - Gulder, Tobias A. M. A1 - Kamel, Mohamed Salah A1 - Abdelmohsen, Usama Ramadan T1 - Bioactive natural products of marine sponges from the Genus Hyrtios JF - Molecules N2 - Marine sponges are known as a rich source for novel bioactive compounds with valuable pharmacological potential. One of the most predominant sponge genera is Hyrtios, reported to have various species such as Hyrtios erectus, Hyrtios reticulatus, Hyrtios gumminae, Hyrtios communis, and Hyrtios tubulatus and a number of undescribed species. Members of the genus Hyrtios are a rich source of natural products with diverse and valuable biological activities, represented by different chemical classes including alkaloids, sesterterpenes and sesquiterpenes. This review covers the literature until June 2016, providing a complete survey of all compounds isolated from the genus Hyrtios with their corresponding biological activities whenever applicable. KW - alkaloids KW - bioactive KW - marine natural products KW - marine sponges KW - Hyrtios Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158227 VL - 22 IS - 5 ER - TY - JOUR A1 - Selcho, Mareike A1 - Millán, Carola A1 - Palacios-Muñoz, Angelina A1 - Ruf, Franziska A1 - Ubillo, Lilian A1 - Chen, Jiangtian A1 - Bergmann, Gregor A1 - Ito, Chihiro A1 - Silva, Valeria A1 - Wegener, Christian A1 - Ewer, John T1 - Central and peripheral clocks are coupled by a neuropeptide pathway in Drosophila JF - Nature Communications N2 - Animal circadian clocks consist of central and peripheral pacemakers, which are coordinated to produce daily rhythms in physiology and behaviour. Despite its importance for optimal performance and health, the mechanism of clock coordination is poorly understood. Here we dissect the pathway through which the circadian clock of Drosophila imposes daily rhythmicity to the pattern of adult emergence. Rhythmicity depends on the coupling between the brain clock and a peripheral clock in the prothoracic gland (PG), which produces the steroid hormone, ecdysone. Time information from the central clock is transmitted via the neuropeptide, sNPF, to non-clock neurons that produce the neuropeptide, PTTH. These secretory neurons then forward time information to the PG clock. We also show that the central clock exerts a dominant role on the peripheral clock. This use of two coupled clocks could serve as a paradigm to understand how daily steroid hormone rhythms are generated in animals. KW - circadian clock KW - Drosophila KW - neuropeptide pathway KW - peripheral clocks KW - central clocks Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170831 VL - 8 IS - 15563 ER - TY - JOUR A1 - Seher, Axel A1 - Lagler, Charlotte A1 - Stühmer, Thorsten A1 - Müller-Richter, Urs Dietmar Achim A1 - Kübler, Alexander Christian A1 - Sebald, Walter A1 - Müller, Thomas Dieter A1 - Nickel, Joachim T1 - Utilizing BMP-2 muteins for treatment of multiple myeloma JF - PLoS ONE N2 - Multiple myeloma (MM) represents a haematological cancer characterized by the pathological hyper proliferation of antibody-producing B-lymphocytes. Patients typically suffer from kidney malfunction and skeletal disorders. In the context of MM, the transforming growth factor β (TGFβ) member Activin A was recently identified as a promoter of both accompanying symptoms. Because studies have shown that bone morphogenetic protein (BMP)-2-mediated activities are counteracted by Activin A, we analysed whether BMP2, which also binds to the Activin A receptors ActRII and ActRIIB but activates the alternative SMAD-1/5/8 pathway, can be used to antagonize Activin A activities, such as in the context of MM. Therefore three BMP2 derivatives were generated with modified binding activities for the type II (ActRIIB) and/or type I receptor (BMPRIA) showing either increased or decreased BMP2 activity. In the context of MM these BMP2 muteins show two functionalities since they act as a) an anti-proliferative/apoptotic agent against neoplastic B-cells, b) as a bone-formation promoting growth factor. The molecular basis of both activities was shown in two different cellular models to clearly rely on the properties of the investigated BMP2 muteins to compete for the binding of Activin A to the Activin type II receptors. The experimental outcome suggests new therapeutic strategies using BMP2 variants in the treatment of MM-related pathologies. KW - multiple myeloma KW - signaling KW - cell proliferation KW - cell binding KW - membrane receptor signaling KW - BMP KW - gene expression KW - B cell receptors KW - B cells Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158144 VL - 12 IS - 5 ER - TY - JOUR A1 - Schönegge, Anne-Marie A1 - Gallion, Jonathan A1 - Picard, Louis-Philippe A1 - Wilkins, Angela D. A1 - Le Gouill, Christian A1 - Audet, Martin A1 - Stallaert, Wayne A1 - Lohse, Martin J. A1 - Kimmel, Marek A1 - Lichtarge, Olivier A1 - Bouvier, Michel T1 - Evolutionary action and structural basis of the allosteric switch controlling β\(_2\)AR functional selectivity JF - Nature Communications N2 - Functional selectivity of G-protein-coupled receptors is believed to originate from ligand-specific conformations that activate only subsets of signaling effectors. In this study, to identify molecular motifs playing important roles in transducing ligand binding into distinct signaling responses, we combined in silico evolutionary lineage analysis and structure-guided site-directed mutagenesis with large-scale functional signaling characterization and non-negative matrix factorization clustering of signaling profiles. Clustering based on the signaling profiles of 28 variants of the β\(_2\)-adrenergic receptor reveals three clearly distinct phenotypical clusters, showing selective impairments of either the Gi or βarrestin/endocytosis pathways with no effect on Gs activation. Robustness of the results is confirmed using simulation-based error propagation. The structural changes resulting from functionally biasing mutations centered around the DRY, NPxxY, and PIF motifs, selectively linking these micro-switches to unique signaling profiles. Our data identify different receptor regions that are important for the stabilization of distinct conformations underlying functional selectivity. KW - toxicology KW - functional clustering KW - molecular modelling KW - protein design KW - receptor pharmacology Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172268 VL - 8 ER - TY - JOUR A1 - Schäfer, Kristina A1 - Bauer, Boris A1 - Donhauser, Julian A1 - Kerstan, Andreas A1 - Hamm, Henning T1 - Becker Naevus Syndrome of the Lower Body: A New Case and Review of the Literature JF - Acta Dermato-Venereologica N2 - Becker naevus syndrome is a rare epidermal naevus syndrome defined by the co-occurrence of a Becker naevus with various cutaneous, muscular and skeletal anomalies. In the majority of cases, abnormalities exclusively consist of ipsilateral hypoplasia of the breast, areola and/or nipple in addition to the naevus. Here, we report on a 42-year-old woman with an extensive Becker naevus reaching from the left buttock to the left calf verified on histological examination. In addition, there was marked hypoplasia of the fatty tissue of the left thigh confirmed by magnetic resonance imaging in contrast to hyperplasia of the fatty tissue of the left gluteal area. Underlying muscles and bones were not affected. There was no difference in leg lengths. In addition, we review and discuss the features of Becker naevus syndrome with emphasis on 10 reported cases with involvement of the lower body. KW - lower body KW - Becker naevus KW - Becker naevus syndrome KW - hypoplasia of fatty tissue Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171057 VL - 97 IS - 4 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 - Schwab, Andrea A1 - Meeuwsen, Annick A1 - Ehlicke, Franziska A1 - Hansmann, Jan A1 - Mulder, Lars A1 - Smits, Anthal A1 - Walles, Heike A1 - Kock, Linda T1 - Ex vivo culture platform for assessment of cartilage repair treatment strategies JF - ALTEX - Alternatives to animal experimentation N2 - There is a great need for valuable ex vivo models that allow for assessment of cartilage repair strategies to reduce the high number of animal experiments. In this paper we present three studies with our novel ex vivo osteochondral culture platform. It consists of two separated media compartments for cartilage and bone, which better represents the in vivo situation and enables supply of factors pecific to the different needs of bone and cartilage. We investigated whether separation of the cartilage and bone compartments and/or culture media results in the maintenance of viability, structural and functional properties of cartilage tissue. Next, we valuated for how long we can preserve cartilage matrix stability of osteochondral explants during long-term culture over 84 days. Finally, we determined the optimal defect size that does not show spontaneous self-healing in this culture system. It was demonstrated that separated compartments for cartilage and bone in combination with tissue-specific medium allow for long-term culture of osteochondral explants while maintaining cartilage viability, atrix tissue content, structure and mechanical properties for at least 56 days. Furthermore, we could create critical size cartilage defects of different sizes in the model. The osteochondral model represents a valuable preclinical ex vivo tool for studying clinically relevant cartilage therapies, such as cartilage biomaterials, for their regenerative potential, for evaluation of drug and cell therapies, or to study mechanisms of cartilage regeneration. It will undoubtedly reduce the number of animals needed for in vivotesting. KW - ex vivo model KW - osteochondral biopsy KW - cartilage repair KW - critical size defect KW - replacement Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181665 VL - 34 IS - 2 ER - TY - JOUR A1 - Schuster, Sarah A1 - Krüger, Timothy A1 - Subota, Ines A1 - Thusek, Sina A1 - Rotureau, Brice A1 - Beilhack, Andreas A1 - Engstler, Markus T1 - Developmental adaptations of trypanosome motility to the tsetse fly host environments unravel a multifaceted in vivo microswimmer system JF - eLife N2 - The highly motile and versatile protozoan pathogen Trypanosoma brucei undergoes a complex life cycle in the tsetse fly. Here we introduce the host insect as an expedient model environment for microswimmer research, as it allows examination of microbial motion within a diversified, secluded and yet microscopically tractable space. During their week-long journey through the different microenvironments of the fly´s interior organs, the incessantly swimming trypanosomes cross various barriers and confined surroundings, with concurrently occurring major changes of parasite cell architecture. Multicolour light sheet fluorescence microscopy provided information about tsetse tissue topology with unprecedented resolution and allowed the first 3D analysis of the infection process. High-speed fluorescence microscopy illuminated the versatile behaviour of trypanosome developmental stages, ranging from solitary motion and near-wall swimming to collective motility in synchronised swarms and in confinement. We correlate the microenvironments and trypanosome morphologies to high-speed motility data, which paves the way for cross-disciplinary microswimmer research in a naturally evolved environment. KW - none KW - tsetse fly KW - Trypanosoma KW - biophysics KW - microswimmer KW - sleeping sickness KW - structural biology Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158662 VL - 6 ER - TY - JOUR A1 - Schulz, Herbert A1 - Ruppert, Ann-Kathrin A1 - Herms, Stefan A1 - Wolf, Christiane A1 - Mirza-Schreiber, Nazanin A1 - Stegle, Oliver A1 - Czamara, Darina A1 - Forstner, Andreas J. A1 - Sivalingam, Sugirthan A1 - Schoch, Susanne A1 - Moebus, Susanne A1 - Pütz, Benno A1 - Hillmer, Axel A1 - Fricker, Nadine A1 - Vatter, Hartmut A1 - Müller-Myhsok, Bertram A1 - Nöthen, Markus M. A1 - Becker, Albert J. A1 - Hoffmann, Per A1 - Sander, Thomas A1 - Cichon, Sven T1 - Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus JF - Nature Communications N2 - Emerging evidence emphasizes the strong impact of regulatory genomic elements in neurodevelopmental processes and the complex pathways of brain disorders. The present genome-wide quantitative trait loci analyses explore the \(cis\)-regulatory effects of single-nucleotide polymorphisms (SNPs) on DNA methylation (meQTL) and gene expression (eQTL) in 110 human hippocampal biopsies. We identify \(cis\)-meQTLs at 14,118 CpG methylation sites and \(cis\)-eQTLs for 302 3′-mRNA transcripts of 288 genes. Hippocampal \(cis\)-meQTL-CpGs are enriched in flanking regions of active promoters, CpG island shores, binding sites of the transcription factor CTCF and brain eQTLs. \(Cis\)-acting SNPs of hippocampal meQTLs and eQTLs significantly overlap schizophrenia-associated SNPs. Correlations of CpG methylation and RNA expression are found for 34 genes. Our comprehensive maps of \(cis\)-acting hippocampal meQTLs and eQTLs provide a link between disease-associated SNPs and the regulatory genome that will improve the functional interpretation of non-coding genetic variants in the molecular genetic dissection of brain disorders. KW - psychiatry KW - epigenetics in the nervous system KW - epigenomics KW - gene expression KW - neurological disorders Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173168 VL - 8 ER - TY - JOUR A1 - Schuhmann, Michael K. A1 - Langhauser, Friederike A1 - Kraft, Peter A1 - Kleinschnitz, Christoph T1 - B cells do not have a major pathophysiologic role in acute ischemic stroke in mice JF - Journal of Neuroinflammation N2 - Background Lymphocytes have been shown to play an important role in the pathophysiology of acute ischemic stroke, but the properties of B cells remain controversial. The aim of this study was to unravel the role of B cells during acute cerebral ischemia using pharmacologic B cell depletion, B cell transgenic mice, and adoptive B cell transfer experiments. Methods Transient middle cerebral artery occlusion (60 min) was induced in wild-type mice treated with an anti-CD20 antibody 24 h before stroke onset, JHD\(^{−/−}\) mice and Rag1\(^{−/−}\) mice 24 h after adoptive B cell transfer. Stroke outcome was assessed at days 1 and 3. Infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain sections, and neurological scores were evaluated. The local inflammatory response was determined by real-time PCR and immunohistochemistry. Apoptosis was analyzed by TUNEL staining, and astrocyte activation was revealed using immunohistochemistry and Western blot. Results Pharmacologic depletion of B cells did not influence infarct volumes and functional outcome at day 1 after stroke. Additionally, lack of circulating B cells in JHD\(^{−/−}\) mice also failed to influence stroke outcome at days 1 and 3. Furthermore, reconstitution of Rag1\(^{−/−}\) mice with B cells had no influence on infarct volumes. Conclusion Targeting B cells in experimental stroke did not influence lesion volume and functional outcome during the acute phase. Our findings argue against a major pathophysiologic role of B cells during acute ischemic stroke. KW - ischemic stroke KW - transient middle cerebral artery occlusion KW - B cells Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158155 VL - 14 IS - 112 ER - TY - JOUR A1 - Schuhmann, Michael K. A1 - Guthmann, Josua A1 - Stoll, Guido A1 - Nieswandt, Bernhard A1 - Kraft, Peter A1 - Kleinschnitz, Christoph T1 - Blocking of platelet glycoprotein receptor Ib reduces “thrombo-inflammation” in mice with acute ischemic stroke JF - Journal of Neuroinflammation N2 - Background: Ischemic stroke causes a strong inflammatory response that includes T cells, monocytes/macrophages, and neutrophils. Interaction of these immune cells with platelets and endothelial cells facilitates microvascular dysfunction and leads to secondary infarct growth. We recently showed that blocking of platelet glycoprotein (GP) receptor Ib improves stroke outcome without increasing the risk of intracerebral hemorrhage. Until now, it has been unclear whether GPIb only mediates thrombus formation or also contributes to the pathophysiology of local inflammation. Methods: Focal cerebral ischemia was induced in C57BL/6 mice by a 60-min transient middle cerebral artery occlusion (tMCAO). Animals were treated with antigen-binding fragments (Fab) against the platelet surface molecules GPIb (p0p/B Fab). Rat immunoglobulin G (IgG) Fab was used as control treatment. Stroke outcome, including infarct size and functional deficits as well as the local inflammatory response, was assessed on day 1 after tMCAO. Results: Blocking of GPIb reduced stroke size and improved functional outcome on day 1 after tMCAO without increasing the risk of intracerebral hemorrhage. As expected, disruption of GPIb-mediated pathways in platelets significantly reduced thrombus burden in the cerebral microvasculature. In addition, inhibition of GPIb limited the local inflammatory response in the ischemic brain as indicated by lower numbers of infiltrating T cells and macrophages and lower expression levels of inflammatory cytokines compared with rat IgG Fab-treated controls. Conclusion: In acute ischemic stroke, thrombus formation and inflammation are closely intertwined (“thrombo-inflammation”). Blocking of platelet GPIb can ameliorate thrombo-inflammation. KW - ischemic stroke KW - occlusion KW - transient middle cerebral artery KW - glycoprotein receptor Ib KW - thrombo-inflammation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157582 VL - 14 IS - 18 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 - Schubert, Lisa A1 - Körner, Anita A1 - Lindau, Berit A1 - Strack, Fritz A1 - Topolinski, Sascha T1 - Open-Minded Midwifes, Literate Butchers, and Greedy Hooligans - The Independent Contributions of Stereotype Valence and Consistency on Evaluative Judgments JF - Frontiers in Psychology N2 - Do people evaluate an open-minded midwife less positively than a caring midwife? Both open-minded and caring are generally seen as positive attributes. However, consistency varies—the attribute caring is consistent with the midwife stereotype while open-minded is not. In general, both stimulus valence and consistency can influence evaluations. Six experiments investigated the respective influence of valence and consistency on evaluative judgments in the domain of stereotyping. In an impression formation paradigm, valence and consistency of stereotypic information about target persons were manipulated orthogonally and spontaneous evaluations of these target persons were measured. Valence reliably influenced evaluations. However, for strongly valenced stereotypes, no effect of consistency was observed. Parameters possibly preventing the occurrence of consistency effects were ruled out, specifically, valence of inconsistent attributes, processing priority of category information, and impression formation instructions. However, consistency had subtle effects on evaluative judgments if the information about a target person was not strongly valenced and experimental conditions were optimal. Concluding, in principle, both stereotype valence and consistency can play a role in evaluative judgments of stereotypic target persons. However, the more subtle influence of consistency does not seem to substantially influence evaluations of stereotyped target persons. Implications for fluency research and stereotype disconfirmation are discussed. KW - stereotypes KW - consistency KW - evaluation KW - valence Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170222 VL - 8 IS - 1723 ER - TY - JOUR A1 - Scholz, Nicole A1 - Guan, Chonglin A1 - Nieberler, Matthias A1 - Grotmeyer, Alexander A1 - Maiellaro, Isabella A1 - Gao, Shiqiang A1 - Beck, Sebastian A1 - Pawlak, Matthias A1 - Sauer, Markus A1 - Asan, Esther A1 - Rothemund, Sven A1 - Winkler, Jana A1 - Prömel, Simone A1 - Nagel, Georg A1 - Langenhan, Tobias A1 - Kittel, Robert J T1 - Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons JF - eLife N2 - Adhesion-type G protein-coupled receptors (aGPCRs), a large molecule family with over 30 members in humans, operate in organ development, brain function and govern immunological responses. Correspondingly, this receptor family is linked to a multitude of diverse human diseases. aGPCRs have been suggested to possess mechanosensory properties, though their mechanism of action is fully unknown. Here we show that the Drosophila aGPCR Latrophilin/dCIRL acts in mechanosensory neurons by modulating ionotropic receptor currents, the initiating step of cellular mechanosensation. This process depends on the length of the extended ectodomain and the tethered agonist of the receptor, but not on its autoproteolysis, a characteristic biochemical feature of the aGPCR family. Intracellularly, dCIRL quenches