Pharmacology, Toxicology and Environmental Health Commons^™

Abl1/2 And Ddr1 Cooperate To Stabilize Braf/Craf To Drive Erk1/2 Reactivation And Promote Mek Inhibitor Resistance In Nras-Mutant Melanomas, Anastasia Lyon

Theses and Dissertations--Pharmacology and Nutritional Sciences

This study addresses the escalating incidence of NRAS-mutant melanomas, a type of skin cancer lacking FDA-approved targeted therapies. Despite ongoing research targeting the RAF/MEK/ERK pathway, existing drugs fail to enhance progression-free survival due to acquired resistance. This project identifies a novel role for ABL1/2 and DDR1 kinases in driving drug resistance and proliferation of NRAS-mutant melanoma cells. ABL1/2 and DDR1 cooperate to promote RAF homodimerization and protein stability in order to reactivate MEK/ERK signaling to drive MEK1/2 inhibitor (MEKi) resistance and promote survival of resistant cells. By targeting ABL1/2 and DDR1 with nilotinib, a FDA-approved anti-leukemic inhibitor, we …

A Review Of Rattlesnake Venoms, Phuc Phan, Anant Deshwal, Tyler Anthony Mcmahon, Matthew Slikas, Elodie Andrews, Brian Becker, Thallapuranam Krishnaswamy Suresh Kumar

Chemistry & Biochemistry Faculty Publications and Presentations

Venom components are invaluable in biomedical research owing to their specificity and potency. Many of these components exist in two genera of rattlesnakes, Crotalus and Sistrurus, with high toxicity and proteolytic activity variation. This review focuses on venom components within rattlesnakes, and offers a comparison and itemized list of factors dictating venom composition, as well as presenting their known characteristics, activities, and significant applications in biosciences. There are 64 families and subfamilies of proteins present in Crotalus and Sistrurus venom. Snake venom serine proteases (SVSP), snake venom metalloproteases (SVMP), and phospholipases A2 (PLA2) are the standard components in Crotalus …

Geochemistry Of Rare Earth Elements In Simulated Natural Waters: Experiments And Modelling Of Precipitation, Complexation, And Bioavailability., Samantha Zulian

Theses and Dissertations (Comprehensive)

Rare earth elements (REEs) are an important part of modern technology and used for many applications. Mining, agriculture, improper recycling and medical applications can increase the concentration of these elements in surface waters. Metals in the environment including REEs can be found naturally but understanding the implications increase concentrations from anthropogenic inputs is important. REE mobility, persistence and toxicity is imperative to risk assessment as Canada begins to mine REE. Ultimately, as with other metals, the impacts of REEs in the environment should be dependent on the specific physical and chemical forms of the elements. Fractionation provides a practical method …

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 …

Assessing Road Dust Impacts On Macroinvertebrates Community Structure In Canadian Arctic Lakes, Hong Yi Gao

Theses and Dissertations (Comprehensive)

In the Canadian Arctic, unpaved gravel roads are essential for regional accessibility but are also potential sources of road dust runoff. My study investigated the impacts of road dust from the Dempster and Inuvik-Tuktoyaktuk Highways on adjacent freshwater ecosystems, focusing on water quality parameters and macroinvertebrate communities. Using a stratified random sampling design, 18 lakes were studied across two regions (boreal forest and tundra) and three distance categories from the road (0-300 m, 300-600 m, and > 600 m). Contrary to my initial hypotheses, findings revealed no significant differences in water quality or invertebrate communities relative to distance from the road. …

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) …

Assessing Stormwater Management Pond Water Quality, Function, And The Potential Biotic Effects To Receiving Waters, Mitchell Elstone

Theses and Dissertations (Comprehensive)

The use of stormwater management ponds (SWMPs) has been increasing over the past five decades. However, an in-depth understanding of the daily performance of SWMPs and functionality during cold periods is limited. This is in part because mandated monitoring is relatively infrequent, and the assumption that SWMPs are inactive between storm events and during the winter. The goals of this research were to better understand daily stormwater (SW) characteristics, the performance of SWMPs based on current forms of evaluation and assess the potential for SWMP effluent to impact downstream biota. Influent and effluent samples from two SWMPs were collected daily …

Fostering Environmental Sustainability Through Early Childhood Education(Ece)., Tahira Jabeen, Fozia Parveen, Nasima Shakeel

Books

No abstract provided.

