Cellular Mechanisms of Resveratrol's Interaction with Mitochondrial Reactive Oxygen Species Metabolism

Resveratrol, a polyphenol found naturally in red wines, has attracted great interest in both the scientific community and the general public for its reported ability to protect against many of the diseases facing Western society today. While the purported health effects of resveratrol are well characterized, details of the cellular mechanisms that give rise to these observations are unclear. Here, the mitochondrial antioxidant enzyme Mn superoxide dismutase (MnSOD) was identified as a proximal target of resveratrol in vitro and in vivo. MnSOD protein and activity levels increase significantly in cultured cells treated with resveratrol, and in the brain tissue of mice given resveratrol in a high fat diet. Preventing the increase in MnSOD levels eliminates two of resveratrol’s more interesting effects in the context of human health: inhibition of proliferative cell growth and cytoprotection. Thus, the induction of MnSOD is a critical step in the molecular mechanism of resveratrol. Mitochondrial morphology is a malleable property that is capable of impeding cell cycle progression and conferring resistance against stress induced cell death. Using confocal microscopy and a novel ‘cell free’ fusion assay it was determined that concurrent with changes in MnSOD protein levels, resveratrol treatment leads to a more fused mitochondrial reticulum. This observation may be important to resveratrol’s ability to slow proliferative cell growth and confer cytoprotection. Resveratrol's biological activities, including the ability to increase MnSOD levels, are strikingly similar to what is observed with estrogen treatment. Resveratrol fails to increase MnSOD levels, slow proliferative cell growth and confer cytoprotection in the presence of an estrogen receptor antagonist. Resveratrol's effects can be replicated with the specific estrogen receptor beta agonist diarylpropionitrile, and are absent in myoblasts lacking estrogen receptor beta. Four compounds that are structurally similar to resveratrol and seven phytoestrogens predicted to bind to estrogen receptor beta were screened for their effects on MnSOD, proliferative growth rates and stress resistance in cultured mammalian cells. Several of these compounds were able to mimic the effects of resveratrol on MnSOD levels, proliferative cell growth and stress resistance in vitro. Thus, I hypothesize that resveratrol interacts with estrogen receptor beta to induce the upregulation of MnSOD, which in turn affects cell cycle progression and stress resistance. These results have important implications for the understanding of RES’s biological activities and potential applications to human health.

Syntrophic relationships between algae and bacteria in a fresh-water stream and in culture /

Interactions between freshwater algae and bacteria were examined in a natural stream habitat and a laboratory model. Field observations provided circumstantial evidence, in statistical correlation for syntrophy between the microbial populations. This relation is probably subject to control by the temperature and pH of the aquatic environment. Several species of a pond community were isolated in axenic culture and tests were performed to determine the nature of mixed species interactions. Isolation procedures and field studies indicated that selected strains of Chlorella and Azotobacter were closely associated in their natural habitat. With the suspected controlling parameters, pH and temperature, held constant, mixed cultures of algae and bacteria were compared to axenic cultures of the same organisms, and a mutual stimulation of growth was observed. A mixed pure culture apparatus was designed in this laboratory to study the algal-bacterial interaction and to test the hypothesis that such an interaction may take place through a diffusable substance or through certain medium-borne conditions, Azotobacter was found to take up a Chlorella-produced exudate, to stimulate protein synthesis, to enhance chlorophyll production and to cause a numerical increase in the interacting Chlorella population. It is not clear whether control is at the environmental, cellular or genetic level in these mixed population interactions. Experimental observations in the model system, taken with field correlations allow one to state that there may be a direct relationship governing the population fluctuations of these two organisms in their natural stream surroundings.

Developmental variations in the peripheral erythrocytic system of the rainbow trout, Salmo gairdneri

The peripheral circulating erythrocytic system of the rainbow trout, l3 almo gairdner , was examined in vitro in relation differences in the morphology and multiple hemoglobin system organization of adult and juvenile red cells. Cells were separated by velocity sedimentation under unit gravity, a procedure requiring red cell exposure to an incubation medium for periods of at least three hours. Therefore , this must provide an environment in which red cells remain in a condition approximaing normalcy. Previous studies having demonstrated commonly employed media to be ineffective in this regard , a medium was developed through modification of Cortl and saline. One of the principal additions to this me dium , norepinephrine, altered cell regulation of intracellular calcium, magnesium and chloride concentrations. Catecholamine involvement was also suggeste d in the synthes is of hemoglobin . The procedure was found to separtate cells primarily by density and, to a lesser extent, by shape. Characterization of red cells revealed two subpopulations to exist . The first comprised the bulk of the cell population, and were of greater l ength, width, volume and major:minor axis ratio than the smaller population; these were adult cells. The later, juvenile cells were of smaller overall size and were more spherical in shape . Juvenile cells also possessed fewer electrophore tpically distinguishable isomorphs than did adults with only eight of eleven hemoglobin component s typically found With maturation,hemoglobin complement with the development of three more bands. The total complement of the adult cell contained 7 cathodal bands and four anodal hemoglobin isomorphs. Bands acquired with maturation comprised the smallest percentage of the cells hemoglobin. each averaging less than one-percent of the total. Whether these additional bands are derived through degradation and reaggregation of existing components or are the product of pe gQy2 synthesis is not yet known.

