Matching Items (95)
Description
Over 40% of adults in the United States are considered obese. Obesity is known to cause abnormal metabolic effects and lead to other negative health consequences. Interestingly, differences in metabolism and contractile performance between obese and healthy weight individuals are associated with differences in skeletal muscle fiber type composition between these groups. Each fiber type is characterized by unique metabolic and contractile properties, which are largely determined by the myosin heavy chain isoform (MHC) or isoform combination that the fiber expresses. In previous studies, SDS-PAGE single fiber analysis has been utilized as a method to determine MHC isoform distribution and single fiber type distribution in skeletal muscle. Herein, a methodological approach to analyze MHC isoform and fiber type distribution in skeletal muscle was fine-tuned for use in human and rodent studies. In the future, this revised methodology will be implemented to evaluate the effects of obesity and exercise on the phenotypic fiber type composition of skeletal muscle.
ContributorsOhr, Jalonna Rose (Author) / Katsanos, Christos (Thesis director) / Tucker, Derek (Committee member) / Serrano, Nathan (Committee member) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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
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
Description
Seven human subjects with body mass indices (BMIs) ranging from 19.4 kg/ m2 to 26.7 kg/ m2 and six human subjects with BMIs ranging from 32.1 kg/ m2 to 37.6 kg/ m2 were recruited and subjected to 45-minute bouts of acute exercise to look at the changes in the plasma concentration of the dopamine metabolite homovanillic acid (HVA) in response to acute physical activity. Plasma HVA concentration was measured before exercise and during the last 10 minutes of the exercise bout via competitive ELISA. On average the optical density (OD) of the samples taken from lean subjects decreased from 0.203 before exercise to 0.192 during exercise, indicating increased plasma HVA concentration. In subjects with obesity OD increased from 0.210 before exercise to 0.219 during exercise, indicating reduced plasma HVA concentration. These differences in OD were not statistically significant. Between the lean group and the group with obesity no significant difference was observed between the OD of the plasma samples taken before exercise, but a significant difference (p = 0.0209) was observed between the ODs of the samples taken after exercise. This indicated that there was a significant difference between the percent changes in OD between the lean group and the group with obesity, which suggested that there may be a body weight-dependent difference in the amount of dopamine released in response to exercise. Because of the lack of significance in the changes in OD within the lean group and the group with obesity the results of this study were insufficient to conclude that this difference is not due to chance, but further investigation is warranted.
ContributorsYoder, Jordan Corinne (Author) / Katsanos, Christos (Thesis director) / Davies, Pauline (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Cancer remains one of the leading killers throughout the world. Death and disability due to lung cancer in particular accounts for one of the largest global economic burdens a disease presents. The burden on third-world countries is especially large due to the unusually large financial stress that comes from late tumor detection and expensive treatment options. Early detection using inexpensive techniques may relieve much of the burden throughout the world, not just in more developed countries. I examined the immune responses of lung cancer patients using immunosignatures – patterns of reactivity between host serum antibodies and random peptides. Immunosignatures reveal disease-specific patterns that are very reproducible. Immunosignaturing is a chip-based method that has the ability to display the antibody diversity from individual sera sample with low cost. Immunosignaturing is a medical diagnostic test that has many applications in current medical research and in diagnosis. From a previous clinical study, patients diagnosed for lung cancer were tested for their immunosignature vs. healthy non-cancer volunteers. The pattern of reactivity against the random peptides (the ‘immunosignature’) revealed common signals in cancer patients, absent from healthy controls. My study involved the search for common amino acid motifs in the cancer-specific peptides. My search through the hundreds of ‘hits’ revealed certain motifs that were repeated more times than expected by random chance. The amino acids that were the most conserved in each set include tryptophan, aspartic acid, glutamic acid, proline, alanine, serine, and lysine. The most overall conserved amino acid observed between each set was D - aspartic acid. The motifs were short (no more than 5-6 amino acids in a row), but the total number of motifs I identified was large enough to assure significance. I utilized Excel to organize the large peptide sequence libraries, then CLUSTALW to cluster similar-sequence peptides, then GLAM2 to find common themes in groups of peptides. In so doing, I found sequences that were also present in translated cancer expression libraries (RNA) that matched my motifs, suggesting that immunosignatures can find cancer-specific antigens that can be both diagnostic and potentially therapeutic.
