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Description
While exercising mammalian muscle increasingly relies on carbohydrates for fuel as aerobic exercise intensity rises above the moderate range, flying birds are extraordinary endurance athletes and fuel flight, a moderate-high intensity exercise, almost exclusively with lipid. In addition, Aves have long lifespans compared to weight-matched mammals. As skeletal muscle mitochondria

While exercising mammalian muscle increasingly relies on carbohydrates for fuel as aerobic exercise intensity rises above the moderate range, flying birds are extraordinary endurance athletes and fuel flight, a moderate-high intensity exercise, almost exclusively with lipid. In addition, Aves have long lifespans compared to weight-matched mammals. As skeletal muscle mitochondria account for the majority of oxygen consumption during aerobic exercise, the primary goal was to investigate differences in isolated muscle mitochondria between these species and to examine to what extent factors intrinsic to mitochondria may account for the behavior observed in the intact tissue and whole organism. First, maximal enzyme activities were assessed in sparrow and rat mitochondria. Citrate synthase and aspartate aminotransferase activity were higher in sparrow compared to rat mitochondria, while glutamate dehydrogenase activity was lower. Sparrow mitochondrial NAD-linked isocitrate dehydrogenase activity was dependent on phosphate, unlike the mammalian enzyme. Next, the rate of oxygen consumption (JO), electron transport chain (ETC) activity, and reactive oxygen species (ROS) production were assessed in intact mitochondria. Maximal rates of fat oxidation were lower than for carbohydrate in rat but not sparrow mitochondria. ETC activity was higher in sparrows, but no differences were found in ROS production between species. Finally, fuel selection and control of respiration at three rates between rest and maximum were assessed. Mitochondrial fuel oxidation and selection mirrored that of the whole body; in rat mitochondria the reliance on carbohydrate increased as the rate of oxygen consumption increased, whereas fat dominated under all conditions in the sparrow. These data indicate fuel selection, at least in part, can be modulated at the level of the mitochondrial matrix when multiple substrates are present at saturating levels. As an increase in matrix oxidation-reduction potential has been linked to a suppression of fat oxidation and high ROS production, the high ETC activity relative to dehydrogenase activity in avian compared to mammalian mitochondria may result in lower matrix oxidation-reduction potential, allowing fatty acid oxidation to proceed while also resulting in low ROS production in vivo.
ContributorsKuzmiak, Sarah (Author) / Willis, Wayne T (Thesis advisor) / Mandarino, Lawrence (Committee member) / Sweazea, Karen (Committee member) / Harrison, Jon (Committee member) / Gadau, Juergen (Committee member) / Arizona State University (Publisher)
Created2012
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Description
A prominent aspect of Alzheimer’s disease (AD) is the presence of neuroinflammation is mediated by the activation of microglial cells, which are the immune cells in the central nervous system (CNS) that express an array of cytokines that may promote an inflammatory response. The main cytokines produced are: tumor

A prominent aspect of Alzheimer’s disease (AD) is the presence of neuroinflammation is mediated by the activation of microglial cells, which are the immune cells in the central nervous system (CNS) that express an array of cytokines that may promote an inflammatory response. The main cytokines produced are: tumor necrosis factor-alpha (TNF-), interleukin-1β (IL-1β), and interleukin-6 (IL-6). The presence of these cytokines in the CNS may lead to neuronal death, to the production of toxic chemicals (such as nitric oxide), and to the generation of amyloid beta (a major pathological feature of AD). Previous studies have shown that modulation of the inflammatory response in the nervous system can potentially prevent and/or delay the onset of neurodegenerative diseases such as AD. Therefore, it is important to identify the process that induces CNS inflammation. For example, mitochondrial lysates have been found to produce an inflammatory response due to their ability to stimulate TNF-, Aβ, and APP mRNA [10]. Interestingly, extracellular mitochondria have been detected in the brain due to neurons degrading old mitochondria extracellularly. Therefore, we set out to study the effect of whole mitochondria isolated by differential centrifugation from human neuroblastoma cells (BE(2)-M17 cells) on the neuroinflammatory response in a human microglia model (THP-1 cells). Despite our best efforts, in the end it was unclear whether the mitochondrial fraction or other cellular components induced the inflammatory response we observed. Thus, further work with an improved mitochondrial isolation method should be carried out to address this issue.
ContributorsStokes, Laura Jean (Author) / DeCourt, Boris (Thesis director) / Sweazea, Karen (Committee member) / Gonzales, Rayna (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
The natural habitat as well as the food abundance and food sources of avian species is changing due to urbanization, and such anthropocentric actions could lead to devastating impacts on bird populations. As changes in distribution and nutrition are thought to be related to the gut microbiome, the goal of

