TY - JOUR A1 - Pache, Florence A1 - Zimmermann, Hanna A1 - Mikolajczak, Janine A1 - Schumacher, Sophie A1 - Lacheta, Anna A1 - Oertel, Frederike C. A1 - Bellmann-Strobl, Judith A1 - Jarius, Sven A1 - Wildemann, Brigitte A1 - Reindl, Markus A1 - Waldman, Amy A1 - Soelberg, Kerstin A1 - Asgari, Nasrin A1 - Ringelstein, Marius A1 - Aktas, Orhan A1 - Gross, Nikolai A1 - Buttmann, Mathias A1 - Ach, Thomas A1 - Ruprecht, Klemens A1 - Paul, Friedemann A1 - Brandt, Alexander U. T1 - MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 4: Afferent visual system damage after optic neuritis in MOG-IgG-seropositive versus AQP4-IgG-seropositive patients JF - Journal of Neuroinflammation N2 - Background Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been reported in patients with aquaporin-4 antibody (AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD). The objective of this study was to describe optic neuritis (ON)-induced neuro-axonal damage in the retina of MOG-IgG-positive patients in comparison with AQP4-IgG-positive NMOSD patients. Methods Afferent visual system damage following ON was bilaterally assessed in 16 MOG-IgG-positive patients with a history of ON and compared with that in 16 AQP4-IgG-positive NMOSD patients. In addition, 16 healthy controls matched for age, sex, and disease duration were analyzed. Study data included ON history, retinal optical coherence tomography, visual acuity, and visual evoked potentials. Results Eight MOG-IgG-positive patients had a previous diagnosis of AQP4-IgG-negative NMOSD with ON and myelitis, and eight of (mainly recurrent) ON. Twenty-nine of the 32 eyes of the MOG-IgG-positive patients had been affected by at least one episode of ON. Peripapillary retinal nerve fiber layer thickness (pRNFL) and ganglion cell and inner plexiform layer volume (GCIP) were significantly reduced in ON eyes of MOG-IgG-positive patients (pRNFL = 59 ± 23 μm; GCIP = 1.50 ± 0.34 mm3) compared with healthy controls (pRNFL = 99 ± 6 μm, p < 0.001; GCIP = 1.97 ± 0.11 mm3, p < 0.001). Visual acuity was impaired in eyes after ON in MOG-IgG-positive patients (0.35 ± 0.88 logMAR). There were no significant differences in any structural or functional visual parameters between MOG-IgG-positive and AQP4-IgG-positive patients (pRNFL: 59 ± 21 μm; GCIP: 1.41 ± 0.27 mm3; Visual acuity = 0.72 ± 1.09 logMAR). Importantly, MOG-IgG-positive patients had a significantly higher annual ON relapse rate than AQP4-IgG-positive patients (median 0.69 vs. 0.29 attacks/year, p = 0.004), meaning that on average a single ON episode caused less damage in MOG-IgG-positive than in AQP4-IgG-positive patients. pRNFL and GCIP loss correlated with the number of ON episodes in MOG-IgG-positive patients (p < 0.001), but not in AQP4-IgG-positive patients. Conclusions Retinal neuro-axonal damage and visual impairment after ON in MOG-IgG-positive patients are as severe as in AQP4-IgG-positive NMOSD patients. In MOG-IgG-positive patients, damage accrual may be driven by higher relapse rates, whereas AQP4-IgG-positive patients showed fewer but more severe episodes of ON. Given the marked damage in some of our MOG-IgG-positive patients, early diagnosis and timely initiation and close monitoring of immunosuppressive therapy are important. KW - Myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) KW - aquaporin-4 antibodies (AQP4-IgG) KW - NMO-IgG KW - neuromyelitis optica KW - Devic syndrome KW - neuromyelitis optica spectrum disorders (NMOSD) KW - optic neuritis KW - optical coherence tomography KW - visual evoked potentials KW - visual acuity KW - retinal neuro-axonal damage Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165551 VL - 13 IS - 282 ER - TY - RPRT A1 - Neukum, Alexandra A1 - Walter, Martina A1 - Schumacher, Markus A1 - Krüger, Hans-Peter T1 - Trainingskonzeption und Evaluation des Moduls A: "Gefahrenkognition" (Projekt: Simulation von Einsatzfahrten im Auftrag des Präsidiums der Bayerischen Bereitschaftspolizei, Abschlussbericht – Teil I) N2 - Mit dem Ziel der Optimierung der bestehenden polizeilichen Fahrausbildung hat das Präsidium der Bayerischen Bereitschaftspolizei im Jahr 2001 ein mehrjähriges Pilotprojekt initiiert, in dem ein technologiegestütztes und didaktisch begründetes Ausbildungssystem entwickelt und erprobt werden sollte. Im Zentrum dieses Pilotprojekts stand die Frage der Anwendung moderner Simulationstechnologie in der Fahrausbildung. Inhaltliche Entwicklung und Projektevaluation oblagen dem IZVW. Das Pilotprojekt ist integriert in das Gesamtcurriculum der Fahrausbildung bei der Bayerischen Bereitschaftspolizei (Rager & Müller, 2000). Dieses basiert auf drei unterschiedlichen Ausbildungsblöcken und umfasst insgesamt 93 Unterrichtseinheiten. Die Inhalte des dreistufigen Programms im Rahmen der Ausbildung für den mittleren Polizeivollzugsdienst sind gekennzeichnet als „Situations- und typenbezogenes Fahrtraining“ (Stufe 1), „Sicherheitstraining mit Gefahrenlehre“ (Stufe II) und „Gefahrentraining zur Bewältigung von Einsatzfahrten mit und ohne Inanspruchnahme von Sonder- und Wegerechten“ (Stufe III). In dieser letzten Ausbildungsstufe ist das Pilotprojekt „Simulation von Einsatzfahrten“ positioniert. Das verkehrswissenschaftliche Projekt setzte sich zum Ziel, in enger Zusammenarbeit mit polizeilichen Experten und Ausbildern eine an den Erfordernissen der beruflichen Praxis