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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

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
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Description
Physician-assisted suicide occurs when a physician facilitates a patient's death by prescribing a lethal medication that they understand will be used for the purpose of ending the patient's life. It is a highly contentious subject and, with the recent addition of California to the list of states that allow physician-assisted

Physician-assisted suicide occurs when a physician facilitates a patient's death by prescribing a lethal medication that they understand will be used for the purpose of ending the patient's life. It is a highly contentious subject and, with the recent addition of California to the list of states that allow physician-assisted suicide, is an increasingly relevant subject. Physician-assisted suicide is rarely framed as a healthcare experience, despite being a choice in the process of end-of-life care. The research seeks to bring together the debates about physician-assisted suicide with conversations about health care experiences. The experiences and perspectives of young people are particularly valuable to evaluate now, as their voices will soon be the leaders in the debate over physician-assisted suicide. Within this research, there is an underlying theme of independence of individuals that is present through both the literature review and the body of data collected and analyzed. The study found that there was no significant relationship between the quality of a person's healthcare and their perspectives about physician-assisted suicide.
ContributorsMoeur, Katherine Elizabeth (Author) / Brian, Jennifer (Thesis director) / Graff, Sarah (Committee member) / Stevenson, Christine (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
This study investigates how the patient-provider relationship between lesbian, gay, and bisexual women and their healthcare providers influences their access to, utilization of, and experiences within healthcare environments. Nineteen participants, ages 18 to 34, were recruited using convenience and snowball sampling. Interviews were conducted inquiring about their health history and

This study investigates how the patient-provider relationship between lesbian, gay, and bisexual women and their healthcare providers influences their access to, utilization of, and experiences within healthcare environments. Nineteen participants, ages 18 to 34, were recruited using convenience and snowball sampling. Interviews were conducted inquiring about their health history and their experiences within the healthcare system in the context of their sexual orientation. The data collected from these interviews was used to create an analysis of the healthcare experiences of those who identify as queer. Although the original intention of the project was to chronicle the experiences of LGB women specifically, there were four non-binary gender respondents who contributed interviews. In an effort to not privilege any orientation over another, the respondents were collectively referred to as queer, given the inclusive and an encompassing nature of the term. The general conclusion of this study is that respondents most often experienced heterosexism rather than outright homophobia when accessing healthcare. If heterosexism was present within the healthcare setting, it made respondents feel uncomfortable with their providers and less likely to inform them of their sexuality even if it was medically relevant to their health outcomes. Gender, race, and,socioeconomic differences also had an effect on the patient-provider relationship. Non-binary respondents acknowledged the need for inclusion of more gender options outside of male or female on the reporting forms often seen in medical offices. By doing so, medical professionals are acknowledging their awareness and knowledge of people outside of the binary gender system, thus improving the experience of these patients. While race and socioeconomic status were less relevant to the context of this study, it was found that these factors have an affect on the patient-provider relationship. There are many suggestions for providers to improve the experiences of queer patients within the healthcare setting. This includes nonverbal indications of acknowledgement and acceptance, such as signs in the office that indicate it to be a queer friendly space. This will help in eliminating the fear and miscommunication that can often happen when a queer patient sees a practitioner for the first time. In addition, better education on medically relevant topics to queer patients, is necessary in order to eliminate disparities in health outcomes. This is particularly evident in trans health, where specialized education is necessary in order to decrease poor health outcomes in trans patients. Future directions of this study necessitate a closer look on how race and socioeconomic status have an effect on a queer patient's relationship with their provider.
Created2016-05
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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

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
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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

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
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Description
Healthcare systems and health insurance are both concepts implemented in every country to provide access to the general population. Countries undergo healthcare reforms in order to increase the performance of the system. In 2010, the Affordable Care Act (ACA) was introduced in the United States to increase coverage and create