The natural habitat as well as the food abundance and food sources of avian species is changing due to urbanization, and such anthropocentric actions could lead to devastating impacts on bird populations. As changes in distribution and nutrition are thought to be related to the gut microbiome, the goal of this study was to determine the relationship between nutritional markers, including body mass, gizzard mass, triglycerides, free glycerol and glycogen, and the gut microbiome in urban and rural house sparrows (Passer domesticus), to understand physiological differences between urban and rural house sparrows. We hypothesized that increased access to human refuse, through urbanization, may significantly alter the gut microbiome and thus, the nutritional physiology-the effects of foods on metabolism-of urban birds. Fecal samples were collected from rural (n=13) and urban (n=7) birds to characterize the gut microbiome and plasma samples were collected to measure nutritional markers using commercially available kits. Following euthanasia, liver samples were collected to measure triglycerides, free glycerol and glycogen. While there were no significant differences in circulating triglycerides or free glycerol between populations, urban birds had significantly greater blood glucose (p=0.046) compared to rural birds, when normalized to body mass. Additionally, rural birds had significantly more plasma uric acid (p=0.016) and liver free glycerol (p=0.044). Higher blood glucose suggests greater accessibility to carbohydrates in an urban setting or higher rates of gluconeogenesis. Uric acid is a byproduct of purine catabolism and a potent antioxidant. Thus, higher uric acid suggests that rural birds may utilize more protein for energy. Finally, higher liver free glycerol in rural birds suggests they metabolize more fat but could also indicate that urban birds have greater glycerol gluconeogenesis, which may consume free glycerol resulting in higher glucose concentrations. However, the current study does not provide evidence for this as there were no significant differences in the gluconeogenic enzyme PEPCK-C levels between urban and rural house sparrows (p= 0.165). While triglyceride, glucose, and uric acid levels differed between urban and rural birds, there were additionally no significant differences in the gut microbiome, indicating that although nutritional physiology can be affected by distribution and varying food availability and sources, differences in the gut microbiome are evident at the phyla level.
ContributorsGadau, Alice (Author) / Sweazea, Karen (Thesis director) / Whisner, Corrie (Committee member) / Crawford, Melisa (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
Speciation, or the process by which one population diverges into multiple populations that can no longer interbreed with each other, has brought about the incredible diversity of life. Mechanisms underlying this process can be more visible in the early stages of the speciation process. The mechanisms that restrict gene flow

