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- Genre: Doctoral Dissertation
Description
There are several visual dimensions of food that can affect food intake, example portion size, color, and variety. This dissertation elucidates the effect of number of pieces of food on preference and amount of food consumed in humans and motivation for food in animals. Chapter 2 Experiment 1 showed that rats preferred and also ran faster for multiple pieces (30, 10 mg pellets) than an equicaloric, single piece of food (300 mg) showing that multiple pieces of food are more rewarding than a single piece. Chapter 2 Experiment 2 showed that rats preferred a 30-pellet food portion clustered together rather than scattered. Preference and motivation for clustered food pieces may be interpreted based on the optimal foraging theory that animals prefer foods that can maximize energy gain and minimize the risk of predation. Chapter 3 Experiment 1 showed that college students preferred and ate less of a multiple-piece than a single-piece portion and also ate less in a test meal following the multiple-piece than single-piece portion. Chapter 3 Experiment 2 replicated the results in Experiment 1 and used a bagel instead of chicken. Chapter 4 showed that college students given a five-piece chicken portion scattered on a plate ate less in a meal and in a subsequent test meal than those given the same portion clustered together. This is consistent with the hypothesis that multiple pieces of food may appear like more food because they take up a larger surface area than a single-piece portion. All together, these studies show that number and surface area occupied by food pieces are important visual cues determining food choice in animals and both food choice and intake in humans.
ContributorsBajaj, Devina (Author) / Phillips, Elizabeth D. (Thesis advisor) / Cohen, Adam (Committee member) / Johnston, Carol (Committee member) / Bimonte-Nelson, Heather A. (Committee member) / Arizona State University (Publisher)
Created2013
Description
In October, 2009, participants of the Arizona Special Supplemental Nutrition Program for Women, Infants and Children (WIC) began receiving monthly Cash Value Vouchers (CVV) worth between six and 10 dollars towards the purchase of fresh fruits and vegetables. Data from the Arizona Department of Health Services (ADHS) showed CVV redemption rates in the first two years of the program were lower than the national average of 77% redemption. In response, the ADHS WIC Food List was expanded to also include canned and frozen fruits and vegetables. More recent data from ADHS suggest that redemption rates are improving, but variably exist among different WIC sub-populations. The purpose of this project was to identify themes related to the ease or difficulty of WIC CVV use amongst different categories of low-redeeming WIC participants. A total of 8 focus groups were conducted, four at a clinic in each of two Valley cities: Surprise and Mesa. Each of the four focus groups comprised one of four targeted WIC participant categories: pregnant, postpartum, breastfeeding, and children with participation ranging from 3-9 participants per group. Using the general inductive approach, recordings of the focus groups were transcribed, hand-coded and uploaded into qualitative analysis software resulting in four emergent themes including: interactions and shopping strategies, maximizing WIC value, redemption issues, and effect of rule change. Researchers identified twelve different subthemes related to the emergent theme of interactions and strategies to improve their experience, including economic considerations during redemption. Barriers related to interactions existed that made their purchase difficult, most notably anger from the cashier and other shoppers. However, participants made use of a number of strategies to facilitate WIC purchases or extract more value out of WIC benefits, such as pooling their CVV. Finally, it appears that the fruit and vegetable rule change was well received by those who were aware of the change. These data suggest a number of important avenues for future research, including verifying these themes are important within a larger, representative sample of Arizona WIC participants, and exploring strategies to minimize barriers identified by participants, such as use of electronic benefits transfer-style cards (EBT).
