Pharmacology, Toxicology and Environmental Health Commons^™

Field And Laboratory Evaluation Of The Interactions Between Pesticides And The Gut Microbiome In Honey Bees (Apis Mellifera), Macee R. Mitchell

EWU Masters Thesis Collection

Western honey bees (Apis mellifera) are important pollinators yet are threatened by a combination of factors such as poor nutrition, pathogens, parasites, and pesticide use. Bees encounter numerous pesticides while foraging (e.g. imidacloprid, a neonicotinoid insecticide) or in the hive colony (e.g. Tau-fluvalinate, a miticide commonly used to treat Varroa mite parasites). Similar to most organisms, the gut microbiome is important for bee health, metabolism, and behavior, however it is not well known how environmental factors like pesticides impact their gut bacterial symbionts. I hypothesized that 1) pesticide concentrations in bees are correlated with gut bacterial community structure, and 2) …

Examining The Effects Of Artemisia Annua On Neuro2a Cells, Wesley Lim

Honors Undergraduate Theses

Artemisia annua L. is a well-known medicinal herb used in Traditional Chinese Medicine for many centuries and contains artemisinin, which exhibits antimalarial properties [1] and is a potential treatment for SARS-CoV-2 [2]. However, the neurological effect of A. annua and its compounds are poorly understood. We hypothesize that A. annua extracts and artemisinin will provide protection against oxidative stress in mouse neuronal Neuro2A cells. Superoxide dismutase 1 (SOD1) is an anti-oxidant enzyme that protects against oxidative damage [3]. Growth Arrest and DNA Damage-inducible 45 alpha (Gadd45a) is involved in DNA repair and is a common biomarker for DNA damage[4]. SOD1 …

Emerging Chromatin Regulators In Response To Heavy Metal Exposure, Wesley Saintilnord

Theses and Dissertations--Molecular and Cellular Biochemistry

Environmental exposure to heavy metals poses significant threats to human health as they are associated with various developmental and chronic pathologies such as reproductive defects and cancers. Despite their profound risks, a comprehensive understanding of their disease-causing mechanisms is lacking. Most studies point to reactive oxygen species-induced DNA damage; however, their mutagenic potential is relatively weak suggesting the involvement of alternative mechanisms. One important, yet underexplored mechanism, is their ability to rewire the epigenome via DNA methylation and histone variant incorporation, leading to aberrant gene regulatory networks.

This study investigates the epigenetic mechanisms targeted by two ubiquitous heavy metals with …

Opioid System's Potential Involvement In Ketamine's Cognitive And Antidepressant-Like Effects In Rats, Fan Zhang

Theses and Dissertations

Depression stands as one of the most pervasive mental health challenges worldwide, including the United States. Conventional antidepressants typically display a delayed onset of therapeutic action (4-8 weeks) and lack efficacy in a substantial portion of patients (over 40% of depressed patients are treatment-resistant). The dissociative anesthetic ketamine, which is a glutamatergic N-methyl-D-aspartate (NMDA) antagonist, has emerged as a promising novel treatment due to its rapid and prolonged antidepressant effects, and it is especially beneficial for treatment-resistant depression. Nevertheless, the precise neurochemical mechanisms underlying ketamine’s antidepressant properties remain elusive, hampering the development of safer and more efficacious treatments. The present …

Characterization Of Cisplatin-Dna Adduct Release From Cancerous And Non-Cancerous Cell Lines, Aleena Alex

Browse all Theses and Dissertations

Cisplatin is an effective chemotherapeutic agent that is used to treat lung, breast, esophageal, ovarian, and pancreatic cancers. Despite being effective in treating a wide variety of cancer types, its cytotoxicity to off-target healthy tissues restricts its therapeutic application. The platinum atom of cisplatin interacts with DNA and results in the formation of inter-and intra-strand crosslinks, which are often referred to as DNA adducts. These adducts are mutagenic and potentially lethal to cells. The sole pathway for cells to excise intra-strand cisplatin-DNA adducts from the genome is through nucleotide excision repair. The fate of unrepaired DNA adducts is not understood …

