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2020 Abstracts

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Gender, Participation, and Institutional Settings for Young Adults in Utah Valley

December 30, 0020 12:00 AM
Caldwell-Gehring, Kailey (Brigham Young University)
Faculty Advisor: Haug, Jordan (Brigham Young University, Anthropology)

My research focuses on how young adult men and women are interacting and participating in institutionalized religious and educational settings in Utah Valley. Men and women in these settings choose to interact with authority and participation differently when in situations with historical precedence for a higher concentration of male voices, views and interpretations. This research focuses on not only the amount of participation, but also the type of interaction that men and women choose to engage in as part of these institutional settings. The focus on how male and female participation varies is necessary in order to value and give space to the ideas and voices of those who interact in these institutional spaces. Through ethnographic research methods including participant observation and interviewing, I was able to research this topic. I attended religious and educational events in Utah Valley and focused on types of participation (comments vs questions, prefacing comments, use of and appeal to authority, and many others). The general trends that I found reflect the division in passive versus active participation between men and women in these situations. Within my research. men are far more likely to engage in independent thought, comments and interpretation while women are more often participating by volunteering to read or answering direct questions. When a woman is in a position of authority both men and women are more likely to engage in more personal participation and involvement than they do when a man is in a position of authority. My research on gender and participation within institutional spaces for young adults in Utah Valley focuses on how men and women are participating in these areas and how that kind of space can be more balanced in gender based interaction.
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Ancestral Pueblo Exploitation of Raw Materials in Kiva Construction

December 30, 0020 12:00 AM
Clark, Jessica (Brigham Young University)
Faculty Advisor: Allison, Jim (Family Home and Social Sciences, Anthropology)

The Kiva was an important element to daily like in the ancient ancestral Puebloan culture. Using construction materials gathered from an excavation at a Pueblo III site in southeastern Utah, the project focuses on how the raw materials of the area were exploited for construction purposes. By examining the composition of plaster, mortar, and masonry rocks I hope to gain a more insightful understanding of how the Ancestral Puebloan people used their available resources. In addition, studying impressions on burned impressed adobe, along with charcoal samples from site, will help me to gain an understanding of the wood used for the kiva roof, as well as potentially showing how the roof of the structure held. Because indigenous people of the American Southwest have strong ties with the earth, gaining a small understanding of how their ancestors used the land is an important study.
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Prophylactic Treatment of Post-Traumatic Stress Disorder with Mifepristone and Propranolol

December 30, 0020 12:00 AM
Boyce, Zach; Smith, Calvin; Martin, Ashlyn; Ketch, Yuko; Dugan, James; Wright, Cole (Brigham Young University)
Faculty Advisor: Jeffrey, Edwards (Brigham Young University, Physiology and Developmental Biology)

Post-traumatic stress disorder (PTSD) is a complex psychological disorder that affects about 1 of 4 individuals after a stressful/traumatic experience. One common model to induce PTSD in rats is social defeat (SD) combined with chronic light exposure. First, we screened rats for natural anxiety to use in the SD protocol. Next, elevated plus maze (EPM) and light-dark transition (LDT) tests were used to detect anxious behavior after SD. The SD protocol induced significant anxious behavior when compared to controls. Next, we performed long-term potentiation (LTP) field electrophysiology synaptic plasticity physiology experiments in brain slices of the ventral hippocampus (VH) and basolateral amygdala (BLA), regions known to have altered enhanced plasticity in PTSD. SD significantly increased LTP in the VH (~25% greater than control) and BLA (~35% greater than control). To determine whether a prophylactic treatment could prevent the physiological changes of PTSD, we simultaneously administered two drugs at 10 mg/kg doses by intraperitoneal injection one week prior to and for the duration of SD. The first, propranolol, is a beta-adrenergic receptor antagonist, and the second, mifepristone, is a glucocorticoid receptor antagonist; thus, treatment would target the action of stress hormones altered in PTSD. To determine whether a prophylactic treatment could prevent the physiological changes of PTSD, propranolol and mifepristone, antagonists of two stress receptors, were simultaneously administered at 10 mg/kg doses by intraperitoneal (IP) injection one week prior to and for the duration of SThese drugs significantly decreased LTP in the VH and BLA back to near-control levels while SD rats with vehicle injections still had elevated LTP. However, SD drug-treated rats did not show significant reductions in anxious behavior compared to non-injected SD rats and also exhibited significantly more anxious behavior than control rats, suggesting the IP injection induced added stress. Next, we used rtPCR to examine gene expression of drug targets and plasticity markers to determine potential mechanisms for observed LTP changes. In both the VH and BLA, SD was associated with a significant decrease in glucocorticoid and mineralocorticoid receptor expression, which was restored to control levels under drug treatment. Overall, our data suggest that propranolol and mifepristone together may be a potential prophylactic treatment for preventing PTSD through a mechanism likely mediated by glucocorticoid/mineralocorticoid receptors.
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Understanding The Role Of Small Non-coding RNA In Bumble Bee Social Behavior

