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 -