2020 Abstracts

Jackson, Erin; Root, Jerry; Kelly, Jessen (University of Utah)
Faculty Advisor: Root, Jerry (College of Humanities, Department of World Languages and Cultures) Kelly, Jessen (College of Fine Arts, Department of Art and Art History)

Approximately 250 extant manuscripts of the Romance of the Rose contain illuminations. The depicted scenes and motifs within these works follow established patterns, a notion that created several iconic scenes from the Romance that can be seen in nearly every illuminated manuscript. Issues of representation and interpretation of the Old French text come to light through the depictions in the images. Inversely, the conversation created between these aspects of the manuscripts emphasizes the ways in which the illuminations inform the understanding of the text. Scholarship focuses predominantly on the former of these visual-textual relationships, and considering the influence of the images on textual understanding will provide new insight into the creation of one of the most highly-produced manuscripts of the Medieval period. These relationships are examined through the depictions of the reoccurring Narcissus scene within the Romance. This research will result in the completion of an interdisciplinary Honors Thesis for both French and Art History. The Romance research focuses on the analysis of series of images throughout the manuscripts available in the Digital Library of Medieval Manuscripts run by John Hopkins University. This is accomplished through a combination of literary and art history approaches to form a more holistic understanding of the visual-textual relationship within the Romance of the Rose manuscripts.

Sommers, Taryn; Veon, Raymond (Utah State University)
Faculty Advisor: Veon, Raymond (Caine College of the Arts, Art and Design Department)

A literature search of research and academic journals suggests that there are few critical examinations of LDS visual culture in visual culture research. The purpose of this exploratory study is to examine the types of gender roles portrayed in contemporary LDS visual culture, the visual codes used to represent these gender roles, and the degree to which the representations of gender used in LDS visual culture align with findings in related visual culture studies. The result of this study will be a description of the current visual strategies used by the LDS church to represent gender roles, a thematic analysis of these visual strategies, and suggestions for future research into the ways that the LDS church visually defines gender in relation to existing trends and themes in visual culture research. The scope will include: “Mormon Ads,” images used in the LDS magazine, “Ensign,” and conference memes used during the years 2016-2019. This will contribute to the field of visual culture and gender studies by examining the visual codes used by the LDS church to portray the role and status of males and females as represented in current LDS visual culture, determining the strategies used in these representations, and discussing the potential research implications of these findings in light of themes in visual culture gender studies. Some research questions are: What visual codes are used in the representation of males, females, and mixed-sex groups in current LDS visual culture? What types of roles and status do these visual codes convey pertaining to the representation of males, females, and mixed-sex groups in current LDS visual culture? What extent do the results of investigating the above research questions align with other research findings in gender and visual culture studies? The methods used in this research will be 1) an inventory of discrete visual codes (e.g. color use, affect/expression, clothing/dress, setting, etc.) used in the LDS visual culture samples, and 2) a separate thematic analysis of the sample will also be conducted. The results of both methods will be compared, analyzed, and discussed in light of current trends in visual culture gender research. While the results of this research are expected to demonstrate that LDS visual culture will emphasize and reinforce traditional gender roles of females as mothers and homemakers and males as leaders and providers, it is hoped that this study will reveal strategies related to gender role representation unique to LDS culture.

Boatright, Greggory; Medrano, Braxton; Goeckeritz, Joel (Brigham Young University)
Faculty Advisor: Roeder, Beverly (Brigham Young University, Life Sciences)

