Pharmacology, Toxicology and Environmental Health Commons^™

Nanoceria Exposure To Kidney Beans (Phaseolus Vulgaris): Implications On Plant Physiology, Nutrition And Their Transfer To Next Trophic Level, Sanghamitra Majumdar

Open Access Theses & Dissertations

Previous studies investigating the effects of cerium oxide nanoparticles (nanoceria, nCeO2) on plants have primarily focused on the physiological and biochemical changes at early growth stages. Comprehensive information on the effects of nCeO2 through the entire life cycle of plants and the nutritional quality of the edible tissues is limited. No studies have been reported on the interactions between nCeO2 and common beans (Phaseolus vulgaris). Common beans are leguminous crops, which are societally important due to their nutritional benefits. The beans are rich in proteins and essential nutrients like folate, iron, zinc, molybdenum and magnesium, and are consumed worldwide. This …

Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown

Theses and Dissertations--Neuroscience

The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity …

Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen

Theses and Dissertations--Pharmacy

Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.

Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most …

High-Content Screening In Zebrafish Embryos Identifies Abamectin As A Potent Neurotoxicant, Tara Diane Raftery

Theses and Dissertations

During development, the nervous system is a sensitive target for chemical exposure in both humans and animal models, and early life-stage exposures can lead to long-term effects on motor activity, sensory function, and cognition. Currently, there are minimal to no developmental neurotoxicity (DNT) data available for thousands of chemicals used in commerce, and it is impractical to screen these chemicals in rodent models using the existing DNT test guideline, as this test is costly, time- and animalintensive, and low-throughput. Therefore, there is a recognized need to use alternative non-mammalian models to support screening and prioritization of chemicals for DNT testing, …

Dna Methylation In Lung Tissues Of Mouse Offspring Exposed In Utero To Polycyclic Aromatic Hydrocarbons: Appendix C. Peak Scores Summary Table For All Methylated Genes In Any Data Set, Trevor Fish, Abby Benninghoff

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No abstract provided.

Utilization Of Placebo Response In Double-Blind Psychopharmacological Studies, Contextual Perspective, Margarita Olegovna Ashirova

Antioch University Dissertations & Theses

Placebo response has been an elusive phenomenon in the fields of medicine, medical research, and psychology. Even though it has been heavily utilized as a comparator treatment in double-blind psychopharmacological studies, the reliable definition and consistent understanding of placebo response are missing. In this contextual exploration, I outlined the state of current placebo response research and variable rates of placebo response reported in double-blind studies. I identified the gap in the literature—lack of consistent understanding of placebo response—that has led to a waste of resources by the psychopharmacological research industry. Further, I compared and contrasted the current inconsistent Western medical …

Detecting Diesel Particulate Matter Using Real Time Monitoring Under The Influence Of An Exhaust Fan System, Yasir Helal Alghamdi

Masters Theses

"Diesel Particulate Matter (DPM) is a complex mixture of diesel exhaust gas that consists of carbon, ash, metallic abrasion particles, sulfates and silicates. The diesel soot particle includes a solid core made of elemental carbon, and organic carbon compound attached to the surface of the soot particle. The main source of DPM is diesel exhaust gas. The National Institute for Occupational Safety and Health (NIOSH) and the Environmental Protection Agency (EPA) have determined that DPM is the source of most of the emissions of carbon monoxide, carbon dioxide, oxide of nitrogen, and hydrocarbons in underground coal, metal and non metal …

Evaluation Of The Methanol Whole Root Extract Of Securidaca Longipedunculata For Antitrypanosomal Activity In Vitro And In Vivo, Eke Ifeanyi Gabriel, Ihedioha Thelma Ebere, Ezeh Ikenna Onyema, Ezeudu Terry Adaku, Eze Ukamaka Uchenna, Okoye Chidozie Nwabuisi, Anaga Aruh Otah

The Thai Journal of Pharmaceutical Sciences

Securidaca longipedunculata is a medicinal plant used in different parts of Africa for treatment of various ailments including sleeping sickness in Northern Nigeria. On this basis, the methanol root extract of S. longipedunculata was investigated for ant...

