Matching Items (223)
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
miRNAs are short non-coding regulatory RNAs that have an important roles in a wide range of biological processes. Dysfunction of miRNA regulation has also been shown to occur in diseases such as cancer. Despite the widespread influence of miRNAs in these contexts, the vast majority of miRNA targets are poorly characterized. The aim of this research project was to gain a better understating of miRNA targeting by using the model organism C. elegans. In order to do this I adapted a novel high-throughput assay to detect miRNA targets for use with the C. elegans 3`UTRome. As a proof of principle I performed this assay on 96 C. elegans 3`UTRs using high-throughput techniques. The results revealed miRNA interactions with two predicted 3`UTR targets for the miRNA lin-4 and ten unpredicted targets. The results also corroborated previous findings that certain worm miRNAs require special modifications to be expressed in human cells.
ContributorsKotagama, Kasuen Indrajith Bandara (Author) / Mangone, Marco (Thesis director) / Anderson, Karen (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2013-12
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
Alternative polyadenylation (APA) is the biological mechanism in which the same gene can have multiple 3'untranslated region (3'UTR) isoforms due to the presence of multiple polyadenylation signal (PAS) elements within the pre mRNAs. Because APA produces mRNA transcripts that have different 3'UTR isoforms, certain transcripts may be subject to post-transcriptional regulation by regulatory non-coding RNAs, such as microRNAs or RNA binding proteins defects of which have been implicated in diseases such as cancer. Despite the increasing level of information, functional understanding of the molecular mechanisms involved in transcription is still poorly understood, nor is it clear why APA is necessary at a cell or tissue-specific level. To address these questions I wanted to develop a set of sensor strain plasmids capable of detecting cleavage and polyadenylation in vivo, inject the complete sensor strain plasmid into C. elegans and prepare stable transgenic lines, and perform proof-of-principle RNAi feeding experiments targeting genes associated with the cleavage and polyadenylation complex machinery. I demonstrated that it was possible to create a plasmid capable of detecting cleavage and polyadenylation in C. elegans; however, issues arose during the RNAi assays indicating the sensor strain plasmid was not sensitive enough to the RNAi to effectively detect in the worms. Once the problems involved with sensitivity and variability in the RNAi effects are resolved, the plasmid would be able to better address questions regarding the functional understanding of molecular mechanisms involved in transcription termination.
ContributorsWilky, Henry Patrick (Author) / Mangone, Marco (Thesis director) / Newbern, Jason (Committee member) / Blazie, Stephen (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Background
The purpose of this study is to determine the feasibility of three widely used wearable sensors in research settings for 24 h monitoring of sleep, sedentary, and active behaviors in middle-aged women.
Methods
Participants were 21 inactive, overweight (M Body Mass Index (BMI) = 29.27 ± 7.43) women, 30 to 64 years (M = 45.31 ± 9.67). Women were instructed to wear each sensor on the non-dominant hip (ActiGraph GT3X+), wrist (GENEActiv), or upper arm (BodyMedia SenseWear Mini) for 24 h/day and record daily wake and bed times for one week over the course of three consecutive weeks. Women received feedback about their daily physical activity and sleep behaviors. Feasibility (i.e., acceptability and demand) was measured using surveys, interviews, and wear time.
Results
Women felt the GENEActiv (94.7 %) and SenseWear Mini (90.0 %) were easier to wear and preferred the placement (68.4, 80 % respectively) as compared to the ActiGraph (42.9, 47.6 % respectively). Mean wear time on valid days was similar across sensors (ActiGraph: M = 918.8 ± 115.0 min; GENEActiv: M = 949.3 ± 86.6; SenseWear: M = 928.0 ± 101.8) and well above other studies using wake time only protocols. Informational feedback was the biggest motivator, while appearance, comfort, and inconvenience were the biggest barriers to wearing sensors. Wear time was valid on 93.9 % (ActiGraph), 100 % (GENEActiv), and 95.2 % (SenseWear) of eligible days. 61.9, 95.2, and 71.4 % of participants had seven valid days of data for the ActiGraph, GENEActiv, and SenseWear, respectively.
Conclusion
Twenty-four hour monitoring over seven consecutive days is a feasible approach in middle-aged women. Researchers should consider participant acceptability and demand, in addition to validity and reliability, when choosing a wearable sensor. More research is needed across populations and study designs.
The purpose of this study is to determine the feasibility of three widely used wearable sensors in research settings for 24 h monitoring of sleep, sedentary, and active behaviors in middle-aged women.
