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The development of autoimmune diseases is frequently linked to exposure to environmental factors such as chemicals, drugs or infections. In the experimental model of metal-induced autoimmunity, administration of subtoxic doses of mercury (a common environmental pollutant) to genetically susceptible mice induces an autoimmune syndrome with rapid anti-nucleolar antibody production and immune system activation. Regulatory components of the innate immune system such as the costimulatory molecules PD-1, CTLA-4 and their ligands PD-L1, PD-L2, B7-1 and B7-2 can also modulate the autoimmune process. We examined the interplay among environmental chemicals and these costimulatory molecules in the regulation of autoimmunity. Additionally, we studied PD-1, CTLA-4 and its ligands in a tolerance model where pre-administration of a low dose of mercury in the steady state renders animals tolerant to metal-induced autoimmunity. Overall, PD-1/CTLA-4 blockade by blocking antibodies enhanced the manifestations of metal-induced autoimmunity. Although we expected that the blockade of both PD-1 ligands would mimic blocking the receptor, blocking the ligands resulted in the opposite effect when co-injected with mercury, reducing the manifestations of metal-induced autoimmunity. Individual PD-1 ligands differed in their ability to enhance the mercury treatment, with PD-L1 being the major regulator in the model. Likewise, we showed that PD-L1 is essential to keep the recall response to mercury at check. Our data suggest that these effects could be mediated by the modification of cytokine profiles, B cells and T cell subpopulations numbers. / Microbiology and Immunology

Mercury (Hg) is a global pollutant that has received much attention due to its ability to bioaccumulate, biomagnify, and maternally transfers in humans and wildlife. In vertebrates, exposure to Hg can impair growth, alter behavior and morphology, decrease survival, and reduce reproductive success. Unfortunately, most ecotoxicology studies euthanize animals to quantify the concentrations of Hg bioaccumulation and in doing so eliminate the ability to relate Hg accumulation to observed effects. The development of non-destructive sampling techniques is a critical step for sustainable monitoring of Hg bioaccumulation and associated effects because it eliminates adult harvest, enables repeated sampling of the same individual over time, and allows the collection of larger sample sizes. My research aimed to develop and validate non-destructive sampling techniques for assessing Hg bioaccumulation, maternal transfer, and consumption risks in a long-lived aquatic omnivore, the common snapping turtle (Chelydra serpentina). I collected blood, nail, muscle, and egg tissues from turtles inhabiting an Hg contaminated gradient at a historically contaminated river, the South River, located in central Virginia. In my first chapter, I developed mathematical models describing relationships between the four tissues sampled and in doing so, described important demographic, spatial, and temporal factors that influence Hg bioaccumulation in turtles that may be important for ecological risk assessment and consumption. Additionally, I found that my mathematical models were applicable to other Hg contaminated locations in Virginia. In my second chapter, I examined the effects Hg bioaccumulation and maternal transfer has on turtle reproduction. I collected and incubated eggs from gravid females from reference and contaminated sites and quantified embryonic morality, infertility, and hatching success of each clutch, and assessed all hatchlings and dead embryos for gross morphological malformations. I found that Hg exposure negatively influenced hatching success through increased egg infertility and embryonic mortality. Taken together, my results are applicable to a wide array of systems where biomonitoring and assessing the ecological and consumption risk of contamination in turtles needs to be accomplished in a sustainable and conservation-minded fashion. / Master of Science

Laboratory bioassays results suggest that early life stages of freshwater mussels are sensitivity to toxicants. However, toxicological databases for unionids are rather limited because standard test methods are yet developed, and no published studies report endpoints for chronic test that are > 9 days. The primary goals of my thesis research were to assess acute and chronic toxicities of chlorine and mercury to early life stages. Inter- and intra-specific species variability in the tolerances of glochidia was observed during acute laboratory bioassays as endpoints were between 8 - 43 ppb for Hg tests, 1.0 - 2.5 ppm for NaCl tests, and 70 - 260 ppb for chlorine (TRC) tests. Glochidia of several species had equal or greater sensitivities to Hg and NaCl than test organisms commonly used to assess environmental risk (i.e.Ceridaphnia dubia, Daphnia magna, Pimephales promelas), whereas they were far more tolerant to TRC than many species. Twenty-one day chronic test endpoints for juveniles were substantially lower than those calculated during acute bioassays with glochidia. Villosa iris 3-mo old juveniles were found to be quite sensitive to Hg as growth was significantly impaired at 8 ppb Hg. Chronic bioassays with TRC revealed a distinct decrease in susceptibility with increased aged for V. iris (relative sensitivities 3-mo > 6-mo > 12-mo), and that 2-mo old Epioblasma capsaeformis were more sensitive than comparable age classes of V. iris. However, both species were tolerant compared to other aquatic organisms, as the lowest endpoint was 20 ppb TRC. / Master of Science

