TY - JOUR A1 - Apostolidis -Gkarpousis, Alexandros A1 - Koch, Christian T1 - Convergences et divergences dans les articles «Langage» de Louis de Jaucourt et «Langue» de Nicolas Beauzée. Une comparaison de deux articles de l’Encyclopédie de Diderot et D’Alembert JF - promptus - Würzburger Beiträge zur Romanistik N2 - The two articles of «Langage» and «Langue», published in 1765 in the 9th volume of the great French Encyclopédie by Diderot and D’Alembert, treat some essential philosophical questions on the human ability of communication with linguistic signs. Nevertheless, as the two authors Jaucourt and Beauzée did not share completely identic points of view, the comparative lecture of both articles reveals a complementary perspective, particularly relating to the origin of language as a divine gift or humans’ creation for communicative needs. A further aspect of divergence concerns the textual composition of the article « Langage » as a structured informative text, and the article « Langue » as a long and freely composed writing including personal remarks by the author. The following article deals with the potential of approaches to the Encyclopédie in modern linguistics, concretely demonstrated in the comparative analysis of these two articles. KW - Encyclopédie KW - Lumières KW - philosophie du langage KW - Beauzée KW - Jaucourt Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172843 SN - 2510-2613 VL - 3 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Sheikhbahaei, Sara A1 - Jones, Krystyna M. A1 - Javadi, Mehrbod S. A1 - Solnes, Lilja B. A1 - Ross, Ashley E. A1 - Allaf, Mohamad E. A1 - Pienta, Kenneth J. A1 - Lapa, Constantin A1 - Buck, Andreas K. A1 - Higuchi, Takahiro A1 - Pomper, Martin G. A1 - Gorin, Micheal A. A1 - Rowe, Steven P. T1 - Patterns of uptake of prostate-specific membrane antigen (PSMA)-targeted \(^{18}\)F-DCFPyL in peripheral ganglia JF - Annals of Nuclear Medicine N2 - Objective: Radiotracers targeting prostate-specific membrane antigen (PSMA) have increasingly been recognized as showing uptake in a number of normal structures, anatomic variants, and non-prostate-cancer pathologies. We aimed to explore the frequency and degree of uptake in peripheral ganglia in patients undergoing PET with the PSMA-targeted agent \(^{18}\)F-DCFPyL. Methods: A total of 98 patients who underwent \(^{18}\)F-DCFPyL PET/CT imaging were retrospectively analyzed. This included 76 men with prostate cancer (PCa) and 22 patients with renal cell carcinoma (RCC; 13 men, 9 women). Scans were evaluated for uptake in the cervical, stellate, celiac, lumbar and sacral ganglia. Maximum standardized uptake value corrected to body weight (SUV\(_{max}\)), and maximum standardized uptake value corrected to lean body mass (SUL\(_{max}\)) were recorded for all ganglia with visible uptake above background. Ganglia-to-background ratios were calculated by dividing the SUV\(_{max}\) and SUL\(_{max}\) values by the mean uptake in the ascending aorta (Aortamean) and the right gluteus muscle (Gluteusmean). Results: Overall, 95 of 98 (96.9%) patients demonstrated uptake in at least one of the evaluated peripheral ganglia. With regard to the PCa cohort, the most frequent sites of radiotracer accumulation were lumbar ganglia (55/76, 72.4%), followed by the cervical ganglia (51/76, 67.1%). Bilateral uptake was found in the majority of cases [lumbar 44/55 (80%) and cervical 30/51 (58.8%)]. Additionally, discernible radiotracer uptake was recorded in 50/76 (65.8%) of the analyzed stellate ganglia and in 45/76 (59.2%) of the celiac ganglia, whereas only 5/76 (6.6%) of the sacral ganglia demonstrated \(^{18}\)F-DCFPyL accumulation. Similar findings were observed for patients with RCC, with the most frequent locations of radiotracer uptake in both the lumbar (20/22, 90.9%) and cervical ganglia (19/ 22, 86.4%). No laterality preference was found in mean PSMA-ligand uptake for either the PCa or RCC cohorts. Conclusion: As PSMA-targeted agents become more widely disseminated, the patterns of uptake in structures that are not directly relevant to patients’ cancers must be understood. This is the first systematic evaluation of the uptake of \(^{18}\)F-DCFPyL in ganglia demonstrating a general trend with a descending frequency of radiotracer accumulation in lumbar, cervical, stellate, celiac, and sacral ganglia. The underlying biology that leads to variability of PSMA-targeted radiotracers in peripheral ganglia is not currently understood, but may provide opportunities for future research. KW - 18F-DCFPL KW - Positronen-Emissions-Tomografie KW - Prostata KW - PSMA KW - Ganglia KW - Pitfall KW - PET KW - Tracer KW - Radiotracer KW - Imaging pitfalls KW - Prostate Cancer Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166971 SN - 0914-7187 VL - 31 IS - 9 ER - TY - JOUR A1 - Schindler, Julia A1 - Richter, Tobias A1 - Eyßer, Carolin T1 - Mood moderates the effect of self-generation during learning JF - Frontline Learning Research N2 - Generating information, compared to reading, improves learning and enhances long-term retention of the learned content. This so-called generation effect has been demonstrated repeatedly for recall and recognition of single words. However, before adopting generating as a learning strategy in educational contexts, conditions moderating the effect need to be identified. This study investigated the impact of positive and negative mood states on the generation effect with short expository texts. According to the dual-force framework (Fiedler, Nickel, Asbeck, & Pagel, 2003), positive mood should facilitate generation by