933 resultados para NONGENOMIC ACTIONS


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The neo-classical economics view that behavior is driven by - and reflective of - hedonic utility is challenged by psychologists' demonstrations of cases in which actions do not merely reveal preferences but rather create them. In this view, preferences are frequently constructed in the moment and are susceptible to fleeting situational factors; problematically, individuals are insensitive to the impact of such factors on their behavior, misattributing utility caused by these irrelevant factors to stable underlying preferences. Consequently, subsequent behavior might reflect not hedonic utility but rather this erroneously imputed utility that lingers in memory. Here we review the roles of these streams of utility in shaping preferences, and discuss how neuroimaging offers unique possibilities for disentangling their independent contributions to behavior.

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Inappropriate activation of the renin-angiotensin system (RAS) contributes to many CKDs. However, the role of the RAS in modulating AKI requires elucidation, particularly because stimulating type 1 angiotensin II (AT1) receptors in the kidney or circulating inflammatory cells can have opposing effects on the generation of inflammatory mediators that underpin the pathogenesis of AKI. For example, TNF-α is a fundamental driver of cisplatin nephrotoxicity, and generation of TNF-α is suppressed or enhanced by AT1 receptor signaling in T lymphocytes or the distal nephron, respectively. In this study, cell tracking experiments with CD4-Cre mT/mG reporter mice revealed robust infiltration of T lymphocytes into the kidney after cisplatin injection. Notably, knockout of AT1 receptors on T lymphocytes exacerbated the severity of cisplatin-induced AKI and enhanced the cisplatin-induced increase in TNF-α levels locally within the kidney and in the systemic circulation. In contrast, knockout of AT1 receptors on kidney epithelial cells ameliorated the severity of AKI and suppressed local and systemic TNF-α production induced by cisplatin. Finally, disrupting TNF-α production specifically within the renal tubular epithelium attenuated the AKI and the increase in circulating TNF-α levels induced by cisplatin. These results illustrate discrepant tissue-specific effects of RAS stimulation on cisplatin nephrotoxicity and raise the concern that inflammatory mediators produced by renal parenchymal cells may influence the function of remote organs by altering systemic cytokine levels. Our findings suggest selective inhibition of AT1 receptors within the nephron as a promising intervention for protecting patients from cisplatin-induced nephrotoxicity.

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Summary of the finding from the 2007 Queen's LibQUAL+ survey and action items developed by the Library.

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The two major incretin hormones, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP), are currently being considered as prospective drug candidates for treatment of type 2 diabetes. Interest in these gut hormones was initially spurred by their potent insulinotropic activities, but a number of other antihyperglycaemic actions are now established. One of the foremost barriers in progressing GLP-1 and GIP to the clinic concerns their rapid degradation and inactivation by the ubiquitous enzyme, dipeptidyl peptidase IV (DPP IV). Here, we compare the DPP IV resistance and biological properties of Abu(8)/ Abu(2) (2-aminobutyric acid) substituted analogues of GLP-1 and GIP engineered to impart DPP IV resistance. Whereas (Abu(8))GLP-1 was completely stable to human plasma (half-life > 12h), GLP-1, GIP, and (Abu(2))GIP were rapidly degraded (half-lives: 6.2, 6.0, and 7.1 h, respectively). Native GIP, GLP-1, and particularly (Abu(8))GLP-1 elicited significant adenylate cyclase and insulinotropic activity, while (Abu(2))GIP was less effective. Similarly, in obese diabetic (ob/ob) mice, GIP, GLP-1, and (Abu(8))GLP-1 displayed substantial glucose-lowering and insulin -releasing activities, whereas (Abu(2))GIP was only weakly active. These studies illustrate divergent effects of penultimate amino acid Ala(8)/Ala(2) substitution with Abu on the biological properties of GLP-1 and GIP, suggesting that (Abu(8))GLP-1 represents a potential candidate for future therapeutic development. (C) 2004 Elsevier Inc. All rights reserved.

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In the last fifty years, Nunavut has developed a deep dependence on diesel for virtually all of its energy needs, including electricity. This dependence has created a number of economic, environmental and health related challenges in the territory, with an estimated 20% of the territory’s annual budget being spent on energy, thereby limiting the Government of Nunavut’s ability to address other essential infrastructure and societal needs, such as education, nutrition and health care and housing. One solution to address this diesel dependency is the use of renewable energy technologies (RETs), such as wind, solar and hydropower. As such, this thesis explores energy alternatives in Nunavut, and through RETScreen renewable energy simulations, found that solar power and wind power are technically viable options for Nunavut communities and a potentially successful means to offset diesel-generated electricity in Nunavut. However, through this analysis it was also discovered that accurate data or renewable resources are often unavailable for most Nunavut communities. Moreover, through qualitative open-ended interviews, the perspectives of Nunavut residents with regards to developing RETs in Nunavut were explored, and it was found that respondents generally supported the use of renewable energy in their communities, while acknowledging that there still remains a knowledge gap among residents regarding renewable energy, stemming from a lack of communication between the communities, government and the utility company. In addition, the perceived challenges, opportunities and gaps that exist with regards to renewable energy policy and program development were discussed with government policy-makers through further interviews, and it was discovered that often government departments work largely independently of each other rather than collaboratively, creating gaps and oversights in renewable energy policy in Nunavut. Combined, the results of this thesis were used to develop a number of recommended policy actions that could be undertaken by the territorial and federal government to support a shift towards renewable energy in order to develop a sustainable and self-sufficient energy plan in Nunavut. They include: gathering accurate renewable resource data in Nunavut; increasing community consultations on the subject of renewable energy; building strong partnerships with universities, colleges and industry; developing a knowledge sharing network; and finally increasing accessibility to renewable energy programs and policies in Nunavut.

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The purpose of this study was to test whether a constant bearing angle strategy could account for the displacement regulations produced by a moving observer when attempting to intercept a ball following a curvilinear path. The participants were asked to walk through a virtual environment and to change, if (deemed) necessary, their walking speed so as to intercept a moving ball that followed either a rectilinear or a curvilinear path. The results showed that ball path curvature did indeed influence the participants' displacement kinematics in a way that was predicted by adherence to a constant bearing angle strategy mode of control. Velocity modifications were found to be proportional to the magnitude of target curvature with opposing curvatures giving rise to mirror displacement velocity changes. The role of prospective strategies in the control of interceptive action is discussed

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Histidine is a naturally occurring amino acid with antioxidant properties, which is present in low amounts in tissues throughout the body. We recently synthesized and characterized histidine analogues related to the natural dipeptide carnosine, which selectively scavenge the toxic lipid peroxidation product 4-hydroxynonenal (HNE). We now report that the histidine analogue histidyl hydrazide is effective in reducing brain damage and improving functional outcome in a mouse model of focal ischemic stroke when administered intravenously at a dose of 20 mg/kg, either 30 min before or 60 min and 3 h after the onset of middle cerebral artery occlusion. The histidine analogue also protected cultured rat primary neurons against death induced by HNE, chemical hypoxia, glucose deprivation, and combined oxygen and glucose deprivation. The histidine analogue prevented neuronal apoptosis as indicated by decreased production of cleaved caspase-3 protein. These findings suggest a therapeutic potential for HNE-scavenging histidine analogues in the treatment of stroke and related neurodegenerative conditions.