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In 2006, the Minister of Fisheries and Oceans Canada (DFO) accepted an industry proposal called the Commercial Groundfish Integration Pilot Program (CGIPP), which integrated each of the seven commercial groundfish fisheries in British Columbia. The industry proposal, developed by the Commercial Industry Caucus (CIC), was the result of guiding principles developed by DFO that focused on the conservation of certain rockfish species on the Pacific Coast. If industry had not developed a plan, DFO would have developed an alternative fishing plan (AFP). This thesis evaluates whether DFOs conservation objectives were met under the CGIPP and if there were any social and economic impacts. These same impacts are compared to what may have occurred under the AFP. The results of this thesis indicate that the CGIPP is a sustainable template for multi-species commercial fisheriesa first step in achieving an ecosystem-based approach to fisheries management.

In 2006, the Minister of Fisheries and Oceans Canada (DFO) accepted an industry proposal called the Commercial Groundfish Integration Pilot Program (CGIPP), which integrated each of the seven commercial groundfish fisheries in British Columbia. The industry proposal, developed by the Commercial Industry Caucus (CIC), was the result of guiding principles developed by DFO that focused on the conservation of certain rockfish species on the Pacific Coast. If industry had not developed a plan, DFO would have developed an alternative fishing plan (AFP). This thesis evaluates whether DFOs conservation objectives were met under the CGIPP and if there were any social and economic impacts. These same impacts are compared to what may have occurred under the AFP. The results of this thesis indicate that the CGIPP is a sustainable template for multi-species commercial fisheriesa first step in achieving an ecosystem-based approach to fisheries management.

Introduction The effective specific activity of a radioisotope is an indirect and highly useful way to describe a radioactive sample’s purity. A high effective specific activity combines the concept of an isotopically pure product with suitability via selectivity of a particular chelating body. The primary goals of this work are twofold: 1) To determine which metallic impurities have the largest impact on the effective specific activity for a given chelator, and 2) to form a model based on the binding affinities of each metal for to calculate a ‘theoretical effective specific activ-ity’ from broad band trace metal analysis. If successful, this information can be used to guide the production of high specific activity products through the systematic elimination of high-impact metallic impurities. Material and Methods Phosphor plate thin layer chromatography (TLC) was used to measure the effective specific activ-ity of 64Cu by NOTA and DOTA, and 89Zr by des-feral (DF). Typical measured effective specific activities are 2–5 Ci/μmol for 64Cu and 1–2 Ci/μmol for 89Zr. Samples were created containing increasing cod competitive burdens (X) of CuCl2, ZnCl2, FeCl2, NiCl2, CrCl3, CoCl2, MnCl2, and YCl3. Standard concentrations were measured by microwave plasma atomic emission spectrometry. 50 pmol of NOTA, DOTA, or DF were added following the activity aliquots of 64Cu or 89Zr. Labeling efficien-cies (64Cu-NOTA, 64Cu-DOTA, 89Zr-DF) were measured using TLC’s, and were fit by linear regression to the form f(X) = b/(1 − AX), where A is the chelation affinity (inverse of dissociation constant) and X is the molar ratio of the metallic impurity to the amount of chelator. Results and Conclusion Affinity of Zr for DF was assumed to be unity, while the affinities of Cu for NOTA and DOTA were explicitly measured and were found to be 0.93 ± 0.13 and 5.2 ± 3.2 respectively. It was found that Cu had the highest affinity for NOTA by a factor of 266, and that Zr had the highest affinity for DF by a factor of 40. • In order of decreasing affinity to NOTA: Cu, Zn, Fe, Co, Cr, Y, and Ni • In order of decreasing affinity to DOTA: Cu, Y, Zn, Co, Ni, Cr, and Fe • In order of decreasing affinity to DF: Zr, Y, Cu, Zn, Ni, Fe, Co, Cr These results suggest that aside from the carrier element it is most important to remove zinc from 64Cu products prior to chelation with NOTA and yttrium from 64Cu and 89Zr products prior to chelation with DOTA and DF, respectively. Therefore, it is logical to believe that 89Zr effective specific activities could be greatly improved by secondary separations with the goal of re-moving additional yttrium target material. Chelation affinities of NOTA, DOTA, and DF for several common metals have successfully been investigated. These values will guide our future attempts to provide high effective specific activity 64¬Cu and 89Zr. Furthermore, a preliminary model has been formed to calculate effective specific activity from the quantitative broad band analysis of trace metals. Future work will include chelator affinity measurements for other likely contaminants, such as scandium, titanium, zirconium, molybdenum, niobium, gold, gallium, and germanium. Details will be presented.

