1,720,981 research outputs found
The activity and biosynthesis of beta-cell peptide hormones : implications in diabetes, obesity, and pancreatic cancer
No full textType 1 and type 2 diabetes are characterized by hyperglycemia and loss of beta-cell mass, function, and peptide hormones. Beyond hyperglycemia, diabetes is also associated with obesity and increased risk of cancer, particularly pancreatic cancer. Islet amyloid polypeptide (IAPP) is the second most abundant beta-cell hormone, co-secreted with insulin, and reduced in diabetes. Paracrine actions of endogenous IAPP have been proposed in glycemic regulation and tumour growth suppression, but remain incompletely understood. To further characterize the effects of IAPP loss, we used an IAPP-knockout mouse fed a high-fat or control diet and assessed glycemia and adiposity. We also generated a genetic mouse model of pancreatic ductal adenocarcinoma in IAPP-knockout mice to investigate IAPP loss as a potential mechanism for the association of diabetes and pancreatic cancer. Trends in IAPP-knockout mice suggest elevated adiposity and glycemia in the absence of IAPP. We observed no effect of IAPP on pancreatic ductal adenocarcinoma survival in mice, or cancer cell proliferation, death, or glycolysis.
A reduction in the processing efficiency of beta-cell peptide prohormones is also observed in diabetes. Pcsk1 and Pcsk2 are the two major prohormone endoproteases within insulin granules, and are responsible for multiple steps in the proIAPP and proinsulin processing pathways. To determine whether impaired processing functions as a biomarker or driver of beta-cell dysfunction, we generated mouse models of beta-cell specific (Ins1cre-driven) Pcsk1 and Pcsk2 deficiency using Cre-lox recombination. Loss of Pcsk1 in beta cells caused severe proinsulin processing impairments and increased diabetes susceptibility in male mice, while female mice remained euglycemic. In contrast, male and female beta-cell Pcsk2-deficient mice were euglycemic with minimally impaired proinsulin processing, but severely impaired proIAPP processing. Deletion of both Pcsk1 and Pcsk2 in beta cells blocked proinsulin processing, drove hyperglycemia, increased beta-cell glucose responsiveness and mass, and reduced beta-cell maturity and proliferative capacity. In a mouse model expressing amyloidogenic human IAPP in beta cells, Pcsk1 deficiency significantly increased amyloid deposition. Collectively, these findings show that loss of beta-cell prohormone processing alters beta-cell function and drives hyperglycemia, and that endogenous IAPP does not act as a pancreatic tumour suppressor but may alter glycemia and adiposity.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat
Islet macrophages response to beta cell stresses
No full textThe full abstract for this thesis is available in the body of the thesis, and will be available when the embargo expires.Medicine, Faculty ofPathology and Laboratory Medicine, Department ofGraduat
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
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