Matching Items (91)
Description
The purpose of this experiment was to use real-time quantitative polymerase chain reactions (RT-qPCR) to quantify and analyze differences in expression of U1 snRNA variants across four different human Leukemia cell lines. We found a number of interesting results in the four cell lines. Two variants in particular (vU1.15 and

The purpose of this experiment was to use real-time quantitative polymerase chain reactions (RT-qPCR) to quantify and analyze differences in expression of U1 snRNA variants across four different human Leukemia cell lines. We found a number of interesting results in the four cell lines. Two variants in particular (vU1.15 and vU1.19), were only expressed in one leukemia cell line each, indicating a potential link between their specific mutations and the type of leukemia associated with the cell lines in which they were expressed. Further research should be conducted to understand these differences and uncover potential clinical applications.
ContributorsLawrence, Ethan (Author) / Mangone, Marco (Thesis director) / Sharma, Shalini (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor)
Created2023-12
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Description
Speciation, or the process by which one population diverges into multiple populations that can no longer interbreed with each other, has brought about the incredible diversity of life. Mechanisms underlying this process can be more visible in the early stages of the speciation process. The mechanisms that restrict gene flow

Speciation, or the process by which one population diverges into multiple populations that can no longer interbreed with each other, has brought about the incredible diversity of life. Mechanisms underlying this process can be more visible in the early stages of the speciation process. The mechanisms that restrict gene flow in highly mobile species with no absolute barriers to dispersal, especially marine species, are understudied. Similarly, human impacts are reshaping ecosystems globally, and we are only just beginning to understand the implications of these rapid changes on evolutionary processes. In this dissertation, I investigate patterns of speciation and evolution in two avian clades: a genus of widespread tropical seabirds (boobies, genus Sula), and two congeneric passerine species in an urban environment (cardinals, genus Cardinalis). First, I explore the prevalence of gene flow across land barriers within species and between sympatric species in boobies. I found widespread evidence of gene flow over all land barriers and between 3 species pairs. Next, I compared the effects of urbanization on the spatial distributions of two cardinal species, pyrrhuloxia (Cardinalis sinuatus) and northern cardinals (Cardinalis cardinalis), in Tucson, Arizona. I found that urbanization has different effects on the spatial distributions of two closely related species that share a similar environmental niche, and I identified environmental variables that might be driving this difference. Then I tested for effects of urbanization on color and size traits of these two cardinal species. In both of these species, urbanization has altered traits involved in signaling, heat tolerance, foraging, and maneuverability. Finally, I tested for evidence of selection on the urban populations of both cardinal species and found evidence of both parallel selection and introgression between the species, as well as selection on different genes in each species. The functions of the genes that experienced positive selection suggest that light at night, energetics, and air pollution may have acted as strong selective pressures on these species in the past. Overall, my dissertation emphasizes the role of introgression in the speciation process, identifies environmental stressors faced by wildlife in urban environments, and characterizes their evolutionary responses to those stressors.
ContributorsJackson, Daniel Nelson (Author) / McGraw, Kevin J (Thesis advisor) / Amdam, Gro (Committee member) / Sweazea, Karen (Committee member) / Taylor, Scott (Committee member) / Arizona State University (Publisher)
Created2023
Description
The objective of this meta-analysis is to holistically evaluate the existing body of literature on the anti-neoplastic potential of snake and bee venom. In recent years, venom-based therapeutics have emerged as a promising solution for combating cancer, generating a notable rise in publications on the topic. Consequently, this comprehensive study

