Thesis (Ph. D.)--Syracuse University, 2005. / "Publication number AAT 3194015."

Thesis (Ph. D.)--Texas A&M University, 2005. / "Major Subject: Medical Sciences" Title from author supplied metadata (automated record created on Nov. , 09:45:50.) Vita. Abstract. Includes bibliographical references.

Passive samplers are not only a versatile tool to integrate environmental concentrations of pollutants, but also to avoid the use of live sentinel organisms for environmental monitoring. This study introduced the use of magnetic silicone polymer composites (Fe-PDMS) as passive sampling media to pre-concentrate a wide range of analytes from environmental settings. The composite samplers were assessed for their accumulation properties by performing lab experiments with two model herbicides (Atrazine and Irgarol 1051) and evaluated for their uptake properties from environmental settings (waters and sediments). The Fe-PDMS composites showed good accumulation of herbicides and pesticides from both freshwater and saltwater settings and the accumulation mechanism was positively correlated with the log Kow value of individual analytes. Results from the studies show that these composites could be easily used for a wide number of applications such as monitoring, cleanup, and/or bioaccumulation modeling, and as a non-intrusive and nondestructive monitoring tool for environmental forensic purposes.

Background: Obesity is an ongoing socio-economic worldwide epidemic and major modifiable risk for cardiovascular disease (CVD), which continues to be the main determinant of all-cause mortality. A potential mechanism by which obesity associates with CVD is an increased stiffness of the arteries leading to a decreased vascular function and development of hypertension. Moreover, muscle strength and mass are inversely related to arterial stiffness and obesity. Although exercise training is a proficient intervention for treating CVD risk factors and increasing muscle strength/mass, the most effective intervention for decreasing arterial stiffness is still unclear. Whole-body vibration training (WBVT) is a relatively novel exercise mode which requires static or dynamic movements on a vibrating platform and has similar adaptations in the skeletal muscle as resistance training (RT). However, the effects of whole-body high intensity RT seem to be adverse, although controversial to arterial function in young healthy adults and middle-aged with prehypertension or hypertension. WBVT is usually performed with leg exercises using the body weight (unloaded) as resistance to the exercise. However, the addition of an external load or resistance to WBVT (WBVT+EX) has shown beneficial adaptations in improving arterial function, bone mineral density, hormonal responses, and muscle strength/mass. Purpose: The purpose of this study was to evaluate whether WBVT+EX would induce greater benefits than unloaded WBVT on arterial function and muscle strength in young-overweight and obese (body mass index, BMI= 30.9 ± 0.7 kg/m²) women. Methods: Twenty-two young (20 ± 1 yr) overweight/obese women were randomly assigned to a non-exercising overweight/obese control (O-CON), WBVT, or WBVT+EX for 6 weeks. Thirteen lean women were assigned to a lean control (L-CON) group in order to compare them at baseline to the age-matched overweight/obese women. Pulse wave velocity (PWV), brachial blood pressure (BP), aortic BP, wave reflection, muscle strength, and body composition were measured before and after 6 weeks. Results: Statistical significance was set at P < 0.05. Data were presented as mean ± SE. There were no significant time effects or group-by-time interactions for brachial-ankle PWV (baPWV), carotid-femoral PWV (cfPWV), brachial systolic BP (bSBP), brachial diastolic BP (bDBP), aortic diastolic BP (aDBP), augmentation index (AIx), augmentation pressure (AP), and transit time for the reflected wave (Tr). cfPWV and aSBP decreased (P < 0.05) in the WBVT group while baPWV and aDBP decreased in the WBVT+EX. There was a significant group-by time interaction (P < 0.01) for faPWV, aSBP, aortic mean arterial pressure (aMAP), and AIx adjusted at 75 bpm (AIx@75). In addition, group-by-time interaction was detected for P1 and P2 such that the reductions observed in the WBVT and WBVT+EX groups were significantly different (P < 0.05) from the O-CON group. The WBVT and the WBVT+EX groups had significant increases in leg strength (P < 0.01) when compared to the O-CON group (group-by-time P < 0.01) while a time-effect (P < 0.01) was observed in the chest 1RM only in the WBVT+EX group. Conclusion: To our knowledge, this is the first study to detect beneficial effects of WBVT+EX on arterial parameters, as shown by improvements in aortic BP, PWV, and wave reflection while still maintaining increases in muscle strength in young overweight/obese women. Although unloaded WBVT seems to