Matching Items (106)
171582-Thumbnail Image.png
Description
High throughput transcriptome data analysis like Single-cell Ribonucleic Acid sequencing (scRNA-seq) and Circular Ribonucleic Acid (circRNA) data have made significant breakthroughs, especially in cancer genomics. Analysis of transcriptome time series data is core in identifying time point(s) where drastic changes in gene transcription are associated with homeostatic to non-homeostatic cellular

High throughput transcriptome data analysis like Single-cell Ribonucleic Acid sequencing (scRNA-seq) and Circular Ribonucleic Acid (circRNA) data have made significant breakthroughs, especially in cancer genomics. Analysis of transcriptome time series data is core in identifying time point(s) where drastic changes in gene transcription are associated with homeostatic to non-homeostatic cellular transition (tipping points). In Chapter 2 of this dissertation, I present a novel cell-type specific and co-expression-based tipping point detection method to identify target gene (TG) versus transcription factor (TF) pairs whose differential co-expression across time points drive biological changes in different cell types and the time point when these changes are observed. This method was applied to scRNA-seq data sets from a SARS-CoV-2 study (18 time points), a human cerebellum development study (9 time points), and a lung injury study (18 time points). Similarly, leveraging transcriptome data across treatment time points, I developed methodologies to identify treatment-induced and cell-type specific differentially co-expressed pairs (DCEPs). In part one of Chapter 3, I presented a pipeline that used a series of statistical tests to detect DCEPs. This method was applied to scRNA-seq data of patients with non-small cell lung cancer (NSCLC) sequenced across cancer treatment times. However, this pipeline does not account for correlations among multiple single cells from the same sample and correlations among multiple samples from the same patient. In Part 2 of Chapter 3, I presented a solution to this problem using a mixed-effect model. In Chapter 4, I present a summary of my work that focused on the cross-species analysis of circRNA transcriptome time series data. I compared circRNA profiles in neonatal pig and mouse hearts, identified orthologous circRNAs, and discussed regulation mechanisms of cardiomyocyte proliferation and myocardial regeneration conserved between mouse and pig at different time points.
ContributorsNyarige, Verah Mocheche (Author) / Liu, Li (Thesis advisor) / Wang, Junwen (Thesis advisor) / Dinu, Valentin (Committee member) / Arizona State University (Publisher)
Created2022
171902-Thumbnail Image.png
Description
Beta-Amyloid(Aβ) plaques and tau protein tangles in the brain are now widely recognized as the defining hallmarks of Alzheimer’s disease (AD), followed by structural atrophy detectable on brain magnetic resonance imaging (MRI) scans. However, current methods to detect Aβ/tau pathology are either invasive (lumbar puncture) or quite costly and not

Beta-Amyloid(Aβ) plaques and tau protein tangles in the brain are now widely recognized as the defining hallmarks of Alzheimer’s disease (AD), followed by structural atrophy detectable on brain magnetic resonance imaging (MRI) scans. However, current methods to detect Aβ/tau pathology are either invasive (lumbar puncture) or quite costly and not widely available (positron emission tomography (PET)). And one of the particular neurodegenerative regions is the hippocampus to which the influence of Aβ/tau on has been one of the research projects focuses in the AD pathophysiological progress. In this dissertation, I proposed three novel machine learning and statistical models to examine subtle aspects of the hippocampal morphometry from MRI that are associated with Aβ /tau burden in the brain, measured using PET images. The first model is a novel unsupervised feature reduction model to generate a low-dimensional representation of hippocampal morphometry for each individual subject, which has superior performance in predicting Aβ/tau burden in the brain. The second one is an efficient federated group lasso model to identify the hippocampal subregions where atrophy is strongly associated with abnormal Aβ/Tau. The last one is a federated model for imaging genetics, which can identify genetic and transcriptomic influences on hippocampal morphometry. Finally, I stated the results of these three models that have been published or submitted to peer-reviewed conferences and journals.
ContributorsWu, Jianfeng (Author) / Wang, Yalin (Thesis advisor) / Li, Baoxin (Committee member) / Liang, Jianming (Committee member) / Wang, Junwen (Committee member) / Wu, Teresa (Committee member) / Arizona State University (Publisher)
Created2022
190962-Thumbnail Image.png
Description
Wastewater-based epidemiology (WBE) has emerged as a powerful tool for community health assessment, using wastewater-borne biological and chemical markers as analytical targets. This study investigates the critical influence of sampling frequency on the resultant estimates of opioid consumption and the prevalence of SARS-CoV-2 infections at the neighborhood level using common