The objective of this meta-analysis is to holistically evaluate the existing body of literature on the anti-neoplastic potential of snake and bee venom. In recent years, venom-based therapeutics have emerged as a promising solution for combating cancer, generating a notable rise in publications on the topic. Consequently, this comprehensive study aims to assess the current state of research and identify trends that may guide future investigations. Following the guidelines established by PRISMA, a total sample of 26 research papers were extracted from the electronic databases, PubMed and Scopus. These papers were categorized based on their publication dates, and research questions were formulated regarding three main topics: venom type, cancer-targeting mechanism, and cancer type. Statistical analysis of the research questions was performed using 2x2 contingency tables for a chi-square test. The results of the analysis reveal a statistically significant increase in publications focused on cell death mechanisms and breast cancer in recent years. This increase in publications reflects a growing interest in the potential for venom to induce apoptosis in cancer cells and target the unique biological properties of breast cancer. Overall, this meta-analysis offers insight into the evolving sphere of venom-based cancer research, providing a glimpse into the potential trajectory of this field.
ContributorsHolder, Marina (Author) / Amdam, Gro (Thesis director) / Mana, Miyeko (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Economics Program in CLAS (Contributor)
Created2023-12
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Description
Cocaine induces long-lasting changes in mesolimbic ‘reward’ circuits of the brain after cessation of use. These lingering changes include the neuronal plasticity that is thought to underlie the chronic relapsing nature of substance use disorders. Genes involved in neuronal plasticity also encode circular RNAs (circRNAs), which are stable, non-coding RNAs

Cocaine induces long-lasting changes in mesolimbic ‘reward’ circuits of the brain after cessation of use. These lingering changes include the neuronal plasticity that is thought to underlie the chronic relapsing nature of substance use disorders. Genes involved in neuronal plasticity also encode circular RNAs (circRNAs), which are stable, non-coding RNAs formed through the back-splicing of pre-mRNA. The Homer1 gene family, which encodes proteins associated with cocaine-induced plasticity, also encodes circHomer1. Based on preliminary evidence from shows cocaine-regulated changes in the ratio of circHomer1 and Homer1b mRNA in the nucleus accumbens (NAc), this study examined the relationship between circHomer1 and incentive motivation for cocaine by using different lengths of abstinence to vary the degree of motivation. Male and female rats were trained to self-administer cocaine (0.75 mg/kg/infusion, IV) or received a yoked saline infusion. Rats proceeded on an increasingly more difficult variable ratio schedule of lever pressing until they reached a variable ratio 5 schedule, which requires an average of 5 lever presses, and light and tone cues were delivered with the drug infusions. Rats were then tested for cocaine-seeking behavior in response to cue presentations without drug delivery either 1 or 21 days after their last self-administration session. They were sacrificed immediately after and circHomer1 and Homer1b expression was then measured from homogenate and synaptosomal fractions of NAc shell using RT-qPCR. Lever pressing during the cue reactivity test increased from 1 to 21 days of abstinence as expected. Results showed no group differences in synaptic circHomer1 expression, however, total circHomer1 expression was downregulated in 21d rats compared to controls. Lack of change in synaptic circHomer1 was likely due to trends toward different temporal changes in males versus females. Total Homer1b expression was higher in females, although there was no effect of cocaine abstinence. Further research investigating the time course of circHomer1 and Homer1b expression is warranted based on the inverse relationship between total circHomer1and cocaine-seeking behavior observed in this study.
ContributorsJohnson, Michael Christian (Author) / Neisewander, Janet L (Thesis advisor) / Perrone-Bizzozero, Nora (Thesis advisor) / Mangone, Marco (Committee member) / Arizona State University (Publisher)
Created2022
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Description
Type 1 diabetes (T1D) is the result of an autoimmune attack against the insulin-producing β-cells of the pancreas causing hyperglycemia and requiring the individual to rely on life-long exogenous insulin. With the age of onset typically occurring in childhood, there is increased physical and emotional stress to the child as

