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Description
The pathogenesis of type 1 diabetes (T1D) is still not fully understood in the scientific community. Evidence has shown that viral infections are one of the important environmental factors associated with the disease development. Seven of the top T1D related viruses were selected to study the prevalence of viral humoral response in T1D patients using our innovative protein array platform called Nucleic Acid Programmable Protein Array (NAPPA). In this study, each viral gene was individually captured using various PCR based techniques, cloned into a protein expression vector, and assembled as the first version of T1D viral protein array. Humoral responses of IgG, IgA, and IgM were examined. Although each class of immunoglobulin generated a wide-range of reactivity, responses to various viral proteins from different proteins were observed. In summary, we captured most of the T1D related viral genes, established viral protein expression on the protein array, and displayed the serum response on the viral protein array. The successful progress will help to fulfill the long term goal of testing the viral infection hypothesis in T1D development.
ContributorsDavis, Amy Darlene (Author) / LaBaer, Joshua (Thesis director) / Qiu, Ji (Committee member) / Desi, Paul (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2013-05
Description
Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer deaths in females worldwide, accounting for 23% of all new cancer cases and 14% of all total cancer deaths in 2008. Five tumor-normal pairs of primary breast epithelial cells were treated for infinite proliferation by using a ROCK inhibitor and mouse feeder cells. Methods: Raw paired-end, 100x coverage RNA-Seq data was aligned to the Human Reference Genome Version 19 using BWA and Tophat. Gene differential expression analysis was completed using Cufflinks and Cuffdiff. Interactive Genome Viewer was used for data visualization. Results: 15 genes were found to be down-regulated by at least one log-fold change in 4/5 of tumor samples. 75 genes were found to be down-regulated in 3/5 of our tumor samples by at least one log-fold change. 11 genes were found to be up-regulated in 4/5 of our tumor samples, and 68 genes were identified to be up-regulated in 3/5 of the tumor samples by at least one-fold change. Conclusion: Expression changes in genes such as AZGP1, AGER, ALG11, and S1007 suggest a disruption in the glycosylation pathway. No correlation was found between Cufflink's Her2 gene-expression and DAKO score classification.
ContributorsHernandez, Fernando (Author) / Anderson, Karen (Thesis director) / Mangone, Marco (Committee member) / Park, Jin (Committee member) / Barrett, The Honors College (Contributor) / Department of Information Systems (Contributor)
Created2013-05
Description
Protein AMPylation is a recently discovered and relatively unstudied post-translational modification (PTM). AMPylation has previously been shown to play an important role in metabolic regulation and host pathogenesis in bacteria, but the recent identification of potential AMPylators across many species in every domain of life has supported the possibility that AMPylation could be a more fundamental and physiologically significant regulatory PTM. For the first time, we characterized the auto-AMPylation capability of the human protein SOS1 through in vitro AMPylation experiments using full-length protein and whole-domain truncation mutants. We found that SOS1 can become AMPylated at a tyrosine residue possibly within the Cdc25 domain of the protein, the Dbl homology domain is vital for efficient auto-AMPylation activity, and the C-terminal proline-rich domain exhibits a complex regulatory function. The proline-rich domain alone also appears to be capable of catalyzing a separate, unidentified covalent self-modification using a fluorescent ATP analogue. Finally, SOS1 was shown to be capable of catalyzing the AMPylation of two endogenous human protein substrates: a ubiquitous, unidentified protein of ~49kDa and another breast-cancer specific, unidentified protein of ~28kDa.
ContributorsOber-Reynolds, Benjamin John (Author) / LaBaer, Joshua (Thesis director) / Borges, Chad (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
One of the major challenges that were yet to be solved for solid phase peptide synthesis was the lack of an efficient peptide sequencing technique that was less hazardous, easier to perform , and was more cost-effective. Sequencing peptides were held important in the field of Chemistry and Biochemistry because it aided in drug discovery, finding ligands that bind to a specific target protein and finding alternative agents in transporting molecules to its desired location. Therefore, the overall purpose of this experiment was to develop a method of solid phase sequencing technique that was more environmental friendly, sequences at a faster rate, and was more cost-effective.
