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Description
A major challenge with tissue samples used for biopsies is the inability to monitor their molecular quality before diagnostic testing. When tissue is resected from a patient, the cells are removed from their blood supply and normal temperature-controlled environment, which causes significant biological stress. As a result, the molecular composition and integrity undergo significant change. Currently, there is no method to track the effects of these artefactual stresses on the sample tissue to determine any deviations from the actual patient physiology. Without a way to track these changes, pathologists have to blindly trust that the tissue samples they are given are of high quality and fit for molecular analysis; physicians use the analysis to make diagnoses and treatment plans based on the assumption that the samples are valid. A possible way to track the quality of the tissue is by measuring volatile organic compounds (VOCs) released from the samples. VOCs are carbon-based chemicals with high vapor pressure at room temperature. There are over 1,800 known VOCs within humans and a number of these exist in every tissue sample. They are individualized and often indicative of a person’s metabolic condition. For this reason, VOCs are often used for diagnostic purposes. Their usefulness in diagnostics, reflectiveness of a person’s metabolic state, and accessibility lends them to being beneficial for tracking degradation. We hypothesize that there is a relationship between the change in concentration of the volatile organic compounds of a sample, and the molecular quality of a sample. This relationship is what would indicate the accuracy of the tissue quality used for a biopsy in relation to the tissue within the body.
ContributorsSharma, Nandini (Co-author) / Fragoso, Claudia (Co-author) / Grenier, Tyler (Co-author) / Hanson, Abigail (Co-author) / Compton, Carolyn (Thesis director) / Tao, Nongjian (Committee member) / Moakley, George (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Dielectrophoresis has been shown in the recent past to successfully separate bioparticles of very subtle differences at high resolutions using biophysical forces. In this study, we test the biophysical differences of methicillin resistant and susceptible Staph. aureus that are known to have very similar genomes by using a modified gradient insulator-based dielectrophoresis device (g-iDEP). MRSA is commonly seen in hospitals and is the leading killer of infectious bacteria, claiming the lives of around 10,000 people annually. G-iDEP improves many capabilities within the DEP field including sample size, cost, ease of use and analysis time. This is a promising foundation to creating a more clinically optimized diagnostic tool for both separation and detection of bacteria in the healthcare field. The capture on-set potential for fluorescently tagged MRSA (801 ± 34V) is higher than fluorescently tagged MSSA (610 ± 32V), resulting in a higher electrokinetic to dielectrophoretic mobility ratio for MRSA. Since the strains have proven to be genomically similar through sequencing, it is reasonable to attribute this significant biophysical difference to the added PBP2a enzyme in MRSA. These results are consistent with other bacterial studied within in this device and have proven to be reproducible.
ContributorsSmithers, Jared (Author) / Hayes, Mark (Thesis director) / Woodbury, Neal (Committee member) / School of Criminology and Criminal Justice (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Diabesity is a global epidemic affecting millions worldwide. Diabesity is the term given to the link between obesity and Type II diabetes. It is estimated that ~90% of patients diagnosed with Type II diabetes are overweight or have struggled with excess body fat in the past. Type II diabetes is characterized by insulin resistance which is an impaired response of the body to insulin that leads to high blood glucose levels. Adipose tissue, previously thought of as an inert tissue, is now recognized as a major endocrine organ with an important role in the body's immune response and the development of chronic inflammation. It is speculated that adipose tissue inflammation is a major contributor to insulin resistance particular to Type II diabetes. This literature review explores the popular therapeutic targets and marketed drugs for the treatment of Type II diabetes and their role in decreasing adipose tissue inflammation. rAGE is currently in pre-clinical studies as a possible target to combat adipose tissue inflammation due to its relation to insulin resistance. Metformin and Pioglitazone are two drugs already being marketed that use unique chemical pathways to increase the production of insulin and/or decrease blood glucose levels. Sulfonylureas is one of the first FDA approved drugs used in the treatment of Type II diabetes, however, it has been discredited due to its life-threatening side effects. Bariatric surgery is a form of invasive surgery to rid the body of excess fat and has shown to normalize blood glucose levels. These treatments are all secondary to lifestyle changes, such as diet and exercise which can help halt the progression of Type II diabetes patients.
