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Student Research Fellows 2015

Janelle Dykstra, Pharmacy Major

Faculty Mentor: Kim Hancock, Pharmacy, Pharmaceutical Sciences

The Effect of Sleeve Gastrectomy on Venlafaxine Dissolution: An In Vitro Biorelevant Model

Laparoscopic Sleeve Gastrostomy (LSG) is becoming an increasingly utilized form of bariatric surgery for the treatment of obesity. LSG reduces the size of the stomach from approximately 1 Liter to approximately 100 milliliters and reduces gastric acid production in the stomach. Reduced gastric acid production causes the pH of the stomach to increase. Both the volume change and the change in pH could alter dissolution of drugs. Venlafaxine, a common antidepressant taken pre and post bariatric surgery, was used to determine if dissolution was affected by the LSG altered environment. Biorelevant dissolution media simulating both the “normal” stomach and the LSG stomach was developed. Dissolution tests were run using these biorelevant environments. Dissolution of venlafaxine was decreased in the bariatric environment. This suggests that drug dissolution may be altered in patients following LSG, potentially reducing drug absorption.

Amanda Kruse, Pre-Optometry Major

Faculty Mentor: Christopher DeFraia, Arts & Sciences, Biological Sciences

Characterization of Plant Development Genes in Arabidopsis thaliana

Arabidopsis is a model organism with many characteristics that allow plant genes to be efficiently studied. When gene function in Arabidopsis is determined, that knowledge can help produce better crops because most Arabidopsis genes are also present in crops plants. Arabidopsis has many mutated plant lines, allowing us to study the function of the mutated genes. Each mutant plant line has a mutation in one gene, causing the gene to no longer function. We screened ~1500 mutant plants to look for any differences in appearance. Any change in appearance is likely caused by the mutation of the gene, suggesting that the gene functions in the affected aspect of plant development. When a mutant with altered appearance was identified, the mutant line was regrown to confirm this result. We also performed a series of bioinformatics tests to better understand the mutated genes. We identified two plant lines that had pointed and spiked leaves, respectively, implying that their mutated genes function in leaf shape. We confirmed that both mutant plants had both gene copies mutated by performing PCR. Leaf shape determines the amount of biomass produced. Higher crop yield and better produce can be attributed to the most effective leaves.

Hayden Larson, Optometry Major

Faculty Mentor: Amy Dinardo, Optometry

Analyzing the Neutralization of Brown Bottle Hydrogen Peroxide in Hydrogen Peroxide Contact Lens Care Systems

Hydrogen peroxide (H2O2) contact lens solutions are a popular and effective way to clean, disinfect, and store contact lenses. Occasionally, brown bottle peroxide is used as a cheap alternative to the supplied solution. Solutions are bottled at 3% peroxide (30,000 ppm) and are neutralized to a safe concentration over a period of several hours (below a 100 ppm maximum value). This experiment analyzed the neutralization process of brown bottle hydrogen peroxide in three commonly used contact lens cases. Samples were taken every 10 minutes for the first hour and at every following hour until two consecutive neutral (0 ppm) readings were made. Solutions were neutralized using the platinum-disc catalyst in their supplied cases and percent remaining peroxide determined using a potassium permanganate assay (USP). All three cases showed a significant drop in H2O2 concentration within the first 10 minutes, plateauing around two hours. Of the three, Alcon Clear Care was shown to neutralize the slowest of the brands, compared to Peroxiclear (Bausch + Lomb) and Sauflon (bottled for Walmart as Equate).

Kacie Krogman, Social Studies Education Major; Art History and English Teaching Minor

Faculty Mentor: Rachel Foulk, Arts & Sciences, Humanities

Love, Beauty, and Sexuality: Women in the Guise of Venus on Ancient Roman Sarcophagi

Venus was the ancient Roman goddess of love, beauty, and sexuality. She was believed to be the divine mother of the Romans and held an important place in the Roman pantheon. This project explores how Roman women adopted the iconography of Venus to express that they personally embodied the values for which she stood. In the funerary context, women were often represented in the guise of Venus on their sarcophagi (stone coffins) with their own recognizable portrait, but with the body of Venus. In these hybrid images, attributes of Venusv— including nudity and recognizable poses—are used to refer to the goddess. Analyzing over forty works of art, we have established a typology of the ways in which women are portrayed as Venus on ancient Roman sarcophagi. The range of depictions of women in the guise of Venus helps us to understand the roles women played in ancient Roman society. Historical sources indicate that upholding the values associated with Venus was not just a personal choice, but a societal expectation. These works of art encourage women in marriage, motherhood, and domesticity.