cAMP levels upon mechanical activation thereby specifically increasing the mechanosensitivity of neurons. These results provide direct evidence that the aGPCR dCIRL acts as a molecular sensor and signal transducer that detects and converts mechanical stimuli into a metabotropic response. KW - Latrophilin KW - adhesion GPCR KW - dCIRL KW - sensory physiology KW - metabotropic signalling KW - mechanotransduction Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170520 VL - 6 IS - e28360 ER - TY - JOUR A1 - Schneider, Wolfgang A1 - Niklas, Frank T1 - Intelligence and verbal short-term memory/working memory: their interrelationships from childhood to young adulthood and their impact on academic achievement JF - Journal of Intelligence N2 - Although recent developmental studies exploring the predictive power of intelligence and working memory (WM) for educational achievement in children have provided evidence for the importance of both variables, findings concerning the relative impact of IQ and WM on achievement have been inconsistent. Whereas IQ has been identified as the major predictor variable in a few studies, results from several other developmental investigations suggest that WM may be the stronger predictor of academic achievement. In the present study, data from the Munich Longitudinal Study on the Genesis of Individual Competencies (LOGIC) were used to explore this issue further. The secondary data analysis included data from about 200 participants whose IQ and WM was first assessed at the age of six and repeatedly measured until the ages of 18 and 23. Measures of reading, spelling, and math were also repeatedly assessed for this age range. Both regression analyses based on observed variables and latent variable structural equation modeling (SEM) were carried out to explore whether the predictive power of IQ and WM would differ as a function of time point of measurement (i.e., early vs. late assessment). As a main result of various regression analyses, IQ and WM turned out to be reliable predictors of academic achievement, both in early and later developmental stages, when previous domain knowledge was not included as additional predictor. The latter variable accounted for most of the variance in more comprehensive regression models, reducing the impact of both IQ and WM considerably. Findings from SEM analyses basically confirmed this outcome, indicating IQ impacts on educational achievement in the early phase, and illustrating the strong additional impact of previous domain knowledge on achievement at later stages of development. KW - intelligence KW - short-term memory KW - working memory KW - academic achievement KW - domain knowledge KW - LOGIC study Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-198004 SN - 2079-3200 VL - 5 IS - 2 ER - TY - JOUR A1 - Schmidt, Marianne A1 - Skaf, Josef A1 - Gavril, Georgiana A1 - Polednik, Christine A1 - Roller, Jeanette A1 - Kessler, Michael A1 - Holzgrabe, Ulrike T1 - The influence of Osmunda regalis root extract on head and neck cancer cell proliferation, invasion and gene expression JF - BMC Complementary and Alternative Medicine N2 - Background: According to only a handful of historical sources, Osmunda regalis, the royal fern, has been used already in the middle age as an anti-cancer remedy. To examine this ancient cancer cure, an ethanolic extract of the roots was prepared and analysed in vitro on its effectiveness against head and neck cancer cell lines. Methods: Proliferation inhibition was measured with the MTT assay. Invasion inhibition was tested in a spheroid-based 3-D migration assay on different extracellular matrix surfaces. Corresponding changes in gene expression were analysed by qRT-PCR array. Induction of apoptosis was measured by fluorescence activated cell sorting (FACS) with the Annexin V binding method. The plant extract was analysed by preliminary phytochemical tests, liquid chromatography/mass spectroscopy (LC-MS) and thin layer chromatography (TLC). Anti-angiogenetic activity was determined by the tube formation assay. Results: O. regalis extract revealed a growth inhibiting effect on the head and neck carcinoma cell lines HLaC78 and FaDu. The toxic effect seems to be partially modulated by p-glycoprotein, as the MDR-1 expressing HLaC79-Tax cells were less sensitive. O. regalis extract inhibited the invasion of cell lines on diverse extracellular matrix substrates significantly. Especially the dispersion of the highly motile cell line HlaC78 on laminin was almost completely abrogated. Motility inhibition on laminin was accompanied by differential gene regulation of a variety of genes involved in cell adhesion and metastasis. Furthermore, O. regalis extract triggered apoptosis in HNSCC cell lines and inhibited tube formation of endothelial cells. Preliminary phytochemical analysis proved the presence of tannins, glycosides, steroids and saponins. Liquid chromatography/mass spectroscopy (LC-MS) revealed a major peak of an unknown substance with a molecular mass of 864.15 Da, comprising about 50% of the total extract. Thin layer chromatography identified ferulic acid to be present in the extract. Conclusion: The presented results justify the use of royal fern extracts as an anti-cancer remedy in history and imply a further analysis of ingredients. KW - head and neck carcinoma KW - invasion KW - plant extract KW - proliferation KW - HNSCC KW - metastasis KW - gene expression KW - Osmunda regalis Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158704 VL - 17 IS - 518 ER - TY - JOUR A1 - Schmid, Tobias A1 - Falter, Lena A1 - Weber, Sabine A1 - Müller, Nils A1 - Molitor, Konstantin A1 - Zeller, David A1 - Weber-Steffens, Dorothea A1 - Hehlgans, Thomas A1 - Wajant, Harald A1 - Mostböck, Sven A1 - Männel, Daniela N. T1 - Chronic inflammation increases the sensitivity of mouse Treg for TNFR2 costimulation JF - Frontiers in Immunology N2 - TNF receptor type 2 (TNFR2) has gained attention as a costimulatory receptor for T cells and as critical factor for the development of regulatory T cells (Treg) and myeloid suppressor cells. Using the TNFR2-specific agonist TNCscTNF80, direct effects of TNFR2 activation on myeloid cells and T cells were investigated in mice. \(In\) \(vitro\), TNCscTNF80 induced T cell proliferation in a costimulatory fashion, and also supported \(in\) \(vitro\) expansion of Treg cells. In addition, activation of TNFR2 retarded differentiation of bone marrow-derived immature myeloid cells in culture and reduced their suppressor function. \(In\) \(vivo\) application of TNCscTNF80-induced mild myelopoiesis in naïve mice without affecting the immune cell composition. Already a single application expanded Treg cells and improved suppression of CD4 T cells in mice with chronic inflammation. By contrast, multiple applications of the TNFR2 agonist were required to expand Treg cells in naïve mice. Improved suppression of T cell proliferation depended on expression of TNFR2 by T cells in mice repeatedly treated with TNCscTNF80, without a major contribution of TNFR2 on myeloid cells. Thus, TNFR2 activation on T cells in naïve mice can lead to immune suppression \(in\) \(vivo\). These findings support the important role of TNFR2 for Treg cells in immune regulation. KW - molecular medicine KW - inflammation KW - immune regulation KW - costimulation KW - MDSC KW - TNFR2 KW - regulatory T cell Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173259 VL - 8 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 - Schielmann, Marta A1 - Szweda, Piotr A1 - Gucwa, Katarzyna A1 - Kawczyński, Marcin A1 - Milewska, Maria J. A1 - Martynow, Dorota A1 - Morschhäuser, Joachim A1 - Milewski, Sławomir T1 - Transport deficiency is the molecular basis of \(Candida\) \(albicans\) resistance to antifungal oligopeptides JF - Frontiers in Microbiology N2 - Oligopeptides incorporating \(N3\)-(4-methoxyfumaroyl)-L-2,3-diaminopropanoic acid (FMDP), an inhibitor of glucosamine-6-phosphate synthase, exhibited growth inhibitory activity against \(Candida\) \(albicans\), with minimal inhibitory concentration values in the 0.05–50 μg mL\(^{-1}\) range. Uptake by the peptide permeases was found to be the main factor limiting an anticandidal activity of these compounds. Di- and tripeptide containing FMDP (F2 and F3) were transported by Ptr2p/Ptr22p peptide transporters (PTR) and FMDP-containing hexa-, hepta-, and undecapeptide (F6, F7, and F11) were taken up by the oligopeptide transporters (OPT) oligopeptide permeases, preferably by Opt2p/Opt3p. A phenotypic, apparent resistance of \(C. albicans\) to FMDP-oligopeptides transported by OPT permeases was triggered by the environmental factors, whereas resistance to those taken up by the PTR system had a genetic basis. Anticandidal activity of longer FMDP-oligopeptides was strongly diminished in minimal media containing easily assimilated ammonium sulfate or L-glutamine as the nitrogen source, both known to downregulate expression of the OPT genes. All FMDP-oligopeptides tested were more active at lower pH and this effect was slightly more remarkable for peptides F6, F7, and F11, compared to F2 and F3. Formation of isolated colonies was observed inside the growth inhibitory zones induced by F2 and F3 but not inside those induced by F6, F7, and F11. The vast majority (98%) of those colonies did not originate from truly resistant cells. The true resistance of 2% of isolates was due to the impaired transport of di- and to a lower extent, tripeptides. The resistant cells did not exhibit a lower expression of \(PTR2\), \(PTR22\), or \(OPT1–3\) genes, but mutations in the \(PTR2\) gene resulting in T422H, A320S, D119V, and A320S substitutions in the amino acid sequence of Ptr2p were found. KW - microbiology KW - Candida albicans KW - oligopeptides KW - resistance mechanism KW - permease KW - antifungals Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173245 VL - 8 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 - Scheiner, Ricarda A1 - Entler, Brian V. A1 - Barron, Andrew B. A1 - Scholl, Christina A1 - Thamm, Markus T1 - The Effects of Fat Body Tyramine Level on Gustatory Responsiveness of Honeybees (Apis mellifera) Differ between Behavioral Castes JF - Frontiers in Systems Neuroscience N2 - Division of labor is a hallmark of social insects. In the honeybee (Apis mellifera) each sterile female worker performs a series of social tasks. The most drastic changes in behavior occur when a nurse bee, who takes care of the brood and the queen in the hive, transitions to foraging behavior. Foragers provision the colony with pollen, nectar or water. Nurse bees and foragers differ in numerous behaviors, including responsiveness to gustatory stimuli. Differences in gustatory responsiveness, in turn, might be involved in regulating division of labor through differential sensory response thresholds. Biogenic amines are important modulators of behavior. Tyramine and octopamine have been shown to increase gustatory responsiveness in honeybees when injected into the thorax, thereby possibly triggering social organization. So far, most of the experiments investigating the role of amines on gustatory responsiveness have focused on the brain. The potential role of the fat body in regulating sensory responsiveness and division of labor has large been neglected. We here investigated the role of the fat body in modulating gustatory responsiveness through tyramine signaling in different social roles of honeybees. We quantified levels of tyramine, tyramine receptor gene expression and the effect of elevating fat body tyramine titers on gustatory responsiveness in both nurse bees and foragers. Our data suggest that elevating the tyramine titer in the fat body pharmacologically increases gustatory responsiveness in foragers, but not in nurse bees. This differential effect of tyramine on gustatory responsiveness correlates with a higher natural gustatory responsiveness of foragers, with a higher tyramine receptor (Amtar1) mRNA expression in fat bodies of foragers and with lower baseline tyramine titers in fat bodies of foragers compared to those of nurse bees. We suggest that differential tyramine signaling in the fat body has an important role in the plasticity of division of labor through changing gustatory responsiveness. KW - behavior KW - biogenic amines KW - division of labor KW - nurse bee KW - forager KW - PER KW - octopamine KW - insect Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157874 VL - 11 IS - 55 ER - TY - JOUR A1 - Schampel, Andrea A1 - Kuerten, Stefanie T1 - Danger: high voltage - the role of voltage-gated calcium channels in central nervous system pathology JF - Cells N2 - Voltage-gated calcium channels (VGCCs) are widely distributed within the central nervous system (CNS) and presumed to play an important role in the pathophysiology of a broad spectrum of CNS disorders including Alzheimer’s and Parkinson’s disease as well as multiple sclerosis. Several calcium channel blockers have been in clinical practice for many years so that their toxicity and side effects are well studied. However, these drugs are primarily used for the treatment of cardiovascular diseases and most if not all effects on brain functions are secondary to peripheral effects on blood pressure and circulation. While the use of calcium channel antagonists for the treatment of CNS diseases therefore still heavily depends on the development of novel strategies to specifically target different channels and channel subunits, this review is meant to provide an impulse to further emphasize the importance of future research towards this goal. KW - cells KW - calcium KW - calcium channel antagonists KW - CNS KW - EAE KW - neurodegeneration KW - MS KW - regeneration KW - remyelination Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172653 VL - 6 IS - 4 ER - TY - JOUR A1 - Schamel, Johannes T1 - A demographic perspective on the spatial behaviour of hikers in mountain areas: the example of Berchtesgaden National Park JF - eco.mont - Journal on Protected Mountain Areas Research and Management N2 - In Germany, as in many Western societies, demographic change will lead to a higher number of senior visitors to natural recreational areas and national parks. Given the high physiological requirements of many outdoor recreation activities, especially in mountain areas, it seems likely that demographic change will affect the spatial behaviour of national park visitors, which may pose a challenge to the management of these areas. With the help of GPS tracking and a standardized questionnaire (n=481), this study empirically investigates the spatial behaviour of demographic age brackets in Berchtesgaden National Park (NP) and the potential effects of demographic change on the use of the area. Cluster analysis revealed four activity types in the study area. More than half of the groups with visitors aged 60 and older belong to the activity type of Walker. KW - geography KW - demographic change KW - spatial behaviour KW - GPS tracking KW - outdoor recreation KW - Berchtesgaden NP Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172128 SN - 2073-1558 VL - 9 IS - Special issue ER - TY - JOUR A1 - Sbirkov, Yordan A1 - Kwok, Colin A1 - Bhamra, Amandeep A1 - Thompson, Andrew J. A1 - Gil, Veronica A1 - Zelent, Arthur A1 - Petrie, Kevin T1 - Semi-quantitative mass spectrometry in AML cells identifies new non-genomic targets of the EZH2 methyltransferase JF - International Journal of Molecular Sciences N2 - Alterations to the gene encoding the EZH2 (KMT6A) methyltransferase, including both gain-of-function and loss-of-function, have been linked to a variety of haematological malignancies and solid tumours, suggesting a complex, context-dependent role of this methyltransferase. The successful implementation of molecularly targeted therapies against EZH2 requires a greater understanding of the potential mechanisms by which EZH2 contributes to cancer. One aspect of this effort is the mapping of EZH2 partner proteins and cellular targets. To this end we performed affinity-purification mass spectrometry in the FAB-M2 HL-60 acute myeloid leukaemia (AML) cell line before and after all-trans retinoic acid-induced differentiation. These studies identified new EZH2 interaction partners and potential non-histone substrates for EZH2-mediated methylation. Our results suggest that EZH2 is involved in the regulation of translation through interactions with a number of RNA binding proteins and by methylating key components of protein synthesis such as eEF1A1. Given that deregulated mRNA translation is a frequent feature of cancer and that eEF1A1 is highly expressed in many human tumours, these findings present new possibilities for the therapeutic targeting of EZH2 in AML. KW - acute myeloid leukaemia KW - EZH2 KW - mass spectrometry KW - methylation KW - eEF1A1 Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285541 SN - 1422-0067 VL - 18 IS - 7 ER - TY - JOUR A1 - Sayed, Sameh A1 - Schimmer, Christoph A1 - Shade, Ina A1 - Leyh, Rainer A1 - Aleksic, Ivan T1 - Combined pulmonary and left ventricular support with veno-pulmonary ECMO and impella 5.0 for cardiogenic shock after coronary surgery JF - Journal of Cardiothoracic Surgery N2 - Background: Mechanical circulatory support is a common practice nowadays in the management of patients after cardiogenic shock due to myocardial infarction. The single or combined use of one or more devices for mechanical support depends not only on the advantage or disadvantage of these devices but also on the timing of use of these devices before the development of multi organ failure. In our case we used more than one tool for mechanical circulatory support during the prolonged and complicated course of our patient with postcardiotomy cardiogenic shock after coronary artery bypass surgery. Case Presentation: We describe the combined use of Impella 5.0 and veno- pulmonary extra corporeal membrane oxygenation (VP-ECMO) for biventricular failure in a 52 years—old man. He presented with cardiogenic shock after inferior wall ST-elevation myocardial infarction. After emergency coronary artery bypass surgery and failure to wean from extracorporeal circulation we employed V-P ECMO and consecutively Impella 5.0 to manage the primarily failing right and secondarily failing left ventricles. He remained hemodynamically stable on both Impella 5.0 and VP-ECMO until Heart Mate II left ventricular assist device implantation on the 14th postoperative day. Right sided support was weaned on 66th postoperative day. The patient remained in the intensive care unit for 77 days. During his prolonged stay, he underwent renal replacement therapy and tracheostomy with complete recovery. Six months later, he was successfully heart transplanted and has completed three and half years of unremarkable follow up. Conclusions: The combined use of VP ECMO and Impella 5.0 is effective in the management of postcardiotomy biventricular failure as a bridge for further mechanical support or heart transplantation. KW - cardiogenic shock KW - extra corporeal membrane oxygenator KW - impella 5.0 Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157598 VL - 12 IS - 38 ER - TY - JOUR A1 - Sauer, Alexander A1 - Li, Mengxia A1 - Holl-Wieden, Annette A1 - Pabst, Thomas A1 - Neubauer, Henning T1 - Readout-segmented multi-shot diffusion-weighted MRI of the knee joint in patients with juvenile idiopathic arthritis JF - Pediatric Rheumatology N2 - Background: Diffusion-weighted MRI has been proposed as a new technique for imaging synovitis without intravenous contrast application. We investigated diagnostic utility of multi-shot readout-segmented diffusion-weighted MRI (multi-shot DWI) for synovial imaging of the knee joint in patients with juvenile idiopathic arthritis (JIA). Methods: Thirty-two consecutive patients with confirmed or suspected JIA (21 girls, median age 13 years) underwent routine 1.5 T MRI with contrast-enhanced T1w imaging (contrast-enhanced MRI) and with multi-shot DWI (RESOLVE, b-values 0–50 and 800 s/mm\(^2\)). Contrast-enhanced MRI, representing the diagnostic standard, and diffusion-weighted images at b = 800 s/mm\(^2\) were separately rated by three independent blinded readers at different levels of expertise for the presence and the degree of synovitis on a modified 5-item Likert scale along with the level of subjective diagnostic confidence. Results: Fourteen (44%) patients had active synovitis and joint effusion, nine (28%) patients showed mild synovial enhancement not qualifying for arthritis and another nine (28%) patients had no synovial signal alterations on contrast-enhanced imaging. Ratings by the 1st reader on contrast-enhanced MRI and on DWI showed substantial agreement (κ = 0.74). Inter-observer-agreement was high for diagnosing, or ruling out, active arthritis of the knee joint on contrast-enhanced MRI and on DWI, showing