ContributorsBertmann, Farryl M. W (Author) / Wharton, Christopher (Christopher Mack), 1977- (Thesis advisor) / Ohri-Vachaspati, Punam (Committee member) / Johnston, Carol (Committee member) / Hampl, Jeffrey (Committee member) / Dixit-Joshi, Sujata (Committee member) / Barroso, Cristina (Committee member) / Arizona State University (Publisher)
Created2013
Description
Understanding why animals form social groups is a fundamental aim of sociobiology. To date, the field has been dominated by studies of kin groups, which have emphasized indirect fitness benefits as key drivers of grouping among relatives. Nevertheless, many animal groups are comprised of unrelated individuals. These cases provide unique opportunities to illuminate drivers of social evolution beyond indirect fitness, especially ecological factors. This dissertation combines behavioral, physiological, and ecological approaches to explore the conditions that favor group formation among non-kin, using as a model the facultatively social carpenter bee, Xylocopa sonorina. Using behavioral and genetic techniques, I found that nestmates in this species are often unrelated, and that non-kin groups form following extensive inter-nest migration.Group living may arise as a strategy to mitigate constraints on available breeding space. To test the hypothesis that nest construction is prohibitively costly for carpenter bees, I measured metabolic rates of excavating bees and used imaging techniques to quantify nest volumes. From these measurements, I found that nest construction is highly energetically costly, and that bees who inherit nests through social queuing experience substantial energetic savings. These costs are exacerbated by limitations on the reuse of existing nests. Using repeated CT scans of nesting logs, I examined changes in nest architecture over time and found that repeatedly inherited tunnels become indefensible to intruders, and are subsequently abandoned. Together, these factors underlie intense competition over available breeding space. The imaging analysis of nesting logs additionally revealed strong seasonal effects on social strategy, with social nesting dominating during winter. To test the hypothesis that winter social nesting arises from intrinsic physiological advantages of grouping, I experimentally manipulated social strategy in overwintering bees. I found that social bees conserve heat and body mass better than solitary bees, suggesting fitness benefits to grouping in cold, resource-scarce conditions. Together, these results suggest that grouping in X. sonorina arises from dynamic strategies to maximize direct fitness in response to harsh and/or competitive conditions. These studies provide empirical insights into the ecological conditions that favor non-kin grouping, and emphasize the importance of ecology in shaping sociality at its evolutionary origins.
ContributorsOstwald, Madeleine (Author) / Fewell, Jennifer H (Thesis advisor) / Amdam, Gro (Committee member) / Harrison, Jon (Committee member) / Pratt, Stephen (Committee member) / Kapheim, Karen (Committee member) / Arizona State University (Publisher)
Created2022
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 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
Scientists are entrusted with developing novel molecular strategies for effective prophylactic and therapeutic interventions. Antivirals are indispensable tools that can be targeted at viral domains directly or at cellular domains indirectly to obstruct viral infections and reduce pathogenicity. Despite their transformative potential in healthcare, to date, antivirals have been clinically approved to treat only 10 out of the greater than 200 known pathogenic human viruses. Additionally, as obligate intracellular parasites, many virus functions are intimately coupled with host cellular processes. As such, the development of a clinically relevant antiviral is challenged by the limited number of clear targets per virus and necessitates an extensive insight into these molecular processes. Compounding this challenge, many viral pathogens have evolved to evade effective antivirals. Therefore, a means to develop virus- or strain-specific antivirals without detailed insight into each idiosyncratic biochemical mechanism may aid in the development of antivirals against a larger swath of pathogens. Such an approach will tremendously benefit from having the specific molecular recognition of viral species as the lowest barrier. Here, I modify a nanobody (anti-green fluorescent protein) that specifically recognizes non-essential epitopes (glycoprotein M-pHluorin chimera) presented on the extra virion surface of a virus (Pseudorabies virus strain 486). The nanobody switches from having no inhibitory properties (tested up to 50 μM) to ∼3 nM IC50 in in vitro infectivity assays using porcine kidney (PK15) cells. The nanobody modifications use highly reliable bioconjugation to a three-dimensional wireframe deoxyribonucleic acid (DNA) origami scaffold. Mechanistic studies suggest that inhibition is mediated by the DNA origami scaffold bound to the virus particle, which obstructs the internalization of the viruses into cells, and that inhibition is enhanced by avidity resulting from multivalent virus and scaffold interactions. The assembled nanostructures demonstrate negligible cytotoxicity (<10 nM) and sufficient stability, further supporting their therapeutic potential. If translatable to other viral species and epitopes, this approach may open a new strategy that leverages existing infrastructures – monoclonal antibody development, phage display, and in vitro evolution - for rapidly developing novel antivirals in vivo.