L'alumini és un metall amb un ampli ús industrial, que es troba àmpliament distribuïtpel medi ambient, i amb un elevat ús dins la nostre vida quotidiana. Tot i així, l'aluminino és un metall essencial i no té propietats biològiques importants conegudes.Diversos estudis ambientals i experimentals han mostrat que l'alumini és un potenttòxic i neurotòxic amb importants riscs per la salut humana. L'alumini s'ha relacionatamb diverses malalties neurodegeneratives, incluïda la malaltia d'Alzheimer (MA).S'han proposat diversos mecanismes mitjançant els quals l'alumini podria exercir elsseus efectes neurotòxics, però sobretot s'ha estudiat el seu paper com a agentprooxidant.Per altre banda, la melatonina és un conegut agent antioxidant, que pot actuar deforma directa neutralitzant els radicals lliures, i de forma indirecta al induir l'expressiógènica d'alguns gens relacionats amb la defensa antioxidant. Així mateix, ladesferoxamina (DFO) és un conegut agent quelant del ferro i l'alumini.En aquest estudi es van avaluar els efectes neurotòxics d'una exposició oral a aluminisobre el sistema antioxidant cel·lular en un model animal per a la MA (Tg2576APPswe), a més de valorar els canvis cognitius i conductuals produïts i determinar elsnivells d'alumini i d'altres metalls relacionats amb la MA en diferents teixits i regionscerebrals. Per altre banda, es va estudiar el possible efecte protector de la melatonina ide la DFO.Els nostres resultats han mostrat que dels tres teixits cerebrals estudiats l'aluminis'acumula majoritàriament a l'hipocamp dels animals.En general, l'anàlisi dels sistemes antioxidants enzimàtics i no enzimàtics i els resultatsde l'expressió dels nivells d'mRNA dels enzims CAT, SOD i GR, han mostrat quel'alumini podria actuar com a un possible agent prooxidant, Altrament, els resultats hanmostrat que la melatonina actuaria com a un agent antioxidant, mentre que la DFO noexerciria cap acció antioxidant clara. Per altre banda ni la melatonina ni la DFO hanmostrat capacitat per detoxificar l'alumini del cervell dels animals. / Aluminum is an abundant element in the environment, which has a considerable number of usesand industrial applications. However, aluminum is a non essential metal, with no importantbiological propierties. Environmental and experimental studies has shown that aluminum is apotential toxic and neurotoxic metal with important risks to human health.Aluminum has been implicated in various neurodegenerative disorders including Alzheimer'sdisease (AD). Various mechanisms have been proposed for Al-induced neurotoxicity, including freeradical damage via enhanced lipid peroxidation, impaired glucose metabolism, effects on signaltransduction and protein modification, alterations on the axonal transport, and alteration ofphosphorylation levels of neurofilaments, as well as, neuronal death.On the other hand, melatonin is a known antioxidant, which can directly act as free radicalscavenger, or indirectly by inducing the expression of some genes linked to the antioxidantdefense. Also, desferoxamine (DFO) is an effective iron and aluminum chelator that has beenwidely used to facilitate aluminum removal in chronic aluminum overload in patients with end-stagerenal failure under long-term dialysis.The aim of these study was to evaluate neurotoxics effects of oral aluminum exposure oncognitive, oxidative stress parameters and metal levels in a mice model for Alzheimer's disease(Tg2576 APPswe mice) and to evaluate the possible protective role of melatonin and DFO.Results showed that aluminum accumulates in predominance in hippocampus of mice aftertreatment.In general terms, the biochemical changes observed in hipocamppus, cortex and cerebellum ofTg2576 and wild mice suggest that aluminum acts as a pro-oxidant agent while melatonin exertsan antioxidant action independent of the animal model. In contrast, DFO administration would nothelp in preventing these deleterious effects.

