PURPOSE: Diving operations may require personnel to be immersed for extended periods while breathing compressed air or 100% O2. The main objective of this study was to investigate the physiological effects of single and repetitive diving-induced hyperoxic conditions on skeletal muscle performance at 1.35 atmospheres absolute (ATA) on skeletal muscle performance. We hypothesized that following five days of consecutive, resting, long-duration hyperoxic water immersion (WI)s 1) neuromuscular performance would be reduced with a longer recovery time in comparison to air WIs, and 2) an increase in the production of free radicals with augmented inflammatory responses following consecutive hyperbaric, normoxic WIs. METHODS: Twenty-eight healthy, active male divers [30 ± 1 (24-43) yrs, mean ± SEM] completed five consecutive 6-hour resting WIs with 18-hour surface intervals while breathing compressed air (n=15) or 100% O2 (n=13) at 1.35 ATA. Using mixed repeated measures analysis of variance (RANOVA), skeletal muscle performance was assessed immediately before and after each WI, and 24 and 72 hours after the final WI. Assessments included maximum voluntary isometric contractions (MVIC), maximal isokinetic (IK) contractions, 50-repetition maximal IK knee extension (50-rep), maximum handgrip (MHG), and 40% maximal handgrip endurance (MHE). Surface electromyography (sEMG) of the vastus lateralis, rectus femoris, vastus medialis, biceps brachii, and brachioradialis, and local tissue oxygenation via near-infrared spectroscopy (NIRS) on the vastus lateralis, biceps brachii, and forearm flexor muscles were measured during the exercise protocols. All exercise tests were performed on the subject’s right side regardless of limb dominance. Muscle oxidative capacity (MOC) was measured on the vastus lateralis for the Air group only. Venous serum samples were analyzed for superoxide dismutase (SOD), hydrogen peroxide, total antioxidant capacity (TAC), nitrates (NO3), and heat shock protein 90 (HSP90) in the Air group only. RESULTS: Significant decreases were seen in maximal strength on day (D)3 (MVIC knee extension: Air: p<0.001, 2.5%; O2: p=0.016, 4.3%; MVIC elbow flexion: p=0.002, 3.5%, combined group result). The O2 group neuromuscular activation decreased throughout the dive week (DW) and remained reduced through the DW recovery period. The Air group neuromuscular activation increased throughout the DW but returned to baseline by 72-hr post-dive. The O2 group presented with greater post-dive performance measurements (MVIC knee extension: p<0.001, 4.6%) than the Air group. A combined group day main effect demonstrated a decrease in time-to-fatigue for MHE on D5 (p=0.015, 10.2%). The Air group fully recovered by 24-hr post-dive whereas the O2 group time-to-fatigue performance did not recover by 72-hr post-dive (p=0.019, 12.2%). A 24.9% increase (p=0.04) in the MOC rate constant (k) occurred on D4 with a return to baseline by D5. The Air group showed a greater change in deoxygenated hemoglobin formation during MHE than the O2 group (p=0.04, 46.7% difference). In the Air group, the hyperbaric normoxic conditions increased TBARS formation by 11% within 15 minutes post-dive (p=0.018) with SOD formation increased by 8.5% post-dive (p=0.029) and 5% overall by D5 (p=0.04). CONCLUSION: Consecutive, resting, long-duration normoxic and hyperoxic WIs caused small, but noticeable decrements to neuromuscular activation and performance after three days of WI with an adaptation towards recovery by the end of the WI 5. However, subsequent neuromuscular activation is highly affected by the hyperoxic conditions. From the two-group statistical comparison, these changes are due to the hyperoxic exposures, appear to last beyond the 72-hr post-dive recovery period, and seem to delay the onset of muscular fatigue through increased neuromuscular hyperexcitability. Hyperbaric normoxic exposures cause statistically significant increases in oxidative stress and anti-oxidant concentrations. The effects of hyperbaric hyperoxic exposures on free radical production are not tested. / 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. / Fall Semester 2017. / December 11, 2017. / diving, hyperooxia, near-infrared spectroscopy, surface electromyography, water immersion / Includes bibliographical references. / Jeong-Su Kim, Professor Directing Dissertation; P. Bryant Chase, University Representative; Lynn B. Panton, Committee Member; Michael J. Ormsbee, Committee Member; John P. Florian, Committee Member.

