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Description
Alzheimer’s Disease (AD) affects over 5 million individuals in the U.S. and has a direct cost estimated in excess of $200 billion per year. Broadly speaking, there are two forms of AD—early-onset, familial AD (FAD) and late-onset-sporadic AD (SAD). Animal models of AD, which rely on the overexpression of FAD-related mutations, have provided important insights into the disease. However, these models do not display important disease-related pathologies and have been limited in their ability to model the complex genetics associated with SAD.
Advances in cellular reprogramming, have enabled the generation of in vitro disease models that can be used to dissect disease mechanisms and evaluate potential therapeutics. To that end, efforts by many groups, including the Brafman laboratory, to generated patient-specific hiPSCs have demonstrated the promise of studying AD in a simplified and accessible system. However, neurons generated from these hiPSCs have shown some, but not all, of the early molecular and cellular hallmarks associated with the disease. Additionally, phenotypes and pathological hallmarks associated with later stages of the human disease have not been observed with current hiPSC-based systems. Further, disease relevant phenotypes in neurons generated from SAD hiPSCs have been highly variable or largely absent. Finally, the reprogramming process erases phenotypes associated with cellular aging and, as a result, iPSC-derived neurons more closely resemble fetal brain rather than adult brain.
It is well-established that in vivo cells reside within a complex 3-D microenvironment that plays a significant role in regulating cell behavior. Signaling and other cellular functions, such as gene expression and differentiation potential, differ in 3-D cultures compared with 2-D substrates. Nonetheless, previous studies using AD hiPSCs have relied on 2-D neuronal culture models that do not reflect the 3-D complexity of native brain tissue, and therefore, are unable to replicate all aspects of AD pathogenesis. Further, the reprogramming process erases cellular aging phenotypes. To address these limitations, this project aimed to develop bioengineering methods for the generation of 3-D organoid-based cultures that mimic in vivo cortical tissue, and to generate an inducible gene repression system to recapitulate cellular aging hallmarks.
Advances in cellular reprogramming, have enabled the generation of in vitro disease models that can be used to dissect disease mechanisms and evaluate potential therapeutics. To that end, efforts by many groups, including the Brafman laboratory, to generated patient-specific hiPSCs have demonstrated the promise of studying AD in a simplified and accessible system. However, neurons generated from these hiPSCs have shown some, but not all, of the early molecular and cellular hallmarks associated with the disease. Additionally, phenotypes and pathological hallmarks associated with later stages of the human disease have not been observed with current hiPSC-based systems. Further, disease relevant phenotypes in neurons generated from SAD hiPSCs have been highly variable or largely absent. Finally, the reprogramming process erases phenotypes associated with cellular aging and, as a result, iPSC-derived neurons more closely resemble fetal brain rather than adult brain.
It is well-established that in vivo cells reside within a complex 3-D microenvironment that plays a significant role in regulating cell behavior. Signaling and other cellular functions, such as gene expression and differentiation potential, differ in 3-D cultures compared with 2-D substrates. Nonetheless, previous studies using AD hiPSCs have relied on 2-D neuronal culture models that do not reflect the 3-D complexity of native brain tissue, and therefore, are unable to replicate all aspects of AD pathogenesis. Further, the reprogramming process erases cellular aging phenotypes. To address these limitations, this project aimed to develop bioengineering methods for the generation of 3-D organoid-based cultures that mimic in vivo cortical tissue, and to generate an inducible gene repression system to recapitulate cellular aging hallmarks.
ContributorsBounds, Lexi Rose (Author) / Brafman, David (Thesis director) / Wang, Xiao (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Genetic manipulation of human cell lines has widespread applications in biomedical research ranging from disease modeling to therapeutic development. Human cells are generally difficult to genetically engineer, but exogenous nucleic acids can be expressed by viral, chemical, or nonchemical means. Chemical transfections are simpler in practice than both viral and nonchemical delivery of genetic material, but often suffer from cytotoxicity and low efficiency. Novel aminoglycoside antibiotic-derived lipopolymers have been synthesized to mediate transgene delivery to human cells. These polymers are comprised of either paromomycin or apramycin crosslinked with glycerol diglycidylether and derivatized with stearoyl chloride in varying molar ratios. In this work, three previously identified target lipopolymers were screened against a library of human embryonic and induced pluripotent stem cell lines. Cells were transfected with a plasmid encoding green fluorescent protein (GFP) and expression was quantified with flow cytometry 48 hours after transfection. Transfection efficiency was evaluated between three distinct lipopolymers and four lipopolymer:DNA mass ratios. GFP expression was compared to that of cells transfected with commercially available chemical gene delivery reagent controls\u2014JetPEI, Lipofectamine, and Fugene\u2014at their recommended reagent:DNA ratios. Improved transgene expression in stem cell lines allows for improved research methods. Human stem cell-derived neurons that have been genetically manipulated to express phenotypic characteristics of aging can be utilized to model neurodegenerative diseases, elucidating information about these diseases that would be inaccessible in unmanipulated tissue.
