1,720,964 research outputs found
Role of Glutathione (GSH) in hypoglicaemia-induced cell death
No full textLe diabète est une maladie dont le fardeau économique est important, avec un nombre de personnes diagnostiquées qui devrait atteindre 700 millions en 2045. Les patients diabétiques de type 1 et de type 2 développent des pathologies secondaires, dont la rétinopathie diabétique (RD), qui est l'une des principales causes de cécité acquise dans le monde. La rétinopathie diabétique est une maladie qui a été depuis longtemps associée à l'effet d'une hyperglycémie prolongée, principalement sur les cellules vasculaires et les péricytes. Cependant, il a récemment été proposé que la neurodégénérescence (c'est-à- dire la mort des cellules neuronales) joue un rôle important dans l’établissement de cette maladie. En effet, certaines études indiquent que la mort des cellules rétiniennes pourrait intervenir avant les dommages vasculaires typiques des rétinopathies. Par conséquent, une meilleure compréhension et un contrôle des mécanismes de mort des cellules neuronales pourraient être bénéfiques afin de prévenir l'apparition et/ou la progression de la rétinopathie diabétique.
La production de radicaux libres, produits pendant la respiration mitochondriale, joue un rôle prépondérant dans ces mécanismes. le niveaux de radicaux libres sont généralement bien régulée par les défenses antioxydantes de la cellule. Le glutathion (GSH) est l'un des antioxydants les plus importants de la cellule. Dans la rétine ce sont les photorécepteurs qui consomment la fraction de glucose la plus élevée, car ils ont un métabolisme très actif. Ils sont de ce fait le plus sensible aux radicaux libres. Ne disposant pas de réserves de glycogène l’ensemble du glucose dont ils ont besoin doit être fourni par les vaisseaux rétiniens, ce qui les rend sensible à une diminution du glucose. En 2011, une étude du groupe du Dr Roduit a montré qu’une hypoglycémie de 5 heures induisait la mort des cellules de la rétine qui est corrélée à une diminution des taux de GSH. Une observation similaire a été faite lors de la culture à bas glucose (1mM) des cellules photoréceptrices 661W ; en plus d’une augmentation de la production de radicaux libres. L’administration de GSH éthyl ester était capable de restaurer le pool de GSH et de bloquer l'apoptose ; au contraire, une diminution du pool de GSH était capable d’induire la mort cellulaire.
Dans mon travail de thèse, nous avons analysé les effets de l’hypoglycémie sur le stress du réticulum endoplasmique (RE). Nous avons montré, in vitro et in vivo, que le bas glucose induit une réponse au niveau de RE, et ceci indépendamment des niveaux de GSH de la cellule. Nous avons cherché à déterminer si la modulation stress du RE permettait de protéger les photorécepteurs contre la mort cellulaire. Cette hypothèse fait l’objet d’une étude actuellement en cours dans notre laboratoire. De plus, nous nous sommes intéressé au rôle spécifique du GSH dans notre modèle en utilisant des antioxydants (N-acétylcystéine et N-acétylcystéine amide) afin de restaurer les niveaux de GSH et de prévenir la mort cellulaire induite par le bas glucose. Les deux composés utilisés sont toxique pour les cellules
photoréceptrices à bas glucose, Nous essayons de mieux comprendre les modifications métabolomiques engendrées par le bas glucose afin de déterminer la toxicité surprenante de ces composés.
Nous pensons que la protection des photorécepteurs contre la mort cellulaire induite par l'hypoglycémie peut représenter une fenêtre thérapeutique intéressante pour protéger la vue des patients atteint de RD, en particulier pour ceux qui sont dans les premières phases de cette maladie.
--
Diabetes is a disease with a significant economic burden, with an expected number of diagnosed people to rise until 700 million in 2045. Both type 1 and type 2 diabetic patients are at risk of developing secondary side effects, including diabetic retinopathy (DR), which is one of the leading cause of acquired blindness worldwide. Diabetic retinopathy is a disease that has long been associated with the effect of prolonged hyperglycaemia, primarily on vascular cells and pericytes. However, it has recently been proposed that neurodegeneration (i.e. neural cell death) plays an important role in the establishment of the disease. Indeed some studies showed that retinal cell death might happen earlier than vascular damages. Therefore, blocking or delaying neural cell death mechanisms might be beneficial in preventing the onset and/or progression of diabetic retinopathy. It has been recently proposed that the most important molecular mechanism involved in cell death are the increased flux of glucose in the polyol and hexosamine pathways, the increase of advanced glycation end products production and the protein kinase C activation.
All these mechanisms share the unifying reactive oxygen species (ROS) production as a harmful consequence for both vascular and neural cells. ROS are normally produced during mitochondrial respiration: however, usually ROS production is well counteracted by the antioxidant defenses of the cell. Glutathione (GSH) is one of the most important antioxidant defense in the cells. Indeed, the cells which are the most damaged by ROS production are the most metabolically active: in the retina, the highest glucose fraction is consumed by photoreceptors. Despite the huge amount of glucose required for their homeostasis, photoreceptors do not have glycogen reserves. Therefore, all the glucose they need must be supplied by retinal vessels, and this makes them directly damaged in case of glucose decrease. In 2011, a study from Dr.Roduit’s group showed that a 5-hour hypoglycaemia induced retinal cell death which is correlated with a decrease in GSH levels. A similar observation was made when 661W photoreceptor cells were cultured at low glucose (1mM); in addition to an increase in free radical production. Administration of GSH ethyl ester was able to restore the GSH pool and block apoptosis; in contrast, a decrease in the GSH pool was able to induce cell death.
In addition, we addressed the specific role of GSH in our model by using anti-oxidants (N-acetylcysteine and N-acetylcysteine amide) to restore GSH levels and prevent low-glucose induced cell death. Both compounds used are toxic to low photoreceptor cells cultured at low glucose. We are trying to better understand the metabolomic changes caused by low glucose in order to determine the surprising toxicity of these compounds.
In my thesis work, we assessed the effects of hypoglycemia on endoplasmic reticulum (ER) stress. We showed both, in vitro and in vivo, that ER stress was induced by low glucose and this independently of
GSH levels. We sought to investigate whether ER stress modulation is able to protect photoreceptors. This hypothesis is currently under investigation in our laboratory.
We believe that protecting photoreceptors from hypoglycaemia-induced cell death may represent an interesting therapeutic window to protect the eyesight of patients with DR, especially for those in the early phases of this disease
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
- …
