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The Role of IL-17RA on Microglial Activation in Alzheimer’s Disease
No full textMicroglia are brain resident immune cells which play a pivotal role in brain development, maintenance and disease. Previously, we have identified two major microglial phenotypes: the homeostatic microglia (M0) and neurodegenerative (MGnD) microglia. Interleukin-17A (IL-17A) secreted by T helper 17 (Th17) cells and meningeal dgT cells has been recently proved to exacerbate disease pathogenesis in the central nervous system (CNS). IL-17 receptor A (IL-17RA) is highly expressed on microglia, and its expression was significantly reduced in MGnD-microglia associated with amyloid-b Ab plaques in a transgenic Alzheimer’s Disease (AD) mouse model as well as MGnD-like microglia in AD human brains. However, it is unknown how IL-17RA signaling regulates microglia in AD. We hypothesize that adaptive immunity modulates microglia phenotype via IL-17RA signaling to fight against AD pathogenesis. To address this, I used global knockout (IL-17RA-/-) and microglia-specific knockout (Cx3cr1creERT2-IL-17RAfl/fl) mouse models, immunohistochemistry (IHC), and bulk RNA sequencing. I found that global deletion of IL-17RA promoted microglia inflammation in physiological, acute inflammatory (Ab1-42 peptides/dead neurons/synaptosomes injection into cortex and hippocampus) and chronic inflammatory (AD) conditions, which may result from systemic inflammation from fungal/bacterial infection due to the loss of IL-17RA in the barrier. However, the Ab-plaque load and plaque density in the cortex was decreased and the microglia infiltration into single plaques was more in the APP/PS1:IL-17RA-/- mice. Thus, blocking IL-17RA might alleviate AD. On the contrary, deletion of IL-17RA on microglia before clinical onset (1.5 months of age) suppressed microglial inflammation but did not affect microglia phagocytosis, antigen presentation or other immune responses. In acute inflammatory and chronic inflammatory (AD) conditions, microglia in IL-17RA conditionally knockout mice did not show significant difference from the control. In conclusion, deleting IL-17RA globally can induce systemic inflammation, while microglia-specifical deletion of IL-17RA can reduce microglial inflammation but does not influence the other functions. This study has shown that blocking IL-17RA signaling in microglia can prevent microglia being inflammatory and dysfunctional, which is likely to ameliorate AD
Depletion of microglia and inhibition of exosome synthesis halt tau propagation
No full textAccumulation of pathological tau protein is a major hallmark of Alzheimer's disease. Tau protein spreads from the entorhinal cortex to the hippocampal region early in the disease. Microglia, the primary phagocytes in the brain, are positively correlated with tau pathology, but their involvement in tau propagation is unknown. We developed an adeno-associated virus-based model exhibiting rapid tau propagation from the entorhinal cortex to the dentate gyrus in 4 weeks. We found that depleting microglia dramatically suppressed the propagation of tau and reduced excitability in the dentate gyrus in this mouse model. Moreover, we demonstrate that microglia spread tau via exosome secretion, and inhibiting exosome synthesis significantly reduced tau propagation in vitro and in vivo. These data suggest that microglia and exosomes contribute to the progression of tauopathy and that the exosome secretion pathway may be a therapeutic target
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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