Master of Arts (MA), Bowling Green State University, 2024, Psychology

Shared reward pathways in the brain unveil the potential for the development of dependence on a variety of substances, including commonly recognized drugs of abuse and, more insidiously, sugar. Sugar overconsumption has been associated with compulsivity and impulsivity repetitive behaviors which are predictors of later substance abuse. Furthermore, previous research has shown that rats can develop symptoms mirroring addiction such as binging, craving, tolerance, and withdrawal in response to sugar alone. Motivation research has indicated that impaired reward relativity is a key component of vulnerability to addiction. The ability of an animal to discriminate between differing levels of rewards for the amount of work exerted to receive that reward may predict later addictive behavior to a variety of substances. This thesis examined the appetitive and consummatory behavior of non-food restricted female Wistar rats in self-administration tasks of sucrose and ethanol solutions. Relative reward effects were evaluated by using trials that differ in time of access to the reward (20s vs 10s vs 5s). The results suggest that non-food restricted Wistar rats show discrimination between substance and length of trial, as well as some sensitivity to intra-session alterations in ethanol reward. They exhibit diminished sensitivity to sucrose in consumption and lick rate. Behavioral measures like consumption and nosepoke latency had some predictive potential in regard to behavioral response to ethanol. The incentive contrast paradigm used in this project allows a closer examination of the motivational processes shared by alcohol and sugar that could result in addiction. Using natural reward sensitivity to predict future addiction could aid significantly in preventing and treating substance use disorders.

Committee: Howard Casey Cromwell Ph.D. (Committee Chair); Melissa Keith Ph.D. (Committee Member); Jari Willing Ph.D. (Committee Member) Subjects: Animals; Neurosciences; Psychology

Doctor of Philosophy, The Ohio State University, 2022, Human Ecology: Human Nutrition

Approximately 48 million people, per year, are estimated to contract some form of foodborne disease[1], but foodborne infection is a risk which can be mitigated with appropriate food safety behaviors. [2]. Cancer patients experience a compromised immune system, both due to the mechanisms of cancer and due to the means by which treatments for cancer act upon the body[3]. This means that patients receiving treatment are at significantly higher risk of acquiring a foodborne infection than people living without cancer[4], and the Centers for Disease Control (CDC) has issued specialized guidelines for immunocompromised people [5]. Currently, approximately 5% of the US population are cancer survivors, with the raw number anticipated to increase from the current 16.9 million to 22.2 million, by 2030[6]. A person's risk of developing foodborne disease depends on a number of factors related to the host, their environment, and the pathogen is question. In 1998, Coleman et al. posited the design of the Disease Triangle, a framework whereby microbial risk analysis could be performed by assessing the host, pathogen, and environment[7]; an updated version of this model, now called the Health Triangle, expands upon what, explicitly, might be controlled within each of these three categories[8]. Environmental factors include aspects such as diet, nutrition, exposure (i.e., through air, occupational exposure, and the indoor/outdoor environment). Host factors depend on the general host of the health, with factors such as age, genetics, immune system, and underlying illness being harder or even impossible to change. Coleman et al. add a third aspect to the Health Triangle, which includes the microbiota and modulators. Use of antibiotics, chemotherapy, fecal transplants, and pre-, pro-, and syn-biotics can all impact the microbiome, and some can be modulated with diet or treatment. By performing appropriate food safety behaviors, cancer patients are able to decrease their ris (open full item for complete abstract)

Committee: Sanja Ilic (Advisor); Tonya Orchard (Committee Member); Ellen Evans (Committee Member); Dayssy Diaz Pardo (Committee Member); Irene Hatsu (Committee Member) Subjects: Behavioral Sciences; Biology; Health Education; Health Sciences; Microbiology; Nutrition

PHD, Kent State University, 2021, College of Arts and Sciences / School of Biomedical Sciences

