1,010 research outputs found

    Mastery motivation: moving towards a better understanding of college student success

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    2019 Spring.Includes bibliographical references.This comparative and associational quantitative study applied a pragmatic theoretical perspective to the exploration of college student dispositions. First, the study evaluated the Dimensions of Adult Mastery Motivation Questionnaire College (DAMMQ-C) as a measure of mastery motivation in U.S. college students. Secondly, the study explored the relationship between mastery motivation, high school grade point average (HSGPA), ACT composite score, and college academic performance. Finally, the study examined differences in mastery motivation across various student characteristics, including developmental education status. Participants at a four year regional comprehensive, n = 288 , and a two-year community college, n = 37, completed a 35-item adapted version of the Dimensions of Adult Mastery Motivation Questionnaire (DAMMQ) that included three college specific social persistence scales to better align the instrument with the broader student success literature. Principal axis exploratory factor analysis with a varimax rotation was conducted to evaluate the underlying structure of the 35 items. Multiple iterations of hierarchical multiple regression were conducted with the aggregate sample and disaggregated groups based on development education status to explore the ability of dispositional and cognitive factors. to explain variance in college GPA. Logistic regression analysis was conducted to explore the ability of dispositional and cognitive factors to correctly classify participants that did or did not pass all attempted hours. Finally, t-tests and one-way ANOVA were conducted to examine potential difference in DAMMQ-C scale scores by student characteristics. Following exploratory factor analysis, 27 items were retained within seven factor structure: (a) preference for challenge, (b) task persistence, (c) task pleasure, (d) task absorption, (e) social persistence with peers, (f) social persistence with faculty, and (g) academic relationship with faculty. The factors displayed adequate to good internal consistency. Regression analysis results indicated that the DAMMQ-C dispositional scales provided increased explanation of variance in college GPA over and above traditional cognitive factors for the aggregate, developmental, and non-developmental education groups. However, the amount of variance explained varied by group. For the aggregate and non-developmental education groups the DAMMQ-C scales contributed an additional 5% and 2%, respectively. Within the developmental education group, the model failed to significantly explain variance in college GPA until the DAMMQ-C scales were added in the final block. The model then explained 15% of the variance in college GPA. A few statistically significant differences were found based on student characteristics. Developmental education students reported statistically significantly lower scores in academic relationship with faculty, task-related pleasure, and total mastery motivation. Black students reported statistically significantly lower scores in social persistence with peers, social persistence with faculty, academic relationship with faculty, and total mastery motivation. The results supported continued use of dispositional factors in understanding and supporting student success, in faculty and staff training, admission practices, and identifying and developing student success interventions, especially for developmental education students. Finally, the study carried implications for future research through the initial validation of a multi-faceted dispositional instrument that was concise and practical for use in longitudinal studies needed to (in)validate more comprehensive models of college student success

    Opportunistic screening for asymptomatic type 2 diabetes

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    Many individuals who are at risk for type 2 diabetes do not experience symptoms of diabetes, and therefore are not aware of this condition. Screening for type 2 diabetes and impaired glucose tolerance (IGT) can identify individuals at risk for type 2 diabetes, and prevent or delay complications. The purpose of this study is to evaluate a three step screening strategy for asymptomatic individuals with one or more cardiac risk factors for type 2 diabetes and provide validity for the Diabetes Risk Score. The organizing framework is criteria for opportunistic screening for Diabetes Risk factors. Lindstrom and Tuomilehto (2003) assert that screening can identify individuals for type 2 diabetes or (IGT), and as a result treatment can begin to prevent complications. A sample of 200 patients from three primary care offices in the Fort Wayne, Indiana area will be recruited over 3 months to be screened with the Diabetes Risk Score tool. Patients who are identified as at risk for type 2 diabetes will receive follow-up screening. The validation and use of the opportunistic screening tool for type 2 diabetes or IGT will allow primary health care providers to identify at risk individuals and recommend early intervention and follow-up care.School of NursingThesis (M.S.

    Mouse models for preeclampsia: disruption of redox-regulated signaling

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    The concept that oxidative stress contributes to the development of human preeclampsia has never been tested in genetically-defined animal models. Homozygous deletion of catechol-Omethyl transferase (Comt-/-) in pregnant mice leads to human preeclampsia-like symptoms (high blood pressure, albuminurea and preterm birth) resulting from extensive vasculo-endothelial pathology, primarily at the utero-fetal interface where maternal cardiac output is dramatically increased during pregnancy. Comt converts estradiol to 2-methoxyestradiol 2 (2ME2) which counters angiogenesis by depleting hypoxia inducible factor-1 alpha (HIF-1 alpha) at late pregnancy. We propose that in wild type (Comt++) pregnant mice, 2ME2 destabilizes HIF-1 alpha by inhibiting mitochondrial superoxide dismutase (MnSOD). Thus, 2ME2 acts as a pro-oxidant, disrupting redox-regulated signaling which blocks angiogenesis in wild type (WT) animals in physiological pregnancy. Further, we suggest that a lack of this inhibition under normoxic conditions in mutant animals (Comt-/-) stabilises HIF-1 alpha by inactivating prolyl hydroxlases (PHD). We predict that a lack of inhibition of MnSOD, leading to persistent accumulation of HIF-1 alpha, would trigger inflammatory infiltration and endothelial damage in mutant animals. Critical tests of this hypothesis would be to recreate preeclampsia symptoms by inducing oxidative stress in WT animals or to ameliorate by treating mutant mice with Mn-SOD-catalase mimetics or activators of PHD

