299 research outputs found

    Phenotypes and glia-immune cell interactions in animal models of multiple sclerosis

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    MS is a complex chronic immune-mediated disease of the central nervous system that is associated with the development of large demyelinated plaques, oligodendrocyte destruction, and axonal degeneration. Underlying mechanisms of demyelination and neurodegeneration in MS are still poorly understood. In many studies, anti-CC1 antibodies, presumably recognizing the protein adenomatous polyposis coli (APC) antigen, are used to label mature, myelinating oligodendrocytes. However, anti-CC1 antibodies could as well recognize other cell populations, particularly astrocytes, under pathological conditions. To examine this hypothesis, we used the cuprizone animal model, which is an appropriate model to study the mechanism of the apoptosis of oligodendrocytes and demyelination. We applied transgenic mice in which astrocytes are labeled by an eGFP under the control of the human GFAP promoter. Furthermore, we investigated the co-localization of oligodendrocyte markers, including anti-OLIG2, anti-CC1, anti-NG2, and the astrocyte marker anti-GFAP in the control and five weeks curprizone intoxicated eGFP-GFAP mice. Results of this study suggest that not all CC1+ cells are mature oligodendrocytes, and a continuum might exist between activated astrocytes and oligodendrocytes in cuprizone intoxicated mice. In the context of elucidating underlying mechanism of MS lesion development, some results suggest that inflammatory lesion development starts with a degenerative process within the brain, most likely oligodendrocyte stress, or even degeneration. Therefore, appropriate animal models to study the interplay of inflammation and metabolic injury are necessary. To this end, we introduced a combinatory Cup-EAE animal model, in which lymphocyte recruitment into the forebrain occurs as a consequence of simultaneous cuprizone intoxication and active EAE induction. This model recapitulates important histopathological characteristics of type III MS lesions. In summary, we provide a protocol that allows to study the direct interplay of immune-mediated and metabolic oligodendrocyte injury, and its consequences for the cerebral white and gray matter.Bei der Multiplen Sklerose handelt es sich um eine immunvermittelte chronische Erkrankung des Zentralnervensystems, die mit der Zerstörung von Oligodendrozyten, großen demyelinisierten Plaques und axonaler Schädigung einhergeht. Der genaue Mechanismus der Demyelinisierung und Neurodegeneration bei MS ist noch unklar. In vielen Studien werden anti-CC1 Antikörper, die das adenomatous polyposis coli (APC) Protein binden, verwendet um reife und myelinisierende Oligodendrozyten darzustellen. Studien weißen allerdings darauf hin, dass Antikörper gegen CC1 unter pathologischen Bedingungen auch andere Zell-Populationen, insbesondere Astrozyten binden können. Um diese Hypothese zu testen, habe ich das Cuprizone-Tiermodell verwendet, welches ein geeignetes Modell zur Untersuchung der Apoptose von Oligodendrozyten und der Demyelinisierung darstellt. Im Rahmen meiner Experimente habe ich transgene Mäuse verwendet, in deren Astrozyten eGFP unter Kontrolle des Promotors für das humane GFAP exprimiert wird. Zusätzlich führte ich Immunofloureszenz-Dopplemarkierung mit anti-CC1, anti-OLIG2 und anti-NG2 in den transgenen Tieren durch. Die Ergebnisse meiner Untersuchungen zeigen eine deutlichen Co-Lokalisation von eGFP und verschiedenen Oligodendrozyten Markerproteinen. In dieser Arbeit konnte ich somit zeigen, dass nicht alle CC1+-Zellen reife Oligodendrozyten sind, sondern dass vermutlich auch aktivierten Astrozyten CC1 exprimieren können. Zur Entwicklung von MS Läsionen gibt es einige Hinweise, dass die Bildung inflammatorischer Läsionen mit degenerativen Prozessen im Gehirn beginnen, insbesondere Stress oder Degeneration von Oligodendrozyten. Zu genaueren Untersuchung dieses Wechselspiels zwischen Entzündung und Stoffwechselschädigung sind geeignete Tiermodelle notwendig. Hierfür haben wir ein kombiniertes Cup-EAE-Tiermodell etabliert, bei dem durch die gleichzeitige Behandlung mit Cuprizone und der Induktion einer aktiven EAE eine Rekrutierung von Lymphozyten ins Vorderhirn induziert wird. Dieses Modell spiegelt wichtige histopathologische Eigenschaften von Typ-III MS Läsionen wider. Zusammenfassend lässt sich feststellen, dass wir ein geeignetes Protokoll erarbeiten konnten, mit dem es möglich ist, das Wechselspiel der immunvermittelten und der metabolischen Oligodendrozytenschädigung und deren Auswirkung auf die die weiße und graue Substanz des Gehirns zu untersuchen

    Bias adjustment of infrared-based rainfall estimation using Passive Microwave satellite rainfall data

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    This study explores using Passive Microwave (PMW) rainfall estimation for spatial and temporal adjustment of Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks-Cloud Classification System(PERSIANN-CCS). The PERSIANN-CCS algorithm collects information from infrared images to estimate rainfall. PERSIANN-CCS is one of the algorithms used in the IntegratedMultisatellite Retrievals for GPM (Global Precipitation Mission) estimation for the time period PMW rainfall estimations are limited or not available. Continued improvement of PERSIANN-CCS will support Integrated Multisatellite Retrievals for GPM for current as well as retrospective estimations of global precipitation. This study takes advantage of the high spatial and temporal resolution of GEO-based PERSIANN-CCS estimation and the more effective, but lower sample frequency, PMW estimation. The Probability Matching Method (PMM) was used to adjust the rainfall distribution of GEO-based PERSIANN-CCS toward that of PMW rainfall estimation. The results show that a significant improvement of global PERSIANN-CCS rainfall estimation is obtained

    Investigating the Effects of Authentic Leadership of Managers on Organizational Commitment of Teachers with Organizational Justice as the Mediator Variable

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    The present study was conducted by the aim of investigating the fit of the presented model for the relationship between authentic leadership and organizational commitment of staff with a mediating role of organizational justice. The population of the research included all the teachers in high schools (for male students) in Education district 2 in Qom city. From the population, 300 individuals were selected through cluster sampling. For gathering the data, authentic leadership questionnaire (Avolio et al., 2007), organizational justice questionnaire of Niehoff & Moorman (1993), and Allen & Meyer's Organizational Commitment Questionnaire (2002) were used. For analyzing the data, structural equation modeling – fit indices and path coefficients – was used. The results of the analysis showed that authentic leadership has a direct and significant effect on the organizational commitment of teachers. Also, authentic leadership has an indirect effect, through organizational justice, on organizational commitment. The other finding of the research is that organizational justice has a direct and significant effect on organizational commitment of teachers, and the offered conceptual model has a significant statistical fit, that means the explanatory model for organizational commitment based on authentic leadership and organizational justice has fitness with empirical data. Finally, based on the information obtained from structural equations model, it can also be said that all the components existing in the 3 variables of the research have positive and significant relationships with one another
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