1,721,056 research outputs found
The role of the fat mass and obesity-associated gene in appetite regulation
No full textFTO encodes a nucleic acid demethylase with substrate preference towards N6-methyladenosisne (m6A). Variation in the FTO gene confers the single greatest genetic risk for common obesity amongst all obesity susceptibility loci identified to date. The mechanisms via which FTO variation promotes adiposity remain unknown. Increased hunger, increased energy intake, and enhanced preference for palatable, calorically-rich foods constitute a common denominator between ghrelin signalling and FTO perturbation. Hence, we hypothesized that altered ghrelin levels mediate the FTO-related obesogenic feeding patterns, and we undertook human, rodent and cellular studies to test our hypothesis. Here we show that Caucasian males, homozygous for the high-risk allele A of FTO rs9939609 exhibit increased BMI and adiposity compared to homozygotes for the protective variant T, even within the normal BMI-spectrum; before the development of overweight and obesity. In two independent cohorts we show that normal-BMI AA subjects exhibit attenuated hunger suppression post-meal and aberrant ghrelin profile compared to adiposity-matched TT controls; with the ghrelin phenotype of normal-BMI AA subjects reminiscing ghrelin changes seen in human obesity. Moreover, we show that global Fto deletion in mice results in alterations in circulating ghrelin levels. Utilizing reward-trait assessment questionnaires we demonstrate weight-independent increases in reward responsiveness in AA subjects. Using fMRI we show that FTO genotype weight-independently alters neuronal responsiveness to visual food cues within homeostatic and reward appetitive circuitries. Furthermore, we report that peripheral blood cells from healthy normal-weight Caucasian AA males have increased FTO and GHRL mRNA relative abundance, with decreased m6A GHRL mRNA residues compared to TT controls. Finally, we show that overexpression of FTO in HeLa cells increases abundance of pre-proghrelin, pro-ghrelin and ghrelin peptides, as well as GOAT protein in the cell lysates. Collectively, these data reveal a novel link between FTO and ghrelin, and implicate ghrelin deregulation to the adipogenic effects of FTO
Investigating the role of gut hormones in energy and glucose homeostasis
Get PDFObesity is associated with type-2 diabetes mellitus. Gut hormones are peptides secreted in response to nutrient intake that act to regulate food intake, energy and glucose homeostasis. Thus, alterations in gut hormone abundance and/or signalling can contribute to the development of the obese and T2DM phenotype. The incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic hormone augment glucose-mediated insulin secretion. Peptide YY is released from the gut post-prandially and acts primarily as a satiety signal. Recently studies have highlighted a role for PYY in regulating glucose homeostasis, which to date remains partially understood. Dipeptidyl peptidase-4 is involved in the biological inactivation of the incretins hence; DPP-4 inhibition is used to treat T2DM. DPP-4 also regulates PYY. Thus, DPP-4 inhibition may potentially impact on pancreatic PYY function and signalling and may alter the effects of the PYY system on glucose homeostasis. In addition, gut peptides have been identified as possible contributors to cases of hyperinsulinaemic-hypoglycaemia resulting from bariatric surgery. Therefore, this thesis aimed to (1) determine the contribution of pancreatic PYY deletion to the intra-islet PYY system; glucose homeostasis and body weight phenotype and (2) establish the impact of hyperinsulinism on DPP-4 and its gut hormone substrates. To address the first point, pancreatic-specific Pyy null mice were phenotyped for changes in the pancreatic endocrine system, followed by body weight and glucose metabolism, in vivo. Further investigations measuring gut hormone mRNA suggested the intra-islet system was contributing to the observed reduction in weight gain and hyperinsulinaemia. Finally, patients with congenital forms of HI were evaluated for PYY, the incretins and DPP-4. This study highlighted a role for DPP-4, PYY and GIP in mediating HI. In conclusion, this thesis demonstrates a role for gut hormones in energy and glucose homeostasis. Further work is required to understand the interaction of gut peptides on islet function
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
Switching the focus from weight to health: Canada's adult obesity practice guideline set a new standard for obesity management
Get PDFkoamabayili/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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