2014 Abstracts

Xin Wan, University of Utah Life Sciences Endothelial dysfunction exists in individuals with diet-induced obesity (DIO) and type 2 diabetes (T2DM). Markers of endothelial dysfunction include reduced phosphorylation (p) of endothelial nitric oxide (NO) synthase (eNOS) to total eNOS (p-eNOS:eNOS), and attenuated endothelium-dependent vasorelaxation. Free fatty acids (FFAs) are elevated in individuals with DIO and T2DM. Our laboratory has shown that when: (i) endothelial cells are incubated with saturated FFA palmitate; (ii) mice are infused with lard-oil; and/or (iii) when mice are fed with high-fat diet, protein phosphatase 2A (PP2A) binds directly with eNOS. When this occurs, the association among Akt-Hsp90-eNOS is disrupted, p-eNOS:eNOS is impaired, and endothelium-dependent dysfunction occurs. This is prevented using pharmacological and genetic approaches that limit production of FFA metabolite ceramide. It is unknown whether PP2A inhibition per se is protective. We hypothesized that arterial dysfunction in obese vs. lean mice is prevented by PP2A inhibition. Seven-week-old, male, C57B16 mice consumed standard (CON, n=20) or high-fat (HF, n=20) chow for 12-weeks. Subgroups (n=10) of CON and HF mice received IP injections of saline (vehicle; V) or Lixte Biotechnology 100 (LB1, 1 mg/kg/day) for the last 14-days. Preliminary experiments verified that LB1-treatment for 3 and 21 days decreases (p<0.05) arterial PP2A activity. HF mice gained weight and developed peripheral glucose intolerance vs. CON mice regardless of LB1 treatment. Endothelium-dependent vasorelaxation was impaired (p<0.05) in HF-V vs. CON-V mice, but dysfunction was less severe (p<0.05) in HF-LB1 mice. p-eNOS:eNOS was reduced (p<0.05) in arteries from HF-V vs. CON-V mice, but p-eNOS:eNOS was similar in arteries from HF-LB1 and CON-LB1 mice. Akt and Hsp90 co-immunoprecipitation with eNOS was impaired (p<0.05) in HF-V vs. HF-CON mice, but this was not observed in arteries from HF-LB1 and CON-LB1 mice. These findings suggest that PP2A activity suppression in vivo is sufficient to preserve endothelial function in obese mice.

Teresa St. Pierre Nufer, Brigham Young University Life Sciences Acute stress has been shown to decrease Long-Term Potentiation (LTP) in the CA1 region of the mouse hippocampus. Stressed animals also show signs of anxiety and suffer decreases in spatial memory tasks such as object recognition and maze navigation. Conversely, exercise has been shown to increase spatial memory task performance in mice, attenuate anxiety-like behaviors and enhance neurogenesis and LTP in the dentate-gyrus. While the effects of stress and exercise have been examined independently, there is currently a lack of experimental evidence that connects how stress and exercise, when experienced by the same animal, might modulate LTP in the CA1 region of the hippocampus. In our ongoing study, mice have been separated into a control group, a stress group (restraint and tail-shock), and an exercise with stress group where mice have voluntary access to a running wheel (for 30 days) before undergoing the stress protocol.

Janweb Lagazo, Brigham Young University Life Sciences The scientific community and the general public have long been interested in the effects of water pollution. Most studies on water pollution have focused solely on industrial pollution, but have failed to consider the potential impact of pharmaceuticals that unintentionally accumulate in aquatic ecosystems via wastewater treatment effluents. The purpose of this study is to advance our understanding on how these wastewater effluents affect aquatic ecosystems in Utah. We quantified the concentration of select pharmaceuticals in Hobble Creek using mass spectrometry. Then we sampled above the treatment plant, at the effluent outlet, and downstream of the effluent to determine pre-effluent and post-effluent drug concentrations. We are currently using this preliminary data to investigate how common endocrine disrupting, anti-inflammatory, analgesic, and anti-anxiety drugs may potentially affect the aquatic ecosystem of the endangered Chasmistes liorus, commonly known as June sucker.

Dani Peterson, Brigham Young University Life Sciences Due to its long and complicated trajectory through the cranium, facial nerve VII (CN VII) can be damaged in surgeries, sometimes resulting in facial muscle paralysis. Surgical removal of acoustic neuromas and parotid tumors, in addition to surgical repair of the temporomandibular joint disorder are associated with a risk of damage to CN VII. In addition, insertion of auditory implants can damage the nerve, as can improper stimulation to the nerve after the implantation has occurred. We will create a three-dimensional (3D) model based off of data from dissection of the nerve in a human cadaver in order to give physicians a greater in vivo knowledge of the pathway of CN VII. We have dissected the lateral side of the right half of the head to the level of the parotid gland, identified the parotid plexus of CN VII, and followed its five branches. In addition, we are currently following the nerve through the internal auditory meatus on its pathway through the temporal bone. In preparation for the modeling MicroScribe technique described below, we have imaged the head using Magnetic Resonance Imaging (MRI) at BYU. These images will be used as a template for the nerve reconstruction model. After completing the dissection, we will track the nerve trajectory using a MicroScribe 3D Digitizer. The MicroScribe technique is used to create 3D computer models of any physical object. The user sets reference points and uses the stylus to trace data points of the object’s contours. Our final product will be a 3D spatial computer mapping of CNVII, as well as a mapping of the skull, parotid gland, and other landmarks to put the nerve model into context. We hypothesize that with our approach and MicroScribe technique, we will be successful in creating an accurate model of CN VII in the head.

Lauren Archibald, Brigham Young University Life Sciences Increased intake of selenium (Se) and soy have both been shown to reduce risk for prostate cancer, especially if these dietary treatments are combined. The purpose of this project is to determine how the timing of Se supplementation of either a low- or high-soy diet affects prostate cancer risk. [C57BL/6 X FVB] F1 TRAMP (TRansgenic Adenocarcinoma of Mouse Prostate) male mice were fed stock diets low or high in soy. Half of the mice received Se supplementation (4.0 mg Se/kg BW as Se-methylselenocysteine) by gavage 5 d/wk in a 2 X 2 factorial design. Se supplementation began at conception, 6 weeks, 12 weeks, or 18 weeks of age. The mice were then sacrificed at different stages of maturation (4, 12, 18, and 24 weeks). Our results showed that, at 12 weeks of age, urogenital tract weights, a measure of prostate proliferation and tumor volume, were significantly reduced by Se supplementation (p<0.001) and by soy (p=0.044), independent of time of dietary intervention. Histological scores of prostate cancer progression also showed a protective effect of Se supplementation (p=0.030). At this writing, statistical analysis of data from mice sacrificed at 18 weeks is in process. Data derived from 18-week mice, combined with our previous findings from 12-week animals, will allow us to chart the progress of prostate cancer in this model. In addition, results will show how dietary Se and soy may alter disease progression and how the timing of dietary intervention may determine its effects.