Type 1 diabetes (T1D) is the result of an autoimmune attack against the insulin-producing β-cells of the pancreas causing hyperglycemia and requiring the individual to rely on life-long exogenous insulin. With the age of onset typically occurring in childhood, there is increased physical and emotional stress to the child as well as caregivers to maintain appropriate glucose levels. The majority of T1D patients have antibodies to one or more antigens: insulin, IA-2, GAD65, and ZnT8. Although antibodies are detectable years before symptoms occur, the initiating factors and mechanisms of progression towards β-cell destruction are still not known. The search for new autoantibodies to elucidate the autoimmune process in diabetes has been slow, with proteome level screenings on native proteins only finding a few minor antigens. Post-translational modifications (PTM)—chemical changes that occur to the protein after translation is complete—are an unexplored way a self-protein could become immunogenic. This dissertation presents the first large sale screening of autoantibodies in T1D to nitrated proteins. The Contra Capture Protein Array (CCPA) allowed for fresh expression of hundreds of proteins that were captured on a secondary slide by tag-specific ligand and subsequent modification with peroxynitrite. The IgG and IgM humoral response of 48 newly diagnosed T1D subjects and 48 age-matched controls were screened against 1632 proteins highly or specifically expressed in pancreatic cells. Top targets at 95% specificity were confirmed with the same serum samples using rapid antigenic protein in situ display enzyme-linked immunosorbent assay (RAPID ELISA) a modified sandwich ELISA employing the same cell-free expression as the CCPA. For validation, 8 IgG and 5 IgM targets were evaluated with an independent serum sample set of 94 T1D subjects and 94 controls. The two best candidates at 90% specificity were estrogen receptor 1 (ESR1) and phosphatidylinositol 4-kinase type 2 beta (PI4K2B) which had sensitivities of 22% (p=.014) and 25% (p=.045), respectively. Receiver operating characteristic (ROC) analyses found an area under curve (AUC) of 0.6 for ESR1 and 0.58 for PI4K2B. These studies demonstrate the ability and value for high-throughput autoantibody screening to modified antigens and the frequency of Type 1 diabetes.
ContributorsHesterman, Jennifer (Author) / LaBaer, Joshua (Thesis advisor) / Borges, Chad (Committee member) / Sweazea, Karen (Committee member) / Mangone, Marco (Committee member) / Arizona State University (Publisher)
Created2022
Description

Insect pheromones are crucial for survival and reproduction because they influence insect behavior, communication, and interactions within and outside the colony. Honey bees (Apis mellifera) have one of the most complex pheromonal communication systems. One pheromone, known as Queen Mandibular Pheromone (QMP), is released by the queen bee to regulate

Insect pheromones are crucial for survival and reproduction because they influence insect behavior, communication, and interactions within and outside the colony. Honey bees (Apis mellifera) have one of the most complex pheromonal communication systems. One pheromone, known as Queen Mandibular Pheromone (QMP), is released by the queen bee to regulate physiology, behavior, and gene expression in the female worker caste. The pheromone acts as a signal of queen presence that suppresses worker reproduction. In the absence of reproduction, young workers focus on taking care of the queen and larvae, known as nurse tasks, while older workers forage. In nurse bees, QMP has fundamental physiological impacts, including increasing abdominal lipid stores and increasing the protein content of hypopharyngeal glands (HPG). The HPG are worker-specific glands that can synthesize royal jelly used in colony nourishment. In workers, larger HPG signifies the ability to secrete royal jelly, while shrunken glands are characteristic of foragers that do not make jelly. While it is known that QMP increases abdominal lipid stores, the underlying mechanism is unclear: Does the pheromone simply make workers consume more pollen which provides lipids and protein, or does QMP also increase lipogenesis? In this study, I measured abdominal lipogenesis as fatty acid synthase (FAS) activity and monitored abdominal protein content and HPG size in caged, nurse-aged worker bees. In cages, workers were exposed to QMP or not, and they were provided with a lipid less diet in a full factorial design experiment. I found that QMP did not influence abdominal FAS activity or protein, but significantly increased HPG size. The data also revealed a significant positive correlation between abdominal protein and HPG size. My results do not support the idea that QMP modulates lipogenesis in worker bees, but my data can be interpreted to reflect that QMP mobilizes abdominal protein for the production of jelly in the HPG. This finding is in line with a previous study revealing a role of honey bee Brood Pheromone in mobilization of a major protein used in jelly production. Overall, my results support a fundamental role of QMP in worker metabolic processes associated with colony nourishment.

ContributorsOreshkova, Angela (Author) / Amdam, Gro (Thesis director) / Scofield, Sebastian (Committee member) / Barrett, The Honors College (Contributor) / College of Health Solutions (Contributor) / School of Life Sciences (Contributor)
Created2023-05
Description

Bdellovibrio bacteriovorus (B. bacteriovorus) is a predatory bacterium that preys on other gram-negative bacteria. In order to survive and reproduce, B. bacteriovorus invades the periplasm of other bacterial cells creating the potential for it to act as a “living antibiotic”. In this work, a comparison was made between the rates