full agreement between 1st and 2nd reader and disagreement in one case (3%) between 1st and 3rd reader. In contrast, ratings in cases of absent vs. little synovial inflammation were markedly inconsistent on DWI. Diagnostic confidence was lower on DWI, compared to contrast-enhanced imaging. Conclusion: Multi-shot DWI of the knee joint is feasible in routine imaging and reliably diagnoses, or rules out, active arthritis of the knee joint in paediatric patients without the need of gadolinium-based i.v. contrast injection. Possibly due to “T2w shine-through” artifacts, DWI does not reliably differentiate non-inflamed joints from knee joints with mild synovial irritation. KW - diffusion-weighted MRI KW - juvenile idiopathic arthritis KW - synovitis Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158095 VL - 15 IS - 73 ER - TY - JOUR A1 - Sander, Bodo A1 - Xu, Wenshan A1 - Eilers, Martin A1 - Popov, Nikita A1 - Lorenz, Sonja T1 - A conformational switch regulates the ubiquitin ligase HUWE1 JF - eLife N2 - The human ubiquitin ligase HUWE1 has key roles in tumorigenesis, yet it is unkown how its activity is regulated. We present the crystal structure of a C-terminal part of HUWE1, including the catalytic domain, and reveal an asymmetric auto-inhibited dimer. We show that HUWE1 dimerizes in solution and self-associates in cells, and that both occurs through the crystallographic dimer interface. We demonstrate that HUWE1 is inhibited in cells and that it can be activated by disruption of the dimer interface. We identify a conserved segment in HUWE1 that counteracts dimer formation by associating with the dimerization region intramolecularly. Our studies reveal, intriguingly, that the tumor suppressor p14ARF binds to this segment and may thus shift the conformational equilibrium of HUWE1 toward the inactive state. We propose a model, in which the activity of HUWE1 underlies conformational control in response to physiological cues—a mechanism that may be exploited for cancer therapy. KW - Medicine KW - Structural Biology KW - Molecular Biophysics KW - HUWE1 KW - HECT Ligase KW - Ubiquitin KW - P14ARF KW - X-Ray Chrystallography KW - Enzyme Regulation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171862 VL - 6 ER - TY - JOUR A1 - Sancho, Ana A1 - Vandersmissen, Ine A1 - Craps, Sander A1 - Luttun, Aernout A1 - Groll, Jürgen T1 - A new strategy to measure intercellular adhesion forces in mature cell-cell contacts JF - Scientific Reports N2 - Intercellular adhesion plays a major role in tissue development and homeostasis. Yet, technologies to measure mature cell-cell contacts are not available. We introduce a methodology based on fluidic probe force microscopy to assess cell-cell adhesion forces after formation of mature intercellular contacts in cell monolayers. With this method we quantify that L929 fibroblasts exhibit negligible cell-cell adhesion in monolayers whereas human endothelial cells from the umbilical artery (HUAECs) exert strong intercellular adhesion forces per cell. We use a new in vitro model based on the overexpression of Muscle Segment Homeobox 1 (MSX1) to induce Endothelial-to-Mesenchymal Transition (EndMT), a process involved in cardiovascular development and disease. We reveal how intercellular adhesion forces in monolayer decrease significantly at an early stage of EndMT and we show that cells undergo stiffening and flattening at this stage. This new biomechanical insight complements and expands the established standard biomolecular analyses. Our study thus introduces a novel tool for the assessment of mature intercellular adhesion forces in a physiological setting that will be of relevance to biological processes in developmental biology, tissue regeneration and diseases like cancer and fibrosis. KW - intercellular adhesion KW - mature cell-cell contacts KW - atomic force microscopy KW - biophysics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170999 VL - 7 IS - 46152 ER - TY - JOUR A1 - Salker, Madhuri S. A1 - Singh, Yogesh A1 - Zeng, Ni A1 - Chen, Hong A1 - Zhang, Shaqiu A1 - Umbach, Anja T. A1 - Fakhri, Hajar A1 - Kohlhofer, Ursula A1 - Quintanilla-Martinez, Leticia A1 - Durairaj, Ruban R. Peter A1 - Barros, Flavio S. V. A1 - Vrljicak, Pavle A1 - Ott, Sascha A1 - Brucker, Sara Y. A1 - Wallwiener, Diethelm A1 - Madunić, Ivana Vrhovac A1 - Breljak, Davorka A1 - Sabolić, Ivan A1 - Koepsell, Hermann A1 - Brosens, Jan J. A1 - Lang, Florian T1 - Loss of endometrial sodium glucose cotransporter SGLT1 is detrimental to embryo survival and fetal growth in pregnancy JF - Scientific Reports N2 - Embryo implantation requires a hospitable uterine environment. A key metabolic change that occurs during the peri-implantation period, and throughout early pregnancy, is the rise in endometrial glycogen content. Glycogen accumulation requires prior cellular uptake of glucose. Here we show that both human and murine endometrial epithelial cells express the high affinity Na\(^+\)-coupled glucose carrier SGLT1. Ussing chamber experiments revealed electrogenic glucose transport across the endometrium in wild type (\(Slc5a1^{+/+}\)) but not in SGLT1 defcient (\(Slc5a1^{−/−}\)) mice. Endometrial glycogen content, litter size and weight of offspring at birth were signifcantly lower in \(Slc5a1^{−/−}\) mice. In humans, \(SLC5A1\) expression was upregulated upon decidualization of primary endometrial stromal cells. Endometrial \(SLC5A1\) expression during the implantation window was attenuated in patients with recurrent pregnancy loss when compared with control subjects. Our fndings reveal a novel mechanism establishing adequate endometrial glycogen stores for pregnancy. Disruption of this histiotrophic pathway leads to adverse pregnancy outcome. KW - biology KW - embryology KW - intrauterine growth KW - paediatric research Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173814 VL - 7 ER - TY - JOUR A1 - Salinger, Tim A1 - Hu, Kai A1 - Liu, Dan A1 - Herrmann, Sebastian A1 - Lorenz, Kristina A1 - Ertl, Georg A1 - Nordbeck, Peter T1 - Cardiac amyloidosis mimicking severe aortic valve stenosis - a case report demonstrating diagnostic pitfalls and role of dobutamine stress echocardiography JF - BMC Cardiovascular Disorders N2 - Background Aortic valve stenosis is a common finding diagnosed with high sensitivity in transthoracic echocardiography, but the examiner often finds himself confronted with uncertain results in patients with moderate pressure gradients and concomitant systolic heart failure. While patients with true-severe low-gradient aortic valve stenosis with either reduced or preserved left ventricular systolic function are primarily candidates for valve replacement, there is a relevant proportion of patients with pseudo-severe aortic valve stenosis anticipated not to benefit but actually rather deteriorate by interventional therapy or surgery. Case presentation In this article we present a case report of a male patient with pseudo-severe aortic valve stenosis due to cardiac amyloidosis highlighting the diagnostic schedule. The patient underwent stress echocardiography because of discrepant findings in transthoracic echocardiography and cardiac catheterization regarding the severity of aortic valve stenosis. After evaluation of the results, it became clear that he had a need for optimum heart failure medication and implantation of a cardiac resynchronization therapy defibrillator. Conclusion Due to the pitfalls in conventional as well as invasive diagnostics at rest, Stress echocardiography should be considered part of the standard optimum diagnostic spectrum in all unclear or borderline cases in order to confirm the correct diagnosis and constitute optimal therapy. KW - aortic valve stenosis (AS) KW - case report KW - pseudo-severe AS KW - low-gradient AS KW - dobutamine stress echocardiography KW - cardiac amyloidosis Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171109 VL - 17 IS - 86 ER - TY - JOUR A1 - Rössler, Wolfgang A1 - Spaethe, Johannes A1 - Groh, Claudia T1 - Pitfalls of using confocal-microscopy based automated quantification of synaptic complexes in honeybee mushroom bodies (response to Peng and Yang 2016) JF - Scientific Reports N2 - A recent study by Peng and Yang in Scientific Reports using confocal-microscopy based automated quantification of anti-synapsin labeled microglomeruli in the mushroom bodies of honeybee brains reports potentially incorrect numbers of microglomerular densities. Whereas several previous studies using visually supervised or automated counts from confocal images and analyses of serial 3D electron-microscopy data reported consistent numbers of synaptic complexes per volume, Peng and Yang revealed extremely low numbers differing by a factor of 18 or more from those obtained in visually supervised counts, and by a factor 22–180 from numbers in two other studies using automated counts. This extreme discrepancy is especially disturbing as close comparison of raw confocal images of anti-synapsin labeled whole-mount brain preparations are highly similar across these studies. We conclude that these discrepancies may reside in potential misapplication of confocal imaging followed by erroneous use of automated image analysis software. Consequently, the reported microglomerular densities during maturation and after manipulation by insecticides require validation by application of appropriate confocal imaging methods and analyses tools that rely on skilled observers. We suggest several improvements towards more reliable or standardized automated or semi-automated synapse counts in whole mount preparations of insect brains. KW - confocal-microscopy based automated quantification KW - mushroom bodies KW - honeybees KW - brain Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170451 VL - 7 IS - 9786 ER - TY - JOUR A1 - Rösler, Lara A1 - End, Albert A1 - Gamer, Matthias T1 - Orienting towards social features in naturalistic scenes is reflexive JF - PLoS ONE N2 - Saliency-based models of visual attention postulate that, when a scene is freely viewed, attention is predominantly allocated to those elements that stand out in terms of their physical properties. However, eye-tracking studies have shown that saliency models fail to predict gaze behavior accurately when social information is included in an image. Notably, gaze pattern analyses revealed that depictions of human beings are heavily prioritized independent of their low-level physical saliency. What remains unknown, however, is whether the prioritization of such social features is a reflexive or a voluntary process. To investigate the early stages of social attention in more detail, participants viewed photographs of naturalistic scenes with and without social features (i.e., human heads or bodies) for 200 ms while their eye movements were being recorded. We observed significantly more first eye movements to regions containing social features than would be expected from a chance level distribution of saccades. Additionally, a generalized linear mixed model analysis revealed that the social content of a region better predicted first saccade direction than its saliency suggesting that social features partially override the impact of low-level physical saliency on gaze patterns. Given the brief image presentation time that precluded visual exploration, our results provide compelling evidence for a reflexive component in social attention. Moreover, the present study emphasizes the importance of considering social influences for a more coherent understanding of human attentional selection. KW - social features KW - visual attention KW - gaze patterns KW - reflexive component Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170586 VL - 12 IS - 7 ER - TY - JOUR A1 - Rösch, Manfred A1 - Biester, Harald A1 - Bogenrieder, Arno A1 - Eckmeier, Eileen A1 - Ehrmann, Otto A1 - Gerlach, Renate A1 - Hall, Mathias A1 - Hartkopf-Fröder, Christoph A1 - Herrmann, Ludger A1 - Kury, Birgit A1 - Lechterbeck, Jutta A1 - Schier, Wolfram A1 - Schulz, Erhard T1 - Late neolithic agriculture in temperate Europe—a long-term experimental approach JF - Land N2 - Long-term slash-and-burn experiments, when compared with intensive tillage without manuring, resulted in a huge data set relating to potential crop yields, depending on soil quality, crop type, and agricultural measures. Cultivation without manuring or fallow phases did not produce satisfying yields, and mono-season cropping on freshly cleared and burned plots resulted in rather high yields, comparable to those produced during modern industrial agriculture - at least ten-fold the ones estimated for the medieval period. Continuous cultivation on the same plot, using imported wood from adjacent areas as fuel, causes decreasing yields over several years. The high yield of the first harvest of a slash-and-burn agriculture is caused by nutrient input through the ash produced and mobilization from the organic matter of the topsoil, due to high soil temperatures during the burning process and higher topsoil temperatures due to the soil’s black surface. The harvested crops are pure, without contamination of any weeds. Considering the amount of work required to fight weeds without burning, the slash-and-burn technique yields much better results than any other tested agricultural approach. Therefore, in dense woodland, without optimal soils and climate, slash-and-burn agriculture seems to be the best, if not the only, feasible method to start agriculture, for example, during the Late Neolithic, when agriculture expanded from the loess belt into landscapes less suitable for agriculture. Extensive and cultivation with manuring is more practical in an already-open landscape and with a denser population, but its efficiency in terms of the ratio of the manpower input to food output, is worse. Slash-and-burn agriculture is not only a phenomenon of temperate European agriculture during the Neolithic, but played a major role in land-use in forested regions worldwide, creating anthromes on a huge spatial scale. KW - Neolithic agriculture KW - experimental archaeology KW - slash-and-burn KW - temperate Europe Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-198103 SN - 2073-445X VL - 6 IS - 1 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 - Ryczko, K. A1 - Misiewicz, J. A1 - Hofling, S. A1 - Kamp, M. A1 - Sęk, G. T1 - Optimizing the active region of interband cascade lasers for passive mode-locking JF - AIP Advances N2 - The work proposes possible designs of active regions for a mode-locked interband cascade laser emitting in the mid infrared. For that purpose we investigated the electronic structure properties of respectively modified GaSb-based type II W-shaped quantum wells, including the effect of external bias in order to simultaneously fulfil the requirements for both the absorber as well as the gain sections of a device. The results show that introducing multiple InAs layers in type II InAs/GaInSb quantum wells or introducing a tensely-strained GaAsSb layer into “W-shaped” type II QWs offers significant difference in optical transitions’ oscillator strengths (characteristic lifetimes) of the two oppositely polarized parts of such a laser, being promising for utilization in mode-locked devices. KW - physics KW - electrostatics KW - transition radiation KW - oscillator strengths KW - laser spectroscopy KW - optical spectroscopy KW - atomic and molecular spectroscopy, KW - frequency combs KW - quantum wells KW - laser physics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181790 VL - 7 IS - 1 ER - TY - JOUR A1 - Ruppert, Manuela A1 - Franz, Mirjam A1 - Saratis, Anastasios A1 - Escarcena, Laura Velo A1 - Hendrich, Oliver A1 - Gooi, Li Ming A1 - Schwenkert, Isabell A1 - Klebes, Ansgar A1 - Scholz, Henrike T1 - Hangover links nuclear RNA signaling to cAMP regulation via the phosphodiesterase 4d ortholog dunce JF - Cell Reports N2 - The hangover gene defines a cellular stress pathway that is required for rapid ethanol tolerance in Drosophila melanogaster. To understand how cellular stress changes neuronal function, we analyzed Hangover function on a cellular and neuronal level. We provide evidence that Hangover acts as a nuclear RNA binding protein and we identified the phosphodiesterase 4d ortholog dunce as a target RNA. We generated a transcript-specific dunce mutant that is impaired not only in ethanol tolerance but also in the cellular stress response. At the neuronal level, Dunce and Hangover are required in the same neuron pair to regulate experience-dependent motor output. Within these neurons, two cyclic AMP (cAMP)-dependent mechanisms balance the degree of tolerance. The balance is achieved by feedback regulation of Hangover and dunce transcript levels. This study provides insight into how nuclear Hangover/RNA signaling is linked to the cytoplasmic regulation of cAMP levels and results in neuronal adaptation and behavioral changes. KW - biology KW - hangover KW - dunce KW - Dunce isoforms KW - PDE4d KW - cellular stress KW - alcohol tolerance KW - Drosophila melanogaster Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171950 VL - 18 IS - 2 ER - TY - JOUR A1 - Rupp, Caroline S. T1 - What’s New in European Property Law? An Overview of Publications in 2015/2016 JF - European Property Law Journal N2 - No abstract available. KW - European Property Law Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-194449 SN - 2190-8362 SN - 2190-8273 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 6 IS - 1 ER - TY - JOUR A1 - Ruf, Franziska A1 - Fraunholz, Martin A1 - Öchsner, Konrad A1 - Kaderschabeck, Johann A1 - Wegener, Christian T1 - WEclMon - A simple and robust camera-based system to monitor Drosophila eclosion under optogenetic manipulation and natural conditions JF - PLoS ONE N2 - Eclosion in flies and other insects is a circadian-gated behaviour under control of a central and a peripheral clock. It is not influenced by the motivational state of an animal, and thus presents an ideal paradigm to study the relation and signalling pathways between central and peripheral clocks, and downstream peptidergic regulatory systems. Little is known, however, about eclosion rhythmicity under natural conditions, and research into this direction is hampered by the physically closed design of current eclosion monitoring systems. We describe a novel open eclosion monitoring system (WEclMon) that allows the puparia to come into direct contact with light, temperature and humidity. We demonstrate that the system can be used both in the laboratory and outdoors, and shows a performance similar to commercial closed funnel-type monitors. Data analysis is semi-automated based on a macro toolset for the open imaging software Fiji. Due to its open design, the WEclMon is also well suited for optogenetic experiments. A small screen to identify putative neuroendocrine signals mediating time from the central clock to initiate eclosion showed that optogenetic activation of ETH-, EH and myosuppressin neurons can induce precocious eclosion. Genetic ablation of myosuppressin-expressing neurons did, however, not affect eclosion rhythmicity. KW - chronobiology KW - infrared radiation KW - light pulses KW - molting KW - Drosophila melanogaster KW - optogenetics KW - eclosion Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170755 VL - 12 IS - 6 ER - TY - JOUR A1 - Rueegg, Corina S. A1 - Kriemler, Susi A1 - Zuercher, Simeon J. A1 - Schindera, Christina A1 - Renner, Andrea A1 - Hebestreit, Helge A1 - Meier, Christian A1 - Eser, Prisca A1 - von der Weid, Nicolas X. T1 - A partially supervised physical activity program for adult and adolescent survivors of childhood cancer (SURfit): study design of a randomized controlled trial [NCT02730767] JF - BMC Cancer N2 - Background: Beyond survival of nowadays >80%, modern childhood cancer treatment strives to preserve long-term health and quality of life. However, the majority of today’s survivors suffer from short- and long-term adverse effects such as cardiovascular and pulmonary diseases, obesity, osteoporosis, fatigue, depression, and reduced physical fitness and quality of life. Regular exercise can play a major role to mitigate or prevent such late-effects. Despite this, there are no data on the effects of regular exercise in childhood cancer survivors from randomized controlled trials (RCTs). \(Primary\) \(outcome\) of the current RCT is therefore the effect of a 12-months exercise program on a composite cardiovascular disease risk score in childhood cancer survivors. \(Secondary\) \(outcomes\) are single cardiovascular disease risk factors, glycaemic control, bone health, body composition, physical fitness, physical activity, quality of life, mental health, fatigue and adverse events (safety). Methods: A total of 150 childhood cancer survivors aged ≥16 years and diagnosed ≥5 years prior to the study are recruited from Swiss paediatric