The Role Of Nkcc2a On The Nervous System Activity, Kavya Annu

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The NKCC2A is a splice variant of the Na+K+2Cl- co-transporter 2 (Slc12a1), which is abundantly expressed in macula densa and in the apical membrane of the tubular cells in the kidney. Most of our knowledge regarding NKCC2 function is limited to the kidney, the organ where NKCC2 is abundantly expressed. However, recent studies have demonstrated that NKCC2 is also expressed in extra-renal tissues. This study was designed to determine if NKCC2A, a splice variant of NKCC2 has an impact on behavior and nervous system activity of mice. To these ends, we used mice (wild type, WT), lacking a single or …

Cross-Talk Between The Tumor Suppressors Par-4 And P53, Tripti Shrestha Bhattarai

Theses and Dissertations--Toxicology and Cancer Biology

This work describes the fascinating interplay between two tumor suppressors Prostate apoptosis response-4 (Par-4) and p53. The guardian of the genome, p53, is frequently mutated in human cancers, and may contribute to therapeutic resistance. However, p53 is intact and functional in normal tissues, and we observed that specific activation of p53 in normal fibroblasts could induce apoptosis selectively in p53-deficient cancer cells. This paracrine apoptotic effect was executed by Par-4 secreted in response to p53 activation. Accordingly, activation of p53 in wild-type mice, but not in p53^-/- or Par-4^-/- mice, caused systemic elevation of Par-4 that induced apoptosis …

Sperm Dna Oxidative Damage And Dna Adducts, Hueiwang Anna Jeng, Chih-Hong Pan, Mu-Rong Chao, Wen-Yi Lin

Community & Environmental Health Faculty Publications

The objective of this study was to investigate DNA damage and adducts in sperm from coke oven workers who have been exposed to polycyclic aromatic hydrocarbons. A longitudinal study was conducted with repeated measurements during spermatogenesis. Coke-oven workers (n =112) from a coke-oven plant served the PAH-exposed group, while administrators and security personnel (n=67) served the control. Routine semen parameters (concentration, motility, vitality, and morphology) were analyzed simultaneously; the assessment of sperm DNA integrity endpoints included DNA fragmentation, bulky DNA adducts, and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo). The degree of sperm DNA fragmentation was measured using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling …

Ramapough/Ford The Impact And Survival Of An Indigenous Community In The Shadow Of Ford Motor Company’S Toxic Legacy, Chuck Stead

Antioch University Dissertations & Theses

The purpose of this study was to examine the history of the Ford Motor Company’s impact upon the Ramapo Watershed of New York and New Jersey, as well as upon the Ramapough Munsi Nation, an indigenous population living there. In a 25 year span the automaker produced a record number of vehicles and dumped a massive amount of lead paint, leaving behind a toxic legacy that continues to plaque the area and its residents. The Ramapough people are not unlike many native nations living in the United States who have experienced industrial excess. This study examines the mindset that allows …

Nutrient Availability And Dynamics Of Compost Bedded Pack Dairy Barn Waste, Leslie Hammond

Theses and Dissertations--Plant and Soil Sciences

Increased adoption of compost bedded pack dairy barns (CBP), a relatively new housing and manure handling strategy, warrants study to facilitate proper use of CBP waste as a soil amendment. This study: 1) characterized in situ nutrient content and availability of CBP waste in terms of nitrogen (N) and phosphorus (P); 2) examined the decomposition of surface-applied CBP waste compared to an alternative processed solid waste amendment; 3) examined nutrient dynamics of incorporated CBP waste in high and low soil test phosphorus (STP) environments. Quick anaerobic mineralization assays revealed that bed management affects nutrient content and availability of CBP waste. …

Islet Dysfunction In Diabetes, Syeda Khadija

Wayne State University Dissertations

Type 2 Diabetes [T2DM] is a chronic condition resulting from gradual failure of pancreatic beta cells to synthesize and secrete sufficient insulin to meet the metabolic demands and the inability of tissues [muscle, adipose and liver] to efficiently utilize the secreted insulin leading to an overall increase in blood glucose levels [hyperglycemia]. As indicated by recent estimates from the International Diabetes Federation, the prevalence of the disease in the year 2014 has risen to a record 387 million worldwide. The main objective of my project was to study the mechanisms involved in pancreatic beta cell dysfunction in diabetes, specifically in …

