Pharmacology, Toxicology and Environmental Health Commons^™

Overexpression Of Abcc1 And Abcg2 Confers Resistance To Bmn-673, A Poly (Adp-Ribose) Polymerase (Parp) Inhibitors, Qiuxu Teng

Theses and Dissertations

Cancer remains a growing public health challenge worldwide. Although the development of chemotherapies has effectively reduced the cancer death rate and improved patients’ prognosis, the frequent occurrence of multi-drug resistance (MDR) in cancer has caused impairments on the efficacy of many structure-unrelated anticancer agents, leading to treatment failure and recurrence. One of the most common causes of MDR is the overexpression of ATP-binding cassette (ABC) transporters on cancer cell membranes, which transport anticancer drugs out of cancer cells, thereby reducing the intracellular drug concentration. BMN-673 (talazoparib) is a potent poly (ADP-ribose) polymerase (PARP) inhibitor that is approved for BRCA-mutated HER2-negative …

Mancozeb Exposure Results In Oxidative Stress And Disruption Of Mitochondrial Complexes Iii & Iv In Transformed Human Colon Cells, Amanda Dhaneshwar

Theses and Dissertations

The ethylene bisdithiocarbamate pesticides, a subclass of the dithiocarbamate pesticides, are broad spectrum organometallic fungicides used on a variety of crops. The fungicide Mancozeb is comprised of an ethylene bisdithiocarbamate backbone complexed to the metals manganese and zinc. Ingestion of food containing pesticide residue and occupational exposure are common routes of Mancozeb exposure. Previous work demonstrated that Mancozeb exposure to HT-29 colon cancer cells resulted in cytotoxicity, apoptosis, and disruption of mitochondrial complex I, II, and V activity. The current study investigated the effect of Mancozeb exposure on mitochondrial complex III and IV activity and oxidative stress parameters in the …

Cytotoxicity Of Copper (Ii) Octanoate On Mouse Hippocampal Astrocytes, Ali A. Shohatee

Theses and Dissertations

Copper, as an essential trace element, is crucial for various biological processes but has also been utilized as a constituent of various pesticides for decades. Copper (II) octanoate is a pesticide utilized as a fungicide and is approved for use in the production of certified organic foods. Previous studies have implicated copper as an inducer of oxidative stress and activator of the Nrf2-ARE pathway. Nrf2 is essential in regulating the transcription of various genes to alleviate toxicity such as those involved in glutathione synthesis and detoxification. Due to the limited toxicological data, this study into the potential induction of oxidative …

Growth And Survival Of Amphibians Exposed To Road Salt And Glyphosate-Based Herbicide, Jerica Eaton

Mahurin Honors College Capstone Experience/Thesis Projects

Amphibian populations are threatened by increasing levels of environmental pollution resulting from human activities. Areas with mixed land use that include agriculture and urban development experience increased contamination from surface herbicide and road deicer application. Upon entering water sources, these chemicals have the capacity to disrupt the natural dynamics of aquatic ecosystems. This study aimed to evaluate the effects of these contaminants on amphibian populations. I used the spotted salamander (Ambystoma maculatum) as a model, rearing larvae from hatching to metamorphosis. I subjected larvae in each of the treatment groups to varying levels of herbicide and salt concentrations. …

Sanfilippo Syndrome: Symptoms, Therapies And The Search For A Cure, Elisheva Garfinkel

The Science Journal of the Lander College of Arts and Sciences

Sanfilippo syndrome, also named Mucopolysaccharidosis III (MPS) is an uncommon disorder that develops due to abnormalities in the nervous system and brain. Aspects of this condition include losing motor and mental function beginning at just a few months old. Four different proteins are involved in the breakdown of Heparin Sulfate (HS) in the extracellular matrix. “When one of these proteins is missing or inadequate, Mucopolysaccharidosis III (MPS), can result (“Sanfilippo Syndrome”, 2019) The specific protein that is insufficient will determine which of the four corresponding forms of Sanfilippo syndrome is present. “All variations of Sanfilippo Syndrome are easily identified by …

Porcine Skin Explants As A New Model To Investigate Microvesicle Particle Generation, Shikshita Singh

Browse all Theses and Dissertations

The skin is exposed to a variety of external stressors, from irritants to toxic agents to ultraviolet radiation (UVR). While mice and human volunteers can be used for research studies, there are limitations in the range of environmental stressors that can be studied using these models. Therefore, our research team has been investigating the use of human skin explants as a model to study the immediate effects of environmental stressors ex vivo. Although this method has been successful, obtaining fresh human skin for these studies is difficult due to limited availability. To overcome this issue, we are evaluating the possibility …