Claudia Gonzalez, Brigham Young University Life Sciences Cortisol has been shown to be a potential bio-marker as it discriminates between individuals with and without depression (Rush et al., 1996 and Ising et al., 2007). However, cortisol has not been used to predict variation in temperament extremes that lead to pathological behaviors in adulthood. In order to examine the relationship between cortisol and temperament extremes, data from the bio-behavioral assessment (BBA) was used. The BBA data base includes data collected from over 2,700 infant rhesus macaques located in California National Primate Research Center (CNPRC). During the BBA four blood samples per subject are obtained and later assayed for plasma cortisol levels. In this study, the plasma cortisol response levels were looked at in a holistic form encompassing all individual cortisol samples. The four points of plasma cortisol concentrations were used to extract patterns of response per subject which provided classifications for each of the monkeys. The pathological patterns of cortisol response were characterized by abnormal plasma cortisol levels in response to Dexamethasone suppression testing and adrenocorticotropin ACTH injections. The variability in plasma cortisol patterns was then compared to BBA temperament ratings of vigilance, gentle, nervousness and confidence. These results showed that 12 of the 26 possible patterns of response were significantly (p<.05) related to each of the temperament ratings of vigilance, gentleness and confidence. Thus cortisol response patterns can be used both as biomarkers for vigilance, gentleness and confidence, and as potential predictors for pathological behaviors in adulthood.

April McMurray, Brigham Young University Life Sciences Diabetes Mellitus Type 2 (DMT2) is a lifestyle-related disease where the body does not produce enough insulin or the cells are unreceptive to it, and it is now the most common form of diabetes. Individuals who do not control the disease can suffer serious complications such as limb amputation, damage to the eyes, kidneys, nerves, heart, and it can be very costly. This problem is particularly serious in Tonga; the prevalence is almost twice as high as that in the United States. The purpose of this research project was to determine to what extent the cultural, economic, and educational factors contribute to such high prevalence. In May I traveled to Tonga with the nursing students from Brigham Young University to conduct my research. I distributed surveys to patients and medical staff in the diabetes clinic in the Vaiola hospital in Nuku’alofa, Tonga. The surveys had questions related to their socioeconomic status, understanding and attitudes of diabetes, as well as patient management practices. While I was there, I also kept extensive field notes on observations related to my research, which provided supplemental information regarding the Tongan lifestyle that was difficult to gather from the surveys. Preliminary analysis indicates that there has been a very small, positive shift in understanding and attitudes towards DMT2, but economic- and culture-based habits still impede Tongans from managing the disease effectively. There were several limitations to this study: small sample numbers, lack of resources, some resistance from Tongan medical personnel, and particularly cultural barriers made it difficult to gather enough information to come to significant conclusions. However, the research does give insight concerning potential future studies and interventions to help the people of Tonga treat this disease.

Benjamin Gann, Utah Valley University Life Sciences (E)-2,4-bis(p-hydroxyphenyl)-2-butenal (2-Butenal) was shown to inhibit various inflammatory responses by inhibiting NF-kB pathway. A pull-down assay proved 2-butenal to bind to IKKb and was proposed as an active site kinase inhibitor through molecular docking experiment. However, 2-butanal has a highly conjugated aldehyde group that makes it very unstable. Therefore, we have designed more stable 2-butenal analogues and prepared them using Heck reaction. Molecular docking experiment shows that many of them have a greater affinity to IKKb.

Sara Fauver, University of Utah Life Sciences We know that novel genetic variants have driven evolution for millions of years and that natural selection favors phenotypes most suited for survival, leading to the enormous diversity of life we see today. However, what remains unclear, are the patterns of mutations that lead to large phenotypic changes. For example, do mutations in a single gene of large effect lead to morphological changes more often than numerous mutations in genes of smaller effect? Also, do these mutations occur more often in protein coding regions or regulatory regions of DNA? Finally, are the same genes or gene pathways used repeatedly across lineages when parallel phenotypes evolve?

Jeffrey Leavitt, Utah Valley University Life Sciences Central Research Question: Heptageniidae is a large family within the order Ephemeroptera (mayflies). This family consists of over 500 described species. Recently a study was done across 200 of the species to break them up into subfamilies, and genera. The studied concluded that there are 29 genera and three subfamilies Ecdyonurinae, Heptageniinae, and Rhithrogeninae (Wang, 2004). Furthermore, Ogden et al. (2009) proposed that the families Arthropleidae and Pseudironidae were derived heptageniid lineages. The phylogenetic relationships of Heptageniidae, Arthropleidae, Pseudironidae, to other closely related families are inconclusive. We propose to study these three families and the three subfamilies of Heptageniidae in detail via molecular systematics.

Daniel Hall, Brigham Young University Life Sciences OBJECTIVE(S): Predictive analytics (PA) is increasingly being used in the delivery of healthcare. Whether PA can improve patient handoffs on a busy surgical service is unknown. This study aims to determine if predictive models for acute cellular rejection (ACR) episodes and biliary complications after orthotropic liver transplantation (OLT) can be built in order to improve patient care.

Spencer Alexander, Dixie State University Life Sciences Antibiotic resistance has increased with each new developed medication, creating new problems as bacteria become more difficult to defeat. Some of these bacteria are resistant because they can excrete an extracellular polymeric substance known as a biofilm. The polysaccharide-based biofilm matrix allows the colony to communicate, absorb nutrients, and exchange genetic material giving it an advantage in possible resistance through plasmid exchange. At present, there are no effective antimicrobial agents that can safely treat and prevent resistant bacteria like ORSA. Biofilms have a negative impact ranging from human pathogenesis down to economic expenses. In order to break down established biofilms, we utilized newly developed organic salts known as ionic liquids. These novel liquids have been observed to prevent bacterial colonies and biofilm formation, possibly by introducing intermolecular interactions that disrupt the chemical bonding in biofilms. The morphology of the microbes was characterized and observed to determine the effect of the ionic liquids on biofilms. Inhibition studies were also performed to determine antimicrobial efficiency of the ionic liquids as a function of organic structures. These novel ionic liquids provide an unprecedented, effective and efficient method to combat resistant bacteria, which could have tremendous impacts in achieving sterile environments in medical and remote settings.

Dasom Kim, Brigham Young University Life Sciences The main purpose of the project is to compare the phylogeography of a species of stonefly (Klapopteryx kuschelli) and a species of dragonfly (Rhionaeshna variegata) in Patagonia. Specifically, the project will study how geography and behavior (i.e., their dispersal abilities) have affected their evolutionary histories. Of all the varied climates and geography in South America, comparatively few phylogeographic studies have been conducted with insects, especially in Patagonia. This study will provide an important foundation for a comparative phlyogeographic study of two insect groups inhabiting the same regions of Patagonia. Also, if funded, this project will give me an exclusive opportunity to interact with international research institutions in South America as well as their scientists.

Derrick Crawford, Brigham Young University Life Sciences Members of the FGF family of signaling factors are key components in distal outgrowth and patterning of the vertebrate limb. These factors are expressed and secreted by the apical ectodermal ridge (AER) on the distal margin of the limb. Blocking their function is known to truncate the limb skeleton. Conversely, replacing the AER with beads soaked in Fgf protein can rescue limb outgrowth and patterning. Our lab has demonstrated that one of the mechanisms whereby the Fgf/AER functions is to mediate directed outgrowth of the adjacent mesenchyme. As the AER regulates growth of mesenchyme toward itself, it would be predicted that the AER’s dimensions would be important for shaping the mesenchyme that it recruits. We have found that the shape of the AER changes over time in a manner that corresponds to the shape of limb elements as they form along the proximal distal axis. Further, mutants that exhibit defects in the dimensions of the AER show corresponding anomalies in the limb skeleton. Given these observations it would be predicted that an Fgf soaked bead being of fixed spherical dimensions would only be capable of forming a cylindrical, rod-shaped limb. A bead placed posteriorly fulfills this expectation whereas a bead placed apically does not. We provide a molecular explanation for this discrepancy. We have also manipulated the shape of the AER surgically and find that similar to beads the shape and the AP position of the AER dictates the shape of the forming limb skeleton.