orientierte Ausbildungs- und Trainingskonzeption zu entwickeln und insbesondere die Anwendung der Simulationsmethodik innerhalb der Fahrausbildung zu evaluieren. Der vorliegende Text konzentriert sich als Teil der Abschlussdokumentation auf die Evaluation des Simulatortrainings. Dieses ist konzipiert als zentraler Bestandteil des inhaltlichen Moduls „Gefahrenkognition“ und wird ergänzt durch ein vorbereitendes computerbasiertes Training. Gegenstand dieses Berichts sind die Arbeiten zur Erfassung von Trainingsakzeptanz und Lernerfolg der Lerneinheit Gefahrenkognition. Hierzu wird zunächst ein Überblick über aktuelle in der Literatur vorliegende Studien gegeben, die sich mit der Evaluation der Simulation als Lehrmethode in der Fahrausbildung beschäftigen. Kapitel 3 gibt einen Überblick über die Inhalte des Moduls und den Aufbau der Übungen in CBT und Simulator. Fragestellungen, Konzeption und methodisches Vorgehen der Evaluationsuntersuchungen sind beschrieben in Kapitel 4. Die Darstellung der Ergebnisse erfolgt in den Abschnitten 5 bis 7. KW - Verkehrssicherheit KW - Fahrsimulator KW - Fahrertraining KW - Einsatzfahrten KW - Trainingsevaluation Y1 - 2006 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-77833 ER - TY - JOUR A1 - Peters, Simon A1 - Kaiser, Lena A1 - Fink, Julian A1 - Schumacher, Fabian A1 - Perschin, Veronika A1 - Schlegel, Jan A1 - Sauer, Markus A1 - Stigloher, Christian A1 - Kleuser, Burkhard A1 - Seibel, Juergen A1 - Schubert-Unkmeir, Alexandra T1 - Click-correlative light and electron microscopy (click-AT-CLEM) for imaging and tracking azido-functionalized sphingolipids in bacteria JF - Scientific Reports N2 - Sphingolipids, including ceramides, are a diverse group of structurally related lipids composed of a sphingoid base backbone coupled to a fatty acid side chain and modified terminal hydroxyl group. Recently, it has been shown that sphingolipids show antimicrobial activity against a broad range of pathogenic microorganisms. The antimicrobial mechanism, however, remains so far elusive. Here, we introduce 'click-AT-CLEM', a labeling technique for correlated light and electron microscopy (CLEM) based on the super-resolution array tomography (srAT) approach and bio-orthogonal click chemistry for imaging of azido-tagged sphingolipids to directly visualize their interaction with the model Gram-negative bacterium Neisseria meningitidis at subcellular level. We observed ultrastructural damage of bacteria and disruption of the bacterial outer membrane induced by two azido-modified sphingolipids by scanning electron microscopy and transmission electron microscopy. Click-AT-CLEM imaging and mass spectrometry clearly revealed efficient incorporation of azido-tagged sphingolipids into the outer membrane of Gram-negative bacteria as underlying cause of their antimicrobial activity. KW - antimicrobials KW - biological techniques KW - imaging KW - microbiology KW - microbiology techniques KW - microscopy Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259147 VL - 11 IS - 1 ER - TY - JOUR A1 - Derakhshani, Shaghayegh A1 - Kurz, Andreas A1 - Japtok, Lukasz A1 - Schumacher, Fabian A1 - Pilgram, Lisa A1 - Steinke, Maria A1 - Kleuser, Burkhard A1 - Sauer, Markus A1 - Schneider-Schaulies, Sibylle A1 - Avota, Elita T1 - Measles virus infection fosters dendritic cell motility in a 3D environment to enhance transmission to target cells in the respiratory epithelium JF - Frontiers in Immunology N2 - Transmission of measles virus (MV) from dendritic to airway epithelial cells is considered as crucial to viral spread late in infection. Therefore, pathways and effectors governing this process are promising targets for intervention. To identify these, we established a 3D respiratory tract model where MV transmission by infected dendritic cells (DCs) relied on the presence of nectin-4 on H358 lung epithelial cells. Access to recipient cells is an important prerequisite for transmission, and we therefore analyzed migration of MV-exposed DC cultures within the model. Surprisingly, enhanced motility toward the epithelial layer was observed for MV-infected DCs as compared to their uninfected siblings. This occurred independently of factors released from H358 cells indicating that MV infection triggered cytoskeletal remodeling associated with DC polarization enforced velocity. Accordingly, the latter was also observed for MV-infected DCs in collagen matrices and was particularly sensitive to ROCK inhibition indicating infected DCs preferentially employed the amoeboid migration mode. This was also implicated by loss of podosomes and reduced filopodial activity both of which were retained in MV-exposed uninfected DCs. Evidently, sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) as produced in response to virus-infection in DCs contributed to enhanced velocity because this was abrogated upon inhibition of sphingosine kinase activity. These findings indicate that MV infection promotes a push-and-squeeze fast amoeboid migration mode via the SphK/S1P system characterized by loss of filopodia and podosome dissolution. Consequently, this enables rapid trafficking of virus toward epithelial cells during viral exit. KW - dendritic cell KW - cell migration KW - measles virus KW - 3D tissue model KW - sphingosine-1-phosphate Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201818 VL - 10 IS - 1294 ER -