Exploring The Dual Role Of Vegf165 In Bleomycin Induced Lung Injury And Recovery In A Aav Mice Model, Igor Ban

Theses and Dissertations

Pulmonary fibrosis (PF) poses a significant challenge in respiratory medicine due to its complex etiology and progression characterized by excessive lung scarring, leading to compromised pulmonary function. The multifaceted roles of Vascular Endothelial Growth Factor A (VEGF-A) and specifically its isoform VEGF-A165 are critical in this context, given their involvement in angiogenesis, lymphangiogenesis, and tissue repair. The dual nature of VEGF-A165, promoting angiogenesis and potentially exacerbating or mitigating fibrosis, underscores its significance in both the progression and recovery phases of PF. Our work, explores the nuanced functions of VEGF-A165 using AAV1 as a gene delivery vector to overexpress this growth …

The Effects Of Length, Weight, Age, And Gender On Mercury Concentrations In Burbot In North-Central Minnesota Lakes, Liam Hanley

Journal of Earth and Life Science

Burbot Lota lota in north-central Minnesota lakes have the potential to reach large sizes and consume large volumes of prey. This caveat may make burbot susceptible to higher rates of biocontamination, bioaccumulation and biomagnification. The objective of this study was to determine how changes in age, length, gender, weight, and lake affect total mercury concentrations in burbot. In this experiment 28 burbot were angled from three lakes: Cass (n = 17), Winnibigoshish (n = 4), and Bad Medicine (n = 7). Then tissue samples were taken from each fish and were lyophilized and homogenized. Homogenized tissue samples were analyzed by …

Therapeutic Intervention Of Neuroinflammation In Alzheimer Disease By Inhibition Of Classical Complement Pathway Using Anti-C1r Loaded Exosomes, Terjahna Richards

Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disease associated with memory decline and cognitive impairment. It is a growing global health and socioeconomic concern, affecting more than 50 million people worldwide. Current therapeutics focus solely on symptomatic management instead of preventative or curative strategies. This is mainly a result of the complexity of the pathophysiological mechanism and the poor understanding of the disease progression. Recently, studies have focused on bridging knowledge gaps giving rise to substantial evidence on the vital role of neuroinflammation in the progression of AD. Neuroinflammation has been shown to be a precursor to apparent amyloid plaque accumulation …

Hjp 272, An Endothelin Receptor Antagonist, And Its Role In Cancer Cell Migration And Invasion, Nabeela Fatima Baig

Theses and Dissertations

Endothelins are a family of versatile peptides composed of 21 amino acids with three isoforms: ET-1, ET-2, and ET-3. As the most abundant of the three isoforms, ET-1 is involved in various biological processes, such as regulation of vascular tone, humoral homeostasis, and neural crest development. However, focus is now being directed towards investigating the functions of the Endothelin axis in the progression of different tumor types including ovarian, prostate, breast, lungs etc. HJP 272 is a novel ETAR antagonist and while our group has previously researched its effects on lung inflammation and preterm birth, this study marks the first …

Characterizing The Role Of Epigenetic Regulator Menin In Pediatric Neuroblastoma Growth Using Pre-Clinical Models, Rameswari Chilamakuri

Theses and Dissertations

Epigenetic regulators such as Menin and MLL1 drive cancer progression, metastasis, and relapse. MLL1 forms a COMPASS complex with its binding partners, including Menin, to function as an epigenetic enzyme H3K4 methyltransferase. H3K4 methyltransferases are known to promote cancer stem cells' (CSCs) self-renewal capacity and metastasis. CSCs are one of the major causes of tumor relapse and metastasis conditions, ultimately leading to poor overall patient survival. Neuroblastoma (NB) is an extracranial solid tumor that accounts for 8-10% of all pediatric cancers, and approximately 50% of patients display metastasis at the time of diagnosis. In this study, we hypothesized and used …

