Pharmacology, Toxicology and Environmental Health Commons^™

Impact Of Cadmium Stress On Soil Virus Reproduction And The Persistence Of Viruses Under Abiotic Conditions, Zhibo Cheng

Doctoral Dissertations

Soil viruses are ubiquitous and greatly impact the structure and function of soil microbial communities, with their effects modulated by various environmental factors. This study investigates the inactivation of naturally occurring soil viruses in sterilized soil, as well as the effects of cadmium (Cd) exposure and carbon (C) and nitrogen (N) nutrient availability on the population dynamics of virus-host communities in agricultural soil.

Lab-scale slurry and unsaturated experiments were performed to examine virus inactivation in the absence of host bacteria in sterilized soil. In slurry experiments, virus abundance declined by over 90% after 10 days of incubation. The addition of …

Roles Of Soil Pores In Determining Water Retention And Microbial Dynamics, Huihui Sun

Doctoral Dissertations

Soil pore provides an essential habitat for microbial communities to participate in various biogeochemical processes. The complex pore spaces, which are defined by the arrangement of particles of varying sizes, govern the distribution of water for microbial dispersal and movement and microbial interaction with one another, such as bacterial cell-to-cell and bacterium-virus interactions. This research focused on exploring how soil pores influence soil water retention and bacterial interactions and quantify the spatial distribution of bacteria and viruses in fine-scale of soil pores. Using a mathematical model, this study simulated a soil water retention curve based on the relationship between soil …

Mechanisms Of Cigarette Smoke-Induced Mitochondrial Dysfunction In Striated Muscle And Aorta, Stephen T. Decker

Doctoral Dissertations

Cigarette Smoke is a significant cause of morbidity and mortality in the United States, accounting for over 480,000 annual deaths. Of these deaths, the most common cause of mortality in chronic smokers is cardiometabolic diseases. Likewise, a significant portion of smokers experience some form of cardiac, vascular, or metabolic dysfunction throughout their lifetime. More specifically, smoking is shown to induce mitochondrial dysfunction in these tissues, causing an increase in oxidative damage and poor overall health. However, despite the advances in the health outcomes related to cigarette smoke exposure, the mechanisms underlying mitochondrial dysfunction in striated muscle and the vasculature remain …

Exposure To Endocrine Disrupting Chemicals And The Effects On Inflammation And Mammary Tumor Progression, Stephanie Morin

Doctoral Dissertations

The vast majority of breast cancers, ~70%, are not directly related to an inherited genetic mutation. Environmental factors play a dominant role in the etiology of most breast cancers. There is a subset of chemicals that are able to affect the homeostasis of hormones called endocrine disrupting chemicals (EDCs). Many of these chemicals are pervasive and persistent making the chances for lifetime exposure more prevalent. While many of these chemicals have been deemed safe, a subset of them have come under review to reassess their safety. As estrogen is critical for breast development and can act as a mitogen in …

Interactions Between Soft Nanoparticles And Mammalian Cells, Mitchell Raith

Doctoral Dissertations

Nanoparticles have been of interest to the pharmaceutical industry since the 1980s. The first FDA approved nanoparticle-based therapies included liposomal anesthesia agents. Since then, the amount of FDA-approved nanoparticle therapies remains low. This is because nanoparticle-patient interactions can be very complex and are not well understood. Complicating factors also include increasing obesity rates among the patient population and many small animal pre-clinical trials are completed with healthy, lean animals. The biochemical differences between lean and obese patients prevents early studies from accurately predicting nanoparticle clinical behaviors. Many nanoparticles fail in trails. In this thesis, I aimed to uncover how nanoparticles …

Oxybenzone And The Mammary Gland: Impact Of An Environmental Pollutant On Health, Disease & Ethical Decision-Making, Klara Matouskova

Doctoral Dissertations

The environmental pollutant and common sunscreen compound oxybenzone is a benzophenone type UV light chemical filter used in industrial and consumer goods. This chemical widely contaminates human tissues, non-human species, and environmental matrices. In this dissertation, oxybenzone is investigated for its effects on the mouse mammary gland in the offspring following perinatal exposure; after perinatal and prepubertal exposures as a dual environmental insult during two sensitive times of development; and in adults after exposure during pregnancy & lactation as an environmental factor potentially increasing the tissue susceptibility to mammary tumors. Chapter 1 introduces the mammary gland. Chapter 2 reviews UV …

Fate And Effect Of Food-Grade Titanium Dioxide Particles/Polystyrene Nanoplastics On Nutrients Bioaccessibility Of Food In The Simulated Human Gastrointestinal Tract, Chunyang Li