Wastewater-based epidemiology (WBE) has emerged as a powerful tool for community health assessment, using wastewater-borne biological and chemical markers as analytical targets. This study investigates the critical influence of sampling frequency on the resultant estimates of opioid consumption and the prevalence of SARS-CoV-2 infections at the neighborhood level using common WBE biomarkers including fentanyl, norfentanyl, and the SARS-CoV-2 N1 gene as targets. The goal was to assess sampling methodologies that include the impact of the day of the week and of the sampling frequency. Wastewater samples were collected two or three times per week over the course of five months (n=525) and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) or reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) for target chemical or molecular indicators of interest. Results showed no statistically significant differences for days of the week (i.e., Tuesday vs. Thursday vs. Saturday) for 24-hour composite samples analyzed for fentanyl or SARS-CoV-2; however, concentrations of the human metabolite of fentanyl, norfentanyl, were statistically different between Tuesday and Saturday (p < 0.05). When data were aggregated either by Tuesday/Thursday or Tuesday/Thursday/Saturday to examine sensitivity to sampling frequency, data were not statistically different except for the Tuesday/Thursday weekly average and Saturday for norfentanyl (p < 0.05). These results highlight how sample collection and data handling methodologies can impact wastewater-derived public health assessments. Care should be taken when selecting an approach to the sampling frequency based on the public health concerns under investigation.
ContributorsAJDINI, ARIANNA (Author) / Halden, Rolf (Thesis advisor) / Driver, Erin (Committee member) / Conroy-Ben, Otakuye (Committee member) / Arizona State University (Publisher)
Created2023
190882-Thumbnail Image.png
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
Current methods for quantifying microplastics via LC-MS/MS analysis have been adapted from environmental monitoring protocols and are often inadequate for sampling within complex matrices. This study explores the application of liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection of microplastics. The initial phase of this research utilized pork kidney

Current methods for quantifying microplastics via LC-MS/MS analysis have been adapted from environmental monitoring protocols and are often inadequate for sampling within complex matrices. This study explores the application of liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection of microplastics. The initial phase of this research utilized pork kidney samples to establish a baseline for background and efficacy of sample processing. These findings underscore the complexity of developing a sensitive and specific analytical technique for microplastics in tissues. The observed discrepancies in contamination and replicability between samples emphasize the need for continual method optimization.
ContributorsBabbrah, Ayesha (Author) / Halden, Rolf (Thesis director) / Newell, Melanie (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2023-12
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
189363-Thumbnail Image.png
Description
This dissertation focused on studying risks associated with emerging drinking water contaminants and tradeoffs related to water management interventions. The built environment impacts health, as humans on average spend ~90% of their time indoors. Federal regulations generally focus on drinking water at the water treatment plant and within the distribution

This dissertation focused on studying risks associated with emerging drinking water contaminants and tradeoffs related to water management interventions. The built environment impacts health, as humans on average spend ~90% of their time indoors. Federal regulations generally focus on drinking water at the water treatment plant and within the distribution system as opposed to when it enters buildings after crossing the property line. If drinking water is not properly managed in buildings, it can be a source or amplifier of microbial and chemical contaminants. Unlike regulations for chemical contaminants that are risk-based, for pathogens, regulations are either based on recommended treatment technologies or designated as zero, which is not achievable in practice. Practice-based judgments are typically made at the building level to maintain water quality. This research focuses on two drinking water opportunistic pathogens of public health concern, Legionella pneumophila and Mycobacterium avium complex (MAC). Multiple aspects of drinking water quality in two green buildings were monitored in tandem with water management interventions. Additionally, a quantitative microbial risk assessment framework was used to predict risk-based critical concentrations of MAC for drinking water-related exposures in the indoor environment corresponding to a 1 in 10,000 annual infection target risk benchmark. The overall goal of this work was to inform the development of water management plans and guidelines for buildings that will improve water quality in the built environment and promote better public health. It was determined that a whole building water softening system with ion exchange softening resin and expansion tanks were unexplored reservoirs for the colonization of L. pneumophila. Furthermore, it was observed that typical water management interventions such as flushing and thermal disinfection did not always mitigate water quality issues. Thus, there was a need to implement several atypical interventions such as equipment replacement to improve the building water quality. This work has contributed comprehensive field studies and models that have highlighted the need for additional niches, facility management challenges, and risk tradeoffs for focus in water safety plans. The work also informs additional risk-based water quality policy approaches for reducing drinking water risks.
ContributorsJoshi, Sayalee (Author) / Hamilton, Kerry A (Thesis advisor) / Abbaszadegan, Morteza (Committee member) / Conroy-Ben, Otakuye (Committee member) / Halden, Rolf (Committee member) / Arizona State University (Publisher)
Created2023
Description

Synthetic plastics are ubiquitously used in a broad range of applications, including food and drink packaging. Plastics often contain chemical additives, including bisphenols, phthalates, and terephthalic acid, which can degrade under thermal stress. The environmental presence of these chemicals is cause for public concern, especially in consumer products that utilize

Synthetic plastics are ubiquitously used in a broad range of applications, including food and drink packaging. Plastics often contain chemical additives, including bisphenols, phthalates, and terephthalic acid, which can degrade under thermal stress. The environmental presence of these chemicals is cause for public concern, especially in consumer products that utilize plastic packaging, as many have been identified as endocrine disruptors. This study sought to determine exposure to phthalates, bisphenols, and terephthalic acid by quantifying a broad spectrum of these analytes within three bottled water brands at varying temperature exposure levels using the combination of solid phase extraction followed by isotope dilution liquid chromatography-tandem mass spectrometry. Monobenzyl phthalate was detected in two of the three brands after bottles were heated to ~100 °C, ranging from 98 – 107 ng/L, and bisphenol A was detected in one brand at ~100 °C at an average concentration of 748 ± 36 ng/L. Subsequent mass loading calculations demonstrated that bioaccumulation of BPA from Brand C after high levels of temperature exposure well exceeded the tolerable daily intake (TDI). Findings in this study indicate that consumers should not be expected to incur harmful exposures to the target compounds under normal conditions as analytes were not measured in water bottle samples at 25 °C or 60 °C. Further studies should explore a more nuisance approach to heating over long durations, including that of ultraviolet exposure.