Mark Soffe, Utah State University Life Sciences SSBs are DNA binding proteins that are essential components of cells and play key roles in DNA replication, repair, and recombination. Here we utilize two biochemical properties associated with the E. coli SSB protein to develop a novel procedure to purify proteins using a resin-free strategy. 1. E. coli SSB binds to single stranded DNA (ssDNA) with extremely high affinity (K = 1013 M-1), indicating very tight binding. 2. It is also a unique protein with respect to its purification – it is possible to obtain greater than 95% pure SSB from the total cell lysate without using any sort of column or resin, utilizing polyethyleneimine (PEI) and ammonium sulfate precipitation. Our design uses SSB as an affinity/solubility tag to enhance the solubility and expression of difficult-to-purify proteins, and allows for the simple, resin-free purification using PEI and ammonium sulfate precipitation. There also may be a possibility to co-express protein dimers and possibly tetramers using this method. Constructs have been made that include the SSB gene, along with the ability to fuse any gene of interest, as well as a TEV Protease cleavage sequence allowing for proteolytic cleavage after gene expression. Two genes of interest have been cloned in thus far—TEV protease and Rad51. In this proposal I outline experiments to develop this strategy further and test our proof of principle concept and its application to a broader set of target proteins.

Teressa Paulsen, University of Utah Life Sciences Breast cancer is still the most common cancer among women regardless of race or ethnicity. The focus of our research is to uncover the mechanism breast cancer cells use to escape the inherent limitations of the telomere and obtain immortality. The protective end of a chromosome, the telomere, degrades with each cellular division. The cellular response to telomere dysfunction is to activate programmed cell death. Therefore, this type of damage normally limits the proliferative potential of the cell and subsequently carcinogenesis.

Marilize Van der Walt, Utah State University Life Sciences Urbanization is accompanied by a lot of changes to the landscape that have the potential to affect the native species inhabiting the area. If animals are chronically exposed to these anthropogenic disturbances and are unable to acclimatize, changes in circulating glucocorticoid hormones may cause adverse effects to the animal’s health, such as an impairment in innate immune activity. One such disturbance is human-induced noise. Using the side-blotched lizard, Uta stansburiana, because of their localized habitat and inability to escape such disturbances within the urban environment, we looked at the field and lab components of noise as a stressor. We first measured decibel levels in urban and rural field sites in their natural habitats in St. George, Utah, and conducted a lab study exposing U. stansburiana to either a synthesized urban sound recording or no sound recording (control) for nine days. We collected blood samples and measured circulating corticosterone and testosterone concentrations and bactericidal ability to determine if there are endocrine and immune alterations in response to increased noise decibels. Our results show that lizards exposed to urban noise experienced increased corticosterone levels indicative of stress. Furthermore, bactericidal ability was indirectly affected by noise through significant correlations between body condition and corticosterone and testosterone concentrations. These results indicate that an increase in ambient decibel levels acts as a stressor to animals in urban areas. By dissecting out an individual component of a complex stressor we can better understand the effects of urbanization as a whole.

Molly Van Engelenhoven, Utah State University Life Sciences For thousands of years farmers have known that soil organisms can destroy crops but only in the past ten years have researchers begun to understand that complex interactions among soil organisms and plants can determine plant diversity and productivity. Much of the research in this young field of study has come from qualitative greenhouse experiments and separately from simple mathematical models. Here, we report findings from a six-year plant-soil feedback (PSF) field experiment that assessed the effects of soil organisms on the growth of twelve plant species common to the intermountain west. Initially, twelve native and exotic species were randomly assigned to 1550 experimental plots in a field. After four years of growth, the plants were killed. Next, the same plant species were randomly assigned to the 1550 plots again to test how each plant species responded to the soil microbial communities ‘cultivated’ by each other plant species. Two years later plant growth responses to different soil types were measured. Most plants showed large growth differences on different soil types. For example, Bromus tectorum grew twice as much on Pseudoroegneria spicata-cultivated soils than on self-cultivated soils. When the plant growth responses observed in this experiment were used in a mathematical model, PSFs were found to play a critical role in determining which plants were likely to be dominant in a community and how productive these different plant communities would be. In summary, this large-scale experiment provides strong evidence for the role of PSFs in plant productivity and diversity. Results have implications for natural methods of effective native plant restoration, biofuel production and weed control.

Jacob Anderson, Utah Sate University Life Sciences Leafy spurge (LS) is an aggressive Eurasian forb that has been successfully reduced in many areas in western North America through the biological control releases of flea beetles. Long term studies of this phenomenon are sparse. Three flea beetle species were released in the mid-1990s at a site dominated by LS in Richmond, Utah. This study assessed the long term effects of LS biocontrol on an ecological community at this site by addressing five questions: (1) Is LS abundance significantly lower now than in the 1990s? (2) What plant species are replacing LS and are they native or non-native? (3) Have the flea beetle populations persisted since their initial release? (4) What part does soil type play in which flea beetle species now dominate at the site? (5) In response to their unexpected presence, what role may long-horned beetles contribute to the long-term reduction of LS? It was found that LS abundance has significantly decreased from the 1990s; the dominant plant species are those of non-native grasses; flea beetles have persisted in significantly smaller numbers, with Aphthona lacertosa being the most abundant; and long-horned beetles appear to play a significant role in the reduction of sexual success of LS. The results of this project have implications for land managers when considering the vegetative response to LS biological control and the importance of long-horned beetles for long-term in managed, LS-reduced habitats.

J David Symons, University of Utah Life Sciences Autophagy plays a central role in cellular quality control by destroying damaged or excess proteins, lipids, membranes, and organelles that accumulate in response to deviations from homeostasis. The existence and role of autophagy in endothelial cells (ECs) and blood vessels has not been established. Autophagy can be quantified by assessing the ratio of the membrane bound conjugate of microtubule-associated protein light chain 3 (LC3-II) to the cytosolic non-lipidated conjugate LC3-1 (LC3-II:LC3-I) or GAPDH (LC3-II:GAPDH) via immunoblotting. We sought to determine the extent to which a variety of cellular stressors induces autophagy in ECs and intact blood vessels. LC3-II:LC3-I or LC3-II:GAPDH was elevated (p<0.05) (i) 450±6% (n=4) in ECs incubated for 2 h in amino acid (AA)-deplete vs. AA-replete media; (ii) 47±3% (n=3) in arteries from fasted (14 h) vs. fasted / refed (1 h) mice; (iii) 40±2% (n=3) in arteries from mice that completed acute exercise vs. sedentary controls; (iv) 38±1% in arteries from exercise-trained vs. sedentary mice under basal conditions (n=2 per group); and was decreased (p<0.05) (v) 57±8% (n=4) in arteries from ~30 month-old (i.e., old) vs. ~6 month-old (i.e., young) mice. Further, indices of autophagy were elevated (p<0.05) 101±6% in ECs exposed to 3 h x 500 uM palmitate vs. vehicle (n=4), and 50±6% in arteries from obese vs. lean mice (n=4 per group). Thus, autophagy is altered in ECs and blood vessels in response to physiological (e.g., fasting, acute exercise, exercise training, aging) and pathophysiological (acute lipotoxicity, diet-induced obesity) stimuli. Ongoing research will determine the functional role of vascular autophagy in health and disease.