The Role Of Suc22-S239f Mutation In Sensitizing Fission Yeast To The Replication Stress Induced By Hydroxyurea, Kajal Davi

Browse all Theses and Dissertations

Genetic mutations can significantly impact the cell’s susceptibility to environmental stress. The fission yeast Schizosaccharomyces pombe is an established eukaryotic model for studying the cellular responses to various environmental stresses. This work investigated a missense mutation (S239F) identified in Suc22, the small subunit of the ribonucleotide reductase (RNR). RNR is an essential enzyme for the biosynthesis of dNTPs required for DNA replication and repair. We found that the suc22-S239F mutation increases the susceptibility to the replication stress induced by hydroxyurea (HU), not the DNA-damaging agents such as UV, methyl methanesulfate, and CPT. HU is a drug commonly used in laboratories …

Enhancing Translation: A Need To Leverage Complex Preclinical Models Of Addictive Drugs To Accelerate Substance Use Treatment Options, Christa Corley, Ashley Craig, Safiyah M. Sadek, Julie A. Marusich, Samar N. Chehimi, Ashley M. White, Lexi J. Holdiness, Benjamin C. Reiner, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Preclinical models of addictive drugs have been developed for decades to model aspects of the clinical experience in substance use disorders (SUDs). These include passive exposure as well as volitional intake models across addictive drugs and have been utilized to also measure withdrawal symptomatology and potential neuro- behavioral mechanisms underlying relapse to drug seeking or taking. There are a number of Food and Drug Administration (FDA)-approved medications for SUDs, however, many demonstrate low clinical efficacy as well as potential sex differences, and we also note gaps in the continuum of care for certain aspects of clinical ex- periences in individuals …

Impacts Of Xylazine On Fentanyl Demand, Body Weight, And Acute Withdrawal In Rats: A Comparison To Lofexidine, Safiyah M. Sadek, Shailesh N. Khatri, Zachary A. Kipp, Kelly E. Dunn, Joshua S. Beckmann, William W. Stoops, Terry D. Hinds, Jr., Cassandra D. Gipson

Markey Cancer Center Faculty Publications

The opioid use landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the fentanyl supply. The health impacts of xylazine as an emerging fentanyl adulterant has raised alarm regarding xylazine as a public health threat, warranting research on the impacts of xylazine on fentanyl’s behavioral effects. No prior studies have evaluated the effects of xylazine on fentanyl consumption at various unit doses, fentanyl demand, or withdrawal as compared to the Food and Drug Administration-approved opioid withdrawal medication, lofexidine (Lucemyra®). This is important because lofexidine and xylazine are both adrenergic α2a (A2aR) agonists, however, lofexidine is …

Oxycodone Withdrawal Is Associated With Increased Cocaine Self-Administration And Aberrant Accumbens Glutamate Plasticity In Rats, Shailesh N. Khatri, Hanaa Ulangkaya, Erin E. Maher, Safiyah M. Sadek, Mei Hong, Andrea M. Woodcox, William W. Stoops, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Individuals with opioid use disorder (OUD) frequently use other substances, including cocaine. Opioid with- drawal is associated with increased likelihood of cocaine use, which may represent an attempt to ameliorate opioid withdrawal effects. Clinically, 30% of co-using individuals take opioids and cocaine exclusively in a sequential manner. Preclinical studies evaluating mechanisms of drug use typically study drugs in isolation. However, polysubstance use is a highly prevalent clinical issue and thus, we established a novel preclinical model of sequential oxycodone and cocaine self-administration (SA) whereby rats acquired oxycodone and cocaine SA in an A-B-A-B design. Somatic signs of withdrawal were evaluated …

Perfluorooctanesulfonic Acid Exposure Leads To Downregulation Of 3-Hydroxy-3-Methylglutaryl-Coa Synthase 2 Expression And Upregulation Of Markers Associated With Intestinal Carcinogenesis In Mouse Intestinal Tissues, Josiane Weber Tessmann, Pan Deng, Jerika Durham, Chang Li, Moumita Banerjee, Qingding Wang, Ryan A. Goettl, Daheng He, Chi Wang, Eun Y. Lee, B. Mark Evers, Bernhard Hennig, Yekaterina Y. Zaytseva

