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- Creators: School of Life Sciences
Description
This study focused on the connection between the EnvZ/OmpR two-component regulatory system and the iron homeostasis system in Escherichia coli, specifically how a mutant form of EnvZ11/OmpR is able to reduce the expression of fepA::lacZ, a reporter gene fusion in E. coli. FepA is one of several outer membrane siderophore receptors that allow extracellular siderophores bound to iron to enter the cells to power various biological processes. Previous studies have shown that in E. coli cells that expressed a mutant allele of envZ, called envZ11, which led to altered expression of various iron genes including down regulation of fepA::lacZ. The wild type EnvZ/OmpR system is not considered to regulate iron genes, but because these envz11 strains had downregulated fepA::lacZ, this study was undertaken to understand the connection and mechanisms of this downregulation. A large number of Lac+ revertants were obtained from the B32-2483 strain (envz11 and fepA::lacZ) and 7 Lac+ revertants that had reversion mutations not directly correcting the envZ11 allele were further characterized. With P1 phage transduction genetic mapping that involved moving a kanamycin resistance marker linked to fepA::lacZ, two Lac+ revertants were found to have their reversion mutations in the fepA promoter region, while the other five revertants had their mutations mapping outside the fepA region. These two revertants underwent DNA sequencing and found to carry two different single base pair mutations in two different locations of the fepA promoter region. Each one is in the Fur repressor binding region, but one also may have affected the Shine-Dalgarno region involved in translation initiation. All 7 reveratants underwent beta-galactosidase assays to measure fepA::lacZ expression. The two revertants that had mutations in the fepA promoter region had significantly increased fepA activity, with the revertant with the Shine-Dalgarno mutation having the most elevated fepA expression. The other 5 revertants that did not map in the fepA region had fepA expression elevated to the same level as that found in the wild type EnvZ/OmpR background. The data suggest that the negative effect of envZ11 can be overcome by multiple mechanisms, including directly correcting the envZ11 allele or changing the fepA promoter region.
ContributorsKalinkin, Victor Arkady (Co-author) / Misra, Rajeev (Co-author, Thesis director) / Mason, Hugh (Committee member) / Foy, Joseph (Committee member) / Biomedical Informatics Program (Contributor) / School of Life Sciences (Contributor) / W. P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Students Organize for Syria (SOS) is the student led initiative for Syria. With 18 registered chapters across the United States, this student organization is targeting a multidimensional cause by different means. Though it is now a national movement, it started off with one group at Arizona State University, with one student. Zana Alattar, founder and student director of SOS, tells the story of how she took an ASU organization, Save Our Syrian Freedom (SOS Freedom), to the national level as SOS. As a pre-medical student, she also combines her work in human rights with her future in healthcare. After all, health and human rights have long maintained a synergistic relationship.
ContributorsAlattar, Zana (Author) / Graff, Sarah (Thesis director) / McClurg, Sharolyn (Committee member) / School of Molecular Sciences (Contributor) / School of Social Transformation (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Mammary gland development in humans during puberty involves the enlargement of breast tissue, but this is not true in non-human primates. To identify potential causes of this difference, I examined variation in substitution rates across genes related to mammary development. Genes undergoing purifying selection show slower-than-average substitution rates, while genes undergoing positive selection show faster rates. These may be related to the difference between humans and other primates. Three genes were found to be accelerated were FOXF1, IGFBP5, and ATP2B2, but only the latter one was found in humans and it seems unlikely that it would be related to the differences between mammary gland development at puberty between humans and non-human primates.
ContributorsArroyo, Diana (Author) / Cartwright, Reed (Thesis director) / Wilson Sayres, Melissa (Committee member) / Schwartz, Rachel (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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
Human subject research is a sensitive ethical topic in today's society, and with good cause. The history of human subject research is full of tragedy and wrongdoing, which is what has led to the firm restrictions we presently have. At the same time, we also acknowledge the value behind human subject research and the information science can obtain from such endeavors. This project analyzes this conundrum through a narrative describing a group of scientists who choose to ignore some of the laws and regulations concerning human subject research in order to pursue neurological based research for a "greater good." In the novella, the scientists end up harming several people while performing their illegal research, but are able to obtain successful results. However, the group is eventually caught, and end up having to face the consequences of their actions. The situations and interactions the story presents are meant to juxtapose both sides of the human subject research ethical argument in a unique way in order to allow the reader to critically think through the argument themselves and form their own opinions on the matter.
ContributorsPirotte, Benjamin Daniel (Author) / Finn, Edward (Thesis director) / Cook, Paul (Committee member) / McGregor, Joan (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Historical, Philosophical and Religious Studies (Contributor)
Created2015-05
Description
In this study, we propose and then assess the efficacy of a new approach to static suspension to correct for facial paralysis. Our method involves placing barbed sutures through the superficial muscular aponeurotic system (SMAS) and anchoring them in the temporal fascia parallel to the underlying facial muscles. We first analyzed the ability of this procedure to improve facial symmetry by comparing the degree of asymmetry between the paralyzed and unaffected sides of a patient's face (N=10) prior to and following surgery. Then, to determine if symmetry is improved as a result of placing the sutures parallel to the direction of facial muscle forces, we measured the vectors of levator labii superioris and zygomaticus major in cadaver hemifaces (N=3) and compared them to the angles of the vectors of correction from the patient sample to angles of muscle vectors in three facial hemispheres from cadaver controls. Results indicate that: (1) facial symmetry was significantly improved in these patients and (2) this improvement. We conclude that, compared to existing protocols, our novel surgical method is a better means of static suspension for reconstruction following onset of facial paralysis as it is simple to perform, easy to replicate, able to be post-operatively adjusted in-office, has a good long-term prognosis, and, as we have demonstrated, effectively corrects the appearance of asymmetry by working with the underlying facial anatomy.
