1,721,071 research outputs found
Impact of type I interferons on melanocytes function and phenotype in vitiligo
No full textLe vitiligo est l’affection dépigmentante la plus fréquente de l’adulte caractérisée par la perte des mélanocytes et associée à une réponse immunitaire de type 1. Des anomalies intrinsèques des mélanocytes ont été décrites, telles que des taux élevés d’espèces réactives de l’oxygène, induisant l’expression de gènes associés à la sénescence. Il est établi que la réponse auto-immune dirigée contre les mélanocytes est dépendante de la voie interféron (IFN) de type 2 (IFNγ). Cependant nos données évoquent l’implication d’une signature IFN de type 1 (IFN-I), mais leur rôle dans la physiopathologie du vitiligo est incomplètement connu. Ce projet vise à mieux caractériser le rôle des IFN-I (IFNα et IFNβ) au cours du vitiligo et d’évaluer leur impact sur le phénotype et la fonction des mélanocytes.Une analyse transcriptomique des cellules épidermiques par « single cell RNA sequencing » réalisée à partir des prélèvements cutanés périlésionnels et non lésionnels de patients atteints de vitiligo retrouve un signal IFN-I au niveau périlésionnel. Alors que les cellules dendritiques plasmacytoïdes produisent de l’IFNα, nous montrons que les kératinocytes stimulés par des agonistes des Toll Like Receptor 3 et9 produisent de l’IFNβ. Les mélanocytes traités par les IFN-I sont caractérisés par une augmentation d’expression des marqueurs de sénescence tels que la β-galactosidase et p21; ces observations sont confirmées par analyse par immunofluorescence sur des modèles 3D d’épidermes reconstruits pigmentés avec mélanocytes. Des composants du phénotype de sécrétion associé à la sénescence tels que l’IL-6, IL-8, CCL5, ICAM1, MMP2 sont élevés dans le surnageant des mélanocytes traités par les IFN-I. Enfin, des biopsies cutanées de patients atteints de vitiligo ont été obtenues avant et après 3 et9 mois de traitement par Baricitinib (BARVIT - NCT04822584), inhibiteur de JAK1/JAK2. Les analyses de l’expression épidermique de voie de signalisation associée aux IFN-I (MX1) et l’expression mélanocytaire de marqueurs de sénescence (p21) sur les biopsies ont montré une diminution de MX1et de p21 après traitement.Nos résultats suggèrent que les IFN-I sont impliqués dans la perte des mélanocytes en induisant leur sénescence.Vitiligo is the most common depigmenting skin disorder in adults, characterized by the loss ofmelanocytes and associated with a type 1 immune response. Intrinsic abnormalities in melanocytes have been described, such as elevated levels of reactive oxygen species, leading to the expression ofsenescence-associated genes. It is known that the autoimmune response directed against melanocytesis dependent on the type 2 interferon (IFN) pathway (IFNγ). However, our data suggest the involvement of a type I IFN signature, although their role in the pathophysiology of vitiligo is not fully understood. This project aims to better characterize the role of type I IFN (IFNα and IFNβ) in vitiligo and assess theirimpact on melanocyte phenotype and function. A transcriptomic analysis of epidermal cells through single-cell RNA sequencing from perilesional and non-lesional skin biopsies of vitiligo patients reveals a type I IFN signal at the perilesional level. While plasmacytoid dendritic cells produce IFNα, we demonstrate that keratinocytes stimulated by Toll-LikeReceptor 3 and 9 agonists produce IFNβ. Melanocytes treated with type I IFN are characterized by an increased expression of senescence markers such as β-galactosidase and p21; these observations are confirmed by immunofluorescence analysis on 3D models of pigmented reconstructed epidermis with melanocytes. Components of the senescence-associated secretory phenotype, such as IL-6, IL-8,CCL5, ICAM1, and MMP2, are elevated in the supernatant of IFN-I-treated melanocytes. Finally, skin biopsies from vitiligo patients were obtained before and after 3 and 9 months of treatment with Baricitinib(BARVIT - NCT04822584), a JAK1/JAK2 inhibitor. Analyses of the epidermal expression of the IFN-Isignaling pathway (MX1) and the melanocyte expression of senescence markers (p21) in the biopsies showed a decrease in MX1 and p21 after treatment. Our results suggest that IFN-I are involved in the loss of melanocytes by inducing their senescence
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
