1,720,957 research outputs found
Perturbateurs endocriniens, récepteurs aux xénobiotiques et métabolisme intestinal : évaluation de réponses biologiques à l'aide d'un modèle in vivo de poisson-zèbre transgénique
No full textWhile human toxicology is reporting links between endocrine disruptors (ED) and metabolic diseases (obesity, type II diabetes, hepatic steatosis...), the need for tests to assess their impact on the body and characterise their mode of actions (MoA) has become a major challenge for the regulation of these substances. Research has therefore focused on the development of bioassays that reproduce metabolic tissues such as liver and adipose tissue, in which the effects of ED are assessed. However, the influence of pollutants and contaminants on other tissues that are strongly involved in the metabolism of xenobiotics and endogenous substances, such as the intestine, remains less investigated. Regulatory developments in assessing the effects of chemical substances have made necessary to develop new alternative methods to animal experimentation, making the embryo of zebrafish (Danio rerio) a promising in vivo model (currently not subject to animal regulation until 120 hours post-fertilization (hpf)), capable of screening a large number of substances in a short space of time. Its proximity to humans, including at the intestinal level, its zootechnical and the malleability of its genome make it possible to create transgenic lines to monitor, for example, the activity of fluorescent reporter genes such as GFP (Green Fluorescent Protein) under the control of the promoter of ED target genes, thus signalling their presence in the environment, in connection with metabolic disruption. The work carried out during this thesis led to the establishment of a new transgenic zebrafish model, tg(cyp3a65:GFP), which expresses the GFP under the control of the promoter of CYP3A65. This cytochrome P450 is an ortholog of the human CYP3A4, a major enzyme involved in the metabolism of xenobiotics and endogenous compounds. Characterisation of this model enabled to show in vivo that GFP is exclusively localised in the anterior part of the intestine at the embryonic stage, expressed dynamically during development (from 0 to 120 hpf) and induced by prototypical ligands of two xenobiotic receptors, zfPXR and zfAhR2, orthologs of PXR (pregnane X receptor) and AhR (aryl hydrocarbon receptor) in humans. Clotrimazole and 2,3,7,8-tetrachlorodibenzo-p-dioxin, agonist ligands for zfPXR and zfAhR2 respectively, induce cyp3a65, either alone or in combination. Based on this tg(cyp3a65:GFP) line, a bioassay called EMERGE (Effect of Metabolic Endocrine disRuptors in Gut of zebrafish Embryos) was developed to screen the effects of chemical substances at the intestinal level. Exposure to around twenty ED belonging to different chemical families, selected for their potential activity on metabolism, showed that various molecules were inactive (e.g. tributyltin) while others induced (e.g. bisphenol A) or inhibited (e.g. cadmium chloride) intestinal cyp3a65 expression, according to a concentration-dependent response after 48h exposure, from 72 to 120 hours post-fertilization. Although their precise MoA on cyp3a65 expression is unknown, these results suggest a potential interaction with different signalling pathways mediated by zfPXR, zfAhR2 and even zfGR, reminding the complex regulation of CYP3A4 expression in humans. This work shows that the use of the tg(cyp3a65:GFP) zebrafish embryo model provides new data, easily collected by imaging, for assessing the danger of ED in a poorly investigated tissue such as the intestine. Although the toxicological consequences of such disturbances in terms of metabolic disorders need to be explored in greater depth, the EMERGE bioassay appears to be a relevant tool for studying the MoA of ED on intestinal metabolism in an in vivo context.Alors que la toxicologie humaine fait état de liens entre les perturbateurs endocriniens (PE) et les maladies métaboliques (obésité, diabète de type II, stéatose hépatique), le besoin de tests permettant d'évaluer leur impact sur l'organisme et de caractériser leurs modes d'action (MoA) est devenu un enjeu majeur pour la réglementation de ces substances. Ainsi, la recherche a mis l'accent sur le développement de bioessais reproduisant des tissus métaboliques comme le foie et le tissu adipeux au sein desquels sont évalués les effets des PE. L'influence des polluants sur d'autres tissus très impliqués dans le métabolisme des xénobiotiques et des substances endogènes, comme l'intestin, reste néanmoins moins investiguée. L'évolution de la réglementation en matière d'évaluation des effets des substances impose de développer de nouvelles méthodes alternatives à l'expérimentation animale, faisant de l'embryon de poisson-zèbre (Danio rerio) un modèle in vivo prometteur (actuellement non soumis à la réglementation animale jusqu'à 120 heures post-fécondation (hpf)), capable de cribler un grand nombre de substances en un temps court. Sa proximité avec l'être humain, y compris au niveau intestinal, ses avantages zootechniques ainsi que la malléabilité de son génome permettent de créer des lignées transgéniques pour suivre par exemple l'activité de gènes rapporteurs fluorescents comme celui de la GFP (Green Fluorescent Protein) sous le contrôle de promoteur de gènes cibles des PE, signalant ainsi leur présence dans l'environnement et ce, en lien avec une perturbation métabolique. Les travaux menés durant cette thèse ont permis l'établissement d'un nouveau modèle de poisson-zèbre transgénique, tg(cyp3a65:GFP), exprimant la GFP sous le contrôle du promoteur de CYP3A65. Ce cytochrome P450 est un orthologue du CYP3A4 humain, enzyme majeure du métabolisme des xénobiotiques et de composés endogènes. La caractérisation de ce modèle a permis de montrer in vivo que la GFP est exclusivement localisée dans l'intestin antérieur au stade embryonnaire, exprimée de façon dynamique au cours du développement (de 0 à 120 hpf) et induite par des ligands prototypiques de deux récepteurs aux xénobiotiques chez le poisson-zèbre, zfPXR et zfAhR2, orthologues de PXR (pregnane X receptor) et AhR (aryl hydrocarbon receptor) chez l'humain. Le clotrimazole et la 2,3,7,8-tétrachlorodibenzo-p-dioxine, respectivement ligands agonistes de zfPXR et zfAhR2, provoquent des inductions de l'expression du cyp3a65, seuls ou en mélange. S'appuyant sur la lignée tg(cyp3a65:GFP), un bioessai nommé EMERGE (Effect of Metabolic Endocrine disRuptors in Gut of zebrafish Embryos) a été développé, pour cribler les effets de substances chimiques au niveau intestinal. L'exposition à une vingtaine de PE appartenant à différentes familles chimiques, sélectionnées en raison de leur activité potentielle sur le métabolisme, montrent que diverses molécules se révèlent inactives (e.g. tributylétain) tandis que d'autres induisent (e.g. bisphénol A) ou inhibent (e.g. chlorure de cadmium) l'expression intestinale de cyp3a65, selon des réponses concentration-dépendantes après 48h d'exposition, entre 72 et 120 hpf. Si leurs MoA précis vis-à-vis de l'expression de cyp3a65 n'est pas connu, ces résultats suggèrent une interaction potentielle avec différentes voies de signalisation médiées par zfPXR, zfAhR2, voire zfGR, rappelant la régulation complexe de l'expression du CYP3A4 chez l'humain. Ces travaux montrent que l'utilisation du modèle d'embryon de poisson-zèbre tg(cyp3a65:GFP) fournit de nouvelles données, facilement collectées par imagerie, pour évaluer le danger des PE sur un tissu peu étudié tel que l'intestin. Bien que les conséquences toxicologiques de telles perturbations en termes de troubles métaboliques doivent être explorées de manière plus approfondie, le bioessai EMERGE apparait comme un outil pertinent pour étudier les MoA des PE sur le métabolisme intestinal dans un contexte in vivo
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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