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Nutrient Release of Tumor Stroma is Controlled by Glucocorticoids

March 21, 2024 12:00 AM
Authors: Libby Brooks. Mentors: Natasha Pavlova. Insitution: University of Utah. About 90% of cancer deaths are from the development of secondary tumor growths from a process called metastasis. As cancer cells divide uncontrollably nutrients from nearby tissue – specifically the amino acid glutamine – are depleted. Glutamine is one of the most abundant amino acids in the bloodstream, and most cells cannot live without it. Tumors have poor vasculature which further contributes to the depletion of nutrients. Even in nutrient-depleted environments, tumors have found ways to grow.Tumors are comprised of cancer cells as well as non-cancerous stromal cells. Studies have shown stromal cells can synthesize glutamine which they release into the tumor microenvironment feeding cancer cells and allowing them to grow. However, the signaling pathway used between the cancer and stromal cells in this relationship remains unclear.To study the signaling pathway by which stromal cells are synthesizing glutamine I treated cells with a common anti-inflammatory drug, dexamethasone. Mice receiving dexamethasone over a long period of time had increased lung metastases when injected with cancer cells. Dexamethasone binds to the glucocorticoid receptor (GR) which activates the expression of glutamine synthetase (GLUL) enzyme mRNA. The expression of GLUL causes the cell to synthesize glutamine. However, the role of GR, in regulating GLUL expression in tumors, remains insufficiently studied.The experiments done for this project show that dexamethasone induces GLUL expression in stromal cells such that they start releasing glutamine. This may promote growth of cancer cells even when there is a deficit of nutrients around. It is hypothesized that due to this property, dexamethasone increases risk of metastasis. This project will aid in the development of cancer therapeutics to treat metastatic cancers.
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Fetal Macrophages Produce Interleukin-7 in the Developing Hematopoietic Niche

March 21, 2024 12:00 AM
Authors: Daniel Barrera. Mentors: Anna Beaudin. Insitution: University of Utah. Tissue-resident macrophages play critical roles in tissue homeostasis and immunity, and many of them have a distinct fetal origin and developmental trajectory as compared to their adult bone marrow-derived counterparts. However, the specific mechanisms underlying their developmental signaling pathways have not been as thoroughly examined as in the adult. Our lab recently demonstrated that fetal-derived macrophage development is regulated by expression of the lymphoid-associated interleukin-7 receptor (IL-7R) in mice, but the fetal source of the cognate cytokine ligand, interleukin-7 (IL-7), has yet to be determined. This project investigated fetal macrophage cells as a potential source of IL-7 production, with the aim of providing further insight into these signaling pathways during prenatal development. A transgenic mouse model was used that expresses IL-7 attached to green fluorescent protein (GFP) in order to measure GFP expression as a proxy for IL-7 expression in developing tissues. Embryonic tissues were extracted from mouse fetuses at 17.5 days post-conception and cells were isolated and stained with antibodies to identify blood, endothelial, and stromal cells as putative sources of IL-7 production. Samples were also intracellularly stained for GFP in order to quantify the IL-7 production across different cell types within different tissues in the embryo. The resulting data preliminarily identifies fetal macrophages as the primary producers of IL-7 across common tissues in the developing embryo. A better understanding of the developmental signaling pathways that regulate fetal immune development can expand comprehension of the origins of early immune dysfunction and help mitigate disease susceptibility from early life.
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EFFECTS OF DOCOSAHEXAENOIC ACID ON NEURONAL OUTCOMES IN A RAT MODEL OF PEDIATRIC TRAUMATIC BRAIN INJURY

March 21, 2024 12:00 AM
Authors: Amber Brooks. Mentors: Michelle Schober. Insitution: University of Utah. Traumatic brain injury (TBI) can cause death or result in long-term disabilities. TBIs are the leading cause of death and disability due to trauma and the leading cause of acquired neurological disability in children. At present, medical treatment using supportive and specific therapies to optimize recovery are lacking. Docosahexaenoic acid (DHA), a component of fish oil and a natural constituent of brain cell membranes, is a potential candidate therapy to improve neurologic recovery after severe TBI. The objective of our project is to test the hypothesis that DHA improves cognitive outcome and brain imaging in a male rat model of pediatric TBI, controlled cortical impact (CCI) in male rat pups. Seventeen-day-old male rat pups received CCI or a minimally invasive (SHAM) surgery. Half of the CCI and SHAM rats were fed a DHA diet for 60 days before experiments began. Learning was tested using a Morris Water Maze (MWM) experiment and memory was tested using a Novel Object Recognition (NOR) experiment. Brain injury assessment was accomplished using T2 and DTI magnetic resonance imaging (MRI). The T2 MRI scans were used to measure the volume of the hippocampus, the center for learning and memory, and to lesion volume, to assess loss of hemisphere volume. The DTI MRI scans were used to observe the injury to the white matter of the brain. Based on preliminary findings, we anticipate that the results of the study will not support our hypothesis and that DHA will have no beneficial effects on improving cognitive outcomes and brain imaging.
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Relationships Between Dominant and Non-Dominant Finger Rate of Force Development (RFD) and Finger Strength, Shoulder Strength, and Lower-Body Strength in Recreational to Advanced Climbers

