Untersuchungen zum Einfluss eines erhöhten Omega-3 Fettsäure Gehaltes auf das Lipidmediatorenprofil und zum anti-inflammatorischen Potential der murinen 15-Lipoxygenase, 17-Hydroxydocosapentaensäure und 10,17-Dihydroxydocosapentaensäure

Long-chain polyunsaturated omega-3 (n-3 PUFA) and omega-6 fatty acids are precursors of highly potent lipid mediators and metabolites, which are synthesized via cyclooxygenases, lipoxygenases (LOX), cytochrome P450 (CYP-450) or via autooxidation processes, and their synthesis can be modulated. The lipid mediator profile, especially of monohydroxy lipid metabolites hydroxyeicosatetraenoic acids, hydroxyeicosapentaenoic acids (HEPE) and hydroxydocosahexaenoic acids, and their modifications due to elevated n-3 PUFA levels was characterized in different organs in healthy mice. Furthermore the role of murine 15-lipoxygenase as well as omega-6 docosapentaenoic acid-derived 17-hydroxydocosapentaenoic acid (17-HDPAn-6) and 10,17-dihydroxydocosapentaenoic acid (10,17-HDPAn-6) in experimental colitis was investigated. In the first study, the profile of monohydroxy lipid metabolites in heart, lung, liver, colon, kidney, spleen and skeletal muscle of healthy wildtype mice were characterized using liquid chromatography–mass spectrometry. We found distinct characteristic lipid metabolite patterns in different organs. Elevated n-3 PUFA levels in transgenic fat-1 mice lead to increased formation of n-3 PUFA derived metabolites. Eicosapentaenoic acid – even though levels were low - was strongly utilized for formation of 12-HEPE in the lung as well as spleen and 9-HEPE and 18-HEPE in the other organs. The second study showed that higher n-3 PUFA levels could be achieved through dietary intervention with a diet enriched with n-3 PUFA compared to the fat-1 mouse model. This was reflected by increased levels of n-3 PUFA derived lipid metabolites. In plasma of mice fed with an enriched n-3 PUFA diet the lipid metabolite profile was dominated by metabolites derived from the LOX and CYP450 pathways. The anti-inflammatory effect of 17-HDPAn-6 and 10,17-HDPAn-6 in dextran sodium sulfate (DSS)-induced colitis was examined in the third study. Intraperitoneal injection of 17-HDPAn-6 or 10,17-HDPAn-6 alleviated DSS-colitis, epithelial damage and macrophage infiltration. Furthermore 17-HDPAn-6 and 10,17-HDPAn-6 increased phagocytosis activity in macrophage cell line RAW 264.7. The role of murine 15-lipoxgenase (Alox15) in DSS-colitis was explored in the fourth study. Alox 15 expression was augmented in wildtype C57BL/6 mice with DSS-colitis. Furthermore, systemic inactivation of the Alox15 gene (Alox15−/−) was associated with less severe colitis signs and preserved function of the intestinal barrier. Lower 12-hydroxyeicosatetraenoic acid (12-HETE) levels were detected in Alox15−/− mice with DSS-colitis. 12-HETE impaired intestinal epithelial barrier function in vitro in CaCo-2 cells. The results indicate a protective effect of systemic Alox15 inactivation, which might be related to reduced formation of 12-HETE, as well as of the lipid mediators 17-HDPAn-6 and 10,17-HDPAn-6 in the context of DSS-colitis.Langkettige mehrfach ungesättigte Omega-3 und Omega-6 Fettsäuren stellen Vorläufer für bioaktive Lipidmediatoren und – metabolite dar, welche enzymatisch über Cyclooxygenasen, Lipoxygenasen (LOX), Cytochrome P450 (CYP-450) sowie Autooxidationsprozessen synthetisiert werden, und können in ihrer Bildung pharmakologisch beeinflusst werden. In den dieser Arbeit zugrundeliegenden Publikationen wurde der Einfluss von erhöhten Omega-3 Fettsäurespiegeln auf die Zusammensetzung des Lipidmediatorenprofils, insbesondere der einfach hydroxylierten Metabolite Hydroxyeicosatetraensäuren, Hydroxyeicosapentaensäuren (HEPE) sowie Hydroxydocosahexaensäuren, in verschiedenen Organen der Maus untersucht. Weiterhin wurde die Rolle der murinen 15-Lipoxygenase sowie der von Omega-6 Docosapentaensäure stämmigen Lipidmetabolite 17-Hydroxydocosapentaensäure (17-HDPAn-6) und 10,17-Dihydroxydocosapentaensäure (10,17-HDPAn-6) im Kontext eines experimentellen Kolitismodells untersucht. In der ersten Studie wurde mittels Flüssigchromatographie mit Massenspektrometrie-Kopplung die Zusammensetzung von Monohydroxy-Lipidmetaboliten in Herz, Lunge, Leber, Kolon, Nieren, Milz und Skelettmuskel der Maus charakterisiert. Es fand sich eine organ- und gewebespezifische Verteilung der untersuchten Monohydroxy-Lipidmetabolite. Ein erhöhter Omega-3 Fettsäurespiegel in der transgenen fat-1 Maus führte zu einem organ- und gewebespezifischen Anstieg der Omega-3 Fettsäure stämmigen Lipidmetabolite. Eicosapentaensäure wurde trotz geringer Mengen hocheffizient zu hauptsächlich 12-HEPE in der Lunge sowie Milz und 9-HEPE und 18-HEPE in den anderen Organen verstoffwechselt. In der zweiten Studie konnte gezeigt werden, dass durch diätetische Intervention mittels Omega-3 Fettsäure angereichertem Futter ein höherer Omega-3 Fettsäurespiegel im Vergleich zum transgenen fat-1 Mausmodell erzielt wurde. Es fanden sich entsprechend erhöhte Spiegel der von Omega-3 Fettsäuren abgeleiteten Lipidmetabolite. Im Plasma von Mäusen auf Omega-3 Fettsäurereichem Futter wurde das Lipidmetabolitenprofil von LOX und CYP-450 Enzymen synthetisierten Lipidmetaboliten dominiert. Der anti-inflammatorische Effekt von 17-HDPAn-6 und 10,17-HDPAn-6 wurde in der dritten Studie im Dextran Natriumsulfat (DSS)-induzierten Kolitismodell in wildtyp C57BL/6 Mäusen untersucht. Eine intraperitoneale Behandlung mit 17-HDPAn-6 oder 10,17-HDPAn-6 milderte die DSS-Kolitis, den epithelialen Schaden sowie die Makrophageninfiltration. Weiterhin erhöhte 17-HDPAn-6 sowie 10,17-HDPAn-6 in der Makrophagen-Zelllinie RAW 264.7 die Phagozytoseaktivität. Die Rolle der murinen 15-Lipoxygenase (Alox15) wurde in der vierten Studie im DSS-Kolitismodell untersucht. Unsere Ergebnisse zeigen eine erhöhte Alox15 Expression in wildtyp Mäusen mit DSS-Kolitis. Eine systemische Inaktivierung des Alox15 Genes (Alox15−/−) war mit einer signifikant milderen Kolitisaktivität und einer erhaltenen Funktion der intestinalen Barriere assoziiert. In Alox15−/− Mäusen mit DSS-Kolitis wurden verminderte 12-Hydroxyeicosatetraensäure (12-HETE) Spiegel gemessen. In vitro Experimente konnten zeigen, dass 12-HETE die epitheliale Barriere in CaCo-2 Zellen stört. Die Ergebnisse weisen auf einen protektiven Effekt der systemischen Alox15 Inaktivierung, möglicherweise bedingt durch eine verminderte Synthese von 12-HETE, sowie der Lipidmediatoren 17-HDPAn-6 und 10,17-HDPAn-6 im DSS-Kolitismodell hin

