Fine Arts
Do Examples of Unethical Conduct Improve or Undermine Ethics Training in Psychology
Authors: Joshua Parmley, Acacia Overono. Mentors: Acacia Overono. Insitution: Utah Valley University. Since its founding over a century ago, the American Psychological Association has adopted several distinct roles in its ongoing pursuit of legitimacy, stability, and growth for the field of psychology. Two of its most important roles include the establishment and enforcement of an ethics code and the standardization and development of undergraduate education. These two goals are related; the best way to uphold an ethics code is to ingrain that code into future researchers and practitioners. The APA Guidelines for the Undergraduate Psychology Major 3.0, which lists the APA’s ideal learning objectives for undergraduate programs, attempts to do just that. In its section on ethics training, it places a great degree of responsibility on undergraduate programs to prepare students for a world of bad actors, exploitative systems, and ethical grey areas. To achieve this, the document recognizes that students must develop an ethical skill or proficiency, not just a knowledge of the codes and principles. Unfortunately, Guidelines recommendations for achieving that goal quickly become clouded, as the document wrestles with the various concerns about teaching ethics. Primarily, the Guidelines section on ethics seems conflicted about whether instructors should give students historical examples of psychologists and psychology systems engaging in unethical behavior The Guidelines expresses the concern that presenting students with examples of ethical failures by psychologists will distract students from the learning outcomes or lead them to view the field negatively and abandon it altogether. Accordingly, the APA tentatively recommends that negative examples be shared cautiously, alongside examples of the positive achievements of the field and ethical systems in place. Are the APA’s fears that blunt ethics courses could turn students away from the major valid? Or do the Guidelines recommendations put too little faith in their instructors and students? This study seeks to examine the validity of the APA’s concerns and the efficacy of their recommendations. One hundred and fifty Intro to Psychology students will be divided into three groups. Each group will be instructed in the principles of the APA ethics code using a) no historical examples, b) a balance of negative and positive examples, or c) several negative examples. Participants will then take a survey that measures their ethical proficiency, their memory of the material, and their confidence in the field of psychology. Measurement of ethical proficiency will be adapted from APA measurement tools. We predict that the group instructed with several negative examples, without balancing positive examples, will result in greater measurements of ethical proficiency, better recall, and a slightly lowered level of confidence in the field. We predict this based on the idea that reviewing negative examples in the instructional material will provide students with a specific model of ethical decision-making.
Infant Identity Among the Tiwanaku
Authors: Matthew Hovorka. Mentors: Connie Ericksen. Insitution: Utah Valley University. This research project examines evidence of individual identity and personhood among perinates, neonates, and young children in the Tiwanaku culture (Western Bolivia, Chile, Peru, A.D. 500-1100) of the ancient Andes. A multifocal approach is taken in examining the topic, and ethnohistorical and archaeological evidence is examined to create a picture of Tiwanaku conceptions of personhood. Through a comprehensive analysis of burial practices, iconography, and ethnohistorical records, this study sheds light on the nuanced conceptions of personhood and individual identity held within the Tiwanaku culture. By delving into the socio-cultural context and material evidence, this research contributes to a deeper appreciation of the complex beliefs and societal values of this ancient Andean civilization.
The utility of ChatGPT in subspecialty consultation for patients (pts) with metastatic genitourinary (GU) cancer.
Authors: Ayana Srivastava, Gliceida Galarza Fortuna, Beverly Chigarira, Emre Dal, Chadi Hage Chehade, Georges Gebrael, Arshit Narang, Neeraj Agarwal, Umang Swami, Haoran Li. Mentors: Neeraj Agarwal. Insitution: University of Utah. The utility of ChatGPT in subspecialty consultation for patients (pts) with metastatic genitourinary (GU) cancer.Ayana Srivastava, Gliceida Galarza Fortuna, Beverly Chigarira, Emre Dal, Chadi Hage Chehade, Georges Gebrael, Arshit Narang, Neeraj Agarwal, Umang Swami, Haoran LiHuntsman Cancer Institute at the University of Utah, Salt Lake City, UT;University of Kansas Cancer Center, Westwood, KSBackground:Cancer management requires a multidisciplinary approach, often requiring medical consultation from subspecialists. With the advent of artificial intelligence (AI) technologies like ChatGPT, it is hypothesized that these tools may help expedite the consultation process. This study aimed to assess the efficacy of ChatGPT in providing guideline-based sub-specialty recommendations for managing pts with metastatic GU cancer.Methods:In this single-institution, IRB-approved, retrospective, proof-of-concept study, pts with metastatic GU cancer over the past 3 years were screened. Those with at least one consultation referral to subspecialty clinics were randomly selected. ChatGPT 3.5 was given the most recent clinic note that triggered sub-specialty consultation. The AI tool was then asked to provide an assessment and plan. Two physicians independently assessed the accuracy of diagnoses made by ChatGPT and subspecialty physicians. The primary outcome was the consistency of ChatGPT recommendations with those of subspecialty physicians. Secondary Outcomes included potential time saved by using ChatGPT and comparison of medical decision-making (MDM) complexity levels between ChatGPT and subspecialty physicians.Results:A total of 39 pts were included. Their primary diagnoses included prostate cancer (51.3%), bladder cancer (23.1%) and kidney cancer (15.4%). The referred subspecialty clinic included cardiology (33.3%), hematology (17.9%), hepatology (2.6 %), hospice (10.3%), neurology (12.8%), pulmonary (15.4 %), and rheumatology (7.7%). The average waiting time for pts to be seen in subspecialty clinics was 44.9 days (SD = 42.4). Of 39 patient’s charts reviewed by ChatGPT, 30/39 (76.9%) had the same diagnosis with consultant sub-specialties. The average diagnoses made by ChatGPT were 8.2, compared with 3.4 made by sub-specialty physicians (p < 0.0001). The accuracy of diagnoses made by ChatGPT was the same, higher, and lower than human physicians in 10 (33.3%), 3 (10%), and 17 (56.7%) cases, respectively. Consistency of treatment plans between ChatGPT and physicians was found in 18 cases (46.2%). ChatGPT recommended additional workup in 32 cases (85.1%). The average number of words written in consultation notes by ChatGPT was 362.7 (SD = 72.9), which was significantly greater than subspecialty physicians (n = 224.7, p < 0.0001).Conclusions:These hypothesis-generating data suggest the potential utility of ChatGPT to assist medical oncologists in managing increasingly complex pts with metastatic cancer. Further studies are needed to validate our findings.
The Effects of State Anxiety on Face Identification
Authors: Patrick R Davies II. Mentors: Acacia Overono. Insitution: Utah Valley University. While there is a dedicated area of the brain for recognizing faces, the efficacy of recognition tasks can vary depending on the context under which they’re performed. The existing literature is undecided on whether anxiety helps or harms tasks relating to emotional content recognition, and some studies have taken steps into researching memory as an additional layer to these recognition tasks. A preliminary study was performed with 16 participants using virtual reality to study the effects of acute anxiety on the ability to correctly identify faces. Participants played either a brief horror game or a brief virtual sandbox in order to induce a desired emotional state, then were asked to complete a brief paired-face identification paradigm. Initial results show that anxiety strengthens identification of neutral emotionally-valent face pairs. Further results may clarify the relationship between anxiety and face identification processes.
The Newborn Behavioral Observation (NBO) and Its Impact on Early Relationships, Postpartum Depression, and Infant Outcomes
Authors: Tara Caplin, Tiffanee Suhaka, Maria Balaceanu, Peg Bird, Dannelle Larsen-Rife. Mentors: Dannelle Larsen-Rife. Insitution: Utah Tech University. Early parent-child interactions have a profound impact on the developing brain, influencing lifelong emotional and social well-being. This review evaluates the Newborn Behavioral Observation (NBO), a relationship-based neurobehavioral approach for families and infants three months old and younger. The NBO supports newborns, caregiver’s, and families by providing individualized information on their infants' behavior and competencies. It facilitates communication and intersubjectivity between infants and caregivers during a critical developmental period, while reducing maternal postpartum depression (PPD). Research on the association between the NBO, PPD, and infant neurodevelopment is reviewed and evaluated in high-risk populations. Although evidence supports approaches like the NBO, they are not yet standard in early intervention due to clinicians' lack of training in infant mental health. The NBO is a foundational tool for cultivating positive early relationships with beneficial implications for clinician standard care of newborns and families. Keywords: Newborn Behavioral Observation (NBO), early relationships, postpartum depression (PPD), infant development, relationship-based, early intervention.