March 21, 2024 12:00 AM
Authors: Ryan Kunkler, Marcus Lawrence, Anna Edler, Casey Webb, Jacob Manning. Mentors: Marcus Lawrence. Insitution: Southern Utah University. Climbing is now an Olympic sport and thus the demand for understanding performance predictors to train with evidence has grown enormously. Previous climbing research has highlighted that finger strength and shoulder strength are important predictors of performance between lower level and higher level climbers. However, no study has examined the rate of force development in the upper body, and lower body strength also has not be assessed in climbing literature. PURPOSE: To determine if relationships exist between dominant and non-dominant finger RFD compared to dominant and non-dominant finger and shoulder strength as well as lower body strength. METHODS: Twenty subjects (n=8 female and n=12 male; age: 24.7±7.5 yrs; height: 177.6±7.8 cm; mass: 76.0±14.9 kg; IRCRA Sport Grade: 14.1±6.7; n=11 beginner/intermediate, n=9 advanced) completed this study. During a single session, following a standardized 3-5 min. warm-up all participants dominant and non-dominant finger strength and RFD (using a Tindeq dynamometer load cell attached via static rope to a 20mm edge) as well as shoulder strength (using the same Tindeq load cell with a static rope and olympic ring), and lower-body compound strength (isometric mid-thigh pull using G-strength dynamometer load cell attached to a straight bar with a static rope) were assessed. Three trials were done on each measurement with 1 min. between trials and 3-5 min. between tests. Pearson correlational analyses were done to determine correlation coefficients (r), with significance set at p<0.05. RESULTS: Both dominant and non-dominant RFD resulted in significant (p<0.05) large to very large positive relationships with dominant finger strength (r = 0.897 and 0.721, respectively), non-dominant finger strength (r = 0.913 and 0.757), dominant shoulder strength (r = 0.670 and 0.709), on-dominant shoulder strength (r = 0.724 and 0.744), and lower body compound strength (r = 0.645 and 0.653). CONCLUSION: Dominant and non-dominant RFD is positively related to upper and lower body strength in recreational to advanced climbers. Therefore, training finger RFD and lower body strength should be consider as important as developing finger and shoulder strength in recreational to advanced climbers.
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Behavioral Effects of Trauma Recruit Separate Populations of Ventral Hippocampal Neurons

March 21, 2024 12:00 AM
Authors: Addison Hedges, Kevin Sattler. Mentors: Moriel Zelikowsky. Insitution: University of Utah. Trauma has been reported to affect over 70% of all adults worldwide. This includes, but is not limited to, physical and sexual violence, injury, threat of death, and natural disasters. Experiencing one or more traumatic events can lead to post-traumatic stress disorder, depression, and anxiety. These symptoms and disorders can negatively affect interpersonal relationships, confidence, aggression, and other aspects of daily behavior. Exactly how these traumatic events are encoded in the brain is poorly understood. Extensive research has been done on the hippocampus with regard to its central role in learning and memory, but only recently has research been done to uncover its role in emotional responses. This research has found distinct functional differences between the dorsal and ventral subregions of the hippocampus. Recent studies suggest that the ventral hippocampus (VH) plays an important role in emotional response. The VH projects to other emotional processing areas of the brain that modulate fear, aggression, and social processing. This project aims to test the hypothesis that distinct populations of neurons in the VH encode individual behavioral effects of trauma as well as discover the extent of overlap between neuronal cells activated by trauma-induced aggression (TIA) vs. trauma-altered sociability (TAS). To test this hypothesis, both male and female mice were injected with an hM4D inhibitory DREADD virus to chemogenetically silence VH. Later the mice underwent either no trauma or a foot shock trauma consisting of 10 1mA foot-shocks randomly applied over 60 minutes. They were then tested for aggression and social response using two distinct behavioral assays known as Resident Intruder and 3-Chamber. Half the mice received DCZ, a ligand used to activate DREADDs, while the other half received a control vehicle prior to each behavioral assay. Our findings show that silencing of the VH led to attenuated TIA and TAS when compared to control groups. Next, using retrograde viral tracing, activity-dependent neuronal tagging, and immunohistochemistry, we examined the existence and extent of overlapping neuron populations in the VH. These findings suggest the VH plays an important role in encoding and responding to trauma. They also highlight the importance of continued research into how behavioral changes are manifested in the brain and how these experiences are studied.
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Sodium to Potassium Ratio Is Associated with Increased Blood Pressure in Males but Not in Females