oncology clinics. Following the baseline assessments patients are randomized 1:1 into an intervention and control group. Thereafter, they are seen at month 3, 6 and 12 for follow-up assessments. The intervention group is asked to add ≥2.5 h of intense physical activity/week, including 30 min of strength building and 2 h of aerobic exercises. In addition, they are told to reduce screen time by 25%. Regular consulting by physiotherapists, individual web-based activity diaries, and pedometer devices are used as motivational tools for the intervention group. The control group is asked to keep their physical activity levels constant. Discussion: The results of this study will show whether a partially supervised exercise intervention can improve cardiovascular disease risk factors, bone health, body composition, physical activity and fitness, fatigue, mental health and quality of life in childhood cancer survivors. If the program will be effective, all relevant information of the SURfit physical activity intervention will be made available to interested clinics that treat and follow-up childhood cancer patients to promote exercise in their patients. KW - Medicine KW - Randomized controlled trial KW - Physical activity KW - Exercise intervention KW - Childhood cancer survivors KW - Late-effects KW - Cardiovascular disease KW - Bone health KW - Body composition KW - Physical fitness KW - Quality of life Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172497 VL - 17 ER - TY - JOUR A1 - Rudno-Rudziński, W. A1 - Syperek, M. A1 - Andrezejewski, J. A1 - Maryński, A. A1 - Misiewicz, J. A1 - Somers, A. A1 - Höfling, S. A1 - Reithmaier, J. P. A1 - Sęk, G. T1 - Carrier delocalization in InAs/InGaAlAs/InP quantum-dash-based tunnel injection system for 1.55 μm emission JF - AIP Advances N2 - We have investigated optical properties of hybrid two-dimensional-zero-dimensional (2D-0D) tunnel structures containing strongly elongated InAs/InP(001) quantum dots (called quantum dashes), emitting at 1.55 μm. These quantum dashes (QDashes) are separated by a 2.3 nm-width barrier from an InGaAs quantum well (QW), lattice matched to InP. We have tailored quantum-mechanical coupling between the states confined in QDashes and a QW by changing the QW thickness. By combining modulation spectroscopy and photoluminescence excitation, we have determined the energies of all relevant optical transitions in the system and proven the carrier transfer from the QW to the QDashes, which is the fundamental requirement for the tunnel injection scheme. A transformation between 0D and mixed-type 2D-0D character of an electron and a hole confinement in the ground state of the hybrid system have been probed by time-resolved photoluminescence that revealed considerable changes in PL decay time with the QW width changes. The experimental discoveries have been explained by band structure calculations in the framework of the eight-band k·p model showing that they are driven by delocalization of the lowest energy hole state. The hole delocalization process from the 0D QDash confinement is unfavorable for optical devices based on such tunnel injection structures. KW - physics KW - surface collisions KW - electronic coupling KW - transition radiation KW - time-resolved photoluminescence KW - photoluminescence excitation KW - modulation spectroscopy KW - quantum dots KW - quantum wells KW - delocalization Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181787 VL - 7 IS - 1 ER - TY - JOUR A1 - Roy, S. A1 - Borzì, A. A1 - Habbal, A. T1 - Pedestrian motion modelled by Fokker-Planck Nash games JF - Royal Society Open Science N2 - A new approach to modelling pedestrians' avoidance dynamics based on a Fokker–Planck (FP) Nash game framework is presented. In this framework, two interacting pedestrians are considered, whose motion variability is modelled through the corresponding probability density functions (PDFs) governed by FP equations. Based on these equations, a Nash differential game is formulated where the game strategies represent controls aiming at avoidance by minimizing appropriate collision cost functionals. The existence of Nash equilibria solutions is proved and characterized as a solution to an optimal control problem that is solved numerically. Results of numerical experiments are presented that successfully compare the computed Nash equilibria to the output of real experiments (conducted with humans) for four test cases. KW - Fokker–Planck equation KW - Nash equilibrium KW - pedestrian motion KW - differential games KW - avoidance KW - optimal control Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170395 VL - 4 IS - 9 ER - TY - JOUR A1 - Rothe, Hansjörg A1 - Brandenburg, Vincent A1 - Haun, Margot A1 - Kollerits, Barbara A1 - Kronenberg, Florian A1 - Ketteler, Markus A1 - Wanner, Christoph T1 - Ecto-5 ' -Nucleotidase CD73 (NT5E), vitamin D receptor and FGF23 gene polymorphisms may play a role in the development of calcific uremic arteriolopathy in dialysis patients - Data from the German Calciphylaxis Registry JF - PLoS One N2 - Introduction: Calciphylaxis/calcific uremic arteriolopathy affects mainly end-stage kidney disease patients but is also associated with malignant disorders such as myeloma, melanoma and breast cancer. Genetic risk factors of calciphylaxis have never been studied before. Methods: We investigated 10 target genes using a tagging SNP approach: the genes encoding CD73/ ecto-5'-nucleotidase (purinergic pathway), Matrix Gla protein, Fetuin A, Bone Gla protein, VKORC1 (all related to intrinsic calcification inhibition), calcium-sensing receptor, FGF23, Klotho, vitamin D receptor, stanniocalcin 1 (all related to CKD-MBD). 144 dialysis patients from the German calciphylaxis registry were compared with 370 dialysis patients without history of CUA. Genotyping was performed using iPLEX Gold MassARRAY(Sequenom, San Diego, USA), KASP genotyping chemistry (LGC, Teddington, Middlesex, UK) or sequencing. Statistical analysis comprised logistic regression analysis with adjustment for age and sex. Results: 165 SNPs were finally analyzed and 6 SNPs were associated with higher probability for calciphylaxis (OR>1) in our cohort. Nine SNPs of three genes (CD73, FGF23 and Vitamin D receptor) reached nominal significance (p< 0.05), but did not reach statistical significance after correction for multiple testing. Of the CD73 gene, rs4431401 (OR = 1.71, 95%CI 1.08-2.17, p = 0.023) and rs9444348 (OR = 1.48, 95% CI 1.11-1.97, p = 0.008) were associated with a higher probability for CUA. Of the FGF23 and VDR genes, rs7310492, rs11063118, rs13312747 and rs17882106 were associated with a higher probability for CUA. Conclusion: Polymorphisms in the genes encoding CD73, vitamin D receptor and FGF23 may play a role in calciphylaxis development. Although our study is the largest genetic study on calciphylaxis, it is limited by the low sample sizes. It therefore requires replication in other cohorts if available. KW - single nucleotide polymorphisms KW - calcification KW - medical dialysis KW - genotyping KW - cancer risk factors KW - vitamin D KW - chronic kidney disease KW - melanoma Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171817 VL - 12 IS - 2 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 - Ritzer, J. A1 - Lühmann, T. A1 - Rode, C. A1 - Pein-Hackelbusch, M. A1 - Immohr, I. A1 - Schedler, U. A1 - Thiele, T. A1 - Stübinger, S. A1 - Rechenberg, B.v. A1 - Waser-Althaus, J. A1 - Schlottig, F. A1 - Merli, M. A1 - Dawe, H. A1 - Karpíšek, M. A1 - Wyrwa, R. A1 - Schnabelrauch, M. A1 - Meinel, L. T1 - Diagnosing peri-implant disease using the tongue as a 24/7 detector JF - Nature Communications N2 - Our ability of screening broad communities for clinically asymptomatic diseases critically drives population health. Sensory chewing gums are presented targeting the tongue as 24/7 detector allowing diagnosis by “anyone, anywhere, anytime”. The chewing gum contains peptide sensors consisting of a protease cleavable linker in between a bitter substance and a microparticle. Matrix metalloproteinases in the oral cavity, as upregulated in peri-implant disease, specifically target the protease cleavable linker while chewing the gum, thereby generating bitterness for detection by the tongue. The peptide sensors prove significant success in discriminating saliva collected from patients with peri-implant disease versus clinically asymptomatic volunteers. Superior outcome is demonstrated over commercially available protease-based tests in saliva. “Anyone, anywhere, anytime” diagnostics are within reach for oral inflammation. Expanding this platform technology to other diseases in the future features this diagnostic as a massive screening tool potentially maximizing impact on population health. KW - peri-implant disease KW - sensory chewing gums KW - tongue KW - detector KW - peptide sensors Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170471 VL - 8 IS - 264 ER - TY - JOUR A1 - Richter, Anne A1 - Weick, Stefan A1 - Krieger, Thomas A1 - Exner, Florian A1 - Kellner, Sonja A1 - Polat, Bülent A1 - Flentje, Michael T1 - Evaluation of a software module for adaptive treatment planning and re-irradiation JF - Radiation Oncology N2 - Background: The aim of this work is to validate the Dynamic Planning Module in terms of usability and acceptance in the treatment planning workflow. Methods: The Dynamic Planning Module was used for decision making whether a plan adaptation was necessary within one course of radiation therapy. The Module was also used for patients scheduled for re-irradiation to estimate the dose in the pretreated region and calculate the accumulated dose to critical organs at risk. During one year, 370 patients were scheduled for plan adaptation or re-irradiation. All patient cases were classified according to their treated body region. For a sub-group of 20 patients treated with RT for lung cancer, the dosimetric effect of plan adaptation during the main treatment course was evaluated in detail. Changes in tumor volume, frequency of re-planning and the time interval between treatment start and plan adaptation were assessed. Results: The Dynamic Planning Tool was used in 20% of treated patients per year for both approaches nearly equally (42% plan adaptation and 58% re-irradiation). Most cases were assessed for the thoracic body region (51%) followed by pelvis (21%) and head and neck cases (10%). The sub-group evaluation showed that unintended plan adaptation was performed in 38% of the scheduled cases. A median time span between first day of treatment and necessity of adaptation of 17 days (range 4–35 days) was observed. PTV changed by 12 ± 12% on average (maximum change 42%). PTV decreased in 18 of 20 cases due to tumor shrinkage and increased in 2 of 20 cases. Re-planning resulted in a reduction of the mean lung dose of the ipsilateral side in 15 of 20 cases. Conclusion: The experience of one year showed high acceptance of the Dynamic Planning Module in our department for both physicians and medical physicists. The re-planning can potentially reduce the accumulated dose to the organs at risk and ensure a better target volume coverage. In the re-irradiation situation, the Dynamic Planning Tool was used to consider the pretreatment dose, to adapt the actual treatment schema more specifically and to review the accumulated dose. KW - re-irradiation KW - lung cancer KW - adaptation KW - re-planning Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158711 VL - 12 IS - 205 ER - TY - JOUR A1 - Richard, Kyalo A1 - Abdel-Rahman, Elfatih M. A1 - Subramanian, Sevgan A1 - Nyasani, Johnson O. A1 - Thiel, Michael A1 - Jozani, Hosein A1 - Borgemeister, Christian A1 - Landmann, Tobias T1 - Maize cropping systems mapping using RapidEye observations in agro-ecological landscapes in Kenya JF - Sensors N2 - Cropping systems information on explicit scales is an important but rarely available variable in many crops modeling routines and of utmost importance for understanding pests and disease propagation mechanisms in agro-ecological landscapes. In this study, high spatial and temporal resolution RapidEye bio-temporal data were utilized within a novel 2-step hierarchical random forest (RF) classification approach to map areas of mono- and mixed maize cropping systems. A small-scale maize farming site in Machakos County, Kenya was used as a study site. Within the study site, field data was collected during the satellite acquisition period on general land use/land cover (LULC) and the two cropping systems. Firstly, non-cropland areas were masked out from other land use/land cover using the LULC mapping result. Subsequently an optimized RF model was applied to the cropland layer to map the two cropping systems (2nd classification step). An overall accuracy of 93% was attained for the LULC classification, while the class accuracies (PA: producer’s accuracy and UA: user’s accuracy) for the two cropping systems were consistently above 85%. We concluded that explicit mapping of different cropping systems is feasible in complex and highly fragmented agro-ecological landscapes if high resolution and multi-temporal satellite data such as 5 m RapidEye data is employed. Further research is needed on the feasibility of using freely available 10–20 m Sentinel-2 data for wide-area assessment of cropping systems as an important variable in numerous crop productivity models. KW - remote sensing KW - RapidEye KW - bi-temporal KW - cropping systems KW - random forest KW - Kenya Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173285 VL - 17 IS - 11 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 - Radu, Laura A1 - Schoenwetter, Elisabeth A1 - Braun, Cathy A1 - Marcoux, Julien A1 - Koelmel, Wolfgang A1 - Schmitt, Dominik R. A1 - Kuper, Jochen A1 - Cianférani, Sarah A1 - Egly, Jean M. A1 - Poterszman, Arnaud A1 - Kisker, Caroline T1 - The intricate network between the p34 and p44 subunits is central to the activity of the transcription/DNA repair factor TFIIH JF - Nucleic Acids Research N2 - The general transcription factor IIH (TFIIH) is a multi-protein complex and its 10 subunits are engaged in an intricate protein–protein interaction network critical for the regulation of its transcription and DNA repair activities that are so far little understood on a molecular level. In this study, we focused on the p44 and the p34 subunits, which are central for the structural integrity of core-TFIIH. We solved crystal structures of a complex formed by the p34 N-terminal vWA and p44 C-terminal zinc binding domains from Chaetomium thermophilum and from Homo sapiens. Intriguingly, our functional analyses clearly revealed the presence of a second interface located in the C-terminal zinc binding region of p34, which can rescue a disrupted interaction between the p34 vWA and the p44 RING domain. In addition, we demonstrate that the C-terminal zinc binding domain of p34 assumes a central role with respect to the stability and function of TFIIH. Our data reveal a redundant interaction network within core-TFIIH, which may serve to minimize the susceptibility to mutational impairment. This provides first insights why so far no mutations in the p34 or p44 TFIIH-core subunits have been identified that would lead to the hallmark nucleotide excision repair syndromes xeroderma pigmentosum or trichothiodystrophy. KW - general transcription factor IIH (TFIIH) KW - DNA repair KW - protein–protein interaction KW - p44 KW - p34 Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170173 VL - 45 IS - 18 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 - Pötter-Nerger, Monika A1 - Reese, Rene A1 - Steigerwald, Frank A1 - Heiden, Jan Arne A1 - Herzog, Jan A1 - Moll, Christian K. E. A1 - Hamel, Wolfgang A1 - Ramirez-Pasos, Uri A1 - Falk, Daniela A1 - Mehdorn, Maximilian A1 - Gerloff, Christian A1 - Deuschl, Günther A1 - Volkmann, Jens T1 - Movement-Related Activity of Human Subthalamic Neurons during a Reach-to-Grasp Task JF - Frontiers in Human Neuroscience N2 - The aim of the study was to record movement-related single unit activity (SUA) in the human subthalamic nucleus (STN) during a standardized motor task of the upper limb. We performed microrecordings from the motor region of the human STN and registered kinematic data in 12 patients with Parkinson’s disease (PD) undergoing deep brain stimulation surgery (seven women, mean age 62.0 ± 4.7 years) while they intraoperatively performed visually cued reach-to-grasp movements using a grip device. SUA was analyzed offline in relation to different aspects of the movement (attention, start of the movement, movement velocity, button press) in terms of firing frequency, firing pattern, and oscillation. During the reach-to-grasp movement, 75/114 isolated subthalamic neurons exhibited movement-related activity changes. The largest proportion of single units showed modulation of firing frequency during several phases of the reach and grasp (polymodal neurons, 45/114), particularly an increase of firing rate during the reaching phase of the movement, which often correlated with movement velocity. The firing pattern (bursting, irregular, or tonic) remained unchanged during movement compared to rest. Oscillatory single unit firing activity (predominantly in the theta and beta frequency) decreased with movement onset, irrespective of oscillation frequency. This study shows for the first time specific, task-related, SUA changes during the reach-to-grasp movement in humans. KW - subthalamic nucleus KW - deep brain stimulation KW - Parkinson’s disease KW - neurophysiology KW - beta oscillation KW - reach-to-grasp movement Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170361 VL - 11 IS - 436 ER - TY - JOUR A1 - Pordzik, Ralph T1 - George Orwell’s Imperial Bestiary: Totemism, Animal Agency and Cross-Species Interaction in “Shooting an Elephant”, Burmese Days and “Marrakech” JF - Anglia N2 - This essay argues that Orwell’s representation of animals as companion species offers a strikingly new, as-yet largely neglected view of animal agency and interiority in his work. In “Shooting an Elephant”, Burmese Days and “Marrakech”, the writer’s focus on the social reject is supplemented by a marked sense of community implying human tragedy yet framing it within precariously situated human-animal, colonial or urban-imperial transitions that visualise animals as agents of change and co-shaping species interdependent with the lives of the humans that utilize and domineer them. Animals are required whenever Orwell aspires to shift from isolation to communality, from the self-conscious outsider to the larger realm of ideas framing the world in which his characters strive to overstep the accepted lines of social performance and conformity. Read in and around disciplinary structures of rationalization, Orwell’s animals appear to secure themselves, quite paradoxically, a place within the normative anthropocentric framework excluding them. They extend beyond anthropomorphising or allegorical modes of description and open up bio-political perspectives within and across regimes of knowledge and empathy. Orwell’s writings thus present a challenge to the culturally accredited fantasy of human exceptionalism, collapsing any epistemic space between humans and animals and burying the idea of sustaining radical species distinction. KW - Georgre Orwell KW - Shooting an Elephant KW - Burmese Days KW - Marrakech Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-194200 SN - 1865-8938 SN - 0340-5222 N1 - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. VL - 135 IS - 3 ER - TY - JOUR A1 - Pollinger, Florian A1 - Schmitt, Stefan A1 - Sander, Dirk A1 - Tian, Zhen A1 - Kirschner, Jürgen A1 - Vrdoljak, Pavo A1 - Stadler, Christoph A1 - Maier, Florian A1 - Marchetto, Helder A1 - Schmidt, Thomas A1 - Schöll, Achim A1 - Umbach, Eberhard T1 - Nanoscale patterning, macroscopic reconstruction, and enhanced surface stress by organic adsorption on vicinal surfaces JF - New Journal of Physics N2 - Self-organization is a promising method within the framework of bottom-up architectures to generate nanostructures in an efficient way. The present work demonstrates that self- organization on the length scale of a few to several tens of nanometers can be achieved by a proper combination of a large (organic) molecule and a vicinal metal surface if the local bonding of the molecule on steps is significantly stronger than that on low-index surfaces. In this case thermal annealing may lead to large mass transport of the subjacent substrate atoms such that nanometer-wide and micrometer-long molecular stripes or other patterns are being formed on high-index planes. The formation of these patterns can be controlled by the initial surface orientation and adsorbate coverage. The patterns arrange self-organized in regular arrays by repulsive mechanical interactions over long