When One is Loved: Attachment Security and Relationship Quality
Authors: Maria Balaceanu, Dannelle Larsen-Rife, Tara Caplin, Peg Bird, Grace Carsey, Tiffanee Suhaka. Mentors: Dannelle Larsen-Rife. Insitution: Utah Tech University. Attachment theory provides a framework for understanding how early experiences with caregivers influence individuals' emotional and relational development throughout their lives. In addition to understanding how an individual interacts with close others, attachment predicts relationship satisfaction (Gardner et al., 2020). Individuals with secure attachments demonstrate greater adaptability in coping and regulating their emotions, leading to improved socio-emotional well-being. In contrast, those with insecure attachment styles tend to encounter difficulties in socio-emotional adjustment (Gardner et al., 2020). This study will examine how insecure attachment is associated with romantic relationship dissatisfaction, specifically those lasting five years or longer. We focus exclusively on romantic relationships lasting five years or more because in adult relationships, each partner serves as an attachment figure for the other (Diamond et al., 2008). Therefore, spouses have the potential to increase each other's attachment security. This means an initially insecure individual can develop earned secure attachment with their spouse's support. Approximately 300 diverse participants over the age of 18 will be recruited for the study. The Relationship Structures Questionnaire (ECR-RS; Fraley et al., 2011) will assess insecure attachment. The Relationship Assessment Scale (Hendrick, 1988) will assess satisfaction. It is expected insecure attachment will be correlated with lower relationship satisfaction with a romantic partner of five years or longer. Results of the analyses will be presented.
Cryopreservation: The Chilly Future of Biobanking
Authors: Jared Barrot, Mackenzie Burr, Isaac Packer, Peyton Worley, Delaney Anderson, Jack Davis, Jeffrey Okojie, Ken Dixon. Mentors: Jared Barrott. Insitution: Brigham Young University. In cancer diagnosis, drug testing, and treatment, analysis is done almost exclusively on formalin-fixed paraffin-embedded (FFPE) tissue samples, a process known to cause chemical cross-linking, DNA fragmentation, and degradation. With the push for genetic testing and personalized medicine, cryopreservation of tissue samples has started to gain traction in the research community. We utilized FFPE samples and cryopreserved samples, extracted DNA, and compared the samples using three criteria: DNA purity, quality, and yield. DNA yield, measured on nanograms of DNA to milligrams of tissue basis, demonstrated a five times the yield in cryopreserved samples than in FFPE. DNA purity did not show significant differences between a cryopreserved tissue sample versus a FFPE tissue sample, confirming valid use of FFPE storage methods if purity is the only factor; however, DNA quality was significantly better in cryopreserved tissue samples, with nearly twice the DNA quality number (DQN) than FFPE samples demonstrated, with significant portions of longer base pair DNA fragments present, widening the range of molecular applications of the sample. These cryopreserved tissues provide higher DNA quality, a higher percentage of significantly longer DNA fragments, and increased DNA yield from individual samples, confirming that cryopreservation is a better option than FFPE when it comes to choosing tissue preservation and storage methods. More molecular assays and tests can be run, and smaller samples are necessary when utilizing cryopreservation, proving it to be a better option than the “gold standard” of FFPE, particularly in regards to cancer diagnosis, drug testing, and treatment exploration.
Investigating the Role of FBXO21 in Hematopoietic Malignancy
Authors: Danielle Alvarado, Kasidy Weber, Shannon Buckley. Mentors: Shannon Buckley. Insitution: University of Utah. The ubiquitin-proteasome system (UPS) plays a critical role in cancer by regulating the degradation of key proteins involved in cell cycle control, DNA repair, apoptosis, and signaling pathways, making it a crucial mechanism for maintaining cellular homeostasis and preventingtumor development and progression. The expression levels of F-box ubiquitin E3 ligase, FBXO21, correlates with patient survival in several types of cancer, suggesting a role in tumorgenesis. We have previously shown silencing FBXO21 in acute myeloid leukemia (AML) cell lines and patient samples leads to differentiation, slowed tumor progression, increased chemotherapy sensitivity, and altered cytokine signaling. Further, we found that FBXO21 ubiquitinates p85α, a regulatory part of the phosphoinositide 3-kinase (PI3K) pathway, for degradation resulting in altered PI3K signaling. Although PI3K inhibitors are used in cancertreatment, issues like off-target effects, dose-limiting toxicities, and resistance necessitate further research and development for optimized efficiency and minimal negative effects in targeting the PI3K pathway. To further understand the role of FBXO21 in cancer, we utilized shRNAs targeting FBXO21 in various cancer cell lines to identify the role of FBXO21 in cellular proliferation, apoptosis, and alteration of the PI3K pathway. The PI3K signaling pathway is initiated through p85α binding to the catalytic subunit, p110, leading to downstream AKT and mTOR activation. We found knockdown of FBXO21 stabilizes p85α, leading to dimerization of free p85 and decreased PI3K pathway activation. Therefore, we hypothesize that FBXO21 may function as a novel regulator of PI3K signaling, offering an alternative approach to PI3K inhibitors. Our findings suggest that FBXO21 may represent a novel therapeutic target acrossvarious cancer subtypes to target the overactive PI3K pathway. Targeting FBXO21 may enhance the efficacy of current therapies and provide potential benefits for improving patient outcomes in the treatment of cancer, including but not limited to AML
Modeling Glioblastoma's Effect on Neural Networks using Brain Organoids
Authors: Jude Werth. Mentors: Alex Shcheglovitov. Insitution: University of Utah. Glioblastoma (GBM) is the deadliest brain tumor that affects more than 10,000 people a year. Unfortunately, our understanding of the mechanisms disrupted by GBM is extremely limited. We are unable to safely manipulate brain cells in live patients, and the complexity of human brain networks are difficult to recapitulate in animals. This study employs brain organoids, derived from induced Pluripotent Stem Cells (iPSCs), to model the impact of GBM on neural activity. Organoid batches, grown under normal conditions and co-cultured with GBM cells, were monitored using microelectrode arrays (MEA) to record power in frequency bands. Over time, drugs influencing neural activity were introduced. Significant behavioral distinctions were observed between control and GBM-cultured organoids. Under Bicuculline and Tetrodotoxin, power in GBM organoids exhibited dramatic changes compared to the minimal difference in control organoids. Conversely, 4-Aminopyridine induced increased high-frequency activity exclusively in control organoids. Correlating power in frequency bands with spike activity, this study provides insight on how brain tumors influence neural networks, furthering disease comprehension to eventually develop effective treatment for patients.
Transcriptomics Meta-Analysis Identifies Upregulation of Clotting and Fibrinolysis Cascades in Colorectal Cancer Tumors Containing Hereditary PMS2 Mismatch Repair Deficiency
Authors: Trenton M. Gibson, Brett E Pickett. Mentors: Brett E Pickett. Insitution: Brigham Young University. Lynch Syndrome, formerly known as Hereditary Non-Polyposis Colorectal Cancer, is an autosomal dominant condition characterized by non-functional DNA mismatch repair genes, leading to mismatch repair deficiency (dMMR). Individuals with dMMR have an increased risk of developing cancerous tumors with microsatellite instability (MSI). The aim of this study was to investigate significant perturbations in gene expression among different dMMR variants within Lynch Syndrome, specifically focusing on variants in the PMS2, MLH1, and MSH2 loci. We obtained 55 public RNA-seq human colorectal tumor samples with specific germline dMMR mutations and 20 samples of healthy colorectal epithelium from the GENE Expression Omnibus (GEO). These samples were subjected to a robust RNA-seq data preprocessing and analytical workflow, which involved quality control, trimming, read pseudomapping and quantification using Salmon, identification of significant differentially expressed genes using edgeR, and gene ontology enrichment analysis using Camera. Signaling pathway impact analysis (SPIA) was employed to assess gene pathway perturbations. Our results revealed that tumor samples from individuals with germline mutations in the PMS2 MMR gene exhibited transcriptomic profiles indicating upregulation in pathways related to intrinsic and extrinsic prothrombin activation, fibrinolysis, and uPA/uPAR-mediated signaling, in comparison to other tumor and healthy samples. Previous research has established a correlation between these pathways and tumor growth, invasiveness, and metastasis. These findings provide a foundation for further research to explore the interactions between PMS2 and these pathways in influencing tumor development.
An Efficient Microwave Assisted Ullmann-Type Amination of 3- Bromopyrazolo[1,5-a]pyrimidine: Key Intermediate for Preparing 3,6-Di-Amino-Substituted Anticancer Heterocycles
Authors: Bryce Tolman, Jasper Terungwa Iorkula , Justin Singleton, Matt Peterson. Mentors: Matt Peterson. Insitution: Brigham Young University. An efficient method for preparing C-3 aminated pyrazolo[1,5-a]pyrimidines was developed. The method consisted of treating 3-bromopyrazolo[1,5-a]pyrimidine with a wide range of 1° or 2° alkylamines with CuI (20 mol%), L-proline (40 mol%), and Et 3 N (2 equiv) in DMSO under microwave heating conditions (130 °C, 4 hours). C-3 aminated products were obtained in good to excellent isolated yields (54–90%; ave. yield = 77%), and represents the most broadly applicable, non-palladium-catalyzed amination of 3-bromopyrazolo[1,5-a]pyrimidine ever reported. The coupling worked well for unfunctionalized 1° alkylamines such as butylamine, benzylamine, isopropylamine or cyclohexylamine, and more densely functionalized 1° amines with CH 2 - or CH 2 CH 2 -linked heterocycles were also well tolerated (e.g. pyridine-, indole-, thiophene-, and furan-linked methyl- or ethylamine derivatives). 2° Alkylamines such as morpholine, pyrrolidine, and piperidine also reacted well under these conditions. Heating under conventional oil-bath conditions required a more extended reaction time (40 h), but also gave products in good yield (72-76%) for both 100-mg and gram-scale reactions. A pegylated azide (11-azido-3,6,9-trioxaundecan-1-amine) was also coupled in good yield (65% yield microwave), demonstrating compatibility of this methodology for potential click-type applications. Our method is simple and efficient, and avoids drawbacks associated with alternative methods, including long reaction times, limited substrate scope, and required use of air-sensitive/extremely expensive palladium catalysts and specialized synthetic ligands.