Methods
Participants were 21 inactive, overweight (M Body Mass Index (BMI) = 29.27 ± 7.43) women, 30 to 64 years (M = 45.31 ± 9.67). Women were instructed to wear each sensor on the non-dominant hip (ActiGraph GT3X+), wrist (GENEActiv), or upper arm (BodyMedia SenseWear Mini) for 24 h/day and record daily wake and bed times for one week over the course of three consecutive weeks. Women received feedback about their daily physical activity and sleep behaviors. Feasibility (i.e., acceptability and demand) was measured using surveys, interviews, and wear time.
Results
Women felt the GENEActiv (94.7 %) and SenseWear Mini (90.0 %) were easier to wear and preferred the placement (68.4, 80 % respectively) as compared to the ActiGraph (42.9, 47.6 % respectively). Mean wear time on valid days was similar across sensors (ActiGraph: M = 918.8 ± 115.0 min; GENEActiv: M = 949.3 ± 86.6; SenseWear: M = 928.0 ± 101.8) and well above other studies using wake time only protocols. Informational feedback was the biggest motivator, while appearance, comfort, and inconvenience were the biggest barriers to wearing sensors. Wear time was valid on 93.9 % (ActiGraph), 100 % (GENEActiv), and 95.2 % (SenseWear) of eligible days. 61.9, 95.2, and 71.4 % of participants had seven valid days of data for the ActiGraph, GENEActiv, and SenseWear, respectively.
Conclusion
Twenty-four hour monitoring over seven consecutive days is a feasible approach in middle-aged women. Researchers should consider participant acceptability and demand, in addition to validity and reliability, when choosing a wearable sensor. More research is needed across populations and study designs.
ContributorsHuberty, Jennifer (Author) / Ehlers, Diane (Author) / Kurka, Jonathan (Author) / Ainsworth, Barbara (Author) / Buman, Matthew (Author) / College of Health Solutions (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-07-30
Description
Mathematical epidemiology, one of the oldest and richest areas in mathematical biology, has significantly enhanced our understanding of how pathogens emerge, evolve, and spread. Classical epidemiological models, the standard for predicting and managing the spread of infectious disease, assume that contacts between susceptible and infectious individuals depend on their relative frequency in the population. The behavioral factors that underpin contact rates are not generally addressed. There is, however, an emerging a class of models that addresses the feedbacks between infectious disease dynamics and the behavioral decisions driving host contact. Referred to as “economic epidemiology” or “epidemiological economics,” the approach explores the determinants of decisions about the number and type of contacts made by individuals, using insights and methods from economics. We show how the approach has the potential both to improve predictions of the course of infectious disease, and to support development of novel approaches to infectious disease management.
ContributorsPerrings, Charles (Author) / Castillo-Chavez, Carlos (Author) / Chowell-Puente, Gerardo (Author) / Daszak, Peter (Author) / Fenichel, Eli P. (Author) / Finnoff, David (Author) / Horan, Richard D. (Author) / Kilpatrick, A. Marm (Author) / Kinzig, Ann (Author) / Kuminoff, Nicolai (Author) / Levin, Simon (Author) / Morin, Benjamin (Author) / Smith, Katherine F. (Author) / Springborn, Michael (Author) / Simon M. Levin Mathematical, Computational and Modeling Sciences Center (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor) / School of Human Evolution and Social Change (Contributor) / W.P. Carey School of Business (Contributor) / Economics (Contributor) / Julie Ann Wrigley Global Institute of Sustainability (Contributor)
Created2015-12-01
Description
In eukaryotes, most messenger RNA precursors (pre-mRNA) undergo extensive processing, leading to the cleavage of the transcript followed by the addition of a poly(A) tail. This process is executed by a large complex known as the Cleavage and Polyadenylation Complex (CPC). Its central subcomplex, the Cleavage and Polyadenylation Specificity Factor (CPSF) complex is responsible for recognizing a short hexameric element AAUAAA located at the 3’end in the nascent mRNA molecule and catalyzing the pre-mRNA cleavage. In the round nematode C. elegans, the cleavage reaction is executed by a subunit of this complex named CPSF3, a highly conserved RNA endonuclease. While the crystal structure of its human ortholog CPSF73 has been recently identified, we still do not understand the molecular mechanisms and sequence specificity used by this protein to induce cleavage, which in turn would help to understand how this process is executed in detail. Additionally, we do not understand in additional factors are needed for this process. In order to address these issues, we performed a comparative analysis of the CPSF3 protein in higher eukaryotes to identify conserved functional domains. The overall percent identities for members of the CPSF complex range from 33.68% to 56.49%, suggesting that the human and C. elegans orthologs retain a high level of conservation. CPSF73 is the protein with the overall highest percent identity of the CPSF complex, with its active site-containing domain possessing 74.60% identity with CPSF3. Additionally, we gathered and expressed using a bacterial expression system CPSF3 and a mutant, which is unable to perform the cleavage reaction, and developed an in vitro cleavage assay to test whether CPSF3 activity is necessary and sufficient to induce nascent mRNA cleavage. This project establishes tools to better understand how CPSF3 functions within the CPC and sheds light on the biology surrounding the transcription process as a whole.