Adgrl1 Is A Glucose Receptor Involved In Mediating Energy And Glucose Homeostasis, Kavaljit H Chhabra, Siresha Bathina, Tumininu S Faniyan, Dennis J Samuel, Muhammad Ummear Raza, Leticia Maria De Souza Cordeiro, Gonzalo Viana Di Prisco, Brady K Atwood, Jorge Robles, Lauren Bainbridge, Autumn Davis

Pharmacology and Nutritional Sciences Faculty Publications

AIMS/HYPOTHESIS: The brain is a major consumer of glucose as an energy source and regulates systemic glucose as well as energy balance. Although glucose transporters such as GLUT2 and sodium-glucose cotransporter 2 (SGLT2) are known to regulate glucose homeostasis and metabolism, the identity of a receptor that binds glucose to activate glucose signalling pathways in the brain is unknown. In this study, we aimed to discover a glucose receptor in the mouse hypothalamus.

METHODS: Here we used a high molecular mass glucose-biotin polymer to enrich glucose-bound mouse hypothalamic neurons through cell-based affinity chromatography. We then subjected the enriched neurons to …

Reducing Short-Chain Pfas Levels In California Water Supplies, Manu Prabandham

Pomona Senior Theses

This thesis proposes twelve specific policies based on precedents set by prior regulation of persistent organic pollutants (such as PCBs), the costs and benefits of short-chain PFAS, technologies available to remove and destroy short-chain PFAS, and the roles and limitations of California’s regulatory institutions. The twelve policies are chosen to be politically and financially feasible, effective at removing short-chain PFAS from water supplies, and equitable towards lower-income and minority Californians, who suffer the most from the consequences of PFAS and other environmental pollutants. The new definitions, education campaigns, studies, taxes, bans, standards, testing, and filtration systems proposed are intended to …

Photoluminescence Switching In Quantum Dots Connected With Fluorinated And Hydrogenated Photochromic Molecules, Ephraiem S. Sarabamoun, Jonathan M. Bietsch, Pramod Aryal, Amelia G. Reid, Maurice Curran, Grayson Johnson, Esther H. R. Tsai, Charles W. Machan, Guijun Wang, Joshua J. Choi

Chemistry & Biochemistry Faculty Publications

We investigate switching of photoluminescence (PL) from PbS quantum dots (QDs) crosslinked with two different types of photochromic diarylethene molecules, 4,4'-(1-cyclopentene-1,2-diyl)bis[5-methyl-2-thiophenecarboxylic acid] (1H) and 4,4'-(1-perfluorocyclopentene-1,2-diyl)bis[5-methyl-2-thiophenecarboxylic acid] (2F). Our results show that the QDs crosslinked with the hydrogenated molecule (1H) exhibit a greater amount of switching in photoluminescence intensity compared to QDs crosslinked with the fluorinated molecule (2F). With a combination of differential pulse voltammetry and density functional theory, we attribute the different amount of PL switching to the different energy levels between 1H and 2F molecules which result in different potential barrier …

Observed Effects Of Physiological Melatonin Dosing On Mda-Mb-231 Breast Cancer Cell Proliferation, Wenli Wu

Williams Honors College, Honors Research Projects

This project seeks to evaluate pharmacological dosing of melatonin on the cell proliferation of MDA-MB-231 breast cancer cell line in culture, using the two solubility carriers: DMSO/water and ethanol. This experiment is a component of ongoing research at the Eaton lab which will elucidate melatonin dose-response toxicology in zebrafish and a possible breast cancer xenograft model for novel treatment therapies.

Maximum Entropy Species Distribution Modeling For The Spring Ephemeral Herb Bloodroot (Sanguinaria Canadensis) In Eastern North America, Velan Manivannan

Williams Honors College, Honors Research Projects

The spring ephemeral plant Bloodroot (Sanguinaria canadensis) has a widespread native range in North America, spanning much of the eastern United States and Canada. While its current NatureServe conservation status is designated as ‘secure’ (NatureServe, 2023), its status as a spring ephemeral places it at a heightened risk for climate change-induced phenological mismatch with advancing forest canopy closure. Additionally, under continued anthropogenic climate change, Bloodroot may also experience range shifts or contractions as the edges of its present range warm past physiological thresholds. To determine the potential for range shifts and contractions under future warming, I generated a …

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 …