Values and the classroom teacher

This is a descriptive study of elementary school teachers' perceptions of values transmitted in classrooms. Through circulation of a survey to teachers in Public and Separate Schools in the "Golden I-Iorseshoe" distt-ict of SOLtthern Ontario (e}{clLtding Toronto), it was found that teachers do see themselves as promoting values which tend to be conceptual or knowledge-based and receptive and pertain to self-perception and personal growth. They also show a tendency t.o Lise nlore conceptL\al teachi ng strategies SLieri as discussiona The respondents had no clear opinion regarding student disposition toward values but did feel very influential in developing that disposition. Demographic factors of gender, age, teaching division and teaching experience affected the responses to the surveYa The study was undertaken to describe a very sensitive area in education in the hope of moving closer toward a more effective school system II.

The impact of tobacco control policies on university students' smoking in Ontario

Objective. Despite steady declines in the prevalence of tobacco use among Canadians, young adult tobacco use has remained stubbornly high over the past two decades (CTUMS, 2005a). Currently in Ontario, young adults have the highest proportion of smokers of all age cohorts at 26%. A growing body of evidence shows that smoking restrictions and other tobacco control policies can reduce tobacco use and consumption among adults and deter initiation among youth; whether young adult university students' smoking participation is influenced by community smoking restrictions, campus tobacco control policies or both remains an empirical question. The purpose of this study is to examine the relationship among current smoking status of students on university campuses across Ontario and various tobacco control policies, 3including clean air bylaws of students' home towns, clean air by-laws of the community where the university is situated, and campus policies. Methods. Two data sets were used. The 200512006 Tobacco Use in a Representative Sample of Post-Secondary Students data set provides information about the tobacco use of 10,600 students from 23 universities and colleges across Ontario. Data screening for this study reduced the sample to 5,114 17-to-24 year old undergraduate students from nine universities. The second data set is researcher-generated and includes information about strength and duration of, and students' exposure to home town, local and campus tobacco control policies. Municipal by-laws (of students' home towns and university towns) were categorized as weak, moderate or strong based on criteria set out in the Ontario Municipal By-law Report; campus policies were categorized in a roughly parallel fashion. Durations of municipal and campus policies were calculated; and length of students' exposure to the policies was estimated (all in months). Multinomial logistic regression analyses were used to examine the relationship between students' current smoking status (daily, less-than-daily, never-smokers) and the following policy measures: strength of, duration of, and students' exposure to campus policy; strength of, duration of, and students' exposure to the by-law in the university town; and, strength of, duration of, and students' exposure to the by-law in the home town they grew up in. Sociodemographic variables were controlled for. Results. Among the Ontario university students surveyed, 7.0% currently use tobacco daily and 15.4% use tobacco less-than-daily. The proportions of students experiencing strong tobacco control policies in their home town, the community in which their university is located and at their current university were 33.9%,64.1 %, and 31.3% respectively. However, 13.7% of students attended a university that had a weak campus policy. Multinomial logistic regressions suggested current smoking status was associated with university town by-law strength, home town by-law strength and the strength of the campus tobacco control policy. In the fmal model, after controlling for sociodemographic factors, a strong by-law in the university town and a strong by-law in students' home town were associated with reduced odds of being both a less-than-daily (OR = 0.64, 95%CI: 0.48-0.86; OR = 0.80, 95%CI: 0.66-0.95) and daily smoker (OR = 0.59, 95%CI: 0.39-0.89; OR = 0.76, 95%CI: 0.58-0.99), while a weak campus tobacco control policy was associated with higher odds of being a daily smoker (OR = 2.08, 95%CI: 1.31-3.30) (but unrelated to less-than-daily smoking). Longer exposure to the municipal by-law (OR = 0.93; 95%CI: 0.90-0.96) was also related to smoking status. Conclusions. Students' smoking prevalence was associated with the strength of the restrictions in university, and with campus-specific tobacco control policies. Lessthan- daily smoking was not as strongly associated with policy measures as daily smoking was. University campuses may wish to adopt more progressive campus policies and support clean air restrictions in the broader community. More research is needed to determine the direction of influence between tobacco control policies and students' smoking.