Assessing Chemical Control Of Earthworms At Airports, Thomas W. Seamans, Bradley F. Blackwell, Glen E. Bernhardt, Daniel A. Potter

United States Department of Agriculture Wildlife Services: Staff Publications

Earthworms originating from Europe (e.g., Lumbricus spp., Aporrectodea spp.), which are common in the United States and southern Canada can create hazardous conditions at airports by attracting birds that pose a threat to aircraft. These nonnative earthworms are also considered pests on golf courses and sports fields, as well as having detrimental effects on temperate boreal forests. No toxicants or repellents are currently registered for earthworm control in the United States. Our purpose was to identify products that could be used to repel or suppress nonnative earthworms on airports or other managed sites where they pose a hazard or nuisance. …

In Vivo Analysis Of A Salt Bridge At The External Gate Of The Drosophila Melanogaster Serotonin Transporter In Response To Amphetamines, Timothy J. Beenen

Open Access Theses

Monoamine neurotransmitter transporters are membrane proteins responsible for the clearing of biogenic amines from a synapse. These transporters are targets for many important pharmaceuticals including antidepressants, as well as psychostimulant drugs such as cocaine and amphetamines. Amphetamines are believed to elicit their psychostimulant activity primarily by inducing a reversal of the transport cycle and increasing neurotransmitter release into the synapse, though the mechanism of this activity is incompletely understood. Previous in vitro research has suggested functional significance of a conserved salt bridge in the serotonin transporter (SERT) in amphetamine-induced 5-HT efflux. This salt bridge is disrupted in the Drosophila melanogaster …

The Association Of Lead With Cataracts And Vision-Related Problems In Perimenopausal Women, Imogene Drakes

Walden Dissertations and Doctoral Studies

Around the world, women are subject to an earlier incidence of cataracts, have a higher risk for cataracts, and also have a higher risk for other vision-related problems than men. Previous research has indicated an association between endogenous lead stored in long bones and cataracts in men over 60 years of age; however, a similar study in women did not reveal an association. This case control study was conducted to investigate whether perimenopausal mobilization of endogenous lead serves as a possible causative factor for women's generalized vision issues and cataract incidence in particular. Secondary data were gathered from 1,416 women …

Development Of Clinically Relevant In Vitro Performance Tests For Powder Inhalers, Xiangyin Wei

Theses and Dissertations

While realistic in vitro testing of dry powder inhalers (DPIs) can be used to establish in vitro–in vivo correlations (IVIVCs) and predict in vivo lung doses, the aerodynamic particle size distributions (APSDs) of those doses and their regional lung deposition remains unclear. Four studies were designed to improve testing centered on the behavior of Novolizer®. Different oropharyngeal geometries were assessed by testing different mouth-throat (MT) models across a realistic range of inhalation profiles (IPs) with Salbulin® Novolizer®. Small and large Virginia Commonwealth University (VCU) and Oropharyngeal Consortium (OPC) models produced similar ranges for total lung dose in vitro (TLD …

Synthetic Cannabinoids Versus Delta-9-Tetrahydrocannabinol: Abuse-Related Consequences Of Enhanced Efficacy At The Cannabinoid 1 Receptor, Travis Grim

Theses and Dissertations

In the past ten years, synthetic cannabinoids (SC) have emerged as drugs of abuse. Unlike D⁹-tetrahydrocannabinol (THC), many SCs are associated with serious health complications and death. One way in which THC and SCs differ lies with their enhanced potency and efficacy at the CB₁ receptor. No current methods exist to measure efficacy at the CB₁ receptor in vivo, and the abuse-related properties of SC cannabinoids are not well explored. Here, we utilized CB₁ wild type (WT), heterozygous (HET), and knockout (KO) mice. By employing CB₁ ligands which differ in efficacy we have …

Developing Proteomic And Cytokine Biomarkers For Vulvodynia, Ashvin Iyer

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Vulvodynia is a chronic, heterogeneous, and multifactorial disease. This condition may affect up to 18 percent of the female population including Caucasians, African Americans, Africans and Hispanics particularly those sexually active at child bearing age. The etiology of this condition is complex and multifactorial and it is frequently accompanied by physical disabilities, psychological distress and sexual dysfunction. Clinically, vulvodynia can be generalized or localized and pain can be provoked or unprovoked. Patients may also describe vulvar paresthesias or dysesthesias that may last hours. The International Society for the Study of Vulvar Disease (ISSVD) recognizes vulvar pain related to a specific …

