Life Sciences

Graham Doherty, Westminster College Biology The Great Salt Lake is home to Artemia Franciscana, a species otherwise known as brine shrimp. These halophiles are able to live in extreme environments that have higher than average salt concentrations. Brine shrimp live their entire life cycles in the Great Salt Lake and can be found in both the north and south arm of the lake. Currently, the genetic information regarding the brine shrimp populations at different locations in the lake is underdeveloped. The Artemia populations live in different microenvironments throughout the lake with different physical characteristics and barriers between one another. The physical environment also affects the salt concentration in each microenvironment. Other studies have shown that the increased salinity of an environment accelerates the rate of change in the mitochondrial genome. We feel that different salinity levels in each microenvironment will create different amounts of genetic variation. Our goal is to determine if the distribution of genetic variation is different at different sites in the Great Salt Lake Artemia population.

Dakota Hawkins, Westminster College Arts and Sciences Abstract. Previous studies have documented effects of urbanization on the behavior, reproduction and survival of wildlife. Specifically, noise pollution in urban areas has been known to mask communication among several avian species. In a previous study in Mexico City, House Finches increased the frequency (pitch) of their songs to help mitigate the effects of low frequency urban noise. To document the average minimum frequency of House Finch song in Utah, we recorded House Finches singing from May 2012 to August 2012. Three sample sites with 1 km radii were established in Salt Lake City, Utah while a fourth site was sampled in Logan, Utah. Ambient sound was recorded at locations where songs were recorded to measure urban noise. Average minimum song frequencies and ambient noise were calculated for three sites. Frequency measurements were not significantly different among the three urban populations. Future studies will compare the minimum frequency of these urban populations to nonurban populations and investigate syllable structure and use.

Jeff Collins, Westminster College Biology The Great Salt Lake (GSL) has some of the highest mercury concentrations ever measured in surface waters. The accumulation of high levels of mercury, particularly its more toxic and readily biomagnified form, methylmercury, has been recorded in many species that inhabit or feed directly in the GSL, including waterfowl. However, no studies at the GSL, and very few studies elsewhere, have investigated the transfer of mercury from aquatic ecosystems to terrestrial ecosystems. We hypothesized that brine flies are able to accumulate mercury during their larval stages in the lake, then transfer this mercury to adjacent terrestrial ecosystems when they become flying adults. Concentrations of total mercury (HgT) and methylmercury (MeHg) were measured in samples of surface water and brine flies (larvae, pupae, and adults) collected once each month between February and July at Antelope Island, in the GSL. Samples were collected from two distinct sites: one along Gilbert Bay on the west side of the Island, and the other along Farmington Bay on the east. On average, HgT concentrations are greater in water samples from Farmington Bay (19.3 ± 9.0 ng/L unfiltered; 13.5 ± 10.1 ng/L filtered) compared to Gilbert Bay (8.5 ± 7.5 ng/L unfiltered; 9.2 ± 9.6 ng/L filtered). MeHg and HgT levels in brine flies displayed the opposite trend, with higher levels at Gilbert Bay (567 ± 123 ppb HgT; 425 ± 12 ppb MeHg) than at Farmington Bay (270 ± 60 ppb HgT; 208 ± 35 ppb MeHg). Potential explanations for the trends observed will be discussed.

Kristie Williamson, Weber State University Athletic Training Context: Cranial Nerve V (CN V; Trigeminal nerve) is responsible for facial sensation. CN V has three separate branches which include ophthalmic, maxillary and mandibular. The ophthalmic nerve (V1) carries sensory information from the forehead; the maxillary nerve (V2) carries information from the cheek; and the mandibular nerve (V3) carries information from the chin. It is important to test all three areas of cranial nerve V to accurately assess full nerve function. Previous research has indicated that pressure threshold is not affected by age, however, normative values for two-point discrimination for CN V have not yet been established and may prove useful in concussion evaluation. Objective: Initial investigation aimed at determining gender-specific normative values for CN V two-point discrimination. Design: Prospective repeated-measures design. Setting: This study was performed in the athletic training facilities on the campus of a large Division I institution. Patients or Other Participants: Convenience sample of 106 healthy students enrolled at our institution (43 females, average age: 23.2; 63 males, average age: 22.1). Participants had no history of concussion within the last year, no facial scaring or plastic surgery and not a current smoker. Interventions: Measurement was taken using a two-point discriminator (Disk-Criminator) on the mid-forehead, mid-cheek, and mid-chin. Participants closed their eyes while each measurement was taken. Light pressure was applied (force equal to approximately 10-15 grams to produce blanching of the skin). Measurements were taken three times on each of three facial locations, sequentially. The smallest number in millimeters (mm) to correctly discriminate one/two points was recorded. The two pressure points were applied at exactly the same time. Main Outcome Measure: Discrimination score for each test location (mid-forehead, mid-cheek, mid-chin). Nested average was calculated within subjects for each test location; average was calculated between subjects for each test location. One-way between-subjects ANOVAs were conducted to evaluate potential differences in gender for each test location. Results: Between-subjects average for mid-forehead was 7.8mm (+/2.9), for mid-cheek was 10.4mm (+/2.6), and for mid-chin was 5.9mm (+/1.9). There was a significant effect for gender for cheek normative value (p<0.01); average discrimination score for males was 11mm, average for female was 9.7mm.