Dataset For Manuscript: Comparing Performance Of Spectral Image Analysis Approaches For Detection Of Cellular Signals In Time-Lapse Hyperspectral Imaging Fluorescence Excitation-Scanning Microscopy, Silas J. Leavesley

BioImaging and BioSystems Research

The dataset contains raw and processed hyperspectral timelapse image data that are described in the manuscript:

Parker, M., Annamdevula, N. S., Pleshinger, D., Ijaz, Z., Jalkh, J., Penn, R., Deshpande, D., Rich, T. C. & Leavesley, S. J. Comparing Performance of Spectral Image Analysis Approaches for Detection of Cellular Signals in Time-Lapse Hyperspectral Imaging Fluorescence Excitation-Scanning Microscopy. Bioengineering 10, 642 (2023).

Keratoconus: The Conical Corneal Conundrum And Its Evolving Treatments, Sima Friedman

The Science Journal of the Lander College of Arts and Sciences

Keratoconus is an eye disease that transforms the shape of the cornea from its normal oval shape to a conical shape. This can lead to a decrease in vision and, if not treated, can lead to a loss of vision. Depending on the severity and progression of each case, many treatment options are now available, ranging from cross linking procedures and special contact lenses to corneal transplants.

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

UROP Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Effects Of Elevated Extracellular Dopamine On Astrocytes In The Nucleus Accumbens, Mengfan Xia

Theses and Dissertations--Pharmacology and Nutritional Sciences

Nucleus accumbens is involved in processing of motivational and affective behaviors and plays a significant role in development and maintenance of substance use. Released from the ventral tegmental area into the nucleus accumbens, the mesolimbic dopamine controls incentive salience and facilitates learning of reinforcement and reward-related motor functions. Recent studies reveal that, in the context of cocaine exposure, dopamine transmission in the ventromedial striatum is pivotal to the regulation of initial drug use. Astrocytes, a major subpopulation of the brain glial cells, are an active component of the so-called tripartite synapse and communicate with neurons through the release of transmitters …

Beyond Mitosis, Plk1-Mediated Phosphorylation Re-Wires Cancer Metabolism And Promotes Cancer Progression, Qiongsi Zhang

Theses and Dissertations--Toxicology and Cancer Biology

Polo-like kinase 1 (PLK1) is a well- characterized regulator of cell division and is known to be highly expressed in certain types of tumors. It has been demonstrated the multifaceted roles of PLK1 in regulation of transcription, translation, epigenetics, DNA damage and cellular metabolism et al. Despite these findings, the precise mechanisms by which PLK1 regulates these processes beyond mitosis remain unclear. PLK1-mediated phosphorylation and misregulation of its substrates has been linked to tumorigenesis, cancer progression, drug resistance and worse prognosis. In this study, we investigated the non-canonical functions of PLK1 in cancer metabolism and drug resistance. We found that …

Selective Gsk3b Overexpression In Medial Prefrontal Cortex Camkiia Cells Produces Sex-Specific Changes In Ethanol Self-Administration, Anxiety-Like Behavior, And Working Memory, Sam Gottlieb, Zachary Tatom, Michael F. Miles

Graduate Research Posters

Background: Glycogen synthase kinase 3 beta (Gsk3b) is central in a gene network regulated by ethanol in mouse medial prefrontal cortex (mPFC). GSK3B abundance/activity modulations regulate ethanol consumption, suggesting GSK3B could be a target in treating alcohol use disorder. However, the critical cell type in this ethanol response is not yet known, nor have sex differences in GSK3B modulations been fully investigated. Here we report results of GSK3B overexpression selectively in CamKIIa⁺ mPFC cells on multiple behaviors.

