1,610 research outputs found

    Untersuchung der Immunantwort von Monozyten nach gezielter pharmakologischer Beeinflussung des APP-Stoffwechsels

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    Background and objective: Morbus Alzheimer is a progressive neurodegenerative disease and the main cause for dementia in more than 60 percent. The disease is characterized by amyloid plaques which contain Aβ as a main component. Aβ itself also shows antimicrobial characteristics and affects the innate immune system. Therefore, the main objective of this publication is to investigate the changes in the inflammatory cytokine production and phagocytosis of macrophages after pharmacological inhibition of Aβ production. Materials and methods: Ex vivo human monocytes were cultivated in vitro and differentiated into macrophages. In these cells Aβ peptide production was reduced by both the β-secretase inhibitor GL-189 and the γ-secretase inhibitor DAPT. The successful reduction was shown by 2D SDS PAGE in combination with western immunoblot. To study phagocytosis, macrophages were exposed to fluorescent microbeads and the particles they ingested were detected by flow cytometry. Measurement of interleukins in cell culture supernatants was performed by ELISA. Results: Incubation with the β-secretase inhibitor GL-189 resulted in a 49% reduced release of IL-6, TNFα decreased by 51%, and IL-10 increased by 73% compared with the control group. The γ-secretase inhibitor DAPT reduced the secreted IL-6 into the supernatant by 53% and TNFα by 52%. IL-10 increased by 97% compared to the control group. Incubation with the β-secretase inhibitor or the γ-secretase inhibitor had no significant effect on phagocytosis performance. Conclusion: These results indicate that modulation of the APP metabolism reduces the release of proinflammatory cytokines by macrophages and thereby could affect the innate immune response. Publication: Some results of this doctoral thesis have been previously published in “Frontiers in Immunology“ (Spitzer et al. 2020).Hintergrund und Ziele: Morbus Alzheimer ist eine irreversibel fortschreitende, neurodegenerative Erkrankung, die für über 60% aller Fälle von Demenz verantwortlich ist. Die für die Erkrankung charakteristischen amyloiden Plaques enthalten als Hauptbestandteil Aβ. Dieses weist jedoch auch antimikrobielle Eigenschaften auf und hat einen Einfluss auf das angeborene Immunsystem. Eine Beeinflussung des Aβ-Stoffwechsels würde sich somit auch auf das Immunverhalten auswirken. Ziel dieser Arbeit ist die Untersuchung der Auswirkungen einer medikamentösen Hemmung der Aβ-Produktion auf das Zytokinprofil sowie das Phagozytoseverhalten bei Makrophagen. Methoden: Es erfolgte die Isolierung von Monozyten aus humanem Blut und die in vitro Ausdifferenzierung zu Makrophagen. Die suffiziente Reduzierung der Aβ Peptide durch den γ-Sekretaseinhibitor DAPT und den β-Sekretaseinhibitor GL-189 wurde im Western Blot gezeigt. Zur Untersuchung der Phagozytose wurden Makrophagen fluoreszierende Mikropartikel hinzugefügt und die von ihnen aufgenommenen Partikel in der Durchflusszytometrie detektiert. Die Messung der Interleukine in den Zellkulturüberständen erfolgte durch ELISA. Ergebnisse: Die Verwendung des β-Sekretaseinhibitors GL-189 führte im Vergleich zur Kontrollgruppe zu einer um 49% reduzierten Freisetzung von IL-6, TNFα ging um 51% zurück, IL-10 stieg um 73%. Der γ-Sekretaseinhibitor DAPT reduzierte das sezernierte IL-6 um 53% sowie TNFα um 52%. Bei IL-10 zeigte sich ein Anstieg von 97% im Zellkulturmedium. Die Inkubation mit β-Sekretaseinhibitor, respektive γ-Sekretaseinhibitor, hatte keinen signifikanten Einfluss auf die Phagozytoseleistung. Schlussfolgerung: Diese Ergebnisse erlauben den Rückschluss, dass die Modulation des APP-Metabolismus die Freisetzung proinflammatorischer Zytokine verringert und damit Funktionen innerhalb der angeborenen Immunabwehr beeinflussen kann. Vorveröffentlichung: Teilergebnisse dieser Arbeit wurden bereits in der Fachzeitschrift Frontiers in Immunology veröffentlicht (Spitzer et al. 2020)

    Supplemental_Material - Analysis of Surface Levels of IL-1 Receptors and Macrophage Scavenger Receptor I in Peripheral Immune Cells of Patients With Alzheimer Disease

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    Supplemental_Material for Analysis of Surface Levels of IL-1 Receptors and Macrophage Scavenger Receptor I in Peripheral Immune Cells of Patients With Alzheimer Disease by Philipp Spitzer, Johannes Weinbeer, Martin Herrmann, Timo Jan Oberstein, Mateja Condic, Piotr Lewczuk, Johannes Kornhuber and Juan Manuel Maler in Journal of Geriatric Psychiatry and Neurology</p

