1,721,026 research outputs found
Neural crete differenciation following constitutive activation of NRAS or BRAF proteins
No full textLes mélanocytes sont des cellules productrices de mélanines, à l’origine de la teinte de la peau, des yeux et des cheveux. Elles dérivent d'une population multipotente appelée cellules de la crête neurale, qui génère entre autres également tout le système nerveux périphérique. Une prolifération accrue des précurseurs des mélanocytes durant le développement entraine chez l’homme l’apparition d’un nævus mélanocytaire congénital (NMC). Cette prolifération est due à une mutation somatique au sein d'un de ces précurseurs, dans des gènes de la voie de signalisation des MAP-Kinases, NRAS ou BRAF. Les plus grandes formes, couvrant des parties entières du corps, sont syndromiques. Ils peuvent associer des mélanocytoses, des malformations ou tumeurs cérébrales ou méningées, parfois épileptogènes, ainsi qu'un risque autour de 5% de dégénérer en mélanome, dans un des sites atteints. Durant ma thèse j’ai exploré des modèles murins où les protéines NRAS ou BRAF constitutivement actives sont exprimées très tôt au cours de l’embryogenèse, dans les cellules de la crête neurale. Les embryons mutants BrafV600E connaissent une létalité embryonnaire, probablement due à une superposition de défauts vasculaires et cérébraux. En revanche, les souris NrasG12D sont viables,présentent des mélanocytoses extracutanées dans des sites divers, ainsi qu’une hyperpigmentation cutanée, visible en postnatal. Cette hyperpigmentation est associée à une augmentation de la densité folliculaire, ainsi qu’à un dérèglement du cycle du follicule pileux. Des cultures de cellules de crête neurale murines, BrafV600E ou NrasG12D et contrôles, ont permis d’élucider sur le plan moléculaire les effets de telles mutations.Melanocytes are the vertebrate cells that produce melanin, conferring color on skin, hair and eyes. They arise from a multipotent embryonic cell population called the neural crest, which also gives rise to the peripheral nervous system of the body and many other cell types. Abnormal proliferation of melanocyte precursors before birth can lead to human congenital melanocytic nevus (CMN). CMN are caused by prenatal somatic mutations in the NRAS or BRAF genes of the MAP-Kinase pathway, in one of these precursors. The largest CMN, covering entire segments of the body or head, are syndromic. They are sometimes associated with epileptogenic brain or meningeal malformations, tumors or melanocytosis, and they present a risk of about 5% in all these sites of becoming pediatric malignant melanoma. During my thesis, I explored mouse models expressing constitutively activated NRAS or BRAF proteins in neural crest cell lineages, from very early in embryogenesis. BrafV600E mutant embryos are embryonic lethal at mid-gestation, probably due to coinciding vascular and brain defects. In contrast, NrasG12D mice are viable, present extracutaneous melanocytosis in various sites as well as postnatal hyperpigmentation of the skin. This is associated with increased hair follicle density, and a deregulated hair cycle. Cell culture of mutant or wildtype mouse neural crest cells of both genotypes has permitted the comparison and discovery of molecular differences introduced by these mutations
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
HABILITATION A DIRIGER LES RECHERCHES UNIVERSITE DE LA MEDITERRANEE AIX-MARSEILLE II
No full textBorn and educated for the most part in the United States, I have enjoyed the luxury of excellent mentorship during my career thus far as an independent scientist in France. All these mentors have taken it on trust that my training for a Ph.D. also included the necessary tools for directing original research responsibly, at all levels. However, the habilitation is an obligate rite of passage for researchers in France, Germany, Sweden and a number of other European countries. It ensures both that I am competent to not only continue to conduct original research, and that I have a directive seam in my research interests over time that is sufficiently rich to support myself and those trainees who will learn from my experience and contribute their efforts by my side to advancing science. To demonstrate that the faith of these esteemed colleagues has been well-placed since my Ph.D., I hereby present, to the best of my ability, my acquired credentials and my near- to mid-term projects
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
Etude du rôle de l'acide rétinoïque dans la morphogenèse de la voie efférente cardiaque
No full textL'acide rétinoïque (AR), métabolite actif de la vitamine A, est une molécule qui a une fonction pléiotropique au cours du développement embryonnaire dont l'excès ou le déficit entraine diverses pathologies cardiaques. Les mutants perte de fonction pour l'enzyme de synthèse de l'AR, la rétinaldéhyde déshydrogénase 2 Raldh2), possèdent de multiples défauts cardiaques. Ces embryons meurent vers le neuvième jour de développement mais cette létalité peut être sauvée en ajoutant de l'AR dans la nourriturre des femelles en gestation. Les mutants Raldh2-/- sauvés ont un Tronc Artériel Commun (TAC) qui est un vaisseau unique au pôle artériel du coeur à la place de l'AO et du TP. Le but de ma thèse a été de comprendre les mécanismes moléculaires et cellulaires conduisant à ce TAC. Ce TAC est à dominance aortique et les connexions des artères coronaires au TAC sont malpositionnées. Nos résultats montrent que la réduction de la longueur de la VE des mutants Raldh2-/- sauvés est associée à une hypoplasie du mésoderme pharyngé. Les mutants Raldh2-/- sauvés possèdent une altération de l'expression de gènes essentiels pour l'élongation de la VE, la rotation de la VE est aussi affectée . Les cellules de la crête neurale cardiaque (CCNC) sont nécessaires pour la septation de la VE et leur contribution à la VE n'est pas altérée dans les mutants Raldh2-/- sauvés. En revanche, elles sont anormalement localisées à proximité du myocarde et anormalement orientées perpendiculairement au futur plan de septation. Cette délocalisation des CCNC est corrélée à une augmentation du processus de transition endothélio-mésenchymateux. L'AR est donc une molécule essentielle pour la morphogenèse de la VE.Retinoic acid (RA), the active metabolite of vitamin A, is a molecule with pleiotropic functions during development. An excess or deficiency of RA during development leads to various cardiac pathologies. Loss-of-function of retinaldehyde dehydrogenase 2 (Raldh2), the enzyme that synthesises RA, results in various cardiac defects. Mutant embryos die at around the ninth day of embryonic development (E9), but this lethality can be rescued by supplementing the gestating female's diet with RA. RA-rescued Raldh2-/- displayed a persistent truncus arteriosus (PTA), a unique artery at the arterial pole of the heart, rather than separate aorta and pulmonary trunk. The aim of my thesis was to understand the molecular and cellular mechanisms leading to PTA. This PTA is predominantly an aortic phenotype, associated with malpositioned of the coronary artery connections. Our results show that the reduced length of RA-rescued Raldh2-/- OFTs was linked to pharyngeal mesoderm hypoplasia. RA-rescued Raldh2-/- mutants expressed altered levels of several genes that are essential for OFT elongation and OFT rotation was also affected. Cardiac neural crest (CNC) cells play an essential role in OFT septation and their contribution to the OFT was not altered in RA-rescued Raldh2-/- mutants. However, CNC cells display abnormal characteristics, and are found in close proximity to the myocardium, oriented perpendicularly to the plane of septation. This mis-location of the CNC cells was associated with increased endothelial-to-mesenchymal transition (EMT). Accordingly, an increased contribution of endocardial EMT to valve mesenchyme. In conclusion, RA is essential for OFT morphogenesis
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
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