ContributorsPradhan, Swechchha (Author) / Hariadi, Rizal (Thesis advisor) / Hogue, Ian (Committee member) / Varsani, Arvind (Committee member) / Chen, Qiang (Committee member) / Arizona State University (Publisher)
Created2022
Description
Monkeypox virus (MPXV) is an orthopoxvirus that causes smallpox-like disease and has up to a 10% mortality rate, depending on the infectious strain. The global eradication of the smallpox virus has led to the decrease in smallpox vaccinations, which has led to a drastic increase in the number of human MPXV cases. MPXV has been named the most important orthopoxvirus to infect humans since the eradication of smallpox and has been the causative agent of the 2022 world-wide MPXV outbreak. Despite being highly pathogenic, MPXV contains a natural truncation at the N-terminus of its E3 homologue. Vaccinia virus (VACV) E3 protein has two domains: an N- terminus Z-form nucleic acid binding domain (Z-BD) and a C-terminus double stranded RNA binding domain (dsRBD). Both domains are required for pathogenesis, interferon (IFN) resistance, and protein kinase R (PKR) inhibition. The N-terminus is required for evasion of Z-DNA binding protein 1 (ZBP1)-dependent necroptosis. ZBP1 binding to Z- form deoxyribonucleic acid/ribonucleic acid (Z-DNA/RNA) leads to activation of receptor-interacting protein kinase 3 (RIPK3) leading to mixed lineage kinase domain- like (MLKL) phosphorylation, aggregation and cell death. This study investigated how different cell lines combat MPXV infection and how MPXV has evolved ways to circumvent the host response. MPXV is shown to inhibit necroptosis in L929 cells by degrading RIPK3 through the viral inducer of RIPK3 degradation (vIRD) and by inhibiting MLKL aggregation. Additionally, the data shows that IFN treatment efficiently inhibits MPXV replication in a ZBP1-, RIPK3-, and MLKL- dependent manner, but independent of necroptosis. Also, the data suggests that an IFN inducer with a pancaspase or proteasome inhibitor could potentially be a beneficial treatment against MPXV infections. Furthermore, it reveals a link between PKR and pathogen-induced necroptosis that has not been previously described.
ContributorsWilliams, Jacqueline (Author) / Jacobs, Bertram (Thesis advisor) / Langland, Jeffrey (Committee member) / Lake, Douglas (Committee member) / Varsani, Arvind (Committee member) / Arizona State University (Publisher)
Created2022
Description
Traditional public health strategies for assessing human behavior, exposure, and activity are considered resource-exhaustive, time-consuming, and expensive, warranting a need for alternative methods to enhance data acquisition and subsequent interventions. This dissertation critically evaluated the use of wastewater-based epidemiology (WBE) as an inclusive and non-invasive tool for conducting near real-time population health assessments. A rigorous literature review was performed to gauge the current landscape of WBE to monitor for biomarkers indicative of diet, as well as exposure to estrogen-mimicking endocrine disrupting (EED) chemicals via route of ingestion. Wastewater-derived measurements of phytoestrogens from August 2017 through July 2019 (n = 156 samples) in a small sewer catchment revealed seasonal patterns, with highest average per capita consumption rates in January through March of each year (2018: 7.0 ± 2.0 mg d-1; 2019: 8.2 ± 2.3 mg d-1) and statistically significant differences (p = 0.01) between fall and winter (3.4 ± 1.2 vs. 6.1 ± 2.9 mg d-1; p ≤ 0.01) and spring and summer (5.6 ± 2.1 vs. 3.4 ± 1.5 mg d-1; p ≤ 0.01). Additional investigations, including a human gut microbial composition analysis of community wastewater, were performed to support a methodological framework for future implementation of WBE to assess population-level dietary behavior. In response to the COVID-19 global pandemic, a high-frequency, high-resolution sample collection approach with public data sharing was implemented throughout the City of Tempe, Arizona, and analyzed for SARS-CoV-2 (E gene) from April 2020 through March 2021 (n = 1,556 samples). Results indicate early warning capability during the first wave (June 2020) compared to newly reported clinical cases (8.5 ± 2.1 days), later transitioning to a slight lagging indicator in December/January 2020-21 (-2.0 ± 1.4 days). A viral hotspot from within a larger catchment area was detected, prompting targeted interventions to successfully mitigate community spread; reinforcing the importance of sample collection within the sewer infrastructure. I conclude that by working in tandem with traditional approaches, WBE can enlighten a comprehensive understanding of population health, with methods and strategies implemented in this work recommended for future expansion to produce timely, actionable data in support of public health.
