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Title: THE DIFFERENCE IN VENTILATORY THRESHOLD AMONG ADOLESCENT MALES BASED ON MATURITY STATUS.
Creator: Loney, Dyane, Stout, Jeffery R., University of Central Florida
Abstract / Description: Previous research has shown an inverse relationship between age and the relative intensity at which ventilatory threshold (VT) occurs in adolescent boys. However, no study has examined the effect of maturity status on VT in the differences in boys from the onset of puberty, adolescents. The purpose of this study was to compare VT among adolescent boys of different maturational groups. Methods: For this study, moderately active adolescent male participants (14 � 3 y) completed this study....
Show morePrevious research has shown an inverse relationship between age and the relative intensity at which ventilatory threshold (VT) occurs in adolescent boys. However, no study has examined the effect of maturity status on VT in the differences in boys from the onset of puberty, adolescents. The purpose of this study was to compare VT among adolescent boys of different maturational groups. Methods: For this study, moderately active adolescent male participants (14 � 3 y) completed this study. Maturational status of the participants was determined via years from peak height velocity (PHV), which is an estimation of somatic maturity status derived from age, standing height, seated height, body mass, and leg length. Participants were categorized into PRE- (lesser than 1 year till PHV), PERI- (within 1 year of PHV), and POST-PHV (greater than 1 year past PHV). All participants completed a ramp graded exercise test on a cycle ergometer. During the test, participants were given a three-minute warm-up with no resistance before starting at a workload of 30 watts which increased at a rate of 1 watt every 3 seconds until volitional fatigue. Throughout the test, oxygen consumption (VO2) and ventilation were measured. VT was determined, as a percentage of VO2max, from the ventilation versus VO2 graph using the maximal deviation method. Differences in VT between maturational groups were examined using one-way ANOVA. Results: A significant (F=5.36; p=0.014) difference in VT among maturational groups was found (Appendix A, Figure 2). Post hoc analysis revealed that PRE (p=0.029) and PERI (p=0.009) had VT occur at a significantly greater relative percentage of VO2max than POST. However, no significant (p=0.970) differences were found between PRE and PERI (Appendix A, Figure 3). Conclusion: Adolescent males in PRE and PERI demonstrated higher VT as a percentage of their VO2max compared to POST. This finding suggests the differences in the delayed switch from aerobic to anaerobic metabolism during incremental exercise in adolescent boys who are PRE and PERI.
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Date Issued: 2016
Identifier: CFH2000145, ucf:45945
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFH2000145

Title: THE EFFECTS OF A STRUCTURED LIFESTYLE INTERVENTION PROGRAM IN CONJUNCTION WITH DIETARY SUPPLEMENTATION ON WEIGHT LOSS AND RISK FACTORS FOR THE METABOLIC SYNDROME.
Creator: Zukley, Linda, Angelopoulos, Theodore, University of Central Florida
Abstract / Description: The objective of this study was to determine the effects of a structured weight loss program that included hypocaloric diet, exercise and dietary supplementation, on weight loss, metabolic syndrome risk factors and antioxidant levels in healthy overweight and obese females. Thirty-seven healthy overweight and obese women (BMI 29.5 ± 2.3 kg/m2, 41.1 ± 7.1 yrs) participated in this study. The subjects were randomized into one of two groups: an exercise, hypocaloric diet and antioxidant...
Show moreThe objective of this study was to determine the effects of a structured weight loss program that included hypocaloric diet, exercise and dietary supplementation, on weight loss, metabolic syndrome risk factors and antioxidant levels in healthy overweight and obese females. Thirty-seven healthy overweight and obese women (BMI 29.5 ± 2.3 kg/m2, 41.1 ± 7.1 yrs) participated in this study. The subjects were randomized into one of two groups: an exercise, hypocaloric diet and antioxidant supplement (LifePak®; LSANT group, n=20) or an exercise, hypocaloric diet and appetite suppression supplement (HTP Complex® and TēGreen®; LSAS group, n=17). A significant weight loss occurred in both groups after 12 weeks (LSANT: -2.8 ± 2.8 kg and LSAS: -4.3 ± 2.7 kg, p<0.001). Body fat mass, percent body fat, and waist circumference significantly improved in both groups (p<0.05). No significant difference was found between the groups for weight loss (p>0.05). However, a significant difference was found between the groups for body fat mass (LSANT: -1.8 ± 2.6 kg; LSAS: -3.4 ± 2.4 kg, p ≤ 0.05). Glucose, insulin and insulin resistance (HOMA-IR) were significantly decreased in the LSAS group (glucose: -5.0 ± 6.8 mg/dl, p=0.008; insulin: -2.6 ± 3.8 uIU/dl, p=0.013; and HOMA-IR: -0.7 ± 1.0, p=0.012) but not in the LSANT group (p>0.05). There were no significant differences (p>0.05) observed within or between the groups for cholesterol, triglycerides or LDL-c. HDL-c decreased significantly in the LSANT group (-2.9 ± 5.3 mg/dl, p=0.024) but not in the LSAS group (p>0.05). Skin carotenoid scores (SCS) increased significantly within the LSANT group (LSANT: 10950 ± 8395 SCS, p<0.001) but not the LSAS group (p>0.05). Lifestyle intervention that involves a structured hypocaloric diet and increased physical activity results in weight loss and improvements in body composition. However, supplementation with an appetite suppressant (HTP Complex®) did not enhance weight loss beyond what was achieved with a structured lifestyle intervention. Antioxidant supplementation may be of benefit during a weight loss program that incorporates physical activity and a low energy diet.
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Date Issued: 2007
Identifier: CFE0001815, ucf:47348
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0001815