December 30, 0020 12:00 AM
Figgins, Anna C.; Hunter, F. Kate; Kapheim, Karen M. (Utah State University)
Faculty Advisor: Kapheim, Karen (College of Science, Biology Department)

Certain species of ants, bees, and wasps have some of the most sophisticated forms of cooperative behavior known throughout the animal kingdom. These eusocial insects live in large family groups made up of castes (e.g., queens and workers) that specialize on different tasks within a colony. In many species, division of labor between queens and workers is associated with behavioral and physiological traits such as dominance interactions, ovary maturation, and lipid stores. Remarkably, these large phenotypic differences between castes emerge from a shared genome. This suggests caste differences stem from changes in how shared genes are regulated. We have been investigating the role of a small regulatory molecule (microRNA miR-13b) as a potential regulator of division of labor in bumble bees (Bombus impatiens). We tested the hypothesis that miR-13b regulates division of labor by inhibiting its function using small-interfering RNA (siRNA). We inhibited miR-13b function by injecting a synthetic antagonist of miR-13b (antagomir) into the abdomens of live bees. The average expression of miR-13b in the fat body of bees that received the antagomir injection was 0.52 relative to those that received the control injection (n = 7). This inhibition of miR-13b expression was accompanied by a significant decrease in fat body size. However, the influence of the antagomir only lasted 1 day. Future experiments will determine if the antagomir can influence gene expression longer than 1 day and assess physiological and behavioral changes in B. impatiens after miR-13b is inhibited. Knowledge gained from this study allows us to understand more about the mechanisms underlying social behavior in bees and helps us investigate how behavior is regulated by gene expression.
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Understanding Drug Addiction Pathways Through Optogenetics

December 30, 0020 12:00 AM
Bird, Devin; Nufer, Teresa; Wu, Bridget; Edwards, Jeffrey (Brigham Young University)
Faculty Advisor: Edwards, Jeffrey (Brigham Young University, Physiology and Developmental Biology)

Drug addiction is a consequence of neural plasticity in the ventral tegmental area (VTA), an area of the brain's reward system, in which higher levels of dopamine are expressed. Research suggests that decreased activity of inhibitory _-aminobutyric acid (GABA) neurons in the VTA could be the cause of increased activity of dopaminergic cells in the VTA, and thus mediate opiate addiction (Tan). However, not much additional research has been performed to evaluate the plasticity of VTA GABA neurons and the role they play in addiction. Why are VTA GABAergic cells being inhibited and how? We hypothesize that inhibitory inputs onto GABA neurons in the VTA directly affect the degree of inhibition of VTA dopaminergic cells. Additionally, we hypothesize that GABAergic neurons of the lateral hypothalamus (LH) is a source input that extends into the VTA and inhibits VTA GABAergic neurons. We believe that inhibition from these LH neurons induces plasticity of VTA GABAergic neurons.

Through the use of optogenetics we have been able to isolate precise GABAergic pathways that lead into the VTA. Specifically, we have isolated input sources from the LH. These optogenetic experiments, in combination with electrophysiology, have allowed us to measure the specific effects that LH GABA neurons have on VTA GABA neurons. Currently, our data suggests that LH GABAergic cells do induce long-term depression (LTD) in VTA GABAergic cells, however, it is too soon to make any conclusions. Although experiments are still underway, we believe that LH GABAergic neurons play an important role in the drug addiction pathway by inhibiting VTA GABAergic neurons and inducing plasticity.
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Does LDS Affiliation Lead to Shame in LGBT+ Members