be an effective exercise modality to improve arterial function in obese postmenopausal women, it does not seem to be as efficient in young obese women. This study suggests that, although WBVT had some positive effects on arterial function in young overweight/obese women, a more evident benefit on arterial function is observed after increasing the exercise intensity of WBVT through an external load progressed from 15 to 8 RM. Future studies should focus on older populations with greater risk of cardiovascular and/or other chronic diseases that are associated with reduced muscle strength/mass. WBVT+EX should be incorporated and recommended for young overweight/obese women in order to improve arterial function and prevent the loss in muscle mass related to weight loss. Additional studies should also consider the use of WBVT+EX as an adjunct exercise modality in order to incorporate its use in clinical populations prone to physical disabilities due to sarcopenia and dynapenia. / A Thesis submitted to the Department of Nutrition, Food, and Exercise Sciences in partial fulfillment of the requirements for the degree of Master of Science. / Fall Semester, 2014. / November 3, 2014. / Arterial stiffness, Cardiovascular diseases, Obesity, Whole-body vibration training / Includes bibliographical references. / Arturo Figueroa, Professor Directing Thesis; Diana Williams, Committee Member; Michael Ormsbee, Committee Member.

As medicine progresses and the population ages neurodegenerative diseases, such as Parkinson's, Huntington's, and Alzheimer's disease, begin to become more and more prevalent. In order to treat these devastating disorders it is important to understand the mechanisms by which they occur. N-methyl-D-aspartate (NMDA) receptors are implicated in the cellular functions responsible for learning and memory and have surfaced as key players underlying various neurological disorders. The focus of this dissertation is to uncover novel mechanisms of NMDA receptor regulation through the regulation of the Src signaling complex. Previous studies have implicated C-terminal Src Kinase (Csk) in the regulation of a variety of NMDA receptor associated functions through Src family kinases (SFKs) and the Src signaling complex. Increases in Src activity are known to up-regulate NMDA functions and play important roles in many physiological and pathophysiological processes. Csk acts to constrain SFK activity by phosphorylating a regulatory tyrosine in the C-terminal tail of the kinase. Our group has previously shown that Csk can associate with the NR2A and NR2B subunits of NMDA receptors in a Src activity-dependent manner to serve as an intrinsic mechanism to provide a "brake" on the induction of long-term synaptic potentiation (LTP) mediated by NMDA receptors. In contrast to the NR2A and NR2B subunits no apparent tyrosine phosphorylation is found in the NR1 subunit of NMDA receptors. In this work, however, we report that Csk can also associate with the NR1 subunit in a Src activity-dependent manner. Furthermore, we found that truncation of the NR1 C-tail, or mutation of its single C-tail tyrosine (Y837), decreased the association of CSK with the NMDA receptor complex and blocked the inhibition of NMDA receptors observed during the intracellular application of Csk. These findings indicate that both the NR1 and NR2 subunits are required for the regulation of NMDA receptor activity by Csk. Src kinase has been shown to play a critical role as the primary regulator of NMDA receptor activity in the Src signaling complex. To further elucidate how Src is regulated within this complex we explored a stability-associated regulation of Src activity. Using a bacterial expression system we were able to purify a neuronal isoform of Src (n-Src). We additionally expressed and purified a constitutively active and an inactive form of n-Src. Characterization of these enzymes revealed that altering n-Src enzyme activity either pharmacologically (e.g., application of ATP or a Src inhibitor) or genetically (mutation of Y535 or K303) was consistently associated with changes in n-Src stability: an increase in n-Src activity was coupled with a decrease in n-Src stability and vice versa. Furthermore, alterations in n-Src stability (e.g., application of urea or arginine) were again coupled with the same changes in n-Src activity. These findings, therefore, indicate that n-Src activity and stability are interdependent. In vivo n-Src activity is modulated through internal interactions by its regulatory SH2 and SH3 domains. Previous studies have demonstrated that these domains act to stabilize the inactive kinase and help maintain the inactive state. In this work we report that the up-regulation of NMDA receptors induced by expression of constitutively active n-Src is significantly reduced by dysfunctions of the SH2 and SH3 domains of the protein. Furthermore, we