ContributorsRobles, Alondra Maria (Author) / Woodbury, Neal (Thesis director) / Redding, Kevin (Committee member) / Allen, James (Committee member) / Hendrickson, Kirstin (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The Heliobacterial Reaction Center (HbRC) is the simplest Type I Reaction Center (RC) known today. However, upon illumination it has been found to produce menaquinol, and this has led to experiments investigating the function of this reduction scheme. The goal of the experiment was to investigate the mechanisms of menaquinol production through the use of Photosystem II (PSII) herbicides that are known to inhibit the QB quinone site in Type II RCs. Seven herbicides were chosen, and out of all of them terbuthylazine showed the greatest effect on the RC in isolated membranes when Transient Absorption Spectroscopy was used. In addition, terbuthylazine decreased menaquinone reduction to menaquinol by ~72%, slightly more than the reported effect of teburtryn (68%)1. In addition, terbuthylazine significantly impacted growth of whole cells under high light more than terbutryn.
ContributorsOdeh, Ahmad Osameh (Author) / Redding, Kevin (Thesis director) / Woodbury, Neal (Committee member) / Allen, James (Committee member) / School of Molecular Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Predicting the binding sites of proteins has historically relied on the determination of protein structural data. However, the ability to utilize binding data obtained from a simple assay and computationally make the same predictions using only sequence information would be more efficient, both in time and resources. The purpose of this study was to evaluate the effectiveness of an algorithm developed to predict regions of high-binding on proteins as it applies to determining the regions of interaction between binding partners. This approach was applied to tumor necrosis factor alpha (TNFα), its receptor TNFR2, programmed cell death protein-1 (PD-1), and one of its ligand PD-L1. The algorithms applied accurately predicted the binding region between TNFα and TNFR2 in which the interacting residues are sequential on TNFα, however failed to predict discontinuous regions of binding as accurately. The interface of PD-1 and PD-L1 contained continuous residues interacting with each other, however this region was predicted to bind weaker than the regions on the external portions of the molecules. Limitations of this approach include use of a linear search window (resulting in inability to predict discontinuous binding residues), and the use of proteins with unnaturally exposed regions, in the case of PD-1 and PD-L1 (resulting in observed interactions which would not occur normally). However, this method was overall very effective in utilizing the available information to make accurate predictions. The use of the microarray to obtain binding information and a computer algorithm to analyze is a versatile tool capable of being adapted to refine accuracy.
ContributorsBrooks, Meilia Catherine (Author) / Woodbury, Neal (Thesis director) / Diehnelt, Chris (Committee member) / Ghirlanda, Giovanna (Committee member) / Department of Psychology (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Fruit flies show a strong attraction to fruit odors. Most fruit odors, including strawberry scent, are complex multimolecular mixtures comprised of many chemically distinct constituents. How animals are able to process these mixtures and derive behaviorally relevant information is largely unknown. A new procedure was created to test odor preference for Heisenberg canton-s strain of Drosophila melanogaster. 30 flies were cold anesthetized at 4.2°C for 30 minutes and then placed in a testing arena. After acclimating for 45 minutes, the flies were exposed to two sources of air, one with ripe strawberry odor and one with only humidified air. Images were captured every minute for an hour and a preference index was calculated for every 10th image. The Drosophila had a positive average preference for the strawberry odor. Five out of six trials showed a general increase in odor preference over the course of the trial. While there was a generally positive trend for average preference over time, there was not a significant increase in average odor preference from time 1 to time 60. The data indicates that Drosophila show a preference for strawberry odor over humidified air, and we propose to extend this test to investigate how Drosophila process and react to complex odors and their chemical constituents.