Speciation, or the process by which one population diverges into multiple populations that can no longer interbreed with each other, has brought about the incredible diversity of life. Mechanisms underlying this process can be more visible in the early stages of the speciation process. The mechanisms that restrict gene flow in highly mobile species with no absolute barriers to dispersal, especially marine species, are understudied. Similarly, human impacts are reshaping ecosystems globally, and we are only just beginning to understand the implications of these rapid changes on evolutionary processes. In this dissertation, I investigate patterns of speciation and evolution in two avian clades: a genus of widespread tropical seabirds (boobies, genus Sula), and two congeneric passerine species in an urban environment (cardinals, genus Cardinalis). First, I explore the prevalence of gene flow across land barriers within species and between sympatric species in boobies. I found widespread evidence of gene flow over all land barriers and between 3 species pairs. Next, I compared the effects of urbanization on the spatial distributions of two cardinal species, pyrrhuloxia (Cardinalis sinuatus) and northern cardinals (Cardinalis cardinalis), in Tucson, Arizona. I found that urbanization has different effects on the spatial distributions of two closely related species that share a similar environmental niche, and I identified environmental variables that might be driving this difference. Then I tested for effects of urbanization on color and size traits of these two cardinal species. In both of these species, urbanization has altered traits involved in signaling, heat tolerance, foraging, and maneuverability. Finally, I tested for evidence of selection on the urban populations of both cardinal species and found evidence of both parallel selection and introgression between the species, as well as selection on different genes in each species. The functions of the genes that experienced positive selection suggest that light at night, energetics, and air pollution may have acted as strong selective pressures on these species in the past. Overall, my dissertation emphasizes the role of introgression in the speciation process, identifies environmental stressors faced by wildlife in urban environments, and characterizes their evolutionary responses to those stressors.
ContributorsJackson, Daniel Nelson (Author) / McGraw, Kevin J (Thesis advisor) / Amdam, Gro (Committee member) / Sweazea, Karen (Committee member) / Taylor, Scott (Committee member) / Arizona State University (Publisher)
Created2023
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Description

Bioindicators of wildlife health are useful tools for studying the viability of various organisms and populations, and can include a range of phenotypic variables, such as behavior, body size, and physiological parameters, such as circulating hormones and nutrients. Few studies have investigated the utility of total plasma protein as a

Bioindicators of wildlife health are useful tools for studying the viability of various organisms and populations, and can include a range of phenotypic variables, such as behavior, body size, and physiological parameters, such as circulating hormones and nutrients. Few studies have investigated the utility of total plasma protein as a predictor of environmental or nutritional variation among birds, as well as variation across different seasons and life-history stages. Here I examined relationships between plasma protein and season, urbanization, sex, body condition, molt status, and disease state in house finches (Haemorhous mexicanus). I sampled blood from house finches across three seasons (winter, summer and fall 2021) and measured plasma protein levels using a Bradford assay. I also collected data including condition, sex, and poxvirus infection state at capture, as well as fecal samples to assess gut parasitism (coccidiosis). During the fall season I also estimated molt status, as number of actively growing feathers. I found circulating plasma protein concentration to be lower in the fall during molt than during winter or summer. I also found a significant relationship between circulating protein levels and capture site, as well as novel links to molt state and pox presence, with urban birds, those infected with pox, and those in more intense molt having higher protein levels. My results support the hypotheses that plasma protein concentration can be indicative of a bird’s body molt (which demands considerable protein for feather synthesis) and degree of habitat urbanization, although future work is needed to determine why protein levels were higher in virus-infected birds.

ContributorsDrake, Dean (Author) / McGraw, Kevin (Thesis director) / Sweazea, Karen (Committee member) / Jackson, Daniel (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2022-05
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Description
Mealworms (Tenebrio molitor), the larval stage of yellow mealworm beetles, are a popular feeder insect for birds, amphibians, reptiles, fish, and even human populations throughout the world. As such, the goal of this work was to understand how the diet of mealworms impacts their nutritional quality as variations in quality