Title: Deciphering the Role of Adrenergic Hormones in Embryonic Cardiac Calcium Signaling and Metabolism.
Creator: Peoples, Jessica, Ebert, Steven, Davidson, Victor, Phanstiel, Otto, Yooseph, Shibu, University of Central Florida
Abstract / Description: The adrenergic hormones norepinephrine (NE) and epinephrine (EPI) are critical regulators of mammalian cardiovascular physiology. NE and EPI mediate stress responses to enhance cardiovascular function, however dysregulation of adrenergic signaling leads to heart failure, congenital heart malformations, and sudden cardiac death. Adrenergic hormone-expressing cells were found in the early embryonic heart, and NE has been determined essential for embryonic cardiac development. Despite extensive...
Show moreThe adrenergic hormones norepinephrine (NE) and epinephrine (EPI) are critical regulators of mammalian cardiovascular physiology. NE and EPI mediate stress responses to enhance cardiovascular function, however dysregulation of adrenergic signaling leads to heart failure, congenital heart malformations, and sudden cardiac death. Adrenergic hormone-expressing cells were found in the early embryonic heart, and NE has been determined essential for embryonic cardiac development. Despite extensive work in adults, the regulatory roles and adrenergic targets of these hormones during embryonic cardiac development have not yet been fully determined. Prior transcriptomic studies from our lab showed that expression of signal transduction and metabolic genes in embryos lacking adrenergic hormones were by far the most affected categories of genes. Thus, we hypothesized that adrenergic hormones stimulate early calcium signaling, and are required for sufficient supply of energy substrates for the metabolic shift from anaerobic glycolysis to aerobic respiration during heart development. We utilized the dopamine ?-hydroxylase knock-out (Dbh-/-) mouse model to examine effects of adrenergic-deficiency on calcium signaling and metabolism during heart development. Using calcium-imaging and patch-clamp techniques, we found that calcium transients, voltage-gated calcium channels, and L-type calcium currents in adrenergic-deficient embryonic hearts were not affected relative to controls indicating adrenergic stimulation did not influence early calcium signaling. Metabolomics analyses of adrenergic-deficient hearts revealed disruption in glycolytic and pentose-phosphate pathways as well as reduced activity of respective regulatory enzymes, glyceraldehyde 3-phosphate dehydrogenase and glucose 6-phosphate dehydrogenase indicating compromised glucose metabolism. Addition of pyruvate to embryonic hearts led to significant recovery of ATP concentrations and oxygen consumption rates, thereby supporting the hypothesis that adrenergic-deficient hearts are (")starved(") of metabolic substrates required for transitions from anaerobic glycolysis to aerobic metabolism. Overall, we showed that adrenergic hormones are not necessary for calcium signaling in the embryonic heart, but are essential regulators ensuring sufficient metabolic substrate and boosting enzymatic activities to fuel aerobic metabolism.
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Date Issued: 2018
Identifier: CFE0007233, ucf:52223
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0007233

Title: NURSING INTERVENTIONS IN THE CARE OF PATIENTS UNDERGOING INDUCED HYPOTHERMIA.
Creator: Zimmerman, Angela, Amidei, Christina, University of Central Florida
Abstract / Description: Use of induced hypothermia for the purpose of lowering intracranial pressure and preserving neuronal function has increased as research data reveals a trend of positive outcomes in patients treated with this therapy. Recently induced hypothermia following cardiac arrest due to ventricular fibrillation has been deemed successful. Current research has expanded to evaluate the effectiveness of induced hypothermia as a treatment modality for severe stroke and head trauma. In spite of its efficacy...
Show moreUse of induced hypothermia for the purpose of lowering intracranial pressure and preserving neuronal function has increased as research data reveals a trend of positive outcomes in patients treated with this therapy. Recently induced hypothermia following cardiac arrest due to ventricular fibrillation has been deemed successful. Current research has expanded to evaluate the effectiveness of induced hypothermia as a treatment modality for severe stroke and head trauma. In spite of its efficacy, complications exist with this treatment modality. The purpose of this literature review is to examine potential complications secondary to induced hypothermia and highlight the nurse's role in managing patient care. At the present, patient protocols for induced hypothermia are lacking. The success of treatment is largely dependent on the skill of the healthcare team to prevent further harm and enhance therapeutic outcomes by providing astute assessment and management of complications in patients undergoing induced hypothermia. The desired outcome of this review is to promote integration of research in the development of evidence-based protocols for induced hypothermia.
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Date Issued: 2011
Identifier: CFH0003836, ucf:44718
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFH0003836