enhancing creative knowledge-based top-down processing (assimilation). Negative mood, however, should facilitate learning in the read-condition by enhancing critical stimulus-driven bottom-up processing (accommodation). In contrast to our expectations, we found no general generation effect but an overall learning advantage of read compared to generated texts. However, a significant interaction of learning condition and mood indicates that learners in a better mood recall generated texts better than learners in a more negative mood, whereas no mood effect was found when the texts were read. The results of the present study partially support the predictions of the dual-force framework and are discussed in the context of recent theoretical approaches to the generation effect. KW - mood states KW - generation effect KW - learning with expository texts Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159282 VL - 5 IS - 4 ER - TY - JOUR A1 - Koessler, Juergen A1 - Schwarz, Michaela A1 - Weber, Katja A1 - Etzel, Julia A1 - Koessler, Angela A1 - Boeck, Markus A1 - Kobsar, Anna T1 - The role of adenosine diphosphate mediated platelet responsiveness for the stability of platelet integrity in citrated whole blood under ex vivo conditions JF - PLoS ONE N2 - Background: Platelets are important for effective hemostasis and considered to be involved in pathophysiological processes, e.g. in cardiovascular diseases. Platelets provided for research or for therapeutic use are frequently separated from citrated whole blood (WB) stored for different periods of time. Although functionally intact platelets are required, the stability of platelet integrity, e.g. adenosine diphosphate (ADP) mediated responsiveness, has never been thoroughly investigated in citrated WB under ex vivo conditions. Objectives: Platelet integrity was evaluated at different time points in citrated WB units, collected from healthy donors and stored for 5 days at ambient temperature. The analysis included the measurement of activation markers, of induced light transmission aggregometry and of purinergic receptor expression or function. Inhibitory pathways were explored by determination of basal vasodilator-stimulated phosphoprotein (VASP)-phosphorylation, intracellular cyclic nucleotide levels and the content of phosphodiesterase 5A. Fresh peripheral blood (PB) samples served as controls. Results: On day 5 of storage, thrombin receptor activating peptide-6 (TRAP-6) stimulated CD62P expression and fibrinogen binding were comparable to PB samples. ADP induced aggregation continuously decreased during storage. Purinergic receptor expression remained unchanged, whereas the P2Y1 activity progressively declined in contrast to preserved P2Y12 and P2X1 function. Inhibitory pathways were unaffected except for a slight elevation of VASP phosphorylation at Ser\(^{239}\) on day 5. Conclusion: After 5 days of storage in citrated WB, platelet responsiveness to TRAP-6 is sufficiently maintained. However, ADP-mediated platelet integrity is more sensitive to deterioration, especially after storage for more than 2 days. Decreasing ADP-induced aggregation is particularly caused by the impairment of the purinergic receptor P2Y1 activity. These characteristics should be considered in the use of platelets from stored citrated WB for experimental or therapeutic issues. KW - fibrinogen KW - phosphorylation KW - platelets KW - blood KW - specimen storage KW - flow cytometry Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159879 VL - 12 IS - 11 ER - TY - JOUR A1 - Mülek, Melanie A1 - Seefried, Lothar A1 - Genest, Franca A1 - Högger, Petra T1 - Distribution of constituents and metabolites of maritime pine bark extract (Pycnogenol\(^{®}\)) into serum, blood cells, and synovial fluid of patients with severe osteoarthritis: a randomized controlled trial JF - Nutrients N2 - The present randomized controlled study aimed to investigate the in vivo distribution of constituents or metabolites of the standardized maritime pine bark extract Pycnogenol\(^{®}\). Thirty-three patients with severe osteoarthritis scheduled for a knee arthroplasty were randomized to receive either 200 mg per day Pycnogenol\(^{®}\) (P+) or no treatment (Co) over three weeks before surgery. Serum, blood cells, and synovial fluid samples were analyzed using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization (LC-ESI/MS/MS). Considerable interindividual differences were observed indicating pronounced variability of the polyphenol pharmacokinetics. Notably, the highest polyphenol concentrations were not detected in serum. Catechin and taxifolin primarily resided within the blood cells while the microbial catechin metabolite δ-(3,4-dihydroxy-phenyl)-γ-valerolactone, ferulic, and caffeic acid were mainly present in synovial fluid samples. Taxifolin was detected in serum and synovial fluid exclusively in the P+ group. Likewise, no ferulic acid was found in serum samples of the Co group. Calculating ratios of analyte distribution in individual patients revealed a simultaneous presence of some polyphenols in serum, blood cells, and/or synovial fluid only in the P+ group. This is the first evidence that polyphenols distribute into the synovial fluid of patients with osteoarthritis which supports rationalizing the results of clinical efficacy studies. KW - osteoarthritis KW - randomized controlled study KW - LC-ESI/MS/MS KW - human KW - pine bark extract KW - polyphenols Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159862 VL - 9 IS - 5 ER - TY - JOUR A1 - Schuhmann, Michael K. A1 - Fluri, Felix T1 - Effects of