Pharmacology, Toxicology and Environmental Health Commons^™

Metabotropic Glutamate Receptor 2 Activation: Computational Predictions And Experimental Validation, Amr Ellaithy

Theses and Dissertations

G protein-coupled receptors (GPCRs) are the largest family of signaling proteins in animals and represent the largest family of druggable targets in the human genome. Therefore, it is of no surprise that the molecular mechanisms of GPCR activation and signal transduction have attracted close attention for the past few decades. Several stabilizing interactions within the GPCR transmembrane (TM) domain helices regulate receptor activation. An example is a salt bridge between 2 highly conserved amino acids at the bottom of TM3 and TM6 that has been characterized for a large number of GPCRs. Through structural modeling and molecular dynamics (MD) simulations, …

Complexities Of Chronic Opioid Exposure, Maciej Gonek

Theses and Dissertations

Studies on repeated exposure to opioids have been carried out for decades yet the mechanisms for certain phenomena such as tolerance are still not fully understood. Furthermore, different medications, such as frequently prescribed benzodiazepines, or different disease states, such as HIV, have their own effects and interactions with chronic opioid exposure that are not fully understood. The overall objective of this dissertation was to investigate the complexities of chronic opioid exposure and how different disease states and medications may modulate the effects of chronic opioids. Our findings demonstrate that the administration of diazepam, at doses that are not antinociceptive or …

Environmental Impacts On Enterococcus In Shem Creek, South Carolina, And Characterization Of Changing Land Use, Maria Elizabeth Zubizarreta

Theses and Dissertations

Zoning and land-use practices have a direct influence on hydrologic systems and can impact water resources. Linkages between change in land uses and degradation of water quality in stream and watershed environments have been well established. Shem Creek, located in Mount Pleasant, SC, has a history of fecal indicator bacteria levels that exceed the Environmental Protection Agency’s recreational water quality standards. With recent coastal population and development trends, proper management and the sustainability of beach and estuary environments are a rising public health concern. The objective of this study is to determine what climatic and water quality parameters are associated …

Linking Microbial Phylogenetic And Functional Gene Diversity To Microbial Mat Ecosystem Function Following Environmental Disturbance, Eva Christine Preisner

Theses and Dissertations

The ability of ecosystems to adapt to environmental perturbations depends on the duration and intensity of change and the overall biological diversity of the system. In this study, a microbial mat ecosystem located on San Salvador Island, the Bahamas was used as a model to examine how environmental disturbance affects microbial community resistance, their protein synthesis potential (PSP), ecosystem function as measured by biogeochemical cycling, community stability, and resilience. This ecosystem experienced a large shift in salinity (230 to 65 g kg-1) during 2011–2012 following the landfall of Hurricane Irene on San Salvador Island. High throughput sequencing and analysis of …

Understanding The Impact Of Land Use On Microbial Water Quality To Support Decisions For A Future Land Use Plan, Mohammed Tawfiq Aljassim

Theses and Dissertations

May River meandering through the Town of Bluffton, South Carolina has been known for its high level of water quality. The May River is one of the major sources of shellfish harvesting in South Carolina. Due to the non-point source pollution of fecal coliform, the water quality of the May River became degraded. As a result, shellfish harvesting classification in the May River was downgraded for the first time in its history. The rapid growth of the Town has led to a change in land use, which might be related to the increased levels of fecal coliform in the stream …

Inhibition Of Aflatoxin Biosynthesis With Vibrio Gazogenes, Phani Madhuri Gummadidala

Theses and Dissertations

Aflatoxin, a mycotoxin, is one of the world’s most potent carcinogen. It contaminates major food products such as milk, grains, nuts, corn, etc., leading to greater than $ 1 billion in economic losses and when ingested causes hepatocellular carcinoma (HCC). It is the primary risk factor for 75% HCC cases in the developing world and 3% HCC cases in developed world. Most common methods used in agriculture to reduce aflatoxin contamination are expensive, time consuming and have low efficiency with limited success rates where as biological controls were proven to be most effective in inhibiting aflatoxins and aflatoxin producing fungi. …

Individual Understanding Of The Risks Associated With Polypharmacy, Michelle Patricia Mchenry