Circadian rhythms play a prominent role in psychiatric health with disruption in rhythms associated with poor mental health. Corticosterone (CORT) is an important hormone in entraining the biological rhythms of many cells throughout the body and coordinating peripheral rhythms with the central master clock. In aim 1, we tested the hypothesis that excess CORT during the circadian trough would lead to a flattening of period genes (Per1 and Per2) rhythms in limbic brain areas, and thus impact emotional behaviors. This was not expected to be mirrored when excess CORT occurred during the circadian peak. Male rats were injected daily with 2.5 mg/kg CORT or vehicle for 21 days at either ZT0 or ZT12 and sucrose preference, open field, and forced swim behaviors measured during the dark phase of the light cycle. After three weeks of injections, a reduction in sucrose preference was observed in animals injected with CORT at ZT0 and the reduction significantly correlated with reductions in Per2 mRNA expression in the central amygdala (CeA) and bed nucleus of the stria terminalis (BNST). No changes in behavior were observed in animals injected with CORT at ZT12, and period gene expression was mostly unaffected except for an increase in Per2 within the prefrontal cortex. In aim 2, we hypothesized that disruption of limbic period genes in the CeA or BNST would be sufficient to induce behavioral changes. DsiRNA was used to directly reduce Per2 levels in either the CeA or BNST and behavior was assessed. Despite reductions in Per2 expression in the CeA, no behavioral changes were observed. In contrast, a reduction in Per2 expression in the BNST was sufficient to reduce sucrose preference. The results demonstrate that CORT significantly contributes to the circadian expression of Period genes in certain limbic brain areas and disruption in diurnal CORT or Per2 expression can lead to impaired emotional behavioral responses.

Committee: John Johnson (Advisor) Subjects: Biomedical Research; Neurosciences

Master of Science, Miami University, 2021, Microbiology

Environmental salt concentration is an important abiotic factor indicative of environmental change and stress. As the environment changes the productivities of plants plummet thus, draining resources of the agriculture industry. Cyanobacteria are photosynthetic organisms that utilize both light and CO2 for their metabolism. Their evolutionary similarities with plants coupled with the ability to be used as a microbial feedstock make them ideal model organisms. Synthetic biology utilizes rational engineering approaches to increase the biomass and sucrose productivity of Synechococcus elongatus (Se) PCC 7942. However, these approaches are limited by a plateau effect seen in product synthesis and exhaustion of the cell. Through accelerated evolution, it is possible to induce mutations under specific stressors to drive distinct adaptations. Employing a hypermutator strain, we evolved the cells in increasing concentrations of salt and found increasing sucrose productivity following each round of evolution. Additionally, one evolved strain, Se2-192, exhibited increased salt tolerance and growth when re-exposed to salt. This project provides evidence of salt adaptation in S. elongatus PCC 7942 strains when evolved in high salt concentrations. Furthermore, the mutants produced in these studies can be used to identify adaptative mechanisms employed by the cell to deepen our understanding of metabolic plasticity.

Committee: Xin Wang Dr. (Advisor); Luis Actis Dr. (Committee Member); Donald J. Ferguson Dr. (Committee Member) Subjects: Microbiology

Master of Arts (MA), Bowling Green State University, 2021, Psychology/Experimental

Research on sex differences for preferences of reward outcomes, such as flavors, show mixed results between male and female rats. Some studies suggest that females perform consistently and at higher rates for sucrose concentrations than males; however, these finding are not consistently shown. This study examined sex difference in motivation for sucrose reward and focused on relative reward effects as they interact with basic motivation. Motivational drives help to maximize rewarding outcomes and avoid unpleasant states or punishments; an example of a motivational state is hunger. Inducing hunger through food restriction is a method that is used in the present study to examine its influence on reward processing. This study uses three levels of sucrose solution concentrations as rewards. All reward items have a value and past research suggests that a set of rewards can vary in value demonstrated by a preference hierarchy. In this study we are focused on determining if there is a difference between the sexes on their ability to change performance on the original concentration (control) given when an up-shift or down-shift occurs. If differences in responses to the same outcome occurs, then it is labeled as an incentive contrast. Results support few to no sex differences in reward discrimination or incentive contrast, but large sex differences in sucrose consumption. Moreover, significant effects were found for the influence of motivational state and behavioral context. Animals expressed incentive contrast when food restricted and in the context of their home cage. These effects were diminished to absent when animals ate freely or were tested in an operant task for relative reward effects. Overall, the findings point to diverse influences.

Committee: Howard Cromwell Ph.D. (Advisor); Jari Willing Ph.D. (Committee Member); Abby Braden Ph.D. (Committee Member) Subjects: Behavioral Psychology; Psychology

PhD, University of Cincinnati, 2017, Medicine: Neuroscience/Medical Science Scholars Interdisciplinary