Michael Morgan, Utah State University Life Sciences The advancement of biologically derived alternatives to petroleum diesel fuel requires a multifaceted approach. At Utah State University we use an interdisciplinary team including the Colleges of Engineering, Agriculture & Applied Sciences, and Science in conjunction with industry partners to drive innovation in improving the science behind petroleum diesel alternatives. With increasing petroleum use, depleting reserves, increasing emissions standards, and other factors, there is need for petroleum diesel alternatives that are cost effective, offer improvement, and perform similarly to petroleum diesel. Our team has focused on the use of oleaginous microbes utilizing low value effluent and waste sources including sugars and CO2 to create biofuels. We have focused on a yeast, Cryptococcus curvatus, and a microalgae, Nannochloropsis salina which have shown high yields of fuel per cell mass. Using these microbes we have utilized USU’s own direct trans-esterification reaction to create sufficient quantities of biodiesel for engine performance and emissions testing, including a subset of ASTM tests characterizing the fuels from each organism. Our initial engine testing used petroleum diesel as a baseline in conjunction with commercial soybean biodiesel to establish the quality of our microbially derived biodiesel. Testing in stationary diesel engines and on the Bonneville Salt Flats has proven our microbial fuels perform similarly to soybean biodiesel and comparably to petroleum diesel. To further improve biological diesel replacements we have begun working to create green diesel, hydrocarbons from a biological source, using a novel method of hydrothermal liquefaction. Preliminary results of those tests are presented here. Through a multifaceted and interdisciplinary approach USU is successfully improving petroleum diesel alternatives from microbial sources including characterization of the properties of these fuels and is working to create the fuels at the scale necessary for exhaustive engine performance and emissions testing including ASTM testing of all important fuel properties.

Laurel Thompson, Utah Valley University Life Sciences Breast cancer is divided into subtypes which are defined by their proteomics, histology, and genetic expression profile. Current methods, therefore, are aimed at testing these, and include DNA microarrays, immunohistochemical staining, and proteomic analysis. These methods are effective classifiers, but are not easily transferable to real-time clinical applications, such as the determination of cancerous status during operation or when taking a biopsy. The determination of molecular subtype by other means would be a significant advancement in cancer detection and treatment. We have made some preliminary studies that suggest high-frequency ultrasound may be sensitive to variations among the cancer subtypes as manifest in cell cultures through their cytoskeletal protein structure, which has a distinct spectral signature. The object of this study was to explore the basis for this variation through a combination of experimental and theoretical analysis. We used first-principal modeling methods and compared the model spectra generated from these to spectra obtained in the cell culture lab. Variations in bulk modulus, cell position and size were modeled and combined with experimental spectra in principal component analysis (PCA), and the Euclidean distances between each principal component of the experimental were found as they relate to the theoretical principal components. A graphical method similar to heat maps used for gene expression profiling was then developed to display the relative distances (similarities) between spectra. The program was tested by comparing experimental spectra of three breast cancer cell lines to model spectra. The results indicate the properties and thus molecular subtypes of breast cancer cells could potentially be determined by comparing their measured spectra to model spectra using a feature classification program such as PCA and that these classifying features can be displayed in a convenient graphical representation according to their spectral similarities.

Austin Spence, Utah State University Life Sciences This study investigated the physiological effects of localized habitat disturbances around two well-studied hibernacula of the wandering gartersnake Thamnophis elegans. After three years of monitoring snake morphology and physiology at several hibernacula, several disturbance events occurred, including log clearing, stream bank disturbance, and vegetation removal. Individuals from three populations, two with disturbed hibernacula and one control population with no disturbance, were collected during the spring emergence immediately following the disturbance. Blood samples were collected upon capture and following a uniform stressor to measure baseline and post-stress physiological conditions. The samples were analyzed using a radioimmunoassay to measure corticosterone levels and a bacterial killing assay to measure innate immunocompetence. Baseline and post-stress corticosterone levels were higher in both populations with disturbance events compared to the control population. The bacterial killing ability of the site with the most anthropogenic activity was lower than the control site, indicating immunocompromise. Data are currently being analyzed to assess differences within the same populations between years with and without disturbance events. Pre-disturbance data are a rare and useful commodity and allow us to facilitate a better understanding of the various effects of anthropogenic change on natural populations. This study was funded through the Undergraduate Research and Creative Opportunity Grant from Utah State University.

Jacob Bassett, Utah Valley University Life Sciences Many discoveries regarding the complex interplay between biological pathways within a cell begin with attempts to link new observations to scrupulously studied cellular mechanisms. Our lab is studying the soluble inter-mitochondrial space protein mdm35, which has been observed to facilitate the function of ups1 & 2 proteins, as they in turn regulate the mitochondria’s phosphatidic acid metabolism. In addition to this phenotype, our lab has observed a copper resistance at 0.17% on YPD plate and 0.14% in liquid cultures of S. cerevisiae lacking the mdm35 protein, when compared to the Wild Type strain. Our investigation measures the levels of expression in the cup1 and ctr1 promoters in an attempt to link this observation to a potential mechanism contributing to this resistance.

Bryan D Merrill, Brigham Young University Life Sciences The spore-forming bacteria Paenibacillus larvae causes American Foulbrood (AFB), a highly contagious disease that is lethal in honey bee larvae. P. larvae is the most serious pathogen affecting honey bees. Its increasing antibiotic resistance has led to more research in characterizing bacteriophages which infect and destroy P. larvae. Of the 13 P. larvae phages that have been described in publications, six have been fully sequenced and are currently available for genomic analysis. To understand how P. larvae phages are related to each other and to other phages, the computer program Phamerator was used to analyze more than 100 phage genomes and group phage genes into “phams” based on similarity. Through analysis of grouped phage genes (structural proteins, terminases, recombinases, etc.) we can better understand in vivo replication strategies and evolutionary history of these P. larvae phages.

Taylor Woodward, Brigham Young University Life Sciences The prevailing view is that enhancement of dopamine (DA) transmission in the mesocorticolimbic system, consisting of DA neurons in the ventral tegmental area (VTA) that innervate the nucleus accumbens (NAc), underlies the rewarding properties of alcohol and nicotine (NIC). Dopamine neurotransmission is regulated by inhibitory VTA GABA neurons. We have shown previously that VTA GABA neurons are excited by low-dose ethanol, but inhibited by moderate to high-dose ethanol. The aim of this study was to evaluate the role of []6 nicotinic cholinergic receptors (nAChRs) in ethanol effects on VTA GABA neurons as well as DA release in the NAc. In electrophysiology studies, superfusion of ethanol enhanced the frequency, but not amplitude, of mIPSCs recorded in acutely dissociated VTA GABA neurons from GAD GFP mice. The []6 nAChR antagonist []-conotoxin P1A did not affect mIPSCs, but prevented the ethanol (30 mM)-induced increase in mIPSC frequency. While microdialysis studies show that ethanol enhances DA release in the NAc, we and others have found that ethanol decreases DA release at terminals using fast scan cyclic voltammetry (FSCV). We have reported that ethanol inhibition of DA release at terminals in the NAc of ethanol-naïve animals is mediated by GABA. Using FSCV in the slice preparation, ethanol inhibited DA release in the NAc. Superfusion of the []6 nAChR antagonist []-conotoxin MII did not affect DA release, but prevented ethanol inhibition of DA release. Taken together, these findings suggest that ethanol enhancement of GABA inhibition of VTA GABA neurons is mediated by []6 nAChRs located on GABA terminals to other VTA neurons, affecting DA release in the NAc. Results from this study could provide a pharmacologic rationale for considering drugs that act selectively on nAChRs as therapeutic agents for the treatment of alcohol dependence and alcohol and NIC co-dependence.