Role of Plasmacytoid Dendritic Cells and Langerhans Cells in the control of adaptative immune response in a model of auto-immune disease and under steady-state condition
No full textLes Cellules Dendritiques sont un groupe hétérogène de cellules présentatrices d’antigènes, importantes pour le contrôle des réponses innées et adaptatives. Les Cellules Dendritiques Plasmacytoïdes (pCD) en représentent une population unique, aux caractéristiques phénotypiques et fonctionnelles particulières, notamment par leur capacité à produire de grande quantité d’Interféron de type I (IFN). Cette signature IFN marque la physiopathologie du Lupus Erythémateux Systémique (LES), maladie auto-immune systémique. Les mécanismes à l’origine de cette production excessive d’IFN par les pCD restent incomplètement élucidés. Nous montrons, dans notre étude, chez l’homme comme dans un modèle murin que les plaquettes, activées dans le LES, participent à la production d’IFN via le CD40L. Cette production en excès d’IFN, a pour conséquence une maturation et activation d’autres Cellules Dendritiques (CD) entrainant l’activation inappropriée des lymphocytes T. Chez le sujet sain, cette activation inappropriée du système immunitaire adaptatif doit être strictement contrôlée afin d’assurer l’homéostasie du système immunitaire. Il a été montré précédemment que de nombreux lymphocytes aux caractéristiques phénotypiques de type mémoire-effecteur (TEM) peuplent les tissus périphériques, notamment le tissu cutané. Ces TEM sont capables de s’activer et proliférer localement en réponse à un stimulus. Les Cellules de Langerhans (LC) sont des cellules dendritiques résidant au niveau cutané dans l’épiderme. Leur fonction est à ce jour l’objet d’une controverse entre une fonction immuno-stimulante (modèle humain) et une fonction immuno-régulatrice (modèle murin). Nous démontrons dans cette étude que les LC, à l’état basal, chez l’homme, induisent la prolifération de Lymphocytes T régulateurs (Treg) au niveau cutané, capables de bloquer la stimulation inappropriée des TEM cutanés. Cependant en présence d’un stimulus infectieux, les LC induisent préférentiellement la prolifération des TEM en limitant celle des Treg. Les LC semblent être à la fois immuno-régulatrices ou stimulantes en fonction du contexte biologique auquel elles sont confrontées.Dendritic Cell (DC) are a heterogeneous group of antigen-presenting leukocytes that are important in activation of both the innate and adaptative arms of the immune system. Plasmacytoid Dendritic Cells (pDC) represent a unique population, characterized by their ability to produce large amounts of type I Interferon (IFN). This « IFN signature » is a prominent feature of Systemic Lupus disease (SLE). Mechanisms leading to the excessive production of type I IFN remain largely unknown. Here, in our present study, we demonstrate that platelets are activated in SLE patients by circulating immune complexes and represent a major reservoir of CD40L. Activated platelets potentiate the production of type I IFN by pCD through a CD40L/CD40 interaction. Excessive production of type I IFN by pCD leads to DC activation and maturation and inappropriate activation of auto-reactive T cells.Under steady state condition, inappropriate activation of the immune system must be tightly controlled. It has been previously shown that normal adult human skin contains a large number of resident T cells (TRM) expressing the phenotype of Effector Memory T cells (TEM). These TEMTRM are specific for antigens previously encountered through skin and can be activated and proliferate under specific stimulation. Langerhans Cells (LC) are a group of skin resident DC living in epidermis. There is currently substantial controversy regarding the physiologic role of LC with regard to immunoregulation versus immunostimulation. Here we show that under steady state condition, LC induce the proliferation of a small subset of TRM. These proliferating TRM express the phenotype of TREG and are functional. However this stimulation of TREG could be reversed in the presence of foreign antigen in a dose-dependant fashion, as the addition of a pathogen to LC and TRM led to diminished TREG proliferation and increased TEM proliferation. These findings establish a novel immunological role for LC in human skin, allowing for the constitutive maintenance of tolerance, while also permitting the stimulation of resident immune memory in response to infectious challeng
Role of Plasmacytoid Dendritic Cells and Langerhans Cells in the control of adaptative immune response in a model of auto-immune disease and under steady-state condition