Expression Of Aquaporins In Mouse Choroid Plexus And Ependymal Cells, Pankaj Patyal

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The choroid plexuses (CPs) are highly vascularized epithelial structures lying in the brain ventricles, forming the blood-cerebrospinal fluid (CSF) barrier. CPs are composed of a monolayer of cuboidal epithelial cells, derived from ependymal cells (EPCs), joined by tight junctions, and surrounding a core of fenestrated capillaries. Choroid plexus epithelial cells (CPECs) secrete most of the CSF through poorly understood mechanisms that involve aquaporins (AQPs) and various solute transport proteins like the Na+-K+-2Cl- cotransporter 1 (NKCC1). It is thought that the concerted action of these membrane proteins directs the transepithelial movement of solutes and water across CPECs. Net water movement across …

Effect Of Progesterone, Terbutaline And Leptin On The Function Of Alveolar Type Ii Cells, Shamili Sammohi

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The "surfactant" produced by type II pneumonocytes is deficient in term and preterm infants born and diagnosed with Respiratory Distress Syndrome (RDS). Corticosteroids such as dexamethasone or betamethasone are clinically used as the primary line of treatment to stimulate the production of surfactant. The steroidal hormone, progesterone appears to play a role in the fetal lung development and also appears to increase the expression of inflammatory markers in both term and preterm infants. However, the impact of progesterone on surfactant production remains unknown. Like progesterone, the tocolytic drug terbutaline has also been implicated in phosphatidylcholine production in the pneumonocytes of …

Na+/K+ Pump And Cl--Coupled Na+ And K+ Co-Transporters In Mouse Embryonic Fibroblasts Lacking The Tuberous Sclerosis Complex Tsc1 And Tsc2 Genes., Jasser Ali S. Alzhrani

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The tuberous sclerosis complex 1 and 2 (TSC1 and TSC2) genes and their products hamartin and tuberin, respectively, are involved in several regulatory cellular mechanisms, including the mTOR pathway that is important for proliferation, cell migration, and protein synthesis. In addition, it has been suggested that this pathway plays a role in regulating Na+-K+-2Cl- and K+-Cl- cotransporters (NKCC and KCC, respectively) [41, 42, 43]. Therefore, the TSC1 and TSC2 genes are expected to play a significant role in regulating cell volume, and K+ and Cl- homeostasis. This study tests the hypothesis that the TSC1 and TSC2 genes, which control cell …

Role Of Angiotensin Ii Type 1a Receptors On Renal And Urinary Angiotensin Converting Enzyme 2 (Ace2) And Neprilysin (Nep) In The Two-Kidney One-Clip (2k1c) Model Of Renovascular Hypertension, Laale F. Alawi

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Activation of the renin angiotensin system (RAS) and increased formation of angiotensin (Ang) II contribute to the progression of chronic kidney disease (CKD). Ang II, the major biologically active peptide of RAS, acts mainly as a vasoconstrictor through binding to the Ang II type 1 receptor (AT1R), which leads to increased blood pressure, fluid retention, and aldosterone secretion. The actions of Ang II are antagonized by its conversion to the vasodilator Ang (1-7), partly generated by the action of angiotensin converting enzyme 2 (ACE2) and/or neprilysin (NEP). The metalloprotease ADAM17 has a crucial role in the shedding of renal ACE2 …

Identification And Quantification Of The Collagen Type I, Iii And V In Rabbit Patellar Tendons, Mahesh Chandra Kodali

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Tendon injuries pose a great clinical challenge to orthopedic surgeons. Over 200,000 patients undergo tendon repair every year in the United States alone. The role of progression of a tendon injury is multifactorial as a lot of factors come into play during and after the injury at various phases of healing process. There is a still a vast requirement for thorough elucidation and understanding of the pathophysiology and the factors involved in the progression of tendon injury. Although the degenerative role of several MMPs and ADAMTs have been reported, yet there is very less information on the actual role and …

Interaction Between Na/ K-Atpase And Bcl-2 Proteins Bclxl And Bak, Tariq M. Alqahtani