Healthcare systems and health insurance are both concepts implemented in every country to provide access to the general population. Countries undergo healthcare reforms in order to increase the performance of the system. In 2010, the Affordable Care Act (ACA) was introduced in the United States to increase coverage and create a more inclusive health insurance market. For comparison, the recent reforms in Chile and Singapore were observed as points to determine what concepts work well and what can be implemented in the U.S. system. Unlike the United States, Chile and Singapore completely altered the system that was previously in use. In Chile, the reforms began in the 1970s and made two more major changes in 1973 and early 2000s. Singapore began its reform in the 1960s and created the medical savings account system that is still in use today. To analyze the system further, the medical professions of neurology, physician assistants and optometry were compared in each country. In regards to neurology, the coverage of services in Chile and Singapore are similar in that select medical procedures are covered. In contrast, the United States offers coverage on a case-by-case basis. For physician assistants, such a profession does not exist in Chile or Singapore. In the United States, the profession is rapidly expanding, and coverage is offered for most services provided. Optometry is a stand-alone profession in both the U.S. and Singapore. The services provided by the optometrists are selectively covered by insurance, depending on whether it is considered a medical problem. Chile covers the services often provided by optometrists, however, the ophthalmologist is the provider, as optometry does not exist. This study concluded that the U.S. should continue to provide a more inclusive healthcare system that includes vision and dental care. The U.S., like Singapore, should also adopt a more integrative system. Under this system, patient care would be provided in a way that professionals specializing in the care are included in every step of the process.
ContributorsLa, Jenny (Co-author) / Feruj, Farihah (Co-author) / Morrison, Sarah (Co-author) / Gaughan, Monica (Thesis director) / Essary, Alison (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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Description
The introduction of novel information technology within contemporary healthcare settings presents a critical juncture for the industry and thus lends itself to the importance of better understanding the impact of this emerging "health 2.0" landscape. Simply, how such technology may affect the healthcare system is still not fully realized, despite

The introduction of novel information technology within contemporary healthcare settings presents a critical juncture for the industry and thus lends itself to the importance of better understanding the impact of this emerging "health 2.0" landscape. Simply, how such technology may affect the healthcare system is still not fully realized, despite the ever-growing need to adopt it in order to serve a growing patient population. Thus, two pertinent questions are posed: is HIT useful and practical and, if so, what is the best way to implement it? This study examined the clinical implementation of specific instances of health information technology (HIT) so as to weigh its benefits and risks to ultimately construct a proposal for successful widespread adoption. Due to the poignancy of information analysis within HIT, Information Measurement Theory (IMT) was used to measure the effectiveness of current HIT systems as well as to elucidate improvements for future implementation. The results indicate that increased transparency, attention to patient-focused approaches and proper IT training will not only allow HIT to better serve the community, but will also decrease inefficient healthcare expenditure.
ContributorsMaietta, Myles Anthony (Author) / Kashiwagi, Dean (Thesis director) / Kashiwagi, Jacob (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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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

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
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Description
With advances in biotechnology, personalized medicine has become an ever-expanding field. Even with so much growth, the critics equally match the proponents of personalized medicine. The source of their disagreement is rooted in the concept of empowerment. This analysis utilizes the personal genomics company 23andMe and their relationship with the

With advances in biotechnology, personalized medicine has become an ever-expanding field. Even with so much growth, the critics equally match the proponents of personalized medicine. The source of their disagreement is rooted in the concept of empowerment. This analysis utilizes the personal genomics company 23andMe and their relationship with the Federal Food and Drug Administration to illustrate varying views of empowerment. Specifically, the case study focuses on the ability to provide direct-to-consumer health reports to patients independent of physicians. In doing this, larger issues of what is at stake in personalized medicine are uncovered. These include but are not limited to: who determines what individuals get empowered and what information is determined good versus bad.
ContributorsSilverman, Adam Mattern (Author) / Brian, Jennifer (Thesis director) / Hurlbut, Ben (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Department of Psychology (Contributor)
Created2015-05
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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

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