Functional Near-Infrared Spectroscopy and Dementia
Authors: Natalia Rubio, Madison Farrer. Mentors: Christopher Anderson. Insitution: Utah Valley University. Functional Near-Infrared Spectroscopy (fNIRS) is a neuroimaging technique used to monitor brain activity by measuring the changes in blood oxygenation levels, especially when presented with stimuli or given tasks. This is due to the principle that active brain regions require more oxygen, resulting in changes of blood flow and concentrations of hemoglobin. These observable results are achieved by diodes placed on the surface of the scalp that emit near-infrared (NIR) light into the skull. The absorption of this light by the hemoglobin in the brain’s blood vessels is then detected, localizing neural activity. Due to its portability and cost-efficient nature, fNIRS is being widely used across various fields of research and clinical applications whereas other neuroimaging methods might be less feasible or practical. Psychologists and neuroscientists are able to utilize fNIRS to understand how different regions of the brain are involved in various cognitive processes. It has been used in studying conditions like Alzheimer's disease, stroke, traumatic brain injury, autism, schizophrenia, mood disorders, and dementia. In the context of dementia research, fNIRS has emerged as a promising tool . While fNIRS has a low spatial resolution with measurements restricted to the outer cortex of the brain, it enables the study of the progression of dementia by providing real-time data and offering relative tolerance to subject motion. In fact, a neuro-clinic in Provo, Utah (Cognitive FX) has been studying the use of this fNIRS technique on patients with dementia while they perform language tasks. Although no patient data will be used in this study, the use of fNIRS as a technique to learn about the progression of dementia is noteworthy. Therefore, following IRB approval I will perform semi-structured qualitative interviews with two neuro-technicians using fNIRS in this clinic. Items will focus on the strengths and challenges of using fNIRS with dementia patients. Additionally, I will shadow these technicians to gain hands-on experience. Qualitative results will be analyzed and presented. It is anticipated that this research project will raise awareness of the use of fNIRS as a technique in neuroscience as well as its potential to benefit those with dementia.
Using Gut Microbiota Derived Metabolites As a Proxy for Gut Permeability and Subsequent Risk of Cachexia
Authors: Ellie P. Evans, Mmadili Ilozumba, Sheetal Hardikar, Neli Ulrich, Jennifer Ose. Mentors: Mmadili Ilozumba. Insitution: Utah Valley University. Cachexia is a complex syndrome characterized by severe weight loss and muscle wasting. It is also a prevalent complication in various chronic diseases, including cancer and acquired immunodeficiency syndrome. Recent research has underscored the pivotal role of the gut microbiome in systemic well-being. Furthermore, it has been shown that cancer patients suffering from cachexia have unique bacteria composition in the gut compared to that of non-cachectic patients. In the absence of stool samples, there are a few metabolites in the circulatory system that can be directly linked to gut microbiota. Examples include bile acids, and short chain fatty acids as metabolites produced by specific Phylum. The presence of these gut microbiota derived metabolites (GMDM) in the circulation indicate a compromise in the integrity of tight junctions in the intestines. These results prompted an investigation of GMDM as an indicator of gut permeability. Our hypothesis is that an increased concentration of GMDM in the circulation is linked to gut permeability, leading to the development of cachexia in patients with colorectal cancer. This literature review provides a comprehensive analysis of the relationship between gut permeability and cachexia, seeking to identify which GMDMs are the most accurate indicators of specific bacteria linked to gut permeability, and subsequently, are accurate projectors of cachexia. Acetic acid, a short chain fatty acid (SCFA) is a GMDM detected in the plasma of patients with gut permeability. Acetic acid makes up about 60% of the SCFAs produced by a healthy gut flora and 90% of it is produced by the genus Bifidobacterium. Our literature review will cover how closely a measurement of acetic acid and other GMDMs measured in plasma can be linked to gut permeability and to Bifidobacterium levels in the gut. Similarly, Indole is a GMDM produced by Escherichia coli and other indole-producing bacteria. Indole isn’t produced naturally anywhere else in the body. When it is naturally absorbed into the liver through the portal vein, it’s mostly converted into indoxyl sulfate. The heightened presence indole in plasma in sulfate-free forms could indicate that indole is being absorbed through holes in the tight junctions of the intestines, rather than through the portal vein. This information would allow cohorts that have collected plasma samples in the past to measure gut permeability by proxy, even if they’re unable to investigate the gut microbiota and metabolites present from stool samples. These connections found could further help us to use-already collected samples to find accurate biomarkers for early cachexia development in cancer patients. If an oral presentation is unavailable, a poster presentation would be great.
Inhibiting CDK9 and Autophagy in Pancreatic Cancer
Authors: Isabella Scalise. Mentors: Conan Kinsey. Insitution: University of Utah.
Elucidating the Role of TOX on Melanoma Cell Migration and Invasion
Authors: Allison Stevens, Gennie Parkman. Mentors: Gennie Parkman. Insitution: Weber State University. The principal genes that are responsible for the conversion of benign nevi, or pigmented lesions, to cancerous melanomas have been discovered and validated. However, we are still identifying the additional genetic alterations that are responsible for the migration and invasion of melanoma cells and ultimately metastasis of these melanomas as that is where treatment needs remain. (Davies, et al., 2002)One gene that has been identified to potentially play a role in the metastasis of melanoma is thymocyte selection associated high mobility group box, or TOX. Based on one study, the levels of TOX gene expression were found to be elevated in melanoma brain metastases versus extracranial metastases (Bierman et al., 2022). These findings have led us to hypothesize that TOX plays a role in the migration and invasion of melanoma into the brain. Preliminary work has been completed to clone our gene of interest, TOX, into an expression vector and transduce mammalian melanoma cells to evaluate their effects on melanoma cell rate growth and migration. These experiments will identify the effect of TOX on the initiation and progression of melanoma cells through in vitro melanoma cell culture and experimentation before potentially progressing to well-validated mouse models of melanoma.
Combined Inhibition of RAF, MEK, and FAK Attenuates Melanoma Brain Metastases and Prolongs Survival in Preclinical Models
Authors: Ana Paulina Medellin-Alvarez, Jared Almazan, Tursun Turapov, David A. Kircher, Karly A. Stanley, Gennie L. Parkman, MiKaela N. Field, Katie M. Culver, Silvia Coma, Jonathan A. Pachter, Howard Colman, Sheri L. Holmen. Mentors: Sheri Holmen. Insitution: University of Utah. Despite promising results from recent FDA-approved therapies, many advanced melanoma patients develop resistance to both immunotherapy and targeted therapy. A common resistance mechanism to targeted therapy is upregulation of the PI3K/AKT signaling pathway, which has also been shown to promote the development of melanoma brain metastases. Historically, AKT inhibitors have failed in the clinic due to their limited efficacy or intolerable toxicity. Proteomic analysis comparing non-metastatic vs brain metastatic primary tumors in mice revealed focal adhesion kinase (FAK) as an AKT1 specific effector and a potential alternative therapeutic target. FAK is a non-receptor tyrosine kinase that localizes primarily to focal adhesions to regulate cell migration. To determine whether targeting FAK alone or in combination with the RAF/MEK inhibitor avutometinib reduces brain metastases and prolongs survival, we utilized both autochthonous and syngeneic melanoma mouse models. Mice with either subcutaneous tumors or established brain metastases were treated with FAK inhibitor, RAF/MEK inhibitor, or the combination of FAK and RAF/MEK inhibitors. Each cohort was assessed for tumor onset, growth, metastasis, and survival. Our results show that combined RAF/MEK/FAK inhibition significantly delays tumor onset, causes regression of established tumors, prevents the development of brain metastases, promotes the regression of established brain metastases, and prolongs survival. In addition, patient-derived BRAF V600E melanoma xenograft mouse models resistant to the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib, were sensitive to combined RAF/MEK/FAK blockade. The addition of the BRAF inhibitor encorafenib to these models further enhanced the effect on tumor growth. These results support the initiation of a clinical trial evaluating the efficacy of the RAF/MEK inhibitor avutometinib in combination with the FAK inhibitor defactinib in patients with brain metastases from cutaneous melanoma. Additionally, we are assessing non-canonical roles of FAK in modulating the tumor microenvironment to determine whether avutometinib and defactinib also enhance the efficacy of immune checkpoint inhibition in this disease.
