1,720,966 research outputs found
From IL-15 to IL-33: the never-ending list of new players in inflammation. Is it time to forget the humble aspirin and move ahead?
No full textThe study of the inflammatory response has seen a tremendous expansion over the last 30 years. Advancements in technology and better knowledge of the ethiopathogenesis of several inflammatory conditions have facilitated this process allowing researchers to almost reach the core of problem. Thus, we now know that inflammation can be manifested in many different ways depending on the context that has elicited it. Viral and infectious, allergic and autoimmune, carcinogenic and resolutive are just a few examples of how inflammation can disguise itself. However, and most intriguingly, it appears that the more we try to discover "an ideal target" and delineate borders for a specific class of inflammatory conditions the more we find similarities, overlaps or often links that we did not predict. These somehow disappointing findings have pushed researchers towards a frantic search for new and more "reliable" targets. As result, we have recently seen a surge of many novel mediators of inflammation. If we just limit our focus to inflammatory cytokines, the main topic of this commentary, the list seems never-ending: IL-15, IL-17, IL-18, IL-21, IL-22, IL-23, IL-27 and IL-33. Are these cytokines destined to supersede prostaglandins and other autacoids for their key role in inflammation? Are we going to see a cheap and effective alternative to aspirin on the supermarket shelves in the next few years? Here we summarize the most recent findings on the biological effects of these new inflammatory cytokines and discuss how these discoveries might influence our current view on therapeutic approaches to treat inflammatio
Design and characterization of a cleavage-resistant Annexin A1 mutant to control inflammation in the microvasculature
No full textHuman polymorphonuclear leukocytes adhesion to endothelial cells during the early stage of inflammation leads to cell surface externalization of Annexin A1 (AnxA1), an effector of endogenous anti-inflammation. The antiadhesive properties of AnxA1 become operative to finely tune polymorphonuclear leukocytes transmigration to the site of inflammation. Membrane bound proteinase 3 (PR3) plays a key role in this microenvironment by cleaving the N terminus bioactive domain of AnxA1. In the present study, we generated a PR3-resistant human recombinant AnxA1-named superAnxA1 (SAnxA1)-and tested its in vitro and in vivo properties in comparison to the parental protein. SAnxA1 bound and activated formyl peptide receptor 2 in a similar way as the parental protein, while showing a resistance to cleavage by recombinant PR3. SAnxA1 retained anti-inflammatory activities in the murine inflamed microcirculation (leukocyte adhesion being the readout) and in skin trafficking model. When longer-lasting models of inflammation were applied, SAnxA1 displayed stronger anti-inflammatory effect over time compared with the parental protein. Together these results indicate that AnxA1 cleavage is an important process during neutrophilic inflammation and that controlling the balance between AnxA1/PR3 activities might represent a promising avenue for the discovery of novel therapeutic approaches
Neutrophil-expressed p21/waf1 Favors Inflammation Resolution in Pseudomonas aeruginosa Infection
No full textNeutrophil-associated inflammation during Pseudomonas aeruginosa lung infection is a determinant of morbidity in cystic fibrosis (CF). Neutrophil apoptosis is a key factor in inflammation resolution and is controlled by cytosolic proliferating cell nuclear antigen (PCNA). p21/Waf1, a cyclin-dependent kinase inhibitor, is a partner of PCNA and its mRNA is upregulated in human neutrophils during lipopolysaccharide challenge. We here show that after 7 days of persistent infection with Pseudomonas aeruginosa, neutrophilic inflammation was more prominent in p21-/- compared to wild type mice. Notably, no intrinsic defect in the phagocytosis of apoptotic cells by macrophages was found in p21-/- compared to wild type mice. Inflammatory cells analysis in the peritoneal lavages after zymosan-induced peritonitis showed a significant increased number of neutrophils at 48h in p21-/- compared with wild type mice. In vitro analysis was consistent with a delayed neutrophil apoptosis in p21-/- compared with wild type mice. Ectopic expression of p21/waf1 in neutrophil-differentiated PLB985 cells potentiated apoptosis and reversed the prosurvival effect of PCNA. In human neutrophils, p21 mRNA was induced by TNF-α, G-CSF and LPS. Neutrophils isolated from CF patients showed enhanced survival, which was reduced after treatment with a carboxy-peptide derived from the sequence of p21/waf1. Notably, p21/waf1 was detected by immunohistochemistry in neutrophils within lung from CF patients. Our data reveals a novel role for p21/waf1 in the resolution of inflammation via its ability to control neutrophil apoptosis. This mechanism may be relevant in the neutrophil dominated inflammation observed in CF and other chronic inflammatory lung conditions
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
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