1,720,968 research outputs found

    Characterising the phenotypic and functional role of monocyte-derived foam cells in atherosclerosis

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    Atherosclerosis is a chronic inflammatory disease characterised by the accumulation lipid deposits within the arterial wall, leading to restricted blood flow and increased risk of cardiovascular events. Central to the development of atherosclerosis is the formation of foam cells which are derived from macrophages as a result of excessive accumulation of modified low-density lipoproteins (LDL). Upon oxLDL internalisation, macrophages transform into foam cells through the storage of lipid droplets that are primarily composed of cholesteryl esters which can be hydrolysed to generate free cholesterol. The balance between lipid uptake, storage, and degradation within foam cells is critical to maintain cholesterol homeostasis. Dysregulation in these processes contribute to foam cell persistence and plaque progression. Foam cells contribute significantly to the inflammatory microenvironment within plaque, causing perpetual local inflammation, recruitment of immune cells and plaque instability. The interplay between lipid metabolism and inflammatory signalling within foam cells exacerbates their retention and survival. Understanding the inflammatory role of foam cells in atherosclerosis is crucial for identifying novel therapeutic targets aimed specifically at reducing foam cell-driven inflammation. However, till today identifying and characterising foam cells within atherosclerotic plaques remains a challenge due to significant overlap in markers with other immune cells. One of the aims of this study is to characterise foam cells both at a protein and genomic level via flow cytometry analysis, bulk RNA-sequencing and whole genome spatial transcriptomics to identify potential markers specific to foam cells themselves. Contradictory to the nature of a foam cell phenotype, our results show that foam cells exhibit an anti-inflammatory and lipid metabolising profile genomic profile which coincides with existing data from recent transcriptomic studies. Given that plaque is a heterogenous cellular environment, investigating the role of foam cells in isolation may not accurately represent their realistic function. Therefore, in this study I also examined the functional characteristics of foam cells in co-culture with endothelium in vitro. This approach allowed us to identify changes in lipid mediator secretion due to cell-cell crosstalk where I identified an enrichment in pro-inflammatory prostaglandin secretion in foam cell-endothelial cell co-cultures compared to foam cells alone. In conclusion this study explores the characterisation of foam cells using multiple different avenues. I found that minimal differences were observed between macrophage and foam cell profiles and that monocyte-origin appear to have little to no effect on the genotype of foam cells. Additionally, I show that the foam cells potentially exhibit their pro-inflammatory functional phenotype through cellular crosstalk with endothelium via the secretion of pro-inflammatory lipid mediators

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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

    Galectin-9 supports primary T cell transendothelial migration in a glycan and integrin dependent manner

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    Adaptive immunity relies on the efficient recruitment of T cells from the blood into peripheral tissues. However, the current understanding of factor(s) coordinating these events is incomplete. Previous studies on galectin-9 (Gal-9), have proposed a functionally significant role for this lectin in mediating leukocyte adhesion and transmigration. However, very little is known about its function in T cell migration. Here, we have investigated the role of the Gal-9 on the migration behaviour of both human primary CD4+ and CD8+ T cells. Our data indicate that Gal-9 supports both CD4+ and CD8+ T cell adhesion and transmigration in a glycan dependent manner, inducing L-selectin shedding and upregulation of LFA-1 and CXCR4 expression. Additionally, when immobilized, Gal-9 promoted capture and firm adhesion of T cells under flow, in a glycan and integrin-dependent manner. Using an in vivo model, dorsal air pouch, we found that Gal-9 deficient mice display impaired leukocyte trafficking, with a reduction in pro-inflammatory cytokines/chemokines generated locally. Furthermore, we also demonstrate that Gal-9 inhibits the chemotactic function of CXCL12 through direct binding. In conclusion, our study characterises, for the first time, the capture, adhesion, and migration behaviour of CD4+ and CD8+ T cells to immobilised /endothelial presented Gal-9, under static and physiological flow conditions. We also demonstrate the differential binding characteristics of Gal-9 to T cell subtypes, which could be of potential therapeutic significance, particularly in the treatment of inflammatory-based diseases, given Gal-9 ability to promote apoptosis in pathogenic T cell subsets
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