Title: EFFECTS OF FOOD DEPRIVATION ON BLOOD LIPID CONCENTRATION AND COMPOSITON IN STELLER SEA LIONS (EUMETOPIAS JUBATUS).
Creator: Berman, Michelle, Worthy, Graham, University of Central Florida
Abstract / Description: Steller sea lions, the largest Otariid, fast during their breeding season; during this time they refrain from ingesting food for a period of 12-43 days. Fasting, while undertaking an extremely energetically demanding activity (breeding and pupping), requires specific physiological adaptations. This study examined the physiological response to fasting of two age classes, juveniles and sub-adults, during the breeding and non-breeding seasons to determine how these animals utilize lipids and the...
Show moreSteller sea lions, the largest Otariid, fast during their breeding season; during this time they refrain from ingesting food for a period of 12-43 days. Fasting, while undertaking an extremely energetically demanding activity (breeding and pupping), requires specific physiological adaptations. This study examined the physiological response to fasting of two age classes, juveniles and sub-adults, during the breeding and non-breeding seasons to determine how these animals utilize lipids and the pattern of fatty acid mobilization from lipid stores during fasting. Four juveniles and 5 sub-adults were fasted for one and two weeks, respectively, and blood samples were collected approximately every 3 days for lipid analysis. The concentrations of plasma non-esterified fatty acids (NEFA) were analyzed spectrophotometrically. Serum fatty acid composition was analyzed using gas chromatography (GC) and their individual weight percent (wt %) were correlated with their peak retention time and calculated using the area under each peak. Sixty-nine fatty acids were quantified from each sample. However, only those with concentrations above 0.2 wt. % were included in the analysis. Sub-adult samples were grouped on a percent mass loss basis (0%, 7-8% and 15% mass loss) to facilitate comparison with the juveniles. These data represent the total lipid fatty acid composition of each blood sample. Relative lipid concentration was calculated by multiplying the total lipid fatty acid compositional analysis (wt %) by the NEFA concentrations measured in that respective blood sample. Plasma NEFA concentrations in juvenile Steller sea lions ranged from 1.2 ¡Ó 0.51 mM to 3.7 „b 0.69 during fasting and was within the range of fasting phocids. Concentrations of NEFAs in the sub-adult Steller sea lions ranged from 1.00 mM up to 9.70 mM and were generally higher than fasting phocids. The wt % of only one fatty acid (20:0) was significantly different between the breeding and non-breeding season in fasting juveniles. However, the wt % of seven fatty acids changed significantly during fasting in the juveniles and five of these were most significant in separating the beginning and end of the fasts using principal components analysis. In contrast, the wt % of 10 fatty acids were significantly different during the breeding and non-breeding season fasts of the sub-adults. Additionally, the wt % of 10 fatty acids changed significantly during fasting in the sub-adults and four of these (16:1n-7, 18:2n-6, 20:0, and 20:1n-9) were most significant in separating the beginning and end of the fasts using principal components analysis. These trends reveal the physiological differences between the juvenile and sub-adult Steller sea lions and suggest that the sub-adults may be better physiologically and metabolically adapted to fast than the juveniles in this study.
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Date Issued: 2005
Identifier: CFE0000621, ucf:46526
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0000621

Title: TESTING MICE AT RISK OF PANCREATIC CANCER FOR ALTERED PROTEIN PATHWAYS FOUND IN DIABETES.
Creator: Cheung, Henley, Altomare, Deborah A., University of Central Florida
Abstract / Description: Pancreatic cancer is nearly asymptomatic, which can result in extensive grow and even metastasis to other organs before detection. When diagnosed at a late stage, the survival rate is 3%. Early detection is therefore the key to treating pancreatic cancer. Diabetes was identified as a risk factor for the development of pancreatic cancer, but the mechanism remains unknown. In this project, the objective was to delineate a link between diabetes and pancreatic cancer by examining their shared...
Show morePancreatic cancer is nearly asymptomatic, which can result in extensive grow and even metastasis to other organs before detection. When diagnosed at a late stage, the survival rate is 3%. Early detection is therefore the key to treating pancreatic cancer. Diabetes was identified as a risk factor for the development of pancreatic cancer, but the mechanism remains unknown. In this project, the objective was to delineate a link between diabetes and pancreatic cancer by examining their shared protein signaling pathways. In a previous study, hyper-activation of AKT1 resulted in a pre-diabetic phenotype and also increased upregulation of downstream phosphorylated mTOR and phosphorylated p70S6 kinase. More recently, mice with mutations that hyper-activated AKT1 and KRAS showed a significantly higher blood glucose level compared to littermate matched wild-type, mutant AKT1, or mutant KRAS mice. Interestingly, mice with a combination of mutations that hyper-activated AKT1 and KRAS also showed faster development of pancreatic cancer compared to these other groups of littermate mice. Toward determining a molecular basis for the crosstalk between AKT1 and KRAS, pancreas and liver tissues were collected from all four groups of mice including wild-type, mutant AKT1, mutant KRAS, and mice with dual AKT1/KRAS hyper-activation. One strategy was to examine expression and/or phosphorylation of downstream protein signaling crosstalk by analysis of p70S6K using Western Blots. Erk 1/2 proteins were also tested as downstream proteins of KRAS to provide a molecular view of the individual and cooperative roles of AKT1 and KRAS in the mouse models. A potential feedback mechanism to affect insulin receptor signaling in the pancreas was examined using enzyme-linked immunosorbent assays (ELISA). A significant decrease in insulin receptor phosphorylation, possibly contributing to insulin resistance, was found when mice had mutant hyper-activated KRAS. Contrary to the original expectations, mice with combined mutations of AKT1 and KRAS may contribute to the accentuated diabetic phenotype by targeting two different points in the AKT and KRAS protein signaling pathways. The information can help understand the relationship between glucose metabolism, diabetes, and pancreatic cancer development. By thoroughly studying the interactions between targets in the AKT1/KRAS signaling pathways, key molecular events that induce metabolic changes and potentially early biomarkers may lead to an improved understanding of risk and/or detection of pancreatic cancer.
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Date Issued: 2017
Identifier: CFH2000273, ucf:45895
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFH2000273