Sarah Mathie, Biology Major

Faculty Mentor: Anne Spain, Arts & Sciences, Biological Sciences

Nutritional Factors Affecting Growth of Bacterial Isolates A1 and A3

Whether it's to flee from predation or to move toward nutrients, cellular motility is an important factor for bacterial competition and survival. Paenibacillus sp. strains A1 and A3 are bacterial isolates that display a unique "scattering" growth pattern when grown on solid surfaces. Preliminary research has shown that percentage of the solidifying agent (agar) in solid medium is a major component in determining surface growth pattern. However, further questions remain as to what nutritional factors affect growth and surface growth pattern of these two bacterial isolates. In this study, growth experiments in liquid minimal media with the addition of a variety of carbon sources showed that the isolates grow optimally with glucose, sucrose, and maltose. Growth experiments on different solid media types, [also displayed varying surface growth patterns; isolates grown on glycerol yeast extract agar displayed the optimal scattering phenotype whereas isolates grown on media containing complex polymers, such as gelatin, were stagnant] (did not display surface movement). Based on results obtained, future experiments will be designed to target specific nutrients that either promote or inhibit the scattering growth pattern. These findings will be important to better predict the spread of bacteria in environmental settings.

Danielle Winkler, Public Health Major

Faculty Mentor: Emmanuel Jadhav, Health Professions, Public Health

Contemporary Vaccination Trends Survey

Vaccination coverage levels among adults (18 years to 65 years) are low. The stable vaccination waiver rates in MIcoupled with low vaccination coverage levels among adults could lead to geographical clustering of vaccine preventable diseases. Mistaken information and poor communication are among some of the known barriers to vaccination uptake. Not much is known about the attitude, experiences and barriers that influence the vaccination choices of young adults. This study will examine the contemporary trends in young adult vaccination. The objectives of the study include to categorize characteristics of young adults by vaccination waiver status and to identify contemporary trends associated with benefits, barriers and influencers of adult vaccination. The study design involves a cross-sectional survey of Ferris State University students. The survey is currently open. Exploratory and bivariate analysis will be used to categorize characteristics and identify trends. Findings of the study will inform development of adult vaccination programs at the campus, local and regional levels.

Mason Moody, Pharmacy Major

Faculty Mentor: Tracey Boncher, Pharmacy, Physical Sciences

Solid Phase Synthesis of Antidepressive PPAR Receptor Agonists

19 million Americans are diagnosed with depression each year, and 15% of those people will go on to commit suicide. There are a variety of anti-depressive medications on the market, but they are associated with many adverse side effects. The need for further drug discovery is vital. Dr. Boncher's research has provided compound 9 that, when compared to a known anti-depressant ProzacR, has shown to be quite active without the stimulant effects. This is important because psychostimulant effects can often be confused as anti-depressant effects. These compounds are PPAR delta/gamma dual agonists and have proven to benefit other neurological diseases as well. A series of compounds similar to our lead have been designed, synthesized and purified to analyze their binding affinities for PPAR delta/gamma as well as their anti-depressant effects on a mice model. Solid phase synthesis and solution phase organic synthesis were used to build these molecules. After 10-weeks of research we have three molecules and another five that just need the final HPLC purification to complete a new series of 8 compounds to be further analyzed. All compounds will be tested for activity and computational analysis of binding affinity. Results will be published in a peer-reviewed scientific journal.

Shaughna Langerak, Biotechnology and Environmental Biology Major

Faculty Mentor: Changqi Zhu, Arts & Sciences, Biological Sciences

Functional Study of Drosophilia Activin Signaling in Aging Regulation in Fruit Flies

Drosophila Activin signaling is a branch of Transforming Growth Factor β (TGF-β) signaling in fruit flies. This signaling pathway is well conserved from fruit flies to vertebrate animal species and is known to play a large role during development. Previous published work has implicated this signaling pathway in regulation of cell proliferation, apoptosis, larval axon guidance, photoreceptor axon targeting, and neuromuscular junction development. Our study has shown that knocking down various signaling components from Drosophila Activin signaling pathway either in the whole body or the muscle tissues in adults shortened the mean as well as maximum life span. In addition, our preliminary results show that overexpression of many components of this pathway may extend life span. Because the signaling components and events from Drosophila Activin signaling are highly conserved across different animal phyla (species), we believe that a thorough study of the function of Drosophila Activin signaling in aging regulation in fruit flies can shed light on the roles that the vertebrate TGF-β signaling plays in aging regulation and disease development during the aging process such as Sarcopenia, Cardiovascular disease, Neurodegeneration, Cancer, general loss of the ability to maintain homeostasis resulting in eventual organ failure, and accelerated aging diseases caused by genetic disorders.

