Expression and function of endothelin and its receptors in vascular adventitial fibroblasts

Objective: The adventitia has been recognized to play important roles in vascular oxidative stress, remodelling and contraction. We recently demonstrated that adventitial fibroblasts are able to express endothelin-1 (ET-1) in response to angiotensin II (ANG II). However, the mechanisms by which ANG II induces ET-1 expression are unknown. It is also unclear whether the ET-1 receptors are expressed in the adventitia. We therefore examined the role of oxidative stress in the regulation of ET-1. We also investigated the expression of both the ETA and ETB receptors and the roles of these two types of receptors in collagen synthesis and ET-1 clearance in adventitial fibroblasts. Methods and Results: Adventitial fibroblasts were isolated and cultured from the thoracic mouse aorta. Cells were treated with ANG II (lOOnM), ET-1 (lOpM), NADPH oxidase inhibitor apocynin (lOOfiM), the superoxide anion scavenger tempol (lOOfiM), the ANG II receptor antagonists (100[aM), losartan (AT| receptor) and PD 1233 19 (AT2 receptor), the ET-1 receptor antagonists (lOOuM), BQ123 (ETA receptor) and BQ788 (ETB receptor), and the ETB receptor agonist (lOOnM) Sarafotoxin 6C. ET-1 peptide levels were determined by ELISA, while ETA ,ETB and collagen levels were determined by Western blot. ANG II increased ET-1 peptide levels in a time-dependent manner reaching significance when incubated for 24 hours. NAD(P)H oxidase inhibitor, apocynin, as well as the superoxide scanverger, tempol, significantly reduced ANG Il-induced ET-1 peptide levels while over-expression of SOD1 (endogenous antioxidant enzyme) significantly decreased ANG Il-induced collagen I expression, therefore implicating reactive oxygen species in the mediation of ET-1. ANG II increased ETA receptor protein as well as collagen in a similar fashion, reaching significance after 4, 6, and 24 hours treatment. ANG II induced collagen was reduced while in the presence of the ETA receptor antagonist suggesting the role of the ETa receptor in the regulation of the extracellular matrix. ANG II treatment also increased ETB receptor protein levels in a time-dependent manner. ANG II treatment in the presence of the ETB receptor antagonist significantly increased ET-1 peptide levels. On another hand, the ETB receptor agonist, Sarafotoxin 6C, significantly decreased ET-1 peptide levels. These data implicate the role of the ETb receptor in the clearance of the ET-1 peptide. Conclusion: ANG II-induced increases of ET-1 peptide appears to be mediated by reactive oxygen species derived from NAD(P)H oxidase. Both the ETA and ETB receptors are expressed in adventitial fibroblasts. The ETA receptor subtype mediates collagen I expression, while the ETB receptor may play a protective role through increasing the clearance of the ET- 1 peptide.

Aspects of the hemes and modulation of hydrogen donors in catalases from bovine liver, yeast, and escherichia coli

Catalase is the enzyme which decomposes hydrogen peroxide to water and oxygen. Escherichia coli contains two catalases. Hydroperoxidase I (HPI) is a bifunctional catalase-peroxidase. Hydroperoxidase II (HPII) is only catalytically active toward H202. Expression of the genes encoding these proteins is controlled by different regimes. HPJI is thought to be a hexamer, having one heme d cis group per enzymatic subunit. HPII wild type protein and heme containing mutant proteins were obtained from the laboratory of P. Loewen (Univ. of Manitoba). Mutants constructed by oligonucleotidedirected mutagenesis were targeted for replacement of either the His128 residue or the Asn201 residue in the vicinity of the HPII heme crevice. His128 is the residue thought to be analogous to the His74 distal axial ligand of the heme in the bovine liver enzyme, and Asn201 is believed to be a residue critical to the function of the enzyme because of its role in orienting and interacting with the substrate molecule. Investigation of the nature of the hemes via absorption spectroscopy of the unmodified catalase proteins and their derived pyridine hemochromes showed that while the bovine and Saccharomyces cerevisiae catalase enzymes are protoheme-containing, the HPII wild type protein contains heme d, and the mutant proteins contain either solely protoheme, or heme d-protoheme mixtures. Cyanide binding studies supported this, as ligand binding was monophasic for the bovine, Saccharomyces cerevisiae, and wild type HPII enzymes, but biphasic for several of the HPII mutant proteins. Several mammalian catalases, and at least two prokaryotic catalases, are known to be NADPH binding. The function of this cofactor appears to be the prevention of inactivation of the enzyme, which occurs via formation of the inactive secondary catalase peroxide compound (compound II). No physiologically plausible scheme has yet been proposed for the NADPH mediation of catalase activity. This study has shown, via fluorescence and affinity chromatography techniques, that NADPH binds to the T (Typical) and A (Atypical) catalases of Saccharomyces cerevisiae, and that wild type HPII apparently does not bind NADPH. This study has also shown that NADPH is unlike any other hydrogen donor to catalase, and addresses its features as a unique donor by proposing a mechanism whereby NADPH is oxidized and catalase is protected from inactivation via the formation of protein radical species. Migration of this radical to a position close to the NADPH is also proposed as an adjunct hypothesis, based on similar electron migrations that are known to occur within metmyoglobin and cytochrome c peroxidase when reacted with H202. Validation of these hypotheses may be obtained in appropriate future experiments.