Title: ANATOMICAL AND FUNCTIONAL ASSESSMENT OF PNMT+ NEURONS IN THE MOUSE HYPOTHALAMUS AND CEREBELLUM: POTENTIAL ROLES IN ENERGY METABOLISM AND MOTOR CONTROL.
Creator: Lindo, Lake A, Ebert, Steven, University of Central Florida
Abstract / Description: Phenylethanolamine N-methyltransferase (Pnmt) is the enzyme in the catecholamine pathway responsible for converting norepinephrine to epinephrine. Pnmt is present in numerous areas; however, the scope of its expression in the mouse brain is not fully understood. A genetic mouse model was generated by the Ebert lab that exhibited the selective destruction of all Pnmt+ cells through the induction of apoptosis by Diphtheria Toxin A. Unexpected phenotypic defects arose that are characterized by...
Show morePhenylethanolamine N-methyltransferase (Pnmt) is the enzyme in the catecholamine pathway responsible for converting norepinephrine to epinephrine. Pnmt is present in numerous areas; however, the scope of its expression in the mouse brain is not fully understood. A genetic mouse model was generated by the Ebert lab that exhibited the selective destruction of all Pnmt+ cells through the induction of apoptosis by Diphtheria Toxin A. Unexpected phenotypic defects arose that are characterized by metabolic weight deficits and motor ataxia. The distribution of Pnmt+ neurons was examined throughout the hypothalamus and cerebellum to generate an anatomical map of current and historical Pnmt expression using various histochemical methods. Historical Pnmt expression appears more extensive than current expression levels at the adult stage, indicating that certain cells in the mouse brain may have experienced transient Pnmt expression. The presence of Pnmt in these regions suggests that the destruction of these neurons may play a role in the phenotypic defects observed in the ablation mouse model. Gaining a more comprehensive understanding of the potential role of Pnmt in these areas may elucidate new drug targets or novel methods to treat obesity and motor control disorders such as ataxia.
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Date Issued: 2018
Identifier: CFH2000547, ucf:45689
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFH2000547

Title: MANIPULATING AKTIVATED METABOLISM VIA MTORC1.
Creator: von Hack-Prestinary, Ivan, Altomare, Deborah, University of Central Florida
Abstract / Description: Although poorly understood, normal cells and cancerous cells of the same type exhibit different patterns of nutrient consumption, processing and utility of metabolic substrates. Differences in substrate uptake, preference, and alternately emphasized metabolic pathways offer opportunities for selective targeting of cancer versus stroma. This may be accomplished by using a sequential approach of nutrient deprivation and pharmaceutical perturbation of metabolic pathways to inhibit cellular...
Show moreAlthough poorly understood, normal cells and cancerous cells of the same type exhibit different patterns of nutrient consumption, processing and utility of metabolic substrates. Differences in substrate uptake, preference, and alternately emphasized metabolic pathways offer opportunities for selective targeting of cancer versus stroma. This may be accomplished by using a sequential approach of nutrient deprivation and pharmaceutical perturbation of metabolic pathways to inhibit cellular proliferation. The purpose of this study was to investigate the effects of restricting glucose and glutamine concentrations, in vitro, to levels that resemble a potential human fasting state. The mammalian target of rapamycin (mTOR), a mediator of nutrient sensation, was then inhibited with rapamycin in the nutrient-restricted conditions. Because active Akt/mTOR is implicated in cancer cell pro-survival, the hypothesis is that pharmaceutical inhibition of active Akt/mTOR signaling in combination with the stress of restricted nutrient supply will be more effective than nutrient deprivation alone at disrupting metabolic processes to impair cancer cell proliferation and/or pro-survival mechanisms. Untreated and treated conditions were tested to determine if an additive or synergistic effect would result from a sequential insult of nutrient deprivation followed by inhibited mTORC1 signaling. The cell line used for this study was cultivated from a murine pancreatic intraepithelial neoplasia (PANIN) derived from a transgenic mouse with pancreatic tissue-specific expression of constitutively active Akt. The transgene of Akt, isoform 1, contains a myristoyl tag that facilitates co-localization of Akt to the plasma membrane, thereby promoting the activation of this signaling protein. This aberrantly activated Akt represents a prosurvival condition observed in most cancers, and impacts metabolic balance with increased downstream signaling to metabolic sensors and regulators, including mTORC1. Several methods were used to evaluate changes in metabolic and physiological response to nutrient deprivation and mTORC1 inhibition. These included tetrazolium reduction/absorbance readings to qualitatively evaluate differences in cell proliferation, and Western immunoblots for observing changes in protein expression and phosphorylation. ATP luminescence assays were applied to quantify intracellular ATP content, and citrate synthase spectrophotometry used to quantify specific activity/indicate changes in the TCA/OXPHOS production of ATP. Results from the above methods suggest that, individually, nutrient deprivation and rapamycin treatment share some similar effects on metabolically-related protein phosphorylation and in reducing cellular proliferation. Collectively, nutrient deprivation plus rapamycin treatment, however, resulted in unanticipated metabolic alterations under conditions used for this study, the complexities of which would need to be delineated in future studies.
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Date Issued: 2013
Identifier: CFH0004373, ucf:45006
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFH0004373