    Potent and selective chemical probe of hypoxic signaling downstream of HIF-α hydroxylation via VHL inhibition

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    Chemical strategies to using small molecules to stimulate hypoxia inducible factors (HIFs) activity and trigger a hypoxic response under normoxic conditions, such as iron chelators and inhibitors of prolyl hydroxylase domain (PHD) enzymes, have broad-spectrum activities and off-target effects. Here we disclose VH298, a potent VHL inhibitor that stabilizes HIF-α and elicits a hypoxic response via a different mechanism, that is the blockade of the VHL:HIF-α protein-protein interaction downstream of HIF-α hydroxylation by PHD enzymes. We show that VH298 engages with high affinity and specificity with VHL as its only major cellular target, leading to selective on-target accumulation of hydroxylated HIF-α in a concentration- and time-dependent fashion in different cell lines, with subsequent upregulation of HIF-target genes at both mRNA and protein levels. VH298 represents a high-quality chemical probe of the HIF signalling cascade and an attractive starting point to the development of potential new therapeutics targeting hypoxia signalling

    A Simple Procedure for Constructing 5'-Amino-Terminated Oligodeoxynucleotides in Aqueous Solution

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    A rapid method for the synthesis of oligodeoxynucleotides (ODNs) terminated by 5'-amino-5'-deoxythymidine is described. A 3'-phosphorylated ODN (the donor) is incubated in aqueous solution with 5'-amino- 5'-deoxythymidine in the presence of N-(3-dimethylaminopropyl)-)N'-ethylcarbodiimide hydrochloride (EDC), extending the donor by one residue via a phosphoramidate bond. Template- directed ligation of the extended donor and an acceptor ODN, followed by acid hydrolysis, yields the acceptor ODN extended by a single 5'-amino-5'-deoxythymidine residue at its 5'terminus

    Decoding Warburg's hypothesis: tumor-related mutations in the mitochondrial respiratory chain

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    Otto Warburg observed that cancer cells derived their energy from aerobic glycolysis by converting glucose to lactate. This mechanism is in opposition to the higher energy requirements of cancer cells because oxidative phosphorylation (OxPhos) produces more ATP from glucose. Warburg hypothesized that this phenomenon occurs due to the malfunction of mitochondria in cancer cells. The rediscovery of Warburg's hypothesis coincided with the discovery of mitochondrial tumor suppressor genes that may conform to Warburg's hypothesis along with the demonstrated negative impact of HIF-1 on PDH activity and the activation of HIF-1 by oncogenic signals such as activated AKT. This work summarizes the alterations in mitochondrial respiratory chain proteins that have been identified and their involvement in cancer. Also discussed is the fact that most of the mitochondrial mutations have been found in homoplasmy, indicating a positive selection during tumor evolution, thereby supporting their causal role.España, Ministerio de Economía y Competitividad PI12/00137España, Ministerio de Economía y Competitividad PI15/00045España, Ministerio de Economía y Competitividad RD12/0036/0028Unión Europea, Consejería de Ciencia e Innovación CTS-6844Unión Europea, Consejería de Ciencia e Innovación CTS-1848España, Junta de Andalucía,Consejería de Salud PI-0135-2010España, Junta de Andalucía,Consejería de Salud PI-0306-2012España, Junta de Andalucía,Consejería de Salud PI-0096-201

    Studies on the substrate selectivity of the hypoxia-inducible factor prolyl hydroxylase 2 catalytic domain

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    In animals, the response to chronic hypoxia is mediated by upregulation of the α,β-heterodimeric hypoxia inducible factors (HIFs). Levels of HIFα isoforms, but not HIFβ, are regulated by their post-translational modification as catalysed by prolyl hydroxylase domain enzymes (PHDs). Different roles for human HIF-1/2α isoforms and their two oxygen dependent degradation domains (ODDs) are proposed. We report kinetic and NMR analyses on the ODD selectivity of the catalytic domain of wildtype PHD2 (which is conserved in nearly all animals) and clinically observed variants. Studies using Ala-scanning and 'hybrid' ODD peptides imply the relatively rigid conformation of the (hydroxylated) proline plays an important role in ODD binding. They also reveal differential roles in binding for the residues on the N- and C-terminal sides of the substrate proline. The overall results inform on how the PHDs achieve selectivity for HIFα ODDs and may be of use in identifying substrate selective PHD inhibitors

    Conditional HIF-1α Expression Produces a Reversible Cardiomyopathy

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    The response to hypoxia in tissues is regulated by the heterodimeric transcription factor Hypoxia Inducible Factor-1 (HIF-1).We have created a strain of mice with inducible cardiomyocyte-specific expression of a mutated, oxygen-stable, form of HIF-1alpha. Cardiac function steadily decreased with transgene expression, but recovered after the transgene was turned off. Using long-oligo microarrays, we identified 162 transcripts more than 3-fold dysregulated in these hearts after transgene expression. Among the down-regulated genes the transcript for SERCA was reduced 46% and the protein 92%. This led us to an evaluation of calcium flux that showed diminished reuptake of cytoplasmic calcium in myocytes from these hearts, suggesting a mechanism for cardiac dysfunction.These results provide a deeper understanding of transcriptional activity of HIF in the heart, and show that enhanced HIF-1 activity is sufficient to cause contractile dysfunction in the adult heart. HIF is stabilized in the myocardium of patients with ischemic cardiomyopathy, and our results suggest that HIF could be contributing directly to the contractile dysfunction in this disease
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