found that dysfunctions of SH2 and SH3 domains reduce auto-phosphorylation of the kinase activation loop, depress kinase activity, and decrease NMDA receptor phosphorylation. The SH2 domain plays a greater role than the SH3 domain in the regulation of the active kinase. We additionally found that n-Src binds directly to the C-terminus of the NMDA receptors NR2A subunit in vitro, with a KD of 108.2 ± 13.3 nM. This binding is not Src kinase activity-dependent and dysfunctions of the SH2 and SH3 domains do not significantly affect the binding. These data indicate that the SH2 and SH3 domains may function to promote the catalytic activity of active n-Src in addition to constraining the activity of the inactive kinase. These regulatory functions are important in the regulation of activity-dependent neuroplasticity by NMDA receptors. The importance of NMDA receptors and the necessity for their proper regulation is demonstrated by the wide variety of disorders with which NMDA receptors are associated. In this work we have explored novel mechanisms of NMDA receptor regulation by the Src signaling complex, which is tightly controlled by the regulation of Src kinase itself both extrinsically and intrinsically. Exploration into the regulation of SFKs and the association of SFKs with NMDA receptors will bring with it a better understanding of synaptic plasticity as well as yield potential therapeutic strategies to treat the growing number of NMDA receptor associated disorders. / A Dissertation submitted to the Department of Biomedical Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Summer Semester, 2011. / April 28, 2011. / Kinase, Src, NMDA Receptor / Includes bibliographical references. / Xian-Min Yu, Professor Directing Dissertation; Ewa Bienkiewicz, Professor Co-Directing Dissertation; Peter Fajer, University Representative; Branko Stefanovic, Committee Member.

Background: Nighttime eating, particularly before bed, has received considerable media attention in recent years. The common thought was to avoid caloric intake post-dinner and pre-sleep due to worries of weight gain and a negative impact on cardiometabolic health. It appears that minimizing nighttime caloric intake by providing a structured low calorie option with a high satiating value (e.g., greater protien content) may alter the risk for overcomsumption and long-term weight gain. Indeed, recent work from our laboratory and others have demonstrated that low-calorie, nighttime snacking options consisting primarily of protein may be beneficial. To date, no studies have investigated the impact of casein intake before bed on overnight and next morning fat metabolism in obese men. Purpose: To determine if casein protein (CAS) consumed at night before sleep will alter overnight subcutaneous abdominal adipose tissue (SCAAT) lipolysis, and next morning whole-body fat oxidation and appetite in overweight and obese men compared to a non-caloric placebo (PLA). Methods: Twelve overweight and obese men participated in this randomized, cross-over, double-blind and placebo-controlled study. Participants came to the laboratory at baseline and twice during each of the treatment periods with CAS and PLA. Each treatment period consisted of one visit in the evening and another the next morning. Participants consumed CAS or PLA and overnight lipolysis was measured with microdialysis, a minimally invasive method used to monitor SCAAT interstitial glycerol concentrations. The next morning fat oxidation and metabolism (indirect calorimetry), and appetite (visual analog scales for hunger, satiety, and desire to eat) were measured. Results: There were no significant differences in overnight SCAAT interstitial glycerol concentrations (CAS, 175.0 ± 26.5; PLA, 184.8 ± 20.7 μmol/L; p =0.77), fat oxidation (CAS, 0.76 ± 0.01; PLA, 0.76 ± 0.01; p =0.75), metabolic rate (CAS, 2126 ± 111; PLA, 2145 ± 106 kcals/day; p =0.94) or any markers of appetite between CAS and PLA. However, the participants in the present study were hyperinsulinemic (fasting insulin > 30 μUL), which may have masked any potential differences in the dependent variables. Conclusion: Despite common concern for eating at night before bed, it appears that casein protein had no impact on overnight lipolysis or whole-body fat oxidation and therefore does not appear to have any negative effects compared to a non-caloric placebo in obese men. (ClinicalTrials.gov NCT02211391) / A Dissertation submitted to the Department of Nutrition, Food and Exercise Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Summer Semester 2015. / July 1, 2015. / Casein, Lipolysis, Metabolism, Nighttime Eating, Obesity, Protein / Includes bibliographical references. / Michael J. Ormsbee, Professor Directing Dissertation; Robert Contreras, University Representative; Lynn B. Panton, Committee Member; Kimberly Driscoll, Committee Member.