Bdellovibrio bacteriovorus (B. bacteriovorus) is a predatory bacterium that preys on other gram-negative bacteria. In order to survive and reproduce, B. bacteriovorus invades the periplasm of other bacterial cells creating the potential for it to act as a “living antibiotic”. In this work, a comparison was made between the rates of predation of B. bacteriovorus in vitro and in vivo. In vitro, the behavior of B. bacteriovorus was examined in the presence of prey. In vivo, the behavior of B. bacteriovorus was examined in the presence of prey and a living host, Caenorhabditis elegans (C. elegans). C. elegans were infected with Escherichia coli (E. coli) and treated with B. bacteriovorus. In previous studies that analyzed B. bacteriovorus in vitro, a decrease in concentrations of bacteria has been observed after introduction of B. bacteriovorus. In vivo, B. bacteriovorus were found to not have a net reduction of E. coli but to reproducibly raise the level of fluctuations in E. coli concentrations.

ContributorsPerry, Nicole (Author) / Presse, Steve (Thesis director) / Mangone, Marco (Committee member) / Barrett, The Honors College (Contributor) / Economics Program in CLAS (Contributor) / School of Molecular Sciences (Contributor)
Created2023-05
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Description
The RNA editing enzyme adenosine deaminase acting on double stranded RNA 2 (ADAR2) converts adenosine into inosine in regions of double stranded RNA. Here, it was discovered that this critical function of ADAR2 was dysfunctional in amyotrophic lateral sclerosis (ALS) mediated by the C9orf72 hexanucleotide repeat expansion, the most common

The RNA editing enzyme adenosine deaminase acting on double stranded RNA 2 (ADAR2) converts adenosine into inosine in regions of double stranded RNA. Here, it was discovered that this critical function of ADAR2 was dysfunctional in amyotrophic lateral sclerosis (ALS) mediated by the C9orf72 hexanucleotide repeat expansion, the most common genetic abnormality associated with ALS. Typically a nuclear protein, ADAR2 was localized in cytoplasmic accumulations in postmortem tissue from C9orf72 ALS patients. The mislocalization of ADAR2 was confirmed using immunostaining in a C9orf72 mouse model and motor neurons differentiated from C9orf72 patient induced pluripotent stem cells. Notably, the cytoplasmic accumulation of ADAR2 coexisted in neurons with cytoplasmic accumulations of TAR DNA binding protein 43 (TDP-43). Interestingly, ADAR2 overexpression in mammalian cell lines induced nuclear depletion and cytoplasmic accumulation of TDP-43, reflective of the pathology observed in ALS patients. The mislocalization of TDP-43 was dependent on the catalytic activity of ADAR2 and the ability of TDP-43 to bind directly to inosine containing RNA. In addition, TDP-43 nuclear export was significantly elevated in cells with increased RNA editing. Together these results describe a novel cellular mechanism by which alterations in RNA editing drive the nuclear export of TDP-43 leading to its cytoplasmic mislocalization. Considering the contribution of cytoplasmic TDP-43 to the pathogenesis of ALS, these findings represent a novel understanding of how the formation of pathogenic cytoplasmic TDP-43 accumulations may be initiated. Further research exploring this mechanism will provide insights into opportunities for novel therapeutic interventions.
ContributorsMoore, Stephen Philip (Author) / Sattler, Rita (Thesis advisor) / Zarnescu, Daniela (Committee member) / Brafman, David (Committee member) / Van Keuren-Jensen, Kendall (Committee member) / Mangone, Marco (Committee member) / Arizona State University (Publisher)
Created2021
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Description
This dissertation describes a series of four studies on cognitive aging, working memory, and cognitive flexibility in dogs (Canis lupus familiaris) and their wild relatives. In Chapters 2 and 3, I designed assessments for age-related cognitive deficits in pet dogs which can be deployed rapidly using inexpensive and accessible materials.

