Browsing by Subject "endocrine disruptors"
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Item Comparative activation of estrogen receptor alpha (er alpha) by endocrine disruptors(2009-05-15) Wu, FeiEstrogen receptor ? (ER?) is a ligand activated transcription factor. Many widely used synthetic compounds and natural chemicals can activate ER?. The compounds investigated in this study include 17?-estradiol (E2), diethylstilbestrol (DES), antiestrogens ICI 182,780, 4-hydroxytamoxifen, the phytoestrogen resveratrol, and the xenoestrogens bisphenol A (BPA), nonylphenol (NP), octylphenol (OP), endosulfan, kepone, 2,2-bis(p-hydroxyphenyl)-1,1,1- trichloroethane (HPTE) and 2,3,4,5-tetrachlorobiphenylol-4-ol (HO-PCB-Cl4). With the exception of the antiestrogens, all the compounds induced transactivation in MCF-7 or MDA-MB-231 cells transfected with wild-type ER? and a construct (pERE3) containing three tandem estrogen responsive elements (EREs) linked to a luciferase gene. However, these compounds differentially activated C-terminal deletion mutants of ER?. For example, neither E2 nor DES induced transactivation in MCF-7 transfected with ER?(1-537) due to partial deletion of helix 12 of ER?; however, OP, NP, resveratrol, kepone and HPTE induced this ER? mutant, demonstrating that the estrogenic activity of these synthetic compounds do not require activation function 2 (AF-2) of ER?. This study also investigated the effects of xenoestrogens on activation of reporter gene activity in MCF-7 and MDA-MB-231 cells transfected with a construct (pSp13) containing three tandem GC-rich Sp binding sites linked to the luciferase gene. In MCF-7 cells, antiestrogen-induced activation of ER?/Sp1 required the zinc finger motifs of ER?, whereas activation by estrogen and some xenoestrogens activation, such as endosulfan, NP and OP required the H12 of ER?. In contrast, xenoestrogens, such as HPTE, BPA, kepone and HO-PCBCl4, significantly induced transactivation of all four ER? deletion mutants tested in this study. Moreover, RNA interference assays demonstrated structuredependent differences in activation of ER?/Sp1, ER?/Sp3 and ER?/Sp4. The in vivo activities of E2, ICI 182,780, BPA and NP were further investigated in a transgenic mouse model containing pSp13 transgene. All the compounds induced luciferase activity in the mouse uterus; however activities observed in the penis and testis of male and stomach of both male and female mice were structure-dependent,. These results demonstrate that various ER ligands differentially activate ER? in breast cancer cells and transgenic mice, and their activities are dependent on ER? variants, promoter-, cell-context and selective use of different Sp proteins, suggesting these structurally diverse compounds are selective ER modulators (SERMs).Item Manganese Based Oxidative Technologies For Water/Wastewater Treatment(2013-08-27) Desai, IshanManganese is a commonly occurring mineral found in soil and sediments that takes part in chemical reactions in groundwater and soil systems. It plays a significant role in controlling the environmental fate and transport of organic and inorganics by facilitating redox reactions. The reactivity of manganese oxides with some emerging contaminants like 4-tert octylphenol (OP) in aqueous systems is yet to be explored. Additionally, manganese's use within treatment systems designed to remove trace organics is yet to be fully developed. This research work explores the reactivity of manganese oxide to degrade OP in aqueous systems. The rate equation has been determined by conducting experiments at various conditions of oxide and organic loading as well as different pH's. The reaction order was found to be ? 1.1 for both oxide as well as the organic. The reactivity was much higher under acidic conditions. The presence of metals and humic acids greatly reduced the reactivity. The primary reaction by-product observed in the system was 4-(2,4,4-trimethylpentan-2yl)benzene-1,2-diol. Magnetic manganese ferrites were further created in the laboratory using a novel combustion method in order to blend the catalytic properties of manganese with the magnetic and structural properties of ferrites. These laboratory prepared catalysts were thoroughly characterized using XRD, SEM, TEM, HR-TEM, and BET. Their magnetic properties have also been studied. These manganese ferrites offer the potential to enhance hydroxyl radical production within catalytic ozonation systems. Thus their catalyst effectiveness was determined by measuring R_(ct), ozone exposure, hydroxyl radical production, and ozone decomposition. The effect of catalyst type, catalyst dosage, pre-ozonation, pH, and presence of dissolved organic matter (DOM) on the hydroxyl radical production during catalytic ozonation was also explored. An increase in ozone dosage, catalyst dosage, and PVA content enhanced organic removal in the system. Organic removal was lower at a decreased system pH, in the presence of DOM, and with increasing levels of Mn incorporated into the catalyst. Pre-ozonation of the catalyst at lower dosages did not have an effect on the system, though extensive pre-ozonation greatly reduced catalyst activity. Overall, R_(ct) and organic removal were not correlated.Item The Effect of Environmental Contaminants on Mating Dynamics and Population Viability in a Sex-Role-Reversed Pipefish(2010-07-14) Partridge, Charlyn G.Understanding how anthropogenic activity impacts the health and viability of wildlife populations is one of the most important tasks of environmental biology. A key concern related to bi-products of human activity is the accumulation of environmental pollutants within aquatic environments. Pollutants such as endocrine disruptors and heavy metals have the potential to impact both human and wildlife populations in contaminated areas. While much research has focused on how these compounds impact natural selection processes, such as viability and reproduction, their effect on sexual selection processes is not as clear. The goal of this dissertation was to address how environmental contaminants impact sexual selection processes in a sex-role reversed pipefish and evaluate how these effects may impact long-term population viability. Here we show that short periods of exposure to environmentally relevant concentrations of a synthetic estrogen result in male pipefish with female-like secondary sexual traits. While these males are capable of reproduction, exposed males are discriminated against by females in mate choice tests. In natural populations, this type of discrimination could reduce male mating opportunities, potentially reducing their reproductive success. In an additional component of this dissertation, it was discovered that pipefish populations around Mobile Bay, specifically Weeks Bay, are currently being exposed to significantly elevated levels of mercury. These populations are genetically distinct from coastal populations but moderate levels of gene flow occur among sites, and gene flow between contaminated and non-contaminated population may be influencing how environmental contaminants are impacting genetic diversity and population viability. In the case of endocrine disruptors, migration between contaminated and non-contaminated sites may negatively impact population viability. Morphological traits induced with exposure to contaminants may be maintained for extended periods of time, therefore, the effect the exposed phenotype has on mating dynamics and sexual selection could be carried to non-contaminated sites if exposed individuals move to new populations. On the other hand, immigration of individuals from non-contaminated sites into contaminated areas may help maintain genetic diversity within exposed populations. In conclusion, the work presented in this dissertation shows that the presence of environmental toxins can significantly impact sexual selection processes, which in turn can have profound effects on the viability and future evolutionary trajectory of populations. Future work in this area should not only address how these toxins impact individual fitness, but should also address how population structure may be influencing the severity of these compounds on natural populations.