ContributorsLeach, Garrison Alecsander (Co-author) / Joganic, Jessica (Co-author) / Hooft, Nicole (Co-author) / Joganic, Edward (Co-author, Committee member) / Foy, Joseph (Thesis director) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The Dorrance Center for Rare Childhood Disorders is a unique research division at TGen (The Translational Genomics Research Institute) that provides personalized care to children and young adults facing rare, undiagnosed diseases. TGen scientists believe that the answers to these enigmatic disorders can often be found in a person's genetic code. They aim to solve these genetic mysteries using whole exome sequencing, a method that prioritizes the protein-coding portion of the genome in the search for disease-causing variants. Unfortunately, a communication gap sometimes exists between the TGen scientists and the patients they serve. I have seen, first hand, the kind of confusion that this study elicits in the families of its participants. Therefore, for my thesis, I decided to create a booklet that is meant to provide some clarity as to what exactly The Dorrance Center for Rare Childhood Disorders does to help diagnose children with rare disorders. The purpose of the booklet is to dispel any confusion regarding the study by providing a general review of genetics and an application of these lessons to the relevant sequencing technology as well as a discussion of the causes and effects of genetic mutations that often times are linked to rare childhood disorders.
ContributorsCambron, Julia Claire (Author) / LaBelle, Jeffrey (Thesis director) / Huentelman, Matt (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Schizophrenia affects 1.1% of the population worldwide. Schizophrenia is a complex, multifactorial disorder. Stress can trigger psychotic episodes and exacerbate schizophrenic symptoms. For humans, one gene implicated in stress and schizophrenia in humans is the early growth response 3 (EGR3). Patients with genomic variations in EGR3 have reduced levels of EGR3 in the prefrontal brain region compared with healthy patients. Schizophrenic patients also have less serotonin 2A receptor (5HT2AR), which is coded by the gene Htr2a, in their prefrontal cortex. Mice that are Egr3-deficient also have decreased levels of 5HT2AR, suggesting that Egr3 may be involved in the regulation of 5HT2AR. The purpose of the experiment is to determine if EGR3 binds to the Htr2a gene promoter region by using a Chromatin immunoprecipitation (ChIP) assay. We will use ECS to increase EGR3 expression. Previously we have identified two upstream sites of interest where EGR3 potentially binds to the Htr2a gene, one which is distal and one proximal to the transcription start site. After ECS, increased binding is seen in the Htr2a distal region with EGR3 via the ChIP assay. Increased binding was not observed at either of the promoter sites; however, the t-test comparing the distal site of the ECS and the No ECS groups to have a p-value of 0.056, suggesting that increasing the number of animals (n=7) could possibly give a more accurate representation to test our hypothesis. However, the experiment still suggests increased expression and that EGR3 may bind to the distal site of Htr2a. Keywords: stress, environment, genetics, schizophrenia, EGR3, chromatin immunoprecipitation
ContributorsMishra, Abhinav (Author) / Buetow, Kenneth (Thesis director) / Gallitano, Amelia (Committee member) / Zhao, Xiuli (Committee member) / Barrett, The Honors College (Contributor) / School of Politics and Global Studies (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Curative arts and art therapy have been increasingly implicated in promoting health and well-being for patients, but little research has been done for the benefits of drawing therapy for stress management or individuals in a non-diseased state. College students and healthcare professionals are particularly susceptible to high levels of stress, as I experienced firsthand as a medical scribe in the Emergency Room during my undergraduate experience. For this reason, I wanted to focus on using curative arts as a mediator for high-stress situations. My creative project is therefore a portable framework for curative drawing. The framework is designed to help people process complex emotional states in a more effective way using mark-making and color. Specifically, the framework is designed for those who have limited experience with art making but can be used by anyone who feels a need for curative drawing. I used this framework in both individual and group settings, culminating in a final gallery show in which viewers were able to participate in the framework and take home a booklet with the framework printed inside. In conjunction with outside research, the help of my thesis committee, and the students of Drawing and Painting as Seeing and Thinking, the final project can be viewed as one part of the intersection between art and medicine in our ever-changing healthcare environment.
ContributorsCadigan, Megan Sierra (Author) / Button, Melissa (Thesis director) / Belgrave, Melita (Committee member) / School of Art (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Influenza is a deadly disease for which effective vaccines are sorely lacking. This is largely due to the phenomena of antigenic shift and drift in the influenza virus's surface proteins, hemagglutinin (HA) and neuraminidase (NA). The ectodomain of the matrix 2 protein (M2e) of influenza A, however, has demonstrated high levels of conservation. On its own it is poorly immunogenic and offers little protection against influenza infections, but by combining it with a potent adjuvant, this limitation may be overcome. Recombinant immune complexes, or antigens fused to antibodies that have been engineered to form incredibly immunogenic complexes with one another, were previously shown to be useful, immunogenic platforms for the presentation of various antigens and could provide the boost in immunogenicity that M2e needs to become a powerful universal influenza A vaccine. In this thesis, genetic constructs containing geminiviral replication proteins and coding for a consensus sequence of dimeric M2e fused to antibodies featuring complimentary epitopes and epitope tags were generated and used to transform Agrobacterium tumefaciens. The transformed bacteria was then used to cause Nicotiana benthamiana to transiently express M2e-RICs at very high levels, with enough RICs being gathered to evaluate their potency in future mouse trials. Future directions and areas for further research are discussed.
ContributorsFavre, Brandon Chetan (Author) / Mason, Hugh (Thesis director) / Mor, Tsafrir (Committee member) / Diamos, Andrew (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05