March 21, 2024 12:00 AM
Authors: Karen Hoggan, Adia Migliori, Jonathan Harr, David Aguilar Alvarez. Mentors: David Aguilar Alvarez. Insitution: Weber State University. BackgroundElevated blood pressure (BP) is a significant risk factor for cardiovascular disease. The effects of high sodium (Na) intake on blood pressure are widely recognized. Of late, potassium (K) intake has gained recognition as a factor in hypertension. Recent studies have shown that the Na/K ratio consumed may be more predictive of hypertension than solely sodium intake. This study examines the association between the Na/K ratio and BP in males and females.MethodsWe utilized a cross-sectional design to evaluate self-reported two-day diet records for 73 male and 183 female students. Sodium and potassium intake were calculated using Diet and Wellness Plus. BP measurements were taken from each participant. Partial correlations were conducted between systolic (SBP) and diastolic blood pressure (DBP), and the following variables: Na, K, and Na/K. SBP means were compared between high sodium consumers and low sodium consumers with the same Na/K ratio using independent samples t-test.ResultsNeither male nor female participants’ SBP or DBP were associated with Na or K intake (p>0.05). However, an increased Na/K ratio was associated with higher DBP in males (r=0.254, p=0.29), but not in females (r=0.04 p=0.79). When the Na/K ratio was paired, participants who consumed over 3000 mg of sodium had a significantly higher SBP (121.1 ± 12.9) than those who consumed less than 3000 mg (115.9 ± 10.7, p=.004).ConclusionsConsumption of Na and K may affect male and female BP differently. In males, the Na/K ratio was predictive of increases in blood pressure. Although Na/K ratio seems to be more predictive of this parameter, within the same Na/K ratio, having lower sodium consumption was associated with lower SBP. This illustrates the complex interaction between BP regulation and nutrition, emphasizing the significance of both lowering sodium intake and maintaining a balanced Na/K ratio for optimal heart health.
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How different students' groups perceive learning in out-of-class collaborative environment?

March 21, 2024 12:00 AM
Authors: Sophia Kramer, Violeta Vasilevska. Mentors: Violeta Vasilevska. Insitution: Utah Valley University. Preliminary literature review showed that studies have been conducted following either elementary or middle/high school students’ after-school math programs. However, this preliminary lit review did not provide any relevant comparison of the data collected from these students’ groups. In this study, we will conduct two after-school meetings with elementary and high school students in the spring semester. During the meetings, students will be working collaboratively on hands-on, discovery math activities. This hands-on learning experience will be adjusted for different grade levels. Both student groups will be given a pre-survey consisting of attitude questions. They will assess perceptions about learning that occurs in after-school (out-of-classroom) learning environments that encourage mathematical thinking and collaboration. At the end of each after-school meeting, students will be given a post-survey (that will contain some questions matching the pre-survey ones). The collected survey data will be compared to examine the different responses resulting from the two different age groups, maturity levels, gender, etc. Survey results will be used to obtain observations about the effect of such after-school programs on student attitude toward math.In this presentation, we present the preliminary data collected during the first after school meeting held at the beginning of the spring semester and provide a comparison of the collected data. Additional meetings and surveys will be conducted later in the semester.
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Gender disparities in the pursuit of biology at UVU