Parent and Peer Factors Relating to Adolescent Antisocial Behaviour: Investigating the Moderating Role of Temperament

The purpose of this study was to examine whether certain temperament characteristics (fearfulness, surgency, frustration, and effortful control) moderate the association between authoritative parenting dimensions (psychological autonomy granting, acceptance-involvement, and monitoring knowledge) or friends' antisocial behaviour, and self-reported antisocial behaviour among adolescents. Questionnaires on adolescent temperament and authoritative parenting were completed by 484 mothers and their adolescent children (54.8% female). In addition, the adolescents responded to measures regarding friends' antisocial behavior and their own antisocial behaviour. Adolescent participants ranged between 13 and 17 years of age (M = 14.96 years, SD = 1.39) and lived in a region of southern Ontario. As predicted, the results indicated that effortful control moderated the association between parental monitoring knowledge and adolescent antisocial behaviour. Also, as predicted, effortful control moderated the relation between friends' antisocial behaviour and adolescents' self-reports of antisocial behaviour although the relation was sex-specific to girls. Unexpected results included a significant monitoring knowledge by frustration by sex interaction, and a significant friends' antisocial behaviour by age interaction. In general, the findings were consistent with the expectation that the relation of parenting and peer factors to antisocial behaviour would depend on adolescents' temperamental predispositions. However, effortful control, which contributes to individual differences in self-regulation abilities, served this moderating role to a greater extent than the measures of temperamental reactivity, including fearfulness, surgency and frustration-proneness. Implications of these results are discussed with reference to parenting or classroom-based interventions that may be especially helpful for adolescents with poor self-regulation abilities.

Effects of Instruction on Walking and Turning Performance in Individuals with Parkinson's Disease

Parkinson’s disease (PD) is characterized by postural instability and gait impairment. Verbal instructions can reduce postural sway and improve gait performance in PD. For gait, this evidence is limited to unobstructed straight-path walking. As falls in PD often occur when turning, the purpose of this thesis was to determine if instructions can benefit turning performance in this population. Twelve individuals with PD performed two walking tasks (normal walking, walking with a 180 degree turn) under four instruction conditions (no instruction, take big steps, make larger trunk movements, focus on end and/or turn point). Task duration and trunk yaw and roll sway were calculated. In general, the results demonstrated that the instruction to take big steps improved performance for both tasks compared to providing no instruction or externally based instruction. These results suggest that instructions related to step amplitude may facilitate walking and turning performance in PD.

L-Fuzzy Structured Query Language

Lattice valued fuzziness is more general than crispness or fuzziness based on the unit interval. In this work, we present a query language for a lattice based fuzzy database. We define a Lattice Fuzzy Structured Query Language (LFSQL) taking its membership values from an arbitrary lattice L. LFSQL can handle, manage and represent crisp values, linear ordered membership degrees and also allows membership degrees from lattices with non-comparable values. This gives richer membership degrees, and hence makes LFSQL more flexible than FSQL or SQL. In order to handle vagueness or imprecise information, every entry into an L-fuzzy database is an L-fuzzy set instead of crisp values. All of this makes LFSQL an ideal query language to handle imprecise data where some factors are non-comparable. After defining the syntax of the language formally, we provide its semantics using L-fuzzy sets and relations. The semantics can be used in future work to investigate concepts such as functional dependencies. Last but not least, we present a parser for LFSQL implemented in Haskell.

Single-Molecule Magnets and Multifunctional Molecular Magnetic Materials Based on Polynuclear Metal Complexes

Our work on single molecule magnets and multifunctional magnetic materials is presented in four projects. In the first project we show for first time that heteroatomic-type pseudohalides, such as OCN-, can be employed as structure-directing ligands and ferromagnetic couplers in higher oxidation state metal cluster chemistry. The initial use of cyanato groups in Mn cluster chemistry has afforded structurally interesting MnII/III14 (1) and MnII/III/IV16 (2) clusters in which the end-on bridging cyanates show a preference in binding through their O-atom. The Mn14 compound shows entirely visible out-of-phase alternating currect signals below 5 K and large hysteresis loops below 2 K. Furthermore, the amalgamation of azido groups with the triethanolamine tripodal ligand in manganese carboxylate cluster chemistry has led to the isolation of a new ferromagnetic, high-nuclearity and mixed-valence MnII/III15Na2 (3) cluster with a large ground-state spin value of S = 14. In the second project we demonstrate a new synthetic route to purely inorganic-bridged, transition metal-azido clusters [CoII7 (4) and NiII7 (5)] and coordination polymers [{FeII/III2}n (6)] which exhibit strong ferromagnetic, SMM and long-range magnetic ordering behaviors. We also show that access to such a unique ferromagnetic class of inorganic, N-rich and O-free materials is feasible through the use of Me3SiN3 as the azido-ligand precursor without requiring the addition of any organic chelating/bridging ligand. In the last projects we have tried to bring together molecular magnetism and optics via the synthesis of multifunctional magnetic materials based on 3d- or 4f-metal ions. We decided to approach such challenge from two different directions: firstly, in our third project, by the deliberate replacement of non-emissive carboxylato ligands in known 3d-SMMs with their fluorescent analogues, without perturbing the metal-core structure and SMM properties (complexes 7, 8, and 9). The second route (last project) involves the use of naphthalene or pyridine-based polyalcohol bridging ligands for the synthesis of new polynuclear LnIII metal clusters (Ln = lanthanide) with novel topologies, SMM behaviors and luminescent properties arising from the increased efficiency of the “antenna” organic group. This approach has led us to the isolation of two new families of LnIII8 (complexes 10-13) and LnIII4 (complexes 14-20) clusters.