1,720,961 research outputs found
Beta-glucosyl-sitosterol triggers intestinal inflammation in zebrafish and mouse models possibly contributing to neurodegeneration through the gut-brain axis
No full textGlucosylsterols (GlcSt) are lipids composed of a sterol-derived molecule and a glucose moiety, but little is known about their functions in metabolism. The alteration of their homeostasis, however, has been recognized as a risk factor for the onset of neurodegenerative diseases such as Parkinson’s Disease (PD) and Amyotrophic Lateral Sclerosis (ALS), suggesting they play a role in the physiology of the nervous system. These molecules can be synthetized endogenously, as in the case of b-glucosyl-cholesterol, or they can derive from pathogens, like -glucosyl-cholesterol. The plant-derived b-glucosyl-sitosterol (b-GlcSito), abundant in the seeds of Cycas micronesica, gained scientific relevance since it was recognized as a contributor to the so-called Amyotrophic Lateral Sclerosis-Parkinsonism Dementia Complex (ALS-PDC). This neurodegenerative disorder interested Chamorro people of Guam, who ate Cycas seeds-derived products. Among the main neurodegenerative diseases, PD is characterized by the loss of dopaminergic neurons in substantia nigra. Neuronal death is mainly associated with alteration of cell proteostasis, accumulation of proteinaceous aggregates that become cytotoxic and chronic neuroinflammatory state. Dopamine depletion is responsible for classic motor symptoms, but there is also a plethora of non-motor symptoms characteristic of an early prodromal phase or that may occur at later stages of the disease. Constipation has been recognized as a precocious hallmark that affects patients years before a possible diagnosis. ALS is a neurodegenerative disease caused by the degeneration of upper motor neurons and lower motor neurons, which innervate skeletal muscle. The key-feature of this pathology is progressive muscular wasting towards paralysis, that leads to death for respiratory failure. The presence of non-motor symptoms is peculiar also in this disorder, in which gastrointestinal defects account for constipation and delayed food transit along the digestive tract.
ALS-PDC shows PD features, such as neuronal loss, proteinaceous inclusions, motor symptoms and dementia; ALS features, like muscle atrophy, or both. These observations strengthened the hypothesis that impaired GlcSt homeostasis could drive neurodegeneration, underlining the urgency of studying the impact of these molecules on central nervous system metabolism. My PhD project is focused on the characterization of the effects elicited by the plant-derived b-GlcSito using a completely new zebrafish model treated with this molecule and, in parallel, to deepen the knowledge on the actions triggered in the mouse model. In the first chapter, I present the results obtained exploiting our zebrafish model, at larval and adult life stages. Direct b-GlcSito absorption through the water or following prolonged treatment with a b-GlcSito-enriched-diet seems to cause a gut inflammatory state characterized by altered gene expression and motility. Intestinal dysfunction is paralleled by the impairment of pathways associated with the occurrence of neurodegeneration, like autophagy. In the second chapter, I describe the data obtained from the mouse model fed with b-GlcSito-enriched diet. The increase in the levels of this molecule seems to induce changes in the morphology of gut epithelium, besides the alteration of genes involved in the modulation of inflammation, as revealed by RNAseq of intestinal tissue. Evidence of incoming neurodegeneration was also established through gene and protein expression analyses. In the third chapter, I present preliminary results on b-GlcSito possible mechanism of action. Due to its molecular structure it could interact with steroid hormone receptors, such as the Glucocorticoid Receptor (GR). Thanks to zebrafish mutant lines devoid of genes involved in glucocorticoid synthesis and metabolism, we tried to assess whether b-GlcSito could interact with GR and influence the expression of GR-related genes. Our data seem to support this hypothesis
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
Knockout in zebrafish reveals the role of the glucocorticoid receptor in shaping behavioral syndromes
Get PDFGlucocorticoids (GCs) have a wide spectrum of effects on animal behavior. A recently suggested effect involves determining the structure of individual differences, that is how the behavioral traits of an individual covary, forming the so-called behavioral syndromes. As GCs can exert their action in multiple ways, e.g., via rapid non- genomic effects or via the activation of two highly homologous members of the steroid receptor family acting as transcription factors, it is unclear how the GC modulation of behavioral syndromes takes place. We exploited a zebrafish line with a frameshift mutation in the gene encoding the GC receptor (Gr), to investigate this question. We found that lack of Gr altered the average score of several behavioral traits in the mutant line, determining reduced boldness, and increased activity and sociability. Critically, the pattern of covariation between these traits was also substantially affected by the loss of Gr. The most evident effect was an association of traits involved in boldness in the gr mutant line. This study reveals that, in zebrafish, Gr is not only involved in the modulation of the average value of behavioral traits, but also in how the behavioral traits of an individual are interrelated and determine the behavioral syndromes
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
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