Many individuals increase their intake of tasty, high-calorie foods during times of stress. In turn, these palatable foods can reduce physiological and psychological measures of stress, a concept reflected in the term `comfort food.' Obesity is one of the major public health issues facing the United States, and stress eating may be a contributing factor. Thus, investigating the mechanisms behind palatable food-mediated stress relief could provide important insights into treatments or prevention of obesity-related disorders. A limited sucrose intake (LSI) paradigm of palatable foods has been shown to reduce stress responses in male rats through a basolateral amygdala (BLA) mediated neurocircuit. However, women may be more prone to `comfort feeding' than men, and these eating behaviors may fluctuate across the menstrual cycle. This suggests there may be sex differences in how palatable food affects stress responses. It is unknown if palatable foods reduce stress responses in female rats, and if the effects vary with estrous cycle. Therefore, we characterized the effects of limited sucrose intake on stress responses in female rats. We found that a history of LSI reduces HPA axis responsivity and behavioral anxiety; notably this stress blunting is estrous-cycle dependent. LSI only reduces stress responses during the proestrus/estrus (P/E) stage of the estrous cycle, and not the diestrus 1/diestrus 2 (D1/D2) stage. This suggests fluctuating levels of gonadal hormones may be interacting with palatable foods to modulate stress responses. We used traditional neuroanatomical methods and innovative mathematical modeling techniques to identify a potential neurocircuit underlying this cycle-specific stress relief. We found estrous cycle-specific effects of LSI in the BLA, central amygdala, and the bed nucleus of the stria terminalis. Furthermore, Bayesian modeling, which was used to analyze predicted relationships among multiple brain regions, indicated that during P/E LSI (open full item for complete abstract)

Committee: Teresa Reyes Ph.D. (Committee Chair); James Herman Ph.D. (Committee Member); Brent Myers (Committee Member); Matia Solomon Ph.D. (Committee Member); Yvonne Ulrich-Lai Ph.D. (Committee Member) Subjects: Neurology

Doctor of Philosophy, The Ohio State University, 1977, Graduate School

Committee: Not Provided (Other) Subjects: Health Sciences

MS, University of Cincinnati, 2009, Engineering : Chemical Engineering

A microemulsion is an optically clear, thermodynamically stable mixture of a hydrophilic species (typically water) and a hydrophobic species (oil) stabilized by a flexible surfactant film. They exist primarily as dispersions of swollen micelles of oil in water (O/W), swollen reverse micelles of water in oil (W/O), or as bicontinuous structures. While there are many applications for these formulations, one that has received much attention is the use of microemulsions as structure-directing agents for polymerization reactions. Of particular interest is arresting the structure of a bicontinuous microemulsion in polymer form for use in synthesizing ultra filtration membranes. However, previous attempts to do so using aqueous microemulsions have fallen short due to surfactant film rearrangement, non-uniform reaction initiation, and breakthrough of the template. Replacing water in typical microemulsion formulations with sugar has been shown to mimic traditional microstructure of aqueous microemulsions but in a solid, glassy form. These microemulsion glasses have been used as templates for free-radical polymerizations with 1-to-1 copies of the microemulsion structure formed as a polymer membrane. However, in the interest of broadening their potential applications, two different research projects were proposed. First, the glass transition temperature of the initial system of sucrose, trehalose, sucrose ester surfactant, and limonene oil was determined to be 570C. While this is acceptable for low-temperature applications, higher temperature applications run the risk of crystallization and phase separation of the template. In order to combat this, it was proposed that sodium citrate, having been shown to increase the glass transition temperature of sucrose significantly, replace trehalose in the formulation in hopes that the glass transition temperature increases for the system. Phase behavior studies confirmed that bicontinuous microemulsion glasses can be formed with the (open full item for complete abstract)

Committee: Chia Chi Ho PhD (Committee Chair); Carlos Co Phd (Committee Member); Stephen Clarson PhD (Committee Member); Soon Jai Khang PhD (Committee Member) Subjects: Chemical Engineering

PhD, University of Cincinnati, 2009, Engineering : Chemical Engineering

In aqueous systems, the hydrophobic effect drives the self-assembly of amphiphilesinto a broad range of micellar, rod-like, bicontinuous, and liquid-crystalline complex fluids, which have myriad biological, materials, and product applications. However, amphiphilic self-assembly is not limited to aqueous systems. We have explored the self assembly of surfactants in anhydrous sugars. Our study reveals that anhydrous powders of sugars and surfactants suspended in oil spontaneously form molten microemulsion glasses with nanometer-size domains of sugar and liquid oil without mixing. The low cost, water solubility, low toxicity and stabilizing properties of glassy sugars make them ideal water replacements for many pharmaceutical, food and materials synthesis applications. The optical clarity and solid appearance of these glasses at room temperature belie their inclusion of more than 50% (vol.) oil, which confers liquid-like diffusivity. We have also investigated the phase behavior and characterization studies of edible microemulsions of d-limonene (orange oil) with concentrated sugar solutions (>65 wt%) using sucrose laurate and sucrose oleate as surfactants. The phase behavior of these mixtures is studied as a function of temperature and surfactant composition, identifying the specific effects of sugar concentration, surfactant chain length, and oil loading on the formation of microemulsion and lamellar phases. Small-angle neutron scattering experiments confirm the presence of well-structured microemulsions with domain sizes ranging from ~35 to 60 nm. With few exceptions, the patterns of microemulsion phase behavior with concentrated sugar solutions are very similar to that of aqueous systems. These studies simulate the effect of either increasing sugar concentrations or removing water (e.g. spray drying) on the one phase microemulsion region. In addition to providing better understanding of the underlying phenomena of formation of sugar based microemulsion glasses, the (open full item for complete abstract)