Doctoral Dissertations

Food grade titanium dioxide particles (E171), as whitening agent, are commonly used in chewing gums, candies, sauces, salad dressings, and powdered milk. Recently, nanoplastics (NPs) (defined as < 1 µm), which are degraded from plastic debris undergoing environmental process, have received global attention. Because nanoplastics are ubiquitous in aquatic and terrestrial systems, and have been detected in marine animals, table salts, drinking water, and air. Thus, the presence of E171 as additives in the food, and the nanoplastics in food chains, both pose potential risks to human health through retarded processes in the gastrointestinal tract (GIT). However, the knowledge about the fate of E171 or nanoplastics and their impact on digestive enzymes activity or nutrient bioaccessiblity are currently limited. Therefore, it is necessary to investigate potential impacts of E171 or nanoplastics on digestion processes and nutrient bioaccessibility in the simulated human gastrointestinal tract, which includes mouth, stomach and intestinal phases, to mimic the digestion processes of food incubating with E171 or polystyrene (PS) nanoplastics. The objectives of my dissertation and major findings are presented below: 1) The impacts of E171 on lipid digestion and vitamin D₃ (VD₃) bioaccessibility encapsulated within oil-in-water emulsions in a simulated human gastrointestinal tract model were explored; 2) The impacts of E171 on the bioaccessibility of minerals (Ca, K, Mg, Fe, Mn, Zn, P and S) released from spinach leaves using a simulated human digestion tract were investigated; 3) The impacts of various concentrations or different functional group (-COOH, -NH₂) of PS NPs on the starch hydrolysis in the simulated …

Investigating The Developmental Impacts Of 3,3’-Dichlorobiphenyl (Pcb-11) In Zebrafish (Danio Rerio), Monika A. Roy

Doctoral Dissertations

The environmental pollutant 3,3’-dichlorobiphenyl (PCB-11) is a lower-chlorinated polychlorinated biphenyl (PCB) congener present in air and water samples. Both PCB-11 and its metabolite, 4-PCB-11-Sulfate, are detected in humans, including in pregnant women. The work conducted for this dissertation takes a developmental toxicology approach and uses zebrafish (Danio rerio) to investigate PCB-11’s potential impacts to the liver and pancreas. Chapter 1 introduces PCBs and the current knowledge gaps. Chapter 2 investigates PCB-11 interactions in short-term 4-day exposures with the Aryl hydrocarbon receptor (Ahr) pathway in both 0-20 mM individual and mixture exposures with other Ahr agonists. In Chapter 3, …

Monitoring Mammals At Multiple Scales: Case Studies From Carnivore Communities, Kadambari Devarajan

Doctoral Dissertations

Carnivores are distributed widely and threatened by habitat loss, poaching, climate change, and disease. They are considered integral to ecosystem function through their direct and indirect interactions with species at different trophic levels. Given the importance of carnivores, it is of high conservation priority to understand the processes driving carnivore assemblages in different systems. It is thus essential to determine the abiotic and biotic drivers of carnivore community composition at different spatial scales and address the following questions: (i) What factors influence carnivore community composition and diversity? (ii) How do the factors influencing carnivore communities vary across spatial and temporal …

Anti-Inflammatory And Chemopreventive Activity Of Lunasin From Tofu Whey For The Management Of Gastrointestinal Diseases, Cindy Andrea Nieto Veloza

Doctoral Dissertations

Gastrointestinal diseases such as inflammatory bowel diseases (IBD) and colorectal cancer (CRC) are pathological conditions associated with chronic inflammation, characterized by intestinal damage, debilitating symptoms, and detrimental health consequences. The increased risk of CRC in IBD patients, and the adverse effects associated with current therapeutic strategies, point out the need for safer alternatives to reduce chronic inflammation in the bowel. Lunasin is a bioactive peptide naturally occurring in soybeans, with chemopreventive and anti-inflammatory properties demonstrated in several extra-intestinal diseases. However, to date, there is no evidence of the biological activity of lunasin on the gastrointestinal tract as a target site. …

Interactions Between Titanium Dioxide Nanoparticles (Nps) And Mucin, . Boimin

Doctoral Dissertations

Titanium dioxide nanoparticles (TiO₂ NPs) are widely used in many food, consumer, and industrial products. However, little is known about the overall effects of TiO₂ NPs on the environment or human health. In order to elucidate the fate, transformation, transport, and toxicological impact of TiO₂ NPs, a better understanding is needed of how the physicochemical properties of TiO₂ NPs (e.g. size, charge, curvature, hydrophobicity, and surface functionality) interact with their microenvironments (e.g. pH, temperature, bile acids, microbiome, enzymes, surface-active components, and biopolymers). Living organisms including humans have a natural mechanism to protect themselves from physical, biological, …