Title: Energy Expenditure and Stability During Self-Paced Walking on Different Slopes.
Creator: Raffaelli, Alanna, Huang, Helen, Fu, Qiushi, Kassab, Alain, University of Central Florida
Abstract / Description: Metabolic power and cost of transport (COT) are common quantifiers for effort when performing tasks including walking and running. Most studies focus on using a range of normal walking speeds over level ground or varied slopes. However, these studies use fixed-speed conditions. Fatigue, stability, metabolic expenditure, heart rate, and many other factors contribute to normal walking speed varying over time. This study aimed to show that allowing a subject to walk with a self-paced speed...
Show moreMetabolic power and cost of transport (COT) are common quantifiers for effort when performing tasks including walking and running. Most studies focus on using a range of normal walking speeds over level ground or varied slopes. However, these studies use fixed-speed conditions. Fatigue, stability, metabolic expenditure, heart rate, and many other factors contribute to normal walking speed varying over time. This study aimed to show that allowing a subject to walk with a self-paced speed should correlate to a minimum COT at a given slope. This study also aimed to determine if a preferred slope exists based on minimizing metabolic expenditure or maximizing stability. In this study, subjects walked at four different speed conditions including three fixed speeds (0.75 m/s, 1.0 m/s, 1.25 m/s) and their self-paced speed at five different slopes (-6(&)deg;, -3(&)deg;, 0(&)deg;, 3(&)deg;, 6(&)deg;) while metabolic energy expenditure and motion were recorded. The minimum COT occurred at a 3(&)deg; decline. At this slope, some subjects preferred to walk at a faster speed compared to level ground, whereas other subjects walked with a slower speed compared to level ground. Thus, there was a greater range of self-paced speeds, from 0.745 m/s-2.045 m/s. In comparison, at a 6(&)deg; incline, the range of self-paced speeds was much smaller, from 0.767 m/s-1.434 m/s. The variance among self-paced speeds and slope conditions between subjects suggests that COT, alone, does not explain walking decisions; stability might play a greater role than initially believed. These results provide greater insight into why humans choose to walk at a certain speed over a range of slopes and terrains.
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Date Issued: 2019
Identifier: CFE0007515, ucf:52629
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0007515

Title: Cardiac Autonomic Control in Patients with Metabolic Syndrome.
Creator: Mitchell, Jonathan, Cassisi, Jeffrey, Bedwell, Jeffrey, Beidel, Deborah, University of Central Florida
Abstract / Description: Metabolic syndrome (MetS) encompasses metabolic abnormalities that substantially increase risk for chronic illnesses. MetS and stress are closely related; the pathophysiology of MetS involves dysregulated stress response in both the physiological and psychological domains. In an effort to further clarify the relationship between metabolic abnormalities and autonomic dysregulation, we used ambulatory impedance cardiography to examine indicators of cardiac autonomic control (CAC) in a sample of...
Show moreMetabolic syndrome (MetS) encompasses metabolic abnormalities that substantially increase risk for chronic illnesses. MetS and stress are closely related; the pathophysiology of MetS involves dysregulated stress response in both the physiological and psychological domains. In an effort to further clarify the relationship between metabolic abnormalities and autonomic dysregulation, we used ambulatory impedance cardiography to examine indicators of cardiac autonomic control (CAC) in a sample of 50 adult primary care patients with and without MetS. Indices of sympathetic and parasympathetic influences on cardiovascular functioning were assessed in the context of psychological stressors and compared across experimental groups and examined in relation to self-reported health measures. Primary results suggest that while our experimental groups did not differ significantly on baseline measures, patterns of responses to experimentally induced stressors were largely consistent with our predictions, and demonstrate that individuals with MetS responded to stress cues with more maladaptive CAC scores. Moreover, in line with previous work, we found that elements of CAC in our sample were predictive of both cardiovascular disease and self-reported environmental quality of life. Overall, our results suggest that maladaptive physiological manifestations of the stress response are evident among individuals with MetS and may also be related to long-term health outcomes. The present study carries implications for both evaluation and assessment as well as treatment delivery and monitoring. In addition, the ambulatory nature of data collection demonstrated here supports trends toward mHealth and related initiatives in emerging modes of healthcare delivery.
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Date Issued: 2016
Identifier: CFE0006359, ucf:51519
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0006359