Committee: Carlos Co PhD (Advisor); Chia-Chi Ho PhD (Committee Member); Gerald Kasting PhD (Committee Member); Steve Clarson PhD (Committee Member) Subjects: Chemical Engineering

Doctor of Philosophy, The Ohio State University, 2007, Molecular, Cellular, and Developmental Biology

Efficient translation of mRNA is an essential step in expression of all genes. Retroviruses encode obstacles to efficient viral mRNA translation. Study of retrovirus mRNA translational control is relevant to the processes of immunodeficiency, progression to neoplasia, and safe and efficacious gene transfer vector by this diverse class of RNA virus. This dissertation investigated fundamental mechanisms that control translation of retroviral mRNA and applied our findings to improve translation of transgene mRNA in lentiviral vectors. Chapter 2 unraveled a dynamic interface between HIV-1-induced cell cycle arrest and host translation suppression. Metabolic labeling experiments demonstrated that HIV-1-induced cell cycle arrest attributable to Vpr and Vif accessory proteins significantly limits the translation capacity of infected lymphocytes. Kinetic and ribosomal profile analysis determined that HIV-1 gag mRNA translation is resistant to this potential block to virus production. Cytosolic fractionation experiments demonstrated that gag RNA/ribosome complexes are translated on membrane-bound ribosomes and that amino-terminal myristate of Gag provides an ER partitioning signal. These results overturn the common notion that retrovirus translation is confined to soluble polyribosomes. HIV-1 mRNA partitioning to ER ribosomes represents a novel co-adaptation strategy to promote synthesis of viral structural protein. Chapter 3 developed a sucrose gradient fractionation method to interrogate the translation activity of the entire HIV transcriptome in lymphocytes. The assay verified that alternatively spliced transcripts are associated with polyribosomes. Chapter 4 applied for the first-time the post-transcriptional control element (PCE) of spleen necrosis virus (SNV) to facilitate translation of vector transgene mRNA. Coordinate enhancement of transgene transcription and translation in a lentiviral vector was achieved by combination of SNV PCE with a CMV transcriptional enhanc (open full item for complete abstract)

Committee: Kathleen Boris-Lawrie (Advisor) Subjects: Biology, Molecular

Doctor of Philosophy, Case Western Reserve University, 2004, Pathology

Identifying which processes and proteins control glucose transport could provide important clues to understanding and treating a number of clinical entities including diabetes and some cancers. Glucose transport across the plasma membrane occurs by either sodium-dependent or independent glucose transporters. In order to study the mechanisms which control acute changes in glucose transport by sodium-independent glucose transporters, we use the non-transformed rat liver – derived Clone 9 cell line. These cells respond to the acute inhibition of oxidative phosphorylation by azide with a 4-6 fold stimulation of glucose transport and a 1.8 fold increase in the amount of glucose transporter 1 (Glut1) in the plasma membrane. In Clone 9 cells under basal conditions, ~38 % of Glut1 in the post-nuclear lysate is localized to the detergent-resistant membrane (DRM) microdomains. Acute exposure to azide decreased this figure by ~40 %. In order to examine the effects of azide on Glut1 localization to the plasma membrane of the Clone 9 cell, we performed subcellular fractionation of the post-nuclear homogenates. Approximately 30 % of the Glut1 in the post-nuclear homogenate was recovered in the plasma membrane (PM) compartment and 50 % of this PM Glut1 localized to the DRM fraction. Acute inhibition of oxidative phosphorylation with azide resulted in a 1.6-fold increase in the total abundance of Glut1 in the PM and was associated with a 2.9 fold increase in the abundance of Glut1 in the non-DRM fraction but no significant change in the content of Glut1 in the DRM fraction. We conclude that in the Clone 9 cell Glut1 localizes to detergent-resistant membrane microdomains in the plasma membrane. Moreover, in these cells the azide – induced increase in glucose transport is associated with an increase of Glut1 abundance in the non – DRM fraction of the plasma membrane and a decrease of Glut1 association with the DRM fraction of a membrane compartment other than the plasma membrane. The (open full item for complete abstract)

Committee: Faramarz Ismail-Beigi (Advisor) Subjects: Biology, Cell