Synthesis and Optimization of Novel Macrocylic TRK Inibitors For Treating Drug-Resistant Cancers
Authors: Matthew Stecher, Terungwa Iorkula, Matt A. Peterson. Mentors: Matt A. Peterson. Insitution: Brigham Young University. Tropomyosin Receptor Kinase (TRK) inhibition has become an effective therapeutic approach for treatment of a variety of cancers including soft tissue sarcoma, pilocytic astrocytoma, non-small cell lung cancers, colorectal cancers, glioblastomas, pediatric gliomas, papillary thyroid cancers, and secretory breast carcinoma. Despite the successful use of first-generation TRK inhibitors Larotrectinib and Entrectinib which have shown significant therapeutic response in patients, acquired resistance to these drugs has emerged and is creating serious barriers to maintaining long-term therapeutic efficacy. A common mechanism for acquired resistance is associated with the emergence of mutations. Hence, mutation-induced drug resistance continues to be a major challenge for both first- and second-generation TRK inhibitors. Here, we present the design of novel macrocyclic 3,5-diaminated pyrazolo[1,5-a] pyrimidine ligands with high potential for combating drug-resistant disease.
Drawing on Memory
Authors: Corin Marsh, Acacia Overono. Mentors: Acacia Overono. Insitution: Utah Valley University. A variety of memorization techniques have been shown to enhance the ability to recall important information. While many of these techniques focus on repetition and retrieval of verbal information, the drawing superiority effect (DSE, Wammes et al., 2016) is a phenomenon where drawing leads to better recall compared to re-writing. The present study investigates the extent of these findings by combining the DSE with retrieval practice. This experiment utilized a within-subjects, single-blind design consisting of 32 undergraduate students ranging in age from 18 to 42. Participants were tasked with learning 20 vocabulary terms through a guided slideshow, then studied terms through; reading definitions (verbal restudy), viewing images of the definitions (visual restudy), writing definitions (verbal retrieval), and drawing definitions from memory (DSE with retrieval). After a brief distractor task, participants were tested on their recall of the definitions. Finally, subjects completed a shortened version of the Vividness of Visual Imagery Questionnaire (VVIQ) and a funnel debrief. Preliminary analyses using a repeated measures ANOVA revealed that re-reading was the study method that resulted in the highest recall scores (M = .57) compared to all other conditions (F (3, 93) = 14.9, p < .001, ηp2 = .324). Further — VVIQ ability showed no significant correlation with participant scores for any of the study methods. These results indicate that re-reading was a more effective study strategy for memorizing vocabulary terms with a short delay when compared to viewing images, writing definitions, and drawing definitions from memory. Future work will examine how longer delays and providing feedback influence may modulate the benefits of re-reading, drawing, and retrieval as study strategies. Keywords: drawing superiority effect, retrieval practice, memory, VVIQ
Isolation on Plant Growth promoting bacteria from the hybrid buffaloberry Shepherdia x utahensis ‘Torrey'
Authors: Ty Wilson. Mentors: Amita Kaundal. Insitution: Utah State University. Climate-induced environmental stresses and the increased use of fertilizers to meet the increasing demand for food significantly threaten food production and soil health. In natural environments, microbes are vital to the growth and development of plants. Their presence in the soil allows for enormous flexibility and nutritional availability for plants, particularly those living in harsh conditions. A plant’s microbiome, especially the underground, plays a significant role in its growth and development and mitigates environmental stresses. Idaho and Utah are particularly challenging environments due to extreme temperatures and arid soil. However, despite these difficult environmental factors, the native plants of Utah and Idaho can thrive. Here, we are exploring the rhizosphere microbiome of Shepherdia x utahensis ‘Torrey,’ a hybrid of two highly drought-tolerant buffaloberry species, S. argentea and S. rotundifolia native to the Intermountain West region of the US to isolate plant growth promoting bacteria. In this study, we isolated drought-resistant plant growth-promoting microbes from the rhizosphere of hybrid buffaloberry. Root samples of hybrid buffaloberry were collected from three locations in Utah: the USU campus, Greenville Farm USU, and the USU botanical garden, Kaysville. The rhizosphere was removed from these root samples and pooled together. The bacteria were isolated on five different bacterial growth media twice. The isolated microbes were then purified using the streak plate method. Forty-six unique isolates were selected based on morphological characteristics and tested for four plant growth-promoting traits. Fourteen bacteria could show the ability to fix nitrogen fix, 18 produced a siderophore, 17 could solubilize phosphate, and 11 produced catalases. IAA production, ACC deaminase, and protease activity assays are in progress. All isolates will be identified by 16S rRNA Sanger sequencing.
Insane in the Membrane: Amino acid sequence evolution and conservation in vital protein complex in gram-negative bacteria
Authors: Alexander Everett, David Bean, Jeremy W Bakelar, Randy L Klabacka. Mentors: Randy L Klabacka. Insitution: Utah Tech University. β-barrel assembly machinery (BAM) is a protein complex vital to cell survival in gram-negative bacteria that functions to insert proteins into the cell’s outer membrane. BamA, a protein composed of a membrane-bound beta barrel and several POTRA domains that protrude into the cytosol, is the primary subunit within BAM. It is suggested that BamA is conserved due to its widespread presence across the bacterial tree of life. Here we quantify the conservancy of BamA in 142 species of gram-negative bacteria from across the bacterial tree of life, with a focus on 120 species belonging to the order Enterobacterales. In addition, we compared the conservancy of BamA with other proteins with high and moderate levels of conservation in Enterobacterales. Lastly, we discuss regions of BamA that are of high conservation in the context of their potential as antibiotic targets.
Eolian Sediment as a Potential Soil Parent Material in Cache Valley
Authors: Kylie Hansen. Mentors: Janis Boettinger. Insitution: Utah State University. Cache Valley, Utah, has unique soils due to environmental events such as Pleistocene pluvial Lake Bonneville. This lake extended about 20,000 square miles in Northern Utah, and its depletion left numerous shorelines, the most relevant being the Bonneville and Provo shorelines. These various water levels influence the geological formations in Cache Valley and the different characteristics of soil formation. An important soil-forming factor used to characterize varying soils is the parent material. Parent material is the original sediments the soil formed on and can be various things such as sediments deposited by gravity, streams, lake sediments, or wind. These different materials depend on the location and alter the soil properties. A dominant soil parent material in the Lake Bonneville area is sediment deposited by this lake. This type of parent material is identifiable by coarser-sized sediments, such as cobbles, gravel, and sand. This pattern is evident on terraces in Cache Valley’s lower soil layers, but the near-surface layers have fewer rock fragments and more fine sand, silt, and clay. This distinct difference in particle size leads to the question of what is the parent material source in the surface horizons of soil formed in Lake Bonneville deposits in Cache Valley. There is not much literature on this question and little documentation compares the soil profiles for different Lake Bonneville terrace levels (Bonneville shoreline compared to Provo shoreline). We hypothesize that the different particle sizes of parent material in the surface of soils formed dominantly in Lake Bonneville deposits is eolian sediment transported and deposited by wind. To determine this, we will sample soils across Cache Valley and analyze the fine and very fine sand sediments in plane-polarized and cross-polarized light. This process will identify various minerals within each soil horizon, showing possible differences in the upper and lower horizons. The minerals present in each soil will indicate the parent materials, allowing us to understand what is causing the different textured horizons in these soils and where the sediment originated from.
fr10 Evolution
Authors: Reagan McKee, Vicente Fernández Lara, Jeremy Bakelar, Randy Klabacka, Dustin Kolste. Mentors: Randy Klabacka. Insitution: Utah Tech University. The capability to survive freezing temperatures is of crucial importance to ectothermic organisms inhabiting cold climates. The mechanisms that have evolved to minimalize the cellular damage incurred by freezing are of interest due to their applications in agriculture and medicine. fr10 is a gene identified in the wood frog (Rana sylvatica)that has been shown to reduce the cellular damage sustained in freezing temperatures. To date, fr10 has not been identified in any taxa beyond R. sylvatica and as such, the evolution of this novel gene remains ambiguous. Furthermore, the exact mechanism by which fr10 reduces freezing related damage has yet to be determined. We use bioinformatics scripts to scan 38 frog genomes to identify orthologs in divergent frog lineages across varying elevational and latitudinal gradients and examine the evolution of this novel gene. Understanding the evolutionary and ecological context of this gene can elucidate its function and may inform commercial and medical applications.
Using Technician Statistics For Productive Animal Care
Authors: Grace Moore. Mentors: Aaron Olsen. Insitution: Utah State University. AbstractAnimal care technicians for research labs have many responsibilities in order to maintain the integrity of a research project. However, it is difficult to determine what tasks will require most of a technician’s time and effort. Thus, it is proposed that tracking what each individual does during a given shift can allow supervisors and technicians to create an efficient schedule of how they will work and provide a standard for individuals to meet every day. This project consists of tracking in detail what an animal care technician does in a given “shift”, including observation hours, handling and restraining, working in different biosafety levels, cleaning and prepping caging, and changing the caging. This data collection, over several months of work, finds relationships between tasks, the frequencies of being completed, and the time they take. The key tasks of an animal care technician are observing, providing nourishment, maintaining clean environments for both the researchers and the subjects, and maintaining supplies and accurate records. Additionally, many hours are dedicated solely to observing the animals to ensure their health and safety. Moreover, cleaning and prepping of caging or supplies are completed more than half of the time during a given shift. Finally, working with a given species may require more time to complete a task (such as cage changing or cage preparation) compared to another species despite the task being the same. If each technician were to track their tasks and create a profile of personal statistics, they would be able to easily determine how long a task should take. Moreover, a supervisor would be able to determine if a technician is working more efficiently or even falling behind during daily tasks. Overall, these findings could be used to incorporate better time management or planning for institutions to know what more time or resources may need to be devoted to in order to maintain a safe environment, provide exceptional care for the subjects, and follow every protocol.
