Medicine and Health Sciences Commons^™

Cortisol Receptor Sensitivity As A Risk Factor For Depression, Michela Michielli

Honors Theses

In 2020, the World Health Organization reported over 264 million people across the world were suffering from depression. Studies have demonstrated that one source of depression is a hormonal imbalance involved in the stress response. Cortisol is a stress hormone regulated by the Hypothalamic-Anterior-Pituitary (HPA) Axis. Its effects on the stress response and other metabolic activities in the body are exerted through the glucocorticoid and mineralocorticoid receptors (GR and MR respectively).

Our research has examined mutations known as single-nucleotide-polymorphisms (SNPs) relating to cortisol-receptor sensitivity and the behavior of cortisol in the body to investigate the link between cortisol activity and …

Expression And Purification Of The Bacterial Protein Curli Csga And Its Cross-Interactions With Amyloid-B, Leah Grace Cantrell

Honors Theses

One of the main causes of neurodegenerative diseases is aggregation of amyloid proteins that are toxic to the neurons. Proteins like amyloid-β (Aβ) and α-syneuclein (α-syn) form hallmark aggregate lesions that contribute to pathological processes in the brain in Alzheimer and Parkinson’s patients, respectively. Recent ground-breaking studies have suggested a link between the microbiota of the gut and neurodegenerative diseases, called the “gut-brain axis.” It has been long known that the protein, CsgA found in many enteric bacteria, forms amyloid fibers of its own called Curli. Curli fibrils are a structural component of bacterial colonies and maintain the integrity of …

Isolation Of Sphingolipids From Sphingomonas Echinoides B-3126 And Their Characterization By Ms/Ms Analysis, Edgar David Uribe Sanchez

Honors Theses

EDGAR DAVID URIBE SANCHEZ: Isolation of Sphingolipids from Sphingomonas echinoides B-3126 and their Characterization by MS/MS Analysis

Sphingolipids are important components in human cellular lipid membranes and are differentiated by the incorporation of serine with an amide bond between the amino acid and a lipid tail. Sphingolipids produced by bacteria differ in both headgroups attached to the serine alcohol and the architecture of the lipid backbone. While the synthesis of sphingolipids in mammalian cells is well studied, only a handful of steps in the pathway are described in bacteria.¹ The observations that although sphingolipid synthesis is rare in bacteria, …

Lectin-Glycan Complexes: A Comprehensive Analysis Of Docking Calculations, Ashton Custer

Honors Theses

Lectins are a type of glycan-binding protein that noncovalently bind glycans. Carbohydrates are molecules consisting of sugar units joined together. Glycans are carbohydrates. Hence, glycans are also sugars. Lectins and lectin-glycan complexes have a range of biological roles and can be found in animals (including humans), plants, bacteria, viruses, and yeasts and fungi.¹ Many scientists focus on the computational study of these complexes due to their intricate roles in many living organisms. Computational study is important in furthering our knowledge of lectin-glycan complexes and other such protein complexes. However, computational study is not perfect. There are many challenges in …

Determining The Distribution Of Elemental Compounds And Oxidative Potential Across Fine Particulate Matter (Pm2.5) Filters, Allie Michelle Sidwell

Honors Theses

Fine particulate matter (PM_2.5) is a complex mixture of particles and sorbed chemicals that poses serious, adverse effects on human health such as increasing cardiovascular and respiratory morbidity and mortality. There is ongoing research into the impacts of PM_2.5 of differing chemical compositions, sampling location, and the mechanisms for the observed health effects. To conduct these analytical and toxicology studies of PM_2.5, researchers often split filters into sections. This process allows multiple, often destructive, assays to be performed. Our previous research showed chemical composition differences across PM_2.5 filters. The goal of our study was …

Finding The Optimal Ionic Liquid To Target White Blood Cell Subpopulations Using Nanoparticles, Meghan Gorniak

Honors Theses

Disorders and diseases of the immune system have become more prevalent in recent decades and can have life-threatening effects on those afflicted. Granulocyte disorders disproportionately affect infants and children, while chronic lymphocytic leukemia is the most common type of leukemia in adults. Unfortunately, current treatments have many drawbacks such as everyday injection, short-lived efficacy, and unknown levels of safety and effectiveness. It is imperative to find more effective treatment options that could allow for easier drug delivery to specific populations of white blood cells (WBCs). Nanoscale medicine shows promising application, but complications remain in reaching the desired target site and …

Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant

Honors Theses

Laromustine is an experimental chemotherapeutic sulfonyl hydrazine prodrug shown in clinical trials to be effective against acute myeloid leukemia. The mechanism of action of laromustine involves interstrand crosslinking, via chloroethylation, and enzyme inhibition, caused by carbamoylation. The work described herein aims to investigate whether inhibition of the replication-dependent interstrand crosslink repair Fanconi Anemia pathway further sensitizes cells to laromustine. By measuring metabolic activity immediately after drug exposure, we find laromustine to be equally as cytotoxic towards Fanconi Anemia deficient and wild type cells. However, through clonogenic assays we show Fanconi Anemia mutations sensitize cells to laromustine’s anti-proliferative effect. Furthermore, we …

Breast Cancer Sub-Clones That Metastasize To Lung And Bone Exhibit Different Metabolic Preferences, Mollie Merrell

Honors Theses

Metastasis is responsible for the majority of cancer related deaths. In breast cancer the lungs and bones are the major sites for metastasis. Previous studies used the metastatic aggressive MDA-MB-231 breast cancer line to isolate sub-clones that preferentially invade the lungs (LM line) or bones (BoM line). While genes associated with the tissue specific metastasis have been identified, it is unknown if metabolic adaptations contribute to the growth of the LM and BoM lines in their respective organs. The goal of this study was to test the hypothesis that the LM and BoM lines exhibit differences in glucose and glutamine …

The Raphe-Hippocampal Tract And Its Age Differences: Diffusion Tensor Imaging And Probabilistic Tractography Study, Ashley Sekul

Honors Theses

The raphe-hippocampal tract links the raphe nuclei to the hippocampus and is responsible for the production of the neurotransmitter serotonin. The hippocampus is key in regulating emotional and stress responses. This study utilized diffusion tensor imaging which uses Functional Magnetic Resonance Imaging to provide scans of the brain for analyzing differences in the raphe-hippocampal tract as one ages. In this specific study, 491 samples were visually analyzed to gather data about the fractional anisotropy of the raphe nuclei in both male and female brains ranging from 6 to 85 years old. Through the ranking of images, some were discarded, and …

Studies Of Salvinorin-Based Antagonists To Elucidate Pertinent Interactions For Kappa Opioid Receptor Antagonism, Madeline Keane

Honors Theses

Opioid abuse, leading to addiction and related deaths, has created a chronic epidemic in the United States for the past 30 years. This crisis has sprung from reliance on the prescription of opioid analgesics as the primary method for the management of pain in the 1990s. At that time, these drugs, specifically Purdue Pharma’s OxyContin, were marketed as non-addictive. Due to this systemic minimization of the addictive properties of opioid analgesics, as prescription rates increased, opioid-related mortality rates climbed. This epidemic continues to be pervasive, as opioid-related overdose resulted in 47,600 deaths in 2017. In addition to the opioid epidemic, …

A Study Of The Antioxidant Versus Pro-Oxidant Nature Of The Amyloid Beta Peptide And An Analysis Of The Natural Products, Isorhamnetin And Narignenin, As Antioxidants, Kaylee Holmes

Honors Theses

Alzheimer’s disease is a neurodegenerative disorder with no cure. Due to the widespread effects of this disease, abundant research efforts have gone towards finding a cure. The amyloid beta (Ab) peptide has been shown to be a potential cause of the disease due to destructive effects on tissues that it can have both by itself and through reactive oxygen species (ROS) generation. This study was performed in order to assess the structural properties of Ab₄₂monomers, fibrils and oligomers, to assess the antioxidant versus pro-oxidant behavior of the Ab peptide, and to assess the antioxidant nature of the natural …

The Biochemical Characterization Of Cellular Retinoic Acid Binding Protein Type 1 (Crabp1), Emma Magna

Honors Theses

The goal of this research was to express and purify Cellular Retinoic Acid Binding Protein Type 1 (CRABP1). CRABP1 binds to retinoic acid in the cell and shuttles the retinoic acid from one area in the cell to another. The overproduction of CRABP1 appears to be problematic because it can sequester the retinoic acid and prevent it from regulating gene expression. Previous studies have shown that increased levels of CRABP1 can result in tumor-promoting activity and disruption of lipid biology in the cell. Our objective was to express this protein in an inducible bacterial system, so that we could purify …