Although cognition declines with age, cancer may increase that decline, either through cancer treatment or decreased quality of life (QOL) accompanied with increased anxiety and depression. Cross-sectional research shows that more active breast cancer survivors (BCS) have higher cognitive function and better QOL; however, longitudinal data are needed. Purpose: This study evaluated the effects of 3 months of functional impact training (FIT) on cognition and QOL compared to yin yoga in BCS. It was hypothesized that FIT would experience greater improvements in cognition compared to yin yoga, but similar improvements in QOL compared to yin yoga. Methods: Forty-five BCS (60.5±8.3 yrs; BMI: 29.2±7.1 kg/m2) were recruited to complete Trail-Making Test A and B [TMTA (processing speed), TMTB (executive function)], Digit Span Forward (attention) and Backward (working memory), and Controlled Oral Word Association Test [COWAT (executive function)] to assess cognitive domains. QOL was measured using the 36-item Short Form Survey (SF-36). The BCS were stratified by breast cancer stage, type of cancer treatment, and lean mass to participate in either FIT or yin yoga. Participants assigned to the FIT group completed 3 months of supervised exercise training sessions consisting of exercises that were performed using body weight, dumbbells, step benches, stability balls, and mats. These exercises were high impact and included jumping and hopping. Each exercise session lasted approximately 45 minutes and was completed twice per week. The intensity of the exercise program started out low to prevent injury and to introduce participants to the exercises and then intensity was gradually increased over the course of the 3 months. Exercises performed included squat jumps, jump lunges, push-ups, dumbbell rows, shoulder presses, biceps curls, triceps extensions, and planks. The participants progressed to more high impact versions of these exercises throughout the duration of the exercise program. All sessions were monitored and led by a certified fitness professional and all exercise sets and repetitions were recorded. Participants assigned to the yin yoga group completed 3 months of supervised yin yoga training sessions, which consisted of exercises that focus on stretching and relaxation. Exercises were lying or seated and were performed on a yoga mat using equipment such as yoga blocks, straps, and bolsters. Each yin yoga session lasted approximately 45 minutes and was completed twice per week. Baseline and 3-month changes in cognitive function and QOL were assessed using repeated measures analysis of variance (ANOVA). Significance was accepted at p≤0.05. Results: There were no group by time differences on any of the cognitive or QOL measures in the intent-to-treat analysis or for those that completed the study. There were no significant differences from baseline on any of the cognitive measures for FIT; however, yin yoga significantly improved in the COWAT Total score from baseline (p=.03). From baseline to 3 months, FIT significantly improved in role limitations/physical (p=.04), emotional well-being (p=.01), and general health (p=.01) while yin yoga saw significant improvements in physical functioning (p=.03), emotional well-being (p=.03), and general health (p=.02) domains within the SF-36. Conclusion: In conclusion, our findings indicate that neither a FIT, combining resistance and aerobic training, nor a yin yoga program had significant improvements in cognition over 3 months. Both FIT and yin yoga may be viable options for maintenance of cognition during aging, since both saw neither a significant increase or decrease in scores. FIT and yin yoga did however demonstrate significant improvements in QOL over the 3 months of the study. Along with recent literature, it seems that exercise and yoga may both be non-pharmaceutical options for improving QOL in BCS. Further research is needed to examine the effects of FIT and yin yoga on cognition in BCS. / 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. / Spring Semester 2018. / March 7, 2018. / breast, cancer, cognition, exercise, survivors, yoga / Includes bibliographical references. / Lynn Panton, Professor Directing Thesis; Jeong-Su Kim, Committee Member; Laurie Grubbs, Committee Member.