Schwann cells play a major role in helping heal injured nerves. They help clear debris, produce neurotrophins, upregulate neurotrophin receptors, and form bands of Büngner to guide the healing nerve. But nerves do not always produce enough neurotrophins and neurotrophin receptors to repair themselves. Nerve growth factor (NGF) is an important neurotrophin for promoting nerve healing and lysophosphatidylcholine (LPC) has been shown to stimulate NGF receptors (NGFR). This study tested the administration of a single intraneural injection of LPC (1 mg/mL for single LPC injection and 10 mg/mL for multiple LPC injections) at day 0 and one (day 7), two (days 5 and 7), or three (days 5, 7, and 9) injections of NGF (160 ng/mL for single injections and 80 ng/mL for multiple injections) to determine baseline effects on crushed sciatic nerves in rats. The rats were randomly divided into four groups: control, crush, crush-NGF, and crush-LPC-NGF. The healing of the nerves was measured weekly by monitoring gait; electrophysiological parameters: compound muscle action potential (CMAP) amplitudes; and morphological parameters: total fascicle areas, myelinated fiber counts, fiber densities, fiber packing, and mean g-ratio values at weeks 3 and 6. The crush, crush-NGF, and crush-LPC-NGF groups statistically differed from the control group for all six weeks for the electrophysiological parameters but only differed from the control group at week 3 for the morphological parameters. The crush, crush-NGF, and crush LPC-NGF groups did not differ from each other over the course of the study. Single injections of LPC and NGF one week apart or multiple treatments of NGF at 5, 7 and 9 days post-injury did not alter the healing rate of the sciatic nerves during weeks 1-6 of the study. These findings are important to define the baseline effects of NGF and LPC injections, as part of a larger effort to determine the minimal dose regimen of NGF to regenerate peripheral nerves.

Hyman, Rachel; Light, Tim; Montague, Angela; Lucero, Jessica (Utah State University)
Faculty Advisor: Lucero, Jessica (College of Humanities and Social Sciences; Sociology, Social Work and Anthropology Department)

Refugees are recognized as having unique and complex health needs which demand attention upon arrival and throughout the resettlement process (Agrawal & Venkatesh, 2016). Refugee populations are particularly vulnerable to health disparities due to push factors influencing forced migration (Tempany, 2009). These factors include exposure to political violence, natural disasters, and other forms of anthropogenic conflict (UNHCR, 2014). Refugees may arrive in the host country with undiagnosed and untreated health issues, such as infectious diseases, mental distress due to prior traumas, undiagnosed chronic illness, and nutritional deficiencies (Deen & Bridges, 2011). Refugee populations represent high rates of mental and physical health problems compared with the host population (Kirmayer, Gomez-Carrillo, & Veissi�re, 2017). Additional dynamics compound health disparities facing refugees. These include: language barriers, unfamiliarity with a complex health care system, limited health literacy, and inadequate alignment of medical treatments with religious and cultural beliefs (Bowen, 2001; Brown, Carroll, Fogarty, & Holt, 2010). Though there is robust scholarship in the literature and analysis of prevalent health disparities and needs of refugees post-resettlement, few studies address the specific health care concerns of refugees resettled in northern Utah. This study seeks to expand previous findings related to the most salient health care issues facing the refugee community and develop community response to address health disparity. A secondary aim of the research is to determine best practices for the provision of appropriate and effective health services.

McQuinn, Sophie; Love, Tiffany (University of Utah)
Faculty Advisor: Love, Tiffany (University of Utah, Psychiatry)

Chronic pain is a major health crisis, and is considered the second major cause of disability in the world. People with chronic pain that lasts 6 months or longer often experience other symptoms as well, including depression. While the causes of chronic pain are often unknown, it has been shown that people with chronic pain exhibit brain structure differences compared to those who do not. It is important to know how chronic pain and brain structure are interconnected so that we can find a better way to treat patients. Gaining more knowledge of this connection can lead to a better understanding of the underlying causes. Brain structure goes hand in hand with neuroplasticity, which plays a key role in normal brain development. While it has been shown that chronic pain can have a significant effect on brain structure, it is unknown whether different symptoms affect different areas of the brain. The effects of chronic pain on the brain have only been looked at in a holistic sense and have not been quantified according to symptoms. Because chronic pain can have a variety of causes, this makes it difficult to determine a good method of treatment for individuals. Our aim was to determine how different symptoms of chronic pain affect the brain individually and evaluate possible overlap. The categories we tested were sensory, affective, unpleasantness, intensity, and depression. We used MRI scans from both healthy individuals and participants experiencing chronic lower back pain. The relative levels of each symptom that the participants were experiencing were determined via the McGill Pain Questionnaire and the Center for Epidemiologic Studies Depression Scale. Having a better understanding of how different symptoms of chronic pain affect the brain can aid in finding more personalized treatment for those experiencing it.