December 30, 0020 12:00 AM
Nielson, Madison; Salas, Jessica; Baird, Todd (Weber State University)
Faculty Advisor: Baird, Todd (Weber State university, Psychology)

The reason for shame stems from feelings of inadequacy and that conflicts have become too overwhelming for an individual to handle. This creates emotional dysfunction because the conflict is not aligning with the individual feelings of what is appropriate on a societal level (Kilborne, 2019). Shame is created by an individual thinking about another's perception of them, it is a highly socially involved emotion. Religion is a large cultural proponent adding to an individual's feeling of shame, there are rigid structures of what behaviors are found acceptable and lifestyle standards to achieve the highest level of being and what happens to an individual after death. LGBTQ+ individuals who are religious have unique struggles. They face more internalized heterosexism which reduces self-esteem and life satisfaction and increases distress (Foster et. al., 2017). Religion intermixed with same-sex attraction or gender identification can be linked to shame proneness which leads to lower self-esteem (Green & Britton, 2013) because the nature of the beliefs is strongly against their identification. This is an extremely problematic issue that affects their familial relationships, many do not feel comfortable coming out to their parents in fear that they will be judged. The Church of Jesus Christ of Latter-day Saints has stringent policies about same-sex attraction. Policy 21.4.6 the LDS Church states that "homosexual behavior violates the commandments of God, is contrary to the purposes of human sexuality, and deprives people of the blessings that can be found in family life and in the saving ordinances of the gospel". We predict that individuals who are LGBTQ+ and LDS will have more shame, have lower self-esteem, will have greater difficulty in identifying as LGBTQ+, will conceal their sexuality more, and have lower pride in being LGBTQ+ than those who are LGBTQ+ and non-LDS.
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Exploring consumer travel mode decision making

December 30, 0020 12:00 AM
Garrison, Mackenzie; (Utah State University)
Faculty Advisor: Graul, Antje (Jon M. Huntsman School of Business, Marketing and Strategy Department); Thompson, Greg (Brigham Young University, Anthropology)

The means of transportation is forever changing and just recently multiple means of electric transport have emerged in our cities. People are taking full advantage of all means of transportation but the framework for decision making has not adapted to include all means of transport. Current frameworks are largely utilitarian based and do not account for a large portion of travel mode choice behaviors. The goal for this project was to identify alternate decision frameworks for understanding and modeling consumers' personal travel mode choices and determine the appropriateness of a non-compensatory Maslow-like framework for explaining consumers decision making processes for travel mode choice. To complete this goal, we followed two objectives:
1) Qualitatively determine the structure and contents of consumers' pre-consumption perceived satisfaction of needs for understanding the personal transportation mode choice decision-making process and consumers' intention to engage into a particular mode of transport from a consumer behavior perspective, and
2) Quantitatively validate the proposed framework by taking both pre-consumption perceptions and post-consumption evaluations into consideration.
To collect data, we used two means of research: conducting focus groups and collecting surveys. This allowed us to collect both quantitative and qualitative data. From this data we concluded that travel mode decisions are influenced by a number of factors ranging from convenience to environmental concern. Depending on the type of transportation, some factors were considered more than others. Some factors included health when bicycling, traffic when driving an independent vehicle, and relationship building with bicycle and scooter share. As we predicted, there are many factors, both utilitarian and non-utilitarian, that drive transportation decision making.
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Precipitation and Thunder Associated Vocalizations in Mantled Howler Monkeys (Alouatta palliata)

December 30, 0020 12:00 AM
Pehkonen, Eliza (Salt Lake Community College)
Faculty Advisor: Seaboch, Melissa (Salt Lake Community College, Anthropology)