ContributorsMehta, Frea (Author) / Brafman, David (Thesis director) / Rege, Kaushal (Committee member) / Chemical Engineering Program (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
This is the study of Acute Impact of Ujjayi Yogic Pranayama vs Aerobic Exercise on Cognitive Performance and Short Term Memory. The purpose of this research was to compare two forms of exercise and their effects on someone's cognitive performance and short term memory. The research was performed in an acute setting were both exercises was conducted in under 15 minutes of active participation. The research question was; will aerobic exercise or the Pranayama breathing exercise provide better results and demonstrate a more effective way to increase the cognitive performance and short term memory for a college student aged 18-30. This was accomplished by using an aerobic exercise on an elliptical machine and then participating in the breathing exercise for 10 minutes in both scenarios. This study had two scenarios. Each scenario had a preliminary cognitive performance and short-term memory, post-Ujjayi exercise had a cognitive performance and short-term memory and a post-aerobic exercise had a cognitive performance and short-term memory. There was an hour break between Ujjayi exercise and aerobic exercise in both scenarios to prevent any type of bias. Scenario 1 had these three settings but the students were not given a breakfast supplement. In Scenario 2 the students were given a break supplement and followed the same procedures as scenario 1. There were 25 students for scenario 1 and 25 students for scenario 2. The students were allowed to participate in scenario 1 and 2 but it had to be a week after their first participation. All participants were originally signed up for scenario 1 and they could come back to perform scenario 2 a week later. The first scenario was completing the tests in the absence of food. Scenario two was completing the tests after having been given a Clif Bar to consume. The results of both of these scenarios showed that for cognitive performance and short term memory aerobic exercise had a beneficial impact on their performance. However, students who had a breakfast performed better on the preliminary tests and scored better after the yogic Ujjayi Pranayama exercise on their cognitive performance and short term memory tests. There was also a negligible difference between the test results after the preliminary tests and yogic Ujjayi Pranayama. However, in scenario one the overall tests scores for preliminary and yogic Ujjayi Pranayama were less than those in scenario two. Students who recorded that they were more actively engaging in regular physical exercise 3-7 days a week also did worse in scenario 1, but when presented with scenario 2 they scored equal with those who did not perform regular exercise. The overall purpose for this research was to find out how to increase cognitive performance and short term memory ability in college age students 18-30 in a short amount of time. The results of this study will be impactful for the future studies that will be focused on when comparing aerobic exercise and yogic pranayama.
ContributorsKopecky, Zachary (Co-author) / Enright, Roan (Co-author) / McILwraith, Heide (Thesis director) / Lee, Rebecca (Committee member) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
This study confirms that there is stigma attached to how Somali-Americans perceive mental and emotional impairments compared to the perception of physical disabilities and impairments. More Somali-Americans are willing to seek help regarding their mental and physical health which is a positive step in improving the perceptions of Somali-Americans towards mental or emotional impairments and physical disabilities. Findings can contribute to the knowledge of health care professionals (i.e. nurses) in caring for patients identifying as Somali to promote culturally competent care.
ContributorsAden, Amina (Author) / Hosley, Brenda (Thesis director) / Lee, Rebecca (Committee member) / Lyles, Annmarie (Committee member) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Insects have intricate systems they depend on for survival. They live in societies where every individual plays an important role. Ants are a great example of this observation. They are known for having structurally sound societies that ensure the livelihood of the colony. The ant species analyzed for this research, Harpegnathos saltator, portrays a structured colony and serves as a useful example of levels of hierarchy. In the colony of H. saltator, one can find a queen, gamergates, workers, and male ants living underground in Southern India. Recording and analyzing egg-laying rates are important in this study because of the amount of information it provides. It is used especially when observing the relationship among the gamergates in colonies with varying colony sizes. Three different methods were used to record the egg-laying rates, each providing insight into valuable information. Results show that the smaller colonies with fewer identified gamergates do share an equal amount of egg-laying. In larger colonies, it appears that there are more active identified gamergates than others. Egg-laying duration times are smaller in colonies with fewer gamergates. It is also found that the presence of brood does not affect egg-laying rates and reproductive inhibition could be a possibility based on two of the colonies observed F65 and F21. Based on the data found, a more active colony that attempts to maintain stability by demonstrating aggression may be affecting the reproduction of gamergates. Future work that would further strengthen the research and conclusions made would involve further observation of colonies, both large and small, with varying numbers of gamergates. More observation involving behavior among gamergates and workers would also be beneficial. Mathematical modeling could also be incorporated to create equations that could determine information about colonies based on size, number of gamergates, and egg-laying rates.