March 21, 2024 12:00 AM
Authors: Eden Backman, Britt Wyatt, Kandace Flanary, Jessica Cusick, T Heath Ogden, Joshua Premo. Mentors: Joshua Premo. Insitution: Utah Valley University. Utah Valley University serves a unique student population where ~70% of students are Latter-Day Saints (LDS) and ~30% are non-traditional (over the age of 24) (UVU IR, 2023). Compared to the overall 1.6% of LDS individuals in the United States (Pew Research Center, 2023), the identities of UVU students are vastly underrepresented in education research that has been conducted at other institutions. This is especially important as the LDS religion has been related to one of the most conservative religious groups concerning gender roles (Heaton, Bahr, and Jacobson 2004). Additionally, recent preliminary analysis of public institutional data from Utah universities indicates that UVU is graduating more men than women in biology, drastically contrasting other Utah university and national trends. In Utah, the STEM workforce has seen a significant 20% increase since 2016 (UWLP, 2022). However, it's important to note that during this period of expansion, men have disproportionately reaped the benefits in terms of STEM career opportunities. According to IWPR (2019), men in Utah are 2.5 times more likely to secure a STEM career compared to women. Furthermore, in 2020, STEM careers in Utah boasted median annual wages that were over twice as high as those in other occupations, which has direct implications for individuals' lifetime earnings and social capital. Given this information, we questioned why women were not choosing educational paths that will promote a career in STEM? If they are choosing STEM majors, then what are the factors that promote women to leave STEM during their undergraduate careers? This research project focuses on trying to answer these questions specifically at Utah Valley University (UVU). UVU’s biology program reflects similar patterns that are seen in the STEM workforce in Utah. UVU’s biology program was graduating twice as many men compared to women during the most recent academic year (2022-23)(UVU IR). This was the lowest percentage of women earning a four-year biology degree when compared to all other Utah institutions (USHE, 2023). The following research questions were addressed to help inform our understanding of why inequities in degree attainment by gender are being seen at UVU: 1) Are women less accepting of biological ideas (evolution, vaccines, climate change, etc.) that may be impacting women’s pursuits of biology? 2) Are there differences in how women are relating to science (motivation, immersion, or integration) that may be impacting their pursuit of biology? 3) Are there differences in political orientation or religious affiliation that may be impacting women’s pursuits of biology? To answer these questions, we collected data from 1,455 students (22% were biology majors) enrolled in biology classes at UVU in Fall 2023. Comparisons were made using independent samples t-test (with Bonferroni adjustments) to see the extent to which factors varied between men and women both within and outside of the biology major. In contrast to expectations, results for research question #1 show that women biology majors did not agree with science less than men. In fact, women strongly agreed with several science ideas at a higher rate than did men. These ideas included environmental concern and climate change (women = 66% vs. Men = 41%) and vaccination (women = 63% vs. Men = 48%). This result suggests that differences in acceptance of science ideas may not be driving the differences in degree attainment in biology. If anything, these results suggest that women should be more likely to continue in the biology major compared to men. In addition, when students’ immersion (sense of belonging and science identity) in science was assessed by gender women were slightly higher than men with about 8% more strongly agreeing to being immersed in science. This finding suggested that women are not experiencing lower immersion as a potential factor impacting degree attainment. Further examination of additional factors is underway. This study highlights that there are specific factors that may be contributing to gender disparities in biology bachelor's degree attainment at UVU. We recommend specific interventions targeting areas of differences in the biology program to provide additional scaffolds and supports to promote more equitable career trajectory and lifetime earnings for women pursuing Biology at UVU.
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Automating the Analysis of Language Samples Obtained from the Frog Story Series: Step 1

March 21, 2024 12:00 AM
Authors: Tessa Sabin, Derek Bagley, Kylie Olsen, Alexis Klein, Haven Broadhurst. Mentors: Sandi Gillam. Insitution: Utah State University. The purpose of this project was to create systematic, reliable rubrics for using the Frog Story series in language sample analysis for the diagnosis and treatment of children with developmental language disorders (DLD).Language sample analysis is a critical part of the assessment process by speech language pathologists (SLPs) for determining whether a child has a developmental language disorder. This is accomplished by analyzing a child’s use of vocabulary, sentence structures, and grammatical markers (i.e., past tense) and comparing it to their typically developing peers. Once diagnosed, language sampling is used as part of progress monitoring efforts to ensure the child is making reasonable progress toward their language goals in one (or all) of these areas.Elicitation of language from a child is often achieved by asking them to tell a story. One popular way that SLPs have obtained samples is to ask them to retell one of four popular wordless picture books from the Frog Story series by Mercer Mayer. This series involves the antics of a frog and his boy as they encounter different adventures. There is no rubric or “analysis key” associated with the stories leaving the SLP to decide how to use the information obtained from the story independently. This makes it hard to obtain reliable results over multiple time points for use in progress monitoring.In this project, a team analyzed all four Frog stories for their inclusion of specific story elements (i.e., character, setting, episode), vocabulary and sentence structures; and separate rubrics were created. The methodology for identifying the language parameters of interest, reliability in coding, and uses for the rubrics will be described. The rubrics will be automated using a web application so clinicians can upload their child’s story and have them instantly scored, making their use in analysis more reliable and consistent.
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Examination of Effort Belief and Self-Competence in Classrooms Using Mastery-Based Grading and Active Learning