Walden Dissertations and Doctoral Studies

With many individuals experiencing multimorbidity, individuals are being prescribed more medications. Although there are benefits to taking medications to manage symptoms and treat disease processes, there are also risks to taking multiple medications. The purpose of this phenomenological study was to explore participants' understanding of the risks associated with practicing polypharmacy. Game theory, credibility theory, and belief bias were the conceptual frameworks used to explain how individuals experienced their care and being prescribed 5 or more medications. Eight participants residing in subsidized housing in a small Midwest city, who were taking 5 or more medications volunteered to take part in …

Formulation And In Vitro Characterisation Of Fungal Chitosan Nanoparticles Coated With Zein For Improved Oral Delivery Of Selenoamino Acids, Giuliana Vozza

Doctoral

Selenium (Se) is an essential micronutrient in both human and animal nutrition that exists in a wide array of different forms, both organic and inorganic. Selenoamino acids (SeAAs), such as selenocystine (SeCys2), selenomethionine (SeMet), and methylselenocysteine (MSC) are organic species with reported health benefits of cancer prevention, increased fertility and improved immunological status. However, supplementation of SeAAs can be challenging, due to their reported narrow therapeutic range of indices, low bioavailability and increased susceptibility to oxidation. To address this, SeAAs were encapsulated into nanoparticles (NPs) to lower their toxicity profiles in comparison to their native form, in addition to offering …

Molecular Characterization Of The Mummichog (Fundulus Heteroclitus) Ovarian Steroidogenic Pathway And Implications For Exogenous Estrogen Effects During Follicular Development, Thiviya Kanagasabesan

Theses and Dissertations (Comprehensive)

This study investigated ovarian development in Fundulus heteroclitus (mummichog), through molecular characterization of key mediators in the ovarian steroidogenic pathway; these included ovarian StAR (steroidogenic acute regulatory protein), cytochrome P450 enzymes, estrogen receptors (ERα, ERβ1 and ERβ2), and gonadotropin receptors (FSHr and LHr); additionally, hepatic vitellogenin (VTG1) and ERs, and brain P450 aromatase (P450arom; CYP19b) were studied. Fish were staged into cortical alveolus, vitellogenic, early mature, late mature, and ovulating stages of maturation; blood (plasma), ovary (tissue and isolated ovarian follicles per stage), liver, and brains were collected. Testosterone (T), 17β-estradiol (E₂) and maturation inducing steroid (MIS), measured …

Forensic Markers Of Lampricide Toxicity In Oncorhynchsus Mykiss, Chris White

Theses and Dissertations (Comprehensive)

The lampricide 3-trifluoromethyl-4-nitrophenol (TFM) has been used for decades to control invasive sea lamprey (Petromyzon marinus) populations in the Great Lakes, normally with little harm to other fish populations. However, due to the nature of lampricide treatments and the chemical properties of TFM, adverse effects to non-target fishes and non-target mortality occasionally occur. However, investigations of non-target mortality can be complex, particularly if fish deaths are not noticed immediately, due to decomposition of the carcasses. The objectives of this thesis were to expose rainbow trout (Oncorhynchsus mykiss) to TFM in order to: (i) identify forensic markers …

Remobilization Of Heavy Metals By Mangrove Leaves, Hanan Almahasheer, Oscar Serrano, Carlos M. Duarte, Xabier Irigoien

Research outputs 2014 to 2021

Several studies have been carried out on heavy metal pollution in mangrove ecosystems. However, the role of mangroves in heavy metal remobilization is still relatively unknown. On one side, mangrove woody organs and soils sequester heavy metals for long time periods, but on the other hand, senescence of mangrove leaves may return these metals collected by roots to the upper layers of the soil. Here, we analyzed the concentration of chemical elements (Al, As, Cd, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Sr, V, and Zn) as a function of age in mangrove leaves to understand heavy metals retention by …

Examining The Issue Of Compliance With Personal Protective Equipment Among Wastewater Workers Across The Southeast Region Of The United States, Tamara L. Wright