    Philipp Melanchthon

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    Philipp Melanchthon (1497–1560) was, with Martin Luther, the most influential reformer of the church during the 16th century. He was also a reformer of university education, especially theological studies, as well as the school system in Germany. He was responsible for a theological curriculum that included Greek, Hebrew, and philosophy. He, as a professor of Greek at the University of Wittenberg since 1518, was the author of the first generally accepted Protestant confession, known as the Confessio Augustana (1530). He also wrote the first Protestant commentaries on Paul’s letter to the Romans (1519), as well as the first Protestant handbook in systematic theology (1521). He was the main negotiator of the Protestant movement during the diets and religious discussions with the Roman Catholic Church. He is known as the ‘teacher of Germany and Europe’ and is respected as the father of the ecumenical movement. Yet, Melanchthon is not known to South Africans and especially Afrikaans-speaking people who, traditionally, have close links with the reformational tradition. There is not yet one single publication on Melanchthon in Afrikaans or by a South African scholar, making this book, therefore, the first by an Afrikaans-speaking scholar on Melanchthon

    #Bitcoin : an analysis of the field of a decentralized virtual currency using twitter data

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    Author Philipp AllerstorferAbstract in englischer SpracheMasterarbeit Universität Linz 201

    On Philipp Lersch’s Psychology, Reflection No. 2

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    Автор статті зазначає, що у 1930–1970 рр. Ф. Лерш був головним представником гуманітарної течії в німецькомовній психології. Наукову класифікацію людських прагнень і стремлінь було викладено у головній праці Ф. Лерша «Структура особи» (11-те видання 1970 року). Ф. Лерш зумів об’єднати у своїм творі інформацію із низки наук (біології, психопатології, із різних психологічних теорій та концепцій).The author of the article notes that in 1930-1970, Philipp Lersch was the main representative of the humanitarian direction in German psychology. A scientific classification of human aspirations and ambitions was described in the main work by Philipp Lersch “Building the Person” (11th ed. of 1970). In his work, Philipp Lersch managed to combine information from a number of sciences (biology, psychopathology, various psychological theories and concepts)

    Deformation Behavior and Damage Modeling of Polypropylene and Polycarbonate

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    Author Philipp Siegfried StelzerKurzfassungen in deutscher und englischer SpracheMasterarbeit Universität Linz 201

    Philipp Timischl x Numeró Art

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    This article discusses the intersections of gender and class drag in the work of Austrian artist Philipp Timischl. The essay takes the form of a letter of refusal, discussing why the author is simply too busy, then goes on to discuss other performances of industriousness, from Kevin Floyd's proposal that modern masculinity is a labour based performance through to the artist's own gender enhancing or swapping works

    Astrocytes and microglia but not neurons preferentially generate N-terminally truncated Aβ peptides

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    AbstractThe neuropathological hallmarks of Alzheimer's disease include extracellular neuritic plaques and neurofibrillary tangles. The neuritic plaques contain β-amyloid peptides (Aβ peptides) as the major proteinaceous constituent and are surrounded by activated microglia and astrocytes as well as dystrophic neurites. N-terminally truncated forms of Aβ peptides are highly prevalent in neuritic plaques, including Aβ 3-x beginning at Glu eventually modified to pyroglutamate (Aβ N3pE-x), Aβ 2-x, Aβ 4-x, and Aβ 5-x. The precise origin of the different N-terminally modified Aβ peptides currently remains unknown. To assess the contribution of specific cell types to the formation of different N-terminally truncated Aβ peptides, supernatants from serum-free primary cell cultures of chicken neurons, astrocytes, and microglia, as well as human astrocytes, were analyzed by Aβ-ELISA and one- and two-dimensional SDS-urea polyacrylamide gel electrophoresis followed by immunoblot analysis. To evaluate the contribution of β- and γ-secretase to the generation of N-terminally modified Aβ, cultured astrocytes were treated with membrane-anchored “tripartite β-secretase (BACE1) inhibitors” and the γ-secretase inhibitor DAPT. Neurons, astrocytes, and microglia each exhibited cell type-specific patterns of secreted Aβ peptides. Neurons predominantly secreted Aβ peptides that begin at Asp1, whereas those released from astrocytes and microglia included high proportions of N-terminally modified Aβ peptides, presumably including Aβ 2/3-x and 4/5-x. The inhibition of BACE1 reduced the amount of Aβ 1-x in cell culture supernatants but not the amount of Aβ 2-x

