1,720,958 research outputs found
L'influence du Muramyl-Dipeptide sur la modulation de l'immunité innée dans la pathologie d'Alzheimer
No full textLa maladie d'Alzheimer (MA) est la maladie neurodégénérative complexe et multifactorielle la plus fréquente des démences des personnes âgées. Elle engendre des dérégulations du système immunitaire inné, provoquant une dégénérescence de l'environnement cérébral et des troubles cognitifs majeurs, tels que des changements de personnalité, de l'apathie et des problèmes de langage. Cette maladie est due, entre autres, à l'accumulation d'un peptide neurotoxique l'amyloïde bêta (Aβ) dans le parenchyme, et particulièrement dans les vaisseaux sanguins du cerveau. La protéine Aβ s'accumule au cours du temps en forme neurotoxique dû à des facteurs génétiques et environnementaux, formant ainsi des dépôts amyloïdes. Depuis quelques années, des études portant sur de nouvelles voies thérapeutiques ont été investiguées, en vue de retarder les symptômes voire potentiellement de guérir la maladie d'Alzheimer. Parmi elles, la modulation des cellules immunitaires innées est d'un grand intérêt, car elle offre un nouvel voie thérapeutique sécuritaire et efficace aux patients. Cette modulation est principalement périphérique, grâce à la conversion populationnelle monocytaire en un phénotype thérapeutique d'intérêt. Les expériences et résultats présentés dans ce mémoire de maîtrise ont pour but de caractériser les différences sexuelles de la voie thérapeutique du muramyl-dipeptide (MDP) dans la conversion monocytaire ciblant la MA. Différentes études ont indiqué le fort pouvoir immunomodulateur du MDP passé par le récepteur NOD2. Pour la caractérisation sur les souris APP[indice swe]/PS1, nous avons administré le MDP sur des souris de 3 à 6 mois pour évaluer le pouvoir thérapeutique préventif contre la formation des plaques d'Aβ. Ainsi nous avons caractérisé davantage les modifications engendrer par le MDP sur les populations monocytaire sur des souris de type sauvage, et NOD2[exposant -/-]. Dans un second temps, sur les souris Alzheimer, l'administration de MDP a permis de retarder l'apparition des symptômes de la MA chez les deux sexes, avec une diminution de la charge d'amyloïde bêta, une conservation des facultés cognitives, de l'intégrité de la barrière hématoencéphalique (BHE), de la membrane basale (BM), avec un système de clairance stimulé pour une élimination périphérique adéquate. Cependant, les souris femelles démontrent des résultats différents. L'ensemble de ces données démontre que le MDP peut être utilisé comme moyen d'immunomodulation préventif capable de retarder les symptômes de la MA avant que celles-ci ne se développent.Alzheimer's disease (AD) is the most common complex and multifactorial neurodegenerative disease in our society. It causes dysregulation of the innate immune system, resulting in degeneration of the brain environment and major cognitive problems, such as personality changes, apathy and language problems. This pathology is due, among other things, to the accumulation of a neurotoxic peptide, amyloid beta (Aβ), in the parenchyma and particularly in the blood vessels of the brain. In recent years, new therapeutic avenues have been investigated to delay symptoms and potentially cure Alzheimer's. Among them, the modulation of innate immune cells is of great interest because it offers a new hope to patients. This modulation is mainly peripheral through monocyte population conversion to a therapeutic phenotype of interest. The experiments and results presented in this master thesis aim to characterize the sex differences of the muramyl dipeptide (MDP) therapeutic pathway in AD-targeted monocyte conversion. Different studies have indicated the strong immunomodulatory power of MDP passed through the NOD2 receptor. We used the APP[subscript swe]/PS1 transgenic model mimicking the genetic form of Alzheimer's disease. For the characterization on APP[subscript swe]/PS1 mice, we administered MDP on these mice from 3 to 6 months to evaluate the preventive therapeutic effect against Aβ plaque formation. Thus, we have further characterized the changes caused by MDP on monocyte populations in healthy and NOD2[superscript -/-] mice. First, we were able to determine that the dose necessary to allow maximal monocyte conversion was 10mg/kg and that the administration named induction/priming (1 injection per day for 3 days) was necessary to start the monocyte stimulation and it is maintained at more than 5 days post-induction. In a second step, in Alzheimer mice, the administration of MDP delayed the onset of AD symptoms in both sexes, with a decrease in beta amyloid load, preservation of cognitive faculties, integrity of the blood-brain barrier (BBB), basal membrane (BM), an increase in phagocytosis and brain anti-inflammatory markers with a stimulated clearance system for an adequate peripheral elimination. However, female mice only showed a delay in AD symptoms, improved cognition, and BBB
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
Bone marrow transplantation increases sulfatase activity in somatic tissues in a multiple sulfatase deficiency mouse model
Get PDFBACKGROUND: Multiple Sulfatase Deficiency (MSD) is an ultra-rare autosomal recessive disorder characterized by deficient enzymatic activity of all known sulfatases. MSD patients frequently carry two loss of function mutations in the SUMF1 gene, encoding a formylglycine-generating enzyme (FGE) that activates 17 different sulfatases. MSD patients show common features of other lysosomal diseases like mucopolysaccharidosis and metachromatic leukodystrophy, including neurologic impairments, developmental delay, and visceromegaly. There are currently no approved therapies for MSD patients. Hematopoietic stem cell transplant (HSCT) has been applied with success in the treatment of certain lysosomal diseases. In HSCT, donor-derived myeloid cells are a continuous source of active sulfatase enzymes that can be taken up by sulfatase-deficient host cells. Thus, HSCT could be a potential approach for the treatment of MSD.
METHODS: To test this hypothesis, we used a clinically relevant mouse model for MSD, B6-Sumf1
RESULTS: After 10 months post-transplant, flow cytometric analysis shows an average of 90% of circulating leukocytes of donor origin (Sumf1
CONCLUSIONS: Our results indicate that HSCT could be a suitable approach to treat MSD-pathology affecting peripheral organs, however that benefit to CNS pathology might be limited
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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