College of Graduate Studies: Theses & Dissertations

Wastewater workers are exposed to different occupational hazards such as chemicals, gases, viruses, and bacteria. Personal Protective Equipment (PPE) is a significant factor that can reduce or increase the probability of an accident from hazardous exposures to chemicals and microbial contaminants. The purpose of this study was to identify wastewater worker’s beliefs and practices on wearing PPE and protections offered by PPE through the integration of the Health Belief Model (HBM). Participants were workers in the wastewater industry, which included wastewater operators, laboratory analysts, maintenance workers, wastewater collection workers, equipment operators, managers, and supervisors (n=272). The instrument was a self-administered …

Combating Staphylococcus Aureus And Its Methicillin Resistance Gene (Meca) With Cold Plasma, Xinyu Liao, Patrick J. Cullen, Donghong Liu, Aliyu Idris Muhammad, Shiguo Chen, Xingqian Ye, Jun Wang, Tian Ding

Articles

The increase in antibiotic resistance has become a global challenge to public health. In this study, an atmospheric cold plasma (ACP) system was applied for combating methicillin-resistant Staphylococcus aureus (MRSA) and its methicillin resistance gene (mecA) during food wastewater treatment. The plate count and flow cytometry methods were employed to estimate the damage in MRSA induced by plasma treatment. A quantitative real-time PCR (qPCR) method was used to assess the plasma-induced degradation of the mecA genes. The inactivation of MRSA and degradation of extracellular (e-) and intracellular (i-)mecA genes were investigated in phosphate buffered solution as a function of plasma …

Tumor Multicomponent Targeting Polymer-Lipid Hybrid Nanoparticles To Overcome Drug Resistance In Renal Cell Carcinoma, Hashem Obaid Alsaab

Wayne State University Dissertations

Renal Cell Carcinoma (RCC) contributes to more than 90% of the most common form of kidney tumor and remains one of the ten leading causes of cancer death in the United States. Although surgery remains an option for operable tumors, high metastatic index and resistance to radiation and chemotherapies prompted recent development of therapeutics that target the RCC angiogenesis and cell proliferation pathways. Tyrosine kinase inhibitors or TKIs (Cabozantinib, Axitinib, Sorafenib, and Sunitinib) and mammalian target of rapamycin (mTOR) inhibitors (Temsirolimus and Everolimus) have increased the therapeutic options for treating RCC. Although the impact towards decreasing disease progression is encouraging, …

Design, Synthesis And Biological Evaluation Of Pyrido[2,3-D]Pyrimidines As Inhibitors Of N5-Cair Synthetase, Qian Lin

Wayne State University Dissertations

The spread of drug-resistant bacterial infections has increased the need for novel antimicrobial agents. One potential but unexplored target is the de novo purine biosynthetic pathway. PurK, found only in bacteria, yeast, and fungi, catalyzes the sixth step in purine biosynthesis and has no human homolog. Herein we disclose the discovery of the first PurK inhibitor with submicromolar potency.

PurK is a member of the ATP-grasp superfamily of enzymes and recently, nanomolar inhibitors of biotin carboxylase, a related enzyme, were published. We hypothesized that those inhibitors, which target the ATP-binding site, could also inhibit PurK. To explore this hypothesis, four …

Test Of Bpa's Estrogenic Effects On Brain Aromatase Expression, Neural Activity, And Locomotive Behavior In Zebrafish Larvae, Ryan J. Mcauley

Cal Poly Humboldt theses and projects

Bisphenol A (BPA) is a well-known endocrine disrupting chemical that mimics the effects of estrogens. Aromatase B (Cyp19a1b) is a brain-specific enzyme that converts testosterone to estrogen and is highly upregulated in response to estrogen receptor activation localized to radial glial cells. During embryonic zebrafish development, there is a small window of time denoted by an increase in neurogenesis and estrogen receptor activity. Previous studies have demonstrated that a low dose BPA exposure (0.1µM) during this window causes hyperlocomotion in larval zebrafish, yet no further explanation for this behavior change has been described. The purpose of this study was to …

Possible Causes Of Preeclampsia And Potential Treatments, Helene Weinreb

The Science Journal of the Lander College of Arts and Sciences

Preeclampsia is a common complication of pregnancy characterized by hypertension and proteinuria. Its symptoms are well-defined, but the pathophysiology is not fully understood. This paper analyzes several of the most credible causes of this syndrome and attempts to relate these to the known risk factors. Current preeclampsia treatments are examined, and special focus is given to novel experimental treatments which offer hope of ending preeclampsia and eclampsia.