No full textLes Cellules Dendritiques sont un groupe hétérogène de cellules présentatrices d’antigènes, importantes pour le contrôle des réponses innées et adaptatives. Les Cellules Dendritiques Plasmacytoïdes (pCD) en représentent une population unique, aux caractéristiques phénotypiques et fonctionnelles particulières, notamment par leur capacité à produire de grande quantité d’Interféron de type I (IFN). Cette signature IFN marque la physiopathologie du Lupus Erythémateux Systémique (LES), maladie auto-immune systémique. Les mécanismes à l’origine de cette production excessive d’IFN par les pCD restent incomplètement élucidés. Nous montrons, dans notre étude, chez l’homme comme dans un modèle murin que les plaquettes, activées dans le LES, participent à la production d’IFN via le CD40L. Cette production en excès d’IFN, a pour conséquence une maturation et activation d’autres Cellules Dendritiques (CD) entrainant l’activation inappropriée des lymphocytes T. Chez le sujet sain, cette activation inappropriée du système immunitaire adaptatif doit être strictement contrôlée afin d’assurer l’homéostasie du système immunitaire. Il a été montré précédemment que de nombreux lymphocytes aux caractéristiques phénotypiques de type mémoire-effecteur (TEM) peuplent les tissus périphériques, notamment le tissu cutané. Ces TEM sont capables de s’activer et proliférer localement en réponse à un stimulus. Les Cellules de Langerhans (LC) sont des cellules dendritiques résidant au niveau cutané dans l’épiderme. Leur fonction est à ce jour l’objet d’une controverse entre une fonction immuno-stimulante (modèle humain) et une fonction immuno-régulatrice (modèle murin). Nous démontrons dans cette étude que les LC, à l’état basal, chez l’homme, induisent la prolifération de Lymphocytes T régulateurs (Treg) au niveau cutané, capables de bloquer la stimulation inappropriée des TEM cutanés. Cependant en présence d’un stimulus infectieux, les LC induisent préférentiellement la prolifération des TEM en limitant celle des Treg. Les LC semblent être à la fois immuno-régulatrices ou stimulantes en fonction du contexte biologique auquel elles sont confrontées.Dendritic Cell (DC) are a heterogeneous group of antigen-presenting leukocytes that are important in activation of both the innate and adaptative arms of the immune system. Plasmacytoid Dendritic Cells (pDC) represent a unique population, characterized by their ability to produce large amounts of type I Interferon (IFN). This « IFN signature » is a prominent feature of Systemic Lupus disease (SLE). Mechanisms leading to the excessive production of type I IFN remain largely unknown. Here, in our present study, we demonstrate that platelets are activated in SLE patients by circulating immune complexes and represent a major reservoir of CD40L. Activated platelets potentiate the production of type I IFN by pCD through a CD40L/CD40 interaction. Excessive production of type I IFN by pCD leads to DC activation and maturation and inappropriate activation of auto-reactive T cells.Under steady state condition, inappropriate activation of the immune system must be tightly controlled. It has been previously shown that normal adult human skin contains a large number of resident T cells (TRM) expressing the phenotype of Effector Memory T cells (TEM). These TEMTRM are specific for antigens previously encountered through skin and can be activated and proliferate under specific stimulation. Langerhans Cells (LC) are a group of skin resident DC living in epidermis. There is currently substantial controversy regarding the physiologic role of LC with regard to immunoregulation versus immunostimulation. Here we show that under steady state condition, LC induce the proliferation of a small subset of TRM. These proliferating TRM express the phenotype of TREG and are functional. However this stimulation of TREG could be reversed in the presence of foreign antigen in a dose-dependant fashion, as the addition of a pathogen to LC and TRM led to diminished TREG proliferation and increased TEM proliferation. These findings establish a novel immunological role for LC in human skin, allowing for the constitutive maintenance of tolerance, while also permitting the stimulation of resident immune memory in response to infectious challeng
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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