Precipitation-associated behaviors have been observed in several species of primate including bonobos (e.g., building leafy shelters), chimpanzees (e.g., drinking, rain dancing displays), and mantled howler monkeys (e.g., licking rain from the air, altering typical behavior based on weather and season). The purpose of this study is to determine if mantled howler monkeys (Alouatta palliata) exhibit precipitation-associated vocalizations. A. palliata is well known for its vocalizations, which are the loudest sound made by any terrestrial mammal and are used for a wide variety of communicative purposes, such as attracting mates, defending territory, and deterring predation. Given the purpose with which A. palliata vocalizes and the existence of precipitation-associated behaviors within primate species, including A. palliata, it was hypothesized that A. palliata would vocalize in association with climatic events (precipitation and thunder). To test this hypothesis, 41.75 hours of data were collected on A. palliata over a two-week time period during the rainy season at La Selva Biological Station in Costa Rica. All-occurrence sampling was used to record the timing and duration of all A. palliata vocalizations, precipitation, and thunder events. Events were considered accompanied if they occurred within five minutes of one another. Of the 59 observed vocalization events 53% were associated with climatic events. Of the 20 observed precipitation events 90% were accompanied by vocalizations and of the 37 observed thunder events 57% were accompanied by vocalization. Associated vocalizations occurred before, during and after climatic events, however, during or after were most common. The data indicate an association between A. palliata vocalization and precipitation, confirming the hypothesis. Further research is warranted to investigate a possible purpose of precipitation-associated vocalizations, an understanding of which could provide further insight into A. palliata's behavioral interaction with climatic events.
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Positioning Nucleosomes with 601 DNA Sequence to Restore GFP Expression

December 30, 0020 12:00 AM
Hales, Emily; Lundgren, Jane; Carter, John; Kempton, Colton; Johnson, Steven (Brigham Young University)
Faculty Advisor: Johnson, Steven (Brigham Young University, Molecular and Microbiology)

The mechanisms of transgene silencing in C. elegans are poorly understood, despite the importance of the nematode as a model for genetic research. Insertion of a transgene led to the expression of GFP in both the body wall and pharyngeal muscle cells of C. elegans as expected. However, subsequent generations stopped expressing body wall GFP. To reverse silencing, we have flanked the enhancers responsible for GFP expression with 601 sequences. The 601 sequence strongly positions nucleosomes. We hypothesize that this positioning will eliminate transgenerational gene silencing of body wall GFP.
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Using CRISPR and gRNA to Alter the HIV Genome

December 30, 0020 12:00 AM
McRae, Elisa; Solis Leal, Antonio; Giler, Noemi; Karlinsey, Dalton; Quaye, Abraham; Berges, Bradford (Brigham Young University)
Faculty Advisor: Berges, Bradford (Brigham Young University, Microbiology and Molecular Biology)

HIV-1 infects CD4 T-cells by inserting its genome into a cell's genetic sequence. CRISPR technology allows for gene editing within the cell, causing a break in DNA sequences targeted by specific guide RNAs. Plasmids encoding CRISPR and guide RNA (gRNA) genes, in the context of lentiviral delivery vectors, will be transfected to produce two lentiviral vectors. In vitro experiments include human T cells that will be transduced with the lentiviral vectors and analyzed with flow cytometry to determine cells that express CRISPR and gRNAs. These cells will then be sorted to create a population of cells that express both the CRISPR and gRNA genes and will then be infected with the NL4-3 strain of HIV. For in vivo experiments, human hematopoietic stem cells will be transduced with the lentivirus vectors, after which they will be transplanted into humanized mice, thus producing a human-like immune system for testing the efficacy of our anti-HIV approach. After the human immune system has sufficiently developed in the mice, HIV-1 will be introduced. We expect that human immune cells with CRISPRs will be protected against HIV infection and death due to the use of gRNAs. These cells are postulated to no longer be susceptible to HIV-1 infection, thus preventing further cell lineages from becoming infected. We will analyze data for three main endpoints: 1. Cell killing of HIV, 2. HIV rebound due to the high mutation rate of the virus, 3. Amount of HIV replication, examined by assessing the viral RNA outside of cells using Q-RT-PCR. Data from this project will support whether cells transfected with CRISPR and guide RNAs offer cell lineages that adequately disrupt the HIV-1 genome. Efforts of this study hope to address HIV infection in humans following trials with humanized mice.
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Verification of microbial genes that affect host dietary preference in Drosophila melanogaster

December 30, 0020 12:00 AM
Call, Tanner; Bean, Joseph; Chaston, John (Brigham Young University)
Faculty Advisor: Chaston, John (Life Sciences, Plant and Wildlife Sciences)