This dissertation describes a series of four studies on cognitive aging, working memory, and cognitive flexibility in dogs (Canis lupus familiaris) and their wild relatives. In Chapters 2 and 3, I designed assessments for age-related cognitive deficits in pet dogs which can be deployed rapidly using inexpensive and accessible materials. These novel tests can be easily implemented by owners, veterinarians, and clinicians and therefore, may improve care for elderly dogs by aiding in the diagnosis of dementia. In addition, these widely deployable tests may facilitate the use of dementia in pet dogs as a naturally occurring model of Alzheimer’s Disease in humans.In Chapters 4 and 5, I modified one of these tests to demonstrate for the first time that coyotes (Canis latrans) and wolves (Canis lupus lupus) develop age-related deficits in cognitive flexibility. This was an important first step towards differentiating between the genetic and environmental components of dementia in dogs and in turn, humans. Unexpectedly, I also detected cognitive deficits in young, adult dogs and wolves but not coyotes. These finding add to a recent shift in understanding cognitive development in dogs which may improve cognitive aging tests as well as training, care, and use of working and pet dogs. These findings also suggest that the ecology of coyotes may select for flexibility earlier in development. In Chapter 5, I piloted the use of the same cognitive flexibility test for red and gray foxes so that future studies may test for lifespan changes in the cognition of small-bodied captive canids. More broadly, this paradigm may accommodate physical and behavioral differences between diverse pet and captive animals. In Chapters 4 and 5, I examined which ecological traits drive the evolution of behavioral flexibility and in turn, species resilience. I found that wolves displayed less flexibility than dogs and coyotes suggesting that species which do not rely heavily on unstable resources may be ill-equipped to cope with human habitat modification. Ultimately, this comparative work may help conservation practitioners to identify and protect species that cannot cope with rapid and unnatural environmental change.
ContributorsVan Bourg, Joshua (Author) / Wynne, Clive D (Thesis advisor) / Aktipis, C. Athena (Committee member) / Gilby, Ian C (Committee member) / Young, Julie K (Committee member) / Arizona State University (Publisher)
Created2022
Description
The partitioning of photosynthates between their sites of production (source) and their sites of utilization (sink) is a major determinant of crop yield and the potential of regulating this translocation promises substantial opportunities for yield increases. Ubiquitous overexpression of the plant type I proton pyrophosphatase (H+-PPase) in crops improves several

The partitioning of photosynthates between their sites of production (source) and their sites of utilization (sink) is a major determinant of crop yield and the potential of regulating this translocation promises substantial opportunities for yield increases. Ubiquitous overexpression of the plant type I proton pyrophosphatase (H+-PPase) in crops improves several valuable traits including salt tolerance and drought resistance, nutrient and water use efficiencies, and increased root biomass and yield. Originally, type I H+-PPases were described as pyrophosphate (PPi)-dependent proton pumps localized exclusively in vacuoles of mesophyll and meristematic tissues. It has been proposed that in the meristematic tissues, the role of this enzyme would be hydrolyzing PPi originated in biosynthetic reactions and favoring sink strength. Interestingly, this enzyme has been also localized at the plasma membrane of companion cells in the phloem which load and transport photosynthates from source leaves to sinks. Of note, the plasma membrane-localized H+-PPase could only function as a PPi-synthase in these cells due to the steep proton gradient between the apoplast and cytosol. The generated PPi would favor active sucrose loading through the sucrose/proton symporter in the phloem by promoting sucrose hydrolysis through the Sucrose Synthase pathway and providing the ATP required to maintain the proton gradient. To better understand these two different roles of type I H+-PPases, a series of Arabidopsis thaliana transgenic plants were generated. By expressing soluble pyrophosphatases in companion cells of Col-0 ecotype and H+-PPase mutants, impaired photosynthates partitioning was observed, suggesting phloem-localized H+-PPase could generate the PPi required for sucrose loading. Col-0 plants expressed with either phloem- or meristem-specific AVP1 overexpression cassette and the cross between the two tissue specific lines (Cross) were generated. The results showed that the phloem-specific AVP1-overexpressing plants had increased root hair elongation under limited nutrient conditions and both phloem- and meristem-overexpression of AVP1 contributed to improved rhizosphere acidification and drought resistance. It was concluded that H+-PPases localized in both sink and source tissues regulate plant growth and performance under stress through its versatile enzymatic functions (PPi hydrolase and synthase).
ContributorsLi, Lin (Author) / Park, Yujin (Thesis advisor) / Mangone, Marco (Committee member) / Roberson, Robert (Committee member) / Vermaas, Willem (Committee member) / Arizona State University (Publisher)
Created2022