Introduction The effective specific activity of a radioisotope is an indirect and highly useful way to describe a radioactive sample’s purity. A high effective specific activity combines the concept of an isotopically pure product with suitability via selectivity of a particular chelating body. The primary goals of this work are twofold: 1) To determine which metallic impurities have the largest impact on the effective specific activity for a given chelator, and 2) to form a model based on the binding affinities of each metal for to calculate a ‘theoretical effective specific activ-ity’ from broad band trace metal analysis. If successful, this information can be used to guide the production of high specific activity products through the systematic elimination of high-impact metallic impurities. Material and Methods Phosphor plate thin layer chromatography (TLC) was used to measure the effective specific activ-ity of 64Cu by NOTA and DOTA, and 89Zr by des-feral (DF). Typical measured effective specific activities are 2–5 Ci/μmol for 64Cu and 1–2 Ci/μmol for 89Zr. Samples were created containing increasing cod competitive burdens (X) of CuCl2, ZnCl2, FeCl2, NiCl2, CrCl3, CoCl2, MnCl2, and YCl3. Standard concentrations were measured by microwave plasma atomic emission spectrometry. 50 pmol of NOTA, DOTA, or DF were added following the activity aliquots of 64Cu or 89Zr. Labeling efficien-cies (64Cu-NOTA, 64Cu-DOTA, 89Zr-DF) were measured using TLC’s, and were fit by linear regression to the form f(X) = b/(1 − AX), where A is the chelation affinity (inverse of dissociation constant) and X is the molar ratio of the metallic impurity to the amount of chelator. Results and Conclusion Affinity of Zr for DF was assumed to be unity, while the affinities of Cu for NOTA and DOTA were explicitly measured and were found to be 0.93 ± 0.13 and 5.2 ± 3.2 respectively. It was found that Cu had the highest affinity for NOTA by a factor of 266, and that Zr had the highest affinity for DF by a factor of 40. • In order of decreasing affinity to NOTA: Cu, Zn, Fe, Co, Cr, Y, and Ni • In order of decreasing affinity to DOTA: Cu, Y, Zn, Co, Ni, Cr, and Fe • In order of decreasing affinity to DF: Zr, Y, Cu, Zn, Ni, Fe, Co, Cr These results suggest that aside from the carrier element it is most important to remove zinc from 64Cu products prior to chelation with NOTA and yttrium from 64Cu and 89Zr products prior to chelation with DOTA and DF, respectively. Therefore, it is logical to believe that 89Zr effective specific activities could be greatly improved by secondary separations with the goal of re-moving additional yttrium target material. Chelation affinities of NOTA, DOTA, and DF for several common metals have successfully been investigated. These values will guide our future attempts to provide high effective specific activity 64¬Cu and 89Zr. Furthermore, a preliminary model has been formed to calculate effective specific activity from the quantitative broad band analysis of trace metals. Future work will include chelator affinity measurements for other likely contaminants, such as scandium, titanium, zirconium, molybdenum, niobium, gold, gallium, and germanium. Details will be presented.

Iron has a dualistic character. On the one hand it is essential for the life of most organisms, on the other hand it is involved in the generation of reactive oxygen species that are implicated in diseases and aging. During evolution efficient mechanisms for uptake, handling and storage of iron in a safe way have developed to keep the balance between iron availability and minimizing the hazards. In eukaryotes, mitochondria are the central organelle for “metabolizing” iron and consequently play an important role in cellular iron homeostasis. Mitoferrins are mitochondrial carrier proteins, which are involved in iron transport into mitochondria. In vertebrates two mitoferrins exist, one (mitoferrin1) of which is essential for heme synthesis during erythropoiesis, while the function of the other (mitoferrin2) is not well defined. In the fruit fly we found only one mitoferrin gene (dmfrn), which codes most likely for a functional homologueof vertebrate mitoferrin2. In Drosophila cell culture, dmfrn overexpression resulted in an overestimation of cell sensed iron levels. The signal responsible for this, is most likely a yet unidentified compound of ISC synthesis. In the cell culture system we also showed that iron chelation blocks the progression of the cell cycle in a reversible and therefore most likely controlled way. Study of different dmfrn mutants indicates a role of dmfrn during spermatogenesis and development to adulthood. As dmfrn deletion mutants are not lethal, it is likely that other lower affinity iron transporters exist. A similar conclusion has been drawn by others from the study of yeast mitoferrin homologuemutants. Rim2p/Mrs12p has recently been implicated in mitochondrial iron transport, and might be an alternative metal carrier. We identified a putative homologuein the fruit fly and found a possible link between mutants in this gene and iron. Our results emphasize the importance of the mitochondrial iron metabolism in cellular iron homeostasis. We also show for the first time, a direct connection between the mitochondrial iron metabolism and spermatogenesis. Mutants characterized and developed by us will help to study these processes in further detail and reveal the underlying mechanisms.