distances accompanied by a significant enhancement of surface stress. We demonstrate this effect using the planar organic molecule PTCDA as adsorbate and Ag(10 8 7) and Ag(775)surfaces as substrate. The patterns are directly observed by STM, the formation of vicinal surfaces is monitored by highresolution electron diffraction, the microscopic surface morphology changes are followed by spectromicroscopy, and the macroscopic changes of surface stress are measured by a cantilever bending method. The in situ combination of these complementary techniques provides compelling evidence for elastic interaction and a significant stress contribution to long-range order and nanopattern formation. KW - physics KW - patterning KW - reconstruction KW - surface stress KW - STM KW - SPA-LEED KW - vicinal surfaces KW - adsoption Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171947 VL - 19 ER - TY - JOUR A1 - Polat, Bülent A1 - Kaiser, Philipp A1 - Wohlleben, Gisela A1 - Gehrke, Thomas A1 - Scherzad, Agmal A1 - Scheich, Matthias A1 - Malzahn, Uwe A1 - Fischer, Thomas A1 - Vordermark, Dirk A1 - Flentje, Michael T1 - Perioperative changes in osteopontin and TGFβ1 plasma levels and their prognostic impact for radiotherapy in head and neck cancer JF - BMC Cancer N2 - Background: In head and neck cancer little is known about the kinetics of osteopontin (OPN) expression after tumor resection. In this study we evaluated the time course of OPN plasma levels before and after surgery. Methods: Between 2011 and 2013 41 consecutive head and neck cancer patients were enrolled in a prospective study (group A). At different time points plasma samples were collected: T0) before, T1) 1 day, T2) 1 week and T3) 4 weeks after surgery. Osteopontin and TGFβ1 plasma concentrations were measured with a commercial ELISA system. Data were compared to 131 head and neck cancer patients treated with primary (n = 42) or postoperative radiotherapy (n = 89; group B1 and B2). Results: A significant OPN increase was seen as early as 1 day after surgery (T0 to T1, p < 0.01). OPN levels decreased to base line 3-4 weeks after surgery. OPN values were correlated with postoperative TGFβ1 expression suggesting a relation to wound healing. Survival analysis showed a significant benefit for patients with lower OPN levels both in the primary and postoperative radiotherapy group (B1: 33 vs 11.5 months, p = 0.017, B2: median not reached vs 33.4, p = 0.031). TGFβ1 was also of prognostic significance in group B1 (33.0 vs 10.7 months, p = 0.003). Conclusions: Patients with head and neck cancer showed an increase in osteopontin plasma levels directly after surgery. Four weeks later OPN concentration decreased to pre-surgery levels. This long lasting increase was presumably associated to wound healing. Both pretherapeutic osteopontin and TGFβ1 had prognostic impact. KW - perioperative changes KW - osteopontin KW - TGFβ1 KW - head and neck cancer KW - survival Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157529 VL - 17 IS - 6 ER - TY - JOUR A1 - Piroth, Tobias A1 - Boelmans, Kai A1 - Amtage, Florian A1 - Rijntjes, Michel A1 - Wierciochin, Anna A1 - Musacchio, Thomas A1 - Weiller, Cornelius A1 - Volkmann, Jens A1 - Klebe, Stephan T1 - Adult-Onset Niemann-Pick Disease Type C: Rapid Treatment Initiation Advised but Early Diagnosis Remains Difficult JF - Frontiers in Neurology N2 - Niemann–Pick type C disease (NP-C) presents with heterogeneous neurological and psychiatric symptoms. Adult onset is rare and possibly underdiagnosed due to frequent lack of specific and obvious key symptoms. For both early and adolescent/adult onset, the available data from studies and case reports describe a positive effect of Miglustat (symptom relief or stabilization). However, due to the low frequency of NP-C, experience with this therapy is still limited. We describe two adult-onset cases of NP-C. In both cases, vertical supranuclear gaze palsy was not recognized at symptom onset. Correct diagnosis was delayed from onset of symptoms by more than 10 years. The video demonstrates the broad spectrum of symptoms in later stages of the disease. Compared with published data, the treatment outcome observed in our cases after delayed initiation of Miglustat therapy was disappointing, with continuing disease progression in both cases. Thus, early treatment initiation could be necessary to achieve a good symptomatic effect. Hence, early biochemical testing for NP-C should be considered in patients suffering from atypical neurological/neuropsychological and psychiatric symptoms, even in cases of uncertainty. KW - Niemann–Pick disease type C KW - adult-onset KW - NPC1 gene KW - NPC2 gene KW - plasma oxysterols Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171001 VL - 8 IS - 108 ER - TY - JOUR A1 - Pieczykolan, Aleks A1 - Huestegge, Lynn T1 - Cross-modal Action Complexity: Action- and Rule-related Memory Retrieval in Dual-response Control JF - Frontiers in Psychology N2 - Normally, we do not act within a single effector system only, but rather coordinate actions across several output modules (cross-modal action). Such cross-modal action demands can vary substantially with respect to their complexity in terms of the number of task-relevant response combinations and to-be-retrieved stimulus-response (S-R) mapping rules. In the present study, we study the impact of these two types of cross-modal action complexity on dual-response costs (i.e., performance differences between single- and dual-action demands). In Experiment 1, we combined a manual and an oculomotor task, each involving four response alternatives. Crucially, one (unconstrained) condition involved all 16 possible combinations of response alternatives, whereas a constrained condition involved only a subset of possible response combinations. The results revealed that preparing for a larger number of response combinations yielded a significant, but moderate increase in dual-response costs. In Experiment 2, we utilized one common lateralized auditory (e.g., left) stimulus to trigger incompatible response compounds (e.g., left saccade and right key press or vice versa). While one condition only involved one set of task-relevant S-R rules, another condition involved two sets of task-relevant rules (coded by stimulus type: noise/tone), while the number of task-relevant response combinations was the same in both conditions. Here, an increase in the number of to-be-retrieved S-R rules was associated with a substantial increase in dual-response costs that were also modulated on a trial-by-trial basis when switching between rules. Taken together, the results shed further light on the dependency of cross-modal action control on both action- and rule-related memory retrieval processes. KW - task rules KW - cross-modal action KW - dual tasks KW - dual-response costs KW - oculomotor control Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157794 VL - 8 IS - 529 ER - TY - JOUR A1 - Pfister, Roland A1 - Schwarz, Katharina A. A1 - Wirth, Robert A1 - Lindner, Isabel T1 - My Command, My Act: Observation Inflation in Face-To-Face Interactions JF - Advances in Cognitive Psychology N2 - When observing another agent performing simple actions, these actions are systematically remembered as one’s own after a brief period of time. Such observation inflation has been documented as a robust phenomenon in studies in which participants passively observed videotaped actions. Whether observation inflation also holds for direct, face-to-face interactions is an open question that we addressed in two experiments. In Experiment 1, participants commanded the experimenter to carry out certain actions, and they indeed reported false memories of self-performance in a later memory test. The effect size of this inflation effect was similar to passive observation as confirmed by Experiment 2. These findings suggest that observation inflation might affect action memory in a broad range of real-world interactions. KW - observation inflation KW - memory bias KW - action observation KW - motor simulation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170739 VL - 13 IS - 2 ER - TY - JOUR A1 - Petruski-Ivleva, Natalia A1 - Kucharska-Newton, Anna A1 - Palta, Priya A1 - Couper, David A1 - Meyer, Katie A1 - Graff, Misa A1 - Haring, Bernhard A1 - Sharrett, Richey A1 - Heiss, Gerardo T1 - Milk intake at midlife and cognitive decline over 20 years. The Atherosclerosis risk in communities (ARIC) study JF - Nutrients N2 - Background: Faster rates of cognitive decline are likely to result in earlier onset of cognitive impairment and dementia. d-galactose, a derivative of lactose, is used in animal studies to induce neurodegeneration. Milk is the primary source of lactose in the human diet, and its effects on cognitive decline have not been fully evaluated. Objective: Assess the association of milk intake with change in cognitive function over 20 years. Methods: A total of 13,751 participants of the Atherosclerosis Risk in Communities (ARIC) cohort completed a food frequency questionnaire and three neurocognitive evaluations from 1990 through 2013. Two single nucleotide polymorphisms (SNPs) were used to determine lactase persistence (LCT-13910 C/T for Whites and LCT-14010 G/C for Blacks). Mixed-effects models were used to study the association of milk intake with cognitive change. Multiple imputations by chained equations were used to account for attrition. Results: Milk intake greater than 1 glass/day was associated with greater decline in the global z-score over a 20-year period. The difference in decline was 0.10 (95% CI: 0.16, 0.03) z-scores, or an additional 10% decline, relative to the group reporting “almost never” consuming milk. Conclusions: Replication of these results is warranted in diverse populations with greater milk intake and higher variability of lactase persistence genotype. KW - lactose KW - lactase persistence KW - oxidative stress KW - cognitive decline KW - dementia KW - aging Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173909 VL - 9 IS - 10 ER - TY - JOUR A1 - Paxton, Naomi A1 - Smolan, Willi A1 - Böck, Thomas A1 - Melchels, Ferry A1 - Groll, Jürgen A1 - Jungst, Tomasz T1 - Proposal to assess printability of bioinks for extrusion-based bioprinting and evaluation of rheological properties governing bioprintability JF - Biofabrication N2 - The development and formulation of printable inks for extrusion-based 3D bioprinting has been a major challenge in the field of biofabrication. Inks, often polymer solutions with the addition of crosslinking to form hydrogels, must not only display adequate mechanical properties for the chosen application but also show high biocompatibility as well as printability. Here we describe a reproducible two-step method for the assessment of the printability of inks for bioprinting, focussing firstly on screening ink formulations to assess fibre formation and the ability to form 3D constructs before presenting a method for the rheological evaluation of inks to characterise the yield point, shear thinning and recovery behaviour. In conjunction, a mathematical model was formulated to provide a theoretical understanding of the pressure-driven, shear thinning extrusion of inks through needles in a bioprinter. The assessment methods were trialled with a commercially available crème, poloxamer 407, alginate-based inks and an alginate-gelatine composite material. Yield stress was investigated by applying a stress ramp to a number of inks, which demonstrated the necessity of high yield for printable materials. The shear thinning behaviour of the inks was then characterised by quantifying the degree of shear thinning and using the mathematical model to predict the window of printer operating parameters in which the materials could be printed. Furthermore, the model predicted high shear conditions and high residence times for cells at the walls of the needle and effects on cytocompatibility at different printing conditions. Finally, the ability of the materials to recover to their original viscosity after extrusion was examined using rotational recovery rheological measurements. Taken together, these assessment techniques revealed significant insights into the requirements for printable inks and shear conditions present during the extrusion process and allow the rapid and reproducible characterisation of a wide variety of inks for bioprinting. KW - bioprinting KW - rheology KW - modelling KW - bioink Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254061 VL - 9 IS - 4 ER - TY - JOUR A1 - Paeth, Heiko A1 - Paxian, Andreas A1 - Sein, Dimitry V. A1 - Jacob, Daniela A1 - Panitz, Hans-Jürgen A1 - Warscher, Michael A1 - Fink, Andreas H. A1 - Kunstmann, Harald A1 - Breil, Marcus A1 - Engel, Thomas A1 - Krause, Andreas A1 - Toedter, Julian A1 - Ahrens, Bodo T1 - Decadal and multi-year predictability of the West African monsoon and the role of dynamical downscaling JF - Meteorologische Zeitschrift N2 - West African summer monsoon precipitation is characterized by distinct decadal variability. Due to its welldocumented link to oceanic boundary conditions in various ocean basins it represents a paradigm for decadal predictability. In this study, we reappraise this hypothesis for several sub-regions of sub-Saharan West Africa using the new German contribution to the coupled model intercomparison project phase 5 (CMIP5) near-term prediction system. In addition, we assume that dynamical downscaling of the global decadal predictions leads to an enhanced predictive skill because enhanced resolution improves the atmospheric response to oceanic forcing and landsurface feedbacks. Based on three regional climate models, a heterogeneous picture is drawn: none of the regional climate models outperforms the global decadal predictions or all other regional climate models in every region nor decade. However, for every test case at least one regional climate model was identified which outperforms the global predictions. The highest predictive skill is found in the western and central Sahel Zone with correlation coefficients and mean-square skill scores exceeding 0.9 and 0.8, respectively. KW - geography KW - decadal predictability KW - West Africa KW - monsoon rainfall KW - dynamical downscaling Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172018 VL - 26 IS - 4 ER - TY - JOUR A1 - Ott, Christine T1 - Literarisches Dorfleben in Maienfeld oder Wie Heidi lebte. JF - kjl&m – Kinder-/Jugendliteratur und Medien in Forschung, Literatur und Bibliothek N2 - Kein Abstract verfügbar. KW - Kinderbuchwelt KW - Erlebnisgesellschaft Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-210610 UR - http://www.kopaed.de/ VL - 69 IS - 3 ER - TY - JOUR A1 - Oezkur, Mehmet A1 - Magyar, Attila A1 - Thomas, Phillip A1 - Stork, Tabea A1 - Schneider, Reinhard A1 - Bening, Constanze A1 - Störk, Stefan A1 - Heuschmann, Peter U. A1 - Leyh, Rainer G. A1 - Wagner, Martin T1 - TIMP-2*IGFBP7 (Nephrocheck®) Measurements at Intensive Care Unit Admission After Cardiac Surgery are Predictive for Acute Kidney Injury Within 48 Hours JF - Kidney & Blood Pressure Research N2 - Background/Aims: Acute kidney injury (AKI) is a postoperative complication after cardiac surgery with a high impact on mortality and morbidity. Nephrocheck® [TIMP-2*IGFBP7] determines markers of tubular stress, which occurs prior to tubular damage. It is unknown at which time-point [TIMP-2*IGFBP7] measurement should be performed to ideally predict AKI. We investigated the association of [TIMP-2*IGFBP7] at various time-points with the incidence of AKI in patients undergoing elective cardiac surgery including cardio-pulmonary bypass. Methods: In a prospective cohort study, serial blood and urine samples were collected from 150 patients: pre-operative, at ICU-admission, 24h and 48h post-surgery. AKI was defined as Serum-Creatinine rise >0.3 mg/dl within 48hrs. Urinary [TIMP-2*IGFBP7] was measured at pre-operative, ICU-admission and 24h post-surgery; medical staff was kept blinded to these results. Results: A total of 35 patients (23.5%) experienced AKI, with a higher incidence in those with high [TIMP-2*IGFBP7] values at ICU admission (57.1% vs. 10.1%, p<0.001). In logistic regression [TIMP-2*IGFBP7] at ICU admission was independently associated with the occurrence of AKI (Odds Ratio 11.83; p<0.001, C-statistic= 0.74) after adjustment for EuroSCORE II and CBP-time. Conclusions: Early detection of elevated [TIMP-2*IGFBP7] at ICU admission was strongly predictive for postoperative AKI and appeared to be more precise as compared to subsequent measurements. KW - postoperativ KW - Akutes Nierenversagen Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157988 VL - 42 ER - TY - JOUR A1 - Oehler, Beatrice A1 - Mohammadi, Milad A1 - Perpina Viciano, Cristina A1 - Hackel, Dagmar A1 - Hoffmann, Carsten A1 - Brack, Alexander A1 - Rittner, Heike L. T1 - Peripheral interaction of Resolvin D1 and E1 with opioid receptor antagonists for antinociception in inflammatory pain in rats JF - Frontiers in Molecular Neuroscience N2 - Antinociceptive pathways are activated in the periphery in inflammatory pain, for instance resolvins and opioid peptides. Resolvins are biosynthesized from omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid. Resolvin D1 (RvD1) and resolvin E1 (RvE1) initiate the resolution of inflammation and control of hypersensitivity via induction of anti-inflammatory signaling cascades. RvD1 binds to lipoxin A4/annexin-A1 receptor/formyl-peptide receptor 2 (ALX/FPR2), RvE1 to chemerin receptor 23 (ChemR23). Antinociception of RvD1 is mediated by interaction with transient receptor potential channels ankyrin 1 (TRPA1). Endogenous opioid peptides are synthesized and released from leukocytes in the tissue and bind to opioid receptors on nociceptor terminals. Here, we further explored peripheral mechanisms of RvD1 and chemerin (Chem), the ligand of ChemR23, in complete Freund’s adjuvant (CFA)-induced hindpaw inflammation in male Wistar rats. RvD1 and Chem ameliorated CFA-induced hypersensitivity in early and late inflammatory phases. This was prevented by peripheral blockade of the μ-opioid peptide receptor (MOR) using low dose local naloxone or by local injection of anti-β-endorphin and anti-met-enkephalin (anti-ENK) antibodies. Naloxone also hindered antinociception by the TRPA1 inhibitor HC-030031. RvD1 did not stimulate the release of β-endorphin from macrophages and neutrophils, nor did RvD1 itself activate G-proteins coupled MOR or initiate β-arrestin recruitment to the membrane. TRPA1 blockade by HC-030031 in inflammation in vivo as well as inhibition of the TRPA1-mediated calcium influx in dorsal root ganglia neurons in vitro was hampered by naloxone. Peripheral application of naloxone alone in vivo already lowered mechanical nociceptive thresholds. Therefore, either a perturbation of the balance of endogenous pro- and antinociceptive mechanisms in early and late inflammation, or an interaction of TRPA1 and opioid receptors weaken the antinociceptive potency of RvD1 and TRPA1 blockers. KW - transient receptor potential channels KW - pain behavior KW - resolvin KW - opioid receptors KW - opioid peptides KW - inflammation KW - animals Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158642 VL - 10 IS - 242 ER - TY - JOUR A1 - Oehler, Beatrice A1 - Kistner, Katrin A1 - Martin, Corinna A1 - Schiller, Jürgen A1 - Mayer, Rafaela A1 - Mohammadi, Milad A1 - Sauer, Reine-Solange A1 - Filipovic, Milos R. A1 - Nieto, Francisco R. A1 - Kloka, Jan A1 - Pflücke, Diana A1 - Hill, Kerstin A1 - Schaefer, Michael A1 - Malcangio, Marzia A1 - Reeh, Peter W. A1 - Brack, Alexander A1 - Blum, Robert A1 - Rittner, Heike L. T1 - Inflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation JF - Scientific Reports N2 - Phospholipids occurring in cell membranes and lipoproteins are converted into oxidized phospholipids (OxPL) by oxidative stress promoting atherosclerotic plaque formation. Here, OxPL were characterized as novel targets in acute and chronic inflammatory pain. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) and its derivatives were identified in inflamed tissue by mass spectrometry and binding assays. They elicited calcium influx, hyperalgesia and induced pro-nociceptive peptide release. Genetic, pharmacological and mass spectrometric evidence in vivo as well as in vitro confirmed the role of transient receptor potential channels (TRPA1 and TRPV1) as OxPAPC targets. Treatment with the monoclonal antibody E06 or with apolipoprotein A-I mimetic peptide D-4F, capturing OxPAPC in atherosclerosis, prevented inflammatory hyperalgesia, and in vitro TRPA1 activation. Administration of D-4F or E06 to rats profoundly ameliorated mechanical hyperalgesia and inflammation in collagen-induced arthritis. These data reveal a clinically relevant role for OxPAPC in inflammation offering therapy for acute and chronic inflammatory pain treatment by scavenging OxPAPC. KW - chronic pain KW - ion channels in the nervous system KW - molecular medicine KW - pain Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158536 VL - 7 IS - 5447 ER - TY - JOUR A1 - Nürnberger, Fabian A1 - Steffan-Dewenter, Ingolf A1 - Härtel, Stephan T1 - Combined effects of waggle dance communication and landscape heterogeneity on nectar and pollen uptake in honey bee colonies JF - PeerJ N2 - The instructive component of waggle dance communication has been shown to increase resource uptake of Apis mellifera colonies in highly heterogeneous resource environments, but an assessment of its relevance in temperate landscapes with different levels of resource heterogeneity is currently lacking. We hypothesized that the advertisement of resource locations via dance communication would be most relevant in highly heterogeneous landscapes with large spatial variation of floral resources. To test our hypothesis, we placed 24 Apis mellifera colonies with either disrupted or unimpaired instructive component of dance communication in eight Central European agricultural landscapes that differed in heterogeneity and resource availability. We monitored colony weight change and pollen harvest as measure of foraging success. Dance disruption did not significantly alter colony weight change, but decreased pollen harvest compared to the communicating colonies by 40%. There was no general effect of resource availability on nectar or pollen foraging success, but the effect of landscape heterogeneity on nectar uptake was stronger when resource availability was high. In contrast to our hypothesis, the effects of disrupted bee communication on nectar and pollen foraging success were not stronger in landscapes with heterogeneous compared to homogenous resource environments. Our results indicate that in temperate regions intra-colonial communication of resource locations benefits pollen foraging more than nectar foraging, irrespective of landscape heterogeneity. We conclude that the so far largely unexplored role of dance communication in pollen foraging requires further consideration as pollen is a crucial resource for colony development and health. KW - Apis mellifera KW - orientation KW - recruitment KW - landscape ecology KW - foraging behaviour KW - floral resource distribution Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170813 VL - 5 IS - e3441 ER - TY - JOUR A1 - Nord, Ilona A1 - Palkowitsch-Kühl, Jens T1 - RELab digital: Ein Projekt zu religiöser Bildung in einer mediatisierten Welt JF - Zeitschrift für Pädagogik und Theologie N2 - Schule als Lern- und Lebensort zukünftiger Generationen partizipiert an global sich vollziehenden medialen Transformationsprozessen. Religionspädagogik und -didaktik sind, wie alle anderen Fachwissenschaften auch, herausgefordert, die Integration digitaler Medien in Theorie und Praxis zu reflektieren und konzeptionieren. Dies hat in mindestens drei Dimensionen zu erfolgen: beim Lernen mit digitalen Medien, beim Lernen über digitale Medien sowie in der Einübung in eine konstruktiv-kritische Medienbildung. Das Projekt ist der Entwicklung, Erprobung und Evaluation von Lernszenarien im Religionsunterricht und im Austausch mit außerschulischen religiösen Bildungsorten gewidmet. KW - Media Education KW - Learning with digital Media KW - Learning about digital Media KW - digitalized teaching material KW - SAMR-Model KW - Didactics of Religion KW - Medienbildung KW - Lernen mit digitalen Medien KW - Lernen über digitale Medien KW - digitales Unterrichtsmaterial KW - SAMR-Modell KW - Religionsdidaktik Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-194880 SN - 2366-7796 SN - 1437-7160 N1 - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. VL - 69 IS - 3 ER - TY - JOUR A1 - Nord, Ilona T1 - Wolfhard Schweiker, Prinzip Inklusion. Grundlagen einer interdisziplinären Metatheorie in religionspädagogischer Perspektive. Göttingen: Vandenhoeck & Ruprecht 2017. JF - Zeitschrift für Pädagogik und Theologie N2 - Kein Abstract verfügbar. KW - Rezension Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-194874 SN - 2366-7796 SN - 1437-7160 N1 - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. VL - 69 IS - 3 ER - TY - JOUR A1 - Neuchel, Christine A1 - Fürst, Daniel A1 - Niederwieser, Dietger A1 - Bunjes, Donald A1 - Tsamadou, Chrysanthi A1 - Wulf, Gerald A1 - Pfreundschuh, Michael A1 - Wagner, Eva A1 - Stuhler, Gernot A1 - Einsele, Hermann A1 - Schrezenmeier, Hubert A1 - Mytilineos, Joannis T1 - Impact of donor activating KIR genes on HSCT outcome in C1-ligand negative myeloid disease patients transplanted with unrelated donors - a retrospective study JF - PLOS One N2 - Natural Killer cells (NK) are lymphocytes with the potential to recognize and lyse cells which escaped T-cell mediated lysis due to their aberrant HLA expression profiles. Killer cell immunoglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon interaction with HLA-C (C1, C2) ligands. Therefore, absence of ligands for donor inhibitory KIRs following hematopoietic stem cell transplantation (HSCT) may have an influence on its outcome. Previous studies showed that C1 negative patients have a decreased HSCT outcome. Our study, based on a cohort of 200 C1-negative patients, confirmed these findings for the endpoints: overall survival (OS: HR = 1.41, CI = 1.14–1.74, p = 0.0012), disease free survival (DFS: HR = 1.27, CI = 1.05–1.53, p = 0.015), treatment related mortality (TRM: HR = 1.41, CI = 1.01–1.96, p = 0.04), and relapse incidence (RI: HR = 1.33, CI = 1.01–1.75, p = 0.04) all being inferior when compared to C1-positive patients (n = 1246). Subsequent analysis showed that these findings applied for patients with myeloid malignancies but not for patients with lymphoproliferative diseases (OS: myeloid: HR = 1.51, CI = 1.15–1.99, p = 0.003; lymphoblastic: HR = 1.26, CI = 0.91–1.75, p = 0.16; DFS: myeloid: HR = 1.31, CI = 1.01–1.70, p = 0.04; lymphoblastic: HR = 1.21, CI = 0.90–1.61, p = 0.21; RI: myeloid: HR = 1.31, CI = 1.01–1.70, p = 0.04; lymphoblastic: HR = 1.21, CI = 0.90–1.61, p = 0.21). Interestingly, within the C1-negative patient group, transplantation with KIR2DS2 resulted in better OS (9/10 matched: HR = 0.24, CI = 0.08–0.67, p = 0.007) as well as DFS (9/10 matched: HR = 0,26, CI = 0.11–0.60, p = 0.002), and transplantation with KIR2DS1 positive donors was associated with a decreased RI (HR = 0.30, CI = 0.13–0.69, p = 0.005). TRM was increased when the donor was positive for KIR2DS1 (HR = 2.61, CI = 1.26–5.41, p = 0.001). Our findings suggest that inclusion of KIR2DS1/2/5 and KIR3DS1-genotyping in the unrelated donor search algorithm of C1-ligand negative patients with myeloid malignancies may prove to be of clinical relevance. KW - Hematopoietic stem cell transplantation KW - Cancer risk factors KW - Multivariate analysis KW - Stem cell transplantation KW - T-cells KW - Bone marrow transplantation KW - NK-cells KW - Immune receptor signaling KW - Killer cell immunoglobulin-like receptors KW - Acute myeloid leukemia KW - Acute lymphoblastic leukemia KW - Chronic lymphoblastic leukemia KW - Chronic myeloid leukemia Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180995 VL - 12 IS - 1 ER - TY - JOUR A1 - Münchow, Hannes A1 - Mengelkamp, Christoph A1 - Bannert, Maria T1 - The better you feel the better you learn: do warm colours and rounded shapes enhance learning outcome in multimedia learning? JF - Education Research International N2 - The aim of the present study was to examine whether fostering positive activating affect during multimedia learning enhances learning outcome. University students were randomly assigned to either a multimedia learning environment designed to induce positive activating affect through the use of “warm” colours and rounded shapes () or an affectively neutral environment that used achromatic colours and sharp edges (). Participants learned about the topic of functional neuroanatomy for 20 minutes and had to answer several questions for comprehension and transfer afterwards. Affective states as well as achievement goal orientations were investigated before and after the learning phase using questionnaires. The results show that participants in the affectively positive environment were superior in comprehension as well as transfer when initial affect was strong. Preexperimental positive affect was therefore a predictor of comprehension and a moderator for transfer. Goal orientations did not influence these effects. The findings support the idea that positive affect, induced through the design of the particular multimedia learning environment, can facilitate performance if initial affective states are taken into account. KW - shape KW - learning outcome KW - multimedia learning KW - colour Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158566 VL - 2017 ER - TY - JOUR A1 - Müller-Deubert, Sigrid A1 - Seefried, Lothar A1 - Krug, Melanie A1 - Jakob, Franz A1 - Ebert, Regina T1 - Epidermal growth factor as a mechanosensitizer in human bone marrow stromal cells JF - Stem Cell Research N2 - Epidermal growth factors (EGFs) e.g. EGF, heparin-binding EGF and transforming growth factor alpha and their receptors e.g. EGFR and ErbB2 control proinflammatory signaling and modulate proliferation in bone marrow stromal cells (BMSC). Interleukin-6 and interleukin-8 are EGF targets and participate in the inflammatory phase of bone regeneration via non-canonical wnt signaling. BMSC differentiation is also influenced by mechanical strain-related activation of ERK1/2 and AP-1, but the role of EGFR signaling in mechanotransduction is unclear. We investigated the effects of EGFR signaling in telomerase-immortalized BMSC, transfected with a luciferase reporter, comprising a mechanoresponsive AP1 element, using ligands, neutralizing antibodies and EGFR inhibitors on mechanotransduction and we found that EGF via EGFR increased the response to mechanical strain. Results were confirmed by qPCR analysis of mechanoresponsive genes. EGF-responsive interleukin-6 and interleukin-8 were synergistically enhanced by EGF stimulation and mechanical strain. We show here in immortalized and primary BMSC that EGFR signaling enhances mechanotransduction, indicating that the EGF system is a mechanosensitizer in BMSC. Alterations in mechanosensitivity and -adaptation are contributors to age-related diseases like osteoporosis and the identification of a suitable mechanosensitizer could be beneficial. The role of the synergism of these signaling cascades in physiology and disease remains to be unraveled. KW - mechanotransduction KW - bone marrow stromal cells KW - epidermal growth factor KW - signaling Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170247 VL - 24 ER - TY - JOUR A1 - Müller, Bettina A1 - Richter, Tobias A1 - Karageorgos, Panagiotis A1 - Krawietz, Sabine A1 - Ennemoser, Marco T1 - Effects of a syllable-based reading intervention in poor-reading fourth graders JF - Frontiers in Psychology N2 - In transparent orthographies, persistent reading fluency difficulties are a major cause of poor reading skills in primary school. The purpose of the present study was to investigate effects of a syllable-based reading intervention on word reading fluency and reading comprehension among German-speaking poor readers in Grade 4. The 16-session intervention was based on analyzing the syllabic structure of words to strengthen the mental representations of syllables and words that consist of these syllables. The training materials were designed using the 500 most frequent syllables typically read by fourth graders. The 75 poor readers were randomly allocated to the treatment or the control group. Results indicate a significant and strong effect on the fluency of recognizing single words, whereas text-level reading comprehension was not significantly improved by the training. The specific treatment effect provides evidence that a short syllable-based approach works even in older poor readers at the end of primary school. KW - word reading fluency KW - syllable-based intervention KW - older poor readers KW - primary school KW - reading comprehension Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158841 VL - 8 IS - 1635 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 - Musekamp, Gunda A1 - Schuler, Michael A1 - Seekatz, Bettina A1 - Bengel, Jürgen A1 - Faller, Hermann A1 - Meng, Karin T1 - Does improvement in self-management skills predict improvement in quality of life and depressive symptoms? A prospective study in patients with heart failure up to one year after self-management education JF - BMC Cardiovascular Disorders N2 - Background: Heart failure (HF) patient education aims to foster patients’ self-management skills. These are assumed to bring about, in turn, improvements in distal outcomes such as quality of life. The purpose of this study was to test the hypothesis that change in self-reported self-management skills observed after participation in self-management education predicts changes in physical and mental quality of life and depressive symptoms up to one year thereafter. Methods: The sample comprised 342 patients with chronic heart failure, treated in inpatient rehabilitation clinics, who received a heart failure self-management education program. Latent change modelling was used to analyze relationships between both short-term (during inpatient rehabilitation) and intermediate-term (after six months) changes in self-reported self-management skills and both intermediate-term and long-term (after twelve months) changes in physical and mental quality of life and depressive symptoms. Results: Short-term changes in self-reported self-management skills predicted intermediate-term changes in mental quality of life and long-term changes in physical quality of life. Intermediate-term changes in self-reported self-management skills predicted long-term changes in all outcomes. KW - patient education KW - chronic heart failure KW - self-management KW - quality of life KW - latent change KW - cardiac rehabilitation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157501 VL - 17 IS - 51 ER - TY - JOUR A1 - Mumcuoglu, Didem A1 - Siverino, Claudia A1 - Tabisz, Barbara A1 - Kluijtmans, Bas A1 - Nickel, Joachim T1 - How to use BMP-2 for clinical applications? A review on pros and cons of existing delivery strategies JF - Journal of Translational Science N2 - No abstract available. KW - BMP-2 KW - clinical applications Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158678 VL - 3 IS - 5 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 - Moschall, Rebecca A1 - Denk, Sarah A1 - Erkelenz, Steffen A1 - Schenk, Christian A1 - Schaal, Heiner A1 - Bodem, Jochen T1 - A purine-rich element in foamy virus pol regulates env splicing and gag/pol expression JF - Retrovirology N2 - Background: The foamy viral genome encodes four central purine-rich elements localized in the integrase-coding region of pol. Previously, we have shown that the first two of these RNA elements (A and B) are required for protease dimerization and activation. The D element functions as internal polypurine tract during reverse transcription. Peters et al., described the third element (C) as essential for gag expression suggesting that it might serve as an RNA export element for the unspliced genomic transcript. Results: Here, we analysed env splicing and demonstrate that the described C element composed of three GAA repeats known to bind SR proteins regulates env splicing, thus balancing the amount of gag/pol mRNAs. Deletion of the C element effectively promotes a splice site switch from a newly identified env splice acceptor to the intrinsically strong downstream localised env 3′ splice acceptor permitting complete splicing of almost all LTR derived transcripts. We provide evidence that repression of this env splice acceptor is a prerequisite for gag expression. This repression is achieved by the C element, resulting in impaired branch point recognition and SF1/mBBP binding. Separating the branch point from the overlapping purine-rich C element, by insertion of only 20 nucleotides, liberated repression and fully restored splicing to the intrinsically strong env 3′ splice site. This indicated that the cis-acting element might repress splicing by blocking the recognition of essential splice site signals. Conclusions: The foamy viral purine-rich C element regulates splicing by suppressing the branch point recognition of the strongest env splice acceptor. It is essential for the formation of unspliced gag and singly spliced pol transcripts. KW - splice regulation KW - foamy viruses KW - branch point KW - purine-rich element KW - RNA export Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157614 VL - 14 IS - 10 ER - TY - JOUR A1 - Moremi, Nyambura A1 - Claus, Heike A1 - Vogel, Ulrich A1 - Mshana, Stephen E. T1 - Surveillance of surgical site infections by Pseudomonas aeruginosa and strain characterization in Tanzanian hospitals does not provide proof for a role of hospital water plumbing systems in transmission JF - Antimicrobial Resistance and Infection Control N2 - Background The role of hospital water systems in the development of Pseudomonas aeruginosa (P. aeruginosa) surgical site infections (SSIs) in low-income countries is barely studied. This study characterized P. aeruginosa isolates from patients and water in order to establish possible epidemiological links. Methods: Between December 2014 and September 2015, rectal and wound swabs, and water samples were collected in the frame of active surveillance for SSIs in the two Tanzanian hospitals. Typing of P. aeruginosa was done by multi-locus sequence typing. Results: Of 930 enrolled patients, 536 were followed up, of whom 78 (14.6%, 95% CI; 11.6–17.5) developed SSIs. P. aeruginosa was found in eight (14%) of 57 investigated wounds. Of the 43 water sampling points, 29 were positive for P. aeruginosa. However, epidemiological links to wound infections were not confirmed. The P. aeruginosa carriage rate on admission was 0.9% (8/930). Of the 363 patients re-screened upon discharge, four (1.1%) possibly acquired P. aeruginosa during hospitalization. Wound infections of the three of the eight P. aeruginosa SSIs were caused by a strain of the same sequence type (ST) as the one from intestinal carriage. Isolates from patients were more resistant to antibiotics than water isolates. Conclusions: The P. aeruginosa SSI rate was low. There was no evidence for transmission from tap water. Not all P. aeruginosa SSI were proven to be endogenous, pointing to other routes of transmission. KW - Tanzania KW - P. aeruginosa KW - surgical site infection KW - water microbiology Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158168 VL - 6 IS - 56 ER - TY - JOUR A1 - Moremi, Nyambura A1 - Claus, Heike A1 - Vogel, Ulrich A1 - Mshana, Stephen E. T1 - Faecal carriage of CTX-M extended-spectrum beta-lactamase-producing Enterobacteriaceae among street children dwelling in Mwanza city, Tanzania JF - PLoS ONE N2 - Background Data on ESBL carriage of healthy people including children are scarce especially in developing countries. We analyzed the prevalence and genotypes of ESBL-producing Enterobacteriaceae (EPE) in Tanzanian street children with rare contact to healthcare facilities but significant interactions with the environment, animals and other people. Methodology/ Principle findings Between April and July 2015, stool samples of 107 street children, who live in urban Mwanza were analyzed for EPE. Intestinal carriage of EPE was found in 34 (31.8%, 95% CI; 22.7–40.3) children. Of the 36 isolates from 34 children, 30 (83.3%) were Escherichia coli (E. coli) and six Klebsiella pneumoniae (K. pneumoniae). Out of 36 isolates, 36 (100%), 35 (97%), 25 (69%) and 16 (44%) were resistant to tetracycline, trimethoprim-sulfamethoxazole, ciprofloxacin and gentamicin, respectively. Beta-lactamase genes and the multilocus sequence types of E. coli and K. pneumoniae were characterized. ESBL gene bla\(_{CTX-M-15}\) was detected in 75% (27/36) of ESBL isolates. Sequence types (STs) 131, 10, 448 and 617 were the most prevalent in E. coli. Use of local herbs (OR: 3.5, 95% CI: 1.51–8.08, P = 0.003) and spending day and night on streets (OR: 3.6, 95% CI: 1.44–8.97, P = 0.005) were independent predictors of ESBL carriage. Conclusions/ Significance We observed a high prevalence of bla\(_{CTX-M-15}\) in EPE collected from street children in Tanzania. Detection of E. coli STs 131, 10, 38 and 648, which have been observed worldwide in animals and people, highlights the need for multidisciplinary approaches to understand the epidemiology and drivers of antimicrobial resistance in low-income countries. KW - Tanzania KW - children KW - Enterobacteriaceae KW - ESBL Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170331 VL - 12 IS - 9 ER - TY - JOUR