ContributorsMayoral, Alejandra (Author) / Kang, Yun (Thesis director) / Liebig, Juergen (Committee member) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
the project led by Professor Emma Frow, researching of stem cell clinics focused on stem cell applications, adherence to FDA guidelines, and characterization of information available and physician credentials. Regenerative medicine clinics commonly offered stem cell therapy, but introduced platelet rich plasma (PRP) and prolotherapy as regenerative therapies.
PRP and Prolotherapy are individual treatments that were even suggested and used in combination with stem cell therapies. Prolotherapy predates PRP as a chemical irritant therapy originally used to sclerose tissues. Prolotherapy is meant to stimulate platelet derived growth factors release to improve tissue healing response. Prolotherapy shows negligible efficacy improvements over corticosteroids, but may have underlying side effects from being an irritant. PRP is a more modern therapy for improved healing. Speculations state initial use was in an open heart surgery to improve healing post-surgery. PRP is created via centrifugation of patient blood to isolate growth factors by removing serum and other biological components to increase platelet concentration. PRP is comparable to corticosteroid injections in efficacy, but as an autologous application, there are no side effects making it more advantageous. Growth factors induce healing response and reduce inflammation. Growth factors stimulate cell growth, proliferation, differentiation, and stimulate cellular response mechanism such as angiogenesis and mitogenesis. The growth factor stimulation of PRP and prolotherapy both assist stem cell proliferation. Additional research is needed to determine differential capacity to ensure multipotent stem cells regenerate the correct cell type from the increased differential capacity offered by growth factor recruitment. The application of combination therapy for stem cells is unsubstantiated and applications violate FDA ‘minimal manipulation’ guidelines.
PRP and Prolotherapy are individual treatments that were even suggested and used in combination with stem cell therapies. Prolotherapy predates PRP as a chemical irritant therapy originally used to sclerose tissues. Prolotherapy is meant to stimulate platelet derived growth factors release to improve tissue healing response. Prolotherapy shows negligible efficacy improvements over corticosteroids, but may have underlying side effects from being an irritant. PRP is a more modern therapy for improved healing. Speculations state initial use was in an open heart surgery to improve healing post-surgery. PRP is created via centrifugation of patient blood to isolate growth factors by removing serum and other biological components to increase platelet concentration. PRP is comparable to corticosteroid injections in efficacy, but as an autologous application, there are no side effects making it more advantageous. Growth factors induce healing response and reduce inflammation. Growth factors stimulate cell growth, proliferation, differentiation, and stimulate cellular response mechanism such as angiogenesis and mitogenesis. The growth factor stimulation of PRP and prolotherapy both assist stem cell proliferation. Additional research is needed to determine differential capacity to ensure multipotent stem cells regenerate the correct cell type from the increased differential capacity offered by growth factor recruitment. The application of combination therapy for stem cells is unsubstantiated and applications violate FDA ‘minimal manipulation’ guidelines.
ContributorsKrum, Logan (Author) / Frow, Emma (Thesis director) / Brafman, David (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Current research into live-cell dynamics, particularly those relating to chromatin structure and remodeling, are limited. The tools that are used to detect state changes in chromatin, such as Chromatin Immunoprecipitation and qPCR, require that the cell be killed off. This limits the ability of researchers to pinpoint changes in live cells over a longer period of time. As such, there is a need for a live-cell sensor that can detect chromatin state changes. The Chromometer is a transgenic chromatin state sensor designed to better understand human cell fate and the chromatin changes that occur. HOXD11.12, a DNA sequence that attracts repressive Polycomb group (PCG) proteins, was placed upstream of a core promoter-driven fluorescent reporter (AmCyan fluorescent protein, CFP) to link chromatin repression to a CFP signal. The transgene was stably inserted at an ectopic site in U2-OS (osteosarcoma) cells. Expression of CFP should reflect the epigenetic state at the HOXD locus, where several genes are regulated by Polycomb to control cell differentiation. U2-OS cells were transfected with the transgene and grown under selective pressure. Twelve colonies were identified as having integrated parts from the transgene into their genomes. PCR testing verified 2 cell lines that contain the complete transgene. Flow cytometry indicated mono-modal and bimodal populations in all transgenic cell colonies. Further research must be done to determine the effectiveness of this device as a sensor for live cell state change detection.