Corey Wolf, Westminster College Life Sciences The yeast species Saccharomyces cerevisiae is used in numerous industries including brewing, baking, and winemaking. In recent years an increased demand for low ethanol beers has pushed breweries to develop a beer that is both rich in flavor and low in alcohol content. The current strategies employed to decrease the ethanol concentration in beer are costly, time intensive, and result in less flavorful beers. In this study, a method for decreasing alcohol content in the brewing process through the use of metabolic inhibitors of Alcohol Dehydrogenase is tested. Alcohol Dehydrogenase is the enzyme responsible for the conversion of acetaldehyde, an intermediate in the metabolic pathway of yeast, into ethanol. Two competitive inhibitors of Alcohol Dehydrogenase, Pyrazole and Fomepizole, were applied to small scale fermentations in varying concentrations in an attempt to decrease the overall ethanol yield of the beer. The application of either inhibitor resulted in an initial decreased rate of fermentation overall, measured as a change of sugar and ethanol concentration. In the later stages of fermentation, the rate of ethanol production returned to normal, suggesting the inhibitors were either catalyzed or removed by the cell. While this method for manipulating the products of fermentation did not yield the desired effects, this study did highlight the importance of the fermentation pathway for maintaing healthy Saccharomyces cerevisiae cultures. This research may be helpful in understanding the complete metabolic pathway of brewer’s yeast, with further application to organisms with conserved pathways.

Camrin Rivera, Westminster College Life Sciences The Great Salt Lake (GSL) of Utah is home to organisms that are able to survive and reproduce in waters that can have a salt concentration of over 30%. Oil Jetty is located on the saltier north arm of the GSL and is the location of a natural hydrocarbon seep that flows into the lake. Previous work showed that organisms capable of degrading hydrocarbons can be cultured from this area (Ward & Brcok, 1978). It has also been shown that the salt concentration has an inverse relationship with these organisms’ ability to degrade hydrocarbons (Ward & Brock, 1978). This previous study gives insight of the hydrocarbon degrading capabilities of microorganisms in the GSL; however, the identification and characterization of individual hydrocarbon-degrading microorganisms has yet to be completed. The purpose of this study is to identify GSL microorganisms capable of degrading hydrocarbons under high salinities by sequencing of the 16s rRNA gene. Future studies will include the characterization of these microorganisms in order to find isolates whose hydrocarbon degrading abilities could be utilized for bioremediation and biotechnologies.

Hailey Shepherd, Dixie State University Life Sciences Previous studies of canyon tree frogs (Hyla arenicolor) in Zion National Park have shown that some populations test positive for a dangerous fungus in the Chytridiomycosis family. This fungus has been linked to large population losses worldwide in many keystone amphibian species, but appears to have no effect on populations of H. arenicolor. Since Chytrid fungal growth is inhibited at high temperatures, we hypothesized the frogs are able to rid themselves of the fungus because they bask in the sun. During the summer of 2013 we swabbed frogs in multiple slot canyons to test for the presence of the fungus. We also recorded skin temperatures of the frogs we swabbed. Skin temperatures were as high as 38 C°, which is above the previously established lethal threshold of 28 C° for Chytridiomycosis. Our data support the idea that these frogs may be able to rid themselves of infection by allowing skin temperatures to raise enough to become intolerable for this fungus. This is the first known evidence of wild amphibian populations showing a behavior that may clear the infection. If further research supports these findings, it could lead to more effective allocation of limited conservation resources.

Merrill Christensen, Brigham Young University Life Sciences Selenium (Se) has established chemopreventive efficacy against prostate cancer, the second leading cause of cancer death among men in the US. Currently, most studies only employ one single chemical form of Se, even though different forms of Se act through varied mechanisms to achieve their anticancer effects. In this study, we propose that systematically combining multiple forms of Se will produce an optimal combination of Se compounds to inhibit in vitro prostate cancer cell growth. As proof of principle, we (1) synthesized Se nanoparticles (nano Se), (2) determined the IC50s of methylseleninic acid (MSA), sodium selenite, and nano Se in PC-3 cells, (3) utilized mixture designs and response surface methodology to direct our combination experiments with these three compounds, (4) tested the fifteen combinations determined in the previous step, and (5) constructed a polynomial model to derive the optimum combination of MSA, sodium selenite, and nano Se to inhibit PC-3 cell growth. Our results showed that combining different forms of Se compounds enhanced its chemopreventive effect. Future studies will expand the use of three Se-containing compounds to four and demonstrate similar effects in xenograft mice.

Chelsea Moody, Dixie State University Life Sciences A relatively new pathogen, chytrid fungus, has been a major cause of decline in amphibians worldwide. This pathogen has been found on Canyon Tree Frogs in Zion National Park. Earlier data suggested that chytrid did not affect populations of Canyon Tree Frogs in Zion National Park. We predicted that since the populations weren’t impacted by the presence of the fungus, there must exist a mechanism by which the frogs rid themselves of the infective agent. To test this prediction, we captured and swabbed ten frogs in each of nine canyons in Zion National Park during the summer of 2013. Swabs were sent to the San Diego Zoo to be analyzed for the presence of chytrid DNA. Chytrid infection rates and population sizes were compared with data from previous years. As expected, the data showed that two of the three infected canyons experienced declines in the percentage of frogs testing positive for the fungus. Thus, these frogs must possess a mechanism to survive this pathogen, whereas most amphibians do not. Our results may prove helpful to other biologists seeking to understand how amphibians can survive this pathogen.

Eric Swenson, Dixie State University Life Sciences Underwater invasive species such as mussels and algae attach to submersible substrates that are advantageous for growth, and often include recreational boats that are frequently moved from one waterway to another. This can lead to rapid and uncontrolled spread of the invasive species. Through the use of newly developed ionic surfactants, growth and attachment of species on submersible surfaces can be inhibited. New surfactants have been incorporated into the final coating of typical product sealants to prevent the attachment of various marine organisms. By integrating the surfactant into the coating, an increase in the usefulness and longevity of effective inhibition is expected, as compared to commercially available alkali anti-fowling agents that are applied after the sealing process. It is hypothesized that the adherence properties possessed by marine organisms will be compromised by the introduction of ionic surfactants through changes in the chemical makeup of the exposed surfaces. The ultimate goal is to develop a substrate surface in which there is no affinity for attachment and/or causes fatality to the organism. If the desired outcome is reached, the potential benefits that ensue could create drastic improvements in areas of invasive species prevention and management in the desert southwest fresh-water lakes. Additionally, extension of the surfactant application to metal surfaces could have significant impacts on efficiency in water treatment systems, as well as cargo shipping in saltwater environments.