By What Mechanism Does Stress Affect Ovulation?, Chana Minkowicz

The Science Journal of the Lander College of Arts and Sciences

This paper explores the many mechanisms of how stress influences ovulation. For ovulation to occur, there needs to be a series of hormones released in a specific order, and in a specific amount. This paper will discuss the various type of stress a person can experience, and which specific reproductive hormone each different type of stress disrupts. This paper will also bring proof as to how each hormone is disturbed, and by which mechanism it is disrupted. There has not been one main mechanism that has been found thus far, therefore, it is important to take into consideration the various …

Full Issue: Volume 12, Number 1

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.

What Are The Mechanisms And Effects Of Age-Related Shortening Of The Spine?, Joseph Weingarten

The Science Journal of the Lander College of Arts and Sciences

Osteoporosis and Degenerative Disc Disease can cause a loss of height in the spine. This paper focuses on the mechanisms that cause age-related loss of height and its effects. Possible relationships between receptor activator nuclear factor kappa-B ligand (RANKL) and estrogen with osteoporosis are discussed, as well as possible genetic causes. Exercise may prevent osteoporosis. Osteoporosis may cause a loss of height, vertebral fracture, a decrease in maximum lung capacity, and hip fracture. Degenerative disc disease may cause shortening of the spine. Disc height loss can result in a reduction in the range of motion and stiffness at the affected …

New Medical Indications For Thalidomide And Its Derivatives, Chaya Newfield

The Science Journal of the Lander College of Arts and Sciences

Thalidomide is an anti-inflammatory and an anti-angiogenesis drug that is being used around the world for a variety of malignant and inflammatory diseases. Is it justified to continue prescribing and developing thalidomide given the discovery of many well-known side effects including catastrophic birth defects? To answer this question, this paper will discuss the pharmacology and history of thalidomide, as well as many of its proposed mechanisms of action.The medical indications for the current use of thalidomide as well as for several newer and more potent derivatives are mentioned for their therapeutic results, as well as their adverse side effects.

Can Somatic Cell Nuclear Transfer Produce Human Pluripotent Stem Cells For Regenerative Medicine?, Alexandra Iskhakov

The Science Journal of the Lander College of Arts and Sciences

In the last half a century, researchers and scientists discovered the application of somatic cell nuclear transfer (SCNT) to clone mammalian embryos to produce a line of pluripotent stem cells for medical and laboratory use. This is a breakthrough technology that is applied to stem cell research, regenerative medicine, and cloning. Somatic cells are non-germ cells that are differentiated but provide the nuclei that are transferred to enucleated oocytes. The replacement of the nuclei results in a developing embryo that contains the genetic information of the donated nucleus, which can either be transplanted into a surrogate mother to produce a …

Relaxin As A Cure For Fibrosis, Sarah Akilov

The Science Journal of the Lander College of Arts and Sciences

Until recently, relaxin has been known as a hormone that pertained to the female reproductive system. Its ability to remodel the extracellular matrix is responsible for its known reproductive effects. Current research has indicated that it may be useful as a drug to combat fibrosis. Relaxin has been proposed as an antifibrotic drug to target a variety of organs, including the skin, lung, kidney, liver, and heart. Studies done using the relaxin null knockout mouse have given scientists insight into the workings of this hormone. Human studies have also been done to test the efficacy of relaxin in its reversal …

Xenotransplantation:The Science, The Advantages, The Ethics, Chana Erlbaum

The Science Journal of the Lander College of Arts and Sciences

Xenotransplantation is a breakthrough medicinal technology that is an attempt to change the lives of millions of people. The problems in the current organ transplant system risk the lives of patients each and every day. Intense waiting periods and extremely costly procedures exemplify the stress and pressure that these patients face as an attempt to save their own lives. Xenotransplantation is the idea of growing human organs in a different species, using incredible stem-cell and CRISPR technology. This can introduce an answer to some of the issues in the current transplant system. Many technical and ethical issues are becoming relevant …