High Throughput Analysis To Study Emerging Pollutants And Nanoparticle Fate In Biological Systems, Xiaolong He

Doctoral Dissertations

”The increasing applications of emerging and fugitive contaminants (EFCs) and engineered nanoparticles (ENPs) attract significant research interest for their potential risks to human health and the environment. In order to assess the health risks of these emerging contaminants, rapid and reliable analytical methods to measure the concentrations and fates of these contaminants are imperative. This dissertation focuses on the developments of advanced analytical methods and their applications to study those emerging contaminants in crop plant and simulated gastric fluid (SGF). Three types of mass spectrometry based methodologies have been developed, one is freeze-thaw/centrifugation extraction followed by high performance liquid chromatography …

Redox Signaling In The Zebrafish Embryo And Implications For Endocrine Pancreas Morphogenesis, Archit Rastogi

Doctoral Dissertations

The glutathione (GSH) system evolved to combat oxygen toxicity in nearly all living organisms, and serves as the predominant cellular redox buffer in vertebrates. This dissertation explores the roles of GSH during embryogenesis using the zebrafish (Danio rerio). The first agnostic in vivo characterization of GSH utilization in the embryo revealed strict spatiotemporal GSH profiles in developing organ systems. Interruption of these GSH profiles by exogenous xenobiotics led to organ specific adverse developmental outcomes; pancreatic β-cells were found to be especially susceptible and developed atypical morphologies following redox active xenobiotic exposures. Pancreatic β-cells lacked expression of Nrf2a (Nuclear …

Environmental Risk Factors For Inflammatory Bowel Disease: Triclosan And Other Consumer Antimicrobials, Katherine Z. Sanidad

Doctoral Dissertations

Inflammatory bowel disease (IBD) has become a serious health problem since the incidence and prevalence of IBD has dramatically increased throughout the world. There is evidence that environmental factors are primarily responsible for the increase of IBD, therefore, it is important to identify novel environmental risk factors to reduce the risk of IBD and its associated diseases. Antimicrobials used in consumer products might serve as environmental risk factors for IBD and its associated diseases. Triclosan (TCS), triclocarban (TCC), benzalkonium chloride (BAC), benzethonium chloride (BET), and chloroxylenol (PCMX) are widely used antimicrobial ingredients in consumer products and are ubiquitous contaminants in …

Hybridized Polymeric Nano-Assemblies: Key Insights Into Addressing Mdr Infections, Ryan Landis

Doctoral Dissertations

Multidrug-resistant (MDR) bacteria contribute to more than 700,000 annual deaths world-wide. Millions more suffer from limb amputations or face high healthcare treatment costs where prolonged and costly therapeutic regimens are used to counter MDR infections. While there is an international push to develop novel and more powerful antimicrobials to address the impending threat, one particularly interesting approach that has re-emerged are essential oils, phytochemical extracts derived from plant sources. While their antimicrobial activity demonstrates a promising avenue, their stability in aqueous media, limits their practical use in or on mammals. Inspired by the versatility of polymer nanotechnology and the sustainability …

Silver Nanoparticles In Environmental And Biological Systems: Source, Transformation, And Detection, Huiyuan Guo

Doctoral Dissertations

Silver nanoparticles (AgNPs) are the most commonly used nanoparticles in consumer products. Concerns over human exposure to and risk from these particles have resulted in increased interest in novel strategies to detect manufactured AgNPs. This dissertation investigated the feasibility of SERS as a technique for the detection and quantification of manufactured AgNPs in different matrices. By using ferbam as an indicator molecule that binds strongly onto the nanoparticles, AgNPs detection and discrimination were achieved based on the signature SERS response of AgNPs-ferbam complex. AgNPs coated with citrate and polyvinylpirrolidone (PVP) showed strong interactions with ferbam and induced high SERS signals. …

Golfer Exposure To Pesticides, Jeffery Doherty

Doctoral Dissertations

There is concern among industry regulators, turfgrass managers, and the general public over human exposure to pesticides following their application to turfgrass. The residential aspect of turfgrass applications raises concerns about exposure to infants and children, as well as adults. To accurately determine the exposure of golfers to turfgrass pesticides, it is necessary to understand their transfer and absorption dynamics, as well as the routes of golfer exposure. Previous research has demonstrated that exposure to some turfgrass pesticides is at a level that would concern USEPA risk assessors using the USEPA Hazard Quotient (HQ) criteria (1). This current research used …