Leisure-time physical activity in individuals with osteoporosis : associations with psychological well-being

With approximately 16% of the Canadian population living with osteoporosis, and rates expected to increase (Osteoporosis Canada, 2009), cost-effective treatment modalities that improve bone health and psychological well-being reflect an important public health agenda. Physical activity has been implicated as one non-pharmaceutical mechanism to help improve psychological well-being in the general population (Fox, Stathi, McKenna, & Davis, 2007) and in people diagnosed with osteoporosis (Osteoporosis Canada, 2007). The purpose of this investigation was to determine the association between leisure-time physical activity (LTP A) and well-being in people diagnosed with osteoporosis. A secondary purpose, using Basic Needs Theory (BNT; Deci & Ryan, 2002) was to determine if the fulfillment of three psychological needs (i.e., competence, autonomy and relatedness) mediated the relationship between LTP A and well-being. People diagnosed with osteoporosis (N= 190; Mage = 68.14; SDage = 11.54) were asked to complete a battery of questionnaires assessing L TP A, hedonic and eudaimonic well-being and perceived psychological need satisfaction in physical activity contexts. Bivariate correlations revealed a pattern of negligible (r's -0.02 to 0.35) to small correlations between LTP A and well-being with contextual positive affect (r = 0.24) and subjective vitality (r = 0.22) demonstrating statistical significance (p < .01). Results of the multiple mediation analysis indicated that perceived satisfaction of the three psychological needs mediated the relationship between LTPA and well-being with perceived competence emerging as a unique mediator. As such, LTP A was positively associated with well-being in people who are diagnosed with osteoporosis, and the fulfillment of the three psychological needs may be the mechanism through which this 111 effect is carried. Health promotion specialists and practitioners should encourage patients with osteoporosis to engage in LTP A, and support their needs for competence, autonomy and relatedness. Practical implications for researchers and health promotion specialists are discussed in terms ofthe results of this investigation.

Message from the President of the United States, transmitting a report of the Secretary of State, in obedience to a resolution of the thirteenth inst.

Full Title: 47. Message from the President of the United States, transmitting a report of the Secretary of State, in obedience to a resolution of the thirteenth inst. "requesting the President to lay before this House such documents relative to the Russian mediation as in his opinion it may not be improper to communicate." United States,13th Congress, 2d session, 1813-1814. House. Doc. no. 35. January 18, 1814. Ordered to lie on the table. One letter in French with English translation Printed by Roger C. Weightman

Role Differences in the Perception of Injustice

The current dissertation examined role differences in the perception of injustice; specifically, differences in how victims and offenders respond to a situation that they both agree is unfair. Past research has demonstrated that role affects reactions to transgressions and injustice, including recall of transgressions, and attributions of blame and responsibility (e.g., Baumeister, Stillwell, & Wotman, 1990; Mikula, Athenstaedt, Heschgl, & Heimgartner, 1998). However, to date, little work has examined role differences in perceptions of why an event is perceived as unfair (i.e., how an injustice is framed) or how justice should be restored. These were the perceptions I focused on in the present thesis. I also examined potential concerns that may motivate victims' and offenders' justice reactions, as well as the potential interaction between role and relationship quality in predicting justice reactions. In Studies 1 and 2, several of the predicted role differences in concerns were found; however, these did not lead to the expected differences in framing and restoration. In Study 1, using a vignette methodology, I found differences primarily in how victims and offenders believed justice should be restored. Overall, the significant role effects showed an accommodating response pattern (e.g., offenders proposed punishment more than did victims and neutral observers, whereas victims recommended minimal compensation more than did offenders and neutral observers), inconsistent with previous research and my hypotheses. Study 2, which employed a sample of romantic couples, substantiated the accommodating pattern found in Study 1. Study 3, which sampled a broader range of relationships, also showed i \ examples of accommodating reactions. In addition, Study 3 provided some support for the hypothesized interaction between role and relationship quality, such that responses were more accommodating as relationship quality increased. For example, offenders more strongly endorsed methods of restoration such as offender apology and recognition of the relationship with increasing relationship quality. Overall, the results from this dissertation support the general notion that victims and offenders respond to injustice differently, and, in-line with previous research on other justice-related responses (e.g., Mikula et at, 1998), suggest that victims and offenders show an other-serving, accommodating tendency in justice reactions when relationship quality is high.

