1,720,955 research outputs found
The effects of ageing on microglial phenotypes and the central nervous system response to systemic inflammation
No full textMicroglial cells are resident immune cells of the central nervous system (CNS) that participate in the CNS response to systemic inflammation by producing inflammatory mediators, which subsequently contribute to the behavioural and metabolic adaptations to systemic infections collectively termed sickness behaviour. Ageing leads to changes in microglial phenotype and a maladaptive, exaggerated CNS inflammatory and behavioural response to systemic infection has been described in aged rodents, which could have a negative impact on CNS health. However, most studies examining the effects of ageing on microglia have focused on a single region of the brain (the hippocampus) and have used a single model of infection, the bacterial mimetic lipopolysaccharide (LPS). This raises two important questions – are microglia in different parts of the brain equally effected by ageing, and do different models of systemic infections have different effects on sickness behaviour and on microglia? To address these questions we used immunohistochemistry, quantitative PCR and behavioural assays to investigate the effects of region on age related changes in microglial phenotype along a rostral to caudal axis and the CNS inflammatory and behavioural response elicited by LPS was compared to that elicited during a live infection with Salmonella typhimurium. We detected significant differences in the effects of ageing on microglia of different regions of the CNS, with microglia of white matter areas and the cerebellum demonstrating significantly greater changes in expression of activation markers than those of rostral grey matter areas. Co-ordination and balance was impaired in aged mice at baseline and some sickness behaviours were exaggerated in aged mice in response to LPS injection, whereas Salmonella typhimurium infection induced long-lasting reductions in exploratory activity of equal size in young and aged mice and, in aged mice, co-ordination and balance deficits and prolonged weight loss. A low grade, prolonged inflammatory response was detected in the hippocampus which was accompanied by increased expression of microglial activation markers throughout the young and aged CNS, particularly in the spinal cord, where increased axonal stress and changes in the organisation of the paranodal junction were also observed. These changes in cytokine levels and microglial phenotype were mostly of similar magnitude in young and aged mice, contrasting to the effects of LPS. These results highlight regional differences in the sensitivity of microglia to systemic infection and ageing and show extensive differences between the effects of the bacterial mimetic LPS and a live bacterial infection on microglia and on sickness behaviour in young and aged mice. They also have important implications for the study of ageing microglia regarding the selection of the infection models and in deciding which CNS regions to examine
In vitro characterisation of the duration of action of the histamine-1 receptor antagonist azelastine
No full textAzelastine is a selective antagonist at the human histamine-1 receptor and is used clinically in the treatment of allergic rhinitis. In this study we have investigated its duration of action in vitro in an effort to characterise the receptor and tissue components involved. Chinese hamster ovary cell membrane fragments were used to determine the kinetics of azelastine at the H1 receptor in a radioligand binding assay. Further duration of action studies were completed in tissue preparations using guinea-pig trachea and human bronchus. In radioligand binding studies, azelastine reached steady state at the H1 receptor after approximately 41 min and exhibited a significantly slower dissociation rate constant from the receptor than the first generation antihistamine, diphenhydramine. In washout studies completed in guinea-pig and human airway in vitro tissue preparations, azelastine continued to antagonise the effects of histamine at the H1 receptor for at least 18 h post-washout of the antagonist. This outcome was reversed following removal of the epithelium from guinea-pig isolated tracheal strips. These studies indicate there is a tissue component contributing to azelastine's duration of action, in addition to its direct H1 receptor binding, with evidence suggesting a role for the epithelial layer
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
Age related changes in microglial phenotype vary between CNS regions: grey versus white matter differences
No full textSubtle regional differences in microglial phenotype exist in the adult mouse brain. We investigated whether these differences were amplified during ageing and following systemic challenge with lipopolysaccharide (LPS). We studied microglial morphology and phenotype in young (4mo) and aged (21mo) C57/BL6 mice using immunohistochemistry and quantified the expression levels of surface molecules on microglia in white and grey matter along the rostral-caudal neuraxis. We detected significant regional, age dependent differences in microglial phenotypes, with the microglia of white matter and caudal areas of the CNS exhibiting greater upregulation of CD11b, CD68, CD11c, F4/80 and Fc?RI than grey matter and rostral CNS areas. Upregulation of CD11c with age was restricted to the white matter, as was the appearance of multinucleated giant cells. Systemic LPS caused a subtle upregulation of Fc?RI after 24h, but the other markers examined were not affected. Burrowing behaviour and static rod assays were used to assess hippocampal and cerebellar integrity. Aged mice exhibited exaggerated and prolonged burrowing deficits following systemic LPS injection, while in the absence of an inflammatory challenge aged mice performed significantly worse than young mice in the static rod test. Taken together, these findings show that the effects of age on microglial phenotype and functional integrity vary significantly between CNS compartments, as do, albeit to a lesser extent, the effects of systemic LPS
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
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