March 21, 2024 12:00 AM
Authors: Grant Hendrickson, Christian Moody, Nellie Bowman, Nick Jeffery, Cairo Ziebarth, Joel Davis, Melissa Reeves, Heather Wilson Ashworth. Mentors: Heather Wilson Ashworth. Insitution: Utah Valley University. Self-competence and effort belief may impact student motivation and success in introductory chemistry courses. Self-competence is the need to feel efficacious and capable3. Effort belief is the concept that working harder at a task produces better results4. Mastery-Based Grading (MBG), a nonconventional grading method, provides multiple opportunities for students to show mastery of the course learning objectives5. This research examines the effect of Mastery-Based Grading (MBG) in an active learning classroom on student's self-competence and effort belief compared to that of a conventional grading (CG) approach in a traditional lecture-based classroom. Hypothesis: MBG leads to increased student self-competence and effort belief compared to CG courses. Self-determination1 and expectancy-value theories2 provide the context for understanding the self-competence and effort belief data. At a private midwestern college, general chemistry students in an active learning, MBG course (53 students) and a lecture course (48 students) with a conventional grading policy were studied using a mixed methods approach. Surveys containing Likert and reflection questions were given during week 3 and 14 of the semester. A coding scheme was developed, and reflection questions were coded to consensus. Coded data had a Pearsons coefficient greater than 0.76. Results: Notably, students with initially low self-competency Likert scores showed significant improvement (p=0.01) in the MBG-active course, but not in the conventional course. No significant improvement was observed in students' effort-belief scores as the scores were high at the beginning and stayed high at the end of the semester. In response to the reflection question, “Do you believe you have the ability to be successful in this course?”, there was a 15.35 percent increase in responses that reflected effort-belief in the MBG active learning course. This theme was absent in CG courses throughout the semester. It is noteworthy that MBG students recognized (14.29% compared to pre-reflections) the specific components of the course structure that helped students succeed. This early explorative data suggests that students in active learning MBG courses may experience an increase in self-competence and perceived effort belief compared to their counterparts in traditional classes. 1Deci, E. L., Vallerand, R.J., Pelletier, L.G. & Ryan, R.M. (1991). Motivation and education: The self-determination perspective. Educational Psychologist, 26, 325-346. 2Eccles (Parsons), J. (1983). Expectancies, values, and academic behavior. in J.T. Spence (Ed.) Achievement and Achievement Motivation. San Francisco: W.H. Freeman. 3Ferrell, Brent and Jack Barbera. (2017). Analysis of students’ self-efficacy, interest, and effort beliefs in chemistry. Chemistry Education Research and Practice, 16; 31-337. 4Skinner, E., Saxton, E., Currie, C., & Shusterman, G. (2017). A motivational account of the undergraduate experience in science: brief measures of students’ self-system appraisals, engagement in coursework, and identity as a scientist. International Journal of Science Education, 39(17), 2433-2459. 5Toledo, S., & Dubas, J. M. (2017). A learner-centered grading method focused on reaching proficiency with course learning outcomes. Journal of Chemical Education, 94(8), 1043-1050.
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Quaking Aspen Pathogen Defense in the Presence of Climate Change Related Drought