Adam Olson, Brigham Young University Plant and Wildlife Sciences Forests systems of the Central Rocky Mountains rely on an intricate balance of natural disturbance cycles in order to develop properly. Forest fires are one such disturbance, however, certain fire characteristics, particularly fire severity, can vary widely across forest landscapes. In our study, we examined the influence of fire severity on aspen regeneration as well as aspen defense against wildlife and livestock browsing. Our results indicate that high or moderate burn severity is more favorable to aspen regeneration and survival. These areas of severe burn result in a higher density of aspen suckers, more vertical and lateral growth, greater chemical defense concentrations, and less browse damage than the neighboring plots of low or no burn. This data suggests that fire severity should be taken into account when considering plant regeneration and susceptibility to browse damage in burned landscapes.

Matthew Whited, Brigham Young University Biochemistry Several lines of evidence suggest that protein lysine acetylation pathways are deregulated in cancer (1). Moreover, deacetylase inhibitors are emerging as important anti-tumor therapeutics, suggesting that the forced reprogramming of protein-lysine acetylation is toxic to tumor cells. In this study we show that Sirt1, an NAD+-dependent Sirtuin deacetylase that promotes cancer cell survival, is aberrantly mislocalized to the cytoplasm of breast tumor cells. Moreover, the depletion of cytosolic Sirt1 by siRNA sensitizes breast tumor cells to paclitaxel-induced death. Previously, we developed a biotin-switch proteomics approach to identify cytosolic Sirt1 substrates (2). This approach yielded a variety of substrates with roles in metabolism, survival, and oxidative stress signaling. Our current work focuses on three of the proteins identified as Sirt1 substrates: SOD1, DJ-1, and 14-3-3z. SOD1 and DJ-1 both suppress oxidative stress-induced death, and high levels of 14-3-3z expression suppress chemotherapy-induced apoptosis and correlate with negative patient outcomes in breast cancer. Our preliminary results suggest that acetylation of DJ-1 and SOD1 suppress their anti-oxidant functions, while acetylation of 14-3-3z disrupts its binding to pro-survival proteins. Taken together, our data support a model in which cytosolic Sirt1 activates multiple pathways that work together to promote tumor cell survival.

Hyrum Shumway, Brigham Young University Microbiology and Molecular Biology Epigenetics is the study of factors of gene regulation that do not stem from the primary DNA sequence. One such example of epigenetic gene regulation is where DNA wraps around histone proteins to form nucleosomes. The positioning of nucleosomes is the first order of control for genic transcription. Wrapped DNA is less accessible for transcription compared to DNA that is nucleosome free. Model organisms for human epigenetics such as the nematode Caenorhabditis elegans are invaluable because of their ease in manipulation and because the components of nucleosomes (histone proteins and DNA) are highly conserved across phylogeny. The purpose of my particular research is to develop and validate a new protocol for tissue-specific isolation of nucleosomes through immunoprecipitation in young adult C. elegans. This protocol leverages green fluorescent protein fused to histones to research nucleosome positioning in the germ-line cells of C. elegans nematodes. When successful in our animal model, this procedure is the first step in allowing analysis of chromatin architecture of any tissue at any developmental or disease state including human cells. The widespread prevalence and implications of human disease is staggering in magnitude. Research is ongoing to decrease morbidity, increase prevention, and fight infection. With epigenetic tools, this vital research is benefitted and supplemented.