Computational analysis of cyclic aminoborane complexes that exhibit potential to act as hydrogen storage molecules
Authors: Amy Richards, Caleb Shelton, Jordan Colmenero, Mason Warenski. Mentors: Diana Reese. Insitution: Utah Tech University. Hydrogen gas has potential to be an excellent form of clean energy; unfortunately, hydrogen gas is difficult to store safely in its elemental form. Consequently, this research project investigated cyclic aminoborane complexes in which hydrogen (H2) can be safely stored. Utilizing computational methods, molecular dynamics simulations of four cyclic aminoborane compounds were performed using Q-CHEM 6.0, with a t-HCTHh density functional and cc-pVDZ basis set. Results were visualized using Molden 6.7 and VMD 1.9.3 then plotted using Gnuplot 5.2.8. Molecules selected for the investigation involve two constitutional isomers for both the 3- and 4- membered ring cyclic aminoborane complexes. The four molecules studied were (CH2)2NHBH3, (CH2)2BHNH3, (CH2)3NHBH3, and (CH2)3BHNH3, (hereafter 3N-B, 3B-N, 4N-B, 4B-N). Motions inherent in these molecules exhibited surprising differences. Specifically, in the 3-membered rings, the terminal borane (3N-B) exhibited more motion than the terminal amine (3B-N); however in the 4-membered rings (4N-B and 4B-N) the opposite occurred. Differences in these and other motions were quantified and qualified with respect to each molecule to gather data relevant to hydrogen storage potential.
Unveiling Cryptic Avifauna Diversity Using Nanopore DNA Sequencing: A Case Study in the Passerine Genus Emberiza
Authors: Ainsley E Parkins, Sylvia Lee, Elizabeth J Heath, Thomas Petitjean, Kyle Cink, Kyle Kittelberger, Cagan Sekercioglou, Rodolfo S Probst. Mentors: Rodolfo S Probst. Insitution: University of Utah. Biodiversity loss poses a significant threat, requiring accurate species assessment and conservation strategies. Non-invasive and cost-effective techniques should be prioritized, especially when dealing with threatened vertebrate fauna. By focusing on cryptic Eastern European species within the genus Emberiza (Passeriformes: Emberizidae), we designed an affordable molecular pipeline (including DNA primers and bioinformatics) integrating DNA barcoding with Nanopore sequencing to address species boundaries and provide conservation information for avifauna diversity. We conducted non-invasive DNA extractions from individual feathers of 192 specimens collected in the Aras River Riparian Corridor (ARRC), an important ecological hotspot in Turkey. By targeting the cytochrome oxidase subunit I (CO1) region, our goal was to differentiate Emberiza taxa and identify potential cryptic lineages while using cutting-edge next-generation sequencing (NGS) of multiplexed specimens with portable Oxford Nanopore Technologies. Our focal study examined boundaries in Emberiza subspecies (E. shoeniclus shoeniclus and E. shoeniclus caspia) with subtle morphological differences, utilizing DNA barcoding and Nanopore sequencing. We obtained 182 Emberiza DNA barcodes. Clustering analysis recovered a paraphyletic assemblage (n=32) and a clade, the latter recovering majority of the barcodes (n=150), separated by at least 8% genetic difference. In both cases, we observed a mixture of barcodes from the nominal subspecies and Caspian subspecies, suggesting that cryptic morphological characteristics are not reflected in genetic separation. Our results also suggest putative cryptic Emberiza species, highlighting the importance of the ARRC for conserving avian diversity. We demonstrate that our pipeline, integrating real-time Nanopore sequencing with non-invasive DNA barcoding, can be used for conservation initiatives (particularly aiding cryptic species identification). This study expands our knowledge of avian diversity and highlights the potential of NGS DNA barcodes as a powerful tool for aiding conservation efforts amidst biodiversity loss.
University Course Timetabling: From Sticky Notes to Automation
Authors: Alyssa Muller, Russ Ross. Mentors: Russ Ross. Insitution: Utah Tech University. University course timetabling assigns rooms and times to courses, considering instructor availability, curriculum conflicts, and quality of life considerations. Computing an optimal solution is computationally intractable. Researchers have refined approximation algorithms that yield far better results than the conventional pencil-and-paper approach used at many universities, including our own. Transitioning to an automated system can be disruptive and poses both real and perceived risks to an institution. The implicit knowledge that humans bring to the problem is hard to fully capture within formal rules that a computer can understand. Our research addresses the impedance mismatch between abstract solutions and the messy real world.In this project we build on prior research to fit the specific needs of our university. We will pilot our system with a set of departments in parallel with the traditional by hand process. We will analyze outcome quality through subjective assessment and quantitative comparison between human and machine generated timetables.
Synthesis and Characterization of Novel Pterostilbene Derivatives for Potential use as Therapeutics
Authors: Ashley Staten. Mentors: Jennifer Meyer. Insitution: Utah Tech University. Pterostilbene, a natural product found in blueberries and nuts, has been shown to be multifunctional. In low doses, it has been shown to be a potent antioxidant, while in higher doses, it has been shown to reduce cell proliferation, induce autophagy, and increase apoptosis. Recent literature has indicated that derivatives of pterostilbene can improve the functionality of pterostilbene in both cancer cell viability (reduction) and antioxidant capacity (increase). Previously, our group has synthesized and characterized the antioxidant capacity of a select group of pterostilbene derivatives, which have been functionalized to contain an additional alcohol and amine group. Most recently, we have synthesized a derivative containing benzylamine as the amine. This amine was chosen as benzylamine and drugs functionalized with benzylamine groups have been shown to have antiapoptotic properties. Currently, we aim to further characterize this novel pterostilbene derivative as we believe it has the potential to be utilized as a therapeutic in various disease states such as cancer and type 2 diabetes.
Rock Column Displacement in Zion National Park: A statistical Analysis
Authors: Michael Orr. Mentors: Md Sazib Hasan, Alex Tye. Insitution: Utah Tech University. Every year Landslides claim lives and cause billions in property damage. Zion National Park in Southwestern Utah has been monitoring a precarious rock column contained within the parks borders since 2019. The results of this rockfall will be damage to the land and historical structures located in the fall area. The data are collected by two instruments called vibrating-wire crackmeters that are connected from the cliff face to the pillar—these are electronic and provide a continuous feed of distance measurements. The project will be focused on analyzing a 4-year record of displacement of a precarious rock pillar from the adjacent cliff face from which it will eventually separate and topple onto a slope below. We will also be analyzing the environmental factors causing the movement of the rock column. Results of this modeling will help us better understand the driving forces behind rockfalls, possibly helping to mitigate future damage.
Hollow hair and how its structure helps big game animals thermoregulate
Authors: Taylor Millett, Wendy Schatzberg, Samuel Tobler. Mentors: Wendy Schatzberg. Insitution: Utah Tech University. This study delves into the intriguing world of hollow hair strands in animals, focusing on their role in thermoregulation, and the ability to maintain a stable body temperature in the face of fluctuating external conditions. While the Pronghorn antelope is widely known for having hollow hair strands among hunters and conservationists, little is known about their internal structure. Employing scanning electron microscopy (SEM), we explored the inner composition of these hollow hair strands and their contribution to thermoregulation. Our investigation centered on several notable North American big game animals, including Mule deer, Rocky Mountain elk, and Pronghorn antelope, all of which exhibit a unique adaptation: the transition between summer and winter coats. Through SEM analysis, we measured and compared the winter and summer coats of these animals to gain insights into how they effectively regulate their body temperatures during the extremes of hot summers and cold winters. These seasonal changes manifest in alterations in fur and hair thickness and length. Under the microscope, we unveiled the distinct topography of the inner structure of individual hair strands. Notably, our findings revealed that the inner hair structure contains larger hollow pockets in the winter coats of these animals. Our research thus sheds light on the role of these hollow structures in heat transfer and their pivotal contribution to the thermoregulation abilities of these remarkable creatures, expanding our understanding of their unique adaptations.
Optimization of Subcritical Water Hydrolysis of Microalgae Biomass for Clean Meat Production
Authors: Bradley Lawson, Lukas Keller, Marshall Burrows, Sam Perkins, Emery Wheeler. Mentors: Ronald Sims. Insitution: Utah State University. Subcritical water hydrolysis (SWH) is a developing method of processing organic materials/waste without the use of acids and alkali materials. SWH lyses peptides differently than acid hydrolysis and can produce Maillard products, which have various effects in cell culture. In this study, a batch-mode pressure vessel with a semi-continuous sampling apparatus will be used to optimize temperature and retention time for the hydrolysis of Chlorella vulgaris biomass for the development of serum-free (or low-serum) cell culture media. Hydrolysis will be done at temperatures from 140°C to 300°C and retention times from 5 minutes to 30 minutes. The SWH products will be assessed for their general protein content, lipid content, bioactivity, and carbohydrate content. These efforts will be of use to Upside Foods in its efforts to create sustainable and ethical cultured meat products.