Title: Consequences of Altered Short-Chain Carbon Metabolism in Heart Failure.
Creator: Horton, Julie, Estevez, Alvaro, Kelly, Daniel, Parthasarathy, Sampath, Crawford, Peter, University of Central Florida
Abstract / Description: Cardiovascular disease is currently the foremost cause of death within the United States. Heart failure (HF) is a syndrome defined by the inability of the heart to adequately execute requisite pump function in order to deliver nutrients and oxygen to peripheral tissues, irrespective of etiology. One of the most common causes of HF is chronic pressure overload due to hypertension. Ischemic heart disease is also a common driver of HF, often in conjunction with hypertension. Pressure overload...
Show moreCardiovascular disease is currently the foremost cause of death within the United States. Heart failure (HF) is a syndrome defined by the inability of the heart to adequately execute requisite pump function in order to deliver nutrients and oxygen to peripheral tissues, irrespective of etiology. One of the most common causes of HF is chronic pressure overload due to hypertension. Ischemic heart disease is also a common driver of HF, often in conjunction with hypertension. Pressure overload initially causes compensatory metabolic changes. Structural changes follow shortly thereafter typically resulting in left ventricular hypertrophy. Eventually, the heart loses the ability to compensate for the aberrant hemodynamic load and begins failing. The failing heart is unable to supply adequate adenosine triphosphate (ATP) for contractile function as evidenced by falling phosphocreatine (PCr) levels. This energy deficit occurs concurrently with a metabolic re-programming that results in a fuel utilization pattern resembling the fetal heart. Notably, enzymes involved in catabolism of fatty acids, the chief fuel substrate for ATP generation in the normal adult heart, are downregulated in the failing heart. However, the extent to which alternative fuels compensate for decreased fatty acid oxidation (FAO) is not well-known. Furthermore, consequences of the fuel substrate switches that occur in heart failure are not well established. In this work, we discover a new paradigm for alternate fuel utilization in the failing heart and define consequences of altered fuel metabolism in HF. We discovered a post-translational modification resultant from an accumulation of acetyl groups (C2) present in a mouse model of early-stage HF and human HF. Mitochondrial proteins were found to be hyperacetylated in the failing heart, and at least some of these alterations result in diminished electron-transport chain (ETC) capacity as shown by mutagenesis studies on succinate dehydrogenase A (SDHA). We also found an accumulation of C4-OH carnitine, a by-product of ketone oxidation in HF. This metabolite aggregation occurred alongside an increase in b-hydroxybutyrate dehydrogenase 1 (BDH1) transcript and protein levels. This signature suggested that the failing heart shifted to ketone bodies as a fuel. Subsequent experiments confirmed increased capacity for myocardial ketone oxidation in compensated cardiac hypertrophy and in HF. The consequences of increased ketone oxidation were then assessed using a cardiac-specific BDH1 knockout (BDH1 KO) mouse. Despite not having any apparent defect at baseline, we found BDH1 KO mouse hearts are completely unable to oxidize 3-hydroxybutyrate. The deficit for ketone oxidation capacity became consequential upon subjugation to transverse aortic constriction with a small apical myocardial infarction (TAC/MI). The BDH1 KO mice exhibit altered pathological cardiac remodeling compared to wild-type controls. These latter data suggest the increased reliance on ketone oxidation in HF, mediated by BDH1, is an adaptive response. Together the results of these studies provide important information regarding the consequences of altered fuel metabolism in HF. Recent reports of reduced HF mortality and elevated circulating ketone levels in patients prescribed Empagliflozin make cardiac ketone metabolism research in this dissertation particularly apropos.
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Date Issued: 2017
Identifier: CFE0006948, ucf:51663
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0006948

Title: Action potentials as indicators of metabolic perturbations for temporal proteomic analysis.
Creator: Kolli, Aditya Reddy, Hickman, James, Clausen, Christian, Ballantyne, John, Gesquiere, Andre, Jha, Sumit, University of Central Florida
Abstract / Description: The single largest cause of compound attrition during drug development is due to inadequate tools capable of predicting and identifying protein interactions. Several tools have been developed to explore how a compound interferes with specific pathways. However, these tools lack the potential to chronically monitor the time dependent temporal changes in complex biochemical networks, thus limiting our ability to identify possible secondary signaling pathways that could lead to potential...
Show moreThe single largest cause of compound attrition during drug development is due to inadequate tools capable of predicting and identifying protein interactions. Several tools have been developed to explore how a compound interferes with specific pathways. However, these tools lack the potential to chronically monitor the time dependent temporal changes in complex biochemical networks, thus limiting our ability to identify possible secondary signaling pathways that could lead to potential toxicity. To overcome this, we have developed an in silico neuronal-metabolic model by coupling the membrane electrical activity to intracellular biochemical pathways that would enable us to perform non-invasive temporal proteomics. This model is capable of predicting and correlating the changes in cellular signaling, metabolic networks and action potential responses to metabolic perturbation.The neuronal-metabolic model was experimentally validated by performing biochemical and electrophysiological measurements on NG108-15 cells followed by testing its prediction capabilities for pathway analysis. The model accurately predicted the changes in neuronal action potentials and the changes in intracellular biochemical pathways when exposed to metabolic perturbations. NG108-15 cells showed a large effect upon exposure to 2DG compared to cyanide and malonate as these cells have elevated glycolysis. A combinational treatment of 2DG, cyanide and malonate had a much higher and faster effect on the cells. A time-dependent change in neuronal action potentials occurred based on the inhibited pathway. We conclude that the experimentally validated in silico model accurately predicts the changes in neuronal action potential shapes and proteins activities to perturbations, and would be a powerful tool for performing proteomics facilitating drug discovery by using action potential peak shape analysis to determine pathway perturbation from an administered compound.
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Date Issued: 2014
Identifier: CFE0005822, ucf:50037
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0005822