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In silico analysis predicts interaction between the Na/ K-ATPase (NKA) and Bcl-2 protein canonical motifs BH3 and BH1. Such interaction is consistent with NKA inhibition by the benzo-phenanthridine alkaloid chelerythrine (CHE), a BH3 mimetic, in human lens epithelial cells (HLEC). This report establishes proof of concept: co-immuno-precipitation and immuno-colocalization showed unequivocal and direct interaction between NKA and Bcl-2 proteins. Particularly, NKA-antibodies co-immunoprecipitated BclXl and BAK in three different epithelial cell lines, HLECs and A549 lung cancer cells, whereas anti-Bcl-2 antibodies failed to pull down NKA. The molecular mass of the BAK proteins pulled down by antibodies against NKA and BclXl …

The Mechanisms Of Α-Amanitin Resistance In The Fruit Fly Drosophila Melanogaster, Chelsea L. Mitchell

Dissertations, Master's Theses and Master's Reports

Insect pesticide resistance has become a costly problem in the US. To make things more problematic, resistance to one pesticide is often associated with cross-resistance to other toxins, including pesticides that have not yet even been developed. In this study, we investigated a possible type of cross-resistance in the model fruit fly Drosophila melanogaster, some stocks of which are resistant to the very potent mushroom toxin α-amanitin. Because α-amanitin is solely produced by mushrooms, and because D. melanogaster does not feed on mushrooms in nature, the fruit flies should not be resistant to this toxin. In order to understand …

Endothelial Cell Derived Mvs And Exosomes: Release And Functional Study, Langni Liu

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Extracellular vesicles are membrane derived vesicles exists in all organs. The two major functioning extracellular vesicles are exosomes (EXMs) and microvesicles (MVs). EXMs released from cell membranes via exocytosis with size between 30-150 nm in diameter and MVs directly budded from plasma membrane and size between 100-1000 nm. Ceramide is one of the most important factor in lipid mechanism for EXM release and also associated with MV release. Ceramide generated from breakdown of sphingomyelin by neutral sphingomyelinase (nSMase). In this study, we used an nSMase inhibitor (GW4869) and an analogue of ceramide (C6-ceramide) to modulate the release of MVs and …

Differential Effects Of The Ahr On Immunoglobulin Gene Expression In Human B Cells, Naga Lakshmi Kaulini Burra

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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent and persistent environmental toxin known to inhibit immunoglobulin (Ig) gene expression in various animal models. TCDD is thought to modulate gene expression through the aryl hydrocarbon receptor (AhR) and thereby a subsequent alteration in gene expression. The AhR is a ligand-activated transcription factor that regulates xenobiotic-metabolizing enzymes. The mouse 3'Ig heavy chain regulatory region (3'IghRR) is a sensitive transcriptional target of TCDD that may mediate, in an AhR-dependent manner, the inhibitory effect of TCDD on Ig expression. Human B cells could also be a sensitive target of TCDD. The current study focuses on determining the …

Mcnair Research Journal - Summer 2015, Kelly Abuali, Starr Bailey, Krystal Courtney D. Belmonte, Brittaney Benson-Townsend, Jennifer Bolick, Mihaela A. Ciulei, Ashley Crisp, Daniel N. Erosa, Richard V. Foster, Gisele Braga Goertz, Michael A. Langhardt, Kara Osborne, Julienne Jochel Paraiso, Shawn M. Rosen, Bella V. Smith, Jeevake Attapattu, Ernesto H. Bedoy, Michael G. Curtis, Wanda Inthavong, Marielle Leo, Primrose Martin, Tamieka Meadows, Rosa Perez, Jessica Recarey, Shea Silver, Linda Tompkins

McNair Journal

Journal articles based on research conducted by undergraduate students in the McNair Scholars Program

Table of Contents

Biography of Dr. Ronald E. McNair

Statements:

Dr. Neal J. Smatresk, UNLV President

Dr. Juanita P. Fain, Vice President of Student Affairs

Dr. William W. Sullivan, Associate Vice President for Retention and Outreach

Mr. Keith Rogers, Deputy Executive Director of the Center for Academic Enrichment and Outreach

McNair Scholars Institute Staff