Menopause leads to an increased risk for osteoporosis in women. Although drug therapies exist, increasing numbers of people prefer alternative therapies such as dietary supplements, e.g. calcium, vitamin D, and collagen hydrolysates for the prevention and treatment of osteoporosis. We have previously shown that a three-month intervention using a calcium-collagen chelate dietary supplement (CC) was efficacious in improving bone mineral density (BMD) and blood biomarkers of bone turnover in osteopenic postmenopausal women. The present study reports the long-term efficacy of CC in reducing bone loss in postmenopausal women with osteopenia. Thirty-nine women were randomly assigned to one of two groups: 5 g of CC containing 500 mg of elemental calcium and 200 IU vitamin D (1,25-dihydroxyvitamin D3) or control (500 mg of calcium and 200 IU vitamin D) daily for twelve months. Total body, lumbar, and hip BMD were evaluated at baseline, six and twelve months using dual-energy x-ray absorptiometry. Blood was collected at baseline, six and twelve months to assess levels of blood biomarkers of bone turnover. Intent-to-treat (ITT) analysis was performed using repeated measures analysis of variance pairwise comparisons as well as multivariate analysis to assess time and group interactions. The loss of whole body BMD in women taking CC was substantially lower than that of the control group at twelve months in those who completed the study and the ITT analysis, respectively (CC: -1.33% and -0.33% vs. control: -3.75% and -2.17%; P = .026, P = .035). The CC group had significantly reduced levels of sclerostin and tartrate-resistant acid phosphatase (TRAP5b) (P < .05), and higher bone-specific alkaline phosphatase (BAP)/TRAP5b ratio (P < .05) than control at six months. These results support the use of CC in reducing bone loss in osteopenic postmenopausal women. / A Dissertation submitted to the Department of Nutrition, Food and Exercise Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Summer Semester 2015. / July 1, 2015. / Bone, Calcium, Hydrolyzed collagen, Osteoporosis, Supplement / Includes bibliographical references. / Bahram H. Arjmandi, Professor Directing Dissertation; Cathy W. Levenson, University Representative; Jeong-Su Kim, Committee Member; Teng Ma, Committee Member.

Liver fibrosis is the common end stage of all chronic liver diseases, such as chronic viral hepatitis, alcoholism, nonalcoholic fatty liver disease, autoimmune hepatitis, alpha 1 anti-trypsin deficiency and some rare metabolic diseases. Fibrosis it is a major cause of morbidity and mortality worldwide. However, the specific and efficient anti-fibrotic therapy is still lacking. Thus, better understanding the underlying mechanism of liver fibrosis is critical in order to find a cure. Liver fibrosis is histologically characterized by excessive deposition of extracellular matrix composed primarily of type I collagen. Type I collagen is a complex protein composed by folding by two α1(I) and one α2(I) polypeptides into triple helix. The production of collagen polypeptides is regulated by the cis-acting sequence of their respective mRNAs, the 5' stem loop (5'SL). In the 5' untranslated region of collagen α1(I) and α2(I) mRNAs, there is a secondary structure forming a stem loop (5'SL). This cis-acting element regulates type I collagen expression in fibrosis by binding an RNA binding protein, La ribonucleoprotein domain family, member 6 (LARP6). LARP6 specifically binds to 5'SL of collagen mRNAs with high affinity and sequence specificity. The binding recruits several effector proteins to stimulate type I collagen production in fibrosis. LARP6 is a phosphor-protein, however, how the phosphorylation of LARP6 is involved in the process of collagen biosynthesis has not been studied before. My dissertation focuses on the role of LARP6 phosphorylation in biosynthesis of type I collagen in fibrosis. I have identified