ContributorsGallante, Christina (Author) / Mangone, Marco (Thesis director) / Sharma, Shalini (Committee member) / Hrach, Heather (Committee member) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
The number of cancer survivors in the United States is growing rapidly and it is expected to double by 2040. Arizona is nationally ranked with the 14th highest number of survivors, many of which experience a wide range of persisting medical complications that result from the cancer and associated treatment. Consequently, there is an increased need for services tailored to the health and wellness of survivors. Studies have shown that exercise rehabilitation is effective in improving the physical and mental health of this patient population. This project aimed to investigate the status of medically-based exercise rehabilitation for cancer survivors in Arizona. It focused on services offered by cancer treatment centers and cardiac rehabilitation clinics, with cardiac rehabilitation providing a possible delivery method for future cancer exercise rehabilitation. A directory of resources was compiled based on responses to structured telephone interviews with the cancer treatment centers (n=32) and cardiac rehabilitation clinics (n=34) within the state. The directory will serve as a resource for both patients and clinicians by identifying statewide related services that are available at the medical institutions and within the community. Results showed that 42.9% and 39.4% of the cancer treatment centers and cardiac rehabilitation clinics, respectively, offered exercise related services for cancer survivors. 78.6% of cancer centers stated that they refer cancer survivors to physical therapy, while only 35.7% refer survivors to community-based programs. Only 2 cardiac rehabilitation clinics, or 6%, offered preventative cardiology exercise consultations to cancer survivors. In conclusion, rehabilitative exercise resources for cancer survivors in Arizona were limited. Additional cancer rehabilitation efficacy studies are needed to further clarify evidence-based practice guidelines and provide direction for optimal methods of healthcare delivery. It is recommended that this directory remains current with routine updates in an effort to increase patient accessibility to care.
ContributorsHitt, Ellen (Author) / Scales, Robert (Thesis director) / Huberty, Jennifer (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-12
Description
The successful reduction of CO2 and protons by a light-induced cobalt porphyrin/cytb562 hybrid metalloenzyme in water is reported. Incorporation of the porphyrin into a protein scaffold results in increases in CO and H2 production over naked porphyrin. Rational point mutations to the CoPPIX binding site of cytb562 modulate production, indicating possible further improvements in catalytic activity.
ContributorsGwerder, Noah D (Author) / Ghirlanda, Giovanna (Thesis director) / Williams, Peter (Committee member) / Mangone, Marco (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Duchenne muscular dystrophy (DMD) is a lethal, X-linked disease which occurs in approximately 1 in 3,500 male births. This disease is characterized by progressive muscle wasting and causes premature death. One of the earliest symptoms of this disease is mitochondrial dysfunction. Dystrophin is a protein found under the sarcolemma. The N terminus binds to actin and the C terminus binds to dystrophin glycoprotein complex (DGC). DMD is caused by mutations in the dystrophin gene. C. elegans possess an ortholog of dystrophin, DYS-1. Though there is evidence that C. elegans can be used as a model organism to model DMD, nematode DGC has not been well characterized. Additionally, while we know that mitochondrial dysfunction has been found in humans and other model organisms, this has not been well defined in C. elegans. In order to address these issues, we crossed the SJ4103 worm strain (myo-3p::GFP(mit)) with dys-1(cx18) in order to visualize and quantify changes in mitochondria in a dys-1 background. SJ4103;cx18 nematodes were found to have less mitochondrial than SJ4103 which suggests mitochondrial dysfunction does occur in dys-1 worms. Furthermore, mitochondrial dysfunction was studied by knocking down members of the DGC, dys-1, dyb-1, sgn-1, sgca-1, and sgcb-1 in SJ4103 strain. Knock down of each gene resulted in decrease in abundance of mitochondria which suggests that each member of the DGC contributes to the overall health of nematode muscle. The ORF of dyb-1 was successfully cloned and tagged with GFP in order to visualize this DGC member C. elegans. Imaging of the transgenic dyb-1::GFP worm shows green fluoresce expressed in which suggests that dyb-1 is a functional component of the muscle fibers. This project will enable us to better understand the effects of dystrophin deficiency on mitochondrial function as well as visualize the expression of certain members of the DGC in order to establish C. elegans as a good model organism to study this disease.
ContributorsObrien, Shannon Nishino (Author) / Mangone, Marco (Thesis director) / Newbern, Jason (Committee member) / Hrach, Heather (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05