March 21, 2024 12:00 AM
Authors: Allison Perkins, Aubrey Hawks, Talia Karasov. Mentors: Talia Karasov. Insitution: University of Utah. Over the past two decades, studies have documented a 20% decline in Quaking Aspen (Populus tremuloides) populations in western North America (Worrall et al., 2015; Stanke et al., 2021). This phenomenon has been fittingly characterized Sudden Aspen Decline (SAD), and is an increasingly pressing issue as the role of aspen as an ecologically irreplaceable keystone species impacts the health of the surrounding forests (Singer et al., 2019). SAD has been attributed to the interplay of climate change-driven drought and other biotic and abiotic factors that are less well characterized (Anderegg et al., 2013a). One potential contributor to SAD is biotic pests and pathogens (Marchetti et al., 2011; Anderegg et al., 2013a; Worrall et al., 2015). My study system includes both natural populations of aspen representing a precipitation gradient and a controlled garden experiment. The field experiments span five distinct sites across Utah & Colorado, selected and montintered by the Anderegg lab of the University of Utah. The experimental garden contains approximately 300 tree saplings subjected to various levels of drought stress, managed by the Anderegg lab on the University of Utah campus. Through the integration of both controlled and natural experiments, my research aims to comprehensively evaluate the impact of drought exposure on pathogen abundance and chemical defenses in aspen trees.Over the past two decades, studies have documented a 20% decline in Quaking Aspen (Populus tremuloides) populations in western North America (Worrall et al., 2015; Stanke et al., 2021). This phenomenon has been fittingly characterized Sudden Aspen Decline (SAD), and is an increasingly pressing issue as the role of aspen as an ecologically irreplaceable keystone species impacts the health of the surrounding forests (Singer et al., 2019). SAD has been attributed to the interplay of climate change-driven drought and other biotic and abiotic factors that are less well characterized (Anderegg et al., 2013a). One potential contributor to SAD is biotic pests and pathogens (Marchetti et al., 2011; Anderegg et al., 2013a; Worrall et al., 2015). Recent investigations have indicated a link between SAD and specific microbial diseases, suggesting that the increasing frequency and severity of droughts due to climate change might make aspen more vulnerable to certain pathogens, even though many of the most common pathogens of aspen in general require more abundant water (Aung et al., 2018). For example, the foliar Melamspora fungal pathogens require abundant water and are not frequently observed in drought stressed trees.On the other hand, Cytospora, which causes a devastating canker disease in aspen trunks, occurs at higher frequency in plots of trees suffering damage from drought (Guyon, 1996). Lin et al. (2023) shows changes to phyllospheric microbiome in aspen during drought, but far less is known about the leaves specifically. Could drought lead to an altered microbiome in aspen leaves? If different or possibly opportunistic pathogens are better able to colonize the leaf tissue under drought stress, this may be the case.It’s known that plants with a reduced diversity of microbiomes are more susceptible to pathogens (Zheng et al., 2020), but the there is little understanding how drought may reduce microbial diversity in aspen. Aspen have two main groups of chemical defenses (SPGs and CTs) that occur in relatively high levels in the leaf (Lindroth et al., 2023). It is well established that these defend against insect herbivores and that they come with a trade-off for plant growth (Marchetti et al, 2011). There is some observational evidence that these secondary compounds have an effect on pathogens (Jacoby et al., 2021), but there are few controlled studies on this idea. Additionally, Metlen et al. 2009 describes how trees in North America produce higher rates of these metabolites under wetter conditions, attributed to possible UV protection. However, the impact of additional environmental changes have of on the abundance of these compounds is understudied. Aspen are an ideal system to study forest disease and drought because the genus’ (Populus) genomes are easily sequenced and relatively tractable, aspen generally exhibit rapid vegetative growth, their defensive chemistry is relatively well known, and most importantly, they grow in cloned groves that reduce the genetic variation in experiments (Lindroth et al., 2023, Luquez et al., 2007).
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Lysine Methyltransferase SETD7 Methylates Two Novel Residues on Histone H3

March 21, 2024 12:00 AM
Authors: Braxton Bird. Mentors: Sarah Franklin. Insitution: University of Utah. Heart disease ends the lives of nearly 700,000 people each year and has been the leading cause of death in the United States since 1950. Around this time researchers discovered that some modifications involving our genetic code could be altered to affect gene expression but leaves the DNA intact, which was later termed epigenetics. Today we’ve discovered that these epigenetic modifications, including post translational modifications (PTMS), regulate genes linked to cardiovascular disease. We recently examined the histone lysine methyltransferase SETD7, which is most prominently known for its ability to methylate histone H3K4. SETD7’s expression is upregulated in multiple types of heart disease in both humans and mice and is essential for cardiomyocyte differentiation in embryonic development. In addition to its ability to methylated H3K4, SETD7 has been shown to methylate 8 other histone residues. To further characterize the histone residues methylated by SETD7, we carried out an unbiased analysis of lysine residues methylated by SETD7 using an in vitro methyltransferase assay coupled with tandem mass spectrometry. We hypothesized that SETD7 may modify additional sites than those that have previously been identified. Our analysis determined that SETD7 monomethylates two novel residues on histone H3: lysine 36 (K36) and lysine 122 (K122). These sites of modification were also confirmed by western blotting for site specific antibodies to these methylation marks. Although our understanding of both these residues is limited, we do know that K36 methylation is linked to DNA replication and genomic stability while K122 methylation is downregulated in drug-resistant MCF-7/ADR cancer cells. These two novel methylation sites suggest that this lysine methyltransferase plays a more complex role in regulating epigenetic modifications and gene expression than previously recognized. Although the identification of this new enzymatic activity for SETD7 is important for understanding the dynamic function of methyltransferases, additional studies will be necessary to fully elucidate the role of SETD7 in cardiac physiology and gene regulation.
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Investigating Neuronal Networks Behind Learning in Drosophila melanogaster

