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- All Subjects: Physiology
- Creators: Johnston, Carol
- Creators: McGraw, Kevin
Description
This dissertation investigates the condition of skeletal muscle insulin resistance using bioinformatics and computational biology approaches. Drawing from several studies and numerous data sources, I have attempted to uncover molecular mechanisms at multiple levels. From the detailed atomistic simulations of a single protein, to datamining approaches applied at the systems biology level, I provide new targets to explore for the research community. Furthermore I present a new online web resource that unifies various bioinformatics databases to enable discovery of relevant features in 3D protein structures.
ContributorsMielke, Clinton (Author) / Mandarino, Lawrence (Committee member) / LaBaer, Joshua (Committee member) / Magee, D. Mitchell (Committee member) / Dinu, Valentin (Committee member) / Willis, Wayne (Committee member) / Arizona State University (Publisher)
Created2013
Description
Birds have plasma glucose levels that are 1.5-2 times greater than mammals of similar body mass in addition to higher free fatty acid concentrations, both of which would typically impair endothelium-dependent vasodilation if observed in mammals. Endothelium-dependent vasodilation can be stimulated in mammals through the use of acetylcholine (ACh), which primarily acts through nitric oxide (NO) and cyclooxygenase (COX)-mediated pathways, with varying reliance on endothelial-derived hyperpolarizing factors (EDHFs). Very few studies have been conducted on small resistance systemic arteries from birds. The hypothesis was that because birds have naturally high glucose and free fatty acid concentrations, ACh-induced vasodilation of isolated arteries from mourning doves (Zenaida macroura) would be independent of endothelial-derived factors and resistant to high glucose-mediated vascular dysfunction. Small resistance mesenteric and cranial tibial (c. tibial) arteries were pre-constricted to 50% of resting inner diameter with phenyleprine then exposed to increasing doses of ACh (10-9 to 10-5 μM) or the NO donor, sodium nitroprusside (SNP; 10-12 to 10-3 μM). For both vessel beds, ACh-induced vasodilation occurred mainly through the activation of potassium channels, whereas vasodilation of mesenteric arteries additionally occurred through COX. Although arteries from both vessel beds fully dilated with exposure to sodium nitroprusside, ACh-mediated vasodilation was independent of NO. To examine the effect of high glucose on endothelium-dependent vasodilation, ACh dose response curves were conducted following exposure of isolated c. tibial arteries to either a control solution (20mM glucose) or high glucose (30mM). ACh-induced vasodilation was significantly impaired (p = 0.013) when exposed to high glucose, but normalized in subsequent vessels with pre-exposure to the superoxide dismutase mimetic tiron (10 mM). Superoxide concentrations were likewise significantly increased (p = 0.0072) following exposure to high glucose. These findings indicate that dove arteries do not appear to have endogenous mechanisms to counteract the deleterious effects of oxidative stress. Additional studies are required to assess whether endogenous mechanisms exist to protect avian vascular reactivity from systemic hyperglycemia.
ContributorsJarrett, Catherine Lee (Author) / Sweazea, Karen L (Thesis advisor) / Johnston, Carol (Committee member) / Gaesser, Glenn (Committee member) / Arizona State University (Publisher)
Created2012
Description
Parental care provides many benefits to offspring. One widely realized benefit is enhanced regulation of offspring's thermal environment. The developmental thermal environment during development can be optimized behaviorally through nest site selection and brooding, and it can be further enhanced by physiological heat production. In fact, enhancement of the developmental thermal environment has been proposed as the initial driving force for the evolution of endothermy in bird and mammals. I used pythons (Squamata: Pythonidae) to expand existing knowledge of behavioral and physiological parental tactics used to regulate offspring thermal environment. I first demonstrated that brooding behavior in the Children's python (Antaresia childreni) is largely driven by internal mechanisms, similar to solitary birds, suggesting that the early evolution of the parent-offspring association was probably hormonally driven. Two species of python are known to be facultatively thermogenic (i.e., are endothermic during reproduction). I expand current knowledge of thermogenesis in Burmese pythons (Python molurus) by demonstrating that females use their own body temperature to modulate thermogenesis. Although pythons are commonly cited as thermogenic, the actual extent of thermogenesis within the family Pythonidae is unknown. Thus, I assessed the thermogenic capability of five previously unstudied species of python to aid in understanding phylogenetic, morphological, and distributional influences on thermogenesis in pythons. Results suggest that facultative thermogenesis is likely rare among pythons. To understand why it is rare, I used an artificial model to demonstrate that energetic costs to the female likely outweigh thermal benefits to the clutch in species that do not inhabit cooler latitudes or lack large energy reserves. In combination with other studies, these results show that facultative thermogenesis during brooding in pythons likely requires particular ecological and physiological factors for its evolution.