Methods: Mice underwent stereotaxic injections to overexpress GSK3B in mPFC CamKIIa⁺ cells or control virus (n=4-6/sex/virus). We assayed working …

Entangled Mangrove Roots: The Shrimp Industry, Ancestral Afro-Descendant People, And Community Resistance In Esmeraldas, Ecuador, O'Philia Le

Pitzer Senior Theses

Mangroves are one of the most important ecosystems because of the many services they provide on a local and global scale, but in contrast, are one of the most threatened by anthropogenic activities at a global level. Being sources of food for various kinds of fish, crustaceans, and mollusks, they are essential for the economy, culture, and livelihood of locals in Esmeraldas, Ecuador. This thesis takes an environmental justice approach in the discussion of the loss of mangroves in Esmeraldas, Ecuador. While toxic industries may not be apparent at first, environmental injustice prevails in adverse human health effects, environmental degradation, …

Nutritional & Colorectal Health, Tariq A. Alam, Brittany R. Rice, Sara B. Police

Journal of Pharmacology & Nutritional Sciences

Kentucky has the highest incidence and mortality rate of all site cancers, and Kentuckians residing in the Appalachian region often have worse outcomes, where cancer is a leading cause of death. Focusing on colorectal cancer (CRC) specifically, Kentucky ranks first nationwide for incidence (50 cases per 100,000 people) and fifth for mortality (about 17 deaths per 100,000 people). The Kentucky Colon Cancer Screening Program increased screening rates and reduced mortality since its launch. Yet, CRC remains a leading cause of death for Kentuckians. Risk factors for CRC include increasing age as well as a history of inflammatory bowel disease (IBD) …

Xeroderma Pigmentosum Type A Deficiency Results In Increased Generation Of Microvesicle Particles In Response To Ultraviolet B Radiation And Solar Simulated Light Via Platelet-Activating Factor Receptor Signaling Pathway, Pranali Sushil Manjrekar

Browse all Theses and Dissertations

Increased vulnerability to the DNA-damaging effects of ultraviolet (UV) radiation is a hallmark of the uncommon genetic disorder Xeroderma Pigmentosum (XP). The Nucleotide Excision Repair (NER) route uses the DNA Damage Recognition and Repair component XPA to identify and get rid of damaged DNA segments. Although the solar UVB (290-320 nm) radiation is necessary for humans to produce vitamin D, it may also induce erythema and inflammatory reactions, and in some pathological situations, such as XPA deficiency, results in increased UV responses (photosensitivity). Our group has previously shown, using cell lines and mice, that increased synthesis of the lipid mediator …

Exposure To Pcb126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance, Brittany B. Rice, Keegan W. Sammons, Sara Y. Ngo Tenlep, Madeline T. Weltzer, Leryn J. Reynolds, Cetewayo S. Rashid, Hollie I. Swanson, Kevin J. Pearson

Human Movement Studies & Special Education Faculty Publications

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 µmole PCB126 per kg of body weight via oral gavage on postnatal …

Trends In Cyanotoxin Production Potential In China Lake: An Edna Analysis Of Microcystis And Dolichospermum And The Environmental Drivers Of Cyanotoxin Production, Gennifer M. Rubin

Honors Theses

Episodes of cyano-harmful algal blooms (cyano-HABs) are hypothesized to be exacerbated by the effects of climate change. However, the dynamics of the interactions between elements of climate change and toxigenic cyanobacteria proliferation are not well defined. China Lake is the drinking water source for 7 municipalities in the Kennebec County and is one of many lakes in central Maine that has been subjected to high levels of cyano-HABs and microcystin toxin contamination in recent years. Monitoring the toxicity of these blooms in relation to various aspects of climate change may lead to identification of the major drivers of microcystin production …

Développement De Stratégie Visant À Contrôler Le Niveau De Contamination Des Piscines Par Les Sous-Produits De Désinfection, Maximilien Debia, Elham Ahmadpour, Isabelle Valois, Sami Haddad, Robert Tardif, Stéphane Hallé, Hélène Proulx, Manuel Rodriguez, François Proulx, Ianis Delpla, Jean Sérodes, Sabrina Simard

Rapports de recherche scientifique

La présence de sous-produits de désinfection dans l’eau et l’air des piscines intérieures est une problématique de santé publique et de santé au travail. L’exposition aux sous-produits de désinfection et notamment à la trichloramine est associée à différents effets délétères comme l’irritation des voies respiratoires, l’irritation oculaire et l’hyperréactivité bronchique. La présence des sous-produits de désinfection résulte des réactions chimiques qui surviennent entre les agents désinfectants ajoutés et les matières organiques ou azotées présentes naturellement dans l’eau ou qui y sont amenées par les baigneurs.