March 21, 2024 12:00 AM
Authors: Dua Azhar, Alexander MacKenzie, Sophie Caron. Mentors: Sophie Caron. Insitution: University of Utah. The mushroom body of the Drosophila melanogaster is a structure in the brain that is necessary for learning, but much of how it functions remains unknown. In this model organism, D. melanogaster’s mushroom body neurons, known as Kenyon cells, and input projection neurons have connections that are random and biased—in which some projection neurons connect with Kenyon cells more than others—allowing the fly to potentially prioritize the learning of particular odors. I investigated the functional consequences and characterizations of these biases in order to understand the biological role they play for the fly using a theoretical and experimental approach. With a computational model of the D. melanogaster olfactory system, how biased connectivity to the mushroom body influences its ability to form associations with various odors and distinguish between similar odors was explored. Experimentally, the morphological features of olfactory circuits were characterized by low to high connectivity rates to the mushroom body, allowing us to see the unique features in these circuits that are beyond the different connectivity rates. Through a combination of immunohistochemistry and confocal microscopy, high-quality images were generated of these different neuronal olfactory circuits and their morphological qualities, such as the number and volume of boutons they project to the mushroom body. Altogether, these findings demonstrate how neural connectivities behind learning shape the representation space in D. melanogaster and impact its learning outcomes.
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Evolution of TETR/TETO system toward orthogonal transcriptional repression

March 21, 2024 12:00 AM
Authors: Alexa N Gormick, Adam M Zahm, Justin G English. Mentors: Justin G English. Insitution: University of Utah. Recent advancements in gene therapy have pushed towards the prevention and treatment of a diverse spectrum of disorders and diseases that are caused by misregulation of gene expression programs and their transcriptional regulators. However, the profoundness of the field means that much of the mechanisms and effects of regulation are unknown and understudied. Here, we explore the limits of flexible exogenous gene expression and its potential use in optimizing efficacy and specificity in gene therapy interventions while minimizing the possible associated risks. This is made possible by exploiting the Tet-On system of inducible transcriptional regulation, which allows the expression of any target gene to be reversibly, specifically, and differentially controlled. In this system, the tetracycline repressor (TetR) binds the tetracycline operator (TetO), impeding transcription of any downstream gene embedded by the researcher; tetracycline dosing causes TetR to adopt a new conformation that removes it from TetO, inducing gene expression on command (Das et al., 2016). Because of the diverse utility of this system, we are in pursuit of developing novel TetR-TetO orthologous pairs that do not interfere with this wild-type circuit and can be used to regulate gene expression in parallel. As a first step to generating TetR-TetO orthologs, we mapped the usage of TetO by TetR in a massively parallel reporter assay (MPRA) by engineering an extensive library of mutant TetOs and quantified the resulting range of TetR regulation through reporter gene expression. From this screen, we identified candidate TetO mutants to direct the evolution of the wild-type TetR towards complementary states to those TetO mutant sequences. Our preliminary findings indicate that the engineering of distinct synthetic expression cassettes based on the TetR-TetO operon is feasible. These novel tools may ultimately allow us to build a synthetic genetic circuit to model regulatory feedback loops that can help discover malfunctions in cell growth, reproduction, and cycling that can arise from genetic disorders and can lead to disease.1. Das, A. T., Tenenbaum, L., & Berkhout, B. (2016). Tet-On Systems For Doxycycline-inducible Gene Expression. Current Gene Therapy, 16(3), 156–167. https://doi.org/10.2174/1566523216666160524144041
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Differentiation of VOC emissions of heat-stressed Populus trichocarpa with varying levels of mycorrhizal colonization