Michael McEntire, Brigham Young University Biology Female mate choice (intersexual selection) and male dominance interactions (intrasexual selection) can each play important roles in sexual selection. These two mechanisms tend to be discussed in isolation. The goal of this study is to explore the interaction between these two forms of sexual selection. To test this idea, we focused on the livebearing tropical fish system Poecilia gillii. We grouped males into similarly sized pairs and observed them for a week to determine which male was dominant. These pairs were then presented to females in mate choice trials to ascertain female preference. We also photo- graphed the males to determine coloration. We found that females were unable to detect dominant males without viewing the physical contest and that carotenoid coloration bore no effect on female preference. Females tended to choose the male to their left, suggesting the preferential use of their right eyes in making decisions on mate choice.

Ji Su Park, Brigham Young University Nutrition, Dietetics, and Food Science Selenium (Se) and soy have each been shown to reduce risk for prostate cancer when consumed at high levels. The purpose of this project was to define the molecular mechanisms of prostate cancer chemoprevention by Se and soy, and to describe how timing of dietary treatment modifies those effects. [C57BL/6 X FVB] F1 TRAMP (TRansgenic Adenocarcinoma of Mouse Prostate) male mice were fed stock diets high or low in soy, with or without a supplement of Se (4.0 mg Se/kg BW as Se-meth- ylselenocysteine) by gavage 5 d/wk in a 2 X 2 factorial design. Mice were exposed to different diets starting from conception, 6 weeks, or 12 weeks of age and were sacrificed at 18 weeks. Three-way ANOVA showed that supplemental Se increased serum and liver Se, with significant interactions with both time and soy intake. Selenium dosing decreased BW independent of soy intake and time of dietary intervention. Both Se and soy decreased epididymal fat pad weights, with Se’s effects being more pronounced in mice exposed to diets from conception than from 6 wk. Urogenital tract weights, a measure of prostate proliferation and tumor volume, were significantly reduced by Se supplementation (P<0.001) and soy (p=0.044), independent of time of dietary intervention. Histological examination of mouse prostates is in progress to determine dietary effects on disease progression. These data suggest that, in this model, chemopreventive efficacy of Se and soy does not differ between prenatal and early post-natal introduction.

Marcus Vranes, Brigham Young University Molecular Biology Recent studies have attempted to discover the correlation that exists between DNA methylation and nucleosome positioning, but none have explored the direct effect of DNA methylation on nucleosome formation and positioning. This proposed research will directly test the effects DNA methylation has on nucleosome positioning and whether the histone octamer has preferred sequences to which it binds, which will in turn add our understanding of gene expression and regulation. A better understanding of these concepts will help to aid efforts in gene therapy to better the quality of life of many who suffer from various genetic conditions.

Whitney Hoopes, Brigham Young University Microbiology and Molecular Biology HspB2 is one of eleven known small Heat Shock Proteins (sHSP) that is expressed in human heart and skeletal muscle. In response to cellular stress, heat shock proteins play a vital role to help misfolded proteins and proteins susceptible to denaturation maintain their structure. Two members of the sHSP family, CryAB and HspB2, are both required for normal heart function and cardiac muscle integrity. CryAB-deficient mice have defects in cardiac muscle structure whereas HspB2-deficient mice display energy deficits (Rajasekaran et al. 2007). The contrasting phenotypes of CryAB and HspB2 suggest differential roles for these molecular chaperones in the heart. HspB2 has been found to localize with the mitochondria in several different cell lines and overexpression of this sHSP has been shown to support survival of cells against heat stress (Nakagawa, 2001). To understand the role and mechanism of HspB2 in cardiac muscle energy regulation, we have used a yeast two-hybrid (Y2H) system to uncover the novel protein binding partners specific to HspB2. From screening a human heart cDNA library, HspB2 interacted with approximately 10,000 out of 20 million plasmids. We have sequenced more than 1000 of these putative interactors and have identified over 100 unique proteins. Over 40% of these protein partners are involved in mitochondrial energy production and another 25% in cardiac muscle structure maintenance. In addition, we have identified an interaction between HspB2 and the related sHSP CryAB. We then compared this data with mitochondrial HspB2 binding partners identified by mass spectroscopy (MS) through a large-scale bioinformatics analysis and constructed a protein-protein network. Y2H dependency tests were conducted to verify interactions identified by both Y2H and MS. Following yeast verification, a subset of the interactions were confirmed in C9H2 cardiac cells through coimmunopurification. Our research describes the first protein-protein interaction network for any sHSP, supports a role for HspB2 in mitochondrial energy production and suggests a link between mitochondrial energy production/redox stasis and stressed cardiac muscle maintenance.