Mealworms (Tenebrio molitor), the larval stage of yellow mealworm beetles, are a popular feeder insect for birds, amphibians, reptiles, fish, and even human populations throughout the world. As such, the goal of this work was to understand how the diet of mealworms impacts their nutritional quality as variations in quality can impact the animals (and humans) that consume them. In this study, 500 mealworms were divided among each of the following substrates designed to model food sources available in urban versus rural, more natural areas: 100% wheat germ (control); 100% Styrofoam; mixture of soil, grasses, and leaves from urban lawns; a mixture of soil, grasses and leaves from rural lawns; 50% mixture of wheat germ + carrots; natural fertilizer; or fertilizer with weed killer. The mealworms were maintained at room temperature and the diets were replaced bi-weekly to prevent spoilage and to remove mealworm waste. Once a week for three weeks, mealworms were sampled from each substrate and frozen at -20°C. After 3 weeks, mealworms housed in wheat germ + carrots weighed significantly more than all other groups (p<0.05), whereas those housed in Styrofoam or urban lawn substrates weighed significantly less at week 3 as compared to week 1 (p<0.01). The urban lawn substrate resulted in greater molting and contained the highest number of pupae, but also the greatest mortality among the substrates. The Bradford method measured the total protein content of mealworms homogenized in phosphate-buffered saline. Mealworms maintained on wheat germ had significantly greater total protein content as compared to mealworms transitioned to any other diet (p<0.05). So, compared to wheat germ, urban foods generally reduced protein, total sugars, and crude fat, although they also decreased oxidized lipoproteins. Urban lawn had lower oxidized lipoprotein content than wheat germ, but levels were higher compared to wheat germ with carrots and natural fertilizer. In addition, urban foods generally increase the water content in mealworms. Urban foods were not much different from rural lawns as no there was difference between urban and rural lawns. Differences in body mass and total protein support the hypothesis that mealworms' nutritional quality is altered by ingesting urban substrates. These data suggest that mealworms (and potentially other insects) in cities may be exposed to food substrates that result in less nutritional value than those living in more natural areas as mimicked by the rural lawn substrates and wheat germ control, although they may be higher in water content.
ContributorsLockett, Rory Earle (Author) / Sweazea, Karen (Thesis advisor) / Deviche, Pierre (Committee member) / Senko, Jesse (Committee member) / Arizona State University (Publisher)
Created2024
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Description
Mitochondria produce the majority portion of ATP required in eukaryotic cells. ATP is generated through a process known as oxidative phosphorylation, through an pathway consisting five multi subunit proteins (complex I-IV and ATP synthase), embedded inside the mitochondrial membrane. Mitochondrial electron transport chain dysfunction increases reactive oxygen species in the

Mitochondria produce the majority portion of ATP required in eukaryotic cells. ATP is generated through a process known as oxidative phosphorylation, through an pathway consisting five multi subunit proteins (complex I-IV and ATP synthase), embedded inside the mitochondrial membrane. Mitochondrial electron transport chain dysfunction increases reactive oxygen species in the cell and causes several serious disorders. Described herein are the synthesis of antioxidant molecules to reduce the effects in an already dysfunctional system. Also described is the study of the mitochondrial electron transport chain to understand the mechanism of action of a library of antioxidants. Illustrated in chapter 1 is the general history of research on mitochondrial dysfunction and reported ways to ameliorate them. Chapter 2 describes the design and synthesis of a series of compounds closely resembling the redox-active quinone core of the natural product geldanamycin. Geldanamycin has been reported to confer cytoprotection to FRDA lymphocytes in a dose dependent manner under conditions of induced oxidative stress. A library of rationally designed derivatives has been synthesized as a part of our pursuit of a better neuroprotective drug. Chapter 3 describes the design and synthesis of a library of pyrimidinol analogues. Compounds of this type have demonstrated the ability to quench reactive oxygen species and sustain mitochondrial membrane potential. Described herein are our efforts to increase their metabolic stability and total ATP production. It is crucial to understand the nature of interaction between a potential drug molecule and the mitochondrial electron transport chain to enable the design and synthesis a better therapeutic candidates. Chapter 4 describes a part of the enzymatic

binding studies between a molecular library synthesized in our laboratory and the mitochondrial electron transport chain using sub mitochondrial particles (SMP).
ContributorsDey, Sriloy (Author) / Hecht, Sidney M. (Thesis advisor) / Angell, Charles A (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2015