Impacts Of Trace Metal Pollution, Urbanization And Aquifer Recharge On Spokane River Macroinvertebrates, Carolyn K. Connelly

EWU Masters Thesis Collection

This study analyzed macroinvertebrate communities of the Spokane River to determine: 1) accumulation of toxic trace metals in macroinvertebrate tissue, 2) effects of aquifer recharge, and 3) impact of urbanization. I predicted that aquifer inflows of cold, clean water would mitigate effects of pollution, and that reaches above the City of Spokane would be less negatively affected by urbanization; both were unsupported. I also predicted that effects of toxic trace metals would decrease within distance downstream; this prediction was supported. I sampled 12 riffles of the Spokane River between the Washington/Idaho border and Riverside State Park in late summer 2010. …

Delay Discounting And Cannabinoid Enzyme Inhibitors, Devin Andrew Galdieri

Graduate Theses, Dissertations, and Problem Reports (ETD)

Delay discounting is a measure of impulsive choice that is correlated with maladaptive behavior and psychological disorders. Disruptions to serotonin and dopamine pathways can cause changes in delay discounting, as can lesions to the prefrontal cortex and nucleus accumbens. The endocannabinoid system modulates other neurotransmitter systems, including dopamine and serotonin pathways. Cannabinoid receptors type 1 are found in relatively high concentrations in the nucleus accumbens and the prefrontal cortex. These receptors are activated by endogenous cannabinoids, which are synthesized on demand and broken down by catabolic enzymes. The action of these enzymes can be inhibited by a class of drugs …

Exploring Science Identity: The Lived Experiences Of Underserved Students In A University Supplemental Science Program, Lynette D. Perrault

LSU New Orleans Theses and Dissertations

Underserved students attending under-resourced schools experience limited opportunities to engage in advanced science. An exploration into the influence a supplemental science program has on underserved students’ acquisition of science knowledge and skills to increase their pursuit of science was conducted to help explain science identity formation in students. The proliferation of supplemental science programs have emerged as a result of limited exposure and resources in science for underserved students, thus prompting further investigation into the influence supplemental science programs have on underserved students interest and motivation in science, attainment of science knowledge and skills, and confidence in science to promote …

Testing The Underlying Chemical Principles Of The Biotic Ligand Model (Blm) To Marine Copper Systems: Measuring Copper Speciation Using Fluorescence Quenching, Tara N. Tait, James C. Mcgeer, Scott Smith

Chemistry Faculty Publications

Speciation of copper in marine systems strongly influences the ability of copper to cause toxicity. Natural organic matter (NOM) contains many binding sites which provides a protective effect on copper toxicity. The purpose of this study was to characterize copper binding with NOM using fluorescence quenching techniques. Fluorescence quenching of NOM with copper was performed on nine sea water samples. The resulting stability con- stants and binding capacities were consistent with literature values of marine NOM, show- ing strong binding with log K values from 7.64 to 10.2 and binding capacities ranging from 15 to 3110 nmole mg C ^{−1 …}

Justin's Save The Frogs Project, Justin Sather

The Transdisciplinary STEAM+ Journal

Justin’s Save the Frog Project goals are 1) to spread the awareness about the rapid decline in frog population 2) inspire others to make the environment a better place for people and animals 3) make an impact by building wetlands in California specifically for the CA Red-Legged Frogs and Foothill Yellow Legged.

9-Aminoacridine Inhibits Ribosome Biogenesis And Synergizes With Cytotoxic Drugs To Induce Selective Killing Of P53-Deficient Cells, Leonid Anikin, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Common cancer treatments target rapidly dividing cells and do not discriminate between cancer and normal host cells. One approach to mitigating negative side‐effects of cancer treatment is to temporarily arrest cell cycle progression and thus protect normal cells during cytotoxic treatments, a concept called cyclotherapy. We recently proposed that transient inhibition of post‐transcriptional steps of ribosome biogenesis (RBG) can be used to selectively arrest p53‐positive host cells and not p53‐null cancer cells. In this study, we investigated whether cytoprotective RBG inhibition can be achieved through small molecule treatment.