Michael Peterson, Brigham Young University Biology A person’s predisposition to Alzheimer’s Disease is known to be influenced by both genetic factors as well as environmental factors. One know environmental factor is that known to affect risk for disease is early parental death. The purpose of this research is to better understand the complex factors that influence the disease by analyzing the relationship between the environmental factor of early parental death with genetic variants known to influence the disease. We used extant data from the CCSMHA, an ongoing aging study including 89.7% (5092 of 5677) of all of the eligible residents of Cache County, Utah. This data includes information about environmental and psychosocial stressor of the subjects as well as information about physical examinations, metal screenings, and individuals’ genotypes at many loci that are known to be related to Alzheimers Disease. We used multivariate logistic regression to determine the effect of early parental death by SNP interactions on risk for AD. For the analysis we cleaned the data by removing SNPs less than a minor allele frequency of 0.01, a Hardy-Weinberg equilibrium value of 110-6, and a maximum missing snp call of 0.2. Individuals were also removed if genotyping rate was less than 0.2. After filtering we had 262 cases, 239 controls and 0 missing Final Results will be presented at the Conference.

Rachel Perry, Brigham Young University Life Sciences Previous studies have indicated that Visinin-like protein (VILIP) may be a powerful tool in predicting disease progression and guiding prognosis of Alzheimer’s disease (AD). Cerebral spinal fluid (CSF) was collected from hundreds of individuals with varying levels of AD. The CSF was then analyzed for levels of VILIP protein using Luminex technology. SNPs were genotyped using the Illumina OmniExpress chip. SNPs found to have a Hardy-Weinberg frequency less than 1×10-4 were not included, assuming that this variance was due to a genotyping error. SNPs and samples missing more than five percent of the data were also not included. Following the cleanup of the data, an association test using linear regression was performed. Covariates used in the analysis included age, gender, and covariates that accounted for population stratification (PC1 and PC2). Over one hundred SNPs were found with a p-value less than 1×10-5. The genomic inflation factor for the generated data was 1. One marker showed significance at the genome-wide level. We have identified a genetic marker that shows significant association with CSF VILIP levels. This finding may provide insight into genetic control of VILIP levels, which may be a useful in understanding the pathological processes involved in AD.

Matthew Schneider, Brigham Young University Physiology and Developmental Biology Alzheimer’s disease, the most common form of dementia, affects millions of people per year. Research has shown that Alzheimer’s affects the hippocampus brain region, which is involved in learning and memory. Understanding learning and memory functions is imperative to comprehending both healthy brain functions and Alzheimer’s disease. Many researchers seek to understand both the causes and treatments of the disease, but tangible information remains elusive. Studies thus far have shown that to encode memories, the brain must change neural synapses to either strengthen or weaken those pathways, a process known as synaptic plasticity. Using electrophysiology techniques on mouse hippocampal slices, this project will provide further insight on memory formation and regulation by imitating synaptic plasticity mechanisms. I will look at a specific cellular pathway involving the protein receptor GPR55, which has recently been shown to induce synaptic plasticity. By understanding how the GPR55 pathway functions, this research will contribute to the understanding and treatments of Alzheimer’s and other neurodegenerative diseases.

David Marriott, Brigham Young University Physiology and Developmental Biology Acute stress has been shown to decrease Long-Term Potentiation (LTP) in the CA1 region of the mouse hippocampus. Additionally, stressed animals 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 + stress group where mice have voluntary access to a running wheel (for 30 days) before undergoing the stress protocol. We hypothesize that exercised animals will experience a protective effect against the reductions in CA1 LTP. In the stress only group, preliminary data shows a modest stress effect on LTP, yet we are learning that factors such as controllability of the stressor or the ability to develop coping mechanisms might potentially attenuate

Tara Hammond, Brigham Young University Microbiology and Molecular Biology Genetic diseases, including Alzheimer’s, cystic fibrosis, and many cancers, can be detrimental to individuals and their families. Gene therapy can possibly cure these diseases by inserting a correct copy of the gene into the chromosome, upregulating good genes, or downregulating the harmful gene. When DNA is packaged into a cell, it wraps around histones-an octamer made up of two tetramers, each containing four different subunits to create nucleosomes. Where the nucleosome sits on the DNA sequence determines whether or not a gene can be transcribed. In heterochromatin, nucleosomes are denser and DNA is tightly packed, thus causing genes to not be transcribed. Euchromatin contains looser packed nucleosomes and therefore has higher transcription levels. This project seeks to determine if modified nucleosomes have DNA sequence preferences. We are working with histone H3 to tri-methylate lysine 4, which has been shown to correlate with euchromatin. The modified histone will be used to create octamers. C. elegans DNA will be added to modified histones and to unmodified histones and allowed to create nucleosomes. The wrapped DNA will be sequenced, allowing us to compare the modified and unmodified nucleosome DNA preference. The difference in preference will enhance our ability to know how to move nucleosomes, thus aiding in gene therapy.