Information Anatomy Over Partition Space
Authors: Nathan Jackson, Ryan James, James Crutchfield. Mentors: Mikhael Semaan. Insitution: University of Utah. Symbolic dynamics allows for modeling---and designing for---the effects of imperfectly measuring a time series of data, by partitioning into a finite number of possibilities. The resulting time series of discrete symbols is then made especially amenable to information-theoretic methods for understanding its temporal structure and correlation. In particular, as long as the partitioning scheme is generating, the resulting estimations for entropy rate---the rate at which the process creates information---converge to a measure of chaos in the underlying system, a dynamical invariant.However, the entropy rate is not sensitive to what kind of generating partition: colloquially, an instrument must be at least accurate enough, but can be more fine-grained as desired. In contrast, its breakdown into a piece which affects future measurements (“bound”) and a piece which does not (“ephemeral”) depends quite dramatically on the choice of generating partition. We ask, then: is there a canonical partitioning scheme for which the full suite of information measures relate to dynamical invariants?To tackle this, we simulate the well-known tent and logistic maps, sweeping over all two-boundary partitions, calculating the full information anatomies for each. We find that ephemeral and bound information are extremized by the single-boundary coarsest generating partition, suggesting a canonical role for the simplest “good enough” instrument. The remaining multivariate measures, meanwhile, reveal hitherto-unseen structure in the process of imperfect measurement.
mitochondrial genes of hybrid whiptail parthenogens
Authors: Dante Celani, Erin Bunch, Randy Klabacka. Mentors: Randy Klabacka. Insitution: Utah Tech University. Hybrid parthenogenic whiptail species have lower endurance capacity and mitochondrial respiration than their sexual parental species. These differences in aerobic performance may be due to reduced compatibility of variable gene products between the divergent parental genomes that are present in the hybrids. If this is the case, we expect to see genetic variation in mitochondrial-targetting genes. We performed whole-genome sequencing for four sexual whiptail species that are parental species to hybrid parthenogenetic species, and we mapped those samples to an annotated whiptail genome. We call gene variants and classify them as coding, non-coding, synonymous, and non-synonymous to understand which variants might contribute to phenotypic variation, and we discuss approaches to further elucidate the genetic mechanism behind the lower aerobic performance in hybrid parthenogens.
Lighting for Different Land Uses: A Case Study in Cedar City
Authors: Sebastian Partida. Mentors: Jamie Spinney. Insitution: Southern Utah University. Lighting levels have an important role in influencing the ambiance and functionality of various land uses. To achieve specified goals while optimizing energy efficiency and sustainability, lighting intensity must be balanced. The purpose of this study was to compare light intensity for different land uses (e.g., residential, commercial, industrial, and recreational). This study measured light intensity (i.e., brightness) for a random sample of different land uses using a digital light meter within Cedar City, UT. GPS coordinates were also acquired in order to map the brightness data. As expected, the results revealed that residential land uses were the darkest, whereas commercial and industrial land uses were the brightest. The findings indicate communities have to maintain a balance between creating a warm and pleasant atmosphere and ensuring appropriate illumination for safety and security purposes. Energy-efficient LED fixtures and smart lighting systems, for example, can provide adjustable and programmable illumination settings that meet both aesthetic and safety requirements.
Evaluating the role of LRRC1 in melanoma growth and metastasis
Authors: Kylee Fernandez. Mentors: Gennie L Parkman. Insitution: University of Utah. Evaluating the role of LRRC1 in melanoma growth and metastasisThe development of brain metastases is a critical problem in Utah, regardless of the novel therapies created for melanoma. The melanoma mortality rates in Utah are 31% higher than the national average and the melanoma incidences are 80% higher. To lower these incidences, our research is aimed at investigating targets in melanoma that play a crucial role in brain metastasis and can be identified as therapeutic interventions.LRRC1 is a gene known as Leucine Rich Repeat Containing 1. LRRC1 is involved in early-stage adipocytic differentiation. Altered gene and protein expression of LRRC1 is observed in melanoma potentially due to the vital role LRRC1 plays in adipose stem cells that differentiate by adopting the phenotypic, biochemical, and functional properties of more terminally differentiated cells. To evaluate the effect of LRRC1 on melanoma growth and metastasis, we are using an established autochthonous in vitro and in vivo model of melanoma based on the RCAS/TVA avian retroviral system. The results of this study will have tremendous potential to contribute to the understanding of the genetics of this heterogeneous disease.
Bx42 is Required for Brain Development and is Linked to Microcephaly
Authors: Adriana Bibo, Nicole Losurdo, Nichole Link. Mentors: Nichole Link, Cindy Greaves. Insitution: University of Utah. Microcephaly is a neurodevelopmental disorder characterized by occipital frontal circumference (OFC) more than two standard deviations below the mean. It can be accompanied by comorbidities including intellectual disabilities, seizures, and other developmental phenotypes. Microcephaly is attributed to malnutrition and exposure to toxins or infection during pregnancy, but genetic mutations are also a leading cause. To investigate the genetic mechanisms behind microcephaly, our lab collaborates with a physician who has completed whole exome sequencing for two hundred microcephaly patients. He identified potentially pathogenic human variants, which we are studying using Drosophila melanogaster as our model organism. We screened for loss of function phenotypes through RNAi knockdown of fly orthologs to determine if these genes are necessary for brain development. In our primary screen, we found that RNAi knockdown of Bx42 in neural stem cells or post-mitotic neurons causes significantly reduced brain lobe volume. In our current study, we are assessing potential causes for reduced brain lobe volume. We seek to determine if RNAi knockdown of Bx42 in neural stem cells or neurons affects cell number, proliferation, or death in developing brains.
Social Effects of Bed Nucleus of the Stria Terminalis Corticotropin-releasing Hormone and Tachykinin 2 Neuronal Activation Using Optogenetic Stimulation
Authors: Nicholas Poll. Mentors: Moriel Zelikowsky. Insitution: University of Utah. Social interaction is one of the chief drivers of evolution and natural selection. Animal interactions shape the ecological world and have shaped the world’s evolutionary timeline. Of the many types of animal interactions, one of the most influential to behavior and development is aggression. Many animals' aggressive behaviors and mechanisms are so distinct that their origins can be traced back to specific selective pressures. These pressures range from reproductive competition to predator-prey interactions and have apparent effects on many species’ developments. There are many stressors that can increase aggressive tendencies found in mammals, yet it’s clear that the neural bases that connect these stressors and their behavioral responses are understudied. The targeted brain region in this project is the bed nucleus of the stria terminalis (BNST). The BNST is a neurochemically diverse node of the extended amygdala that has been implicated in mediating stress and sensory information. It anatomically acts as a relay station between a number of different structures including the hypothalamus and amygdala. The BNST has been implicated to have a role in stressor-induced aggressive behaviors; however, the neural mechanisms that connect this region and these behaviors are relatively understudied. Corticotropin-releasing Hormone (CRH) in mammals displays upregulation following the introduction of a stressor and has been found to mediate aggression and anxiety. Similarly, tachykinin-expressing neurons have been shown to have a role in mediating aggression in mammals. While CRH and tachykinin’s link to anxiety and aggression is well supported, it is not clear to what extent it has on BNST. This project aims to provide data to support the role that CRH and Tachykinin 2 (Tac2) in the BNST have in mediating aggression in mice through optogenetic stimulation.
In the Depths of the Understory: Costa Rican Associations Between Ants and Coccoidea Unraveled using NGS DNA Barcoding
Authors: Sylvia Lee, Ainsley Parkins, Rodolfo S Probst. Mentors: Rodolfo S Probst. Insitution: University of Utah. Mutualisms between ants and plants are ubiquitous interactions and have been evolving for over 100 million years. Studies have been done on systems wherein the plants provide nutritional resources for ants, but the dynamics of mutualistic interactions in environments where host plants do not provide obvious nutritional rewards continue to remain elusive, raising questions about their co-evolutionary histories. In these circumstances, associated fauna, such as mealybugs and soft scales (Hemiptera: Coccoidea: Pseudococcidae and Coccidae), serve as intermediaries of the association, providing honeydew (enhanced plant sap) as a main food source to their host ants. However, the identity of the insects involved in these associations and their co-evolutionary history with ants is poorly understood. By focusing on samples collected in Costa Rica from 33 colonies of the Neotropical plant-ant genus Myrmelachista (Formicinae: Myrmelachistini), we sequenced DNA barcodes (cytochrome oxidase subunit 1 [CO1]) using Oxford Nanopore Technology and employed Next-Generation Sequencing (NGS) for both the Myrmelachista ants and their associated fauna. We aimed to identify their taxonomy, phylogenetic relationships and identify unique interactions between ants and their associated fauna. We recovered DNA barcodes for eleven Myrmelachista species and seven putative species of mealybugs (n=5) and soft scales (n=2). For the seven putative species of Coccoidea, our DNA barcodes, when compared to available sequences from the NCBI database, recovered an average of 85% match similarity. The closest matches associated our putative species to Old World Coccoidea taxa, reinforcing the need for taxonomic studies of this superfamily for the Neotropical region. Each putative species of soft scales was found uniquely associated with two Myrmelachista species (M. flavoguarea and M. cooperi). For all eleven Myrmelachista species, five were associated with two putative mealybug species. One putative mealybug species was associated with five different Myrmelachista species; one was uniquely associated with M. nigrocotea. Same associations were found between the associated fauna of M. flavocotea and M. lauropacifica; M. haberi and M. RSP027; M. plebecula, M. meganaranja, and M. osa, respectively. These results suggest that there may be unique associations between some Myrmelachista species and their Coccoidea associates, unconstrained by the ant phylogeny. Our findings also provide insights on Coccoidea taxonomy, emphasizing NGS DNA barcoding as a tool to illuminate how ant-plant associations might have evolved.