Imidacloprid, A Neonicotinoid Insecticide, Impairs Lipid And Glucose Metabolism, Quancai Sun

Doctoral Dissertations

Emerging evidence suggests that environmental pollutants, including insecticides, are linked to excessive weight gain and altered glucose homeostasis. However, there is currently limited knowledge regarding the biochemical mechanisms by which exposure to insecticides contribute to obesity and its associated pathologies. We first studied the influence of fipronil (a phenylpyrazole family insecticide) on 3T3-L1 adipogenesis. Recently imidacloprid, a neonicotinoid insecticide, was reported to potentiate adipogenesis and insulin resistance in vitro. The current studies also determined the effects of imidacloprid exposure and its interaction with dietary fat in the development of adiposity and insulin resistance using both male and female C57BL/6J …

Robust Biosensors For Healthcare Applications: From High-Content Screening To Point-Of-Care Testing, Ngoc D. B. Le

Doctoral Dissertations

Efficient detection of proteins, mammalian cells, microorganisms and other biological systems in complex mixture is essential in disease diagnosis and environmental health. Therefore, technological platforms that provide sensors of high sensitivity, selectivity and stability are greatly desired. Recently, the ‘chemical-nose’ sensing approach has proved to be an effective strategy for profiling bio-relevant targets in complex mixtures. Detecting analytes in complex mixture is a challenge that conventional specificity-based sensors are still trying to solve due to the requirement of prior knowledge of the analyte, which is unknown in many cases. This thesis focuses on how to develop simple and robust …

Effects Of Permethrin, A Pyrethroid Insecticide, On Glucose And Lipid Metabolism, Xiao Xiao

Doctoral Dissertations

Over the last few decades, the decline of using organochlorine and organophosphorus insecticides has partially contributed to the rising utilization of newer synthetic insecticides, which are considered as less harmful and more environmental friendly than the older generation of insecticides. Pyrethroid insecticides are one of the newer insecticide classes reported with better biodegradability and low mammalian toxicity without sacrificing its insecticidal efficacy. Permethrin is one of the most widely used pyrethroid insecticides with structural similarity with natural pyrethrin insecticide from the flowers of Chrysanthemum cinerariifolium. Since its introduction in the 1970’s, permethrin has been extensively used in medicine, military, …

Total Organic Iodine Quantification And Occurrence In Drinking Water, And Toxicity Assessment Of Iodinated Disinfection By-Products, Rassil El Sayess

Doctoral Dissertations

The focus of this work has been placed is on iodinated DBPs (I-DBPs), measured using total organic iodine (TOI), a surrogate measure of iodinated organics. This is due to the growing toxicity literature that places I-DBPs among the most toxic of all DBPs. To measure TOI in water, a new method was developed. This method combines adsorption, combustion, and trapping of combustion products, with an offline inductively coupled plasma/mass spectrometer (ICP-MS) for iodide detection. Three factors were varied across two levels each in order to optimize the method. The chosen method used a sample pH of less than 1 prior …

Adsorption Of Biomolecules On Carbon-Based Nanomaterial As Affected By Surface Chemistry And Ionic Strength, Peng Du

Doctoral Dissertations

In the first project, we examined adsorption of bovine serum albumin (BSA) and lysozyme (LYZ) on carboxylated (CM), hydroxylated (HM) and graphitized (GM) multi-wall carbon nanotubes (CNTs). All adsorption isotherms were fitted well with Langmuir model. Maximum adsorption capacities (mg/g) followed: HM>CM>GM for both BSA and LYZ, which positively related to the surface areas of the three CNTs. However, after surface area normalization, adsorption capacity (mg/m²) followed: HM>GM>CM for BSA and GM>CM>HM for LYZ, indicating that functional groups and hydrophobicity of CNTs also contributed to protein adsorption. In addition, adsorption of LYZ …

Contributing Factors To Child Stunting In Guatemala: A Systems Analysis Focused On Enteric Disease Transmission And Mycotoxin Exposure, Lee Emerson Voth-Gaeddert

Doctoral Dissertations

"Child stunting -- low height-for-age -- is a United Nation's indicator for chronic malnutrition that has been linked to both acute and chronic health problems. Data from Guatemala suggests for children under five years of age, 49% are classified as stunted. This dissertation tests the following hypotheses, among children in Guatemala 1) environmental enteric dysfunction (EED) is correlated with height-for-age, 2) aflatoxin B (AFB) exposure is correlated with height-for-age, and 3) AFB exposure is correlated with EED. A network analysis was conducted on data from the US Agency for International Development (USAID) collected in 2012 to identify trends in a …