Passey, Abigail; Domyan, Eric (Utah Valley University)
Faculty Advisor: Domyan, Eric (Utah Valley University, Department Of Biotechnology/Biology)

In the United States approximately 3 million people are living with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Approximately 75,000 of those patients represent pediatric cases. We aim to create a new drug delivery system with the intention of establishing a more feasible, stable, and effective form of administering treatments to those with the aforementioned autoimmune diseases, specifically attempting to provide a more ideal treatment for juvenile patients. We are focusing on first providing a rudimentary proof of concept. For the project, we will attempt to engineer mammalian cells that will produce the fusion protein CTLA4-Ig, commonly known as abatacept, a current treatment for RA, and a potential treatment for SLE. Thus far, we have completed and verified success of the molecular cloning necessary to create the recombinant molecule. We have successfully induced expression of the fusion protein in mammalian cell lines COS-7 and B16F10 via lipofections. We are currently working to optimize lipofection conditions and test for successful cellular production of CTLA4-Ig. Ideally, we aim to engineer red blood cells (RBCs) to produce the molecule. If we can complete our proof of concept, we will then attempt to reprogram myeloid and lymphoid progenitors into induced hematopoietic stem cells (iHSCs), and culture the cells ex vivo to allow for massive expansion of these iHSCs, which can then be genetically engineered. Additionally, the iHSCs will be cultured in such a way that, once in vivo, will result in them committing explicitly to erythroid lineages, and secreting the target protein as they mature into fully functional, adult RBCs. Causing RBCs to secrete CTLA4-Ig throughout the body would eliminate the need for regular injections of the drug, and thus potentially improve the quality of pediatric patients' lives.

Petersen, Chrissa; Velaytham, Anandh; Saldivar, Miguel (University of Utah)
Faculty Advisor: Velayutham, Anandh (Integrative Physiology and Nutrition)

Aging is a major risk factor for cardiovascular diseases such as atherosclerosis, which are major causes of disability and mortality in the elderly. Endothelial dysfunction plays a major role in aging-associated vascular complications. Dietary change may be one of the novel strategies to ameliorate endothelial dysfunction and aging-associated complications. Our lab recently showed that dietary supplementation of blueberries improves vascular inflammation and dysfunction in diabetic mice. In our present study, we investigated the effect of dietary blueberries on vascular function in aged mice. Adult male mice (two months old) and old male mice (17 months old) were fed a control rodent diet (Y and O respectively). The subgroups of Y and O mice were fed a diet supplemented with 3.8% freeze-dried blueberries (Y+BB, O+BB respectively) for 15 weeks. Based on normalization to body surface area, this dose in mice is equivalent to ~1.5 servings of blueberries (~240 g) in humans. Mesenteric arteries were collected and used to assess vascular function using a wire myograph system. After arteries were precontracted to ~65% of maximal phenylephrine-induced contraction and tension was stable, responses to acetylcholine (ACh, 10-8-10-6 M) were evaluated to determine endothelium-dependent vasorelaxation. In our study, there is no difference existed between Y vs. O and O vs. O+BB indicating the vascular function was similar among the groups. Our ongoing studies are focused on identifying the effect of dietary blueberries on vascular inflammation in aged mice and the possible molecular mechanisms involved.

Nelson, Andrew; Foutz, Isaac; Hunt, Porter; Wood, David; Bundy, Bradley; (Brigham Young University)
Faculty Advisor: Bundy, Bradley (Brigham Young University, Chemical Engineering)

Cell-free Protein Synthesis (CFPS), an in vitro system for producing recombinant protein, is a rapidly expanding field. To date, applications of this technology, among others, include unnatural amino acid incorporation, protein microarray fabrication, genome engineering, and the production of therapeutics, vaccines, and biocatalysts. Here, we further engineer cell-free protein synthesis as a biosensor for endocrine-disrupting chemicals (EDCs), compounds that mimic hormones and thus disrupt endocrine system physiology in the body.