eight serines of LARP6 that undergo phosphorylation and six of these serines have never been reported to be phosphorylated before. I have characterized the functional consequence of phosphorylation of these serines, identified the responsible kinases, and analyzed the role in collagen biosynthesis. These studies are presented in the dissertation as three logically connected chapters. In the chapter two provide evidence that phosphorylation of LARP6 follows a hierarchical order; namely, that phosphorylation of S451 is the initial event, which is required for phosphorylations of other serines. Phosphorylation of S451depends on the activity of PI3K/Akt signaling pathway. Akt inhibitor, GSK-2141795, which is in clinical trials for treatment of solid tumors, reduced collagen production with EC50 of 150 nM. This effect is explained by inhibition of LARP6 phosphorylation and suggests that Akt inhibitors may be effective in treatment of xi various forms of fibrosis. The S451A mutant of LARP6 lacks phosphorylation, not only at 451 position, but also at several other serines. Its overexpression has a dominant negative effect on collagen biosynthesis; the S451A mutant drastically reduces secretion of type I collagen and induces synthesis of aberrant and over-modified collagen polypeptides. This indicates that LARP6 phosphorylation at S451 is critical for activation of the protein in translation and folding of collagen polypeptides. In the chapter three I have characterized two other phosphorylations of LARP6, the phosphorylation of S348 and S409. These sites are phosphorylated by mTORC1 and are redundant. Mutation of both of these serines is required to inactivate LARP6. The double mutant, S348A/S409A, acts as a dominant negative protein in collagen biosynthesis, which retards secretion of type I collagen and causes excessive posttranslational modifications. Similar effects are seen using mTORC1 inhibitor rapamycin or by knocking down mTORC1 function by siRNA. The phosphorylation of S348A or S409A is needed for two processes: 1. To recruit an accessory protein STRAP to collagen mRNAs and 2. To enable normal subcellular trafficking of LARP6. STRAP is needed to coordinate translation of collagen α1(I) and α2(I) mRNAs, what becomes critical in fibrosis. In the absence of S348/S409 phosphorylation LARP6 is also sequestered in increasing amounts at the ER membrane. The mechanistic details and significance of the S348/S409 phosphorylation are described in chapter 2. The role of TGF-β1 in LARP6 phosphorylation is described in the fourth chapter. TGF-β is the most potent profibrotic cytokine and this discovery provides the link between the TGF-β activity and the LARP6 dependent mechanism of collagen synthesis. The phosphorylation of LARP6 at S396 is stimulated by TGF-β and it promotes the distribution of LARP6 into the nucleus. This is necessary for binding of the newly transcribed collagen mRNAs and their inclusion in the LARP6 dependent metabolic pathway, resulting in more efficient type I collagen expression. In conclusion, my dissertation work has characterized different phosphorylation events of LARP6 and how they are involved in regulating the function of LARP6 in type I collagen biosynthesis. These findings will contribute to better understanding of the underlying mechanism of overproduction of type I collagen in fibrosis, and provide the rationale of using kinase inhibitors for treating fibrotic disorders. / A Dissertation submitted to the Department of Biomedical Science in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Spring Semester 2016. / April 06, 2016. / LARP6, liver fibrosis, phosphorylation, RNA binding protein, type I collagen / Includes bibliographical references. / Branko Stefanovic, Professor Directing Dissertation; Hengli Tang, University Representative; Akash Gunjan, Committee Member; Myra Hurt, Committee Member; Yanchang Wang, Committee Member.

