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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

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
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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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Epigenetic mechanisms such as DNA methylation have been found to affect metabolic processes, which leads to conditions like type 2 diabetes and obesity. The aim of this project was to validate differentially methylated cytosines (DMCs) identified in skeletal muscle from seven obese, non-diabetic women pre- and 3 months post- Roux-en-Y

Epigenetic mechanisms such as DNA methylation have been found to affect metabolic processes, which leads to conditions like type 2 diabetes and obesity. The aim of this project was to validate differentially methylated cytosines (DMCs) identified in skeletal muscle from seven obese, non-diabetic women pre- and 3 months post- Roux-en-Y gastric bypass surgery. DNA samples extracted from skeletal muscle were sent to the Mayo Genotyping Core to undergo reduced representation bisulfite sequencing (RRBS). Differentially methylated cytosines at chr14.105353824 of the gene CEP170B, chr19.16437949 of the KLF2 gene, chr7.130126082 of MEST, and chr15.62457572 of C2CD4B were captured from the RRBS analysis using MethylSig. Bisulfite sequencing PCR (BSP) was performed on all DMCs listed above which resulted in no significant changes in methylation post-surgery. It was concluded that an alternate, more precise method should be used for validation of the RRBS, such as pyrosequencing.
ContributorsKelley, Conley Lane (Author) / Coletta, Dawn K. (Thesis director) / Roust, Lori R. (Committee member) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Breast cancer affects about 12% of women in the US. Arguably, it is one of the most advertised cancers. Mammography became a popular tool of breast cancer screening in the 1970s, and patient-geared guidelines came from the American Cancer Society (ACS) and the US Preventative Task Force (USPSTF). This research

Breast cancer affects about 12% of women in the US. Arguably, it is one of the most advertised cancers. Mammography became a popular tool of breast cancer screening in the 1970s, and patient-geared guidelines came from the American Cancer Society (ACS) and the US Preventative Task Force (USPSTF). This research focuses on ACS guidelines, as they were the earliest as well as the most changed guidelines. Mammography guidelines changed over time due to multiple factors. This research has tracked possible causes of those changes. Research began with an extensive literature search of clinical trials, the New York Times and the Washington Post archives, systematic reviews, ACS and USPSTF archives.

Created2021-02-16
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Science fiction works can reflect the relationship between science and society by telling stories that are set in the future of ethical implications or social consequences of scientific advancements. This thesis investigates how the concept of reproduction is depicted in popular science fiction works.

Created2021-02-10
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By questioning methods of sex selection since their early development, and often discovering that they are unreliable, scientists have increased the creative and technological capacity of the field of reproductive health. The presentation of these methods to the public, via published books on timing methods and company websites for sperm

By questioning methods of sex selection since their early development, and often discovering that they are unreliable, scientists have increased the creative and technological capacity of the field of reproductive health. The presentation of these methods to the public, via published books on timing methods and company websites for sperm sorting, increased interest in, and influence of, sex selection within the global society. The purpose of explaining the history, interest, development, and impact of various sex selection methods in the mid-twentieth century based on the information that is available on them today is to show couples which methods have failed and provide them with the knowledge necessary to make an informed decision on how they choose to go about utilizing methods of sex selection.

Created2021-02-26
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By demonstrating the struggle for sound standard of care for non-medical reproductive health care providers during the nineteenth and early twentieth century, this project emphasizes what the standards of reproductive health care for abortion and contraception might be like if the organizations that made them so readily available, like Planned

By demonstrating the struggle for sound standard of care for non-medical reproductive health care providers during the nineteenth and early twentieth century, this project emphasizes what the standards of reproductive health care for abortion and contraception might be like if the organizations that made them so readily available, like Planned Parenthood, were defunded or criminalized in our modern setting.

Created2021-02-23
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On 29 June 1988, in Bowen v. Kendrick, the US Supreme Court ruled in a five-to-four decision that the 1981 Adolescent Family Life Act, or AFLA, was constitutional. Under AFLA, the US government could distribute federal funding for abstinence-only sexual education programs, oftentimes given to groups with religious affiliations. As

On 29 June 1988, in Bowen v. Kendrick, the US Supreme Court ruled in a five-to-four decision that the 1981 Adolescent Family Life Act, or AFLA, was constitutional. Under AFLA, the US government could distribute federal funding for abstinence-only sexual education programs, oftentimes given to groups with religious affiliations. As a federal taxpayer, Chan Kendrick challenged the constitutionality of AFLA, claiming it violated the separation of church and state. The Supreme Court found that although AFLA funded programs that aligned with certain religious ideologies, it was constitutional because it did not encourage government involvement in religion, and it held a valid secular purpose in seeking to prevent adolescent pregnancy and premarital sexual relations. By upholding AFLA, Bowen v. Kendrick enabled the US government to continue funding abstinence-only education, which researchers have found to be ineffective.

Created2021-02-26
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In 1997, physicians and researchers Ambre Olsen, Virginia Smith, John Bergstrom, Joyce Colling, and Amanda Clark published, “Epidemiology of Surgically Managed Pelvic Organ Prolapse and Urinary Incontinence,” in the journal Obstetrics and Gynecology. In their article, the authors retrospectively analyzed data from patients who underwent surgery for pelvic organ prolapse

In 1997, physicians and researchers Ambre Olsen, Virginia Smith, John Bergstrom, Joyce Colling, and Amanda Clark published, “Epidemiology of Surgically Managed Pelvic Organ Prolapse and Urinary Incontinence,” in the journal Obstetrics and Gynecology. In their article, the authors retrospectively analyzed data from patients who underwent surgery for pelvic organ prolapse or urinary incontinence two years prior in 1995. Often due to a weakening of or damage to their pelvic muscles, women with pelvic organ prolapse can experience a descent of pelvic organs into the lower pelvis and vagina. People with urinary incontinence can experience bladder control issues and urinary leaks. According to the authors, an estimated fifty percent of women who have previously given birth have had a prolapse. In their article, Olsen and colleagues analyze factors such as race, age, and weight in women who had surgery to treat pelvic organ prolapse and ultimately advocate for a standard assessment for the severity of those conditions.

Created2021-02-23
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In 1996, a team of researchers associated with the International Continence Society published “The Standardization of Terminology of Female Pelvic Organ Prolapse and Pelvic Floor Dysfunction” in American Journal of Obstetrics and Gynecology. Pelvic organ prolapse is characterized by the descent of the pelvic organs into the lower portion of

In 1996, a team of researchers associated with the International Continence Society published “The Standardization of Terminology of Female Pelvic Organ Prolapse and Pelvic Floor Dysfunction” in American Journal of Obstetrics and Gynecology. Pelvic organ prolapse is characterized by the descent of the pelvic organs into the lower portion of the pelvis and is often caused by a weakening of the muscles and ligaments that normally hold the organs in place. The authors concluded that physicians and researchers needed to develop a system of standardized terms to use to describe the anatomical position of pelvic organ prolapse in women. They propose using terms that emphasize the location of the prolapse rather than just the involved organ. They also suggest that the system utilizes a series of examinations and imaging to uniformly describe and quantify pelvic organ prolapse. The article by Bump and colleagues was one of the first to call for a standardized system using specific terms to communicate findings about pelvic organ prolapse systematically across clinical and academic research settings.

Created2021-03-10