The gut microbiome, or the microorganisms that colonize the GI tract of all macro-organisms, plays a significant role in host health and physiology. In a study last year, I found that the microbiome of D. melanogaster has a direct influence on dietary preference using a well-established, automated feeding assay. In this study, I extend these findings by performing a metagenome-wide association (MGWA) screen to predict bacterial genes responsible for the effect. Specifically, I measured dietary preferences in flies mono-associated with each of 40 different bacterial species. My mentor compared the dietary preference of these flies with the genomes of their associated bacteria using a MGWA. This analysis predicted 1932 bacterial genes that could be responsible for the feeding preference phenotype. I selected the top 22 genes, including all uncharacterized genes, for which we have knock-out mutants in a laboratory stock of bacterial mutants. I will test if these genes are necessary for inducing specific host feeding preferences by comparing feeding preferences of flies mono-associated with a bacterial mutant with controls, using a generalized mixed linear model. These results will help us understand how different members of the microbiota can influence animal feeding behaviors.
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Using Dendroclimatology To Study A Disjunct Population Of Pinus Ponderosa In Northern Utah

December 30, 0020 12:00 AM
Stapleton, Michael; DeRose, Justin. (Utah State University)
Faculty Advisor: DeRose, Justin (S.J. & Jessie E. Quinney College of Natural Resources, Wildland Resources Department)

Ponderosa pine (Pinus ponderosa) is the most widespread coniferous tree in North America, occurring from Mexico to British Columbia and from California to Nebraska. Surprisingly, however, P. ponderosa is largely absent within the center of this range. Previous studies suggest that this absence may be linked to a range of climatic variables, but collectively fail to identify specific climate-growth responses. Using dendroclimatology, we will analyze how a disjunct population of P. ponderosa in northern Utah responds to local climate conditions. We seek to identify which of these variables the species is most sensitive to by correlating the population's average annual growth to a variety of climate composites. Similar tests will be conducted across three treatment blocks throughout the stand in order to distinguish if previous management altered the population's resilience to climate. Our results will help explain the current distribution of P. ponderosa and suggest how that distribution may respond to changing climate conditions.
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Effects of Grape Seed Extract Metabolites on ß-cell Proliferation and Function

December 30, 0020 12:00 AM
Beales, Joseph; Lloyd, Trevor; Krueger, Emily; Barlow, Andrew (Brigham Young University)
Faculty Advisor: Tessem, Jeffery (Life Sciences; Nutritional, Dietetics, and Food Science)

Worldwide, an estimated 415 million people suffer from diabetes.1 Diabetes is characterized by chronic dysfunction of the pancreatic ß-cell, which leads to unregulated insulin secretion and abnormal blood glucose levels. Therefore, methods which increase the number of ß-cells or improve their function have potential for complementary treatment of type 2 diabetes. Compounds such as antioxidants and their gut metabolites have received attention in literature as having potential ß-cell-regulating properties.2,3 Therefore, we hypothesize that supplementation of grape seed extract (GSE), which is rich in antioxidants, will enhance ß-cell proliferation and insulin secretion. Accordingly, we obtained metabolites, derived from rats on either a control or grape seed extract diet, to measure the metabolites' impact on ß-cell function through in vitro assays such as glucose stimulated insulin secretion (GSIS) and 3H-thymidine incorporation. Discoveries regarding GSE metabolites' effects on ß-cell function could be fundamental to understanding ß-cell regulation and potential pharmaceutical or dietary treatments for diabetes.

1 Ogurtsova, K., et al. "IDF Diabetes Atlas: Global Estimates for the Prevalence of Diabetes for 2015 and 2040." Diabetes Research and Clinical Practice, Elsevier, 31 Mar. 2017, www.sciencedirect.com/science/article/pii/S0168822717303753?via%3Dihub.

2 Bajaj, Sarita, and Afreen Khan. "Antioxidants and diabetes." Indian journal of endocrinology and metabolism vol. 16,Suppl 2 (2012): S267-71. Doi:10.4103/2230-8210.104057

3 Tsuda, Takanori. "Recent Progress in Anti-Obesity and Anti-Diabetes Effect of Berries." MDPI, Multidisciplinary Digital Publishing Institute, 6 Apr. 2016, www.mdpi.com/2076-3921/5/2/13.
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Effects of Mycorrhizal Associations on Tomato Defensive Compounds

December 30, 0020 12:00 AM
Jones, Dalton (Weber State University)
Faculty Advisor: Schramm, Katharina (Science, Botany)