Identifying Metabolites As Markers Of Fatigue In Athletes, Christopher D. George

Honors Theses

Fatigue in athletes caused by inadequate rest and other stressors can be severely detrimental to their health, and yet there is no reliable way to measure and track fatigue. Many classical measures of fatigue like body mass and resting heart rate are not reliable ways to track the physical fatigue of an athlete because they can change with many factors. In addition, it is not known how academic stress on top of physical stress affects fatigue. Metabolomics is a relatively new area of study and tracking metabolites offers the possibility to produce biomarkers to assess fatigue. This study collected saliva …

Evaluating A Culprit: A Review Of The Biochemical Mechanisms Of Non-Celiac Gluten Intolerance, Callie Cinque

Honors Theses

Non-Celiac Gluten Intolerance (NCGI) has evaded biological and chemical mechanisms since it was first reported in 1978. Celiac Disease, a multi-system immune mediated disorder has long served as the most similar counterpart to NCGI. Less cases of celiac disease are going undiagnosed reflecting an improvement on sensitive and decisive diagnostic tools. However, NCGI has been significantly growing as a diagnosis over the past decade with little match or similarity to the markers found in celiac disease patients. Critical evaluation of NCGI theories, experimentation, and existing hypotheses is necessary. This review seeks to synthesize multiple disciplines of gluten research and enhance …

Mutations In The Human Follicle Stimulating Hormone Receptor Caveolin Interaction Motif Cause Increased Basal Activation, Elizabeth Altman

Honors Theses

Over twelve percent of women aged fifteen to forty-five in America suffer from infertility and/or impaired fecundity and over seven million women have used infertility services, such as intrauterine insemination and in vitro fertilization. Some cases of infertility may be due to dysfunctional human follicle stimulating hormone (hFSH) signaling. hFSH plays a role in spermatogenesis in males, as well as follicle maturation and estrogen production in females. Problems with either hFSH or the hFSH receptor (hFSHR) decrease fertility in males and cause complete infertility in females. As part of the hypothalamic-pituitary-gonadal axis, hFSH is released from the pituitary gland and …

Effectiveness And Mechanism Of Action Of Modified Porphyrins For Photodynamic Therapy Of Triple Negative Breast Cancer Cells, Hannah Brandon

Honors Theses

Triple negative breast cancer (TNBC) is a particularly aggressive form of breast cancer that lacks the three molecules typically targeted for treatment. Standard treatment methods leave much to be desired--the rates of metastasis and recurrence are high and the prognosis for most patients with TNBC is poor. One potential treatment for TNBC is photodynamic therapy (PDT), which uses compounds called photosensitizers that are taken up by all tissues in the body. The tumor is exposed to light, activating the photosensitizer and creating reactive oxygen species that cause cell death. This method is relatively pain-free, effective, and does not harm cells …

Testing Bacterial Antibiotic Production Under Carbohydrate And Protein Starvation, Briley Baird

Honors Theses

Bacteria produce antibiotics when they are under stress, including starvation stress. Bacteria were tested under carbohydrate and protein starvation against Bacillus subtilis and Escherichia coli (due to the respective Gram positivity and negativity), in order to check for antibiotic production. The bacteria being tested were isolated by past Microbiology classes and stored in a -80°C freezer in the basement of Jones Science Center at Ouachita Baptist University. These test bacteria were grown on tryptic soy agar (TSA) to produce isolated bacterial colonies. Samples of isolated test colonies were then grown under conditions of carbohydrate starvation (M9 salts agar with 0.1 …

Tubulin Post-Translational Modifications Are Altered By Changes In Actin-Myosin Contractility In Non-Muscle Cells, James Mcgee

Honors Theses

All cells regulate their contractility by the interaction of actin and myosin. In non-muscle cells, however, this interaction is regulated by rho, a GTPase, which is the upstream effector for multiple pathways. Cell contractility increases when rho is active, and prior research has shown the depolymerization of microtubules (MTs) activates rho. Microtubules play a role in many cellular functions and it is thought that either associations with MT-associated proteins and/or post-translational modifications to tubulin regulate MT functions. Numerous post-translational modifications (PTMs) to microtubules have been identified, but their roles are not well understood. A possible relationship between changes in cell …

Development Of A Chemical Genetic Screen To Determine Synergistic Compounds With Laromustine In Treating Glioblastoma Multiforme Cultured Cells, Ryan Weeks