ContributorsShiehzadegan, Shima (Author) / Johnston, Stephen (Thesis director) / Stafford, Phillip (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
Clean water for drinking, food preparation, and bathing is essential for astronaut health and safety during long duration habitation of the International Space Station (ISS), including future missions to Mars. Despite stringent water treatment and recycling efforts on the ISS, it is impossible to completely prevent microbial contamination of onboard water supplies. In this work, we used a spaceflight analogue culture system to better understand how the microgravity environment can influence the pathogenesis-related characteristics of Burkholderia cepacia complex (Bcc), an opportunistic pathogen previously recovered from the ISS water system. The results of the present study suggest that there may be important differences in how this pathogen can respond and adapt to spaceflight and other low fluid shear environments encountered during their natural life cycles. Future studies are aimed at understanding the underlying mechanisms responsible for these phenotypes.
ContributorsKang, Bianca Younseon (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, Mark (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The influenza virus, also known as "the flu", is an infectious disease that has constantly affected the health of humanity. There is currently no known cure for Influenza. The Center for Innovations in Medicine at the Biodesign Institute located on campus at Arizona State University has been developing synbodies as a possible Influenza therapeutic. Specifically, at CIM, we have attempted to design these initial synbodies to target the entire Influenza virus and preliminary data leads us to believe that these synbodies target Nucleoprotein (NP). Given that the synbody targets NP, the penetration of cells via synbody should also occur. Then by Western Blot analysis we evaluated for the diminution of NP level in treated cells versus untreated cells. The focus of my honors thesis is to explore how synthetic antibodies can potentially inhibit replication of the Influenza (H1N1) A/Puerto Rico/8/34 strain so that a therapeutic can be developed. A high affinity synbody for Influenza can be utilized to test for inhibition of Influenza as shown by preliminary data. The 5-5-3819 synthetic antibody's internalization in live cells was visualized with Madin-Darby Kidney Cells under a Confocal Microscope. Then by Western Blot analysis we evaluated for the diminution of NP level in treated cells versus untreated cells. Expression of NP over 8 hours time was analyzed via Western Blot Analysis, which showed NP accumulation was retarded in synbody treated cells. The data obtained from my honors thesis and preliminary data provided suggest that the synthetic antibody penetrates live cells and targets NP. The results of my thesis presents valuable information that can be utilized by other researchers so that future experiments can be performed, eventually leading to the creation of a more effective therapeutic for influenza.
ContributorsHayden, Joel James (Author) / Diehnelt, Chris (Thesis director) / Johnston, Stephen (Committee member) / Legutki, Bart (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
Description
New-onset diabetes after kidney transplantation (NODAT) occurs in 20% of kidney transplant patients. In 5 patients who are at risk for new-onset diabetes after kidney transplantation, skeletal muscle gene expression profiling was performed both before and after kidney transplant. The differences in gene expression before and after transplant were compared in order to identify specific genes that could be linked to developing NODAT. These findings could open new avenues for future research.
ContributorsLowery, Clint Curtis (Author) / Coletta, Dawn (Thesis director) / Katsanos, Christos (Committee member) / Willis, Wayne (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / W. P. Carey School of Business (Contributor)
Created2014-05
Description
DNA methylation, a subset of epigenetics, has been found to be a significant marker associated with variations in gene expression and activity across the entire human genome. As of now, however, there is little to no information about how DNA methylation varies between different tissues inside a singular person's body. By using research data from a preliminary study of lean and obese clinical subjects, this study attempts to put together a profile of the differences in DNA methylation that can be observed between two particular body tissues from this subject group: blood and skeletal muscle. This study allows us to start describing the changes that occur at the epigenetic level that influence how differently these two tissues operate, along with seeing how these tissues change between individuals of different weight classes, especially in the context of the development of symptoms of Type 2 Diabetes.