ContributorsBowes, Devin Ashley (Author) / Halden, Rolf U (Thesis advisor) / Krajmalnik-Brown, Rosa (Thesis advisor) / Conroy-Ben, Otakuye (Committee member) / Varsani, Arvind (Committee member) / Whisner, Corrie (Committee member) / Arizona State University (Publisher)
Created2022
Description
Urinary tract infections (UTIs) disrupt military women’s service obligations and health. Females are more susceptible to UTIs due to their unique anatomical features and hormone fluctuations affecting vaginal flora. During phase 1 of the menstrual cycle (onset of bleeding, menstrual cycle days 1-5), estrogen levels significantly decrease and inhibit the growth of lactobacilli, good bacteria that are essential in warding off harmful bacteria and infections, particularly pathogens of UTIs. To reduce UTI onset, it is recommended to frequently urinate with sufficient urine void volume to facilitate washing out harmful bacteria from the bladder and urethra. While menstruating, increased fluid consumption to support urination frequency and void volume may be critical, as the urethra and urinary tract are more predisposed to pathogenic bacteria found. Yet, there is a lack of research investigating the impact of hydration on urinary tract health during menstruation. The study sought to examine the effects of increased water fluid intake on the uropathogenic bacterial activity of underhydrated menstruating premenopausal females. Thirteen females underwent a 2x2 randomized crossover trial to evaluate the effectiveness of a) additional 1.89 L of water fluid intake and b) maintain habitual fluid intake on two subsequent phase 1 menses. At each phase 1 menses, fluid intake was gathered on days 2 and 5 to determine the fluid amount consumed. First-morning urinations on days 3 and 6 assessed urogenital bacterial activity. Combining data collection days 2 and 5 per intervention (INT) and control (CON), the mean±SD for total fluid intake was INT 2.99±1.05 and CON 1.85±0.89, resulting in a 62% increase, p< 0.001, η2= 0.459. For days 2 and 5, a 48% and 80% increase in total fluid in from CON to INT was found, ps< 0.01. However, only four cultures detected uropathogenic bacteria from four participants, with no patterns between conditions or days, making it difficult to determine the effectiveness of the intervention. Though the intervention results were undetermined, military women’s hydration, menstruation, and urinary tract health remain prominent health concerns. Efforts to assess their fluid consumption and urination behaviors during menstruation and UTI risks are warranted.
