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Description
Pinpoint control over endogenous gene expression in vivo has long been a fevered dream for clinicians and researchers alike. With the recent repurposing of programmable, RNA-guided DNA endonucleases from the CRISPR bacterial immune system, this dream is becoming a powerful reality. Engineered CRISPR based transcriptional regulators have enabled researchers to perturb endogenous gene expression in vivo, allowing for the therapeutic reprogramming of cell and tissue behavior. However, for this technology to be of maximal use, a variety of technological hurdles still need to be addressed. Here, we discuss recent advances and integrative strategies that can help pave the way towards a new class of transcriptional therapeutics.
ContributorsPandelakis, Matthew (Author) / Ebrahimkhani, Mohammad (Thesis director) / Kiani, Samira (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
This study examined crayfish diet within varying hydrologic environment in lotic systems using stable isotope analysis of crayfish and basal resources to add depth to previous findings. Crayfish are numerous and are omnivorous, opportunistic feeders, feeding on invertebrates, vegetation and detritus. Arizona streams stand apart from the Eastern and Northwestern aquatic ecosystems of the United States because Arizona has no native crayfish species. Two species have been introduced and become widely established in Arizona (Orconectes virilis and Procambarus clarkii), with concern for further introduction of crayfish species and more information on how these two species impact the native species in the streams is needed. Previous studies have focused on crayfish abundance with hydrologic variation and crayfish diets within a lentic system, but few have focused on how the diet of consumers varies with hydrologic variability. Crayfish are hardy and have a dramatically increasing population within Arizona and therefore inhabit systems with a wide range of hydrologic variability which may contribute to spatial variability. The results show that crayfish diets do show a significant level of seasonal variation in some study locations, in both C source and trophic level. Hydrologic variation was also shown to impact crayfish diet at several study sites, with increasing magnitude of event (both floods and droughts) correlating with a change toward more aquatic C sources and lower trophic position in several of the study sites. In some locations, the correlation was not as strong with variation and diet change and showed less change in C source and rather showed an increase in trophic position.
ContributorsThompson, Sara Nicole (Author) / Sabo, John L. (Thesis director) / Grimm, Nancy (Committee member) / Baruch, Ethan M. (Committee member) / School of Geographical Sciences and Urban Planning (Contributor) / Dean, W.P. Carey School of Business (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
In cancer, various genetic and epigenetic alterations cause cancer cells to hyperproliferate and to bypass the survival and migration mechanisms that typically regulate healthy cells. The focal adhesion kinase (FAK) gene produces FAK, a protein that has been implicated in tumor progression in various cancers. Compared with normal tissue counterparts, FAK is overexpressed in many cancers. FAK is therefore a promising cancer drug target due to its demonstrated role in cancer invasion and metastasis and inhibition of FAK is important to achieve an optimal tumor response. Small molecule FAK inhibitors have been shown to decrease tumor growth and metastasis in several preclinical trials. However, these inhibitors focus narrowly on the enzymatic portion of FAK and neglect its scaffolding function, leaving FAK’s scaffolding of oncogenic drivers intact. Paxillin, a major focal adhesion-associated protein, binds to FAK, enabling it to localize to focal adhesions, and this is essential for FAK’s activation and function. Therefore, disrupting the protein-protein interaction between FAK and paxillin has been hypothesized to prevent tumor progression. The binding of FAK to paxillin at its focal adhesion targeting (FAT) domain is mediated by two highly conserved leucine-rich sequences, the leucine-aspartic acid (LD) motifs LD2 and LD4. The purpose of this project was to develop novel stapled LD2 peptide analogs that target the protein-protein interaction of FAT to LD2. Peptide stapling was performed to enhance the pharmacological performance of the LD2 peptide analogs. Based on the native LD2 peptide sequence, stapled LD2 peptide analogs were developed with the intent to improve efficacy of cell permeability, while maintaining or improving FAK binding. The LD2 peptide analogs were characterized via surface plasmon resonance, fluorescence polarization, immunofluorescence, and circular dichroism spectroscopy. Successful LD2 stapled peptide analogs can be therapeutically relevant inhibitors of the FAT-LD2 protein-protein interaction in cancer and have the potential for greater efficacy in FAK inhibition, proteolytic resistance, and cell permeability, which is key in preventing tumor progression in cancer.