ContributorsZevitz, Jacob (Author) / Halden, Rolf (Thesis director) / Driver, Erin (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor)
Created2022-12
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
The production and incineration of single-use micropipette tips and disposable gloves, which are heavily used within laboratory facilities, generate large amounts of greenhouse gasses (GHGs) and accelerate climate change. Plastic waste that is not incinerated often is lost in the environment. The long degradation times associated with this waste exacerbates

The production and incineration of single-use micropipette tips and disposable gloves, which are heavily used within laboratory facilities, generate large amounts of greenhouse gasses (GHGs) and accelerate climate change. Plastic waste that is not incinerated often is lost in the environment. The long degradation times associated with this waste exacerbates a variety of environmental problems such as substance runoff and ocean pollution. The objective of this study was to evaluate the efficacy of possible solutions for minimizing micropipette tip and disposable glove waste within laboratory spaces. It was hypothesized that simultaneously implementing the use of micropipette tip washers (MTWs) and energy-from-glove-waste programs (EGWs) would significantly reduce (p < 0.05) the average combined annual single-use plastic micropipette tip and nitrile glove waste (in kg) per square meter of laboratory space in the United States. ASU’s Biodesign Institute (BDI) was used as a case study to inform on the thousands of different laboratory facilities that exist all across the United States. Four separate research laboratories within the largest public university of the U.S. were sampled to assess the volume of plastic waste from single-use micropipette tips and gloves. Resultant data were used to represent the totality of single-use waste from the case study location and then extrapolated to all laboratory space in the United States. With the implementation of EGWs, annual BDI glove waste is reduced by 100% (0.47 ± 0.26 kg/m2; 35.5 ± 19.3 metric tons total) and annual BDI glove-related carbon emissions are reduced by ~5.01% (0.165 ± 0.09 kg/m2; 1.24 ± 0.68 metric tons total). With the implementation of MTWs, annual BDI micropipette tip waste is reduced by 92% (0.117 ± 0.03 kg/m2; 0.88 ± 0.25 metric tons total) and annual BDI tip-related carbon emissions are reduced by ~83.6% (4.04 ± 1.25 kg/m2; 30.5 ± 9.43 metric tons total). There was no significant difference (p = 0.06) observed between the mass of single-use waste (kg) in the sampled laboratory spaces before (x̄ = 47.1; σ = 43.3) and after (x̄ =0.070; σ = 0.033) the implementation of the solutions. When examining both solutions (MTWs & EGWs) implemented in conjunction with one another, the annual BDI financial savings (in regard to both purchasing and disposal costs) after the first year were determined to be ~$7.92 ± $9.31/m2 (7,500 m2 of total wet laboratory space) or ~$60,000 ± $70,000 total. These savings represent ~15.77% of annual BDI spending on micropipette tips and nitrile gloves. The large error margins in these financial estimates create high uncertainty for whether or not BDI would see net savings from implementing both solutions simultaneously. However, when examining the implementation of only MTWs, the annual BDI financial savings (in regard to both purchasing and disposal costs) after the first year were determined to be ~$12.01 ± $6.79 kg/m2 or ~$91,000 ± $51,200 total. These savings represent ~23.92% of annual BDI spending on micropipette tips and nitrile gloves. The lower error margins for this estimate create a much higher likelihood of net savings for BDI. Extrapolating to all laboratory space in the United States, the total annual amount of plastic waste avoided with the implementation of the MTWs was identified as 8,130 ± 2,290 tons or 0.023% of all solid plastic waste produced in the United States in 2018. The total amount of nitrile waste avoided with the implementation of the EGWs was identified as 32,800 ± 17,900 tons or 0.36% of all rubber solid waste produced in the United States in 2018. The total amount of carbon emissions avoided with the implementation of the MTWs was identified as 281,000 ± 87,000 tons CO2eq or 5.4*10-4 % of all CO2eq GHG emissions produced in the United States in 2020. Both the micropipette tip washer and the glove waste avoidance program solutions can be easily integrated into existing laboratories without compromising the integrity of the activities taking place. Implemented on larger scales, these solutions hold the potential for significant single-use waste reduction.
ContributorsZdrale, Gabriel (Author) / Mahant, Akhil (Co-author) / Halden, Rolf (Thesis director) / Biyani, Nivedita (Committee member) / Driver, Erin (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2022-05