UMD Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/3
New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a given thesis/dissertation in DRUM.
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Item Investigating Copper Acquisition And Delivery via Transporters and a Pharmacological Chaperone in Copper-Deficient Worms and Mice(2019) Yuan, Sai; Kim, Byung-Eun; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Copper (Cu) is a key micronutrient required for a variety of essential biochemical pathways. Systemic or tissue-specific Cu-deficiencies, caused by insufficient dietary Cu uptake or mutations in Cu transporting genes, result in impaired growth, neuropathy, ataxia, hypopigmentation, osteoporosis and anemia-like symptoms in mammals. How organisms regulate Cu homeostasis at the systemic levels in response to Cu deficiencies remain elusive. In this study, we use Caenorhabditis elegans (C. elegans), a genetically tractable, multi-tissue metazoan to explore Cu homeostasis and investigate these unknowns. The high-affinity Cu transporters encoded by CTR family genes are required for dietary Cu uptake and maintaining systemic Cu balance from yeast to mammals. However, little is known about Cu acquisition mechanisms in C. elegans. We identified ten CTR ortholog genes in C. elegans; of these, chca-1 was functionally characterized. Cu availability regulates transcription of chca-1 in both the intestine and hypodermis, and chca-1 is essential for normal growth, and reproduction in the worm. Additionally, altered Cu balance caused by the loss of CHCA-1 results in defects in Cu-responsive avoidance behavior. Identification of this CTR-like gene in C. elegans, which appears to be essential for normal Cu homeostasis in the worm, illustrates the importance of Cu delivery via CHCA-1 for normal metazoan development and behavioral phenotypes. In addition, we show that a Cu-binding pharmacological chaperone, elesclomol (ES), fully restores the developmental defects and Cu deficiencies in chca-1-depleted worms, as well as the lethality in worms lacking cua-1 expression (Cu exporter ATP7A ortholog), suggesting ES is able to efficiently deliver Cu from dietary sources to peripheral tissues through the intestine in C. elegans. Our study was further expanded to mammalian models such as cardiac-specific Ctr1-depleted (Ctr1hrt/hrt) mice. We found that ES administration fully restores the postnatal lethality, developmental defects and cardiac hypertrophy found in Ctr1hrt/hrt mice, as well as rescuing the secondary systemic Cu homeostasis responses, including aberrant ATP7A protein levels in the liver and intestine. Moreover, ES shows the potential ability to transport Cu across the blood-brain-barrier in in vitro studies. These results illustrate the capability of ES to rescue systemic Cu deficiency in worms and mice, independent of the presence of functional Cu transporters, and shed light on the therapeutic usage of ES in Cu-deficient human diseases.Item FIELD-SCALE OPTIMIZATION AND EVALUATION OF A RECYCLED-MATERIALS BASED STORMWATER TREATMENT TECHNIQUE(2013) Gleason, David Jacob; Davis, Allen P; Civil Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This research project evaluates and enhances a novel stormwater control measure for heavy metals called the Biomat. The water quality effects of Biomat treatment on a field scale were examined. Dissolved Pb and Cu were major contaminants, found in roof runoff at mean values of 2.7 mg/L Pb and 0.8 mg/L Cu at the research site. Biomat treatment reduced concentrations to mean values of 30 mcg/L Pb and 13 mcg/L Cu. Results indicate that an approximate steady-state concentration was reached for dissolved metals. This concentration appears to result from equilibrium between native metals on the media and metals dissolved in stormwater. Water quality results from a second site where influent metals concentrations were significantly lower (mean influent Pb at 15 mcg/L, Cu at 9 mcg/L) supported this hypothesis. Further water quality improvement was achieved with an additional aluminum-based water treatment residual and sand media, focusing on phosphorous.Item Characterization of Trace Metal Leaching from Maryland Coal Fly Ashes(2011) Ozkok, Enes; Aydilek, Ahmet H; Davis, Allen P; Civil Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Three coal fly ashes with different acid-base characteristics and their mixtures with an embankment soil were analyzed for arsenic, copper, and chromium leaching as function of pH using batch-type water leach tests (pH 4-10). Leach tests results showed that significant Cu release occurred only at pH ~4.3 and dissolved Cr concentrations typically increased with increasing pH. Cr(VI) was determined as the predominant oxidation state in leachates and results from WLTs spiked with Cr(VI) suggest that Cr was strongly sorbed below pH 7. Sorption affinity of fly ashes for Cr(VI) seemed to be to correlated to their oxalate-extractable Fe content, which is presumably a surrogate for amorphous iron (hydr)oxide content. Arsenic release typically followed a similar leaching pattern observed for Cr, with the exception of 100% alkaline fly ash; decreased As release above pH 9 for this sample was attributed to precipitation of Ca-As phases due to its high CaO content.