A1 - Morbach, Caroline A1 - Wagner, Martin A1 - Güntner, Stefan A1 - Malsch, Carolin A1 - Oezkur, Mehmet A1 - Wood, David A1 - Kotseva, Kornelia A1 - Leyh, Rainer A1 - Ertl, Georg A1 - Karmann, Wolfgang A1 - Heuschmann, Peter U A1 - Störk, Stefan T1 - Heart failure in patients with coronary heart disease: Prevalence, characteristics and guideline implementation - Results from the German EuroAspire IV cohort JF - BMC Cardiovascular Disorders N2 - Background: Adherence to pharmacotherapeutic treatment guidelines in patients with heart failure (HF) is of major prognostic importance, but thorough implementation of guidelines in routine care remains insufficient. Our aim was to investigate prevalence and characteristics of HF in patients with coronary heart disease (CHD), and to assess the adherence to current HF guidelines in patients with HF stage C, thus identifying potential targets for the optimization of guideline implementation. Methods: Patients from the German sample of the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EuroAspire) IV survey with a hospitalization for CHD within the previous six to 36 months providing valid data on echocardiography as well as on signs and symptoms of HF were categorized into stages of HF: A, prevalence of risk factors for developing HF; B, asymptomatic but with structural heart disease; C, symptomatic HF. A Guideline Adherence Indicator (GAI-3) was calculated for patients with reduced (≤40%) left ventricular ejection fraction (HFrEF) as number of drugs taken per number of drugs indicated; beta-blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, and mineralocorticoid receptor antagonists (MRA) were considered. Results: 509/536 patients entered analysis. HF stage A was prevalent in n = 20 (3.9%), stage B in n = 264 (51.9%), and stage C in n = 225 (44.2%) patients; 94/225 patients were diagnosed with HFrEF (42%). Stage C patients were older, had a longer duration of CHD, and a higher prevalence of arterial hypertension. Awareness of pre-diagnosed HF was low (19%). Overall GAI-3 of HFrEF patients was 96.4% with a trend towards lower GAI-3 in patients with lower LVEF due to less thorough MRA prescription. Conclusions: In our sample of CHD patients, prevalence of HF stage C was high and a sizable subgroup suffered from HFrEF. Overall, pharmacotherapy was fairly well implemented in HFrEF patients, although somewhat worse in patients with more reduced ejection fraction. Two major targets were identified possibly suited to further improve the implementation of HF guidelines: 1) increase patients´ awareness of diagnosis and importance of HF; and 2) disseminate knowledge about the importance of appropriately implementing the use of mineralocorticoid receptor antagonists. Trial registration: This is a cross-sectional analysis of a non-interventional study. Therefore, it was not registered as an interventional trial. KW - awareness KW - heart failure KW - pharmacotherapy KW - coronary artery disease KW - coronary heart disease KW - euroaspire KW - guideline adherence KW - guideline implementation KW - mineralocorticoid antagonist KW - preserved ejection fraction Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157738 VL - 17 IS - 108 ER - TY - JOUR A1 - Mitjans, M. A1 - Begemann, M. A1 - Ju, A. A1 - Dere, E. A1 - Wüstefeld, L. A1 - Hofer, S. A1 - Hassouna, I. A1 - Balkenhol, J. A1 - Oliveira, B. A1 - Van der Auwera, S. A1 - Tammer, R. A1 - Hammerschmidt, K. A1 - Völzke, H. A1 - Homuth, G. A1 - Cecconi, F. A1 - Chowdhury, K. A1 - Grabe, H. A1 - Frahm, J. A1 - Boretius, S. A1 - Dandekar, T. A1 - Ehrenreich, H. T1 - Sexual dimorphism of \(AMBRA1\)-related autistic features in human and mouse JF - Translational Psychiatry N2 - \(Ambra1\) is linked to autophagy and neurodevelopment. Heterozygous \(Ambra1\) deficiency induces autism-like behavior in a sexually dimorphic manner. Extraordinarily, autistic features are seen in female mice only, combined with stronger Ambra1 protein reduction in brain compared to males. However, significance of \(AMBRA1\) for autistic phenotypes in humans and, apart from behavior, for other autism-typical features, namely early brain enlargement or increased seizure propensity, has remained unexplored. Here we show in two independent human samples that a single normal \(AMBRA1\) genotype, the intronic SNP rs3802890-AA, is associated with autistic features in women, who also display lower \(AMBRA1\) mRNA expression in peripheral blood mononuclear cells relative to female GG carriers. Located within a non-coding RNA, likely relevant for mRNA and protein interaction, rs3802890 (A versus G allele) may affect its stability through modification of folding, as predicted by \(in\) \(silico\) analysis. Searching for further autism-relevant characteristics in \(Ambra1^{+/−}\) mice, we observe reduced interest of female but not male mutants regarding pheromone signals of the respective other gender in the social intellicage set-up. Moreover, altered pentylentetrazol-induced seizure propensity, an \(in\) \(vivo\) readout of neuronal excitation–inhibition dysbalance, becomes obvious exclusively in female mutants. Magnetic resonance imaging reveals mild prepubertal brain enlargement in both genders, uncoupling enhanced brain dimensions from the primarily female expression of all other autistic phenotypes investigated here. These data support a role of \(AMBRA1/Ambra1\) partial loss-of-function genotypes for female autistic traits. Moreover, they suggest \(Ambra1\) heterozygous mice as a novel multifaceted and construct-valid genetic mouse model for female autism. KW - biology KW - clinical genetics KW - molecular neuroscience Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173782 VL - 2017 IS - 7 ER - TY - JOUR A1 - Min, Chul-Hee A1 - Goth, F. A1 - Lutz, P. A1 - Bentmann, H. A1 - Kang, B.Y. A1 - Cho, B.K. A1 - Werner, J. A1 - Chen, K.-S. A1 - Assaad, F. A1 - Reinert, F. T1 - Matching DMFT calculations with photoemission spectra of heavy fermion insulators: universal properties of the near-gap spectra of SmB\(_{6}\) JF - Scientific Reports N2 - Paramagnetic heavy fermion insulators consist of fully occupied quasiparticle bands inherent to Fermi liquid theory. The gap emergence below a characteristic temperature is the ultimate sign of coherence for a many-body system, which in addition can induce a non-trivial band topology. Here, we demonstrate a simple and efficient method to compare a model study and an experimental result for heavy fermion insulators. The temperature dependence of the gap formation in both local moment and mixed valence regimes is captured within the dynamical mean field (DMFT) approximation to the periodic Anderson model (PAM). Using the topological coherence temperature as the scaling factor and choosing the input parameter set within the mixed valence regime, we can unambiguously link the theoretical energy scales to the experimental ones. As a particularly important result, we find improved consistency between the scaled DMFT density of states and the photoemission near-gap spectra of samarium hexaboride (SmB\(_{6}\)). KW - SmB\(_{6}\) KW - heavy fermion insulators KW - dynamical mean field KW - samarium hexaboride KW - near-gap spectra Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170328 VL - 7 IS - 11980 ER - TY - JOUR A1 - Milanos, Sinem A1 - Elsharif, Shaimaa A. A1 - Janzen, Dieter A1 - Buettner, Andrea A1 - Villmann, Carmen T1 - Metabolic Products of Linalool and Modulation of GABA\(_{A}\) Receptors JF - Frontiers in Chemistry N2 - Terpenoids are major subcomponents in aroma substances which harbor sedative physiological potential. We have demonstrated that various monoterpenoids such as the acyclic linalool enhance GABAergic currents in an allosteric manner in vitro upon overexpression of inhibitory α1β2 GABA\(_{A}\) receptors in various expression systems. However, in plants or humans, i.e., following intake via inhalation or ingestion, linalool undergoes metabolic modifications including oxygenation and acetylation, which may affect the modulatory efficacy of the generated linalool derivatives. Here, we analyzed the modulatory potential of linalool derivatives at α1β2γ2 GABA\(_{A}\) receptors upon transient overexpression. Following receptor expression control, electrophysiological recordings in a whole cell configuration were used to determine the chloride influx upon co-application of GABA EC\(_{10-30}\) together with the modulatory substance. Our results show that only oxygenated linalool metabolites at carbon 8 positively affect GABAergic currents whereas derivatives hydroxylated or carboxylated at carbon 8 were rather ineffective. Acetylated linalool derivatives resulted in non-significant changes of GABAergic currents. We can conclude that metabolism of linalool reduces its positive allosteric potential at GABAA receptors compared to the significant potentiation effects of the parent molecule linalool itself. KW - Cys-loop receptor KW - GABA\(_{A}\) KW - receptor KW - linalool KW - linalyl acetate KW - oxygenation KW - patch-clamp Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170779 VL - 5 IS - 46 ER - TY - JOUR A1 - Mielich-Süss, Benjamin A1 - Wagner, Rabea M. A1 - Mietrach, Nicole A1 - Hertlein, Tobias A1 - Marincola, Gabriella A1 - Ohlsen, Knut A1 - Geibel, Sebastian A1 - Lopez, Daniel T1 - Flotillin scaffold activity contributes to type VII secretion system assembly in Staphylococcus aureus JF - PLoS Pathogens N2 - Scaffold proteins are ubiquitous chaperones that promote efficient interactions between partners of multi-enzymatic protein complexes; although they are well studied in eukaryotes, their role in prokaryotic systems is poorly understood. Bacterial membranes have functional membrane microdomains (FMM), a structure homologous to eukaryotic lipid rafts. Similar to their eukaryotic counterparts, bacterial FMM harbor a scaffold protein termed flotillin that is thought to promote interactions between proteins spatially confined to the FMM. Here we used biochemical approaches to define the scaffold activity of the flotillin homolog FloA of the human pathogen Staphylococcus aureus, using assembly of interacting protein partners of the type VII secretion system (T7SS) as a case study. Staphylococcus aureus cells that lacked FloA showed reduced T7SS function, and thus reduced secretion of T7SS-related effectors, probably due to the supporting scaffold activity of flotillin. We found that the presence of flotillin mediates intermolecular interactions of T7SS proteins. We tested several small molecules that interfere with flotillin scaffold activity, which perturbed T7SS activity in vitro and in vivo. Our results suggest that flotillin assists in the assembly of S. aureus membrane components that participate in infection and influences the infective potential of this pathogen. KW - flotillin KW - scaffold protein KW - Staphylococcus aureus KW - type VII secretion system Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170035 VL - 13 IS - 11 ER - TY - JOUR A1 - Middelhoff, Frederike T1 - Literary autozoographies: contextualizing species life in german animal autobiography JF - Humanities N2 - What does it mean to take animal autobiography seriously and how can we account for the representation of life-narrating animals? The article investigates animal autobiographies as ‘literary autozoographies’, drawing attention to both the generic contexts and the epistemological premises of these texts. Adopting a double-bind approach stemming from autobiographical research as well as cultural animal studies, the article focuses on early nineteenth-century equine autozoographies from the German-speaking tradition. These texts are discussed exemplarily in relation to the parameters of fictional autobiographies, before they are contextualized with historical discourses regarding horses in natural history and so-called ‘horse-science’. Due to the fact that the poetics and aesthetics of the genre are modeled on the templates of factual autobiographies, the article argues that literary autozoographies can be read as fictional autobiographies as well as meta-auto/biographical discourse undermining autobiographical conventions. Furthermore, it shows that literary autozoography and zoology share a common historical and ideological epistemology accounting for the representation of animals in both fields. Literary autozoographies thus participate in the negotiation and production of species-specific knowledge. Reading Life of the Mecklenburg Mare Amante (1804), Life of a Job Horse (1807) and Life of a Worn-Out Hack (1819) alongside equine-centric discourses around 1800, the article demonstrates in what ways these texts can be regarded as part of a regime of knowledge attributing emotions and cognitive capacities to horses, while simultaneously arguing for humane treatment on the basis of interspecies homologies. KW - animal autobiography KW - fictional autobiography KW - meta-autobiography KW - life writing KW - contextualist narratology KW - cultural and literary animal studies KW - poetics of knowledge KW - zoology KW - natural history KW - equine autozoography KW - horse-science Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-198052 SN - 2076-0787 VL - 6 IS - 2 PB - MDPI ER - TY - JOUR A1 - Mende, Daniel R. A1 - Letunic, Ivica A1 - Huerta-Cepas, Jaime A1 - Li, Simone S. A1 - Forslund, Kristoffer A1 - Sunagawa, Shinichi A1 - Bork, Peer T1 - proGenomes: a resource for consistent functional and taxonomic annotations of prokaryotic genomes JF - Nucleic Acids Research N2 - The availability of microbial genomes has opened many new avenues of research within microbiology. This has been driven primarily by comparative genomics approaches, which rely on accurate and consistent characterization of genomic sequences. It is nevertheless difficult to obtain consistent taxonomic and integrated functional annotations for defined prokaryotic clades. Thus, we developed proGenomes, a resource that provides user-friendly access to currently 25 038 high-quality genomes whose sequences and consistent annotations can be retrieved individually or by taxonomic clade. These genomes are assigned to 5306 consistent and accurate taxonomic species clusters based on previously established methodology. proGenomes also contains functional information for almost 80 million protein-coding genes, including a comprehensive set of general annotations and more focused annotations for carbohydrate-active enzymes and antibiotic resistance genes. Additionally, broad habitat information is provided for many genomes. All genomes and associated information can be downloaded by user-selected clade or multiple habitat-specific sets of representative genomes. We expect that the availability of high-quality genomes with comprehensive functional annotations will promote advances in clinical microbial genomics, functional evolution and other subfields of microbiology. proGenomes is available at http://progenomes.embl.de. KW - biology KW - genomic sequence KW - prokaryotic clade KW - proGenomes KW - habitat information KW - taxonomic description KW - genome collection KW - comparative genomics KW - genomics research Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171987 VL - 45 IS - D1 ER - TY - JOUR A1 - Memmel, Simon A1 - Sisario, Dmitri A1 - Zöller, Caren A1 - Fiedler, Vanessa A1 - Katzer, Astrid A1 - Heiden, Robin A1 - Becker, Nicholas A1 - Eing, Lorenz A1 - Ferreira, Fábio L.R. A1 - Zimmermann, Heiko A1 - Sauer, Markus A1 - Flentje, Michael A1 - Sukhorukov, Vladimir L. A1 - Djuzenova, Cholpon S. T1 - Migration pattern, actin cytoskeleton organization and response to PI3K-, mTOR-, and Hsp90-inhibition of glioblastoma cells with different invasive capacities JF - Oncotarget N2 - High invasiveness and resistance to chemo- and radiotherapy of glioblastoma multiforme (GBM) make it the most lethal brain tumor. Therefore, new treatment strategies for preventing migration and invasion of GBM cells are needed. Using two different migration assays, Western blotting, conventional and super-resolution (dSTORM) fluorescence microscopy we examine the effects of the dual PI3K/mTOR-inhibitor PI-103 alone and in combination with the Hsp90 inhibitor NVP-AUY922 and/or irradiation on the migration, expression of marker proteins, focal adhesions and F-actin cytoskeleton in two GBM cell lines (DK-MG and SNB19) markedly differing in their invasive capacity. Both lines were found to be strikingly different in morphology and migration behavior. The less invasive DK-MG cells maintained a polarized morphology and migrated in a directionally persistent manner, whereas the highly invasive SNB19 cells showed a multipolar morphology and migrated randomly. Interestingly, a single dose of 2 Gy accelerated wound closure in both cell lines without affecting their migration measured by single-cell tracking. PI-103 inhibited migration of DK-MG (p53 wt, PTEN wt) but not of SNB19 (p53 mut, PTEN mut) cells probably due to aberrant reactivation of the PI3K pathway in SNB19 cells treated with PI-103. In contrast, NVP-AUY922 exerted strong anti-migratory effects in both cell lines. Inhibition of cell migration was associated with massive morphological changes and reorganization of the actin cytoskeleton. Our results showed a cell line-specific response to PI3K/mTOR inhibition in terms of GBM cell motility. We conclude that anti-migratory agents warrant further preclinical investigation as potential therapeutics for treatment of GBM. KW - chemotherapy KW - glioblastoma multiforme KW - migration KW - treatment Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170719 VL - 8 IS - 28 ER - TY - JOUR A1 - Meininger, Susanne A1 - Blum, Carina A1 - Schamel, Martha A1 - Barralet, Jake E. A1 - Ignatius, Anita A1 - Gbureck, Uwe T1 - Phytic acid as alternative setting retarder enhanced biological performance of dicalcium phosphate cement in vitro JF - Scientific Reports N2 - Dicalcium phosphate cement preparation requires the addition of setting retarders to meet clinical requirements regarding handling time and processability. Previous studies have focused on the influence of different setting modifiers on material properties such as mechanical performance or injectability, while ignoring their influence on biological cement properties as they are used in low concentrations in the cement pastes and the occurrence of most compounds in human tissues. Here, analyses of both material and biological behavior were carried out on samples with common setting retardants (citric acid, sodium pyrophosphate, sulfuric acid) and novel (phytic acid). Cytocompatibility was evaluated by in vitro tests with osteoblastic (hFOB 1.19) and osteoclastic (RAW 264.7) cells. We found cytocompatibility was better for sodium pyrophosphate and phytic acid with a three-fold cell metabolic activity by WST-1 test, whereas samples set with citric acid showed reduced cell number as well as cell activity. The compressive strength (CS) of cements formed with phytic acid (CS = 13 MPa) were nearly equal to those formed with citric acid (CS = 15 MPa) and approximately threefold higher than for other setting retardants. Due to a proven cytocompatibility and high mechanical strength, phytic acid seems to be a candidate replacement setting retardant for dicalcium phosphate cements. KW - implants KW - biomedical materials KW - dicalcium phosphate cement KW - phytic acid Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171047 VL - 7 IS - 558 ER - TY - JOUR A1 - Maurer, Jana A1 - Hupp, Sabrina A1 - Bischoff, Carolin A1 - Foertsch, Christina A1 - Mitchell, Timothy J. A1 - Chakraborty, Trinad A1 - Iliev, Asparouh I. T1 - Distinct neurotoxicity profile of listeriolysin O from \(Listeria\) \(monocytogenes\) JF - Toxins N2 - Cholesterol-dependent cytolysins (CDCs) are protein toxins that originate from Gram-positive bacteria and contribute substantially to their pathogenicity. CDCs bind membrane cholesterol and build prepores and lytic pores. Some effects of the toxins are observed in non-lytic concentrations. Two pathogens, \(Streptococcus\) \(pneumoniae\) and \(Listeria\) \(monocytogenes\), cause fatal bacterial meningitis, and both produce toxins of the CDC family—pneumolysin and listeriolysin O, respectively. It has been demonstrated that pneumolysin produces dendritic varicosities (dendrite swellings) and dendritic spine collapse in the mouse neocortex, followed by synaptic loss and astrocyte cell shape remodeling without elevated cell death. We utilized primary glial cultures and acute mouse brain slices to examine the neuropathological effects of listeriolysin O and to compare it to pneumolysin with identical hemolytic activity. In cultures, listeriolysin O permeabilized cells slower than pneumolysin did but still initiated non-lytic astrocytic cell shape changes, just as pneumolysin did. In an acute brain slice culture