Tomatoes (Solanum lycopersicum) are an important agricultural crop around the world. In order to produce food with less impact on the environment, many researchers are looking to utilize natural systems to maximize production with minimal inputs. Maximizing tomato defenses is one possible way to increase productivity. Tomatoes produce both physical and chemical defenses in response to the stress. Increasing the number of trichomes on the plant is a physical means of deterring insects from eating the plant. Trichomes come in two forms glandular trichomes and non-glandular trichomes. The non-glandular trichomes are strictly a physical defense while the glandular trichomes produce chemical defensive compounds against a wide variety of insects. Most land plants can form a symbiosis with arbuscular mycorrhizal fungi (AMF). This symbiosis has been shown to increase nutrient supply, decrease drought stress, and prime plant defenses, all increasing a plant's ability to withstand herbivory stress better. This study examines the response of trichomes and the number of chemical defenses after insect herbivory has occurred with the additional support of the AMF symbiosis. Treatments were exposed to Manduca sexta to stimulate trichome and chemical production. The extracted leaves were analyzed via gas chromatography to examine the make-up of the tomato's chemical defenses. The growth rates of M. sexta were recorded to examine the effects of tomato's chemical defenses after feeding the insects the induced tomato leaves. Measuring trichome density quantifies the change in physical defenses. The addition of the AMF increased the plant defenses, both the number of trichomes present on the plants and the quantity of the chemical defenses. Insects feeding on plants with increased defenses were also shown to have decreased growth. This study shows an alternative strategy for the use of commercial pesticides, lessening the impact of tomato crops on the ecosystem.
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Inhibitory Effect of Probiotics on Streptococcus Agalactiae Serotypes

December 30, 0020 12:00 AM
L'Ecuyer, Katia (Utah Valley University)
Faculty Advisor: Gazdik Stofer, Michaela (Utah Valley University, Microbiology)

Streptococcus agalactiae most commonly known as Group B streptococcus (GBS), are encapsulated gram-positive bacteria encountered in approximately 15-40% of pregnant women's urogenital and gastrointestinal tracts. While most women are asymptomatic, GBS colonization of newborns as they pass through the birth canal can lead to sepsis. GBS bloodstream infections are the leading cause of mortality and morbidity amongst infants in the United States. In recent years, several studies have examined the benefits of oral probiotics to promote a healthy vaginal flora and assessed the inhibitory activity of lactobacilli against urogenital pathogens, with mixed results. The purpose of our research is to examine the effect of Lactobacilli on the growth of different GBS serotypes in the vaginal environment using in vitro culture competition experiments. Previously published microbiome studies were used to determine the dominant species found in the vaginal microbiota. We are examining the growth rate of GBS when co-cultured with vaginal microflora species, both individually and as a mixed community. This will provide a baseline regarding what strains of GBS could easily colonize the vagina in high levels when in competition with different normal flora communities. Different species of probiotic Lactobacilli will then be added to the vaginal culture collection to examine if there is an effect on GBS growth. Our goal is to identify probiotic species that prevent or slow the growth of GBS in a vaginal community.
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Effects of Flavanols on β-cell proliferation.

December 30, 0020 12:00 AM
Tessem, Jeffery; Lloyd, Trevor; Brown, Nathan (Brigham Young University)
Faculty Advisor: Tessem, Jeffery (Brigham Young University; Nutrition, Dietetics and Food Science)

Diabetes is a global epidemic affecting millions of people. The total estimated cost of diabetes in the U.S. during 2017 was 327 billion dollars [1]. Diabetes is characterized by the loss of pancreatic β-cell function which is caused by an autoimmune disorder in Type 1 diabetes or insulin resistance and β-cell exhaustion in Type 2 (T2D) diabetes. Lifestyle changes in diet are beneficial in treating T2D. Phytochemicals are commonly utilized in these diets, and recent studies show diets high in flavanols exert beneficial bioactivity for β-cells. While flavanols demonstrate beneficial effects on β-cells, these flavanols are rarely observed in circulation, suggesting a necessary intermediate step. Flavanols are metabolized by gut bacteria to smaller metabolites that are absorbable. We hypothesize that these gut bacteria derived flavanol metabolites cross the gut and affect β-cell function. We have fed rats catechin supplemented or unsupplemented diets and collected urine as a means to isolate all absorbable gut flavanol metabolites. Here we present the effects of these absorbed metabolites on β-cell proliferation. This study begins to explain the mechanism by which flavanols exert their beneficial effect on glucose metabolism through the β-cell.
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Chemogenetic stimulation of connexin-36 expressing VTA GABA neurons enhances DA neuron firing rate