fullerenols on mouse brain microvascular endothelial cells JF - International Journal of Molecular Sciences N2 - Fullerenols, water-soluble C60-fullerene derivatives, have been shown to exert neuroprotective effects in vitro and in vivo, most likely due to their capability to scavenge free radicals. However, little is known about the effects of fullerenols on the blood–brain barrier (BBB), especially on cerebral endothelial cells under inflammatory conditions. Here, we investigated whether the treatment of primary mouse brain microvascular endothelial cells with fullerenols impacts basal and inflammatory blood–brain barrier (BBB) properties in vitro. While fullerenols (1, 10, and 100 µg/mL) did not change transendothelial electrical resistance under basal and inflammatory conditions, 100 µg/mL of fullerenol significantly reduced erk1/2 activation and resulted in an activation of NFκB in an inflammatory milieu. Our findings suggest that fullerenols might counteract oxidative stress via the erk1/2 and NFκB pathways, and thus are able to protect microvascular endothelial cells under inflammatory conditions. KW - mouse brain microvascular endothelial cell cultur KW - adhesion molecules KW - fullerenes KW - blood-brain barrier KW - inflammation KW - tight junctions Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158072 SN - 1422-0067 VL - 18 IS - 8 ER - TY - JOUR A1 - Born, Dennis-Peter A1 - Zinner, Christoph A1 - Sperlich, Billy T1 - The mucosal immune function is not compromised during a period of high-intensity interval training. Is it time to reconsider an old assumption? JF - Frontiers in Physiology N2 - Purpose: The aim of the study was to evaluate the mucosal immune function and circadian variation of salivary cortisol, Immunoglobin-A (sIgA) secretion rate and mood during a period of high-intensity interval training (HIIT) compared to long-slow distance training (LSD). Methods: Recreational male runners (n = 28) completed nine sessions of either HIIT or LSD within 3 weeks. The HIIT involved 4 × 4 min of running at 90–95% of maximum heart rate interspersed with 3 min of active recovery while the LSD comprised of continuous running at 70–75% of maximum heart rate for 60–80 min. The psycho-immunological stress-response was investigated with a full daily profile of salivary cortisol and immunoglobin-A (sIgA) secretion rate along with the mood state on a baseline day, the first and last day of training and at follow-up 4 days after the last day of training. Before and after the training period, each athlete's running performance and peak oxygen uptake (V·O\(_{2peak}\)) was determined with an incremental exercise test. Results: The HIIT resulted in a longer time-to-exhaustion (P = 0.02) and increased V·O\(_{2peak}\) compared to LSD (P = 0.01). The circadian variation of sIgA secretion rate showed highest values in the morning immediately after waking up followed by a decrease throughout the day in both groups (P < 0.05). With HIIT, the wake-up response of sIgA secretion rate was higher on the last day of training (P < 0.01) as well as the area under the curve (AUC\(_{G}\)) higher on the first and last day of training and follow-up compared to the LSD (P = 0.01). Also the AUC\(_{G}\) for the sIgA secretion rate correlated with the increase in V·O\(_{2peak}\) and running performance. The AUC\(_{G}\) for cortisol remained unaffected on the first and last day of training but increased on the follow-up day with both, HIIT and LSD (P < 0.01). Conclusion: The increased sIgA secretion rate with the HIIT indicates no compromised mucosal immune function compared to LSD and shows the functional adaptation of the mucosal immune system in response to the increased stress and training load of nine sessions of HIIT. KW - high-volume training KW - periodization KW - circadian rhythm KW - cortisol KW - diurnal profile KW - endurance KW - immunoglobin-A Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158025 VL - 8 IS - 485 ER - TY - JOUR A1 - Wallmann-Sperlich, Birgit A1 - Bipp, Tanja A1 - Bucksch, Jens A1 - Froboese, Ingo T1 - Who uses height-adjustable desks? - Sociodemographic, health-related, and psycho-social variables of regular users JF - International Journal of Behavioral Nutrition and Physical Activity N2 - Background: Sit-to-stand height-adjustable desks (HAD) may promote workplace standing, as long as workers use them on a regular basis. The aim of this study was to investigate (i) how common HAD in German desk-based workers are, and how frequently HADs are used, (ii) to identify sociodemographic, health-related, and psycho-social variables of workday sitting including having a HAD, and (iii) to analyse sociodemographic, health-related, and psycho-social variables of users and non-users of HADs. Methods: A cross-sectional sample of 680 participants (51.9% men; 41.0 ± 13.1 years) in a desk-based occupation was interviewed by telephone about their occupational sitting and standing proportions, having and usage of a HAD, and answered questions concerning psycho-social variables of occupational sitting. The proportion of workday sitting was calculated for participants having an HAD (n = 108) and not-having an HAD (n = 573), as well as for regular users of HAD (n = 54), and irregular/non-users of HAD (n = 54). Linear regressions were conducted to calculate associations between socio-demographic, health-related, psychosocial variables and having/not having an HAD, and the proportion of workday sitting. Logistic regressions were executed to examine the association of mentioned variables and participants’ usage of HADs. Results: Sixteen percent report that they have an HAD, and 50% of these report regular use of HAD. Having an HAD is not a correlate of the proportion of workday sitting. Further analysis restricted to participants having available a HAD highlights that only the ‘perceived advantages of sitting less’ was significantly associated with HAD use in the fully adjusted model (OR 1.75 [1.09; 2.81], p < 0.05). Conclusions: The present findings indicate that accompanying behavioral action while providing an HAD is promising to increase the regular usage of HAD. Hence, future research needs to address the specificity of behavioral actions in order to enhance regular HAD use, and needs to give more fundamental insights into these associations. KW - cross-sectional KW - office-workers KW - desk-based KW - height-adjustable desk KW - occupational sitting and physical activity questionnaire KW - sitting time KW - correlates KW - natural approach Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157888 VL - 14 IS - 26 ER - TY - JOUR A1 - Wang Ip, Chi A1 - Klaus, Laura-Christin A1 - Karikari, Akua A. A1 - Visanji, Naomi P. A1 - Brotchie, Jonathan M. A1 - Lang, Anthony E. A1 - Volkmann, Jens A1 - Koprich, James B. T1 - AAV1/2-induced overexpression of A53T-α-synuclein in the substantia nigra results in degeneration of the nigrostriatal system with Lewy-like pathology and motor impairment: a new mouse model for Parkinson’s disease JF - Acta Neuropathologica Communications N2 - α-Synuclein is a protein implicated in the etiopathogenesis of Parkinson’s disease (PD). AAV1/2-driven overexpression of human mutated A53T-α-synuclein in rat and monkey substantia nigra (SN) induces degeneration of nigral dopaminergic neurons and decreases striatal dopamine and tyrosine hydroxylase (TH). Given certain advantages of the mouse, especially it being amendable to genetic manipulation, translating the AAV1/2-A53T α-synuclein model to mice would be of significant value. AAV1/2-A53T α-synuclein or AAV1/2 empty vector (EV) at a concentration of 5.16 x 10\(^{12}\) gp/ml were unilaterally injected into the right SN of male adult C57BL/6 mice. Post-mortem examinations included immunohistochemistry to analyze nigral α-synuclein, Ser129 phosphorylated α-synuclein and TH expression, striatal dopamine transporter (DAT) levels by autoradiography and dopamine levels by high performance liquid chromatography. At 10 weeks, in AAV1/2-A53T α-synuclein mice there was a 33% reduction in TH+ dopaminergic nigral neurons (P < 0.001), 29% deficit in striatal DAT binding (P < 0.05), 38% and 33% reductions in dopamine (P < 0.001) and DOPAC (P < 0.01) levels and a 60% increase in dopamine turnover (homovanilic acid/dopamine ratio; P < 0.001). Immunofluorescence showed that the AAV1/2-A53T α-synuclein injected mice had widespread nigral and striatal expression of vector-delivered A53T-α-synuclein. Concurrent staining with human PD SN samples using gold standard histological methodology for Lewy pathology detection by proteinase K digestion and application of specific antibody raised against human Lewy body α-synuclein (LB509) and Ser129 phosphorylated α-synuclein (81A) revealed insoluble α-synuclein aggregates in AAV1/2-A53T α-synuclein mice resembling Lewy-like neurites and bodies. In the cylinder test, we observed significant paw use asymmetry in the AAV1/2-A53T α-synuclein group when compared to EV controls at 5 and 9 weeks post injection (P < 0.001; P < 0.05). These data show that unilateral injection of AAV1/2-A53T α-synuclein into the mouse SN leads to persistent motor deficits, neurodegeneration of the nigrostriatal dopaminergic system and development of Lewy-like pathology, thereby reflecting clinical and pathological hallmarks of human PD. KW - Lewy-like pathology KW - Parkinson’s disease KW - α-synuclein KW - A53T KW - mutation KW - mouse model Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159429 VL - 5 IS - 11 ER - TY - JOUR A1 - Römer, Daniela A1 - Bollazzi, Martin A1 - Roces, Flavio T1 - Carbon dioxide sensing in an obligate insect-fungus symbiosis: CO\(_{2}\) preferences of leaf-cutting ants to rear their mutualistic fungus JF - PLoS ONE N2 - Defense against biotic or abiotic stresses is one of the benefits of living in symbiosis. Leaf-cutting ants, which live in an obligate mutualism with a fungus, attenuate thermal and desiccation stress of their partner through behavioral responses, by choosing suitable places for fungus-rearing across the soil profile. The underground environment also presents hypoxic (low oxygen) and hypercapnic (high carbon dioxide) conditions, which can negatively influence the symbiont. Here, we investigated whether workers of the leaf-cutting ant Acromyrmex lundii use the CO\(_{2}\) concentration as an orientation cue when selecting a place to locate their fungus garden, and whether they show preferences for specific CO\(_{2}\) concentrations. We also evaluated whether levels preferred by workers for fungus-rearing differ from those selected for themselves. In the laboratory, CO\(_{2}\) preferences were assessed in binary choices between chambers with different CO\(_{2}\) concentrations, by quantifying number of workers in each chamber and amount of relocated fungus. Leaf-cutting ants used the CO\(_{2}\) concentration as a spatial cue when selecting places for fungus-rearing. A. lundii preferred intermediate CO\(_{2}\) levels, between 1 and 3%, as they would encounter at soil depths where their nest chambers are located. In addition, workers avoided both atmospheric and high CO\(_{2}\) levels as they would occur outside the nest