Miles, Leslie; Valentine, Julie (Brigham Young University)
Faculty Advisor: Miles, Leslie (Brigham Young University, College of Nursing); Valentine, Julie (Brigham Young University, College of Nursing)

1 in 10 adolescents (13-18 years old) reported sexual violence in the dating environment with a prevalence rate of 14% among girls and 8% among boys (Wincentak et al., 2017). Additionally, Arliksson-Schmidt et al. (2010) found that adolescent girls with a physical disability or long-term health problem were more likely to experience sexual violence (p=.003). The current literature is limited on describing the characteristics and vulnerabilities of adolescent sexual assault patients. Researchers have found multiple negative sequelae in adolescents who have been sexually assaulted, which includes the following; major depressive disorder, suicide risk, agoraphobia, alcohol abuse & dependence, and substance abuse & dependence (Walt et al., 2014).

To better understand adolescent patients and to guide nursing care, a large (n=5,600) retrospective chart review of SAFEs documentation (2010-2018) examines adolescent descriptors (age 14-18) in a Western state in the United States. Variables include gender, race, age, relationship to suspect, online meeting, pre-existing medical conditions, pre-existing mental illness, previous history of sexual assault, number of non-anogenital injuries, number of anogenital injuries, alcohol and drug use, multiple suspects, and suspect actions (violent physical acts). Comparisons to patients over the age of 18 years will be provided.

The purpose of this podium presentation is to review research findings concerning the demographics and characteristics of adolescents seen for sexual assault forensic examinations to better inform health care professionals. Discussion will include possible medical and nursing interventions to mitigate the potential harmful effects of adolescent sexual assault.

Linder, Caitlin; Linder, Lauri (University of Utah)
Faculty Advisor: Linder, Lauri (College of Nursing, Nursing)

Childhood cancer disrupts children's day-to-day experiences. The purpose of this study was to analyze children's responses to two questions included in a daily symptom reporting app: "What is the best thing about today?" and "What is bothering you the most today?" Responses were part of a larger study evaluating the feasibility and acceptability of the app. Children used the app to record daily symptoms and answer short questions about their day.

Children completed a trial of the app between visits at the hospital for chemotherapy. Daily responses to each question were analyzed using descriptive qualitative content analysis with each response serving as a unit of analysis. Coding was completed by each author and reviewed together to reach agreement. Children's responses were organized into categories and subcategories.

Participants were 19 children 6-12 years of age (median 8 years) (12 boys) receiving chemotherapy who used the app for a total of 83 days (median 4.5 days/child). Children provided 72 responses about the best thing about their day that were organized into nine categories: Activities (n=22), People (n=14), Food (n=9), Well-Being (n=9), School (n=7), Nothing (n=5), Object (n=4), Going Home (n=3), and Don't Know (n=1). Children provided 60 responses about the most bothersome aspect of their day that were organized into six categories: Nothing (n=22), Symptoms (n=17), Port (n=7), Cancer Treatment (n=5), Day-to-Day Stuff (n=5), and People (n=4).

Children's responses provide perspective of the impact of cancer on their daily lives. Their responses indicate the importance of maintaining developmentally normal activities and family relationships. Children's responses further indicate the pervasiveness of the cancer experience, such as symptoms, even on days when children are away from the hospital. Mobile health apps can help children not only track symptoms but also reflect on their day. Clinicians can use children's information to better understand children's experiences.

Bobeck, Erin; McDermott, Max (Utah State University)
Faculty Advisor: Bobeck, Erin (College of Science, Biology Department)

TBD - Updated for publication

Oram, Kathryn; Griffiths, Alayna (Utah Valley University)
Faculty Advisor: Gazdik-Stofer, Michaela (Utah Valley University, Biology)

The World Health Organization currently estimates that 4,384 individuals die per day due to complications of Mycobacterium Tuberculosis and affects 1.8 million people worldwide as it infects individuals through air droplets from a cough or sneeze. Cyclic adenosine monophosphate (cAMP) is known to be a major component in TB because it acts as a macrophage inhibitor that is responsible for blocking the immune defense allowing the M. Tuberculosis to rapidly replicated within cells. The function of cAMP in TB patients is known but the focal point of our research is why and how the increased levels of cAMP effects patients that are infected with TB. Our team uses mutated M. Smegmatis bacteria due to the comparable levels of cAMP secretion and high pathogenicity of M. Tuberculosis. We are currently screening the cAMP secretion in 1,000 mutated M. Smegmatis colonies to identify secretion differences from the wild-type M. Smegmatis. The mutants samples with high variation from the wild-type will be sequenced to identify the genes and determine the proteins that are present. Finding the genes and proteins can help understand why and what causes the inflation on cAMP secretion in TB patients.

