1,720,954 research outputs found
The Role of TREM2 and the Responses Mediated by Galectin-3 During Age-Related Myelin Degeneration
Get PDFIUIAging is the greatest known risk factor for various neurodegenerative diseases. Myelin degeneration is an early pathological indicator of these diseases and normal part of aging; albeit, to a lesser extent. Despite this, little is known about how age-related degeneration could contribute to and impact development of neurodegenerative disease. Microglia participate in a variety of white matter events from demyelination to remyelination. The microglial innate immune receptor triggering receptor expressed on myeloid cells 2 (TREM2) has been implicated in regulating (de)myelination.
We found in response to demyelination, TREM2 is required for large volumes of myelin debris and during extended periods of phagocytosis. In addition to lysosomal regulation, we showed TREM2 can modify the ER stress response prior to overt myelin debris preventing early microglial dysfunction. We found TREM2 is necessary for remyelination by recruiting reparative glia and mediating signaling that promotes OPC differentiation/maturation. One of the signaling factors involved, the β-galactosidase-binding protein galectin-3 (gal-3), was recently identified as a ligand for TREM2, however little is known about this interaction in the context of aging or neurodegenerative disease.
Treating microglia with a pharmacological gal-3 inhibitor, we found overlapping functional deficits with Trem2-deficient microglia during myelin phagocytosis. These shared deficits included impaired myelin uptake, altered lysosomal function, ER stress, and lipid droplet accumulation that were rescued inTrem2-deficient microglia with the addition of recombinant gal-3. RNA-seq analyses revealed common genes and pathways affected that importantly included genes associated with the integrated stress response.
Taken together, these data suggest Gal-3 mediates and throttles the TREM2-dependent stress response during age-related myelin degeneration. Further, it provides support for targeting TREM2 function early to augment reparative signaling preventing overt debris accumulation and/or promoting gal-3 to alleviate stress pathways that can lead to premature microglial dysfunction and onset of pathology
The Role of TREM2 and the Responses Mediated by Galectin-3 During Age-Related Myelin Degeneration
No full textIUIAging is the greatest known risk factor for various neurodegenerative diseases. Myelin degeneration is an early pathological indicator of these diseases and normal part of aging; albeit, to a lesser extent. Despite this, little is known about how age-related degeneration could contribute to and impact development of neurodegenerative disease. Microglia participate in a variety of white matter events from demyelination to remyelination. The microglial innate immune receptor triggering receptor expressed on myeloid cells 2 (TREM2) has been implicated in regulating (de)myelination.
We found in response to demyelination, TREM2 is required for large volumes of myelin debris and during extended periods of phagocytosis. In addition to lysosomal regulation, we showed TREM2 can modify the ER stress response prior to overt myelin debris preventing early microglial dysfunction. We found TREM2 is necessary for remyelination by recruiting reparative glia and mediating signaling that promotes OPC differentiation/maturation. One of the signaling factors involved, the β-galactosidase-binding protein galectin-3 (gal-3), was recently identified as a ligand for TREM2, however little is known about this interaction in the context of aging or neurodegenerative disease.
Treating microglia with a pharmacological gal-3 inhibitor, we found overlapping functional deficits with Trem2-deficient microglia during myelin phagocytosis. These shared deficits included impaired myelin uptake, altered lysosomal function, ER stress, and lipid droplet accumulation that were rescued inTrem2-deficient microglia with the addition of recombinant gal-3. RNA-seq analyses revealed common genes and pathways affected that importantly included genes associated with the integrated stress response.
Taken together, these data suggest Gal-3 mediates and throttles the TREM2-dependent stress response during age-related myelin degeneration. Further, it provides support for targeting TREM2 function early to augment reparative signaling preventing overt debris accumulation and/or promoting gal-3 to alleviate stress pathways that can lead to premature microglial dysfunction and onset of pathology
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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