Markey Cancer Center Faculty Publications

Perfluorooctanesulfonic acid (PFOS) is a widely recognized environment pollutant known for its high bio- accumulation potential and a long elimination half-life. Several studies have shown that PFOS can alter multiple biological pathways and negatively affect human health. Considering the direct exposure to the gastrointestinal (GI) tract to environmental pollutants, PFOS can potentially disrupt intestinal homeostasis. However, there is limited knowledge about the effect of PFOS exposure on normal intestinal tissues, and its contribution to GI- associated diseases remains to be determined. In this study, we examined the effect of PFOS exposure on the gene expression profile of intestinal tissues of …

Interactions Between Multiple Stressors, Nanomaterials And A Pathogen, In Caenorhabditis Elegans, Jarad Cochran

Theses and Dissertations--Plant and Soil Sciences

Metal and metal oxide nanoparticles (NP), which have received interest for use in agriculture, show in vitro and in vivo toxicity at relatively low concentrations. Silver nanoparticles (Ag NP) and zinc oxide nanoparticles (ZnO NP) cause adverse effects in model soil organisms under environmentally relevant conditions. In most toxicity assessments of nanomaterials, model organisms are exposed to a single stressor. Though single stressor experiments are essential to understanding the fate and effects of released NP, in nature, organisms are affected by multiple stressors, including pathogens, which might exacerbate or mitigate negative effects of NP exposure. There is limited research on …

Incorporating Effects-Based Approaches Into Environmental Impact Assessment To Improve Post-Development Monitoring, Carolyn J M Brown

Theses and Dissertations (Comprehensive)

Over the last 50 years, improvements in design of industrial facilities have significantly reduced environmental impacts. But impacts still occur and monitoring programs are the main mechanism to inform when modification/implementation of mitigation is needed. Informed decisions require adequate baseline (pre-development) data to predict impacts based on the development’s design and to understand when the post-development environment has changed. An adaptive monitoring plan provides an effective way to evaluate monitoring results and allow for proactive responses to environmental change before impacts become difficult or challenging to reverse. Unfortunately, baseline data gathered during an environmental impact assessment (EIA) is often inadequate …

Evaluating The Risk Posed By Gadolinium In The Grand River Watershed, Johann Memmel

Theses and Dissertations (Comprehensive)

Gadolinium (Gd) is a rare earth element (REE), primarily used in contrast agents for magnetic resonance imaging (MRI), with additional applications in metallurgy, phosphors, neutron shielding, and other niche applications. Both Gd and Gd-based contrast agents (GBCAs, the form used for MRIs) have been detected downstream of wastewater effluent discharges and there is currently little research into the risk this poses to aquatic ecosystems. This study investigated the potential environmental risks of Gd and GBCAs using the Grand River watershed (GRW) in southwestern Ontario as a model ecosystem due to it containing a variety of land uses (urban, industrial, agricultural) …

Myokine Probdnf-P75ntr Signaling In Skeletal Muscle Injury And Sterile Inflammation, Katherine Aby

Dissertations and Theses

Originally discovered in the brain, brain-derived neurotrophic factor (BDNF) has been shown to be expressed and released from skeletal muscle as a myokine. However, the function of myokine BDNF is not fully understood. Of interest to this study is the function of the BDNF precursor proBDNF in skeletal muscle. We first show that skeletal muscle expresses unique BDNF splice variants compared to the brain, and at the protein level, skeletal muscle expresses significantly more proBDNF than mature BDNF under basal conditions. Consistent with this, expression of major protein convertases in skeletal muscle were significantly lower. The role of myokine proBDNF …

Investigating The Impact Of Chronic Inflammatory Pain On Ethanol Consumption In Mouse Models., Joshua L. Hunt