Varghese, Alyssa; Crandall, Hillary; Blaschke, Anne (University of Utah)
Faculty Advisor: Crandall, Hillary (University of Utah, Department of Pediatrics); Blaschke, Anne (University of Utah, Department of pediatrics)

Haemophilus influenzae serotype b (Hib) causes serious bacterial infections in children associated with high morbidity and mortality. The incidence of Hib disease decreased with widespread vaccination in the mid-1980's. However, other H. influenzae serotypes, such as serotype a (Hia), have emerged in specific pediatric populations, including Utah and indigenous populations in Alaska and Canada. Hia appears to cause disease similar to Hib in both severity and disease presentations.

Cases of invasive H. influenzae disease in children <18 years were identified via a search of electronic medical records within the Intermountain Healthcare system. Phylogenetic division was determined using sodC PCR. Whole genome sequencing (WGS) was performed on available isolates. Gene presence and absence data from resulting assemblies were utilized to build a relationship tree from all available Hia isolates, as well as select Hib, H. influenzae serotype f (Hif), and non-typeable H. influenzae (NTHi) isolates. Multi-locus sequence type (ST) was extracted from WGS data for each isolate.

118 cases of invasive H. influenzae disease were identified from 2007 to 2017. Fifty-one (43.2%) cases were Hia and 11 (9.3%) were Hib. Twenty-eight of 51 (56%) Hia isolates were available for further molecular analysis. Three STs were identified: ST56, ST62, and ST576. Twenty-one isolates (75%) belonged to ST62, clonal division II. The relationship tree indicates that ST62 Hia isolates are most closely related to each other and more closely related to Hif than to other Hia and Hib.

The molecular epidemiology of invasive Hia disease in Utah is unique, with a predominance of ST62 strains, a ST that has been infrequently reported in other studies of invasive Hia. Further genomic analysis will help us understand genetic determinants of virulence. These analyses will be critical in characterizing the clinical and molecular features of invasive H. influenzae disease in Utah.

Brammer, Brianna; Denham, Steven; Wambaugh, Morgan; Brown, Jessica. (University of Utah)
Faculty Advisor: Brown, Jessica (University of Utah, Pathology)

Cryptococcus neoformans is an opportunistic fungal pathogen, which primarily affects those with compromised immune systems, contributing to 15% of global AIDS-related deaths. Initial human exposure occurs after inhalation of desiccated cryptococcal cells, which undergo morphological changes in the lungs, including altering cell body and polysaccharide capsule size. Fatality occurs after C. neoformans disseminates to extrapulmonary organs, including the brain where it causes cryptococcal meningitis. Preliminary data show that fungal cells decrease in size throughout the course of infection; we hypothesize that this shift increases the ability of fungal cells to exit lung epithelium, either extracellularly or via macrophage, as small cryptococcal cells exhibit enhanced extrapulmonary dissemination. We later determined that this effect was not solely due to fungal cell size by inoculating mice with fluorescent beads corresponding to cryptococcal cell size groups. The beads showed similar dissemination trends, but were significantly less efficient at extrapulmonary dissemination, suggesting the necessity of cell surface factors. By measuring the exposure of various fungal factors relative to size, we have identified mannose as a potential key factor in dissemination, as small cells exhibit higher levels of exposed mannose relative to size. The hypothesized role of mannose in cryptococcal dissemination is investigated throughout this project utilizing a variety of techniques, including the addition of polysaccharides to macrophage-cryptococcal association assays to determine mannose-specific recognition, in vivo co-inoculation with mannose and cryptococcal cells, and identifying differential gene expression between cell sizes using RNA sequencing and gene ontology. These data have contributed to our working model of cryptococcal infection, where cryptococcal cells undergo morphological changes in the lungs, yielding a higher prevalence of small cells. Cell size is an important, but not determinant factor in dissemination, suggesting the role of cell surface factors, such as mannose, that increase virulence by promoting phagocytosis and intracellular survival.

