1,721,061 research outputs found
Macroglial diversity and its effect on myelination
Full text linkMultiple sclerosis (MS) is a chronic disease of the central nervous system characterized by local loss of myelin, a protective, isolating layer around axons. Myelin can be restored by a natural regenerative process, called remyelination. However, remyelination ultimately fails in MS. Successful remyelination requires the maturation of oligodendrocyte progenitor cells (OPCs) into myelin forming oligodendrocytes. Remyelination is orchestrated by astrocytes. Notably, remyelination is more efficient in grey compared to white matter. In this thesis we investigated whether astrocytes from grey and white matter distinctly modulate OPC functioning and maturation. We demonstrate that astrocytes and OPCs from grey matter may together provide an environment that is more effective in the regeneration of myelin than astrocytes and OPCs from white matter. White matter astrocytes supported myelin formation less than grey matter astrocytes, partially due to producing more inhibitory fibronectin aggregates. In addition, grey matter OPCs appeared better equipped for remyelination. Unexpectedly, specific inhibition of cholesterol biosynthesis in white matter astrocytes enhanced myelin formation by oligodendrocytes. This finding provides a possible new target for promoting myelin formation in white matter. Taken together, research into the failure of remyelination in MS will benefit from taking into account regional differences between cells from grey and white matter. This awareness will contribute to an improved insight into the disease progression of MS. In addition, this will provide challenging opportunities for the development of more specific and thereby efficiency increasing therapy for the treatment of MS, directed at improving myelin recovery in MS lesions
Diversity of microglia:Their contribution to multiple sclerosis lesion formation
Full text linkMultiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by myelin loss and axonal damage that leads to lesion formation. Microglia are key players in MS pathology as they play a role in demyelination and inflammation. In this thesis we showed that the profile of human microglia isolated from post-mortem brain tissue can reliably be studied in order to identify microglial specific characteristics in relation with neuropathology. Subsequently, microglia are already involved in myelin processing in normal-appearing white matter (NAWM) MS tissue, devoid of MS lesions. Furthermore, microglia showed a region-specific profile, that differs between cortical grey and white matter regions. Microglial clusters, which can appear in NAWM MS tissue, might be the start of lesion formation. They form a heterogenous population and several clusters showed signs of demyelination and reside in an inflammatory environment, consisting of antibodies, T and B cells. In normal-appearing MS tissue, microglia are in a homeostatic state and isolated microglia are tolerogenic to classic immune stimuli. We provide evidence that antibodies, present on MS myelin, act as an additional stimulus and break microglial immune tolerance. In active MS lesions, microglia highly expressed proteins related to phagocytosis and myelin processing, but they do not secrete inflammatory cytokines and infiltrating macrophages are hardly present. Furthermore, demyelination already takes place around chronic active MS lesions, suggesting that they are expanding. Microglia are an interesting target to treat MS; by blocking pro-inflammation and promoting their phagocytic and regenerative capacities, formation of new MS lesion might be prevented
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Tissue donations for multiple sclerosis research: current state and suggestions for improvement
No full textAbstract Although major progress in multiple sclerosis research has been made during the last decades, key questions related to the cause and the mechanisms of brain and spinal cord pathology remain unresolved. These cover a broad range of topics, including disease aetiology, antigenic triggers of the immune response inside and/or outside the CNS and mechanisms of inflammation, demyelination neurodegeneration and tissue repair. Most of these questions can be addressed with novel molecular technologies in the injured CNS. Access to brain and spinal cord tissue from multiple sclerosis patients is, therefore, of critical importance. High-quality tissue is provided in part by the existing brain banks. However, material from early and highly active disease stages is limited. An initiative, realized under the patronage of the European Charcot Foundation, gathered together experts from different disciplines to analyse the current state of multiple sclerosis tissues collected post-mortem or as biopsies. Here, we present an account of what material is currently available and where it can be accessed. We also provide recommendations on how tissue donation from patients in early disease stages could be potentially increased and for procedures of tissue sampling and preservation. We also suggest to create a registry of the available tissues that, depending on the source (autopsy versus biopsy), could be made accessible to clinicians and researchers.Abstract Although major progress in multiple sclerosis research has been made during the last decades, key questions related to the cause and the mechanisms of brain and spinal cord pathology remain unresolved. These cover a broad range of topics, including disease aetiology, antigenic triggers of the immune response inside and/or outside the CNS and mechanisms of inflammation, demyelination neurodegeneration and tissue repair. Most of these questions can be addressed with novel molecular technologies in the injured CNS. Access to brain and spinal cord tissue from multiple sclerosis patients is, therefore, of critical importance. High-quality tissue is provided in part by the existing brain banks. However, material from early and highly active disease stages is limited. An initiative, realized under the patronage of the European Charcot Foundation, gathered together experts from different disciplines to analyse the current state of multiple sclerosis tissues collected post-mortem or as biopsies. Here, we present an account of what material is currently available and where it can be accessed. We also provide recommendations on how tissue donation from patients in early disease stages could be potentially increased and for procedures of tissue sampling and preservation. We also suggest to create a registry of the available tissues that, depending on the source (autopsy versus biopsy), could be made accessible to clinicians and researchers
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe 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
Full text linkWe 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
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