Kristian Johnson, Dixie State University Biology Antimicrobial methods, such antibiotics and Ultraviolet (UV) irradiation, have been a means of suppressing prokaryote proliferation for nearly a century. Over the last several years, scientists have found that numerous strains of prokaryotes have developed resistance to antibiotics. Concurrently, the process of bacterial irradiation using UV-C is common practice in a variety of sterilization applications. As revealed in the seminal work by Chang et al. inactivation curves for Microorganisms such as Staphylococcus aureus (Staph) were established in 1985. Their values indicate survival rates based on Intensity, which is defined as the time of UV irradiance per unit area. Similar to the evolutionary evidence of antibiotic resistance, we are interested in the selective pressure UV-C has on Staph. By recapitulating Chang’s experiment nearly 30 years later, our preliminary results indicate an increased resistance to UV-C in Staph. In this experiment, we determine a current UV-C dose-dependent kill rate function for Staph.

Chancen Hall and Nichkolas Hadley, Dixie State University Biological Sciences Batrachochytrium dendrobatidis (chytrid fungus) is prevalent worldwide, and the resulting chytridiomycosis has contributed to at least 168 amphibian species extinctions. In 2010, B. dendrobatidis was discovered in the greater Zion National Park area of southwestern Utah. Because few populations have shown resistance to chytridiomycosis, we decided to explore the effects of this disease on populations of Hyla arenicolor (canyon tree frog). We tracked the spread of B. dendrobatidis by testing skin samples taken annually from several different canyons and monitored population sizes. During the three years of our study, infected populations did not show subsequent population declines. This suggests that H. arenicolor population size in this region is unaffected by B. dendrobatidis. In the future, testing hypothesized explanations for surviving infection could help us identify populations not at risk and thus allocate conservation resources more efficiently.

Rachel Schneider, Brigham Young University Neuroscience The ability to create distinct memories for very similar stimuli and events is called pattern separation. Pattern separation is thought to be dependent on neurogenesis (the birth of new neurons) in the dentate gyrus, a subregion of the hippocampus. Neurogenesis is reduced in depression, as is overall memory performance. It has been proposed that depression negatively impacts pattern separation abilities, however a link between depression and performance in pattern separation memory tasks has yet to be identified. Accordingly, we designed a study to investigate the relationship between pattern separation performance and level of depression. Eighty-two participants completed a pattern separation memory test and a set of questionnaires to gauge their level of depression. During the task, participants were presented with 600 images one at a time on a computer screen in a continuous recognition paradigm. Participants were asked to determine whether each image was new, old, or similar. Images seen for the first time during the task qualified as “new”, images that were repeated following a variable delay qualified as “old”, and images that were similar to previously presented stimuli, but not exactly the same, qualified as “similar”. A pattern separation score was calculated based on the proportion of correctly identified similar stimuli. We found a negative correlation between depression scores and pattern separation scores (r(82) = – 0.301, p < 0.01). This relationship held constant even when we controlled for other factors known to affect neurogenesis, such as exercise and anxiety levels. These results provide support for the theory that depression is negatively related to pattern separation performance, possibly due to a decrease in neurogenesis in the hippocampus.

