This research examined the suitability of the biotic ligand model (BLM) approach for assessing environmental risk in surface waters consisting substantially of treated sewage effluent, and the implications of its use within a compliance-based regulatory framework aimed at controlling discharges of metals into the aquatic environment. The results from a series of Daphnia magna acute copper toxicity assays conducted in an undiluted sewage effluent medium demonstrated that BLMs could predict an acute copper toxicity endpoint with suitable accuracy. This finding contributes further support for the use of BLMs for assessing risk and compliance, even in effluent impacted waters. Additional studies, however, also demonstrated that effluent derived organic matter contained a greater concentration of metal complexing ligands per milligram of dissolved organic carbon than organic matter derived from natural sources. This indicates that effluent derived organic matter offers greater protection against the potentially adverse effects from metals than the protection offered by organic matter derived from natural sources. These studies also demonstrated that improvements in the accuracy of BLM forecasts were achievable by taking these differences into account which, from a regulatory perspective, is also desirable since this enhances the environmental relevance of compliance criteria. These findings therefore justify that consideration for the influence of site-specific metal complexation characteristics should included as part of the regulatory framework within which BLMs will be applied. The implication of the BLM approach for Severn Trent Water Limited is that, as currently proposed, the approach will require a reduction in the concentration of copper in the effluent discharges for a small number of wastewater treatment works (9), whereas for zinc, concentration reductions may be required for numerous treatment works (126).

No description available.

No description available.

Thesis (Ph. D.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on January 30, 2007) Vita. Includes bibliographical references.

Thesis (M.Phil.)--Murdoch University, 2006. / Thesis submitted to the Division of Health Science. Includes bibliographical references (leaves 153-166).

Thesis (M.S.)--University of Wisconsin--Madison, 1961. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaf 44)

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease and is characterized by progressive paralysis leading to death, typically, within 3-5 years of the onset of symptoms. The majority of ALS cases are sporadic with no known causative agent; however, 5-10% of ALS cases are genetically inherited and termed familial ALS (fALS). Approximately, 15-20% of these fALS cases have been linked to mutations in the gene encoding human Cu/Zn superoxide dismutase (hSOD). To date, over 140 hSOD mutations have been discovered. The mechanisms by which mutant hSOD confers toxicity in fALS patients are still unknown. However, there is growing evidence that ALS is a type of protein conformational disease whereby cell damage or death is caused by the accumulation of protein aggregates in the cell. It is hypothesized that mutations destabilise hSOD and increase its propensity to aggregate. There is some controversy as to which hSOD species contributes to aggregation. Many believe that only apo or mismetallated forms of hSOD are able to aggregate. Due to the abundance of fully metallated or holo hSOD in the cell, we hypothesize that holo hSOD can also lead to aggregation. Holo dimer interface mutants A4S, A4T and I113T as well as G41D were found to be destabilized compared to holo pseudo wildtype (pWT) while zinc binding mutant H80R was shown to form fragments via an unknown mechanism. Holo dimer interface mutants A4S and A4T were also shown to have an increased propensity to aggregate compared to pWT, which correlates to their decreased stability as well a short disease durations.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease and is characterized by progressive paralysis leading to death, typically, within 3-5 years of the onset of symptoms. The majority of ALS cases are sporadic with no known causative agent; however, 5-10% of ALS cases are genetically inherited and termed familial ALS (fALS). Approximately, 15-20% of these fALS cases have been linked to mutations in the gene encoding human Cu/Zn superoxide dismutase (hSOD). To date, over 140 hSOD mutations have been discovered. The mechanisms by which mutant hSOD confers toxicity in fALS patients are still unknown. However, there is growing evidence that ALS is a type of protein conformational disease whereby cell damage or death is caused by the accumulation of protein aggregates in the cell. It is hypothesized that mutations destabilise hSOD and increase its propensity to aggregate. There is some controversy as to which hSOD species contributes to aggregation. Many believe that only apo or mismetallated forms of hSOD are able to aggregate. Due to the abundance of fully metallated or holo hSOD in the cell, we hypothesize that holo hSOD can also lead to aggregation. Holo dimer interface mutants A4S, A4T and I113T as well as G41D were found to be destabilized compared to holo pseudo wildtype (pWT) while zinc binding mutant H80R was shown to form fragments via an unknown mechanism. Holo dimer interface mutants A4S and A4T were also shown to have an increased propensity to aggregate compared to pWT, which correlates to their decreased stability as well a short disease durations.

No description available.

No description available.