Title: EXPRESSION OF HETEROLOGOUS PROTEINS IN TRANSGENIC TOBACCO CHLOROPLASTS TO PRODUCE A BIOPHARMACEUTICAL AND BIOPOLYMER.
Creator: Devine, Andrew, Daniell, Henry, University of Central Florida
Abstract / Description: The chloroplast has been demonstrated to be an ideal compartment to accumulate certain proteins or their biosynthetic products that would be harmful if they were accumulated in the cytoplasm. Hyper-expression of foreign proteins in chloroplast transgenics has accumulated up to 46% total soluble protein, this is possible due to the ~100 chloroplast genomes per chloroplast and ~100 chloroplasts per cell which can therefore, contain up to 10,000 copies of the transgene. Maternal gene inheritance...
Show moreThe chloroplast has been demonstrated to be an ideal compartment to accumulate certain proteins or their biosynthetic products that would be harmful if they were accumulated in the cytoplasm. Hyper-expression of foreign proteins in chloroplast transgenics has accumulated up to 46% total soluble protein, this is possible due to the ~100 chloroplast genomes per chloroplast and ~100 chloroplasts per cell which can therefore, contain up to 10,000 copies of the transgene. Maternal gene inheritance of plastids in most crop plants results in natural gene containment. Chloroplast transformation also eliminates positional effects that are frequently observed with nuclear transformation and no gene silencing has been observed so far at the level of transcription or translation. Consequently, independent chloroplast transgenic lines have very similar levels of foreign gene expression and there is no need to screen hundreds of transgenic events. The chloroplast genome has also been used in molecular farming to express human therapeutic proteins, vaccines for human or animal use and biomaterials. In this study we have produced a Nicotiana tabacum cv. petit Havana chloroplast transgenic line that expresses a cholera toxin B subunit (from Vibrio Cholerae)-human proinsulin (a,b and c chain) fusion protein, designated CTB-Pris. The pLD-PW vector contains the CTB-Pris gene cloned into the universal chloroplast transformation vector pLD-ctv in which the 16S rRNA promoter drives the aadA gene selectable marker, which confers resistance to spectinomycin; the psbA 5' untranslated region (UTR) which enhances translation of CTB-Pris in the presence of light and the psbA 3'UTR confers transcript stability. The trnI and trnA homologous flanking sequences facilitated site-specific integration of transgenes into the tobacco chloroplast genome. Site-specific integration was demonstrated by PCR and Southern blot analysis with probes for CTB-Pris. Western Blot analysis has demonstrated the presence of abundant CTB-Pris in transgenic plants with both CTB polyclonal and proinsulin monoclonal antibodies. Southern blot analysis has also confirmed that homoplasmy had been achieved in the T0 generation. The expression levels for CTB-Proinsulin varied between 270ìg/100mg to 364.8ìg/100mg of plant tissue which equates to ~30% total soluble protein. In the second study the E. coli ubiC gene that codes for chorismate pyruvate-lyase (CPL) was integrated in the tobacco chloroplast genome under the control of the light-regulated psbA 5' untranslated region. CPL catalyzes the direct conversion of chorismate – an important branch point intermediate in the shikimate pathway that is exclusively synthesized in plastids – to pHBA and pyruvate. pHBA is the major monomer in liquid crystal polymers (LCPs). These thermotropic polyesters have excellent properties, including high strength/stiffness, low melt viscosity, property retention at elevated temperatures, environmental resistance and low gas permeability. The leaf content of pHBA glucose conjugates in fully mature T1 plants exposed to continuous light (total pooled material) varied between 13-18% DW, while the oldest leaves had levels as high as 26.5% DW. The highest CPL enzyme activity observed in total leaf material was 50,783 pkat/mg of protein, which is equivalent to ~35% of the total soluble protein. Animal studies in the Daniell lab, suggest that the CTB-Proinsulin producing plants suppress insulitis and clinical symptoms of diabetes in NOD mice. These observations demonstrate the versatility of chloroplast gene expression for production of biopharmaceuticals and biopolymers.
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Date Issued: 2006
Identifier: CFE0001056, ucf:46794
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0001056

Title: THE GLYCINE AND PROLINE REDUCTASE SYSTEMS: AN EVOLUTIONARY PERSPECTIVE AND PRESCENCE IN ENTEROBACTERIACEAE.
Creator: Witt, Joshua, Self, William, University of Central Florida
Abstract / Description: The Glycine and Proline Reduction systems are two of the best characterized selenoenzymes in bacteria and have been found to occur in a wide variety of clostridia . These enzymes are utilized to reduce glycine or D-proline to obtain energy via substrate level phosporylation or membrane gradients, respectively [6, 7]. This includes the pathogens C. difficile and C. botulinum [5, 8]. Strains of C. difficile are activate toxigenic pathways whenever either of these pathways is active within the...
Show moreThe Glycine and Proline Reduction systems are two of the best characterized selenoenzymes in bacteria and have been found to occur in a wide variety of clostridia . These enzymes are utilized to reduce glycine or D-proline to obtain energy via substrate level phosporylation or membrane gradients, respectively [6, 7]. This includes the pathogens C. difficile and C. botulinum [5, 8]. Strains of C. difficile are activate toxigenic pathways whenever either of these pathways is active within the cell [5, 8]. Though evolutionary studies have been conducted on ammonia producing bacteria none has been done to directly characterize these two system by themselves. This includes an understanding of whether or not this system is transferred between organisms, as many of the clostridia that are to be studied are known to have an "open genome." [8, 10] With this information we were able to generate a phylogenic model of the proline and glycine reduction systems. Through this analysis, we were able to account for many clostridial organisms that contain the system, but also many other organisms as well. These included enterobacteriaceae including a strain of the model organism, Escherichia coli. It was further concluded that Glycine Reductase was a much less centralized system and included a wide range of taxa while Proline Reductase was much more centralized to being within the phyla of firmicutes. It was also concluded that the strain of E. coli has a fully functional operon for Glycine Reductase.
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Date Issued: 2013
Identifier: CFH0004506, ucf:45149
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFH0004506

