Beneficial effects of naringenin and indomethacin on white and brown adipocytes

As obesity continues to grow and medical costs in the United States are estimated at $147 billion annually, novel ways to prevent and treat obesity are needed. One approach is to promote thermogenesis to improve energy balance by increasing the activities of thermogenic brown and beige adipocytes. Naringenin, a citrus flavanone, has been shown to act as anti-inflammatory and lipid lowering agent as well as activate PPARgamma. However, it is unclear whether it can activate thermogenic activity in white adipocytes, i.e., promote formation of beige adipocytes. Indomethacin (INDO) is an FDA approved drug used to treat pain related to inflammation by inhibiting cyclooxygenase (COX). It has been demonstrated that INDO is a PPARgamma agonist and is protective against weight gain in mice fed a high fat and high sucrose diet. Whether INDO independently induces brown adipocyte differentiation has not been studied. In this thesis, I investigated the effect of naringenin combined with isoproterenol, a beta- adrenergic receptor agonist on thermogenic activation of a common white adipocyte cell line, 3T3-L1. In addition, I investigated whether INDO induces brown adipocyte differentiation. 3T3- L1 cells were differentiated into mature adipocytes with a standard differentiation cocktail in the presence of naringenin and then stimulated with isoproterenol. While naringenin had little effect at the basal level, it significantly increased mRNA and protein expression of UCP-1 and PGC- 1alpha, browning marker genes. Moreover, naringenin increased mitochondrial DNA, which is indicative of increased mitochondrial biogenesis. The results suggest that in addition to increased UCP-1 expression, naringenin can promote up regulation of PGC-1alpha, leading to increased mitochondrial biogenesis in thermogenic activation of 3T3-L1. To study the effects of INDO on brown adipocyte differentiation I differentiated brown preadipocytes in the presence of increasing doses of INDO using a modified differentiation protocol. INDO dose-dependently increased lipid accumulation and mRNA expression of brown specific marker genes PGC-1alpha, UCP-1 and PRDM16. Protein expression of PGC-1alpha and UCP-1 was confirmed by western analysis. Consistently, INDO dose-dependently increased mitochondrial biogenesis. Mechanistically, INDO increased PPAR responsive promoter activities. These results suggest that INDO may promote brown adipogenesis through activation of PPARgamma

The Relationship between Neighborhood Characteristics and College Academic Outcomes Among an NCAA Division I Student-Athlete Population: A Multilevel Approach

Over 170,000 students participate annually in National Collegiate Athletic Association (NCAA) Division I sports. Approximately one-third of these student-athletes fail to graduate from their initial school of enrollment within six years. While some will go on to graduate from a transfer institution, roughly 15% will fail to earn a degree while competing for an NCAA Division I school. Using U.S. census block group data, this study adds the neighborhood characteristics of education, employment, income, and racial composition to prediction models of first-year GPA and six-year baccalaureate degree attainment among an NCAA Division I student-athlete sample. The use of multilevel modeling accounted for nesting of student-athletes within institutions and controlled for the potential of group effects on individual outcomes. Improving the statistical models used to predict academic outcomes among NCAA student-athletes will help to ensure that they are properly evaluated for the potential to be academically successful and enable early identification of those with heightened academic risk. Early identification can help institutions direct relevant academic support services to those most in need, and in some cases, consider the potential of an academic redshirt year. The findings indicate that while consideration of the educational attainment of the neighborhood adds to the predictive ability of first-year GPA, the meaningful impact is quite small. Cost-benefit analyses may reveal that the added burden of data collection and reduction in transparency is not worth the minimal addition of explained variance in the outcome, particularly in light of the lack of a significant relationship with the other outcomes

The evolution of a learning organization: the evaluation of corporate learning groups in a knowledge management effort