and at deeper soil layers, respectively. In order to prevent fungus desiccation, however, workers relocated fungus to high CO\(_{2}\) levels, which were otherwise avoided. Workers’ CO\(_{2}\) preferences for themselves showed no clear-cut pattern. We suggest that workers avoid both atmospheric and high CO\(_{2}\) concentrations not because they are detrimental for themselves, but because of their consequences for the symbiotic partner. Whether the preferred CO\(_{2}\) concentrations are beneficial for symbiont growth remains to be investigated, as well as whether the observed preferences for fungus-rearing influences the ants’ decisions where to excavate new chambers across the soil profile. KW - fungi KW - nesting habits KW - carbon dioxide KW - ants KW - social systems KW - humidity KW - symbiosis KW - fungal physiology Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159561 VL - 12 IS - 4 ER - TY - JOUR A1 - Hergovits, Sabine A1 - Mais, Christine A1 - Haan, Claude A1 - Costa-Pereira, Ana P. A1 - Hermanns, Heike M. T1 - Oncostatin M induces RIG-I and MDA5 expression and enhances the double-stranded RNA response in fibroblasts JF - Journal of Cellular and Molecular Medicine N2 - Interleukin (IL)-6-type cytokines have no direct antiviral activity; nevertheless, they display immune-modulatory functions. Oncostatin M (OSM), a member of the IL-6 family, has recently been shown to induce a distinct number of classical interferon stimulated genes (ISG). Most of them are involved in antigen processing and presentation. However, induction of retinoic acid-inducible gene (RIG)-I-like receptors (RLR) has not been investigated. Here we report that OSM has the capability to induce the expression of the DExD/H-Box RNA helicases RIG-I and melanoma differentiation antigen 5 (MDA5) as well as of the transcription factors interferon regulatory factor (IRF)1, IRF7 and IRF9 in primary fibroblasts. Induction of the helicases depends on tyrosine as well as serine phosphorylation of STAT1. Moreover, we could show that the OSM-induced STAT1 phosphorylation is predominantly counter-regulated by a strong STAT3-dependent SOCS3 induction, as Stat3 as well as Socs3 knock-down results in an enhanced and prolonged helicase and IRF expression. Other factors involved in regulation of STAT1 or IRF1 activity, like protein tyrosine phosphatase, non-receptor type 2 (PTPN2), promyelocytic leukaemia protein (PML) or small ubiquitin-related modifier 1 (SUMO1), play a minor role in OSM-mediated induction of RLR. Remarkably, OSM and interferon-γ (IFN-γ) synergize to mediate transcription of RLR and pre-treatment of fibroblasts with OSM fosters the type I interferon production in response to a subsequent encounter with double-stranded RNA. Together, these findings suggest that the OSM-induced JAK/STAT1 signalling is implicated in virus protection of non-professional immune cells and may cooperate with interferons to enhance RLR expression in these cells. KW - oncostatin M KW - DExD/H-Box RNA helicase KW - RIG-I KW - STAT1 KW - innate immunity Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159558 VL - 21 IS - 11 ER - TY - JOUR A1 - Klughammer, Johanna A1 - Dittrich, Marcus A1 - Blom, Jochen A1 - Mitesser, Vera A1 - Vogel, Ulrich A1 - Frosch, Matthias A1 - Goesmann, Alexander A1 - Müller, Tobias A1 - Schoen, Christoph T1 - Comparative genome sequencing reveals within-host genetic changes in Neisseria meningitidis during invasive disease JF - PLoS ONE N2 - Some members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanism called phase variation. In line with the hypothesis that phase variation evolved as an adaptation to colonize diverse hosts, computational comparisons of all 27 to date completely sequenced and annotated meningococcal genomes retrieved from public databases showed that contingency genes are indeed enriched for genes involved in host interactions. To assess within-host genetic changes in meningococci, we further used ultra-deep whole-genome sequencing of throat-blood strain pairs isolated from four patients suffering from invasive meningococcal disease. We detected up to three mutations per strain pair, affecting predominantly contingency genes involved in type IV pilus biogenesis. However, there was not a single (set) of mutation(s) that could invariably be found in all four pairs of strains. Phenotypic assays further showed that these genetic changes were generally not associated with increased serum resistance, higher fitness in human blood ex vivo or differences in the interaction with human epithelial and endothelial cells in vitro. In conclusion, we hypothesize that virulence of meningococci results from accidental emergence of invasive variants during carriage and without within host evolution of invasive phenotypes during disease progression in vivo. KW - blood KW - comparative genomics KW - throat KW - genetic loci KW - Neisseria meningitidis KW - genomic libraries KW - genome sequencing KW - sequence assembly tools Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159547 VL - 12 IS - 1 ER - TY - JOUR A1 - Jessberger, Steffen A1 - Högger, Petra A1 - Genest, Franca A1 - Salter, Donald M. A1 - Seefried, Lothar T1 - Cellular pharmacodynamic effects of Pycnogenol\(^{®}\) in patients with severe osteoarthritis: a randomized controlled pilot study JF - BMC Complementary and Alternative Medicine N2 - Background: The standardized maritime pine bark extract (Pycnogenol\(^{®}\)) has previously shown symptom alleviating effects in patients suffering from moderate forms of knee osteoarthritis (OA). The cellular mechanisms for this