Honors Theses

Laromustine is a chemotherapeutic sulfonylhydrazine prodrug used in clinical trials to treat acute myeloid leukemia (AML) and glioblastoma multiforme (GBM). While treatment of AML with laromustine has more demonstrative clinical success, there are enough promising data against GBM to pursue additional pre-clinical and clinical experiments. To determine the synergistic effects caused by treating cultured GBM cells with laromustine and a library of FDA-approved compounds, a chemical genetic screen was developed. To optimize the screen, optimal cultured GBM cell seed density, growth period and maximum well capacity were determined. The treatment period for a lethal dose of laromustine in cultured GBM …

Discovering New Antibiotics: Bacterial Extracts Separated By Thin-Layer Chromatography Inhibit The Growth Of Staphylococcus, Heidi Hughes

Honors Theses

Many bacteria have become resistant to commonly used antibiotics because of antibiotic use in people and animals. Therefore, new antibiotics are needed that will inhibit these resistant bacteria. Bacteria found in soil are a likely source for new antibiotics because of the limited available nutrients found in the soil. We isolated soil bacteria and screened them for antibiotic production against Staphylococcus epidermidids. Methanol extracts were made from entire agar plates of the soil bacteria that inhibited S. epidermidis. These extracts were spotted on a lawn of Staphylococcus aureus; growth inhibition was measured to comfirm that the extracts contained the …

The Impact Of Tricaine Methanesulfonate, 2-Phenoxyethanol, And Carvone-Methyl Salicylate On The Innate Immune Response Of Zebrafish (Danio Rerio), Charles R. Wulff

Honors Theses

Anesthesia plays a vital role in the maintenance of aquaculture species, where it is used to minimize stress during complex handling tasks such as transport, assessment, and harvesting. However, anesthetics have been shown to suppress the innate immune response, which could impact immunity and increase risk of infection. Tricaine methanesulfonate (MS-222) and 2-Phenoxyethanol (2-PE) represent two of the most commonly used anesthetics in aquaculture, with R-(+)-carvone, in the form of carvone-methyl salicylate (CMS) has recently been proposed as an alternative anesthetic for food fish. These three anesthetics were used to assess the influence of anesthetics on the immune system of …

Molecular Evolution Of Insecticidal Spore-Forming Bacteria, John Pool

Honors Theses

Molecular methods are increasingly being used to determine the phylogeny of microorganisms. This research was intended to determine phylogenetic relationships for bacteria of the species Bacillus thuringiensis and other members of the Bacillus cereus group. Each strain was analyzed by its sasp-B gene sequence to determine its species classification and relation to other strains studied. Results of this study indicated that according to the sasp-B gene tree, the species Bacillus thuringiensis is a paraphyletic with respect to both Bacillus cereus and Bacillus anthracis. Some unexpected results and implications for species designations are also discussed.

Oral Cancer Screening, Damon Omar Watson

Honors Theses

Cancers of the oral cavity and pharynx have increased throughout the decades. Since oral cancer represents a small percentage of the total cancers in the United States, it is often overlooked. Though this is the case, the results of this cancer can be devastating. To address this issue, an Oral Cancer Screening was organized on August 14, 1996 at the West Michigan Cancer Center in Kalamazoo. This was a joint collaboration between the author, the West Michigan Cancer Center, and the Kalamazoo Valley Dental Society. This event allowed research to take place concerning the data obtained. Confidential results and information …

Sds Non-Acrylamide Polymeric Gel-Filled Capillary Electrophoresis For Molecular Size Separation Of Protein, Devon Andres

Honors Theses

Sodium dodecyl sulfide (SDS) non-acrylamide gel-filled capillary columns are a new technology being used for analysis and separation of biotechnology-derived proteins. This research was to compare this new technology to the current methods of SDS polyacrylamide gel electrophoresis (SDS-PAGE) and high-performance size-exclusion chromatography (HPSEC). The molecular mass of four different recombinant proteins were determined by two commercialized SDS non-acrylamide gel-filled capillary columns, SDS-PAGE, and HPSEC. The data obtained showed that the SDS non-acrylamide gel-filled capillary columns were compatible with the SDS-PAGE technique for molecular mass determination. HPSEC was shown to be unreliable for molecular weight determination. SDS non-acrylamide gel-filled capillary …