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Obesity impairs skeletal muscle maintenance and regeneration, a condition that can progressively lead to muscle loss, but the mechanisms behind it are unknown. Muscle is primarily composed of multinucleated cells called myotubes which are derived by the fusion of mononucleated myocytes. A key mediator in this process is the cellular

Obesity impairs skeletal muscle maintenance and regeneration, a condition that can progressively lead to muscle loss, but the mechanisms behind it are unknown. Muscle is primarily composed of multinucleated cells called myotubes which are derived by the fusion of mononucleated myocytes. A key mediator in this process is the cellular fusion protein syncytin-1. This led to the hypothesis that syncytin-1 could be decreased in the muscle of obese/insulin resistant individuals. In contrast, it was found that obese/insulin resistant subjects had higher syncytin-1 expression in the muscle compared to that of the lean subjects. Across the subjects, syncytin-1 correlated significantly with body mass index, percent body fat, blood glucose and HbA1c levels, insulin sensitivity and muscle protein fractional synthesis rate. The concentrations of specific plasma fatty acids, such as the saturated fatty acid (palmitate) and monounsaturated fatty acid (oleate) are known to be altered in obese/insulin resistant humans, and also to influence the protein synthesis in muscle. Therefore, it was evaluated that the effects of palmitate and oleate on syncytin-1 expression, as well as 4E-BP1 phosphorylation, a key mechanism regulating muscle protein synthesis in insulin stimulated C2C12 myotubes. The results showed that treatment with 20 nM insulin, 300 µM oleate, 300 µM oleate +20 nM insulin and 300 µM palmitate + 300 µM oleate elevated 4E-BP1 phosphorylation. At the same time, 20 nM insulin, 300 µM palmitate, 300 µM oleate + 20 nM insulin and 300 µM palmitate + 300 µM oleate elevated syncytin-1 expression. Insulin stimulated muscle syncytin-1 expression and 4E-BP1 phosphorylation, and this effect was comparable to that observed in the presence of oleate alone. However, the presence of palmitate + oleate diminished the stimulatory effect of insulin on muscle syncytin-1 expression and 4E-BP1 phosphorylation. These findings indicate oleate but not palmitate increased total 4E-BP1 phosphorylation regardless of insulin and the presence of palmitate in insulin mediated C2C12 cells. The presence of palmitate inhibited the upregulation of total 4EB-P1 phosphorylation. Palmitate but not oleate increased syncytin-1 expression in insulin mediated C2C12 myotubes. It is possible that chronic hyperinsulinemia in obesity and/or elevated levels of fatty acids such as palmitate in plasma could have contributed to syncytin-1 overexpression and decreased muscle protein fractional synthesis rate in obese/insulin resistant human muscle.
ContributorsRavichandran, Jayachandran (Author) / Katsanos, Christos (Thesis advisor) / Coletta, Dawn (Committee member) / Dickinson, Jared (Committee member) / Arizona State University (Publisher)
Created2017
Description
ABSTRACT

This study examines validity evidence of a state policy-directed teacher evaluation system implemented in Arizona during school year 2012-2013. The purpose was to evaluate the warrant for making high stakes, consequential judgments of teacher competence based on value-added (VAM) estimates of instructional impact and observations of professional practice (PP).

ABSTRACT

This study examines validity evidence of a state policy-directed teacher evaluation system implemented in Arizona during school year 2012-2013. The purpose was to evaluate the warrant for making high stakes, consequential judgments of teacher competence based on value-added (VAM) estimates of instructional impact and observations of professional practice (PP). The research also explores educator influence (voice) in evaluation design and the role information brokers have in local decision making. Findings are situated in an evidentiary and policy context at both the LEA and state policy levels.

The study employs a single-phase, concurrent, mixed-methods research design triangulating multiple sources of qualitative and quantitative evidence onto a single (unified) validation construct: Teacher Instructional Quality. It focuses on assessing the characteristics of metrics used to construct quantitative ratings of instructional competence and the alignment of stakeholder perspectives to facets implicit in the evaluation framework. Validity examinations include assembly of criterion, content, reliability, consequential and construct articulation evidences. Perceptual perspectives were obtained from teachers, principals, district leadership, and state policy decision makers. Data for this study came from a large suburban public school district in metropolitan Phoenix, Arizona.

Study findings suggest that the evaluation framework is insufficient for supporting high stakes, consequential inferences of teacher instructional quality. This is based, in part on the following: (1) Weak associations between VAM and PP metrics; (2) Unstable VAM measures across time and between tested content areas; (3) Less than adequate scale reliabilities; (4) Lack of coherence between theorized and empirical PP factor structures; (5) Omission/underrepresentation of important instructional attributes/effects; (6) Stakeholder concerns over rater consistency, bias, and the inability of test scores to adequately represent instructional competence; (7) Negative sentiments regarding the system's ability to improve instructional competence and/or student learning; (8) Concerns regarding unintended consequences including increased stress, lower morale, harm to professional identity, and restricted learning opportunities; and (9) The general lack of empowerment and educator exclusion from the decision making process. Study findings also highlight the value of information brokers in policy decision making and the importance of having access to unbiased empirical information during the design and implementation phases of important change initiatives.
ContributorsSloat, Edward F. (Author) / Wetzel, Keith (Thesis advisor) / Amrein-Beardsley, Audrey (Thesis advisor) / Ewbank, Ann (Committee member) / Shough, Lori (Committee member) / Arizona State University (Publisher)
Created2015