David Baird, Utah Sate University Life Sciences We obtained from the Bureau of Land Management (BLM) 30 years of monthly waterfowl population surveys completed at Pariette Wetlands in the Uintah Basin, Utah between 1980 and 2010. The Pariette Wetlands are the largest wetlands managed by the BLM within the lower-48 states and are comprised of 4,033 acres of land. Pariette Wetlands is surrounded by about 6,000 square miles of land where oil and gas production is the major activity. This waterfowl refuge is a significant location for migrating waterfowl species within the Pacific Flyway and provides important summer habitat for resident waterfowl. Our objectives were to determine what the trends were for waterfowl population abundance, occupancy, and species richness.

Sharisa Nay, Brigham Young University Life Sciences Gene therapy is a growing field of science with the potential to improve thousands of lives. With an eye toward improving the effectiveness and longevity of gene therapies, my project examines the preferential binding tendencies of the histone protein variants Htz1 and Htas1. Htz1 is the Ceanorhabditis elegans homolog of H2AZ, an important variant of the H2A histone. This protein has been shown as necessary for survival and as playing a role in the prevention of ectopic heterochromatin spread. Htas1 is another variant of H2A that plays a role in the increased transcription of sperm-producing genes. The preferred positioning of these variants on naked DNA is not yet known. Through a DNA extraction, nucleosome reconstitution, and DNA digest and sequencing, we will take these variants and examine where they are prone to localize within the N2 Bristol strain of c. elegans. This will allow us to include DNA sequences on our gene insertions possessing a high binding-affinity for these transcription-promoting histones. Thus, if we can identify the locations at which these variants will localize within DNA, we will be able to insert these preferred constructs into the genes used for gene therapy and thereby increase the effectiveness of gene therapies.

Albert Pope, Utah Valley University Life Sciences Few animals are capable of using the creosote plant, Larrea tridentate, as food because of a high level of toxic secondary compounds. Some exceptions to this rule are Neotoma lepida and Dipsosaurus dorsalis which are both capable of sustaining themselves on this desert bush. In 2013, Magnanou et al helped identify heightened transcription of genes correlated with digestion of creosote in N. lepida. Building upon their findings, we explore whether the genes for digesting creosote are under an elevated evolutionary rate for D. dorsalis. We have obtained transcriptomes from whole blood of four Iguaninae species: Ctenosaura pectinata, D. dorsalis, Sauromalus ater, Cyclura lewisi yielding an average of 4 GB of DNA sequence data (~51,000,000 fragments) each. Using Velvet in Sequencher we assembled these data, recovering greater than 6000 unique RNA transcripts per transcriptome. We search through the contigs to identify genes in Iguaninae transcriptomes that are homologous to those showing differential expression in Lepida. Using BLAST, we retrieve homologous genes from the public NCBI database of Anolis carolinensis and other reptiles. Lastly we construct phylogenetic trees of each gene and investigate the rate of change along each reptile lineage.

Cameron Haas, Brigham Young University Life Sciences The influenza A virus contains a proton-selective ion channel, A/M2, through which acidification of the cell is induced. A/M2 is a homotetramer (consists of four identical helices) consisting of 97 residues and activated by low pH levels. Mutations in the amino acid sequences may induce resistance to channel inhibiting drugs. It is believed that residues 26, 27, 30, 31, and 34 are the major contributors of drug resistance, but other nearby residues may prove important as well. The A/California/04/2009 version of the influenza virus is sensitive to the drug AK-11, while its M2 channel is not. The A/Udorn/307/1972 with the S31N mutation M2 channel has been shown to have reduced sensitivity to amantadine compared to its wild type. While both contain a D (aspartic acid) at residue 21, A/Puerto Rico/8/1934 has a mutation from D to G (glycine). The A/Puerto Rico/8/1934 virus A/M2 contains mutations S31N and V27T and has shown sensitivity to the AK-11 drug, but the mechanism of inhibition of the A/M2 channel has not been verified. In these experiments we will be identifying sensitivity to AK11 of A/Udorn/307/1972 with the S31N mutation as well as inducing double mutations with S31N at residues 27 and 21 in the A/M2 from the virus and measure sensitivity by electrophysiological recordings in oocytes of Xenopus laevis. By doing so we may identify the role of these residues in drug resistance and the effects of these amino acid mutations, while verifying the A/M2 channel as the mechanism of acidification inhibition and drug sensitivity. We hypothesize that either D21G, V27T or both mutations causes drug sensitivity in M2 S31N, explaining the sensitivity of A/Puerto Rico/8/1934 to AK-11.

Whitney Badal, Brigham Young University Life Sciences Light therapy has been utilized to treat alcoholism and opiate-dependent rats as well as ameliorating symptoms of Parkinson’s disease. As both addiction and Parkinson’s Disease (PD) are often associated with decreased dopamine transmission in the striatum, it is likely that light therapy is able to increase dopamine release. A similar technique called near-infrared light treatment has also been shown to be effective in mice in restoring the function of dopamine cells in the substantia nigra pars compacta (an area associated with PD). A possible explanation for this is that light catalyzes the formation of neuromelanin. It is likely that neuromelanin is a neuroprotective cellular agent that is able to reduce damage caused by reactive oxygen species. Using UV-IR spectrophotometry, we show that in the presence of photostimulation, dopamine (0.3-30 uM) oxidizes and polymerizes into neuromelanin. Since hydrogen peroxide catalyzes this formation of neuromelanin, it is likely that this is a radical-polymerization reaction, suggesting that neuromelanin may be a radical scavenger. Additionally, the presence of the selective iron chelator desferrioxamine, the calcium chelator EGTA, or lack of calcium in the artificial cerebral spinal fluid markedly reduces the formation of neuromelanin. Using fast scan cyclic voltammetry in mouse horizontal and/or coronal brain slices, dopamine release in the nucleus accumbens core was enhanced by light exposure, in particular UV and short-wavelength visible light. These findings indicate that both iron and calcium are necessary for melanization in neural tissues and that light-induced melanization enhances dopamine release, suggesting a physiological role for melanization in synaptic transmission.

Chase Barker, Utah Valley University Life Sciences Central Research Question: Phylogenetic relationships of mayflies are still not very well known, however molecular and morphological data have begun to shed light on the relationships of these insects (Ogden et al. 2009). Our central question is to elucidate the phylogenetic relationships within the mayfly family Baetidae.

Danielle Holliday, University of Utah Life Sciences Intrauterine growth restriction (IUGR) induces visceral obesity in adulthood, specifically among males. In male rat offspring, IUGR increases visceral adipose tissue (VAT) over subcutaneous adipose tissue (SAT). VAT and SAT functions are regulated by estrogen signaling, and suppressed estrogen signaling contributes to obesity development. Estrogen signaling is composed of estradiol and estrogen receptor alpha (ERα) and beta (ERβ). Estrogen receptors regulate the expression of several obesity related genes, such as lipoprotein lipase (LPL). However, the effects of IUGR on estrogen serum levels and signaling in the adipose tissue are unknown.