Cardiovascular disease is the leading cause of death in the United States and globally. Aortic stiffness has recently been implicated as an independent risk factor and has attracted research efforts to prevent cardiovascular diseases. More recently, vascular smooth muscle cell stiffness has been proven to play an important role in aortic stiffness, but the precise mechanism of how smooth muscle contributes to vascular stiffness is still unknown. Studying VSMCs (vascular smooth muscle cells) in depth is a hot topic for ongoing research in this decade because, by understanding the mechanisms involved, we can discover novel medications to prevent cardiovascular diseases before they even develop. Given the importance and impact of dVSMCs (differentiated vascular smooth muscle cells) on cardiovascular diseases and the recent movement to the mouse as the preferred animal model, to take advantage of genetically modified mice that can mimic human diseases such as aging, hypertension and atherosclerosis in cardiovascular research, we need in-depth studies of dVSMCs in the mouse. Most studies on vascular smooth muscle have focused on cultured cells while very few have examined contractile dVSMCs. The freshly isolated contractile dVSMC is a better model of vivo cells than are cultured cells. Thus, the purpose of this research was to develop protocols to study the contractility, signal transduction, and cytoskeletal regulation in small mouse blood vessels and contractile cells. Firstly, I developed a novel protocol to freshly isolate dVSMCs from a mouse aorta that are viable and respond to stimulation. This will allow us to better understand signaling pathways controlling dVSMCs and thus to discover targets for application of many therapeutic interventions to prevent cardiovascular diseases. Secondly, I successfully developed a modification of the differential ultracentrifugation protocol on mouse tissue to allow the assay of changes in actin polymerization levels in mouse dVSM. Thirdly, I found for the first time that contractile agonists trigger actin polymerization in mouse VSMCs and postulate that actin polymerization is a regulator of dVSM contractility in the mouse. The current literature strongly suggests that actin polymerization may be a valuable drug target for new cardiovascular therapeutics.

From a medical perspective, obesity may be defined as a degree of relative adiposity sufficient to derange metabolic physiology in a manner that negatively impacts the health of the individual. While population-based cut points based on body mass index (BMI) are frequently used as a means of identifying such individuals, this is an imprecise approach since the critical levels of adiposity in this regard differ substantially among individuals. Our common genetic predisposition to increased adiposity, coupled with an environment conducive to positive energy balance results in an increasing prevalence of human obesity. Weight loss, even when initially successful, is very difficult to maintain due, in part, to a feedback system involving metabolic, behavioral, neuroendocrine and autonomic responses that are initiated to maintain somatic energy stores (fat) at a level considered `ideal' by the central nervous system (CNS). Circulating leptin is an important afferent signal to the CNS relating peripheral energy stores with modulations in key leptin sensing area sensitivity possibly implicated in the functional and molecular basis of defense of body weight. These physiological responses, which include increased metabolic efficiency at lower body weight, may be engaged in individuals at different levels of body fat depending on their genetic makeup, as well as on gestational and post-natal environmental factors that have determined the so-called "set-point". In the work presented in this dissertation the following aspects of the physiology of the defense of body weight were explored: 1) whether levels (thresholds) of defended adiposity can be raised or lowered by environmental manipulation; 2) the physiological and molecular changes that mediate increased metabolic efficiency following weight loss, 3) leptin's role in setting the threshold; 4) the effects of ambient temperature on metabolic phenotypes of weight perturbed to assess whether torpor contributes to metabolic adaptation; and 5) whether changes in gut microbiota accompany changes in diet composition and/or body weight. To assess whether the threshold for defended body weight could be increased or decreased by environmental manipulations (i.e. high fat diet and weight restriction), we identified bioenergetic, behavioral, and CNS structural responses of C57BL/6J in long term diet induced obese (DIO) male mice to weight reduction. We found that maintenance of a body weight 20% below that imposed by a high fat diet results in metabolic adaptation - energy expenditure below that expected for body mass and composition - and structural changes of synapses onto arcuate pro-opiomelanocortin (POMC) cell bodies. These changes are qualitatively and quantitatively similar to those observed in weight-reduced animals that were never obese, suggesting that the previously obese animals are now "defending" a higher body weight. Maintenance of a lower body weight for more than 3 months was not accompanied by remission of the increased metabolic efficiency. Thus, the consequence of long term elevation of body weight suggests an increase in defended body fat that does not abate with time. Mice can enter torpor - a state of decreased metabolic rate and concomitant decrease in body temperature - as a defense mechanism in times of low caloric availability and/or decreased ambient room temperatures. Declines in circulating leptin concentrations and low ambient room temperature have both been implicated in the onset of torpor. To assess the effects of ambient room temperature and leptin concentrations on metabolic adaptation, we characterized C57BL/6J and leptin deficient (Lepob) mice following weight perturbation at both 22°C and 30°C ambients. Weight-reduced C57BL/6J mice show metabolic adaptation at both ambient temperatures and do not enter torpor whereas weight-reduced Lepob animals readily enter torpor at 22°C. This suggests that sufficiently high absolute leptin concentrations may impede the onset of torpor and that torpor itself does not contribute to metabolic adaptation in mice that have an intact leptin axis. To assess whether hyperleptinemia per se was capable of increasing the threshold for defended body weight, leptin was infused by minipumps into C57BL/6J mice for 18 weeks and body weight and metabolic parameters were studied following cessation of leptin infusion. Leptin infused mice did not defend elevated body weights compared to PBS infused mice suggesting that leptin alone may not be capable of setting the threshold for body weight defense implying that other changes accompanying obesity (i.e. increased free fatty acids, endoplasmic reticulum stress and/or inflammation of leptin-sensitive neural areas) are implicated. A caveat and possible confound to this study is the possibility of antibody production against the exogenous leptin that could have drastically decreased the amount of bioavailable leptin in these mice. This experiment did not assess antibody production but subsequent studies should do so. Finally, gut microbiota have been implicated in the regulation of body weight possibly by impacting insulin resistance, inflammation, and adiposity via interactions with epithelial and endocrine cells. We assessed changes in relative abundances of cecal microbiota in mice following sustained changes in body weight and diet composition. In diet-induced obese (DIO) mice, we find that weight reduction resulted in shifts in specific bacteria abundance (Akkermansia and Mucispirillum) and that these changes were correlated with leptin concentrations. Leptin modulates mucin production in the gut possibly altering local microniches for certain bacteria providing a functional link between adiposity and gut-specific changes in bacterial populations. Overall, the major findings of these experiments are that the threshold for body weight defense can be raised but not lowered, that metabolic adaptation observed in weight-reduced mice is not a result of torpor, and that hyperleptinemia (if no anti-bodies were produced) per se isolated from other obesity-related changes does not appear capable of raising the threshold.