ContributorsBrashears, Jake (Author) / DeNardo, Dale (Thesis advisor) / Harrison, Jon (Committee member) / Deviche, Pierre (Committee member) / McGraw, Kevin (Committee member) / Smith, Andrew (Committee member) / Arizona State University (Publisher)
Created2012
Description
Background: Vegan and vegetarian diets have gained in popularity in recent years. Stated reasons for this include some possible health benefits and concerns of animal welfare. Though considered to be nutritionally adequate, questions remain over whether current protein recommendations of 0.8 g/kg/d are sufficient to maintain body processes and growth. Protein is unique in that it is the only macronutrient that contains nitrogen. Its status can be determined through nitrogen balance analysis of the urine if protein content of the diet is known. Nitrogen balance is considered the gold standard for determining protein intake requirements. A negative balance indicates a catabolic state, whereas a positive nitrogen balance is seen during anabolism. In healthy people, nitrogen equilibrium is desired under normal circumstances. This equilibrium reflects the net synthesis and breakdown of proteins. While nitrogen balance techniques have been used for decades, currently, there are no known studies measuring nitrogen balance and protein intake in strict vegans. Methods: Twenty vegan, inactive, male participants were recruited and received a 5-day eucaloric diet with a known protein content held constant at 0.8 g/kg/d. On day five, 24-hour urine was collected by participants and aliquoted for future analysis. Nitrogen content of the urine was determined through photometric assay and compared to the known nitrogen content of the diet to calculate nitrogen balance status.
Results: Mean absolute nitrogen balance (-1.38 ± 1.22 g/d, effect size = -1.13) was significantly lower than zero (equilibrium) (p < .001). Mean relative nitrogen balance (-18.60 ± 16.96 mg/kg/d, effect size = -1.10) was significantly lower than zero (p < .001). There were no correlations seen between nitrogen balance and age, years as vegan, or fat- free mass.
Conclusion: Consuming 0.8 g/kg/d of protein is insufficient to produce nitrogen balance in long-term vegans.
ContributorsBartholomae, Eric (Author) / Johnston, Carol (Thesis advisor) / Sweazea, Karen (Committee member) / Wharton, Christopher (Committee member) / Lee, Chong (Committee member) / Kressler, Jochen (Committee member) / Arizona State University (Publisher)
Created2022
Description
Birds have the highest blood glucose concentrations of all vertebrates. Meanwhile, birds do not develop the same physiological complications (e.g., increased oxidative stress and glycation) that mammals do when blood glucose is elevated (i.e., diabetes). Therefore, birds may serve as a negative model animal for hyperglycemic complications. The physiological reason for high blood glucose in birds remains largely unknown although several unique characteristics of birds may contribute including a lack of the insulin responsive glucose transport protein, relatively high glucagon concentrations, as well as reliance on fatty acids to sustain the high energetic demands of flight. In breaking down triglycerides for energy, glycerol is liberated, which can be converted to glucose through a process called gluconeogenesis. In addition, the extent to which birds maintain homeostatic control over blood glucose in response to extreme dietary interventions remains unclear and few dietary studies have been conducted in wild-caught birds. Using Mourning Doves (Zenaida macroura) as a model organism, this dissertation tests four hypotheses: 1) Gluconeogenesis contributes to high circulating blood glucose concentration; 2-4) similar to mammals, a fully refined carbohydrate (i.e., white bread diet); a high saturated fat diet (60% kcal from fat); and an urban-type diet comprised of a 1:1 ratio of French fries and birds seed will increase blood glucose compared to a nutritionally-balanced diet after a four-week duration. Contrary to the hypothesis, 150 mg/kg Metformin (which inhibits glycerol gluconeogenesis) increased blood glucose, but 300 mg/kg resulted in no change. However, when 2.5 mg/kg of 1,4-dideoxy-1,4-imino-D-arabinitol (DAB; a glycogenolysis inhibitor) was given with 150 mg/kg of Metformin, blood glucose was not different from the control (50 ul water). This suggests that glycerol gluconeogenesis does not contribute to the naturally high blood glucose in birds and that a low dose of Metformin may increase the rate of glycogenolysis. In addition, all three experimental diets failed to alter blood glucose compared to control diets. Collectively, these results suggest that, in addition to a negative model for diabetes complications, birds can also serve a negative model for diet-induced hyperglycemia. Future research should further examine dietary manipulation in birds while controlling for and examining different variables (e.g., species, sex, duration, diet composition, urbanization).