Salas, Norma; Condie, Kali; Cook, Lauralee (Utah Valley University)
Faculty Advisor: Jensen, Francine (Utah Valley University, Nursing)

Problem Statement:

Depending on the provider a woman has during her delivery, the education, interventions, and care she receives will differ. Variations of care under an obstetrician and gynecologist (OB/GYN) compared to a midwife may produce differing satisfactory results for women experiencing labor and delivery.

Purpose:

The purpose of this research study is to discover if women who have delivered with both an obstetrician/gynecologist and a midwife are more satisfied with their birthing experience under the care of one provider compared to the other.

Research Question:

Are women who have experienced labor and delivery with an OB/GYN and a midwife more satisfied with their birthing experiences from one provider compared to the other?

Background:

In a patient-centered world, it should be up to the provider and expecting mother to choose the modality of delivery they would like, including the place, medical interventions, positioning, and methods of delivery. OB/GYNs and Midwives vary in practices, and implementations during gestation and delivery. Dissatisfaction with labor and delivery is an aspect of the current healthcare industry that needs to be addressed in order to improve patient care. Coxon, Sandall, and Fulop highlight this issue by pointing out that many women feel constrained with their decisions regarding labor and delivery and that delivery opportunities may be limited due to influences from cultural and historical associations as practiced by the provider (2014). Patient satisfaction is also influenced by pressures women in labor and delivery experience in order to accommodate their providers wishes.

Hope to accomplish:

We hope to determine if women's satisfaction during their labor and delivery experiences are higher with either a midwife or an obstetrician/gynecologist, as well as to promote better education and patient autonomy to increase patient experience satisfaction.

Richardson, Deborah; Valentine, Julie; Miles, Leslie (Brigham Young University)
Faculty Advisor: Valentine, Julie (Brigham Young University, Nursing); Miles, Leslie (Brigham Young university, Nursing)

Purpose: Describe the minimal effect of post-assault bathing or showering on the development of FBI Combined DNA Index System (CODIS) eligible DNA profiles from sexual assault kit evidence.
Sexual assault kit (SAK) submission rates significantly decrease in cases wherein the victim has bathed or showered. The belief that these actions diminish the possibility of finding evidence heavily contributes to be a significant negative predictor of SAK submissions by law enforcement (LE). Now there are improved DNA analysis methods that can yield CODIS eligible DNA profiles from skin regardless of whether the victim bathed or showered.
SAK submission rates and DNA analysis findings from 5,423 cases were evaluated in this retrospective study. 36% of victims reported post-assault bathing or showering. These washing actions was found to be highly correlated with time between assault and sexual assault forensic examination. In a generalized estimating equation (GEE) logistic regression analysis on SAK submission rates, victim reports of post-assault bathing or showering was a consistent predictor of law enforcement not submitting kits. Yet, bivariable statistical analysis determined that victim bathing or showering post-assault was not associated with the lack of development of a DNA probative profile from SAK evidence.
The effect of post-assault bathing or showering must be reconsidered in the forensic science and criminal justice community as DNA analysis can yield probative DNA profiles, even after a victim has bathed or showered. The presentation of these research findings will encourage the submission of SAK by law enforcement and potentially increase SAK submission rates by eradicating any doubt regarding the minimal effect of bathing or showering on the development of CODIS eligible DNA profiles. New research data supports the collection, submission and testing of all SAK especially those with a victim history of post-assault bathing or showering.