Jeffrey Reaerdon, Chemistry Major

Faculty Mentor: Daniel Adsmond, Arts & Sciences, Physical Sciences

Finding the Sweet Spot for Ternary Co-Crystal Formation

A cocrystal is crystal made up of two or more components in a definite stoichiometric ratio. While structures of hundreds of binary cocrystals are known, few ternary cocrystals have been synthesized to date. The goal of this work was to determine the range of conditions under which three newly synthesized ternary cocrystals can form. Each of the three cocrystals contained acridine, 2-amino-4,6-dimethylpyrimidine and a carboxyphenol. Crystals were grown from sixteen different solvents and solvent mixtures as well as five different stoichiometric ratios. The cocrystals formed in solution were analyzed using infrared spectroscopy to determine if a cocrystal was formed, and nuclear magnetic resonance spectroscopy to determine the ratios of components. After completing 120 experiments and analyzing 201 samples, it was clear that the ability to synthesize each of the three cocrystals under different conditions varied. The ternary cocrystal constructed using 6-hydroxy-2-naphthoic acid proved to be the most readily reproducible, forming using five different starting material ratios and in fourteen different organic solvents. However, the ternary cocrystals constructed using m-hydroxybenzoic acid and trans-ferulic acid could only be reproduced under two sets of conditions. These experiments did, however, yield other cocrystals including a possible ethyl acetate solvate cocrystal.

Eleanor Ohm, Business Major; Mathematics Minor

Faculty Mentor: Erin Militzer, Arts & Sciences, Mathematics

'Cops and Robber' on Graphs

Cops and Robber on graphs is a game introduced in the early 1980s. A graph consists of vertices (dots) and edges (straight lines connecting the dots). The first player has a set of cops, who is placed first, and the second has a single robber who is placed after the cops. The objective of the game is for the cop(s) to catch the robber by occupying the same vertex through a series of movements (along one edge to an adjacent vertex per turn). The cop number of a graph is how many cops it would take to capture the robber. We looked at a variation of the game where we have fewer cops than the cop number. We then consider how many devices the cop(s) will need to win. The devices are traps and doors which are placed on vertices to prevent the robber from entering. Traps are able to be moved and doors are stationary. Our research has found general results on the number and placement of doors on various classes of graphs and specific graphs. We also found strategies for a series of movements of traps that make the cops able to win.

Rachel Kempistry, Biology, Pre-Med Major; Psychology Minor

Faculty Mentor: M. Beth Zimmer, Arts & Sciences, Biological Sciences

Changes in Hippocampal Neuro-Chemistry after Spinal Cord Injury

Spinal cord injuries (SCI) result in the damage of nerves extending from the brain to all areas of the body, leading to disturbances in sensory and motor signals below the injury site. This study hypothesizes that the hippocampus, the region of the brain involved in learning and memory, undergoes neurochemical changes after an SCI. Learning and memory was assessed in SHAM (control) and SCI Sprague-Dawley rats through the use of the Morris Water Maze. Results obtained were statistically analyzed and compared to a similar study involving SHAM and SCI Long Evans rats. The mechanisms by which animals retain memories and acquire new information are still unknown. In order to gain a better understanding of these processes, we have begun investigating varying levels of specific proteins found in the hippocampus of SHAM rats compared to SCI rats. We are in the process of examining Brain-Derived Neurotrophic Factor (BDNF) levels, known to be involved in learning and formation of new synapses, by implementing the Western Blot analysis, an immunostaining technique, on the hippocampal tissues. Analyzing BDNF levels in the upcoming weeks may help to explain differences in learning and memory in SCI and provide insight into the mechanics of learning.

Jacqueline Saunders, Pharmacy Major

Faculty Mentor: Eric Nybo, Pharmacy, Pharmaceutical Sciences

Synthesis of Valerenadience Anxiolytic Drugs in an Engineered Microbial Host

Terpenes are a large class of volatile organic compounds naturally produced by plants and some insects. They are used as fragrances, biofuels, and even medicinal compounds. The root of Valerena officinalis yields a terpene derivative called valerenic acid, which holds important medicinal properties for treatment of insomnia and anxiety. Development of valerenic acid as a drug is inhibited by low production in the native plant root and differences in production between plant cultivars. Our strategy to develop new valerenic acid analogues focuses on production of valerenadiene, an intermediate compound with lower anxiety reducing activity, in an E. coli host. Our strategy is two-fold: 1) first, we will engineer the valerenadiene synthase gene into the organism and 2) we will enhance in vivo levels of an important key substrate in the production of valerenadiene known as farnesyl diphosphate (FPP). We envision this production platform to be a forward movement in the development of new pharmacologically active valerenic acid analogues.