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While representation learning aims to derive interpretable features for describing visual data, representation disentanglement further results in such features so that particular image attributes can be identified and manipulated. However, one cannot easily address this task without observing ground truth annotation for the training data. To address this problem, we propose a novel deep learning model of Cross-Domain Representation Disentangler (CDRD). By observing fully annotated source-domain data and unlabeled target-domain data of interest, our model bridges the information across data domains and transfers the attribute information accordingly. Thus, cross-domain joint feature disentanglement and adaptation can be jointly performed. In the experiments, we provide qualitative results to verify our disentanglement capability. Moreover, we further confirm that our model can be applied for solving classification tasks of unsupervised domain adaptation, and performs favorably against state-of-the-art image disentanglement and translation methods.Comment: CVPR 2018 Spotligh

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Although it has been suggested that schoolchildren vaccination reduces influenza morbidity and mortality in the community, it is unknown whether geographical heterogeneity would affect vaccine effectiveness

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Epigallocatechin-3-gallate (EGCG) has been documented for its beneficial effects protecting oxidative stress to cardiac cells. Previously, we have shown the EGCG-mediated cardiac protection by attenuating reactive oxygen species and cytosolic Ca2+ in cardiac cells during oxidative stress and myocardial ischemia. Here, we aimed to seek a deeper elucidation of the molecular anti-oxidative capabilities of EGCG in an H2O2-induced oxidative stress model of myocardial ischemia injury using H9c2 rat cardiomyoblasts

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Salmonella enterica serovar Choleraesuis (S.Choleraesuis), a highly invasive serovar among non-typhoidal Salmonella, usually causes sepsis or extra-intestinal focal infections in humans. S.Choleraesuis infections have now become particularly difficult to treat because of the emergence of resistance to multiple antimicrobial agents. The 4.7 Mb genome sequence of a multidrug-resistant S.Choleraesuis strain SC-B67 was determined. Genome wide comparison of three sequenced Salmonella genomes revealed that more deletion events occurred in S.Choleraesuis SC-B67 and S.Typhi CT18 relative to S.Typhimurium LT2. S.Choleraesuis has 151 pseudogenes, which, among the three Salmonella genomes, include the highest percentage of pseudogenes arising from the genes involved in bacterial chemotaxis signal-transduction pathways. Mutations in these genes may increase smooth swimming of the bacteria, potentially allowing more effective interactions with and invasion of host cells to occur. A key regulatory gene of TetR/AcrR family, acrR, was inactivated through the introduction of an internal stop codon resulting in overexpression of AcrAB that appears to be associated with ciprofloxacin resistance. While lateral gene transfer providing basic functions to allow niche expansion in the host and environment is maintained during the evolution of different serovars of Salmonella, genes providing little overall selective benefit may be lost rapidly. Our findings suggest that the formation of pseudogenes may provide a simple evolutionary pathway that complements gene acquisition to enhance virulence and antimicrobial resistance in S.Choleraesuis

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This work aims for transferring a Transformer-based image compression codec from human vision to machine perception without fine-tuning the codec. We propose a transferable Transformer-based image compression framework, termed TransTIC. Inspired by visual prompt tuning, we propose an instance-specific prompt generator to inject instance-specific prompts to the encoder and task-specific prompts to the decoder. Extensive experiments show that our proposed method is capable of transferring the codec to various machine tasks and outshining the competing methods significantly. To our best knowledge, this work is the first attempt to utilize prompting on the low-level image compression task