March 21, 2024 12:00 AM
Authors: Luis Valdez, Mary Alvarez, Jessica Berryman, Ron Valcarce. Mentors: Jessica Berryman. Insitution: Salt Lake Community College. Plants produce & emit a diverse and substantial amount of Volatile Organic Compounds (VOCs) into the atmosphere. These compounds play important roles in the plant’s tri-trophic interactions, responses to environmental stress, and have been shown to participate in atmospheric chemistry. Although variation in VOC emissions in plants has been extensively studied, there are gaps in knowledge on how symbiotic interactions with soil microbiota shape the VOC profile of plants in the context of environmental stress. Arbuscular Mycorrhizal Fungi (AMF) are fungi that form symbiotic associations with plants by colonizing their roots & providing enhanced micronutrient & water retention in exchange for photosynthates. These associations have also been shown to enhance plant responses against biotic & abiotic stress. In this study, we will look at how the expression of heat stress- induced VOCs changes based on mycorrhizal availability in the soil. Populus b. trichocarpa saplings will be exposed to the respective temperatures of 25° C, 35° C, & 40° C for an extended period of time. Emitted volatiles will be collected and analyzed using GC-MS. For each type of temperature, emissions will be compared between saplings planted under different levels of AMF availability (low, medium, & high). We expect volatile emissions to change based on mycorrhizal availability in one of two scenarios; increased emissions due to increased phosphorus uptake from the fungus or decreased emissions due to carbon allocation to the fungus.
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Comparison of low-cost synthesis methods for pharmaceutical-grade purity of the anticonvulsant Phenytoin using traditional reflux techniques verses Microwave-Assisted Extraction

March 21, 2024 12:00 AM
Authors: Katherine Christensen, Danielle Kemmer. Mentors: Ron Valcarce. Insitution: Salt Lake Community College. Phenytoin is listed by the World Health Organization as an Essential Medicine that is one of the most cost-effective anti-epileptic (AED) treatments available. However, the availability of the drug to pharmacies in developing countries is limited. 85% of those affected with epilepsy live without treatment. Low commercial production, political instabilities, and/or financial barriers prevent the availability of this anti-epileptic drug. A more efficient and cost-effective method for supplying phenytoin to local clinics and medical personnel could alleviate some of these barriers. The initial goal of this project was to refine a small-scale synthesis and purification of phenytoin using the base-catalyzed addition of urea to benzil, followed by pinacol rearrangement and recrystallization. Our procedure emphasized simple laboratory equipment found in the most basic of pharmacy laboratories. Using the International Pharmacopoeia guidelines for pharmaceutical purity, we achieved over 98% purity. Verification of pharmaceutical grade purity was achieved by High-Performance Liquid Chromatography (HPLC). Our Secondary goal was to incorporate a more efficient and accessible synthesis method. This goal was achieved through the implementation of Microwave Assisted Extraction (MAE). This project outlines the comparison between these two methods and the potential benefits and limitations of each of these methodologies.
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Chemical Synthesis of Aerogel Fabrics using Standard Lab Conditions

March 21, 2024 12:00 AM
Authors: Antonio Ruiz Ayala. Mentors: John Flood. Insitution: Salt Lake Community College. Aerogels are a fascinating material that function as great insulators. Nasa has partnered with Aspen Aerogels to produce a commercially viable product that aims to tackle a variety of problems such as space shuttle insulation, space particle collection, thermal safety, and cryogenic applications. The main objective of our project is to reproduce an aerogel blanket using standard lab conditions and chemicals. We will be producing the blanket using the silica gel process. We will compare properties of durability, cost, and thermal conductivity. We plan to pinpoint a procedure that provides the most cost effective, durable, and thermally conductive material under standard lab conditions.
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Exploring the Role of Dopamine and ATP in Microglial Motility and Morphology

March 21, 2024 12:00 AM
Authors: Christopher Galbraith, Derek Langford, Hillary Wadsworth, Eliza White, Erin Taylor, Lauren Ford. Mentors: Jordan Yorgason. Insitution: Brigham Young University. Microglia are monocyte derived immune cells and exhibit complex signaling behavior that include phagocytic activity to threats and prolonged neuronal activity. ATP (adenosine triphosphate) is a known chemoattractant for microglia, but how chemoattraction is modulated by other transmitters is not well understood. ATP is co-packaged and released with dopamine, thus the present work examines microglia morphology and motility in the context of these two transmitters. Microelectroiontophoresis and multiphoton microscopy were used in brain slices from transgenic mice to examine effects of dopamine and ATP signaling on microglia. Lipopolysaccharide (LPS) transitioned the microglia from ramified to amoeboid morphology over a period of 4 hours. LPS also increased both dopamine and ATP release, as measured by fast scan cyclic voltammetry on a similar time course. Surprisingly, dopamine itself did not act as a chemoattractant to microglia, despite increasing after LPS treatment. By examining this relationship between neuronal and microglial activation we can better understand the complex circuitry of the reward pathway and immune system activation.
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