Genetic Mutations in the Genomes of Mother-Offspring Pairs Shows Link Towards Nausea and Vomiting in pregnancy
Authors: Dallin Oyler, Ana Alfaro, Kailee Myxter, Ben Brooks, Amanda Brooks. Mentors: Jessica Pullan. Insitution: Southern Utah University. Nausea and vomiting are common complications that occur in 70% of pregnancies. Hyperemesis Gravidarum (HG) is the most severe form of these symptoms and is estimated to be prevalent in 0.3-2% of pregnancies. Due to the fetal and maternal morbidity associated with HG, identifying the cause and treatment options for these women is a critical task in obstetrics. Research regarding the etiology of HG has been fairly recent and is still ongoing, however, evidence had directed to a positive correlation between increased levels of the serum protein GDF15 and HG symptoms. We hypothesize that polymorphisms in both maternal and fetal DNA plays a role in the upregulated GDF-15 seen in mothers experiencing symptoms of HG during pregnancy. The DNA of 2 mothers and their corresponding children were sequenced and analyzed. The DNA was obtained through buccal swabs from the epithelial cells of the inner cheek, and then purified and ran through PCR. We employed 3 distinct primers that correspond to mutations in the genome that account for the elevated levels of circulating GDF-15 in the mother. As of current, the mother-daughter DNA is still under analysis for single-nucleotide polymorphisms, however recently published literature has suggested results similar to our hypothesis. M. Fejzo et al. shows that upregulated serum GDF-15 is primarily of fetal origin, and that maternal sensitivity to GDF15 increases the risk for developing HG. Additionally, the DNA coding variant GDF15 C211G was shown to elevate the risk of HG
Reconstructing seasonality in African bovids using dental microwear
Authors: Auriana Dunn. Mentors: Kathryn Sokolowski. Insitution: University of Utah. Reconstructing the diet of extinct animals can help us understand how living species are suited to their environments, which can inform paleoecological and zooarchaeological research as well as modern species conservation. Seasonal variation in animals’ diets can further be used to reconstruct seasonality patterns in the past and understand how animals may vary their diet under future climate change. However, determining the diet of extinct species is challenging, and detecting seasonal changes in diet is even more so. Dental microwear texture analysis (DMTA) can be a tool to solve this problem. DMTA analyzes dental microwear by measuring the pits and scratches on teeth to determine what an animal consumed in the days and weeks before it died. This project examines the DMTA of modern African Bovidae species to determine if seasonal dietary changes can be observed. If a difference can be found in the dental microwear of specimens that died during different seasons, seasonal changes in diet can be inferred. Here, I gathered dental microwear data from 407 specimens across five modern studies and matched the data to the museum specimens’ date of death to determine whether it died in a wet or dry season. The analysis found that four of the Bovidae species examined in our study showed evidence of seasonal diet shifts in their DMTA data. Dental microwear can be useful in determining seasonal diets and season of death for specimens. This method can be applied to extinct Bovidae species to understand ancient ecosystems and the evolution of Bovidae dietary strategies.
Murine Model of Hepatitis Delta Virus-Associated Salivary Gland Impairment
Authors: Alexander Romano, Matthew Hesterman, Rachel Hill, Melodie Weller. Mentors: Melodie Weller. Insitution: University of Utah. Sjogren’s Disease (SjD) is an autoimmune disease diagnosed by symptoms of reduced tear and saliva excretion, accumulation of lymphocyte foci in the salivary glands, and the occurrence of antibodies against Ro (SSA), La (SSB), and nuclear proteins. The cause of SjD is unknown, though previous studies have detected the sequence and antigens of Hepatitis Delta Virus (HDV) in the minor salivary gland acinar, ductal, and adipose cells of patients with SjD; without the typical presence of a Hepatitis B coinfection. In this study, murine models were transduced with Adeno-associated virus containing expression cassettes for Luciferase (control), small, large, or a combination of both small and large HDV antigens to evaluate the impact of HDV antigen expression on salivary gland function and SjD autoimmune disease development. After a ten- or four-month period, the models were analyzed. Findings included a significant increase of inflammation for samples expressing both small and large HDV antigens, a significant increase of anti-SSA(La) antibodies in samples expressing the short HDV antigen, and a correlation between increased overall inflammation and decreased overall saliva flow. Performing qPCR methods verified the amount of HDV in the submandibular glands and Illumina sequencing portrayed an increase in glycolysis and beta oxidation metabolism in models with detectible HDV sequence. The models showed significantly increased IgM expression in the HDV exposed murine models, without significant change of other antibodies. Future plans include an ELISA diagnostic assay to verify the antibody levels and further sequencing analysis. With this information we can build a better picture of the direct mechanisms of HDV-mediated changes in salivary gland dysfunction and determine the extent that HDV can inducing systemic SjD symptoms.
Using Past Ecosystems to Understand Modern Climate Change: A Case Study from Utah’s House Mountain Range
Authors: Jane Damstedt, Kasey Cole. Mentors: Kasey Cole. Insitution: University of Utah. In this project, we are analyzing faunal remains recovered from Utah’s House Mountain Range in the Tubafore cave system to create a paleoecological baseline of life in that location over the past 1000 years. All animals have relatively consistent ecological tolerances and preferences, so comparing the data from the information obtained in this study with contemporary accounts of mammalian ecology in the same area will be useful in evaluating the role of anthropogenic climate change in mammalian ecosystems. In this project, I am identifying the animal remains to the lowest level of taxonomic classification possible to determine what kinds of species richness and environment were present at the time in which the animal was alive. Creating an accurate record of the animals found in this cave assemblage is critical because very little is known about the species richness of the Great Basin area. This data will then be stored and compared to modern zoological data, which came from online databases Actos and Vertnet. The information gathered from this project can be used to inform conservation and sustainability efforts aiming at preserving biodiversity in Central Utah’s Mountain Ranges.
Going Green in a General Chemistry Teaching Lab: Assessment of Learning Outcomes
Authors: Cooper Bell-Hunley, Ming Yu, Emily Heider. Mentors: Emily Heider. Insitution: Utah Valley University. Green chemistry involves the redesign of chemical processes and products to reduce hazards to the environment and human health. Reconsidering the teaching curriculum with a view to embrace green chemistry can reduce costs in waste disposal and has the potential to improve accessibility. This research involves the redesign of qualitative analysis general chemistry experiment to eliminate the use of teratogenic mercury (Hg) and neurotoxic lead (Pb). Making this change creates a more inclusive laboratory since expectant mothers should not be exposed to mercury and therefore some students did not feel safe completing the previous version of the experiment. With any change in curriculum, it is important to consider the impact on learning outcomes that students can achieve. This research details the assessment of learning outcomes with a quasi-experimental design. Instructors in multiple general chemistry labs selected the qualitative analysis experiment (with or without Hg and Pb) and learning outcomes achieved were assessed following the experiment.
Nonequilibrium Thermodynamics of Voltage-Gated Ion Channels
Authors: Ada Cottam Allen, Mikhael T Semaan. Mentors: Mikhael T Semaan. Insitution: University of Utah. Regularly buoyed from thermodynamic equilibrium by complex and fluctuating environments, living systems must continually respond and adapt to external stimuli. Recent tools from stochastic thermodynamics place concrete energetic and entropic bounds on these processes, for systems arbitrarily far from equilibrium both in and out of steady-state conditions, and thus reveal mechanisms by which these systems absorb and dissipate energy to function. Here, we leverage these tools to simulate and calculate the thermodynamic signatures of several models of sodium and potassium ion channels---channels crucial to propagating action potentials in mammalian neurons---as driven by biologically-realistic action potential spiking protocols. Thus uncovering their detailed energetic responses to such complex environmental conditions, these results enable detailed comparison between the thermodynamic functionality of each channel type with driving one would expect in-vivo. When applied to competing models of the same channel, these tools also provide additional criteria for model selection; to this end, we close by calculating expected ionic currents, directly facilitating comparison with dynamically-driven patch-clamp experiments.