Marine mammals are known for their low susceptibility to mercury toxicity, and it was hypothesized that selenium may play a role in protection against mercury toxicity. To gain insight into the mechanisms of the low susceptibility of cetaceans, we investigated the in vitro effects (1) of mercuric chloride (HgCl₂) on the ultrastructure and cell death of Atlantic spotted dolphin renal cells (Sp1K cells), (2) of HgCl₂ on the cell proliferation and cell cycle status of Sp1K and Rhesus monkey renal cells (MK2), and (3) of sodium selenite (Na₂SeO₃) on cell proliferation and cell death of control and HgCl₂-treated Sp1K cells. HgCl₂ affected multiple organelles and nuclei in Sp1K cells, and induced apoptosis in a time-and dose-dependent manner. Both ultrastructural changes and induction of apoptosis were milder than seen in other cell types in previous publications. In addition, Sp1K cells were able to proliferate at 25 µM HgCl₂ while MK2 cells were killed at 15 µM HgCl₂. An increase in percentage of cells in the G0/G1 phase in the cell cycle and a decrease in S, and G2/M phase cells were seen in Sp1K cells exposed to more than 10 uM HgCl₂ more than 72 hours. MK2 cells showed cell cycle changes only at 24 hours exposure, and may be due to a sensitive subgroup. These data suggested that Sp1K cells were less susceptible than other cell types in a cell-specific way, which was independent of selenium protection. Concurrent exposure to Na₂SeO₃ provided protection against the HgCl₂-induced decrease in cell proliferation of Sp1K. The protective effects were greater if Na₂SeO₃ and HgCl₂ were premixed, but disappeared if exposures did not overlap. Although pretreatments with Na₂SeO₃ alone did not provide protection, they increased the protection of selenium administered later. Furthermore, Na₂SeO₃ decreased HgCl₂-induced apoptosis. These data demonstrated the Na₂SeO₃ protection against HgCl₂ toxicity in Sp1K cells in terms of cell proliferation and apoptosis. This study is the first report that reveals the existence of mercury-selenium antagonism in cultured cetacean cells. The data supported the hypothesis that selenium protection against mercury toxicity is, at least partially, through competition of binding sites and formation of mercury-selenium complex. / Master of Science

The nature and scope of this problem is to determine from the irradiation of isopropyl alcohol with 2537 A, the behavior and mechanism of the reaction, since it is known that a reaction does occur.

