1,720,972 research outputs found
The role and transcriptional regulation of FAM46A in adipocyte differentiation
Obesity is currently a leading global health concern. Treatments include undergoing a weight-loss regimen. However, successful weight-loss is variable, where the heritability of obesity is considered part of the cause. This patient variability to weight-loss was addressed by Carayol et al. (2017), where protein plasma level changes was associated to genetic variability and changes in BMI under a low-calorie diet intervention. A highly significant association region was found to regulate downstream gene FAM46A; coding for a nucleotidyl-transferase protein. Loss of function mutations in FAM46A have previously been discovered in multiple human diseases, such as osteogenesis imperfecta. However, there is a lack of understanding of FAM46Aâ s function, especially in the context of adipose tissue and metabolism. This thesis aimed to follow up on the Carayol et al. study by investigating the transcriptional regulation of FAM46A and how the associated region is influencing this regulation, as well as how FAM46A is involved in adipose tissue function. When mapping the physical DNA interaction network around the associated region using chromosome conformation capture (3C) in human subcutaneous adipocytes (SGBS cells), no interactions between the FAM46A promoter and selected loci of the associated region were found. Interestingly, significant interaction peaks downstream of the promoter overlapped with regions of open chromatin and were enriched for transcription factor (TF) motifs that are involved in stem cell differentiation and TGFβ signalling. SMAD4, part of the TGFβ signalling pathway, binds to this region, indicating a potential regulator of FAM46A. To address FAM46Aâ s potential role in adipocyte function, FAM46A expression was disrupted in vitro in differentiating adipocytes. Reduction of FAM46A expression in SGBS cells resulted in decreased expression of PPARG and CEBPA, the master regulators of adipogenesis, complemented by a reduction in lipid accumulation. Follow up studies in murine mesenchymal stem cells where Fam46a was over-expressed were controversial as this led to a decrease in adipogenic markers (Adipoq and PPARð Ÿ). Overall, disruption of FAM46A expression led to opposing changes in adipogenic potential, suggesting the requirement for a more stable cell system to study FAM46A in vitro. To further characterise the role of Fam46a, metabolic phenotyping of a Fam46a knockout (KO) mouse model under hyper-caloric stress was performed in collaboration with the IMG in Prague. This model revealed a significantly smaller mouse, and increased plasma alkaline phosphatase, as previously observed. When fed a high-fat diet, KO mice had reduced overall fat mass, improved glucose clearance and reduced adipocyte size in both subcutaneous and visceral white adipose tissue (subWAT/visWAT) depots. Transcriptomic analysis of these two depots revealed an up-regulation of genes expressed in ribosome related pathways in the subWAT, whereas the visWAT showed the up-regulation of fatty acid metabolism pathways, suggesting that the KO adipose tissue is more metabolically active. Other down-regulated pathways involved stem cell differentiation and BMP/TGFβ-signalling. In conclusion, this study found the possible regulation of the FAM46A promoter by TFs involved in adipogenesis regulation, such as SMAD proteins, as well as strengthening its possible functional involvement in TGFβ signalling by enrichment of this pathway in KO studies.UPDEPL
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
Honey as a Source of Natural Antioxidants
Dietary antioxidants might prevent oxidative damage to tissues and therefore protect against chronic diseases. Previous research demonstrated that honeys from various floral sources exhibit significant antioxidant activity, rendering honey effective as a food antioxidant. The objective of the research presented in this dissertation was to extend the knowledge of the protective antioxidant effects of honey in food systems and in in vitro assays into determining the potential of honey as a dietary source of antioxidants. In vitro antioxidant activity of honey as measured by the oxygen radical absorbance capacity (ORAC) assay, was found to be similar to the antioxidant activity of many fruits and vegetables on a fresh weight basis. The ORAC values of honeys from various floral sources were significantly correlated with the in vitro inhibitory effect of honeys on copper-catalyzed serum lipoprotein oxidation. Wide variation in antioxidant activity was observed among honeys from different floral sources, with the darker colored honeys having higher antioxidant capacity. Specific honey components responsible for the observed antioxidant capacity were identified and quantified, including phenolics, proteins, gluconic acid, enzymes, hydroxymethylfuraldehyde and ascorbic acid. A linear correlation was observed between ORAC activity of the investigated honeys and their phenolic and protein content. In addition, the first evidence for an ex vivo antioxidant effect of honey was established in a human intervention study. Consumption of water with buckwheat honey significantly increased deproteinized serum antioxidant capacity relative to water consumption. A hypercholesterolemic rabbit model was used to further elucidate the in vivo effect of soy and buckwheat honey consumption on atherosclerosis. Feeding the rabbits soy or buckwheat honey in addition to cholesterol did not significantly change their serum lipid profiles, serum antioxidant capacity or atherosclerotic plaque formation as compared to feeding the rabbits cholesterol alone. These studies are the first to examine the biological potential of honey as a dietary antioxidant. Now it becomes crucial to study factors such as bioavailability and tissue distribution of honey phenolics and other components to fully understand its biological activity in vivo before incorporation of honey as a source of dietary antioxidants into the human food supply can be supported.Made available in DSpace on 2015-09-25T21:09:57Z (GMT). No. of bitstreams: 2
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Previous issue date: 2002Embargo set by: Seth Robbins for item 84958
Lift date: Forever
Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDsRestricted to the U of I community idenfinitely during batch ingest of legacy ETDsU of I Only146 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2002
Honey as a Source of Natural Antioxidants
146 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2002.Dietary antioxidants might prevent oxidative damage to tissues and therefore protect against chronic diseases. Previous research demonstrated that honeys from various floral sources exhibit significant antioxidant activity, rendering honey effective as a food antioxidant. The objective of the research presented in this dissertation was to extend the knowledge of the protective antioxidant effects of honey in food systems and in in vitro assays into determining the potential of honey as a dietary source of antioxidants. In vitro antioxidant activity of honey as measured by the oxygen radical absorbance capacity (ORAC) assay, was found to be similar to the antioxidant activity of many fruits and vegetables on a fresh weight basis. The ORAC values of honeys from various floral sources were significantly correlated with the in vitro inhibitory effect of honeys on copper-catalyzed serum lipoprotein oxidation. Wide variation in antioxidant activity was observed among honeys from different floral sources, with the darker colored honeys having higher antioxidant capacity. Specific honey components responsible for the observed antioxidant capacity were identified and quantified, including phenolics, proteins, gluconic acid, enzymes, hydroxymethylfuraldehyde and ascorbic acid. A linear correlation was observed between ORAC activity of the investigated honeys and their phenolic and protein content. In addition, the first evidence for an ex vivo antioxidant effect of honey was established in a human intervention study. Consumption of water with buckwheat honey significantly increased deproteinized serum antioxidant capacity relative to water consumption. A hypercholesterolemic rabbit model was used to further elucidate the in vivo effect of soy and buckwheat honey consumption on atherosclerosis. Feeding the rabbits soy or buckwheat honey in addition to cholesterol did not significantly change their serum lipid profiles, serum antioxidant capacity or atherosclerotic plaque formation as compared to feeding the rabbits cholesterol alone. These studies are the first to examine the biological potential of honey as a dietary antioxidant. Now it becomes crucial to study factors such as bioavailability and tissue distribution of honey phenolics and other components to fully understand its biological activity in vivo before incorporation of honey as a source of dietary antioxidants into the human food supply can be supported.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD
Dispelling the Myths Behind First-author Citation Counts
We 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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