L’objectif général de recherche visait à améliorer les connaissances sur les pratiques de gestion et …

Evaluating The Influence Of Concurrently Available Non-Drug Reinforcers On Drug Reinforcement Using Sophisticated Preclinical Models Of Substance Use Disorder, Madison M. Marcus

Theses and Dissertations

The maladaptive allocation of behavior towards cocaine and away from other concurrently available non-drug reinforcers (e.g., family, health, work, etc.) is a key characteristic of cocaine use disorder (CUD) that is embedded into multiple diagnostic criteria for CUD. Accordingly, basic research conducted in a drug-vs-food “choice” context has improved our fundamental knowledge of the behavioral and neurobiological mechanisms of drug reinforcement. However, to date, these preclinical studies have only been conducted with food as the alternative reinforcer. The extent to which other non-drug reinforcers compete with cocaine-taking behavior is unknown. The studies in this dissertation establish two sophisticated discrete-trial cocaine-vs-alternative …

Novel Strategies In Head And Neck Tumor Therapy; Contribution Of Senescence In Therapy Response, And Resistance Development After Cisplatin Treatment, Fereshteh Ahmadinejad

Theses and Dissertations

Therapeutic outcomes achieved in head and neck squamous cell carcinoma (HNSCC) patients by concurrent cisplatin-based chemoradiotherapy initially reflect both tumor regression and tumor stasis. However, local, and distant metastasis and disease relapse as well as cisplatin-induced resistance are common in HNSCC patients. In the current work, we demonstrate that cisplatin treatment induces senescence in both p53 wild- type HN30 and p53 mutant HN12 head and neck cancer models. We also show that tumor cells can escape from senescence both in vitro and in vivo. We further established a cisplatin-resistant cell line from HN30 parental cell line that underwent brief senescence …

Sex Identification Of Mytilus Edulis Following 26 Day Treatment To Ee2 And Kz, Helen C. Poynton, K. Garrett Evensen

Data and Datasets

Blue mussel M. edulis were exposed for 26 days to 50 ng/L 17alpha-ethinylestradiol or 30 ug/L ketoconazole for 26 days in four replicate tanks. Prior to exposure, mussel sex was identified using the VERL-VCL RT-qPCR assay on hemolymph collected from each mussel. Following exposure, mantle tissue was collected from each treated mussel and the VERL-VCL RT-qPCR assay was used to identify the sex of the mussels.

Telomeres: A Tool To Assess The Impacts Of Mining Contaminants On Riparian Songbirds, Lillian Krach, Bridger Creel, Megan Fylling, Zac Cheviron, Creagh Breuner

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Mining has left massive environmental and physical scars across the landscape. Aquatic and riparian landscapes in particular have been significantly impacted by traditional mining practices. Waste products left over from hard-rock mining leech heavy metals onto the landscape and these metals spread from headwater streams to major waterways (Lottermoser 2010). Heavy metals have been shown to cause physiological stress and challenges to organisms depending on the metal and the concentration (Baos et al. 2019, Boyd & Rajakaruna 2013). While some mining-impaired areas have undergone restoration efforts, is it enough? Typical restoration methods replace the contaminated floodplain, but not the riverbed …

Lead And Cadmium Exposure Alters Respiration And Shell Bioadhesive Matrix In A Single-Chambered, Agglutinated Foraminiferan Protist: Implications For Marine Biomonitoring, Amanda L. Andreas

Legacy Theses & Dissertations (2009 - 2024)

Heavy metal exposure from anthropogenic pollutants negatively affects many marine organisms, including foraminiferan protists. Foraminifera are often used as bioindicators in benthic environments due to their sensitivity to environmental stress. Primary research has commonly focused on how heavy metals affect foraminiferal assemblages, distribution, ultrastructure, and shell morphology. Multi-chambered calcareous and agglutinated forams are the primary focus of such ecotoxicological studies; however, less is known about how heavy metals affect the physiology and shell microarchitecture of monothalamid agglutinated species. The research reported here represents an interdisciplinary environmental toxicology approach to study the exposure effects of heavy metal toxicants, lead (Pb) and …

Revisiting The 2018 Corsica Oil Spill - A Preliminary Case Study Of Ecosystem Recovery From Pahs In Yelkouan Shearwater (Puffinus Yelkouan), Makenna Mahrer