The purpose of this study was to examine the effect of live versus recorded music on the nutritional intake of older adults during mealtimes in an assisted living facility. Nutritional health is an important component of maintaining quality-of-life. Poor nutrition in older adults is due to health conditions, life changes, and other symptoms of aging. Attention to proper nutrition is too often neglected or absent in the lives of many older adults, especially those in long-term care. Interventions exist to combat malnutrition and its consequences, including sensory stimulation interventions involving recorded music; however, no research has been done examining the impact of live music therapy, which is extensively regarded as more effective than recorded music in other contexts. Participants in this study were residents at two assisted living facilities. The design of the study was ABAC or ACAB, where A was the no-music control, B was recorded music, and C was live music therapy. Food intake was measured using a plate-waste survey. Results indicated that food intake increased with both recorded music and live music; however, a significant increase in food intake was found between the no music and live music conditions. The increase in food intake between the no music and recorded music conditions was not significant. These results have implications for the role of music therapy in improving the food intake of older adults, and thus, their nutritional health as well. / A Thesis submitted to the College of Music in partial fulfillment of the requirements for the degree of Master of Music. / Fall Semester 2016. / November 3, 2016. / Music Therapy, Nutrition, Older Adults / Includes bibliographical references. / Alice-Ann Darrow, Professor Directing Thesis; Clifford Madsen, Committee Member; Jayne Standley, Committee Member.

Complementary and Alternative Medicine (CAM) is comprised of a range of therapeutic modalities and atypical practices which have been found to successfully accompany standard medical care. Interventions such as guided imagery and stress management education, among many others, have been linked to improved health outcomes and recovery in the area of mind-body research (Freeman, 2005; Tusek et al., 1997). The objective of this study was to ascertain the degree of impact biofeedback and guided imagery have on psychological variables and medical measures as individual and combined interventions among orthopedic patients who underwent joint replacement surgery. Hip and knee arthroplasty patients (n = 60) were randomly assigned to one of four groups where each received some form of preoperative intervention. Participants in the guided imagery, biofeedback, guided imagery and biofeedback, and general education groups all met with the researcher one to two weeks preoperatively where baseline measures were collected, instruction and demonstration on the use of the interventions were provided, and packets were distributed with assessments to be completed during their inpatient stay. Anxiety, stress and coping strategies were all measured at baseline, the day of surgery, and in the hospital on the last day of admission just prior to discharge. In addition, the patients level of reported pain each day following surgery while inpatient was appraised as well as the amount of pain medication needed and length of hospital admission. Results of the present study support continued use of biofeedback and imagery in medicine and demonstrated the enhanced benefit of combining interventions as proposed. The imagery intervention reduced anxiety and perceived pain among the patients. A reduction in state anxiety scores was observed from baseline measurement to the day of discharge and its patients experienced a significant (p < .01) reduction in pain on post-operative day 3 from days 1 and 2. The biofeedback intervention generated positive results on a number of variables evaluated. A steady decline in stress was observed among patients from baseline measurement through discharge from the hospital as well as the continued reduction in medication use from post-operative day 1 through day 3. Furthermore, participants in the biofeedback treatment reported a significant (p < .05) reduction in pain from post-operative day 2 to day 3 (p < .05). Combining both imagery and biofeedback to be used simultaneously as its own intervention elicited the most significant outcomes compared to all other treatment conditions in reducing stress and medication use. Only participants in the combo intervention experienced a significant (p < .001) reduction in stress from the day of surgery to the day of discharge and required significantly (p < .001) less medication administered through the pain pump than any other treatment condition (p < .01). Patients in the general standard of care intervention receiving education experienced a reduction in anxiety from the initial baseline measurement to day of discharge although it was minimal. Positive outcomes were observed for all interventions provided in the present study. Outcomes reflect those reported across much of the CAM research exploring the benefits of interventions such as guided imagery and biofeedback on health related outcomes (Blanchard et al., 1987; Gervitz, Hubbard, & Harpin, 1996; Scherwitz et al., 2005). While guided imagery and biofeedback yielded benefits for the variables evaluated as sole treatment approaches, current findings reflect the efficacy of a combined approach with greater significance. The benefits of patients in any complementary and alternative medical practice can only positively influence the overall experience and potential results. Continued development and evaluation of more multifaceted approaches are essential in order to provide an optimal level of care. / A Dissertation submitted to the Department of Educational Psychology and Learning Systems in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Summer Semester 2016. / July 7, 2016. / Biofeedback, Imagery, Orthopaedics, Psychology, Surgery / Includes bibliographical references. / Gershon Tenenbaum, Professor Directing Dissertation; Lynn Panton, University Representative; Alysia Roehrig, Committee Member; Jeanine Turner, Committee Member.