Impact of Inducible Depletion of Sequestosome-1 (p62) From Endothelial Cells On Intrinsic Arterial Stiffness
Authors: G. Colton Gardner, Lynasi Gapelu, Sohom Mookherjee, Sihem Boudina, J. David Symons. Mentors: J. David Symons. Insitution: University of Utah. With the prevalence of cardiovascular disease increasing world wide and its precise mechanisms remaining elusive, the need for novel treatments is urgent. Autophagy is a conserved process whereby dysregulated intracellular proteins are escorted to the lysosome for recycling. Emerging evidence indicates that autophagy is important in maintaining endothelial cell (EC) proteostasis and function. My laboratory showed that autophagy repression in adult mice ECs produces arterial dysfunction, and indexes of autophagy are repressed in ECs of older mice and humans which display concurrent EC dysfunction. Sequestosome 1 (p62) tethers proteins and enables their entry into the autophagic pathway. The contribution from EC p62 to cardiovascular and metabolic function is unknown and experiments are needed to investigate this. Thus, p62 will be depleted from ECs of adult male and female mice (p62iEC-/-) via tamoxifen regimen, and results will be compared to animals wherein EC p62 is intact (CON). The efficacy and specificity of EC p62 depletion will be evaluated in ECs and vascular smooth muscle by qPCR and immunoblotting. Three adjacent 1 mm thoracic aorta sections will be obtained 14 days after the tamoxifen regimen. The central aorta section will be used to measure intrinsic mechanical stiffness by wire myography, with the other two used to find lumen diameter and intimal medial thickness. These measurements will help create Stress vs. Strain curves and the Elastic Modulus, which will be compared between the groups to show the differences caused by p62 depletion. We expect p62 depletion from ECs to increase intrinsic aortic stiffness.
A Metagenomic Analysis the Microbial Composition of Apis mellifera Pollen Preserves throughout the Foraging Season
Authors: Sydney Larsen. Mentors: Joshua Steffen. Insitution: University of Utah. Pollen preserves are crucial to maintaining Apis mellifera’s hive health. This pollen provides bees with a source of protein, amino acids, lipids, and other nutrients that are vital for larvae development (Dharampal et. Al, 2019). In addition to providing these essential nutrients, bee collected pollen also provides the hive with an excellent source of external pollen-borne microorganisms. These microbes provide a variety of benefits including serving as a major dietary requirement for larvae, assisting in biochemical processes such as bee bread fermentation, and assisting in bee resistance to pathogens (Gilliam, 1997). Despite the importance that these organisms play on bee health, there is currently little research on how the microbial composition of bee foraged pollen changes throughout the foraging season in response to abiotic and biotic factors. Rapid advancements in DNA metabarcoding approaches and DNA sequencing technologies have made the assessment of hive level foraging patterns easily accessible. We attempt to leverage the benefits of these new approaches to characterize how microbial composition in pollen provisions changes in relation to shifts in foraging preferences. Here we describe general patterns plant foraging behaviors for two hives across a single foraging season. In addition, we describe the variability of microbial diversity associated with pollen across this same time frame. Our initial description plant and microbial communities present in pollen provisions suggest that pollinator foraging preferences play a significant role in pollen associated microbial communities. This will allow for further research into how the presence of specific beneficial microbes is affected by changes in climate, floral availability, pathogen presence, etc..ReferencesDharampal, P. S., Carlson, C., Currie, C. R., & Steffan, S. A. (2019). Pollen-borne microbes shape bee fitness. Proceedings of the Royal Society B, 286(1904), 20182894.Gilliam, M. (1997). Identification and roles of non-pathogenic microflora associated with honey bees. FEMS Microbiology Letters, 155(1), 1–10. https://doi.org/10.1016/s0378-1097(97)00337-6
A Glance into the Origin of Life through the Lens of the DNA Repair Enzyme MutY from the Lost City Metagenomes
Authors: My Nha Quyen Tran, Cindy Greaves. Mentors: Martin Horvath, Cindy Greaves. Insitution: University of Utah. I have been studying the DNA repair enzyme MutY found at the Lost City thermal field 3000 feet deep in the Atlantic Ocean with conditions similar to those that may have shaped the origin of life. With no sunlight and very little oxygen, life at the Lost City is driven by chemical transformations in rocks at extremely high levels of pH and temperature. DNA in all organisms strictly follows base pairing rules in which A pairs with T and G pairs with C. We all think of oxygen as beneficial, but it can cause damage to DNA. Oxidized guanine (OG) violates the base pairing rules and pairs with A. This causes mutations, which can lead to changes in the genetic information. The mutagenic potential of OG was a challenge that had to be solved early in the emergence of DNA-encoded life. The enzyme MutY functions in suppressing mutations and therefore protects us from developing cancer by finding and removing A from OG:A mispairs. In my effort to replicate conditions at the Lost City so as to explore how the DNA repair enzyme MutY evolved to function in this strange environment I need to purify the enzyme. I used DNA cloning to attach the MutY-encoding genes to a soluble bacterial protein called GST that hopefully will make it easier to purify the MutY proteins. Encouragingly, these fusion proteins expressed well in bacteria and appeared to be soluble. I am now exploring different conditions looking for optimal enzyme activity, which I predict to be different from what familiar bacteria can tolerate. Basic science research on how DNA repair enzymes adapted to the strange environment at the Lost City may inform future translational applications to treat and cure cancer and thus ensure a healthy society in Utah.
Synthesis and testing of hydrophobicly-modified pyridyl-aza crown ethers as chelators of rare earth elements.
Authors: William Lee, Rishab Nayak, Cecilia Knapp, Camila Soderholm. Mentors: Ryan Stolley. Insitution: University of Utah. Recent publications have shown pyridine carboxylate functionalized aza-crown ethers coordinate strongly to a number of rare earth elements. Considering their strong coordination, we have modified these crown-ethers with a number of hydrophobic moieties to allow for adsorption to non-polar substrates to enable packed bed isolation of these elements to address the broad use and limited availability of these elements.
The use of ecological niche modeling to characterize the microhabitat of oak hybrids (Quercus undulata) in Utah
Authors: Cate Bateman, Carson Veazie, . Sydney Sandall. Mentors: Matt Ogburn. Insitution: Southern Utah University. Western Utah is home to two distinct species of oak, Gambel oak (Quercus gambelii) and Dixie live oak (Quercus turbinella), which can hybridize to form an intermediate species that has been named Quercus undulata. In spite of previous research on these shrubs, we are still unsure of how the hybrid has survived in small isolated locations well outside of the range of one parent species (Dixie live oak, which is restricted in Utah to Washington, Kane, and San Juan Counties). Our primary objective was to perform an ecological niche modeling assessment of Q. undulata within the Three Peaks Recreation Area. Our approach included collecting plot-level data to determine abiotic and biotic niche factors correlating with the presence/absence of Q. undulata, including slope, aspect, soil type, soil chemistry, vegetation cover, and other associated woody plant species. Our results have shown that Q. undulata populations have higher concentrations in south-facing slopes, potentially reflecting the climatic preferences of its Dixie live oak parent. Results also showed that both focal species, Q. undulata and Q. gambelii, prefer areas with shallow soil and rocky outcrops. We plan to continue data collection and our analysis of soil type and chemistry. These results will help us to better understand the evolutionary history and ecological requirements of this fascinating native Utah plant.
Information-Gaining Moves in Game Theory
Authors: Kevin Young. Mentors: Gretchen Ellefson. Insitution: Southern Utah University. The concept of competition is not new to humans, nor is it simple. Countless philosophers throughout the years have approached competition in many ways. One of the core subjects that philosophers have used to discuss competition is that of decision theory. Decision theory, in short, discusses the best things to do. Game theory, a subset of decision theory, discusses the same within the context of games, or in other words, strategy. Both of these subjects have been used to evaluate how best to win games of chance, games of choice, and games in between. I work to explore the concept of making moves to gain information, seeking to learn another person’s moves before you make your own. This subset of moves deserves recognition, especially within the modern eras of competition.
Preferential Capture of Bacteria Using pDA-coated Magnetic Nanoparticles
Authors: Alyson Camacho, Camille Bryner, Bowen Houser. Mentors: William Pitt. Insitution: Brigham Young University. Current methods for the diagnosis of bacterial infections require time consuming cultures. To prevent deaths caused by sepsis, faster methods for bacterial identification and antibiotic susceptibility methods are urgently needed. Necessary to these faster methods is the ability to separate and concentrate bacteria. While techniques such as filtering and centrifugation have been explored for this purpose, we propose an innovative approach. Polydopamine (pDA) is a remarkably adhesive polymer that has been used to create antibacterial and anti-biofouling coatings on medical devices. In this study, however, we show how magnetic nanoparticles (MNPs) coated with pDA can selectively bind and remove specific bacteria from suspensions. For these experiments, pDA- MNPs were added to suspensions of bacteria mixtures and allowed to bind for 10 minutes. The MNP/bacteria mixture was then placed on a holder with a magnet which collected the MNPs on the side of the test tube. Finally, the bacterial supernatant was carefully removed and plated. Capture efficiency of the beads was calculated and it was shown that the pDA-coated MNPs preferentially isolated S. epidermidis from a suspension of both S. epidermidis and E. coli. This approach holds great potential for separating bacteria from clinical samples like urine or blood, enabling faster and more efficient diagnosis of bacterial infections.