December 30, 0020 12:00 AM
Tuttle, Jared; Payne, Andrew; Obray, J Daniel; Steffensen, Scott (Brigham Young University)
Faculty Advisor: Steffensen, Scott (Family, Home, and Social Sciences; Psychology)

A subpopulation of ventral tegmental area (VTA) GABA neurons express connexin-36 (Cx36) gap junctions (GJs). Activation of GJ-mediated electrical coupling between VTA GABA neurons supports brain stimulation reward and alcohol reward is lowered in Cx36 KO mice due to a hyper-dopamine (DA) state. The aim of this study was to further evaluate the role of a subpopulation of Cx36+ VTA GABA neurons in alcohol reward and dependence. To accomplish this study, we customized a Gq-coupled Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) viral vector to only express in Cx36+ neurons (AAV8.hCx36.hM3D(Gq)-mCherry.WPRE.rBG) in the VTA. The hM3Dq viral vector was infused into male CD-1 GAD GFP mice and male Wistar rats. The animals were then given 10-14 days to recover prior to experimentation. A control virus (AAV9.CB7.CI.mCherry.WPRE.rBG) was used for comparison. We implemented standard cell-attached mode electrophysiology to evaluate the effects of clozapine-n-oxide (CNO; the ligand for DREADDs) on VTA GABA and DA neuronal activity. We found a robust enhancement of VTA GABA neuron firing rate in hM3Dq+ neurons with 20 _M CNO ex vivo. Surprisingly, while investigating CNO effects on VTA DA neuron firing rate, we found that CNO activation of hM3Dq+ VTA GABA neurons increased DA neuron activity, suggesting that Cx36+ VTA GABA neurons indirectly modulate local VTA DA neurons. Intraperitoneal CNO (3 mg/kg) also enhanced the firing rate of VTA GABA neurons in vivo. Administration of CNO reduced ethanol consumption (drink-in-the-dark paradigm) in both ethanol naïve and ethanol dependent hM3Dq-injected mice as compared to controls, suggesting that activation of Cx36+ neurons in the VTA is enough to block ethanol consumption in both naïve and dependent animals. Taken together, these findings support previous studies indicating that enhanced electrical coupling between VTA GABA neurons is rewarding and promotes reward and lowers the hedonic value of ethanol.
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Smyd1 Histone Methyltransferase Activity in Heart Failure and Cardiac Hypertrophy Models

December 30, 0020 12:00 AM
Szulik, Marta; Wang, Li; Franklin, Sarah. (University of Utah)
Faculty Advisor: Franklin, Sarah (Medicine, Internal Medicine)

Heart failure (HF) is a type of heart disease characterized by the structural and functional impairment of ventricular filling. In 2016, HF was the underlying cause of death in approximately 78,000 individuals and today more than 6.2 million Americans suffer from heart failure. HF is the final stage for many types of heart disease including cardiac hypertrophy. During hypertrophy, the ventricular walls thicken to help maintain the proper workload needed to continue supplying the body with oxygenated blood. In addition to increase in cell size, cardiac hypertrophy leads to cell death, fibrosis, metabolic reprogramming and reactivation of fetal gene expression. Gene expression is often modulated by changes in chromatin and histone structure via post-translational modifications (PTMs). Histone methylation, a covalent PTM, has been shown to play a significant role in cardiac development.

Smyd1 is a muscle specific lysine histone methyltransferase protein that has a role in early cardiac development and is known to methylate histone H3 on lysine-4. Additionally, loss of Smyd1 in adult mice models has been shown to induce heart failure and hypertrophy whereas overexpression of Smyd1 has been shown to restrict hypertrophic growth in cell model. Although Smyd1 knockdown experiments have been performed in vivo, the effects of knocking down Smyd1 in isolated cardiomyocytes has not been examined. Furthermore, the effects Smyd1 overexpression in adult mammalian heart failure is unknown.

This project seeks to characterize changes in global levels of histone PTM's as a result of either overexpressing or silencing Smyd1. Using proteomic analysis, we have identified the changes in histone methylation and consequently gene expression in the adult heart and isolated cells in response to Smyd1. Our results help us better understand Smyd1 role in the failing heart and help determine it therapeutic potential.
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