ContributorsCordovez, Lalaine Anne Ordiz (Author) / Woodbury, Neal (Thesis director) / Zhao, Zhan-Gong (Committee member) / Legutki, Joseph Barten (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
Description
AMPylation is a post-translation modification that has an important role in the survival of many bacterial pathogens by affecting the host cell's molecular signaling. In the course of studying this intercellular manipulation, there has only been modest progression in the identification of the enzymes with AMPylation capabilities (AMPylators) and their respective targets. The reason for these minimal developments is the inability to analyze a large subset of these proteins. Therefore, to increase the efficiency of the identification and characterization of the proteins, Yu et al developed a high-throughput non-radioactive discovery platform using Human Nucleic Acid Programmable Protein Arrays (NAPPA) and a validation platform using bead-based assays. The large-scale unbiased screening of potential substrates for two bacterial AMPylators containing Fic domain, VopS and IbpAFic2, had been performed and dozens of novel substrates were identified and confirmed. With the efficiency of this method, the platform was extended to the identification of novel substrates for a Legionella virulence factor, SidM, containing a different adenylyl transferase domain. The screening was performed using NAPPA arrays comprising of 10,000 human proteins, the active AMPylator SidM, and its inactive D110/112A mutant as a negative control. Many potential substrates of SidM were found, including Rab GTPases and non-GTPase proteins. Several of which have been confirmed with the bead-based AMPylation assays.
ContributorsGraves, Morgan C. (Author) / LaBaer, Joshua (Thesis director) / Qiu, Ji (Committee member) / Yu, Xiaobo (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2013-05
Description
The purpose of this project was to identify proteins associated with the migration and invasion of non-transformed MCF10A mammary epithelial cells with ectopically expressed missense mutations in p53. Because of the prevalence of TP53 missense mutations in basal-like and triple-negative breast cancer tumors, understanding the effect of TP53 mutations on the phenotypic expression of human mammary epithelial cells may offer new therapeutic targets for those currently lacking in treatment options. As such, MCF10A mammary epithelial cells ectopically overexpressing structural mutations (G245S, H179R, R175H, Y163C, Y220C, and Y234C) and DNA-binding mutations (R248Q, R248W, R273C, and R273H) in the DNA-binding domain were selected for use in this project. Overexpression of p53 in the mutant cell lines was confirmed by western blot and q-PCR analysis targeting the V5 epitope tag present in the pLenti4 vector used to transduce TP53 into the mutant cell lines. Characterization of the invasion and migration phenotypes resulting from the overexpression of p53 in the mutant cell lines was achieved using transwell invasion and migration assays with Boyden chambers. Statistical analysis showed that three cell lines—DNA-contact mutants R248W and R273C and structural mutant Y220C—were consistently more migratory and invasive and demonstrated a relationship between the migration and invasion properties of the mutant cell lines. Two families of proteins were then explored: those involved in the Epithelial-Mesenchymal Transition (EMT) and matrix metalloproteinases (MMPs). Results of q-PCR and immunofluorescence analysis of epithelial marker E-cadherin and mesenchymal proteins Slug and Vimentin did not show a clear relationship between mRNA and protein expression levels with the migration and invasiveness phenotypes observed in the transwell studies. Results of western blotting, q-PCR, and zymography of MMP-2 and MMP-9 also did not show any consistent results indicating a definite relationship between MMPs and the overall invasiveness of the cells. Finally, two drugs were tested as possible treatments inhibiting invasiveness: ebselen and SBI-183. These drugs were tested on only the most invasive of the MCF10A p53 mutant cell lines (R248W, R273C, and Y220C). Results of invasion assay following 30 μM treatment with ebselen and SBI-183 showed that ebselen does not inhibit invasiveness; SBI-183, however, did inhibit invasiveness in all three cell lines tested. As such, SBI-183 will be an important compound to study in the future as a treatment that could potentially serve to benefit triple-negative or basal-like breast cancer patients who currently lack therapeutic treatment options.
ContributorsZhang, Kathie Q (Author) / LaBaer, Joshua (Thesis director) / Anderson, Karen (Committee member) / Gonzalez, Laura (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
Description
Surrounded by a developmental boom in downtown Phoenix, Roosevelt Row fights to maintain the local art influence and historic character. An earthy community of street artists, coffee drinkers, band tees, nose rings, vinyl collectors and rolled denim, the people are facing dramatic urbanization. The hum of drills, hammers, cranes and alarms sound throughout the viscidity, echoing the construction of a new era downtown. In the interest of better understanding the developmental process, resident needs and community, this research project evaluates successful public spaces and similar downtown areas in the United States, synthesized their elements of prosperity in comparison to general attributes of quality public spaces, and implemented the concepts and ideas into Roosevelt Row. This provided the researcher with knowledge of quality public spaces, why public space is important, and how placemaking is routinely accomplished. This also equipped the researcher with the tools to participate in ethnography and collect observational data to learn about Roosevelt Row. The researcher then combined learned material with what she observed on the Row, to condense the artists' district developmental needs into nine proposals for bettering the Row in the immediate, near and long-term future. The study begs to answer the question: is Roosevelt Row a Place or a place? Observation, residential and visitor engagement with the space; locality, pleasurability, inclusiveness and safety of the public spaces; and relationship between residents and quality of space all contribute to the space's qualifications. While Roosevelt Row has the potential and assets to become a Place, especially if the nine proposals are implemented. However, at the time of research, the space is between place and Place.