ContributorsNott, Rohini (Author) / Gould, Ian R. (Thesis director) / Marlowe, Timothy A. (Committee member) / Cance, William G. (Committee member) / School of Life Sciences (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Swing dancing is a form of partnered dancing that has a focus on social interactions. The purpose of this study is to determine how social factors and intrinsic motivation effect how college age students perceive how much energy exertion swing dancing requires compared to traditional exercise. 20 ASU students were split into 10 female-male couples. The participants first completed a 30-minute session of social dancing and then a week later completed a 30-minute session of cycling on a stationary bike. Physiological data was collected using a Polar heart rate (HR) monitor wristwatch and chest strap. The HR of participants was taken after a period of rest and every five minutes during swing dancing and cycling. The rate of perceived exertion (RPE) was measured based on a Borg scale (6-20). RPE was taken after a period of rest and every five minutes during swing dancing and cycling. After both physiological sessions a psychological survey was distributed measuring the social factors of dancing, the intrinsic motivation of dancing, and the intrinsic motivation of traditional exercise. There was no significant difference between average HR during rest (p=0.34) or during the two types of exercises (p=0.26). There also was no significant difference in RPE during rest (p=0.33) or during the two types of exercises (p=0.46). At the same intensity participants perceived swing dancing to require as much energy exertion as cycling. Participants were significantly more intrinsically motivated to swing dance compared to traditional exercise. Participants reported high levels of social factors while swing dancing and these social factors had a moderately positive effect on intrinsic motivation for swing dancing. People are more intrinsically motivated to engage in swing dancing over traditional exercise and this may be due to the high social factors found in partnered dancing. Swing dancing is a form of exercise that can be used to reach the recommended level of physical activity.
ContributorsJones, Roxann Rose (Author) / Nolan, Nicole (Thesis director) / Hoffner, Kristin (Committee member) / College of Health Solutions (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Cytokines induced by inflammasome has been used for blood cancer treatments, yet these treatments have been less successful in the solid tumor microenvironment. Here precise-morphology DNA origami structures were implemented to accurately test the effect and mechanism of activation in the NLRP3 inflammasome. THP1 WT cells, a macrophage cell line, were treated with eleven different DNA origami structures. The inflammasome activation of two cytokines, Interleukin 1 beta (IL-1β) and Interferon beta (IFN-β), was measured using HEK Blue IL-1β cells, HEK Blue IFN-β cells, and enzyme linked immunosorbent assay (ELISA). Differences in activation signaling have the potential to provide the characterization required to address the intrinsic complexity of modulating an immune response. It is hoped that DNA origami will help induce more inflammation for solid tumors. The DNA origami was tested in three different volumes: 1 μL, 5 μL, and 10 μL. Overall, the origami that showed promising results were Mg Square. Tetrahedral and P53 block also showed potential but not as well as Mg square. Further testing of more DNA origami structures and testing them in mice are key to the success of targeted cancer immunotherapies in the neoadjuvant setting.
ContributorsGreenwald, Elinor Vera (Co-author) / Ariola, Amanda (Co-author) / Ning, Bo (Thesis director) / Zhang, Fei (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The British Empire began in the early seventeenth century and continued into the twentieth century. There have been many different answers to the question of what caused imperialism. One solution, proposed most famously by Vladimir Lenin, was that imperialism was a stage of capitalism, and as such developed from it. In this theory monopoly and finance play essential roles in controlling imperialism and are part of the developmental stages of capitalism which led to imperialism. Lenin’s work drew upon that of British economist John A. Hobson, who argued that sectional capitalist interests and under-consumption were what caused imperialism. These theories focus on new imperialism as an abrupt shift in the nature of imperialism. The goal of this thesis is to evaluate the accuracy of this theory of imperialism based on evidence from the British Empire. This thesis presents the details of Lenin’s and Hobson’s arguments to gain an understanding of the foundational ideas of the theory of imperialism as a stage of capitalism. Case studies of areas of the British Empire were done to find if there was evidence that expansion was directed by finance capital and if both political and social forces were controlled by economics in forwarding imperialism. From the data gathered, it was concluded that imperialism was not solely a consequence of capitalism, and imperialism was not a stage of capitalism.