Carrington, James; Xue, Qian; Roh-Johnson, Minna (University of Utah)
Faculty Advisor: Roh-Johnson, Minna (University of Utah, Biochemistry)

Metastasis of melanoma to distant sites of the body result in poor patient prognosis with a high mortality rate (76%). Cell migration has been studied in vitro and focal adhesions, which allow cells to move forward by attaching to extracellular matrix (ECM) on the front of the cell and breaking down at the back of the cell, have been shown to play important roles in locomotion. However, it has been difficult to visualize these structures in vivo, especially during tumor cell dissemination. Understanding how cancer cells are utilizing focal adhesions could play an important role in developing therapeutics to counteract metastasis using focal adhesion inhibitors and lead to improved patient outcomes. This research focuses on identifying if a previously observed focal adhesion marker in melanoma is formed at surfaces where cells are in contact with ECM. Because zebrafish share 80% disease homology with humans and are transparent during early embryonic development, they provide an optimal model for visualizing cell migration while still maintaining physiological significance. To identify if migrating melanoma cells are in contact with ECM, we injected fluorescently labeled melanoma cells in zebrafish. We allowed the melanoma cells to migrate and labeled components of the ECM (laminin, collagen, and fibronectin). We then imaged the zebrafish and determined the proximity of melanoma cells to the ECM. We also used transmission electron microscopy to identify the location of melanoma cells in respect to the ECM. We found that melanoma cells are in contact with ECM in vivo. The in vivo contact of focal adhesion markers in melanoma with ECM suggests that focal adhesions can be visualized and studied in zebrafish. Future studies will examine how focal adhesion formation is regulated and how inhibiting their function will impact tumor cell dissemination.

Symons, J. David; Thompson, Lauren; Ramous, Caroline; Cho, JaeMin; Boudina, Sihem; Margetts, Alex; Buzianis, Skye; Park, Seul Ki; Luu, Kiana; Hansen, Michele; Pires, Karla; Whitehead, Kevin; Carter, Kandis; Buffolo, Marcio (University of Utah)
Faculty Advisor: Symones, J. David (University of Utah, Nutrition and Integrative Physiology)

Protein aggregates accumulate and organelles become damaged and / or dysfunctional during the process of healthy aging. A progressive loss of the cellular quality control mechanism autophagy (i.e., "self-eating") contributes to this age-associated decline in cellular function in many organs. Evidence for an age-associated repression in cardiac autophagy is not consistent. We hypothesized that 24-month old (old) male C57Bl6/J mice exhibit repressed autophagosome formation in the heart, an accumulation of cardiac protein aggregates, myocardial dysfunction, and reduced exercise capacity vs. 6-month old (adult) mice. First, cardiac lysates from old mice displayed reduced (p<0.05) accumulation of LC3II / GAPDH and degradation of p62 vs. adult animals (assessed via immunoblotting; n=12 per group). Second, the lysosomal acidification inhibitor chloroquine (CQ) induced accrual (p<0.05) of LC3II / GAPDH and p62 in hearts from adult but not old mice (quantified by immunoblotting; n=7 per group). Third, the number and size of protein aggregates was higher (p<0.05) in hearts from old vs. adult mice (measured via scanning electron microscopy; n=5 per group). Fourth, left ventricular mass / tibial length was greater (p<0.05), and indices of systolic, diastolic, and global left ventricular function (measured via transthoracic echocardiography) were impaired (p<0.05), in old vs. adult animals (n=12 per group). Finally, maximal workload performed during a treadmill-test, and soleus muscle oxidative enzyme capacity (citrate synthase activity assessed via ELISA), were less (p<0.05) in aged (n=11) vs. adult (n=12) mice. To determine whether late-in-life exercise training improves cardiac autophagy to an extent that demonstrates functional relevance, separate cohorts of older male mice completed a progressive-resistance treadmill-running program (old-ETR) or remained sedentary (old-SED) from 21-24 months. Body composition (estimated via nuclear magnetic resonance), exercise performance during a maximal workload test, soleus muscle citrate synthase activity, indices of cardiac antioxidant enzyme activity (quantified via immunoblotting), markers of cardiac autophagy, accumulation of cardiac protein aggregates, and indices of myocardial function, all improved (p<0.05) in old-ETR (n=11) vs. old-SED (n=12) mice. These data are the first to demonstrate that markers of cardiac autophagy are elevated, and indicators of protein aggregate removal and myocardial function are improved, in older mice that complete a treadmill-training regimen that is sufficient to increase skeletal muscle CS activity and maximal exercise capacity. Our results provide strong proof of concept to evaluate cause and effect relationships among exercise-training, myocardial autophagy, and cardiac function using genetic approaches in pre-clinical models and these studies are ongoing in our laboratory.