positive impact are so far unknown. The purpose of the present randomized pilot controlled study was to span the knowledge gap between the reported clinical effects of Pycnogenol\(^{®}\) and its in vivo mechanism of action in OA patients. Methods: Thirty three patients with severe OA scheduled for a knee arthroplasty either received 100 mg of Pycnogenol\(^{®}\) twice daily or no treatment (control group) three weeks before surgery. Cartilage, synovial fluid and serum samples were collected during surgical intervention. Relative gene expression of cartilage homeostasis markers were analyzed in the patients' chondrocytes. Inflammatory and cartilage metabolism mediators were investigated in serum and synovial fluid samples. Results: The oral intake of Pycnogenol\(^{®}\) downregulated the gene expression of various cartilage degradation markers in the patients' chondrocytes, the decrease of MMP3, MMP13 and the pro-inflammatory cytokine IL1B were statistically significant (p ≤ 0.05). Additionally, protein concentrations of ADAMTS-5 in serum were reduced significantly (p ≤ 0.05) after three weeks intake of the pine bark extract. Conclusions: This is the first report about positive cellular effects of a dietary supplement on key catabolic and inflammatory markers in patients with severe OA. The results provide a rational basis for understanding previously reported clinical effects of Pycnogenol\(^{®}\) on symptom scores of patients suffering from OA. KW - maritime pine bark extract KW - qPCR KW - ADAMTS KW - cartilage KW - clinical study KW - osteoarthritis KW - Pycnogenol KW - serum KW - synovial fluid Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159532 VL - 17 IS - 537 ER - TY - JOUR A1 - Haertle, Larissa A1 - El Hajj, Nady A1 - Dittrich, Marcus A1 - Müller, Tobias A1 - Nanda, Indrajit A1 - Lehnen, Harald A1 - Haaf, Thomas T1 - Epigenetic signatures of gestational diabetes mellitus on cord blood methylation JF - Clinical Epigenetics N2 - Background: Intrauterine exposure to gestational diabetes mellitus (GDM) confers a lifelong increased risk for metabolic and other complex disorders to the offspring. GDM-induced epigenetic modifications modulating gene regulation and persisting into later life are generally assumed to mediate these elevated disease susceptibilities. To identify candidate genes for fetal programming, we compared genome-wide methylation patterns of fetal cord bloods (FCBs) from GDM and control pregnancies. Methods and results: Using Illumina’s 450K methylation arrays and following correction for multiple testing, 65 CpG sites (52 associated with genes) displayed significant methylation differences between GDM and control samples. Four candidate genes, ATP5A1, MFAP4, PRKCH, and SLC17A4, from our methylation screen and one, HIF3A, from the literature were validated by bisulfite pyrosequencing. The effects remained significant after adjustment for the confounding factors maternal BMI, gestational week, and fetal sex in a multivariate regression model. In general, GDM effects on FCB methylation were more pronounced in women with insulin-dependent GDM who had a more severe metabolic phenotype than women with dietetically treated GDM. Conclusions: Our study supports an association between maternal GDM and the epigenetic status of the exposed offspring. Consistent with a multifactorial disease model, the observed FCB methylation changes are of small effect size but affect multiple genes/loci. The identified genes are primary candidates for transmitting GDM effects to the next generation. They also may provide useful biomarkers for the diagnosis, prognosis, and treatment of adverse prenatal exposures. KW - fetal programming KW - insulin treatment KW - DNA methylation KW - fetal cord blood KW - gestational diabetes mellitus Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159459 VL - 9 IS - 28 ER - TY - JOUR A1 - Hillmann, Steffi A1 - Wiedmann, Silke A1 - Rücker, Viktoria A1 - Berger, Klaus A1 - Nabavi, Darius A1 - Bruder, Ingo A1 - Koennecke, Hans-Christian A1 - Seidel, Günter A1 - Misselwitz, Björn A1 - Janssen, Alfred A1 - Burmeister, Christoph A1 - Matthis, Christine A1 - Busse, Otto A1 - Hermanek, Peter A1 - Heuschmann, Peter Ulrich T1 - Stroke unit care in Germany: the German stroke registers study group (ADSR) JF - BMC Neurology N2 - Background: Factors influencing access to stroke unit (SU) care and data on quality of SU care in Germany are scarce. We investigated characteristics of patients directly admitted to a SU as well as patient-related and structural factors influencing adherence to predefined indicators of quality of acute stroke care across hospitals providing SU care. Methods: Data were derived from the German Stroke Registers Study Group (ADSR), a voluntary network of 9 regional registers for monitoring quality of acute stroke care in Germany. Multivariable logistic regression analyses were performed to investigate characteristics influencing direct admission to SU. Generalized Linear Mixed Models (GLMM) were used to estimate the influence of structural hospital characteristics (percentage of patients admitted to SU, year of SU-certification, and number of stroke and TIA patients treated per year) on adherence to predefined quality indicators. Results: In 2012 180,887 patients were treated in 255 hospitals providing certified SU care participating within the ADSR were included in the analysis; of those 82.4% were directly admitted to a SU. Ischemic stroke patients without disturbances of consciousness (p < .0001), an interval onset to admission time ≤3 h (p < .0001), and weekend