CMC Senior Theses

Polycyclic aromatic hydrocarbons (PAHs) are a specific class of persistent organic pollutants (POPs) heavily associated with crude oil, and pose genotoxic and physiological threats to marine life when released into the aquatic environment during a petroleum spill. This study seeks to understand the residual impacts of the 2018 Corsica oil spill on Puffinus yelkouan (Yelkouan Shearwater), a seabird endemic to the Mediterranean basin, using the species as a bioindicator for contamination in the region. Though classified by the IUCN Red List as ‘vulnerable,’ this species remains grossly understudied in present monitoring literature. This study made use of blood samples and …

The Evaluation Of The Efficacy And Safety Of Different Methods Of Myopia Control, Chaya Feuchtwanger

The Science Journal of the Lander College of Arts and Sciences

Myopia is the leading cause of preventable blindness in East Asia and has a rising global prevalence. If no treatment is done to curb myopic progression, the eye will continue to grow leading to high refractive errors. A higher prescription leads to an increased risk of developing sight-threatening diseases that can lead to irreversible blindness later in life. The discovery of a treatment that slows or even stops myopia from progressing is increasingly important with many studies being conducted worldwide. Currently, the most effective forms of myopia control are atropine eye drops and specialty contact lenses, with new studies exploring …

Epilepsy And Treatment Resistance, Eva Kowalsky

The Science Journal of the Lander College of Arts and Sciences

Epilepsy is one of the most common debilitating neurological conditions. Individuals with epilepsy experience frequent seizures. Seizures are caused by hyperexcitable and hyper-synchronized neurons. Anti-seizure medications typically work to normalize the electrical activity in the brain. Many epileptic disorders are caused by genetic mutations, most of which cause mutations in ion channel mechanics. 30% of individuals with epilepsy do not respond to classic anti-seizure medications. A combination of factors typically contributes to treatment resistance. Individuals with drug-resistant epilepsy must turn to novel approaches for seizure relief. These approaches include following a ketogenic diet, using CBD products, utilizing a neurostimulator device, …

The Effects Of Nausea And Vomiting On Mother And Child, Mayane Bensoussan

The Science Journal of the Lander College of Arts and Sciences

Nausea and vomiting are common side effects that can occur during pregnancy. On one hand, it can lead to its severe form called hyperemesis gravidarum, which can lead to hospitalization for electrolyte imbalances, dehydration, muscle weakness, or arrhythmias. On the other hand, nausea and vomiting may be an indication of a statistically healthier fetus. Benefits of maternal nausea and emesis to the developing fetus include improved neural development, decreased risk for congenital heart defects, and decreased incidence of miscarriages. Additionally, benefits to the mother include decreased risk for lung, cervical, and rectal cancer. The mothers also had an overall decreased …

Effects Of Microdosing With Psilocybin Mushrooms, Chavivah Davis

The Science Journal of the Lander College of Arts and Sciences

Microdosing with psilocybin, a psychoactive compound found in certain species of mushrooms, has gained popularity in recent years as a means of enhancing mood, cognition, and creativity without inducing the full-blown psychedelic experience. There are many potential benefits associated with microdosing with psilocybin. Although studies do show many positive effects of microdosing with psilocybin, long-term research is required to make a conclusive statement regarding this topic. Furthermore, there are risks and concerns involved that need to be considered, including the illegality of psilocybin and the lack of research. This paper will review the available literature on microdosing with psilocybin. It …

Epinephrine And Cardiac Arrest: The Catch-22, Shaina Friedman

The Science Journal of the Lander College of Arts and Sciences

Epinephrine has been a standard of care treatment for cardiac arrest for the last century; however, the use of epinephrine began without a significant amount of research. In recent years, many have started to question whether epinephrine is an appropriate treatment for cardiac arrest. While epinephrine causes vasoconstriction of the blood vessels and directs much-needed blood flow to the heart, it has also been shown to harm the microvessels of the brain, causing ischemia and neurological damage. Many trials, studies, and surveys were conducted to determine the correct course of action involving the use of epinephrine during cardiac arrest. Additional …

The Impact Of Maternal Health On Breastfeeding Duration, Yael Weinberg

The Science Journal of the Lander College of Arts and Sciences

The mechanism of breastfeeding is a complex biological process beginning with hormone production from the pituitary gland and ending with the ejection of milk from the breasts. Mothers are recommended to breastfeed exclusively for six months and then continue for another six with the addition of solid food. However, despite the countless health benefits associated with lengthened breastfeeding for both mother and infant, many women dismiss this recommendation. This paper aims to research the aspects of maternal health that can derail the recommended duration of breastfeeding, focusing on emotional health, nutritional intake, and various diseases or surgeries. It is found …