Bioactivity/Cytotoxicity Of Micro-/Nano-Materials And Novel Development Of Fiber-Optic Probes For Single Cell Monitoring, Qingbo Yang

Doctoral Dissertations

"Manufactured nano-/micro-materials (MNMs) have been widely used and their interactions with niche biological environment are highly concerned for both of their biohazardous and bioactive effects, whereas no available comprehensive evaluations or regulations have been provided yet. This dissertation thus focuses on three major aspects: 1) fundamental toxicity understandings of a typical MNMs (zinc oxide nanoparticles), 2) bioactivity evaluations of representative bioactive MNMs, and 3) development of novel micro-probes for high spatial resolution monitoring. Firstly, the NP's concentration, irradiation, hydrodynamic size, and the localized pH, ionic strength, NP zeta-potential as well as dissolved oxygen levels were found correlated with the production …

Lifetime And Effectiveness Evaluation Of Ceramic Pot Filters, Carlo Salvinelli

Doctoral Dissertations

"Poor water quality is a major contributing factor to disease in developing countries. Ceramic pot filters (CPFs) represent an effective and sustainable technology for poor communities, but the characterization of CPF lifetimes is on-going, and the water production seems to be the limiting factor. This dissertation describes laboratory and field investigations conducted to characterize the parameters that impact CPF effectiveness and lifetime in terms of water production and treatment efficacy, both under controlled and real use conditions.

CPF initial flow rate is the most common quality control parameter, but it may not be representative of the long-term effectiveness of the …

Physicochemical And Toxicological Assessment Of Antimicrobial Ε-Polylysine-Pectin Complexes, Cynthia L. Lopez Pena

Doctoral Dissertations

ε-Polylysine is an appealing FDA-approved, all natural antimicrobial biopolymer effective against a wide range of microorganisms. Its implementation is greatly limited by its strong cationic charge, which has been linked to instability in food systems, perceived astringency and bitterness, and the ability to inhibit lipid digestion. Previous studies have shown that controlled complexation of ε-polylysine with anionic pectin is able to prevent instability and astringency in simplified model food systems, while maintaining the antimicrobial character of polylysine. Isothermal titration calorimetry, micro-electrophoresis, microscopy, and turbidity analyses of the stability of electrostatic pectin-polylysine complexes in the presence of strongly anionic κ-carrageenan, and …

Exploring Novel Environmental Link To Obesity: Role Of Parabens In Adipogenesis In Vitro And In Vivo, Pan Hu

Doctoral Dissertations

Parabens are a group of alkyl esters of p-hydroxybenzoic acid that include methylparaben, ethylparaben, propylparaben, butylparaben, and benzylparaben. Paraben esters and their salts are widely used as preservatives in cosmetics, toiletries, food, and pharmaceuticals. Humans are exposed to parabens through the use of such products from dermal contact, ingestion, and inhalation. The extent of the exposure is reflected by the frequent detection of these compounds in urine samples in the general population. Moreover, parabens have been detected in human serum, milk, placental tissues and breast tumor tissues. Parabens have been shown to preserve estrogenic/antiandrogenic effects, and can activate peroxisome proliferator-activated …

Dried Whole Plant Artemisia Annua As A Novel Antimalarial Therapy, Mostafa A. Elfawal

Doctoral Dissertations

Dried Whole plant Artemisia annua as a novel antimalarial therapy September 2014 Mostafa Ahmed Elfawal Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST Directed by: Professor Stephen M. Rich Malaria is one of the worst vector-borne parasitic diseases in the developing world. The World Health Organization (WHO) estimated that 215 million cases of malaria occurred, with >655,000 deaths; half the world’s population is at risk of contracting the disease. Drugs are primary weapons for reducing malaria in human populations. Successful drugs are highly efficacious and inexpensive to manufacture synthetically. However, emergence of resistant parasites has repeatedly curtailed the lifespan of each drug that …

Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres

Doctoral Dissertations

Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of …

Applications And Improvements In The Molecular Modeling Of Protein And Ligand Interactions, Jason Bret Harris

Doctoral Dissertations

Understanding protein and ligand interactions is fundamental to treat disease and avoid toxicity in biological organisms. Molecular modeling is a helpful but imperfect tool used in computer-aided toxicology and drug discovery. In this work, molecular docking and structural informatics have been integrated with other modeling methods and physical experiments to better understand and improve predictions for protein and ligand interactions. Results presented as part of this research include:

1.) an application of single-protein docking for an intermediate state structure, specifically, modeling an intermediate state structure of alpha-1-antitrypsin and using the resulting model to virtually screen for chemical inhibitors that can …