ContributorsBasile, Anthony Joseph (Author) / Sweazea, Karen L (Thesis advisor) / Deviche, Pierre (Committee member) / Johnston, Carol (Committee member) / Trumble, Ben (Committee member) / Parrington, Diane J (Committee member) / Arizona State University (Publisher)
Created2022
Description
Reproduction is energetically costly and seasonal breeding has evolved to capitalize on predictable increases in food availability. The synchronization of breeding with periods of peak food availability is especially important for small birds, most of which do not store an extensive amount of energy. The annual change in photoperiod is the primary environmental cue regulating reproductive development, but must be integrated with supplementary cues relating to local energetic conditions. Photoperiodic regulation of the reproductive neuroendocrine system is well described in seasonally breeding birds, but the mechanisms that these animals use to integrate supplementary cues remain unclear. I hypothesized that (a) environmental cues that negatively affect energy balance inhibit reproductive development by acting at multiple levels along the reproductive endocrine axis including the hypothalamus (b) that the availability of metabolic fuels conveys alterations in energy balance to the reproductive system. I investigated these hypotheses in male house finches, Haemorhous mexicanus, caught in the wild and brought into captivity. I first experimentally reduced body condition through food restriction and found that gonadal development and function are inhibited and these changes are associated with changes in hypothalamic gonadotropin-releasing hormone (GnRH). I then investigated this neuroendocrine integration and found that finches maintain reproductive flexibility through modifying the release of accumulated GnRH stores in response to energetic conditions. Lastly, I investigated the role of metabolic fuels in coordinating reproductive responses under two different models of negative energy balance, decreased energy intake (food restriction) and increased energy expenditure (high temperatures). Exposure to high temperatures lowered body condition and reduced food intake. Reproductive development was inhibited under both energy challenges, and occurred with decreased gonadal gene expression of enzymes involved in steroid synthesis. Minor changes in fuel utilization occurred under food restriction but not high temperatures. My results support the hypothesis that negative energy balance inhibits reproductive development through multilevel effects on the hypothalamus and gonads. These studies are among the first to demonstrate a negative effect of high temperatures on reproductive development in a wild bird. Overall, the above findings provide important foundations for investigations into adaptive responses of breeding in energetically variable environments.
ContributorsValle, Shelley (Author) / Deviche, Pierre (Thesis advisor) / McGraw, Kevin (Committee member) / Orchinik, Miles (Committee member) / Propper, Catherine (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2018
Description
The glycation of plasma proteins leading to the production of advanced glycation end products (AGEs) and subsequent damage is a driving factor in the pathophysiology of diabetic complications. The overall research objective was to elucidate the mechanisms by which birds prevent protein glycation in the presence of naturally high plasma glucose concentrations. This was accomplished through the specific purpose of examining the impact of temperature and glucose concentration on the percent glycation of chicken serum albumin (CSA) in comparison to human serum albumin (HSA). Purified CSA and HSA solutions prepared at four different glucose concentrations (0 mM, 5.56 mM, 11.11 mM, and 22.22 mM) were incubated at three different temperatures (37.0°C, 39.8°C, and 41.4°C) on separate occasions for seven days with aliquots extracted on days 0, 3, and 7. Samples were analyzed by LC-ESI-MS for percent glycation of albumin. The statistically significant interaction between glucose concentration, temperature, albumin type, and time as determined by four-way repeated measures ANOVA (p = 0.032) indicated that all independent variables interacted to affect the mean percent glycation of albumin. As glucose concentration increased, the percent glycation of both HSA and CSA increased over time at all temperatures. In addition, HSA was glycated to a greater extent than CSA at the two higher glucose concentrations examined for all temperature conditions. Temperature differentially affected percent glycation of HSA and CSA wherein glycation increased with rising temperatures for HSA but not CSA. The results of this study suggest an inherent difference between the human and chicken albumin that contributes to the observed differences in glycation. Further research is needed to characterize this inherent difference in an effort to elucidate the mechanism by which birds protect plasma proteins from glycation. Future related work has the potential to lead to the development of novel therapies to prevent or reverse protein glycation prior to the formation of AGEs in humans, thus preventing the development and devastating effects of numerous diabetic complications.