There exists considerable interest in the development of successful knowledge management program initiatives across every industry. This research aims to improve the overall discipline of knowledge management within the context of a corporate environment, so that competitive advantages can be realized from cultivating and sharing tacit knowledge routinely among a company\u27s employees. The analysis of a well-resourced knowledge management program will allow guidelines to be developed to prescribe successful future knowledge management programs. Prior studies may have missed the human factors elements related to how employees learn and build knowledge in the workplace. Specifically, the learning group (LG) portion of this company\u27s knowledge management program was studied to understand if this tool made advancements in the human behavior change needed for a successful knowledge management effort. Three main research questions focused on the communication, support, and evidence of successful collaboration were studied through a qualitative evaluation. LG focus, maturity, and connection to the business processes were considered. This provided evidence of patterns in the infrastructure, scope of the effort, focus of curriculum and workflows that were considered in the LG establishment. For technological companies, LGs are a good vehicle to augment knowledge management efforts. These drive awareness of the effort, help produce content, and establish an atmosphere of collaboration for ongoing professional development and education. The LGs are a compulsory tool to take an organization through the change management needed to generate and utilize the appropriate content of a knowledge management system. Leadership style is a key factor to evolve into a learning organization. A strong organization centric leader seems to provide the interconnectivity to the overarching knowledge management effort. Strategies that connect the LGs to the knowledge database provided a catalyst to change the standard behavior with how information about tacit knowledge was stored/shared. This provided awareness to begin using the knowledge management database as a resource. The LGs are the people based infrastructure required to break down the barriers of collaboration in a corporate setting. The human and social aspects are the most important considerations to address for organizations trying to evolve into learning organizations for strategic benefit

Xylosylation Is an Endoplasmic Reticulum to Golgi Event

The subcellular site of xylosylation, the first carbohydrate modification of the core protein that initiates glycosaminoglycan chain synthesis, was characterized in situ. Methods were developed to combine electron microscopic (EM) autoradiography and the radiolabeling of semi-intact chondrocytes. In the accompanying paper, Kearns et al. (Kearns, A. E., Vertel, B. M., and Schwartz, N. B. (1993) J. Biol. Chem. 268, 11097-11104) presented biochemical and subcellular fractionation studies that utilized semi-intact chondrocytes and radiolabeled UDP sugars to overcome obstacles to the direct analysis of xylosylation. The results suggested that xylosylation begins in the endoplasmic reticulum (ER) and continues in the Golgi. The site of xylosylation was not specified further due to the limitations of subcellular fractionation techniques. The studies described in this report were undertaken to localize these modifications directly in situ. Semi-intact cell preparations were optimized for ultrastructural preservation by modifications of permeabilization methods utilizing nitrocellulose filter overlays. Biochemical analysis demonstrated the exclusive incorporation of UDP-xylose into the cartilage chondroitin sulfate proteoglycan (aggrecan) core protein and 3‘-phosphoadenosine 5‘-phosphosulfate (PAPS) into the highly modified proteoglycan monomer. Immunolocalization studies showed the equivalence of cytoplasmic subcompartments in normal and semi-intact chondrocytes at the levels of light and electron microscopy. Once the biochemical and morphological equivalence of intact and semi-intact cells was established, EM autoradiographic studies were pursued using UDP-[3H]xylose and [35S]PAPS. Based on both qualitative and quantitative data, silver grains resulting from incorporated sulfate were concentrated in the perinuclear Golgi, while those resulting from incorporated xylose were found at the cis or forming face of the Golgi and in vesicular regions of the peripheral cytoplasm associated with the late ER. These data support the view that xylose addition begins in a late ER compartment and continues in intermediate compartments, perhaps including the cis-Golgi

A Republican governor and a Democratic editor : their relationship during the reconstruction in South Carolina