ContributorsStobbe, Brooke Elizabeth (Author) / Larsen, Dale (Thesis director) / Knopf, Richard (Committee member) / College of Public Service and Community Solutions (Contributor) / Walter Cronkite School of Journalism and Mass Communication (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
Background
Weight gain during the childbearing years and failure to lose pregnancy weight after birth contribute to the development of obesity in postpartum Latinas.
Methods
Madres para la Salud [Mothers for Health] was a 12-month, randomized controlled trial exploring a social support intervention with moderate-intensity physical activity (PA) seeking to effect changes in body fat, fat tissue inflammation, and depression symptoms in sedentary postpartum Latinas. This report describes the efficacy of the Madres intervention.
Results
The results show that while social support increased during the active intervention delivery, it declined to pre-intervention levels by the end of the intervention. There were significant achievements in aerobic and total steps across the 12 months of the intervention, and declines in body adiposity assessed with bioelectric impedance.
Conclusions
Social support from family and friends mediated increases in aerobic PA resulting in decrease in percent body fat.
Weight gain during the childbearing years and failure to lose pregnancy weight after birth contribute to the development of obesity in postpartum Latinas.
Methods
Madres para la Salud [Mothers for Health] was a 12-month, randomized controlled trial exploring a social support intervention with moderate-intensity physical activity (PA) seeking to effect changes in body fat, fat tissue inflammation, and depression symptoms in sedentary postpartum Latinas. This report describes the efficacy of the Madres intervention.
Results
The results show that while social support increased during the active intervention delivery, it declined to pre-intervention levels by the end of the intervention. There were significant achievements in aerobic and total steps across the 12 months of the intervention, and declines in body adiposity assessed with bioelectric impedance.
Conclusions
Social support from family and friends mediated increases in aerobic PA resulting in decrease in percent body fat.
ContributorsKeller, Colleen (Author) / Ainsworth, Barbara (Author) / Records, Kathryn (Author) / Todd, Michael (Author) / Belyea, Michael (Author) / Vega Lopez, Sonia (Author) / Permana, Paska (Author) / Coonrod, Dean (Author) / Williams, Allison (Author) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / College of Health Solutions (Contributor) / School of Nutrition and Health Promotion (Contributor) / College of Public Service and Community Solutions (Contributor) / Southwest Interdisciplinary Research Center (Contributor)
Created2014-09-19
Description
In the face of rising rates of substance use among Mexican youth and rapidly narrowing gender differences in use, substance use prevention is an increasingly urgent priority for Mexico. Prevention interventions have been implemented in Mexico but few have been rigorously evaluated for effectiveness. This article presents the long term effects of a Mexico-based pilot study to test the feasibility of a linguistically specific (Mexican Spanish) adapted version of keepin’ it REAL, a school-based substance abuse prevention model program. University affiliated researchers from Mexico and the US collaborated on the study design, program implementation, data collection, and analysis. Students and their teachers from two middle schools (secundarias) in Guadalajara participated in this field trial of Mantente REAL (translated to Spanish). The schools were randomly assigned to treatment and control conditions. The sample of 431 students reported last 30 day substance use at three times (one pretest and two posttests). Changes in substance use behaviors over time were examined using growth curve models. Long term desired intervention effects were found for alcohol and marijuana use but not for cigarettes. The intervention effects were greater for girls than for boys in slowing the typical developmental increase over time in alcohol use. Marijuana effects were based on small numbers of users and indicate a need for larger scale studies. These findings suggest that keepin’ it REAL is a promising foundation for cultural program adaptation efforts to create efficacious school-based universal prevention interventions for middle school students in Mexico.