Ashley Calder, Utah Valley University Life Sciences An estimated 50-80% of dementia patients suffer from Alzheimer’s disease (AD). Currently there is no test to diagnose AD except post mortem. Recent papers indicate that AD affects the cytoskeleton and cellular structure through mutations that alter structural proteins, and that dysfunction of the cytoskeleton may play a pivotal role in AD and other neurodegenerative diseases. In particular, specific genetic components of AD affect microtubule and actin filaments that control endocytosis, exocytosis, the shape and size of the neuron, vesicular transport along neurites (dendrites and axons), and fibril formation. The goal of our research is to determine if breast cancer molecular subtypes can be used as a model for AD. Breast cancer is comprised of five molecular subtypes that contain different molecular structures depending on mutations specific to each subtype and the proteins being synthesized. These mutations and their expressed proteins change the characteristics of the cytoskeleton and resulting properties of the cell such as size, shape and stiffness. Both computer simulation and experiment have demonstrated that high-frequency ultrasound in the 10-100 MHz range is sensitive to these properties. For this study, ultrasonic tests were conducted on monolayer cell cultures of breast cancer cell lines of different subtypes. Ultrasonic waveforms were analyzed by transforming them into their corresponding spectra. The positions, widths, and shapes of the spectral peaks were compared and correlated to model results using a pattern recognition algorithm. Preliminary results indicate that cell stiffness and size can be determined from the measurements. Further analyses of these and additional data will determine if ultrasound is sufficiently sensitive to differentiate between the molecular subtypes of breast cancer. Results from these analyses, future studies with neuron cell cultures, and application of the results to the development of a minimally invasive, in vivo method for accurately diagnosing AD will be discussed.

Brett Gardiner, Brigham Young University Life Sciences Normal human anatomy used in the classroom is not reflective of variations confronted in pathology subjects. Current commercialized models are not products of real data, rather representations of it. While learning complicated medical anatomy, students take an enormous stride from the anatomy lab to situational surgical settings. 3D models can bridge this gap in medical education without patient risk, particularly for the brain where surface regions have strong associations to specific physiological activity. Subject specific models are especially advantageous for comprehending real surface morphology of neurologic diseases. Using rapid prototype technology, we have developed an accessible process to produce physical 3D models from specific MRI data of stroke and Alzheimer’s subjects. The neuroanatomical abnormalities modeled from real data by our 3D printouts will educate students on the anatomical variations encountered in an authentic clinical scenario of neuropathology. Our project consists of three phases: (1) image acquisition, (2) post-processing imaging data with segmentation, and (3) 3D printing. By delineating cortical regions we are providing a unique multidimensional facet of clinically accurate data not before available to the classroom. This powerful and versatile technique can allow students and professionals to visualize the inherently complicated structures as seen in clinical neuropathology. From students in the classroom, lawyers in the courtroom or preoperative surgical explanations, these customizable models will resemble real anatomical information. Through rapid prototyping of specific subject data, unique variations in pathology can be reviewed outside of the clinical setting. Beyond its potential use by teachers, lawyers and doctors can benefit from a 3D production to enhance their explanations of anatomical variations from specific pathological subject data.

Tamara Fox, Weber State University Life Sciences Clostridium botulinum has been implicated in cases of infant botulism across the United States. It is recommended that infants under the age of one year not be fed honey because of the presence of C.botulinum spores. The goal of this project is to determine whether honey produced in small and large apiaries in Utah contain varying amounts of toxin producing C. botulinum. Honey samples will be collected from hives maintained in Utah and tested for the presence of toxin producing strains of C. botulinum. Samples will be dissolved and centrifuged to isolate the spores and then superheated to release the DNA. Testing will then be done through a multiplex polymerase chain reactions (PCR) using primers specific for 16s rRNA, Clostridia species, and toxins A, B, E, and F. The presence and type of toxin producing Clostridia species will be compared with a Chi-Squared Test of Independence. Research will be completed by February of 2014 and we expect small apiaries will have a lower frequency of toxin producing C. botulinum strains than large apiaries and that toxin phenotype will vary between the two groups. The results will increase understanding on the variance of C. botulinum in Utah honey and will contribute to further research on this topic.

Kevin Nay, Southern Utah University Life Sciences Leech taxonomy has traditionally been based on morphological characters, but with new developments in DNA technology many taxonomists are starting to use genetic information in descriptions of new species. Leeches in southern Utah are poorly inventoried with respect to many other aquatic animals. There have been few morphological inventories of leeches and even fewer descriptions of the genetic diversity within leeches. Landscape genetics is a powerful tool used to understand geographic patterns of genetic diversity. Southern Utah has many naturally isolated bodies of water due to the climate and the dramatic changes in elevation in this part of the country. The landscape genetic study of leeches in southern Utah will provide us with a better understanding of genetic differentiation within southern Utah leeches. The mitochondrial DNA (CO I region) will be used to estimate genetic diversity and examine the relationships among individuals in two populations of leeches. I hypothesize that leeches in southern Utah will have greater genetic diversity then historically recognized from morphological studies suggesting a new species of leech. The study will lead to better understanding of the taxonomy and identification of southern Utah leeches.

Ashley Nelson, Brigham Young University Life Sciences The motivational effects of opiates and ethanol switch from a dopamine (DA)-independent to a DA-dependent pathway when the animal is in a drug-dependent state. A corresponding change occurs in ventral tegmental area (VTA) GABA(A) receptors in opiate-dependent animals, which switch from a GABA-induced hyperpolarization of VTA GABA neurons to a GABA-induced depolarization. The aim of this study was to evaluate VTA GABA neuron excitability, GABA synaptic transmission to VTA GABA neurons and GABA-mediated DA release in the nucleus accumbens (NAc) under ethanol-naïve and dependent conditions. To accomplish these studies, we used standard whole-cell and attached-cell mode electrophysiological techniques to evaluate acute and chronic ethanol effects on VTA GABA neurons in GAD GFP mice, which enabled the visual identification of GABA neurons in slice preparation. In naïve animals, superfusion of ethanol (IC50 = 30 mM) and GABA(A) receptor agonist muscimol (IC50 = 100 nM) decreased VTA GABA neuron firing rate in a dose-dependent manner. Compared to saline-injected controls, in animals made dependent on ethanol by twice daily injections of 2.0 g/kg ethanol, neither ethanol nor muscimol significantly affected VTA GABA neuron firing rate on average. We and others have found that ethanol decreases DA release at terminals, as measured by fast scan cyclic voltammetry. We have recently reported that ethanol inhibition of DA release at terminals in the NAc of ethanol-naïve animals is mediated by GABA, possibly from VTA GABA neurons that project to the NAc. We evaluated the effects of ethanol on DA release in the same ethanol-dependent animals. Compared to controls, superfusion of ethanol did not significantly affect DA release. Together, these findings suggest that VTA GABA neurons undergo a switch in GABA(A) receptor function with chronic ethanol, which results in a corresponding switch in DA release, perhaps resulting from adaptations in VTA GABA neuron input to the NAc.