Daniel Henry Chamberlain, as Republican Governor of South Carolina during the last two years of Reconstruction, was sustained in his position by the newly enfranchised Negro electorate. Francis Warrington Dawson, Democratic editor of the powerful News and Courier, was a spokesman of the conservative Charleston business elite and a proponent of fusion or political cooperation with those Republicans who best served the economic and social interests of this influential minority. For a short time the two men came together in a spirit of bipartisan cooperation as a means for obtaining their separate goals. The coalition— temporary and shaky at best—was opposed by elements in both parties. Chamberlain was charged by some in his party with having sold out Republican principles of Negro political equality, and Dawson was charged by an element within his party with abandoning Democratic fundamentals of white supremacy. Finally the connection was severed by the race issue, larger than the men and the beliefs they held

A Qualitative Analysis of Response Elaboration Training Effects

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What constitutes brilliant aged care? A qualitative study of practices that exceed expectation

Aim This study aimed to explore what constitutes brilliant aged care. Background Although many aged care services do not offer the care that older people and carers need and want, some perform better. Rather than focus on problems with aged care, this study examined brilliant aged care—practices that exceeded expectation. Design The methodology for this study was informed by grounded theory, underpinned by constructionism to socially construct meaning. Methods This study invited nominations for a Brilliant Award via a survey, and interviews with the nominees via web conference. After receiving survey responses from 10 nominators, interviews were conducted with 12 nominees. Data were analysed using reflexive thematic analysis and documented according to COREQ guidelines to optimise rigour and transparency. Results According to participants, brilliant aged care involved being relationally attuned to older people, a deep understanding of the older person, recognition of aged care as more than a job, innovative practices and permission to reprioritise. Conclusions This study suggests that, in aged care, brilliance happens. It emphasises the importance of meaningful connections and relationships in aged care, where thoughtful acts acknowledge an older person's value and humanity as well as creativity and innovation. Relevance to Clinical Practice For those who manage and deliver aged care, the findings suggest that small practice changes can make a positive difference to older people. Brilliant aged care can involve acts of empathy; enthusiasm for aged care; innovative practices, even those that are small scale; and reprioritising workplace tasks to spend time with older people. For policymakers, this study highlights the need to recognise and raise the profile of the pockets of brilliance within the aged care sector. This might be achieved via awards and other initiatives that serve to celebrate and learn from brilliance in its myriad forms. Patient or Public Contribution The nominees, who included carers, were invited to participate in workshops with other carers and older people to co-design a model of brilliant aged care, during which workshop participants discussed and critiqued the findings constructed from the data

What constitutes brilliant aged care? : a qualitative study of practices that exceed expectation

Aim: This study aimed to explore what constitutes brilliant aged care. Background: Although many aged care services do not offer the care that older people and carers need and want, some perform better. Rather than focus on problems with aged care, this study examined brilliant aged care—practices that exceeded expectation. Design: The methodology for this study was informed by grounded theory, under-pinned by constructionism to socially construct meaning. Methods: This study invited nominations for a Brilliant Award via a survey, and inter-views with the nominees via web conference. After receiving survey responses from 10 nominators, interviews were conducted with 12 nominees. Data were analysed using reflexive thematic analysis and documented according to COREQ guidelines to optimise rigour and transparency. Results: According to participants, brilliant aged care involved being relationally at-tuned to older people, a deep understanding of the older person, recognition of aged care as more than a job, innovative practices and permission to reprioritise. Conclusions: This study suggests that, in aged care, brilliance happens. It emphasises the importance of meaningful connections and relationships in aged care, where thoughtful acts acknowledge an older person's value and humanity as well as creativity and innovation. Relevance to Clinical Practice: For those who manage and deliver aged care, the findings suggest that small practice changes can make a positive difference to older people. Brilliant aged care can involve acts of empathy; enthusiasm for aged care; innovative practices, even those that are small scale; and reprioritising workplace tasks to spend time with older people. For policymakers, this study highlights the need to recognise and raise the profile of the pockets of brilliance within the aged care sector. This might be achieved via awards and other initiatives that serve to celebrate and learn from brilliance in its myriad forms. Patient or Public Contribution: The nominees, who included carers, were invited to participate in workshops with other carers and older people to co-design a model of brilliant aged care, during which workshop participants discussed and critiqued the findings constructed from the data