ContributorsVento, Kaila Ann (Author) / Wardenaar, Floris C (Thesis advisor) / Johnston, Carol (Committee member) / Kavouras, Stavros (Committee member) / Koskan, Alexis (Committee member) / Lynch, Heidi (Committee member) / Arizona State University (Publisher)
Created2022
Description
Poxviruses such as monkeypox virus (MPXV) are emerging zoonotic diseases. Compared to MPXV, Vaccinia virus (VACV) has reduced pathogenicity in humans and can be used as a partially protective vaccine against MPXV. While most orthopoxviruses have E3 protein homologues with highly similar N-termini, the MPXV homologue, F3, has a start codon mutation leading to an N-terminal truncation of 37 amino acids. The VACV protein E3 consists of a dsRNA binding domain in its C-terminus which must be intact for pathogenicity in murine models and replication in cultured cells. The N-terminus of E3 contains a Z-form nucleic acid (ZNA) binding domain and is also required for pathogenicity in murine models. Poxviruses produce RNA transcripts that extend beyond the transcribed gene which can form double-stranded RNA (dsRNA). The innate immune system easily recognizes dsRNA through proteins such as protein kinase R (PKR). After comparing a vaccinia virus with a wild-type E3 protein (VACV WT) to one with an E3 N-terminal truncation of 37 amino acids (VACV E3Δ37N), phenotypic differences appeared in several cell lines. In HeLa cells and certain murine embryonic fibroblasts (MEFs), dsRNA recognition pathways such as PKR become activated during VACV E3Δ37N infections, unlike VACV WT. However, MPXV does not activate PKR in HeLa or MEF cells. Additional investigation determined that MPXV produces less dsRNA than VACV. VACV E3Δ37N was made more similar to MPXV by selecting mutants that produce less dsRNA. By producing less dsRNA, VACV E3Δ37N no longer activated PKR in HeLa or MEF cells, thus restoring the wild-type phenotype. Furthermore, in other cell lines such as L929 (also a murine fibroblast) VACV E3Δ37N, but not VACV WT infection leads to activation of DNA-dependent activator of IFN-regulatory factors (DAI) and induction of necroptotic cell death. The same low dsRNA mutants demonstrate that DAI activation and necroptotic induction is independent of classical dsRNA. Finally, investigations of spread in an animal model and replication in cell lines where both the PKR and DAI pathways are intact determined that inhibition of both pathways is required for VACV E3Δ37N to replicate.
ContributorsCotsmire, Samantha (Author) / Jacobs, Bertram L (Thesis advisor) / Varsani, Arvind (Committee member) / Hogue, Brenda (Committee member) / Haydel, Shelley (Committee member) / Arizona State University (Publisher)
Created2021
Description
Precise modulation of gene expression is essential for proper tissue and cell-specific differentiation and function. Multiple distinct post-transcriptional regulatory mechanisms, such as miRNA (microRNA)-based regulation and alternative polyadenylation (APA), are an intrinsic part of this modulation and orchestrate intricate pathways to achieve and maintain balanced gene expression.MiRNA-based regulation and APA function through sequence motifs located in the 3’ Untranslated Region (3’UTR) of mRNA transcripts. MiRNAs are short (~22 nt) non-coding RNA molecules that bind target sequences within the 3’UTR of an mRNA transcript, inhibiting its translation or promoting its degradation. APA occurs during RNA transcription termination and leads to the preparation of mature mRNAs with different 3’UTR lengths, allowing shorter 3’UTRs to bypass miRNA regulation.
In addition to these two post-transcriptional forms of regulation, co-transcriptional mechanisms such as alternative RNA splicing, which produces distinct gene products from a precursor mRNA, are also important in controlling gene expression.
While miRNA-based regulation, APA, and alternative RNA splicing are important regulatory mechanisms, there is a lack of comprehensive understanding of how they interact and communicate with each other. This thesis studies these three forms of gene regulation in the nematode C. elegans, with the goal of extracting rules and mechanisms used by each of them in development to establish and maintain somatic tissue identity.
After isolating miRNA targets in multiple C. elegans somatic tissues, it was found that miRNAs can modulate the abundance of hnRNPs and SR proteins, which are known to control alternative RNA splicing in a dosage-dependent manner.To identify tissue-specific miRNAs, a nuclear fluorescent cell sorting (FACS)-based methodology named Nuc-Seq, was developed to isolate and sequence tissue-specific miRNAs from body muscle tissue. Nuc-Seq identified 2,848 muscle-specific protein-coding genes and 16 body muscle-specific miRNAs. This data was used to develop a high-quality body muscle-specific miRNA-APA Interactome which allows studies in regulatory processes in detail.
Taken together, this work highlights some of the complexity of pre- and post-transcriptional gene regulation and sheds light on how miRNA-based regulation, APA, and alternative RNA splicing are interconnected and are responsible for the establishment and maintenance of tissue identity.
ContributorsSchorr, Anna L (Author) / Mangone, Marco (Thesis advisor) / Harris, Robin (Committee member) / Sharma, Shalini (Committee member) / Varsani, Arvind (Committee member) / Arizona State University (Publisher)
Created2023