admission (p < .0001) were more likely to be directly admitted to a SU. A higher proportion of quality indicators within predefined target ranges were achieved in hospitals with a higher proportion of SU admission (p = 0.0002). Quality of stroke care could be maintained even if certification was several years ago. Conclusions: Differences in demographical and clinical characteristics regarding the probability of SU admission were observed. The influence of structural characteristics on adherence to evidence-based quality indicators was low. KW - stroke register KW - stroke unit care KW - quality of health care KW - quality indicators Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159447 VL - 17 IS - 49 ER - TY - JOUR A1 - Bening, Constanze A1 - Hamouda, Khaled A1 - Oezkur, Mehmet A1 - Schimmer, Christoph A1 - Schade, Ina A1 - Gorski, Armin A1 - Aleksic, Ivan A1 - Leyh, Rainer T1 - Rapid deployment valve system shortens operative times for aortic valve replacement through right anterior minithoracotomy JF - Journal of Cardiothoracic Surgery N2 - Background: There is growing evidence from the literature that right anterior minithoracotomy aortic valve replacement (RAT-AVR) improves clinical outcome. However, increased cross clamp time is the strongest argument for surgeons not performing RAT-AVR. Rapid deployment aortic valve systems have the potential to decrease cross-clamp time and ease this procedure. We assessed clinical outcome of rapid deployment and conventional valves through RAT. Methods: Sixty-eight patients (mean age 76 ± 6 years, 32% females) underwent RAT-AVR between 9/2013 and 7/2015. According to the valve type implanted the patients were divided into two groups. In 43 patients (R-group; mean age 74.1 ± 6.6 years) a rapid deployment valve system (Edwards Intuity, Edwards Lifesciences Corp; Irvine, Calif) and in 25 patients (C-group; mean age 74.2 ± 6.6 years) a conventional stented biological aortic valve was implanted. Results: Aortic cross-clamp (42.1 ± 12 min vs. 68.3 ± 20.3 min; p < 0.001) and bypass time (80.4 ± 39.3 min vs. 106.6 ± 23.2 min; p = 0.001) were shorter in the rapid deployment group (R-group). We observed no differences in clinical outcome. Postoperative gradients (R-group: max gradient, 14.3 ± 8 mmHg vs. 15.5 ± 5 mmHg (C-group), mean gradient, 9.2 ± 1.7 mmHg (R-group) vs. 9.1 ± 2.3 mmHg (C-group) revealed no differences. However, larger prostheses were implanted in C-group (25 mm; IQR 23–27 mm vs. 23 mm; IQR 21–25; p = 0.009). Conclusions: Our data suggest that the rapid deployment aortic valve system reduced cross clamp and bypass time in patients undergoing RAT-AVR with similar hemodynamics as with larger size stented prosthesis. However, larger studies and long-term follow-up are mandatory to confirm our findings. KW - aortic valve replacement KW - minimally invasive surgery KW - heart valve prosthesis KW - biological rapid deployment aortic valve Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159439 VL - 12 IS - 27 ER - TY - JOUR A1 - Gilbert, Fabian A1 - Klein, Detlef A1 - Weng, Andreas Max A1 - Köstler, Herbert A1 - Schmitz, Benedikt A1 - Schmalzl, Jonas A1 - Böhm, Dirk T1 - Supraspinatus muscle elasticity measured with real time shear wave ultrasound elastography correlates with MRI spectroscopic measured amount of fatty degeneration JF - BMC Muscoskeletal Disorders N2 - Background: Fatty Degeneration (FD) of the rotator cuff muscles influences functional and anatomical outcome after rotator cuff repair. The MRI based estimation of fatty degeneration is the gold standard. There is some evidence that Ultrasound elastography (EUS) can detect local differences of tissue stiffness in muscles and tendons. Shear-wave elastography (SWE) was evaluated to determine the extent to which shear wave velocity was associated with measures of fatty degeneration. MRI-spectroscopic fat measurement was used as a reference to quantify the amount of fat in the muscle belly. Methods: Forty-two patients underwent SWE of the supraspinatus muscles at its thickest diameter. After ultrasound evaluation an MRI-spectroscopic fat measurement of the supraspinatus muscle was performed using the SPLASH-technique. A gel filled capsule was used to locate the measured area in the MRI. The values of shear wave velocity (SWV) measured with SWE and spectroscopic fat measurement were correlated statistically using Pearson’s correlation test. Results: Correlation of the fat amount measured with MRI-spectroscopy and the SWV measured with SWE was ρ =0.82. Spectroscopic measured fat ratio of the supraspinatus muscle ranged from 0% to 77.41% and SWV from 1.59 m/s to 5.32 m/s. In 4 patients no sufficient SWE could be performed, these individuals showed a larger diameter of the overlying soft tissue. SWV measured with SWE showed a good correlation with MRI spectroscopic fat amount of the supraspinatus muscle. Conclusion: These preliminary data suggest that SWE may be a sufficient tool in detecting and estimating the amount of fatty degeneration in the supraspinatus muscle in real time. Large overlying soft tissue may be a limitation in performing sufficient EUS. KW - shoulder surgery KW - rotator cuff KW - MRI KW - ultrasound KW - fatty degeneration Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159378 VL - 18 IS - 549 ER - TY - JOUR A1 - Becam, Jérôme A1 - Walter, Tim A1 - Burgert, Anne A1 - Schlegel, Jan A1 - Sauer, Markus A1 - Seibel, Jürgen A1 - Schubert-Unkmeir, Alexandra T1 - Antibacterial activity of ceramide and ceramide analogs against pathogenic Neisseria JF - Scientific Reports N2 - Certain fatty