ContributorsSlade, Lauren Nicole (Author) / Barth, Jonathan (Thesis director) / Harper, Tobias (Committee member) / Historical, Philosophical & Religious Studies (Contributor) / Division of Teacher Preparation (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Effectively modeling Alzheimer’s disease will lend to a more comprehensive
understanding of the disease pathology, more efficacious drug development and
regenerative medicine as a form of treatment. There are limitations with current
transgenic mouse models of Alzheimer’s disease and the study of post mortem brain tissue of Alzheimer’s diseases patients. Stem cell models can overcome the lack of clinical relevance and impracticality associated with current models. Ideally, the use of stem cell models provides the foundation to study the biochemical and physiological aspects of Alzheimer’s disease, but at the cellular level. Moreover, the future of drug development and disease modeling can be improved by developing a reproducible and well-characterized model of AD that can be scaled up to meet requirements for basic and translational applications. Characterization and analysis of a heterogenic neuronal culture developed from induced pluripotent stem cells calls for the understanding of single cell identity and cell viability. A method to analyze RNA following intracellular sorting was developed in order to analyze single cell identity of a heterogenic population
of human induced pluripotent stem cells and neural progenitor cells. The population was intracellularly stained and sorted for Oct4. RNA was isolated and analyzed with qPCR, which demonstrated expected expression profiles for Oct4+ and Oct4- cells. In addition, a protocol to label cells with pO2 sensing nanoprobes was developed to assess cell viability. Non-destructive nanoprobe up-take by neural progenitor cells was assessed with fluorescent imaging and flow cytometry. Nanoprobe labeled neurons were cultured long-term and continued to fluoresce at day 28. The proof of concept experiments demonstrated will be further expanded upon and utilized in developing a more clinically relevant and cost-effective model of Alzheimer’s disease with downstream applications
in drug development and regenerative medicine.
understanding of the disease pathology, more efficacious drug development and
regenerative medicine as a form of treatment. There are limitations with current
transgenic mouse models of Alzheimer’s disease and the study of post mortem brain tissue of Alzheimer’s diseases patients. Stem cell models can overcome the lack of clinical relevance and impracticality associated with current models. Ideally, the use of stem cell models provides the foundation to study the biochemical and physiological aspects of Alzheimer’s disease, but at the cellular level. Moreover, the future of drug development and disease modeling can be improved by developing a reproducible and well-characterized model of AD that can be scaled up to meet requirements for basic and translational applications. Characterization and analysis of a heterogenic neuronal culture developed from induced pluripotent stem cells calls for the understanding of single cell identity and cell viability. A method to analyze RNA following intracellular sorting was developed in order to analyze single cell identity of a heterogenic population
of human induced pluripotent stem cells and neural progenitor cells. The population was intracellularly stained and sorted for Oct4. RNA was isolated and analyzed with qPCR, which demonstrated expected expression profiles for Oct4+ and Oct4- cells. In addition, a protocol to label cells with pO2 sensing nanoprobes was developed to assess cell viability. Non-destructive nanoprobe up-take by neural progenitor cells was assessed with fluorescent imaging and flow cytometry. Nanoprobe labeled neurons were cultured long-term and continued to fluoresce at day 28. The proof of concept experiments demonstrated will be further expanded upon and utilized in developing a more clinically relevant and cost-effective model of Alzheimer’s disease with downstream applications
in drug development and regenerative medicine.
ContributorsKnittel, Jacob James (Author) / Brafman, David (Thesis director) / Salvatore, Oddo (Committee member) / School of Life Sciences (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
ABSTRACT
Overview: There has been very little research done into the topic of mental illness in general, and Alzheimer’s Disease specifically, in Guatemala. The existing research accounts for prevalence of mental illness in Guatemala with an estimated prevalence of a mental illness of 27.8% (Guatemalan Government, 2009). Alzheimer’s Disease is less well researched.
Research Question: This research addresses this gap in knowledge by focusing on the stigma felt toward people who had Alzheimer’s Disease and Related Dementia (ADRD) by the people of Guatemala.
Participants: One-hundred twenty-four individuals over the age of 18 were recruited for participation. Participants were recruited through opportunity samples in artisan markets in Antigua.
Procedures: Participants completed a survey including demographic questions, the Dementia Attitudes Scale (O’Connor & McFadden 2010), as well as open-ended questions regarding the causes, symptoms, and treatments for Alzheimer’s. The study was conducted from July 2, 2018 to August 2, 2018.
Results: The average DAS score of 100.31± 14.01 found in this study is similar to results from other studies conducted in the United States (O'Connor & McFadden, 2010). Factor analysis did not verify the existence of sub-scales in the survey, as found in previous studies. The free-response questions indicated that many people may believe that ADRD is an inherited disease or one that is caused by factors outside of their control.
Conclusions: The high DAS score of 100.31± 14.01 matches other studies that used the DAS. Scores of 103.51± 13.43 (Scerri & Scerri, 2013) were reported in other studies and interpreted as positive as it relates to stigma. This points to a low stigma level in Guatemala. The failure to verify the sub-scales leads to the conclusion that although scales are validated in western nations, they may not be culturally portable. The DAS scale may not be measuring the same thing in this sample’s population versus previous studies sample populations.
Overview: There has been very little research done into the topic of mental illness in general, and Alzheimer’s Disease specifically, in Guatemala. The existing research accounts for prevalence of mental illness in Guatemala with an estimated prevalence of a mental illness of 27.8% (Guatemalan Government, 2009). Alzheimer’s Disease is less well researched.