ContributorsRappazzo, Micah Gabriel (Author) / Coletta, Dawn (Thesis director) / Katsanos, Christos (Committee member) / Dinu, Valentin (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / Department of Psychology (Contributor)
Created2013-12
Description
Type 2 diabetes mellitus (T2DM) is a life-long disease that affects over 27 million individuals in the United States alone. There are many different risk factors and pre-indicators of T2DM. One of them is insulin resistance. Insulin resistance occurs when the body is unable to appropriately respond to insulin. This in turn leads to increased levels of glucose and insulin in the bloodstream. Unlike T2DM, insulin resistance is a reversible diagnosis. The purpose of this project was to identify the most influential genetic and dietary factors of insulin resistance and to see if individuals have some extent of control to possibly avoid the diagnosis of insulin resistance and possibly T2DM entirely.
A total of 26 human subjects were used in this study. Each subject was classified as either lean or obese, according to their BMI measurement. First, the subjects underwent an oral glucose tolerance test. Blood samples were taken to measure glucose levels in the blood. After the test subject characteristics for each subject was obtained. These included age, BMI, body fat percentage, fat free mass (FFM), height, total mass, waist circumference, hip circumference, and waist to hip ratio. After the subject characteristics and blood glucose were measured the blood samples taken previously were then centrifuged, and the blood plasma was extracted. The blood plasma was then used to undergo an Insulin ELISA test. After extensive analysis, the Matsuda Index of each subject was obtained. Subjects with a Matsuda value of 6.0 or under were considered insulin resistant while subjects with a Matsuda value higher than 6.0 were considered insulin sensitive. Subjects were also required to submit a dietary record over the course of three days. The food intake was then put into a food processing software which gave a daily average of the macro and micro nutrients for each subject. Both the subject and dietary values were put into a multiple regression with a significance factor of p < 0.5 to see which factors contributed most to the Matsuda value.
It was found that BMI, height, total mass, insulin and fat free mass, all of which were subject characteristics, were considered to be significant. Some of these factors an individual has no control over, such as height and insulin. However other factors such as BMI, total mass and fat free mass can be affected by both a healthy diet and frequent exercise. This study validated that diet and physical activity can greatly influence an individual’s susceptibility to insulin resistance and ultimately T2DM.
A total of 26 human subjects were used in this study. Each subject was classified as either lean or obese, according to their BMI measurement. First, the subjects underwent an oral glucose tolerance test. Blood samples were taken to measure glucose levels in the blood. After the test subject characteristics for each subject was obtained. These included age, BMI, body fat percentage, fat free mass (FFM), height, total mass, waist circumference, hip circumference, and waist to hip ratio. After the subject characteristics and blood glucose were measured the blood samples taken previously were then centrifuged, and the blood plasma was extracted. The blood plasma was then used to undergo an Insulin ELISA test. After extensive analysis, the Matsuda Index of each subject was obtained. Subjects with a Matsuda value of 6.0 or under were considered insulin resistant while subjects with a Matsuda value higher than 6.0 were considered insulin sensitive. Subjects were also required to submit a dietary record over the course of three days. The food intake was then put into a food processing software which gave a daily average of the macro and micro nutrients for each subject. Both the subject and dietary values were put into a multiple regression with a significance factor of p < 0.5 to see which factors contributed most to the Matsuda value.
It was found that BMI, height, total mass, insulin and fat free mass, all of which were subject characteristics, were considered to be significant. Some of these factors an individual has no control over, such as height and insulin. However other factors such as BMI, total mass and fat free mass can be affected by both a healthy diet and frequent exercise. This study validated that diet and physical activity can greatly influence an individual’s susceptibility to insulin resistance and ultimately T2DM.
ContributorsBrinkerhoff, Catalina Marie (Author) / Katsanos, Christos (Thesis director) / Shaffer, Zachary (Committee member) / College of Health Solutions (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05