ContributorsMarsiglia, Flavio (Author) / Kulis, Stephen (Author) / Booth, Jaime (Author) / Nuno-Gutierrez, Bertha L. (Author) / Robbins, Danielle (Author) / College of Public Service and Community Solutions (Contributor) / School of Social Work (Contributor) / College of Liberal Arts and Sciences (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Southwest Interdisciplinary Research Center (Contributor)
Created2015-04-01
Description
Background
Obese Latino adolescents are disproportionately impacted by insulin resistance and type 2 diabetes. Prediabetes is an intermediate stage in the pathogenesis of type 2 diabetes and represents a critical opportunity for intervention. However, to date, no diabetes prevention studies have been conducted in obese Latino youth with prediabetes, a highly vulnerable and underserved group. Therefore, we propose a randomized-controlled trial to test the short-term (6-month) and long-term (12-month) efficacy of a culturally-grounded, lifestyle intervention, as compared to usual care, for improving glucose tolerance and reducing diabetes risk in 120 obese Latino adolescents with prediabetes.
Methods
Participants will be randomized to a lifestyle intervention or usual care group. Participants in the intervention group will attend weekly nutrition and wellness sessions and physical activity sessions twice a week for six months, followed by three months of booster sessions. The overall approach of the intervention is framed within a multilevel Ecodevelopmental model that leverages community, family, peer, and individual factors during the critical transition period of adolescence. The intervention is also guided by Social Cognitive Theory and employs key behavioral modification strategies to enhance self-efficacy and foster social support for making and sustaining healthy behavior changes. We will test intervention effects on quality of life, explore the potential mediating effects of changes in body composition, total, regional, and organ fat on improving glucose tolerance and increasing insulin sensitivity, and estimate the initial incremental cost effectiveness of the intervention as compared with usual care for improving glucose tolerance.
Discussion
The proposed trial builds upon extant collaborations of a transdisciplinary team of investigators working in concert with local community agencies to address critical gaps in how diabetes prevention interventions for obese Latino youth are developed, implemented and evaluated. This innovative approach is an essential step in the development of scalable, cost-effective, solution oriented programs to prevent type 2 diabetes in this and other populations of high-risk youth.
Obese Latino adolescents are disproportionately impacted by insulin resistance and type 2 diabetes. Prediabetes is an intermediate stage in the pathogenesis of type 2 diabetes and represents a critical opportunity for intervention. However, to date, no diabetes prevention studies have been conducted in obese Latino youth with prediabetes, a highly vulnerable and underserved group. Therefore, we propose a randomized-controlled trial to test the short-term (6-month) and long-term (12-month) efficacy of a culturally-grounded, lifestyle intervention, as compared to usual care, for improving glucose tolerance and reducing diabetes risk in 120 obese Latino adolescents with prediabetes.
Methods
Participants will be randomized to a lifestyle intervention or usual care group. Participants in the intervention group will attend weekly nutrition and wellness sessions and physical activity sessions twice a week for six months, followed by three months of booster sessions. The overall approach of the intervention is framed within a multilevel Ecodevelopmental model that leverages community, family, peer, and individual factors during the critical transition period of adolescence. The intervention is also guided by Social Cognitive Theory and employs key behavioral modification strategies to enhance self-efficacy and foster social support for making and sustaining healthy behavior changes. We will test intervention effects on quality of life, explore the potential mediating effects of changes in body composition, total, regional, and organ fat on improving glucose tolerance and increasing insulin sensitivity, and estimate the initial incremental cost effectiveness of the intervention as compared with usual care for improving glucose tolerance.
Discussion
The proposed trial builds upon extant collaborations of a transdisciplinary team of investigators working in concert with local community agencies to address critical gaps in how diabetes prevention interventions for obese Latino youth are developed, implemented and evaluated. This innovative approach is an essential step in the development of scalable, cost-effective, solution oriented programs to prevent type 2 diabetes in this and other populations of high-risk youth.
ContributorsSoltero, Erica (Author) / Konopken, Yolanda P. (Author) / Olson, Micah (Author) / Keller, Colleen (Author) / Castro, Felipe (Author) / Williams, Allison (Author) / Patrick, Donald L. (Author) / Ayers, Stephanie (Author) / Hu, Houchun H. (Author) / Sandoval, Matthew (Author) / Pimentel, Janiel (Author) / Knowler, William C. (Author) / Frick, Kevin D. (Author) / Shaibi, Gabriel (Author) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / Center for Health Promotion and Disease Prevention (Contributor) / College of Public Service and Community Solutions (Contributor) / Southwest Interdisciplinary Research Center (Contributor) / School of Social Work (Contributor)
Created2017-03-16