Research Question: This research addresses this gap in knowledge by focusing on the stigma felt toward people who had Alzheimer’s Disease and Related Dementia (ADRD) by the people of Guatemala.
Participants: One-hundred twenty-four individuals over the age of 18 were recruited for participation. Participants were recruited through opportunity samples in artisan markets in Antigua.
Procedures: Participants completed a survey including demographic questions, the Dementia Attitudes Scale (O’Connor & McFadden 2010), as well as open-ended questions regarding the causes, symptoms, and treatments for Alzheimer’s. The study was conducted from July 2, 2018 to August 2, 2018.
Results: The average DAS score of 100.31± 14.01 found in this study is similar to results from other studies conducted in the United States (O'Connor & McFadden, 2010). Factor analysis did not verify the existence of sub-scales in the survey, as found in previous studies. The free-response questions indicated that many people may believe that ADRD is an inherited disease or one that is caused by factors outside of their control.
Conclusions: The high DAS score of 100.31± 14.01 matches other studies that used the DAS. Scores of 103.51± 13.43 (Scerri & Scerri, 2013) were reported in other studies and interpreted as positive as it relates to stigma. This points to a low stigma level in Guatemala. The failure to verify the sub-scales leads to the conclusion that although scales are validated in western nations, they may not be culturally portable. The DAS scale may not be measuring the same thing in this sample’s population versus previous studies sample populations.
ContributorsPotts, Michael Andrew (Author) / Maupin, Jonathan (Thesis director) / Gaughan, Monica (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Between 1941 and 1953, thousands of Lithuanians were deported by the Soviet Union as far from their homeland as the northern reaches of Siberia. While many perished as they contended with hunger, thirst, illness, harsh weather, ill-suited clothing, and poor housing, several survived, returned, and recounted their experiences. Returned adult deportees often recall solidarity among Lithuanians, interactions with locals and authorities, and efforts to maintain agency and continue cultural traditions. Children remember going to school, relying on their parents, and returning to Lithuania. Deportees and others involved in recording their memoirs wrote them in Lithuanian or translated them into English for different purposes and with different intended audiences. The ways in which deportees describe their experiences and what they omit from their stories have shaped Lithuania’s national identity when it reemerged as the Soviet Union fell following Stalin’s death in 1953 and Lithuania redeclared its independence in 1990. The years in which memoirs were published also likely influence their contents. Despite the horrors of deportation, returnees describe positive aspects of the experience. Many deportees portray themselves as struggling for survival, but not as helpless victims. Relatively rare mention of conflict among Lithuanian deportees and identification of non-Lithuanian deportees’ ethnicities suggest the importance of Lithuanians striving together for a common goal: survival and return to Lithuania. The creation of museums focused on deportation, incorporation of memoirs in school curricula, observation of a Day of Mourning and Hope, and portrayal of deportations in works of literature and film demonstrate their lasting impact and significance.
ContributorsDaulys, Gintare K. (Author) / Manchester, Laurie (Thesis director) / Cichopek-Gajraj, Anna (Committee member) / Watts College of Public Service & Community Solut (Contributor) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
“Tell It to the Frogs: Fukushima’s nuclear disaster and its impact on the Japanese Tree Frog” is a representation of the work from Giraudeau et. al’s “Carotenoid distribution in wild Japanese tree frogs (Hyla japonica) exposed to ionizing radiation in Fukushima.” This paper looked to see if carotenoid levels in the tree frog’s vocal sac, liver, and blood were affected by radiation from Fukushima’s power plant explosion. Without carotenoids, the pigment that gives the frogs their orange color on their necks, their courtship practices would be impacted and would not be as able to show off their fitness to potential mates. The artwork inspired by this research displayed the tree frog’s degradation over time due to radiation, starting with normal life and ending with their death and open on the table. The sculptures also pinpoint where the carotenoids were being measured with a brilliant orange glaze. Through ceramic hand building, the artist created larger than life frogs in hopes to elicit curiosity about them and their plight. While the paper did not conclude any changes in the frog’s physiology after 18 months of exposure, there are still questions that are left unanswered. Why did these frogs not have any reaction? Could there be any effects after more time has passed? Is radiation leakage as big of a problem as previously thought? The only way to get the answers to these questions is to be aware of these amphibians, the circumstances that led them to be involved, and continued research on them and radiation.
ContributorsWesterfield, Savannah (Author) / Beiner, Susan (Thesis director) / McGraw, Kevin (Committee member) / School of Life Sciences (Contributor) / School of Art (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05