@article{SchulzRuppertHermsetal.2017, author = {Schulz, Herbert and Ruppert, Ann-Kathrin and Herms, Stefan and Wolf, Christiane and Mirza-Schreiber, Nazanin and Stegle, Oliver and Czamara, Darina and Forstner, Andreas J. and Sivalingam, Sugirthan and Schoch, Susanne and Moebus, Susanne and P{\"u}tz, Benno and Hillmer, Axel and Fricker, Nadine and Vatter, Hartmut and M{\"u}ller-Myhsok, Bertram and N{\"o}then, Markus M. and Becker, Albert J. and Hoffmann, Per and Sander, Thomas and Cichon, Sven}, title = {Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus}, series = {Nature Communications}, volume = {8}, journal = {Nature Communications}, doi = {10.1038/s41467-017-01818-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173168}, year = {2017}, abstract = {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.}, language = {en} } @article{SchuhmannLanghauserKraftetal.2017, author = {Schuhmann, Michael K. and Langhauser, Friederike and Kraft, Peter and Kleinschnitz, Christoph}, title = {B cells do not have a major pathophysiologic role in acute ischemic stroke in mice}, series = {Journal of Neuroinflammation}, volume = {14}, journal = {Journal of Neuroinflammation}, number = {112}, doi = {10.1186/s12974-017-0890-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158155}, year = {2017}, abstract = {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.}, language = {en} } @article{SchuhmannGuthmannStolletal.2017, author = {Schuhmann, Michael K. and Guthmann, Josua and Stoll, Guido and Nieswandt, Bernhard and Kraft, Peter and Kleinschnitz, Christoph}, title = {Blocking of platelet glycoprotein receptor Ib reduces "thrombo-inflammation" in mice with acute ischemic stroke}, series = {Journal of Neuroinflammation}, volume = {14}, journal = {Journal of Neuroinflammation}, number = {18}, doi = {10.1186/s12974-017-0792-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157582}, year = {2017}, abstract = {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.}, language = {en} } @article{SchuhmannFluri2017, author = {Schuhmann, Michael K. and Fluri, Felix}, title = {Effects of fullerenols on mouse brain microvascular endothelial cells}, series = {International Journal of Molecular Sciences}, volume = {18}, journal = {International Journal of Molecular Sciences}, number = {8}, issn = {1422-0067}, doi = {10.3390/ijms18081783}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158072}, year = {2017}, abstract = {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.}, language = {en} } @article{SchubertKoernerLindauetal.2017, author = {Schubert, Lisa and K{\"o}rner, Anita and Lindau, Berit and Strack, Fritz and Topolinski, Sascha}, title = {Open-Minded Midwifes, Literate Butchers, and Greedy Hooligans - The Independent Contributions of Stereotype Valence and Consistency on Evaluative Judgments}, series = {Frontiers in Psychology}, volume = {8}, journal = {Frontiers in Psychology}, number = {1723}, doi = {10.3389/fpsyg.2017.01723}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170222}, year = {2017}, abstract = {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.}, language = {en} } @article{ScholzGuanNieberleretal.2017, author = {Scholz, Nicole and Guan, Chonglin and Nieberler, Matthias and Grotmeyer, Alexander and Maiellaro, Isabella and Gao, Shiqiang and Beck, Sebastian and Pawlak, Matthias and Sauer, Markus and Asan, Esther and Rothemund, Sven and Winkler, Jana and Pr{\"o}mel, Simone and Nagel, Georg and Langenhan, Tobias and Kittel, Robert J}, title = {Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons}, series = {eLife}, volume = {6}, journal = {eLife}, number = {e28360}, doi = {10.7554/eLife.28360}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170520}, year = {2017}, abstract = {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.}, language = {en} } @article{SchneiderNiklas2017, author = {Schneider, Wolfgang and Niklas, Frank}, title = {Intelligence and verbal short-term memory/working memory: their interrelationships from childhood to young adulthood and their impact on academic achievement}, series = {Journal of Intelligence}, volume = {5}, journal = {Journal of Intelligence}, number = {2}, issn = {2079-3200}, doi = {10.3390/jintelligence5020026}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-198004}, pages = {26}, year = {2017}, abstract = {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.}, language = {en} } @article{SchmidtSkafGavriletal.2017, author = {Schmidt, Marianne and Skaf, Josef and Gavril, Georgiana and Polednik, Christine and Roller, Jeanette and Kessler, Michael and Holzgrabe, Ulrike}, title = {The influence of Osmunda regalis root extract on head and neck cancer cell proliferation, invasion and gene expression}, series = {BMC Complementary and Alternative Medicine}, volume = {17}, journal = {BMC Complementary and Alternative Medicine}, number = {518}, doi = {10.1186/s12906-017-2009-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158704}, year = {2017}, abstract = {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.}, language = {en} } @article{SchmidFalterWeberetal.2017, author = {Schmid, Tobias and Falter, Lena and Weber, Sabine and M{\"u}ller, Nils and Molitor, Konstantin and Zeller, David and Weber-Steffens, Dorothea and Hehlgans, Thomas and Wajant, Harald and Mostb{\"o}ck, Sven and M{\"a}nnel, Daniela N.}, title = {Chronic inflammation increases the sensitivity of mouse Treg for TNFR2 costimulation}, series = {Frontiers in Immunology}, volume = {8}, journal = {Frontiers in Immunology}, doi = {10.3389/fimmu.2017.01471}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173259}, year = {2017}, abstract = {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 na{\"i}ve 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 na{\"i}ve 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 na{\"i}ve mice can lead to immune suppression \(in\) \(vivo\). These findings support the important role of TNFR2 for Treg cells in immune regulation.}, language = {en} } @article{SchindlerRichterEysser2017, author = {Schindler, Julia and Richter, Tobias and Eyßer, Carolin}, title = {Mood moderates the effect of self-generation during learning}, series = {Frontline Learning Research}, volume = {5}, journal = {Frontline Learning Research}, number = {4}, doi = {10.14786/flr.v5i4.296}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159282}, pages = {76-88}, year = {2017}, abstract = {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.}, language = {en} }