<p>Coal fired power plants generate approximately 45% of the electricity produced in the United States every year, and each year, over 100 million tons of coal ash are produced as a by-product of electricity generation. Coal ash is a solid waste made up principally of bottom ash, fly ash, and flue gas desulfurization materials. The chemical composition of coal ash varies depending on the feed coal source, combustion parameters, and the presence and type of air pollution control devices that remove contaminants from the flue gas into the solid waste stream. Although a significant portion of coal ash waste is recycled, the majority of coal ash is disposed in landfills and holding ponds. Coal ash impoundments have a long history of environmental degradation, which includes: contaminant leaching into groundwater, the discharge of contaminant-laden effluent into surface waters, and catastrophic impoundment failures and ash spills. Despite these known problems, coal ash is not considered a hazardous waste, and thus is not subject to stringent disposal requirements. The current coal ash management system is based on risk assessments of coal ash that do not include environmental parameters that have a profound impact on coal ash contaminant mobility, particularly for the toxic elements such as mercury, arsenic, and selenium. This dissertation research focused on the biogeochemical transformations of mercury, arsenic, and selenium associated with coal ash materials in an effort to: (1) define the key environmental parameters controlling mercury, arsenic, and selenium fate during disposal and ash spills; and (2) delineate the relationship between coal ash characteristics, environmental parameters, and leaching potential. </p><p> The impact of coal ash on mercury transformations in anaerobic systems was assessed using anaerobic sediment-ash microcosms to mimic an ash spill into a benthic aquatic system. Anaerobic sediments are the primary zones for the microbial conversion of inorganic mercury to methyl mercury (MeHg), a process that is mediated by anaerobic bacteria, particularly sulfate reducing bacteria (SRB). MeHg is a potent neurotoxin that biomagnifies up the aquatic food chain, presenting a human health risk-- especially to children and pregnant women. The results of the sediment-ash microcosm experiments indicated negligible net production of MeHg in microcosms with no ash and in microcosms amended with the low-sulfate/low-Hg ash. In contrast, microcosms amended with sulfate and mercury-rich ash showed increases in MeHg concentrations that were two to three times greater than control microcosms without ash. The enhancement MeHg production in the microcosms was likely due to large quantities of leachable sulfate that stimulated the activity of methylating bacteria. Overall, these results highlight the importance of considering both the geochemical conditions of the receiving environment and the chemical composition of the coal ash in assessing the MeHg potential of coal ash. </p><p> The hypothesis that sulfate-rich coal ash can change sediment microbial communities, enhancing MeHg production, was tested by analyzing coal ash impacts on the SRB community in the sediment-ash microcosms using Terminal Restriction Fragment Length Polymorphism (T-RFLP), Quantitative Polymerase Chain Reaction (q-PCR), and Reverse Transcription-qPCR (RT-qPCR). Coal ash did not appear to cause significant changes to the structure of the overall bacterial community, though results showed that it may have caused a decrease in the evenness for species distribution for both SRB and the overall microbial community. During the five-day incubation experiment, the coal ash had a temporary significant effect on SRB abundance during the first one to two days of the experiment and a more sustained effect on SRB activity. This stimulation of SRB population growth and activity also corresponded with increasing net MeHg production. Overall, results indicate that coal ash amendments do not cause large shifts in the overall microbial community or the SRB community, but results indicate that there are connections between SRB abundance/activity and MeHg production. More research is needed to determine how coal ash directly impacts Hg methylating microorganisms, which include diverse array of microorganisms outside of SRB.</p><p> The effect of aerobic and anaerobic conditions on arsenic and selenium leaching from coal ash in an ash spill scenario was also assessed using sediment-ash microcosms. The fate of arsenic and selenium associated with coal ash is of particular concern due to the leachability of these elements at neutral pH and their tendency to bioaccumulate in aquatic organisms. Both the redox speciation of arsenic and selenium, and the pH of the aquatic system, are known to influence leaching into the environment, yet current environmental risk assessments of coal ash focus on pH alone as the primary driving force for arsenic and selenium leaching from coal ash and do not take into account the effects of anaerobic conditions and microbial activity. In this research, total dissolved concentrations of arsenic and selenium, dissolved speciation of arsenic, and solid phase speciation of selenium were monitored to determine the biogeochemical transformations and leaching of arsenic and selenium under differing redox conditions. The results from the sediment-ash microcosm studies showed that redox potential was the major determinant of arsenic and selenium mobility in the microcosm systems with greater arsenic leaching occurring in anaerobic microcosms and greater selenium leaching occurring in aerobic microcosms. Furthermore, the experiments provided clues to how coal ash influences the geochemistry of the benthic environment and how these influences affect the speciation and longer term solubility of arsenic and selenium. </p><p> Finally, experiments were conducted to determine how differing CaO, SO3, and Fe2O3 concentrations in coal ash affect the release of arsenic and selenium from sediment-ash mixtures in a simulated ash spill environment. Aerobic and anaerobic sediment-ash microcosms were constructed to mimic an ash spill into a benthic aquatic system, and a variety of coal ash materials were tested as amendments, including seven fly ashes, one lime-treated fly ash sample, and two FGD samples. Results showed that, in most cases, the sediment in the microcosm buffered the system at neutral, which counteracted leaching impacts of differing CaO and SO3 concentrations in the microcosms. Regardless of ash material, leaching of selenium was greater under aerobic conditions and was correlated with the total selenium content of the microcosm. Maximum leaching of arsenic occurred in anaerobic microcosms for some ash materials and in aerobic microcosms for other materials, suggesting that ash material chemistry played a significant role in controlling arsenic mobility. In both aerobic and anaerobic microcosms, dissolved arsenic concentration was correlated with total arsenic content of the ash material and in anaerobic microcosms, dissolved arsenic concentrations also correlated with the total iron content of the ash material. Overall, the results of these experiments showed that arsenic and selenium release under environmentally relevant conditions cannot be predicted by the CaO and SO3 content of the ash material. Rather, the total arsenic, total selenium content, and total iron content of the ash material are good predictors of the worst case environmental leaching scenario.</p><p> These investigations illuminated two major conclusions: (1) microbial activity and differing redox conditions are key in determining the impact of coal ash on the environment and in determining the mobility of coal ash contaminants, and (2) coal ash characteristics, such as sulfate and iron content, can change the redox chemistry and microbial activity of the surrounding environment, further influencing the fate of ash contaminants. This work will be useful in designing a framework that accurately predicts the leaching potential of ash contaminants under environmentally relevant conditions. The results will also be helpful in developing treatment technologies for ash impoundment effluent, guiding decisions on ash pond closure and remediation, and in designing long-term monitoring plans and remediation strategies for ash-impacted sites.</p> / Dissertation