ContributorsSteinmetz, Kyle J (Author) / Smith, Brian (Thesis director) / Jernigan, Chris (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Recent data suggests that olfactory input is important for antennal lobe development in honey bees. Chronic association of a single odor to food resources during crucial stages of development results in delayed antennal lobe development for mature foraging bees. The antennal lobes of these bees instead closely resemble an immature network observed in young, newly emerged bees. Using an odor stimuli variance assay, learning and memory tests can be used to explore how well honey bees discriminate single odors within complex odor mixtures. Here we are validating two different odor mixtures, a Brassica rapa floral blend and a second replicate mixture composed of common molecularly dissimilar odors. Odors in each mixture are either held constant or varied in concentration over 16 conditioning trials. Subsequent memory tests are performed two hours later to observe the ability of bees to distinguish and recognize specific odor components in each mixture. So far in our assay we find high rates of generalization for both odor mixtures. In general, more bees responded to all odors in the replicate treatment group over the Brassica treatment group. Additionally, bees in the Brassica treatment group did not respond to the target odor. More data is being collected to validate this assay. In future studies, I propose to apply this behavioral assay to bees with an altered olfactory developmental in order to see the functional impacts of this chronic odor association treatment.
ContributorsHalby, Rachael (Author) / Smith, Brian (Thesis director) / Jernigan, Christopher (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Asperger's syndrome is a high-functioning subset of Autism Spectrum Disorders (ASD). Diagnosed patients often lack refined social skills but possess a normal level of cognitive skills without delay in language development. These deficient social skills can impact the ability to find and maintain a job, which can be burdensome for all individuals involved in the patient's life. Although the causes of this condition are largely unknown, a wide variety of social and cognitive therapies have been used to reduce symptom severity, one of which is Mindfulness-Based Stress Reduction (MBSR). Mindfulness is the act of being aware on purpose to whatever is being experienced in the present moment with non-judgment and receptivity. MBSR has been used to bring greater awareness to sensations, thoughts and emotions with the result being reduced reactivity and increased purposeful responsiveness. It is therefore the aim of this study to address the use of an 8-week Mindfulness-Based Stress Reduction in adolescents with clinical Asperger's Syndrome to reduce reactive tendencies. This study will utilize a randomized control group of waitlisted participants given MBSR informational material and a practicing MBSR group. Post-MBSR Parent Global Impressions-III (PGI-III) and Social Responsiveness Scale scores are hypothesized to be improved in MBSR group and unaffected in the control for behavioral markers with no change in core autistic symptoms. Daily average cortisol response is also expected to decrease in the experimental group with unaffected levels in the control.
ContributorsBrzezinski, Molly Alexandra (Author) / Smith, Brian (Thesis director) / Sebren, Ann (Committee member) / School of Music (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
The mammalian olfactory system is commonly studied by using the mouse as a model system. Odor habituation is used to investigate odor perception and learning processes. Most previous experimental preparations have been tedious, requiring a researcher to manually change odorants, record investigation time and duration at each odorant, or physical alteration on the mice to enable video tracking. These limitations were overcame by creating an odorized hole-board to allow for systematic and automatic recording of olfactory behavior in mice. A cohort of five male mice were utilized in these experiments and the responses to the odor of strawberries, a diet staple of wile mice, were examined. Experiment 1 showed that free-feeding mice exhibit a preference to locations with strawberry (over control locations), even when these locations can only be identified using olfaction. This preference habituates within a trial but not across days. Experiment 2 showed that strawberry odor without reward causes habituation or extinction to the odor both within trials and across days. From these experiments, it can be concluded that mice innately explore strawberry odor and this can be exploited to the study odor habituation using an odorized hole-board.
ContributorsMa, Jason (Author) / Smith, Brian (Thesis director) / Gerkin, Richard (Committee member) / Oddo, Salvatore (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Animals must learn to ignore stimuli that are irrelevant to survival, a process referred to as latent inhibition. The Amtyr1 gene has been shown through quantitative trait loci mapping to be linked to strong latent inhibition in honey bees. Here we implicate this G-protein coupled receptor for the biogenic amine tyramine as an important factor underlying this form of learning in honey bees. We show that dsRNA targeted to disrupt the tyramine receptors, specifically affects latent inhibition but not excitatory associative conditioning. Our results therefore identify a distinct reinforcement pathway for latent inhibition in insects.
ContributorsPetersen, Mary Margaret (Author) / Smith, Brian (Thesis director) / Wang, Ying (Committee member) / Sinakevitch, Irina (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12