Ryanodine receptor calcium release channels are essential for skeletal muscle contraction, as they mediate the release of calcium ions from intracellular stores into the cytosol. The data presented in this dissertation demonstrate the evolutionarily conserved mechanisms of skeletal muscle ryanodine receptor regulation in the physiological and pathophysiological states. Adrenergic stimulation causes increased skeletal muscle force, however, despite the well-established role of this physiological response, the molecular mechanism is not known. Here we present a mechanism whereby phosphorylation of a single amino acid on the ryanodine receptor is a key signal in the physiological stress-induced inotropic response in mouse skeletal muscle. Therefore acute post-translational modifications of ryanodine receptor channels are important for healthy muscle contraction. Conversely, chronic stress-induced post-translational modifications result in poorly functioning murine ryanodine receptor channels that contribute to skeletal muscle dysfunction in age-dependent skeletal muscle weakness and Muscular Dystrophies. Finally, we present data that demonstrates striking evolutionary conservation in ryanodine receptor regulation in the physiological and pathophysiological states between mice and C. elegans. This work has broad implications for understanding the underlying mechanisms of skeletal muscle contraction and important disorders that affect human health. Furthermore, this works presents ryanodine receptor channels as a viable therapeutic target for age-related skeletal muscle weakness, Muscular Dystrophies, and also implicates C. elegans as a potential model system in which to test future therapeutic targets.

abstract: I examined how competition affects the way animals use thermal resources to control their body temperature. Currently, biologists use a cost benefit analysis to predict how animals should regulate their body temperature. This current theory of thermoregulation does not adequately predict how animals thermoregulate in the wild. While the model works well for animals in low cost habitats, it does not work as well for animals in high cost habitats. For example, animals that are in habitats of low thermal quality thermoregulate more precisely than predicted by the current model. One reason these predictions may be wrong is that they do not account for interactions between animals. By including these interactions in future predictions, a more accurate model of thermoregulatory behavior can be created. Before developing a theory for all animals, a model needs to be developed for a single model animal, such as fruit flies, that can be used to empirically examine how organisms thermoregulate under competition. My work examines how flies behave around other flies and develops a game theory model predicting how they should optimally behave. More specifically, my research accounts for competition among larvae by using game theory to predict how mothers should select sites when laying eggs. Although flies prefer to lay their eggs in places that will offer suitable temperatures for the development of their larvae, these sites become less suitable when crowded. Therefore, at some density of eggs, cooler sites should become equally beneficial to larvae when considering both temperature and competition. Given this tradeoff, an evolutionarily stable strategy (ESS) emerges where some flies should lay eggs in cooler sites while other flies should lay eggs at the warmer temperature. By looking at the fitness of genotypes in habitats of differing quality (competition, temperature, food quality, space), I modeled the ESS for flies laying eggs in a heterogeneous environment. I then tested these predictions by observing how flies compete for patches with different temperatures. / Dissertation/Thesis / Doctoral Dissertation Biology 2018

No description available.

No description available.

No description available.

No description available.