1,720,984 research outputs found
Autophagy and glutamate signaling in the onset of Huntington’s Disease
No full textHuntington’s Disease is an inherited disease caused by the expansion of CAG trinucleotide, which results in translation of a protein containing an enlarged polyglutamine (polyQ) domain. HD is characterized by the progressive degeneration of neurons, resulting in involuntary movement and death. Neuronal cell death is caused by an excess of glutamate, that is maintained and
physiological level by a non autonomous cycle between glia and neurons, also called the glutamate-glutamine cycle. Glutamate removal from the synaptic cleft by neuroglia is reduced in a mouse model of Huntington's disease (HD) and in HD patients, suggesting that glial cells actively participate in the survival of neuronal cells. Is possible to manipulate components of the glutamate-glutamine
to ameliorate to neuronal death in HD? To answer this question we are taking advantage of a Drosophila model that has been successfully used to dissect the cellular and molecular events of neurodegenerative disorders including HD. Our preliminary data show that modulation of the enzyme GS1 that converts glutamate into glutamine, in Drosophila’s neurons expressing the human mutant HttQ93, ameliorate animal motility and reduces neuronal loss in the adults. On the contrary, using enzymes that increase the concentration of glutamate has the opposite effect. Growth factor signaling play a dual role in the onset of HD and both in flies and mammals it was shown that while activation of IGF/Akt signaling in neuroglia ameliorates neuronal degeneration induced by HD, the opposite was seen when autophagy was inhibited by activation of the amino TOR signaling pathway. We are using genetics and biochemistry assays to better understand how components of the Insulin/ and TOR pathways act in the regulation of the glutamate-glutamine cycle, and in controlling autophagy in neuronal and glial cells
Study on the mechanisms that induce autophagy in glia cells versus neurons in a Drosophila model for Huntington’s disease
No full textAutophagy is a highly conserved homeostasis and quality control intracellular pathway widely linked to neurodegenerative and metabolic diseases, cancer and aging. Autophagy has been reported to protect from neurodegeneration in many polyQ disease models, such as HD, Parkinson or Spinocerebellar ataxia, and data suggest that loss of autophagy function is a central feature of neurodegenerative disease. In neurons autophagy is the major clearance process able to decrease cellular debris including the intracellular protein aggregates that are produced in human pathologies like Huntington disease (HD). HD is an inherited neurodegenerative disorder caused by the expansion of a CAG triplet in the first exon of the gene. This encodes for an abnormal mutant Huntingtin (Htt) protein that induces neuronal death. One of the most responsible cause of neuronal cell death is the excitotoxicity induced by an excess of glutamate: its level in the CNS is maintained constant thanks to Glutamine-Glutamate cycle established between neurons and glial cells. Our studies demonstrate that the modulation of the enzyme Glutamine-synthetase 1 (GS1) that converts glutamate in glutamine, in neurons ameliorates the phenotype of animals expressing HttQ93. In neurons GS1 is able to induce TOR-dependent autophagy, with the result of the degradation of mutated protein aggregates partially rescuing the disease phenotype.
In the same manner we are also testing the relationship of GS1and autophagy in glial cells: our preliminary studies show that the inhibition of macroautophagy in glial cells expressing human HttQ93 is not limiting the rescue induced by GS1. This data suggest that in glial cells HD degeneration affects fly viability, through a different pathway than the one involved in brain neuronal toxicity. There are three major types of autophagy related to different pathway: chaperone-mediated autophagy (CMA), microautophagy (a direct engulfment of cytoplasmic components) and macroautophagy (which is TOR dependent). We’re currently investigating the role of autophagy in glial cells in the context of a HD disease, trying to understand if a different type of autophagy, a different pathway or different enzymes are involved and in which manner they contribute to the progression of neurodegeneration
In vivo effect of Flavonoids modulates ATM (adipocytes-macrophage infiltration) in Drosophila’s models of obesity
No full textObesity is a pathological condition associated with cardiovascular disorders, type 2 diabete and chronic inflammation also called Adipocyte Tissue Macrophage Infiltration (ATM). Obesity is caused by the interplay of more elements: environmental toxins, sedentary lifestyle and diet. Accumulation of fats in metabolically active sites, such as adipose tissue and liver, causes the increase of proinflammatory cytokines and of the circulating level of free fatty acids (FFAs). These responses result in increased oxidative stress levels caused by release of reactive oxygen species (ROS), that cause adipocyte macrophage infiltration, with a mechanism poorly understood. In obese people the immune cells infiltrate the adipose tissue to promote a chronic inflammatory state. Similarly to vertebrates, Drosophila's circulating immune cells of the hemolymph, called hemocytes, infiltrate the fat body in obese animals. During development, the fat body controls relevant metabolic pathways and inflammation, contributing to the maintenance of the animal energy homeostasis. In our laboratory we are interested in understanding if bioactive compounds, like flavonoids, phenolic compounds found in fruits and vegetables that have anti-oxidant function, may exert a protective action against obesity and ATM due to their anti-oxidant activity. We performed feeding experiments using different
models of obesity: 1-High Fat Diet (HFD), 2-genetic reduction of brummer/ATGL human adipocyte triglyceride lipase and 3-genetic ablation of ecdysone. Our results demonstrated that the presence of flavonoids, in particular of anthocyanin-rich food, reduces hemocytes infiltration in larval fat body. We are relating this effect to a potential inhibition of ROS and cytokines released from the fat body, data will be presented
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
Autophagy and glutamate signaling in the onset of Huntington's disease
No full textNeuronal cell death is often caused by an excess of glutamate that is maintained and physiological level by an equilibrium of signaling between glia and neurons, also called the glutamate-glutamine cycle. Glutamate removal from the synaptic cleft by neuroglia is reduced in a mouse model of Huntington's disease (HD) and in HD patients, suggesting that glial cells actively participate in the survival of neurons cells in HD. But is the glutamate-glutamine cycle contributing to neuronal death in HD? To answer this question we are taking advantage of a Drosophila model that has been successfully used to dissect the cellular and molecular events of neurodegenerative disorders including HD. HD, an inherited disease caused by expansion of CAG trinucleotide, which results in translation of a protein containing an enlarged polyglutamine (polyQ) domain. HD is characterized by the progressive degeneration of neurons, resulting in involuntary movement and death. Our preliminary data show that modulation of the enzyme GS1 that converts glutamate into glutamine, in Drosophila’s neurons expressing the human mutant HttQ93 ameliorate animal motility. On the contrary, using enzymes that increase the concentration of glutamate has the opposite effect. Growth factor signaling play a dual role in the onset of HD and both in flies and mammals it was shown that while activation of IGF/Akt signaling in neuroglia ameliorates neuronal degeneration induced by HD, the opposite was seen when autophagy was inhibited by activation of the amino TOR signaling pathway.
We would like to better understand how components of the TOR pathways act in the regulation of the glutamate-glutamine cycle, and the potential new role of components of the cycle in controlling autophagy in neuronal and glial cells. With this approach we hope to provide novel insights into the processes that cause neuronal degeneration not only in Huntington's disease but also in other neuronal pathologies
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
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