Title: DETERMINANTS OF CHLOROPLAST GENE EXPRESSION AND APPLICATIONS OF CHLOROPLAST TRANSFORMATION IN LACTUCA SATIVA AND NICOTIANA TABACUM.
Creator: Ruhlman, Tracey, Daniell, Henry, University of Central Florida
Abstract / Description: Genetic modification of plastids in the model plant tobacco (Nicotiana tabacum) has demonstrated that numerous foreign gene products can accumulate to high levels in this setting. Plastid biotechnology is maturing to encompass the improvement of food and feed species and the production of biopharmaceutical proteins for oral delivery necessitating development of stable transplastomic edible plants. In the interest of establishing an edible platform we have investigated the use of native and...
Show moreGenetic modification of plastids in the model plant tobacco (Nicotiana tabacum) has demonstrated that numerous foreign gene products can accumulate to high levels in this setting. Plastid biotechnology is maturing to encompass the improvement of food and feed species and the production of biopharmaceutical proteins for oral delivery necessitating development of stable transplastomic edible plants. In the interest of establishing an edible platform we have investigated the use of native and foreign regulatory elements in relation to foreign gene expression in plastids. Multiple sequence alignments of intergenic regions for 20 species of angiosperm showed that despite 95% identity in the coding region, identity in the psbA upstream region is 59% across all taxa examined, other gene coding regions displayed sequence identity of 80-97%, whereas the non-coding regions were 45-79% suggesting that our physical data can be extrapolated beyond the model presented. We found that by exchanging psbA untranslated regions (UTRs) between N. tabacum and lettuce (Lactuca sativa), the expression of the CTB-proinsulin (CTB-Pins) monocistronic transcript declined by 84% and foreign protein accumulation was reduced by as much as 97% in mature leaves. Polyribosome association assays suggest that ribosome-free transgenic transcripts are stabilized where the native UTR is employed. RNA EMSA revealed that binding proteins interacted with psbA 5' UTRs in a species specific manner and the half life of the L. sativa 5'UTR-CTB-Pins mRNA was reduced by 3.7 fold in N. tabacum stromal extracts. Our data indicate that the use of species-specific regulatory elements could lead to establishment of reproducible plastid transformation in desirable target species such as L. sativa. Using transplastomic L. sativa for oral delivery of bioencapsulated CTB-Pins we delayed the onset of diabetes in NOD mice when retinyl acetate supplement was provided compared to untouched mice. In this 30 week study we monitored blood glucose levels and evaluated the in vitro suppressive capacity of regulatory T cells isolated from diabetic mice. Whether delay or prevention was achieved appeared to be a function of antigen dose as high dose resulted in a nine week delay of onset while low dose reduced the incidence of diabetes by 36%. In addition we have evaluated metabolic engineering in the N. tabacum model where we generated cis-genic lines expressing nucleus-encoded methionine pathway enzymes in plastids. Transplastomic expression of Cystathionine gamma-Synthase led to a three-fold increase in enzyme activity and a doubling of methionine content in leaves without a deleterious phenotype. In exploring molecular mechanisms supporting gene expression in plastids and applying transplastomic technology to real human problems this work seeks address the potential of plastid biotechnology for improvement of commodity crops and production of biopharmaceuticals.
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Date Issued: 2009
Identifier: CFE0002687, ucf:48236
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFE0002687

Title: SUPPORT SYSTEMS IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS AND THE RELATIONSHIP TO DIABETES-RELATED STRESS, CONFLICT, AND METABOLIC CONTROL.
Creator: Foarde, Samuel, LaManna, Jacqueline, University of Central Florida
Abstract / Description: The purpose of this integrated review of the literature was to explore the effects of social support on diabetes-related stress, conflict, and metabolic control in adolescents with type 1 diabetes mellitus (T1DM). Social support was examined in four subgroups: adolescents with T1DM, family caregivers, peers, and teachers. Relevant findings in the literature revealed a significant deficiency of research devoted to adolescent males with diabetes as well as fathers as primary and secondary...
Show moreThe purpose of this integrated review of the literature was to explore the effects of social support on diabetes-related stress, conflict, and metabolic control in adolescents with type 1 diabetes mellitus (T1DM). Social support was examined in four subgroups: adolescents with T1DM, family caregivers, peers, and teachers. Relevant findings in the literature revealed a significant deficiency of research devoted to adolescent males with diabetes as well as fathers as primary and secondary caregivers. Studies highlighted the importance of fostering autonomy and positive self-image in adolescents with T1DM and described effective interventions to improve diabetes-related stress, reduce disease-related conflict, and improve metabolic control. Findings suggested that nurses caring for adolescents with T1DM and their families should foster positive, open communication, while identifying barriers to problem solving, coping, stress, and optimal glycemic control. Interventions that educate caregivers and peers on how to better communicate and provide support are critical in fostering positive psychological and physiological outcomes in the adolescent with T1DM. The findings of this study may provide guidance in the way that nurses assess, identify, and counsel adolescents with TIDM regarding their disease management and access to support systems.
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Date Issued: 2013
Identifier: CFH0004324, ucf:45057
Format: Document (PDF)
PURL: http://purl.flvc.org/ucf/fd/CFH0004324

metabolism (5)	+ -
Diabetes (2)	+ -
Glucose Metabolism (2)	+ -
Metabolic Syndrome (2)	+ -
AKT (1)	+ -

Action potential (1)	+ -
Adrenergic (1)	+ -
Akt (1)	+ -
Biopolymer (1)	+ -
Calcium (1)	+ -
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Cerebellum (1)	+ -
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Cholera Toxin B subunit (1)	+ -
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Development (1)	+ -
E. coli (1)	+ -
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