Adam Jorgensen, Brigham Young University Life Sciences Arrhythmia is a serious heart defect that effects 14 million people in the United States. It is characterized by irregular rhythm in the electrical impulses of the heart. Arrhythmia can cause sudden cardiac arrest and stroke. Recent developments in cardiac ablation have helped in the treatment of arrhythmia. Cardiac ablation works by scarring tissue in the heart, thus preventing abnormal electrical signals to travel through the myocardium. The three-dimensional map created in this project will improve the accuracy of cardiac ablation by offering a more dynamic view of the human heart and associated nerve branches. By properly articulating the intricate nerve branching of the heart, surgeons will be able to better target the nerves themselves when scarring heart tissue, thus allowing a less invasive procedure.

Bradley Prince, Brigham Young University Life Sciences Learning and memory occur due to adaptive brain changes in response to our environment. These changes are mediated by synaptic plasticity, particularly within the hippocampus, where spatial and declarative memories occur. Plasticity can either strengthen or weaken synapses, known as long-term potentiation (LTP) or long-term depression respectively. While many forms of synaptic plasticity are N-methyl-D-Aspartate receptor-dependent, recently endocannabinoids were identified to mediate several new forms of hippocampal synaptic plasticity. Endocannabinoids bind to receptors such as cannabinoid receptor 1 (CB1) and transient receptor potential vanilloid 1 (TRPV1), and mediate several forms of plasticity, including in the hippocampus. However, new research has demonstrated a non-CB1/TRPV1-dependent endocannabinoid synaptic plasticity in the hippocampus. While the receptor(s) involved is currently unknown, several potential candidate receptors that bind the endocannabinoid anandamide have been identified. These are orphan G-protein coupled receptors (GPRs) whose distribution in the brain and/or function is unknown. GPR55 is of particular interest as it activates second message systems, including increasing intracellular calcium. Using quantitative RT-PCR, electrophysiological and memory behavioral tasks we examined hippocampal GPR55 expression and function. GPR55 is indeed expressed in hippocampus of both rats and mice. Cellular expression is currently being examined and appears to be rare in interneurons and more likely expressed by pyramidal cells. Interestingly, application of the GPR55 agonist LPI (2 µM) to wild-type mice demonstrates a decrease of LTD in brain slices. This LPI effect was not noted in GPR55 knock-out mice in the presence of LPI. This data suggest GPR55 is physiologically relevant in the hippocampus. This is the first direct evidence we are aware of that a novel endocannabinoid receptor directly effects hippocampal LTD. Because neurodegeneration that affects memory is typically associated with an increase in LTD, this provides a potential target to slow the advance of diseases such as Alzheimer’s.

Audrey Butler, Utah Valley University Life Sciences High-frequency (HF) ultrasound has been shown to be sensitive to a range of breast pathologies, and is being explored for the intra-operative assessment of lumpectomy margins. This sensitivity is believed to arise from microstructure-dependent interactions of ultrasound in the tissue. The objectives of this study were to develop breast tissue phantoms with microstructures that accurately mimic the histology of normal and malignant tissue, and to determine the effects of these microstructures on HF ultrasonic spectra (10-100 MHz). Phantoms were created from a mixture of water, gelatin, and soluble fiber. To simulate various breast tissue histologies, polyethylene beads, polyethylene fibers, and nylon fibers with a range of diameters were embedded into phantoms. Microstructures ranging from randomly dispersed beads to bead-fiber constructs resembling terminal ductal lobular units (TDLUs) were modeled and tested. Pitch-catch and pulse-echo measurements were acquired using 50-MHz transducers, a HF pulser-receiver, and a 1-GHz digital oscilloscope. Spectra were derived from the data and peak densities were determined from the spectra. Peak density, which is the number of peaks and valleys in a specified spectral range, has been shown to correlate with tissue complexity. Preliminary results from dispersed beads (58-925 µm diameter) of constant volume concentration (0.8%) indicated that the smaller beads produced higher peak densities than the larger beads with a consistent and statistically significant trend. These results substantially improve upon previous phantom studies and upon results from original breast cancer studies, demonstrating the strength of the HF ultrasound response to tissue microstructure. The higher peak densities can be attributed to either the higher number of scatterers for small beads or the size of scatterer in relation to the ultrasonic wavelength. These and other results from more advanced histologically accurate microstructures modeling TDLUs will be discussed.

Chance Christensen, Utah State University Life Sciences Affective disorders such as depression, phobias, schizophrenia, and post-traumatic stress disorder impair the ability to time in the seconds-to-minutes range, i.e., interval timing. According to the Relative Time-Sharing (RTS) model, presentation of task-irrelevant distracters during a timing task results in a delay in responding suggesting a failure to maintain subjective time in working memory, possibly due to attentional and working memory resources being diverted away from timing. Given that some anxiolytic medications have beneficial effects on attention and working memory, e.g., decreasing emotional response to negative events, we hypothesized that they would result in a decreased effect of distracters on the timekeeping abilities. We investigated the effect of acute administration of anxiolytic medication when anxiety-inducing task-irrelevant distracters were presented during an interval timing task, using methods similar to Matthews et. al. (2012) Frontiers in Integrative Neuroscience 6(111): 1-12. Results are discussed in relation to the brain circuits involved in RTS of resources, and the pharmacological management of affective disorders.

Josh Harvey, Brigham Young University Life Sciences Soil CO2 flux represents an important pathway of carbon transfer from ecosystems to the atmosphere. Soil CO2 flux can be altered by global warming-driven changes in seasonal temperature and water availability. Subalpine ecosystems have high levels of carbon in their soils that are stabilized by low temperatures and low microbial activity during long and snowy winter seasons. Subalpine ecosystems can be important sinks for carbon, storing carbon that otherwise would be in the atmosphere contributing to global warming. In our study we show how changes in temperature and water availability during springtime increase the levels of subalpine carbon output. So long as the carbon outputs outweigh carbon inputs, increases in soil flux would amplify global warming. The amplification of global warming would loop back to affect soil fluxes again (by raising temperatures, melting snow earlier, and changing precipitation patterns) thus creating a positive feedback system. Understanding what feedbacks are present in a climate system and their underlying mechanisms will improve our forecasts of changes in atmosphere chemistry and temperature.

Hillary Hansen, University of Utah Life Sciences Type 1 diabetes is an autoimmune disease where pancreatic β-cells are destroyed, resulting in insulin deficiency. Generating new β-cells from stem cells for treating diabetes will benefit from understanding their development in vivo. Pancreatic β-cells, along with all other pancreatic lineages arise from multipotent pancreatic progenitor cells (MPCs). Previous studies demonstrate that the structural and signaling protein β-catenin is required for the development of the exocrine acinar lineage. β-cells still differentiate in the absence of β-catenin, however, β-cell mass is dependent upon β-catenin. We determined that this dependency reflects a role for β-catenin in the maintenance of MPC patterning as well as for expansion of the progenitor pool. Whether our observed effects are due to the signaling or structural function of β-catenin remains unknown, and is the focus of this research. Using mouse genetics we are able to separate the structural and signaling functions of β-catenin. Eliminating both functions in PBKO (full knockout) mice produces decreased β-cell mass and irregular patterning. Decreased β-cell mass is also observed in PBsKO (signaling deficient) mice, though patterning remains unaffected. This suggests that pancreas growth is dependent upon canonical Wnt/β-catenin signaling, and that maintaining progenitor identity requires the structural role of β-catenin. Elucidating distinct roles for β-catenin could be used to drive stem cell-derived MPCs to expand and differentiate to the desired pancreatic cell fate.