ContributorsBarclay, David (Co-author) / Simper, Jan (Co-author) / Haynes, Karmella (Thesis director) / Brafman, David (Committee member) / School of Life Sciences (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Research supports that music therapy can be used in multiple aspects of care for patients living within different environments. There is a gap in the literature when it comes to the impact of music sessions for older adults who do not have a diagnosed disease, therefore this study analyzes this population specifically. This study examines music therapy and its effects on anxiety and depression in adults aged 65 or older living in independent living homes. The adults participated in a mixed-methods study over the span of one month examining music as an intervention to decrease anxiety and depression. Each subject consented into the study, completed a demographic survey, answered open-ended questions regarding their experience with anxiety/sadness and ways to cope, as well as Profile of Moods Scale (POMS) during the first session. On the last week of the study, the participants were asked to fill out the same POMS scale to evaluate whether music influenced anxiety and depression. There was limited evidence found in this study to support the use of music therapy as an intervention to decrease anxiety and depression in adults over the age of 65.
ContributorsWolfus, Sarah Ilyssa (Author) / Lee, Rebecca (Thesis director) / Larkey, Linda (Committee member) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The Centers for Disease Control and Prevention in the United States announced that there has been roughly a 50% increase in the prevalence of food allergies among people between the years of 1997 - 2011. A food allergy can be described as a medical condition where being exposed to a certain food triggers a harmful immune response in the body, known as an allergic reaction. These reactions can range from mild to fatal, and they are caused mainly by the top 8 major food allergens: dairy, eggs, peanuts, tree nuts, wheat, soy, fish, and shellfish. Food allergies mainly plague children under the age of 3, as some of them will grow out of their allergy sensitivity over time, and most people develop their allergies at a young age, and not when they are older. The rise in prevalence is becoming a frightening problem around the world, and there are emerging theories that are attempting to ascribe a cause. There are three well-known hypotheses that will be discussed: the Hygiene Hypothesis, the Dual-Allergen Exposure Hypothesis, and the Vitamin-D Deficiency Hypothesis. Beyond that, this report proposes that a new hypothesis be studied, the Food Systems Hypothesis. This hypothesis theorizes that the cause of the rise of food allergies is actually caused by changes in the food itself and particularly the pesticides that are used to cultivate it.
ContributorsCromer, Kelly (Author) / Lee, Rebecca (Thesis director) / MacFadyen, Joshua (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
Hematopoietic stem cell transplantation (HSCT) is a unique but intense procedure used to save the lives of patients with hematopoietic malignancies. However, patients and caregivers undergoing HSCT can experience prolonged psychological distress due to an intense and distinctive transplant process. Types of psychological distress include anxiety, depression, social isolation, and post-traumatic stress disorder. Although this a significant healthcare problem, limited research has been conducted within the HSCT patient and caregiver population to investigate ways to improve their mental health. The purpose of this study was to examine the effects of an educational video intervention about post-transplant recovery in decreasing emotional distress and promoting emotional well-being in HSCT patients and caregivers. This pilot study utilized a quantitative single-group pretest-posttest design to examine the effect of educational videos on participant's emotional well-being. Four educational videos were developed using information gathered from several reliable bone marrow transplant and cancer websites. A convenience sampling method was used to recruit HSCT patient and caregiver participants. Eleven Caucasian, English-speaking individuals (6 patients, 5 caregivers; 54.5% female; M age= 43.7 years) across the United States were enrolled in the 60-90 minute online intervention. Participant responses were measured using pretest and posttest questionnaires. Results from the study found that the educational videos were effective in decreasing levels of depression and anxiety. Implications for nursing practice include the need to educate HSCT patients and caregivers about transplant recovery to decrease emotional distress. This study demonstrates the impact post-transplant education has on decreasing depression and anxiety in HSCT patients and caregivers.
ContributorsBosselman, Kate Elizabeth (Author) / Kim, Sunny (Thesis director) / Lee, Rebecca (Committee member) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12