system, listeriolysin O produced dendritic varicosities in an NMDA-dependent manner but failed to cause dendritic spine collapse and cortical astrocyte reorganization. Thus, listeriolysin O demonstrated slower cell permeabilization and milder glial cell remodeling ability than did pneumolysin and lacked dendritic spine collapse capacity but exhibited equivalent dendritic pathology. KW - medicine KW - listeriolysin O KW - meningitis KW - acute slices KW - variocosities KW - dendritic spines Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172130 VL - 9 IS - 1 ER - TY - JOUR A1 - Maierhofer, Anna A1 - Flunkert, Julia A1 - Dittrich, Marcus A1 - Müller, Tobias A1 - Schindler, Detlev A1 - Nanda, Indrajit A1 - Haaf, Thomas T1 - Analysis of global DNA methylation changes in primary human fibroblasts in the early phase following X-ray irradiation JF - PLoS ONE N2 - Epigenetic alterations may contribute to the generation of cancer cells in a multi-step process of tumorigenesis following irradiation of normal body cells. Primary human fibroblasts with intact cell cycle checkpoints were used as a model to test whether X-ray irradiation with 2 and 4 Gray induces direct epigenetic effects (within the first cell cycle) in the exposed cells. ELISA-based fluorometric assays were consistent with slightly reduced global DNA methylation and hydroxymethylation, however the observed between-group differences were usually not significant. Similarly, bisulfite pyrosequencing of interspersed LINE-1 repeats and centromeric α-satellite DNA did not detect significant methylation differences between irradiated and non-irradiated cultures. Methylation of interspersed ALU repeats appeared to be slightly increased (one percentage point; p = 0.01) at 6 h after irradiation with 4 Gy. Single-cell analysis showed comparable variations in repeat methylation among individual cells in both irradiated and control cultures. Radiation-induced changes in global repeat methylation, if any, were much smaller than methylation variation between different fibroblast strains. Interestingly, α-satellite DNA methylation positively correlated with gestational age. Finally, 450K methylation arrays mainly targeting genes and CpG islands were used for global DNA methylation analysis. There were no detectable methylation differences in genic (promoter, 5' UTR, first exon, gene body, 3' UTR) and intergenic regions between irradiated and control fibroblast cultures. Although we cannot exclude minor effects, i.e. on individual CpG sites, collectively our data suggest that global DNA methylation remains rather stable in irradiated normal body cells in the early phase of DNA damage response. KW - DNA methylation KW - fibroblasts KW - methylation KW - alu elements KW - DNA damage KW - epigenetics KW - cancer treatment Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170895 VL - 12 IS - 5 ER - TY - JOUR A1 - Lüningschrör, Patrick A1 - Binotti, Beyenech A1 - Dombert, Benjamin A1 - Heimann, Peter A1 - Perez-Lara, Angel A1 - Slotta, Carsten A1 - Thau-Habermann, Nadine A1 - von Collenberg, Cora R. A1 - Karl, Franziska A1 - Damme, Markus A1 - Horowitz, Arie A1 - Maystadt, Isabelle A1 - Füchtbauer, Annette A1 - Füchtbauer, Ernst-Martin A1 - Jablonka, Sibylle A1 - Blum, Robert A1 - Üçeyler, Nurcan A1 - Petri, Susanne A1 - Kaltschmidt, Barbara A1 - Jahn, Reinhard A1 - Kaltschmidt, Christian A1 - Sendtner, Michael T1 - Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease JF - Nature Communications N2 - Autophagy-mediated degradation of synaptic components maintains synaptic homeostasis but also constitutes a mechanism of neurodegeneration. It is unclear how autophagy of synaptic vesicles and components of presynaptic active zones is regulated. Here, we show that Pleckstrin homology containing family member 5 (Plekhg5) modulates autophagy of synaptic vesicles in axon terminals of motoneurons via its function as a guanine exchange factor for Rab26, a small GTPase that specifically directs synaptic vesicles to preautophagosomal structures. Plekhg5 gene inactivation in mice results in a late-onset motoneuron disease, characterized by degeneration of axon terminals. Plekhg5-depleted cultured motoneurons show defective axon growth and impaired autophagy of synaptic vesicles, which can be rescued by constitutively active Rab26. These findings define a mechanism for regulating autophagy in neurons that specifically targets synaptic vesicles. Disruption of this mechanism may contribute to the pathophysiology of several forms of motoneuron disease. KW - autophagy KW - synaptic vesicles KW - Pleckstrin homology containing family member 5 (Plekhg5) KW - regulation KW - motoneuron disease Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170048 VL - 8 IS - 678 ER - TY - JOUR A1 - Lutz, Manfred B. A1 - Strobl, Herbert A1 - Schuler, Gerold A1 - Romani, Nikolaus T1 - GM-CSF monocyte-derived cells and Langerhans cells as part of the dendritic cell family JF - Frontiers in Immunology N2 - Dendritic cells (DCs) and macrophages (Mph) share many characteristics as components of the innate immune system. The criteria to classify the multitude of subsets within the mononuclear phagocyte system are currently phenotype, ontogeny, transcription patterns, epigenetic adaptations, and function. More recently, ontogenetic, transcriptional, and proteomic research approaches uncovered major developmental differences between Flt3L-dependent conventional DCs as compared with Mphs and monocyte-derived DCs (MoDCs), the latter mainly generated in vitro from murine bone marrow-derived DCs (BM-DCs) or human CD14\(^{+}\) peripheral blood monocytes. Conversely, in vitro GM-CSF-dependent monocyte-derived Mphs largely resemble MoDCs whereas tissue-resident Mphs show a common embryonic origin from yolk sac and fetal liver with Langerhans cells (LCs). The novel ontogenetic findings opened discussions on the terminology of DCs versus Mphs. Here, we bring forward arguments to facilitate definitions of BM-DCs, MoDCs, and LCs. We propose a group model of terminology for all DC subsets that attempts to encompass both ontogeny and function. KW - macrophages KW - dendritic cells KW - GM-CSF KW - monocytes KW - Langerhans cells Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158730 VL - 8 IS - 1388 ER - TY - JOUR A1 - Lukeš, Tomáš A1 - Glatzová, Daniela A1 - Kvíčalová, Zuzana A1 - Levet, Florian A1 - Benda, Aleš A1 - Letschert, Sebastian A1 - Sauer, Markus A1 - Brdička, Tomáš A1 - Lasser, Theo A1 - Cebecauer, Marek T1 - Quantifying protein densities on cell membranes using super-resolution optical fluctuation imaging JF - Nature Communications N2 - Quantitative approaches for characterizing molecular organization of cell membrane molecules under physiological and pathological conditions profit from recently developed super-resolution imaging techniques. Current tools employ statistical algorithms to determine clusters of molecules based on single-molecule localization microscopy (SMLM) data. These approaches are limited by the ability of SMLM techniques to identify and localize molecules in densely populated areas and experimental conditions of sample preparation and image acquisition. We have developed a robust, model-free, quantitative clustering analysis to determine the distribution of membrane molecules that excels in densely labeled areas and is tolerant to various experimental conditions, i.e. multiple-blinking or high blinking rates. The method is based on a TIRF microscope followed by a super-resolution optical fluctuation imaging (SOFI) analysis. The effectiveness and robustness of the method is validated using simulated and experimental data investigating nanoscale distribution of CD4 glycoprotein mutants in the plasma membrane of T cells. KW - biology KW - fluorescence imaging KW - imaging the immune system KW - super-resolution microscopy Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172993 VL - 8 ER - TY - JOUR A1 - Lueken, U A1 - Kuhn, M A1 - Yang, Y A1 - Straube, B A1 - Kircher, T A1 - Wittchen, H-U A1 - Pfleiderer, B A1 - Arolt, V A1 - Wittmann, A A1 - Ströhle, A A1 - Weber, H A1 - Reif, A A1 - Domschke, K A1 - Deckert, J A1 - Lonsdorf, TB T1 - Modulation of defensive reactivity by GLRB allelic variation: converging evidence from an intermediate phenotype approach JF - Translational Psychiatry N2 - Representing a phylogenetically old and very basic mechanism of inhibitory neurotransmission, glycine receptors have been implicated in the modulation of behavioral components underlying defensive responding toward threat. As one of the first findings being confirmed by genome-wide association studies for the phenotype of panic disorder and agoraphobia, allelic variation in a gene coding for the glycine receptor beta subunit (GLRB) has recently been associated with increased neural fear network activation and enhanced acoustic startle reflexes. On the basis of two independent healthy control samples, we here aimed to further explore the functional significance of the GLRB genotype (rs7688285) by employing an intermediate phenotype approach. We focused on the phenotype of defensive system reactivity across the levels of brain function, structure, and physiology. Converging evidence across both samples was found for increased neurofunctional activation in the (anterior) insular cortex in GLRB risk allele carriers and altered fear conditioning as a function of genotype. The robustness of GLRB effects is demonstrated by consistent findings across different experimental fear conditioning paradigms and recording sites. Altogether, findings provide translational evidence for glycine neurotransmission as a modulator of the brain’s evolutionary old dynamic defensive system and provide further support for a strong, biologically plausible candidate intermediate phenotype of defensive reactivity. As such, glycine-dependent neurotransmission may open up new avenues for mechanistic research on the etiopathogenesis of fear and anxiety disorders. KW - glycine receptor beta subunit KW - neural fear network activation KW - intermediate phenotype approach KW - defensive system reactivity Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-182381 VL - 7 IS - e1227 ER - TY - JOUR A1 - Ludwigs, Markus A1 - Amann, Hannah T1 - Klausur im Kommunalrecht: Ausschluss aus dem Gemeinderat JF - JURA - Juristische Ausbildung N2 - Kein Abstract verfügbar. KW - Kommunalrecht KW - Klausur KW - Gemeinderat Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195589 SN - 1612-7021 SN - 0170-1452 N1 - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. VL - 39 IS - 9 SP - 1106 EP - 1115 ER - TY - JOUR A1 - Lohse, Christian A1 - Bock, Andreas A1 - Maiellaro, Isabella A1 - Hannawacker, Annette A1 - Schad, Lothar R. A1 - Lohse, Martin J. A1 - Bauer, Wolfgang R. T1 - Experimental and mathematical analysis of cAMP nanodomains JF - PLoS ONE N2 - In their role as second messengers, cyclic nucleotides such as cAMP have a variety of intracellular effects. These complex tasks demand a highly organized orchestration of spatially and temporally confined cAMP action which should be best achieved by compartmentalization of the latter. A great body of evidence suggests that cAMP compartments may be established and maintained by cAMP degrading enzymes, e.g. phosphodiesterases (PDEs). However, the molecular and biophysical details of how PDEs can orchestrate cAMP gradients are entirely unclear. In this paper, using fusion proteins of cAMP FRET-sensors and PDEs in living cells, we provide direct experimental evidence that the cAMP concentration in the vicinity of an individual PDE molecule is below the detection limit of our FRET sensors (<100nM). This cAMP gradient persists in crude cytosol preparations. We developed mathematical models based on diffusion-reaction equations which describe the creation of nanocompartments around a single PDE molecule and more complex spatial PDE arrangements. The analytically solvable equations derived here explicitly determine how the capability of a single PDE, or PDE complexes, to create a nanocompartment depend on the cAMP degradation rate, the diffusive mobility of cAMP, and geometrical and topological parameters. We apply these generic models to our experimental data and determine the diffusive mobility and degradation rate of cAMP. The results obtained for these parameters differ by far from data in literature for free soluble cAMP interacting with PDE. Hence, restricted cAMP diffusion in the vincinity of PDE is necessary to create cAMP nanocompartments in cells. KW - fluorescence resonance energy transfer KW - yellow fluorescent protein KW - radii KW - adenylyl cyclase signaling cascade KW - cell fusion KW - cytosol KW - isoproterenol KW - absorption KW - cyclic nucleotides such as cyclic adenosine monophosphate Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170972 VL - 12 IS - 4 ER - TY - JOUR A1 - Liu, Han A1 - Chen, Chunhai A1 - Gao, Zexia A1 - Min, Jiumeng A1 - Gu, Yongming A1 - Jian, Jianbo A1 - Jiang, Xiewu A1 - Cai, Huimin A1 - Ebersberger, Ingo A1 - Xu, Meng A1 - Zhang, Xinhui A1 - Chen, Jianwei A1 - Luo, Wei A1 - Chen, Boxiang A1 - Chen, Junhui A1 - Liu, Hong A1 - Li, Jiang A1 - Lai, Ruifang A1 - Bai, Mingzhou A1 - Wei, Jin A1 - Yi, Shaokui A1 - Wang, Huanling A1 - Cao, Xiaojuan A1 - Zhou, Xiaoyun A1 - Zhao, Yuhua A1 - Wei, Kaijian A1 - Yang, Ruibin A1 - Liu, Bingnan A1 - Zhao, Shancen A1 - Fang, Xiaodong A1 - Schartl, Manfred A1 - Qian, Xueqiao A1 - Wang, Weimin T1 - The draft genome of blunt snout bream (Megalobrama amblycephala) reveals the development of intermuscular bone and adaptation to herbivorous diet JF - GigaScience N2 - The blunt snout bream Megalobrama amblycephala is the economically most important cyprinid fish species. As an herbivore, it can be grown by eco-friendly and resource-conserving aquaculture. However, the large number of intermuscular bones in the trunk musculature is adverse to fish meat processing and consumption. As a first towards optimizing this aquatic livestock, we present a 1.116-Gb draft genome of M. amblycephala, with 779.54 Mb anchored on 24 linkage groups. Integrating spatiotemporal transcriptome analyses, we show that intermuscular bone is formed in the more basal teleosts by intramembranous ossification and may be involved in muscle contractibility and coordinating cellular events. Comparative analysis revealed that olfactory receptor genes, especially of the beta type, underwent an extensive expansion in herbivorous cyprinids, whereas the gene for the umami receptor T1R1 was specifically lost in M. amblycephala. The composition of gut microflora, which contributes to the herbivorous adaptation of M. amblycephala, was found to be similar to that of other herbivores. As a valuable resource for the improvement of M. amblycephala livestock, the draft genome sequence offers new insights into the development of intermuscular bone and herbivorous adaptation. KW - Megalobrama amblycephala KW - whole genome KW - herbivorous diet KW - intermuscular bone KW - transcriptome KW - gut microflora Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170844 VL - 6 IS - 7 ER - TY - JOUR A1 - Lischke, Alexander A1 - Herpertz, Sabine C. A1 - Berger, Christoph A1 - Domes, Gregor A1 - Gamer, Matthias T1 - Divergent effects of oxytocin on (para-)limbic reactivity to emotional and neutral scenes in females with and without borderline personality disorder JF - Social Cognitive and Affective Neuroscience N2 - Borderline personality disorder (BPD) patients’ hypersensitivity for emotionally relevant stimuli has been suggested be due to abnormal activity and connectivity in (para-)limbic and prefrontal brain regions during stimulus processing. The neuropeptide oxytocin has been shown to modulate activity and functional connectivity in these brain regions, thereby optimizing the processing of emotional and neutral stimuli. To investigate whether oxytocin would be capable of attenuating BPD patients’ hypersensitivity for such stimuli, we recorded brain activity and gaze behavior during the processing of complex scenes in 51 females with and 48 without BPD after intranasal application of either oxytocin or placebo. We found divergent effects of oxytocin on BPD and healthy control (HC) participants’ (para-)limbic reactivity to emotional and neutral scenes: Oxytocin decreased amygdala and insula reactivity in BPD participants but increased it in HC participants, indicating an oxytocin-induced normalization of amygdala and insula activity during scene processing. In addition, oxytocin normalized the abnormal coupling between amygdala activity and gaze behavior across all scenes in BPD participants. Overall, these findings suggest that oxytocin may be capable of attenuating BPD patients’ hypersensitivity for complex scenes, irrespective of their valence. KW - psychology KW - oxytocin KW - amygdala KW - insula KW - borderline personality disorder KW - functional magnetic resonance imaging KW - eye tracking Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173309 VL - 12 IS - 11 ER - TY - JOUR A1 - Lindert, J. M. A1 - Pozzorini, S. A1 - Boughezal, R. A1 - Campbell, J. M. A1 - Denner, A. A1 - Dittmaier, S. A1 - Gehrmann-De Ridder, A. A1 - Gehrmann, T. A1 - Glover, N. A1 - Huss, A. A1 - Kallweit, S. A1 - Maierhöfer, P. A1 - Mangano, M. L. A1 - Morgan, T. A. A1 - Mück, A. A1 - Petriello, F. A1 - Salam, G. P. A1 - Schönherr, M. A1 - Williams, C. T1 - Precise predictions for \(V+\)jets dark matter backgrounds JF - European Physical Journal C N2 - High-energy jets recoiling against missing transverse energy (MET) are powerful probes of dark matter at the LHC. Searches based on large MET signatures require a precise control of the \({Z(ν\overline{ν})}+\) jet background in the signal region. This can be achieved by taking accurate data in control regions dominated by \(Z(ℓ^+ℓ^−)+\) jet, \(W(ℓν)+\) jet and \(γ+\) jet production, and extrapolating to the \({Z(ν\overline{ν})}+\) jet background by means of precise theoretical predictions. In this context, recent advances in perturbative calculations open the door to significant sensitivity improvements in dark matter searches. In this spirit, we present a combination of state-of-the-art calculations for all relevant \(V+\) jets processes, including throughout NNLO QCD corrections and NLO electroweak corrections supplemented by Sudakov logarithms at two loops. Predictions at parton level are provided together with detailed recommendations for their usage in experimental analyses based on the reweighting of Monte Carlo samples. Particular attention is devoted to the estimate of theoretical uncertainties in the framework of dark matter searches, where subtle aspects such as correlations across different \(V+\) jet processes play a key role. The anticipated theoretical uncertainty in the \({Z(ν\overline{ν})}+\) jet background is at the few percent level up to the TeV range. KW - Physics KW - High energy physics KW - High-energy jets KW - Dark matter Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172555 VL - 77 ER - TY - JOUR A1 - Lilla, Nadine A1 - Füllgraf, Hannah A1 - Stetter, Christian A1 - Köhler, Stefan A1 - Ernestus, Ralf-Ingo A1 - Westermaier, Thomas T1 - First Description of Reduced Pyruvate Dehydrogenase Enzyme Activity Following Subarachnoid Hemorrhage (SAH) JF - Frontiers in Neuroscience N2 - Object: Several previous studies reported metabolic derangements and an accumulation of metabolic products in the early phase of experimental subarachnoid hemorrhage (SAH), which may contribute to secondary brain damage. This may be a result of deranged oxygen utilization due to enzymatic dysfunction in aerobic glucose metabolism. This study was performed to investigate, if pyruvate dehydrogenase enzyme (PDH) is affected in its activity giving further hints for a derangement of oxidative metabolism. Methods: Eighteen male Sprague-Dawley rats were randomly assigned to one of two experimental groups (n = 9): (1) SAH induced by the endovascular filament model and (2) sham-operated controls. Mean arterial blood pressure (MABP), intracranial pressure (ICP), and local cerebral blood flow (LCBF; laser-Doppler flowmetry) were continuously monitored from 30 min before until 3 h after SAH. Thereafter, the animals were sacrificed and PDH activity was measured by ELISA. Results: PDH activity was significantly reduced in animals subjected to SAH compared to controls. Conclusion: The results of this study demonstrate for the first time a reduction of PDH activity following SAH, independent of supply of substrates and may be an independent factor contributing to a derangement of oxidative metabolism, failure of oxygen utilization, and secondary brain damage. KW - secondary brain damage KW - aerobic glycolysis KW - CBF KW - metabolism KW - PDH KW - SAH Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157636 VL - 11 IS - 37 ER -