ContributorsZuck, Jessica (Author) / Sweazea, Karen (Thesis advisor) / Johnston, Carol (Committee member) / Lespron, Christy (Committee member) / Arizona State University (Publisher)
Created2016
Description
Why do many animals possess multiple classes of photoreceptors that vary in the wavelengths of light to which they are sensitive? Multiple spectral photoreceptor classes are a requirement for true color vision. However, animals may have unconventional vision, in which multiple spectral channels broaden the range of wavelengths that can be detected, or in which they use only a subset of receptors for specific behaviors. Branchiopod crustaceans are of interest for the study of unconventional color vision because they express multiple visual pigments in their compound eyes, have a simple repertoire of visually guided behavior, inhabit unique and highly variable light environments, and possess secondary neural simplifications. I first tested the behavioral responses of two representative species of branchiopods from separate orders, Streptocephalus mackini Anostracans (fairy shrimp), and Triops longicaudatus Notostracans (tadpole shrimp). I found that they maintain vertical position in the water column over a broad range of intensities and wavelengths, and respond behaviorally even at intensities below those of starlight. Accordingly, light intensities of their habitats at shallow depths tend to be dimmer than terrestrial habitats under starlight. Using models of how their compound eyes and the first neuropil of their optic lobe process visual cues, I infer that both orders of branchiopods use spatial summation from multiple compound eye ommatidia to respond at low intensities. Then, to understand if branchiopods use unconventional vision to guide these behaviors, I took electroretinographic recordings (ERGs) from their compound eyes and used models of spectral absorptance for a multimodel selection approach to make inferences about the number of photoreceptor classes in their eyes. I infer that both species have four spectral classes of photoreceptors that contribute to their ERGs, suggesting unconventional vision guides the described behavior. I extended the same modeling approach to other organisms, finding that the model inferences align with the empirically determined number of photoreceptor classes for this diverse set of organisms. This dissertation expands the conceptual framework of color vision research, indicating unconventional vision is more widespread than previously considered, and explains why some organisms have more spectral classes than would be expected from their behavioral repertoire.
ContributorsLessios, Nicolas (Author) / Rutowski, Ronald L (Thesis advisor) / Cohen, Jonathan H (Thesis advisor) / Harrison, John (Committee member) / Neuer, Susanne (Committee member) / McGraw, Kevin (Committee member) / Arizona State University (Publisher)
Created2016
Description
The omega-3 fatty acids in fatty fish and fish oil, eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), have been associated with a reduction in risk for cardiovascular disease. Blood type is a known contributor to risk for cardiovascular events. This study evaluated the effect of fish oil supplements on cardiovascular risk markers in adults with blood types A or O. An 8-week parallel-arm, randomized, double-blind trial was conducted in healthy adult men and women with either blood type A (BTA) or blood type O (BTO). Participants were randomized to receive fish oil supplements (n=10 [3 BTA/7 BTO]; 2 g [containing 1.2 g EPA+DHA]/d) or a coconut oil supplement (n=7 [3 BTA/4 BTO]; 2 g/d). Markers that were examined included total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), high-sensitivity C-reactive protein (hsCRP), and hemoglobin A1C (HbA1C). Results indicated that the percent change in LDL cholesterol was significantly greater in the coconut oil group vs the fish oil group (-14.8±12.2% vs +2.8±18.9% respectively, p=0.048). There were no other significant differences between treatment groups, or between blood types A and O, for the other cardiovascular risk markers. Further research with a larger and more diverse sample may yield a more conclusive result.
ContributorsHerring, Dana (Author) / Johnston, Carol (Thesis advisor) / Vega-Lopez, Sonia (Committee member) / Shepard, Christina (Committee member) / Arizona State University (Publisher)
Created2014
Description
Foraging has complex effects on whole-organism homeostasis, and there is considerable evidence that foraging behavior is influenced by both environmental factors (e.g., food availability, predation risk) and the physiological condition of an organism. The optimization of foraging behavior to balance costs and benefits is termed state-dependent foraging (SDF) while behavior that seeks to protect assets of fitness is termed the asset protection principle (APP). A majority of studies examining SDF have focused on the role that energy balance has on the foraging of organisms with high metabolism and high energy demands ("high-energy systems" such as endotherms). In contrast, limited work has examined whether species with low energy use ("low-energy systems" such as vertebrate ectotherms) use an SDF strategy. Additionally, there is a paucity of evidence demonstrating how physiological and environmental factors other than energy balance influence foraging behavior (e.g. hydration state and free-standing water availability). Given these gaps in our understanding of SDF behavior and the APP, I examined the state-dependency and consequences of foraging in a low-energy system occupying a resource-limited environment - the Gila monster (Heloderma suspectum, Cope 1869). In contrast to what has been observed in a wide variety of taxa, I found that Gila monsters do not use a SDF strategy to manage their energy reserves and that Gila monsters do not defend their energetic assets. However, hydration state and free-standing water availability do affect foraging behavior of Gila monsters. Additionally, as Gila monsters become increasingly dehydrated, they reduce activity to defend hydration state. The SDF behavior of Gila monsters appears to be largely driven by the fact that Gila monsters must separately satisfy energy and water demands with food and free-standing water, respectively, in conjunction with the timescale within which Gila monsters balance their energy and water budgets (supra-annually versus annually, respectively). Given these findings, the impact of anticipated changes in temperature and rainfall patterns in the Sonoran Desert are most likely going to pose their greatest risks to Gila monsters through the direct and indirect effects on water balance.
ContributorsWright, Christian (Author) / Denardo, Dale F. (Thesis advisor) / Harrison, Jon (Committee member) / McGraw, Kevin (Committee member) / Sullivan, Brian (Committee member) / Wolf, Blair (Committee member) / Arizona State University (Publisher)
Created2014