Theses and Dissertations

Chronic pain affects nearly 20% of Americans annually and for many alcohol provides a convenient and legally acquired palliative. Population-based studies have suggested a link between increased alcohol use and reduced pain, but chronic or excessive alcohol use potentiates the risk to develop alcohol dependence and neuropathy. However, sex differences in chronic pain and alcohol abuse are still not well understood. In the present study, we investigated whether chronic inflammatory pain using the inflammatory agent Complete Freund’s Adjuvant (CFA) model could alter ethanol consumption in male and female C57BL/6J mice. We observed that only CFA-treated male mice increased their ethanol …

Exploring Serotonin 1b Autoreceptor Mediated Regulation Of Serotonin Transporter In Female Mice, Sanyukta Jalihalkar

Theses and Dissertations

Rationale: Serotonin (5-HT) is a crucial neurotransmitter involved in regulating various physiological processes. Dysregulation of the serotonergic system has been implicated in several neuropsychiatric disorders. Though numerous 5-HT receptors exist, the 5-HT transporter (SERT) is responsible for 5-HT clearance in the brain and periphery. 5-HT_1Bautoreceptors regulate 5-HT release and interact with glycogen synthase kinase-3β (GSK3β), which can modulate SERT function via specific Ser44/48 phosphorylation sites. While these findings suggest a potential interplay between 5-HT_1Band GSK3β-mediated SERT phosphorylation in regulating extracellular 5-HT, the primary causal molecular link remains unknown.

Objectives: To investigate if 5-HT_1B activation by …

Shedding Light On Ester Drug Metabolism: Investigating Carboxylesterases In Live Cells With Fluorogenic Chemical Tools, Carolyn J. Karns

Masters Theses

No abstract provided.

Molecular Investigation Of Tick-Borne Pathogens In Feral Swine (Sus Scrofa) From Seven Us States, Sofiane Aiche

Masters Theses

Feral swine (Sus scrofa) have been proposed as part of the lifecycles of multiple tickborne pathogens (TBP). This is a result of the increase in feral swine populations and increased tick populations and geographic ranges. Few surveys exist on the TBP relevant to human and wildlife of feral swine in the US. The aim of this study is to investigate the prevalence of 10 TBP: Anaplasma spp., Borrelia spp., Cytauxzoon felis, Hepatozoon spp., Babesia spp., Mycoplasma spp., Trypanosoma cruzi, Toxoplasma gondii, Yersinia pestis, and Rickettsia spp. A total of 87 feral swine blood samples …

Joint Problem-Solving Orientation, Mutual Value Recognition, And Performance In Fluid Teamwork Environments, Michaela Kerrissey, Zhanna Novikov

Faculty, Staff and Student Publications

INTRODUCTION: Joint problem-solving orientation (JPS) has been identified as a factor that promotes performance in fluid teamwork, but research on this factor remains nascent. This study pushes the frontier of understanding about JPS in fluid teamwork environments by applying the concept to within-organization work and exploring its relationships with performance, mutual value recognition (MVR), and expertise variety (EV).

METHODS: This is a longitudinal, survey-based field study within a large United States healthcare organization

RESULTS: Our results affirm a moderated mediation model wherein JPS enhances performance, both directly and through MVR; EV serves as a moderator in the JPS-MVR relationship. JPS …

Neurodevelopmental Vulnerability To Gestational Ozone Exposure, Vishnupriya Alavala, Sarah E. Brent, Christopher G. Canal, Joseph Wang, Russell P. Hunter, Matthew J. Campen, Andrew K. Ottens

UROP Posters

Ambient air pollution accounts for about 4.2 million premature deaths annually per the World Health Organization. Ozone (O3) is a highly reactive air pollutant found in smog and is implicated in cellular damage leading to organ dysfunction. Ambient air pollution is associated with neurodevelopmental, behavioral, and cognitive disorders though ozone’s role is unknown. Studies here look at ozone exposure shortly after implantation vs. shortly before term to evaluate differences in neurodevelopmental susceptibility over time.

To inquire on the effects of ozone on the fetal brain, pregnant Sprague-Dawley rats were exposed once to 0.3 ppm of O3 or filtered air (FA) …