Ryan Williamson, Brigham Young University Physiology and Developmental Biology The hippocampus is thought to mediate learning and memory by altering the strength of synapses within its circuitry. In many cases, this synaptic plasticity can be induced by intracellular signaling molecules. Lipid-based intracellular signaling molecules called endocannabinoids have been shown to modulate or mediate synaptic plasticity among hippocampal pyramidal cells and stratum radiatum interneurons; however, the role of endocannabinoids in mediating synaptic plasticity among interneurons in the stratum oriens is still unclear. Our goal was to determine whether stratum oriens interneurons have the machinery necessary for endocannabinoid production and, if so, whether this machinery is expressed in a sub-type specific manner. To do this, we used patch clamp electrodes to extract single cells from rat hippocampal slices and analyzed the expression of endocannabinoid biosynthetic enzyme mRNA using quantitative real-time PCR. In this analysis, we examined cellular expression of two interneuron markers, GAD65 and GAD67, as well as several calcium-binding proteins and neuropeptides to determine interneuron subtype. We also analyzed cellular expression of several endocannabinoid biosynthetic enzymes, including N-acyl phosphatidylethanolamine phospholipase D, diacylglycerol lipase alpha, and 12-lipoxygenase, as well as type I metabotropic glutamate receptors. Preliminary data suggests that stratum oriens interneurons express mRNA necessary for endocannabinoid biosynthetic enzymes. Additionally, we identified interneurons that coexpress mRNA for somatostatin and diacylglycerol lipase, suggesting that O-LM cells or another somatostatin-positive interneuron subtype may possess the enzymes necessary to produce the endocannabinoid 2-arachidonoylglycerol. Further work will allow us to examine how endocannabinoid biosynthetic enzyme expression correlates with other interneuron subtypes in the stratum oriens.

Aaron Sharp, Brigham Young University Biology The Cache County study on memory, health, and aging has played a significant role in several studies. However, there is some potential skepticism in the scientific community about its sample. The population in Cache County is derived from a diverse group of founders, but it is perceived by some to be an isolated population. If so, conclusions discovered there might not apply to other populations. Our objective is to compare the Cache County data to a panel of genetic data—provided by the International HapMap Project and the Alzheimer’s Disease Neuroimaging initiative—that is known to be representative of typical European-American populations. Doing so will indicate whether the genetic diversity in the Cache County sample is characteristic of an isolate or not. Analysis will be done using the open source “Plink” analysis toolset, including the –cluster and –mds-plot computational algorithms. Using –cluster groups individuals according to identity by state distances. The –mds-plot algorithm creates a scatter-plot of the individuals in 2-dimensional space, identifying any systematic difference between the Cache County data and the general population. We expect that the Cache County data will be representative of general European-American populations, because of its diverse group of founders.

Rachel Nettles, Brigham Young University Plant and Wildlife Sciences Background/Questions/Methods

Caitlin Munger, Brigham Young University Biology Alzheimer’s is a fatal, non-treatable neurodegenerative disease and the most common cause of dementia. While no one gene has been found to determine the development of Alzheimer’s, past studies have established a strong hereditary influence on Alzheimer’s. So far, only 5 genes have been found which replicably contribute to the genetic risk of developing Alzheimer’s. However, the gene for Chlolesteryl Ester Transfer Protein (CETP) has been identified as a possible new contributor to the genetic risk factor. In order to test this association we obtained data on over 4000 subjects studied in the Cache County Study on Memory, Health and Aging over a 15-year period. This data included DNA samples, cognitive decline rates and incidence of dementia–particularly Alzheimer’s Disease. DNA samples were SNP genotyped using quantitative PCR. The SNP genotypes and corresponding phenotypes for each subject were then analyzed for association usingmixed linear models and for survival, or the amount of time until the disease appeared, using Cox proportional hazard models. We found a correlation between the V405I SNP and a decreased rate of cognitive decline. We found that for each additional G the rate of decline decreased by 0.6 points per year on the MMSE test. The identification of CETP as a player in the genetic risk for Alzheimer’s and dementia will provide much needed information on the genetic factors involved in dementia and allow for possible future therapeutic targets.

Joseph Moulton, Brigham Young University Physiology and Developmental Biology With the advent of recent mutations in the influenza A viral genome, drugs that previously blocked the proton flux responsible for disassembly of the viral envelope and exposure of viral RNA to the transcriptional machinery of the host cell have become ineffective. Our study of the M2 hydrogen ion channel responsible for this flux has led to a vastly-increased under- standing of the mechanisms behind the conductance activity and potential blockage of these transmembrane tetramers. By embedding M2 proton channel subunits of the S31N mutant strain into liposomal bilayers and suspending these bilayers in the buffers and ionic gradients characteristic of the intracellular environment, we have been able to simulate and observe nor- mal functioning of the influenza A virus. Using these liposomal bilayers, we have developed a series of experimental protocols to test a variety of amantadine- and rimantadine-related drugs for successful blockage of M2 S31N proton conductance. Our research presentation will be centered around the mechanisms of this channel and the favorable results that we have obtained from many of these drugs.

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