acids and sphingoid bases found at mucosal surfaces are known to have antibacterial activity and are thought to play a more direct role in innate immunity against bacterial infections. Herein, we analysed the antibacterial activity of sphingolipids, including the sphingoid base sphingosine as well as short-chain C\(_{6}\) and long-chain C\(_{16}\)-ceramides and azido-functionalized ceramide analogs against pathogenic Neisseriae. Determination of the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) demonstrated that short-chain ceramides and a ω-azido-functionalized C\(_{6}\)-ceramide were active against Neisseria meningitidis and N. gonorrhoeae, whereas they were inactive against Escherichia coli and Staphylococcus aureus. Kinetic assays showed that killing of N. meningitidis occurred within 2 h with ω–azido-C\(_{6}\)-ceramide at 1 X the MIC. Of note, at a bactericidal concentration, ω–azido-C\(_{6}\)-ceramide had no significant toxic effect on host cells. Moreover, lipid uptake and localization was studied by flow cytometry and confocal laser scanning microscopy (CLSM) and revealed a rapid uptake by bacteria within 5 min. CLSM and super-resolution fluorescence imaging by direct stochastic optical reconstruction microscopy demonstrated homogeneous distribution of ceramide analogs in the bacterial membrane. Taken together, these data demonstrate the potent bactericidal activity of sphingosine and synthetic short-chain ceramide analogs against pathogenic Neisseriae. KW - ceramide analogs KW - Neisseria KW - ceramide Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159367 VL - 7 ER - TY - JOUR A1 - Rodrigues, Johannes A1 - Ulrich, Natalie A1 - Mussel, Patrick A1 - Carlo, Gustavo A1 - Hewig, Johannes T1 - Measuring prosocial tendencies in Germany: sources of validity and reliablity of the revised prosocial tendency measure JF - Frontiers in Psychology N2 - The prosocial tendencies measure (PTM; Carlo and Randall, 2002) is a widely used measurement for prosocial tendencies in English speaking participants. This instrument distinguishes between six different types of prosocial tendencies that partly share some common basis, but also can be opposed to each other. To examine these constructs in Germany, a study with 1067 participants was conducted. The study investigated the structure of this German version of the PTM-R via exploratory factor analysis, confirmatory factor analysis, correlations with similar constructs in subsamples as well as via measurement invariance test concerning the original English version. The German translation showed a similar factor structure to the English version in exploratory factor analysis and in confirmatory factor analysis. Measurement invariance was found between the English and German language versions of the PTM and support for the proposed six-factor structure (altruistic, anonymous, compliant, dire, emotional and public prosocial behavior) was also found in confirmatory factor analysis. Furthermore, the expected interrelations of these factors of prosocial behavior tendencies were obtained. Finally, correlations of the prosocial behavior tendencies with validating constructs and behaviors were found. Thus, the findings stress the importance of seeing prosocial behavior not as a single dimension construct, but as a factored construct which now can also be assessed in German speaking participants. KW - measurement invariance KW - prosocial tendency measure KW - prosocial behavior KW - altruism KW - validation KW - German translation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159351 VL - 8 ER - TY - JOUR A1 - Zinner, Christoph A1 - Born, Dennis-Peter A1 - Sperlich, Billy T1 - Ischemic preconditioning does not alter performance in multidirectional high-intensity intermittent exercise JF - Frontiers in Physiology N2 - Purpose: Research dealing with ischemic preconditioning (IPC) has primarily focused on variables associated to endurance performance with little research about the acute responses of IPC on repeated multidirectional running sprint performance. Here we aimed to investigate the effects of IPC of the arms and the legs on repeated running sprint performance with changes-of-direction (COD) movements. Methods: Thirteen moderately-to-well-trained team-sport athletes (7 males; 6 females; age: 24 ± 2 years, size: 175 ± 8 cm, body mass: 67.9 ± 8.1 kg) performed 16 × 30 m all-out sprints (15 s rest) with multidirectional COD movements on a Speedcourt\(^{©}\) with IPC (3 × 5 min) of the legs (IPC\(_{leg}\); 240 mm Hg) or of the arms (remote IPC: IPC\(_{remote}\); 180–190 mm Hg) 45 min before the sprints and a control trial (CON; 20 mm Hg). Results: The mean (±SD) time for the 16 × 30 m multidirectional COD sprints was similar between IPC\(_{leg}\) (Mean t: 16.0 ± 1.8 s), IPC\(_{remote}\) (16.2 ± 1.7 s), and CON (16.0 ± 1.6 s; p = 0.50). No statistical differences in oxygen uptake (mean difference: 0%), heart rate (1.1%) nor muscle oxygen saturation of the vastus lateralis (4.7%) and biceps brachii (7.8%) between the three conditions were evident (all p > 0.05). Conclusions: IPC (3 × 5 min) of the legs (220 mm Hg) or arms (180–190 mm Hg; remote IPC) applied 45 min before 16 × 30 m repeated multidirectional running sprint exercise does not improve sprint performance, oxygen uptake, heart rate nor muscle oxygen saturation of the vastus lateralis muscle when compared to a control trial. KW - team sport KW - agility KW - change of direction KW - muscle oxygen saturation KW - near-infrared spectroscopy Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159348 VL - 8 ER -