A variable temperature ^13 C and ^199 Hg NMR study has been conducted for diphenyl-, bis(o-tolyl)-, bis(m-tolyl)-, and bis(2, 6-xylyl)mercury in dimethyl sulfoxide and 1,1,2,2 tetrachloroethane; ^13 C T1 relaxation times are reported as a function of temperature. Barriers to rotation of the aryl rings are obtained. Chemical shifts and couplings in CDCl_3 are given for bis(p-tolyl)-, bis(2, 5-xylyl)-, bis(mesityl)-,phenyl(o-tolyl)-, phenyl(m-tolyl)mercury, and the compounds listed above. The steric interactions of these aryl mercury compounds are discussed.

As the foremost production of electricity in the United State comes from coal-fired plants, there is much more to learn on the topic of mercury which is a common component in coal. The speciation of mercury in the flue gas determines the best control technology for a given system. Because of the difficulty in measuring mercury at different stages of the process, it is practical to use mercury reaction kinetics to theoretically determine mercury speciation based upon coal composition, plant equipment and operating conditions. Elemental mercury cannot be captured in wet scrubbers; however, its oxidized forms can. Chlorine is a reasonable oxidizing agent and is naturally found in bituminous coal, but bromine is an even better oxidizing agent because of its larger size, it has stronger London dispersion force interactions with mercury. Bromine additive technologies have recently been implemented in several companies to enhance mercury oxidation. Because capture technologies are highly dependent upon the form of mercury that is present, investigations into their speciation are extremely important. Though there have been numerous efforts to study mercury compounds as relevant to atmospheric studies, there is little data currently available for mercury compounds found in combustion flue gases. It would be particularly beneficial to obtain kinetic rate constants at various high temperature and pressure conditions typical for a combustion system. Prevalent species of mercury containing bromine in coal combustion flue gases were studied using density functional theory (DFT) and a broad range of ab initio methods. Reaction enthalpies, equilibrium bond distances, and vibrational frequencies were all predicted using DFT as well as coupled cluster (CC) methods. All electronic calculations were carried out using the Gaussian03 or MOLPRO software programs. Kinetic predictions of three first-stage and three second-stage oxidation reactions involving the formation of oxidized mercury via bromine containing compounds are presented. Understanding the speciation of mercury in the flue gases of coal combustion is paramount in developing efficient technologies to ensure its capture.

<p>Interaction between mercury and selenium has previously been observed both in man and in animals. The aim of this work was to study expressions of interaction between mercury and selenium in human K-562 cells. Inorganic and organic forms of mercury and selenium were used and cells were either pre-treated with selenium or simultaneously exposed to selenium and mercury. Concentrations of selenium and mercury chosen were indicated by a study of growth inhibition in the individual compounds: a low concentration of selenium and selenomethionine induced slight cell growth inhibition, while a high concentration resulted in a notable growth inhibition. Two mercury concentrations were chosen: one with minimal toxicity and another with high cell toxicity. In addition, uptake and retention patterns of selenomethionine and selenite differed in both selenocompounds.</p><p>All simultaneous treatments with 3.5 μM methylmercury produced a reduction in cellular mercury with increased selenium concentration. This was particularly obvious in selenite treatments. Growth curves from the simultaneous 3.5 μM methylmercury and selenite treatments indicated protection with increased selenite concentrations. In both exposure protocols, the 5 μM methylmercury treatments were toxic to the cells. </p><p>In both study protocols, cells exposed to selenite and mercuric chloride manifested increased cellular mercury uptake with increased selenium concentration. In all selenite and 35 μM mercuric chloride treatments, no inhibition of growth was observed, while the 50 μM mercuric chloride treatments were toxic to the cells. Selenite-dependent protection was achieved in both exposure protocols when considering the cellular uptake of mercury. With few exceptions, selenomethionine produced similar effects as selenite on mercuric chloride uptake and growth inhibition.</p>