1,720,967 research outputs found
New inflammatory features of human T helper 17 cells in health and multiple sclerosis
Full text linkT helper (Th) 17 cells are a subpopulation of CD4 T lymphocytes characterized by the expression of interleukin (IL)-17 and the transcription factor retinoid acid receptor-related orphan receptor (ROR)gt. Pathogenic role of human Th17 cells has been demonstrated in several autoimmune diseases, including multiple sclerosis (MS), where they promote inflammatory processes. However, the mechanisms leading to the pathogenicity of Th17 cells are largely unknown.
The main objective of this thesis was to identify new mechanisms and molecules inducing inflammatory functions of human Th17 cells that could be potentially involved in the pathogenic processes of MS.
We addressed this aim by using two distinct approaches: 1) analysis of general inflammatory features of Th17 cells acquired during Th17 cell differentiation; 2) analysis of intrinsic features of Th17 cells derived from MS patients.
In order to investigate potential mechanisms responsible for pathogenic functions of human Th17 cells, we dissected their differentiation process by performing a transcriptome analysis of cells at 48 hours and 5 days of differentiation.
We uncovered three time-regulated modules: early modulation, involving exclusively ‘signalling pathways’ genes; late modulation, characterized by genes involved in response to infections; persistent modulation, involving effector immune functions.
To assign them an inflammatory or regulatory potential, we compared Th17 cells differentiated in presence or absence of IL-1b, respectively. We named inflammatory Th17 condition the polarizing milieu containing IL-1b, which is crucially involved in the pathology of Th17-related diseases. In contrast, Th17 regulatory condition refers to the anti-inflammatory IL-10 cytokine produced in Th17 condition lacking IL-1b.
We found that most part of the inflammatory genes belong to the persistent or late module, indicating the crucial role of these genes in the late phases of differentiation.
Thus, we elucidated the global molecular signature that characterizes the acquisition of the inflammatory profile by human Th17 cells, by analysing all genes differentially expressed in regulatory versus inflammatory Th17 conditions. Among inflammatory genes, we identified those sharing pathogenic functions with murine Th17 cells, including IL17A, IFNG, TBX21, EBI3, IRF8, TNFRSF9, TNFRSF14, CCL5, CD40LG, BATF and TNF. In addition, our analysis allowed the identification of novel effector molecules, including interferon (IFN)K, lymphotoxin (LT)-a, IL1A, platelet derived growth factor (PDGF)-A, and transcriptional regulators, such as transcriptional regulators homeodomain-only protein homeobox (HOP)X, SRY (sex determining region Y)-box 2 (SOX2), expression of which was independently validated.
In order to unveil the mechanisms underlying the acquisition of the human Th17 signature, we investigated the potential transcription factors involved in this process. In this context, we analysed the role of RORgt, known master regulator of Th17 cells, and of the two novel transcriptional regulators HOPX and SOX2, by performing RNA-interference experiments. We found that HOPX regulates IL-17A and IFN-g, while SOX2 regulates PDGF-A and IFN-g. As expected, RORgt regulates expression of IL-17A, IL-17F, but also IFN-g, PDGF-A, and IL1A, not previously described. These results, together with the reduced expression of both HOPX and SOX2 in RORC-interfered cells, suggest that HOPX and SOX2 are two transcriptional regulators acting downstream of RORgt signalling in human Th17 cells.
In the second approach, we studied the pathogenic features intrinsically associated to Th17 cells using Th17 cells obtained from MS patients. In particular, we compared in-vitro differentiated Th17 cells of MS patients and healthy donors (HD) and we systematically analysed typical features of Th17 cells, including receptors, transcription factors and soluble factors by flow cytometry, ELISA and Luminex assays. We also included in this study the expression analysis of PDGF and LT-a, two novel effector molecules that we found associated to inflammatory Th17 cells in the previous approach. Results from these analyses unveiled the increased expression of pro-inflammatory proteins IL-21, IL-2, and IL-1 receptor1 (IL-1R1) in Th17 cells derived from MS patients compared to those from HD.
Moreover, we found that Th17 cells derived from MS patients express higher levels of LT-a compared to those from HD, indicating that the pathogenic signature that we previously identified contains intrinsic inflammatory features of Th17 cells derived from patients affected by Th17-related diseases.
In conclusion, the main results of the project were: 1) the identification of the inflammatory signature of human Th17 cells, that includes novel Th17 genes, such as IFNK, IL1A, PDGF-A, and LT-a, and novel transcriptional regulators HOPX and SOX2; 2) the identification of the intrinsic Th17 features specifically overexpressed in Th17 cells of MS patients, that includes IL-21, IL-2, IL-1R1, and LT-a.
Importantly, these factors could become new biomarkers or new therapeutic targets in Th17-related autoimmune diseases
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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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