    Aaron-Aarons-Marcus-Philipp Families Collection 1680-2000

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    Genealogical information and family trees on various families. The collection consists of six folders containing computer generated family trees.The following family names are mentioned in this collection:Aaron ; Aarons ; Adler ; Adolfsson ; Ahlind ; Ahrberg ; Ahrendt ; Ahrens ; Akergreen ; Albahary ; Albert ; Alexander ; Andersson ; Arell ; Arndt ; Arnhold ; Arsi ; Asch ; Bacharach ; Backstroem ; Badt-Jackier ; Barbro ; Baresch ; Bargen ; Baruch ; Barzilai ; Bass ; Bauer ; Beer ; Behrens ; Bendix ; Bentheim ; Ben-Vered (Rosenbaum) ; Bernays ; Bernhardt ; Bing ; Blackwood of Duffering and Ava ; Blake ; Boas ; Bodenheimer ; Bonnier ; Braceland ; Brasch ; Buckley ; Burgess ; Caro ; Cederquist ; Chambers ; Cohen ; Cohn ; Cornet ; Cowherd ; Cronach ; Dahlen ; Daus ; Davidsen (Salomonsen) ; Davidsson ; Davis ; Davison ; De Lenos ; De Leon ; De Nunez ; Dessau ; Dickinson ; Ditlevsen ; Doerum ; Donahue ; Doty ; Drucker ; Dryselius ; Dub ; Eberstein ; Ehnwall ; Ehrick (Rosenbaum) ; Eisenhardt ; Ejefors ; Elford ; Emanuel ; Eurenius ; Fairbairn ; Farnham ; Feldmann ; Flewett ; Flitz ; Floersheim ; Forsell ; Fraenkel ; Frank ; Franke ; Frankforter ; Freud (Halberstadt) ; Freud ; Friedland (Cohn) ; Frizer ; Fuchs ; Fuerst ; Fuller ; Gannon ; Garellick ; Garman ; Gerson ; Gilchrist ; Gluze ; Golan ; Goldschmidt ; Gradenwitz ; Grafstroem ; Grand ; Green ; Grunisch ; Haarbleicher ; Halberstadt ; Hardler ; Harsch ; Hartwig ; Hausen ; Heilbronn ; Heilbut ; Heimanson ; Heine ; Heinemann ; Held ; Heller ; Henriques ; Henschel ; Hertz ; Herz ; Herzheim ; Hess ; Heymann ; Hills ; Hinrichsen ; Hirsch ; Hoffmann ; Hollaender ; Hollitscher; Huettner ; Hullisch ; Hultman ; Hvistendahl ; Hyttner (Huettner) ; Inokaij ; Instanes ; Isenstein ; Israel ; Jackert ; Jaensson ; Jaffe ; Jekel ; Jenning ; Jensen ; Johansson ; Johnson (Jonas) ; Jonas ; Jonsson ; Joseph ; Josephi ; Kaplan ; Kaufmann ; Kayser ; Kirschstein ; Kleibel ; Klein ; Koch ; Kosches ; Krarup ; Kuchla ;Labatt ; Ladimir ; Lager ; Lagerquist ; Landau ; Latimore ; Lauritzen ; Lazarus ; Leibhner, von ; Lenck ; Leunmark ; Leve ; Levertin ; Levin ; Levy ; Levysohn (Levisohn) ; Lewinson ; Leyser ; Liebmann ; Lilie ; Lindgren ; Lindholm ; Lion ; Loeser ; Loewenhaupt ; Loewenstein ; Loewenthal ; Loria ; Loven ; Lublin ; Lundegard ; Lundwall ; Madsen ; Maeland ; Magnus ; Marbe ; Marcus ; Marquis (Marcus) ; Marx ; McCarthy ; Meden ; Melchior ; Mendelsohn ; Mendheim ; Merchant ; Meron ; Merritt ; Mewes ; Meyer ; Meyersson ; Miller ; Millius ; Moglianski ; Morton ; Moses ; Muller ; Mulligan ; Nassau ; Nathan ; Neri ; Nieburg ; Nilson ; Nordberg ; Norrman ; Nussbaum ; Oettinger ; Ohlsson ; Olsson ; Orowan ; Pallin ; Parknell ; Patron ; Pederdsen ; Penney ; Petruson ; Phelps ; Philip ; Philipp ; Philipsson (Aaron) ; Plaut ; Polack ; Porges von Portheim ; Potter ; Pritzwald ; Pyk ; Rahm ; Randolph ; Rasmusen ; Reinlein von Marinburg ; Reis, von ; Rimon (Rosenbaum) ; Rosen ; Rosen, von ; Rosenbaum ; Rosenstern ; Rosenthal ; Ruben ; Rubensson ; Ruekman ; Saenger ; Salomon ; Salomonsen ; Samson ; Samuel ; Sandberg ; Sandick ; Schiff ; Schlesinger ; Schlomann ; Schlotfeldt ; Schmiof ; Schneider ; Schultz ; Schustermann ; Sdeor ; Seessel ; Sendler ; Simonsen ; Sisefsky ; Soendsen ; Soerensen ; Soerlin ; Soltow ; Sorterup ; Spitzer ; Springmann ; Steinfeld ; Steinhardt ; Stenborn ; Stern ; Stiebel ; Stirk ; Strandin ; Sundberg ; Sundquist ; Symons ; Tal ; Tanandier ; Tellier ; Tinggren ; Tobias ; Tosler ; Trinkhaus ; Unge, von ; Unna ; Usriel ; Valentin ; Vecht ; Velander ; Wagnsson ; Wahren ; Warburg ; Warrens ; Warschawski ; Weber, von ; Weil ; Wertheimer ; Wetterling ; Wetzlar ; Wiener ; Wilson ; Wolf ; Wolff ; Wolffenstein ; Worsliezka, von ; Zeidlerdigitize
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