Understanding the Origin of Selectivity in the Asymmetric Lithiation Reaction of N-Heterocycles: A Theoretical Study

The natural abundance of the N-heterocycle containing compounds has pushed the synthetic community toward the invention of new synthetic methods that result in the structural diversity of N-heterocycles. Among this, is the efficient and highly selective diamine mediated asymmetric lithiation process. Amongst the diamine chiral ligands, (-)-sparterine, which is a naturally occurring alkaloid proved to be an efficient one. Many successful, good yielding and highly selective lithiation reactions have been accomplished with the mediation by this chiral diamine base. Although, there are some examples of experimental and theoretical mechanistic studies in the literature, there is a lack of detailed understanding as to how it exactly induces the chirality. In this thesis is described a systematic investigation of how (-)-sparteine influences the stereoselectivity in the course of asymmetric lithiation reaction. This led us to the establishment of the function of A-ring’s β-CH2 effect and D-ring effect. Consequently, the importance of the A-ring and D-ring portions of (-)-sparteine in the stereoselectivity is unraveled. Another part of this thesis deals with the asymmetric lithiation of BF3-activated N,N- dimethylaminoferrocene in the presence of (1R, 2R)-N1,N2-bis(3,3-dimethylbutyl)-N1,N2-dimethylcyclohexane-1,2-diamine ( a (R,R)-TMCDA surrogate) with i-PrLi. Computational findings were in full accord with the experimental observations. Subsequently, the theoretically provided insights into the mechanism of the reaction were exploited in computational design of a new ligand. Unfortunately, the outcome of this design was not experimentally robust and an updated approach towards a successful design was explained.

Linking Ethical Leadership and Employees’ In-Role Performance: Exploring the Mediating Roles of Psychological Capital and Follower-Leader Relational Capital

This study investigates the mediating impact of psychological capital and follower-leader relational capital on the relationship between ethical leadership and in-role performance through the lenses of social exchange theory, social information processing theory, and psychological resources theory. Analysis of data collected from a sample of 171 employees and 24 supervisors from Pakistan reveals that ethical leadership has a positive effect on followers’ in-role job performance, yet this effect is fully explained through the role of psychological capital and partially through follower-leader relational capital. Significant implications of these findings for further research and practice are discussed.

The Efficiency of Collective Bargaining in Public Schools.

This paper develops a bargaining model of wage and employment determination for the public sector. the solution to the model generates structural wage and employment equations that are estimated using data from New York State teacher-school district collective bargaining agreements.

Negative affect mediates the relationship between the Cortisol Awakening Response and Conduct Problems in boys

Ce mémoire débute avec deux chapitres portant sur les problèmes des conduites et la régulation du stress, notamment sur l’axe hypothalamique-pituitaire-surrénal (HPS). Ensuite, la littérature est résumée et nous voyons que les études qui cherchent à établir un lien entre les problèmes des conduites et l’axe HPS ont trouvé des résultats différents et parfois contradictoires. Le chapitre suivant illustre les problèmes méthodologiques qui pourraient expliquer ces résultats différents. Vient ensuite l’étude présentée dans ce mémoire qui cherche à établir un lien entre la réponse cortisolaire à l’éveil (RCE), considérée comme un bon indice du fonctionnent de l’axe HPS, et les problèmes de conduites chez l’enfant. De plus, les émotions négatives ont été associées avec les problèmes des conduites ainsi qu’aux dysfonctions de l’axe HPS, notamment le RCE. L’étude présentée dans ce mémoire cherche aussi à établir si les émotions négatives pourrait être une variable médiatrice dans la relation potentielle entre la RCE et les problèmes des conduites. L’étude révèle que pour les garçons mais pas pour les filles, une RCE réduite est associée avec les émotions négatives, ce qui est successivement associé avec les problèmes des conduites. Le dernier chapitre du mémoire examine les implications théoriques de cette médiatisation et propose également des pistes psychobiologiques pour expliquer les différences sexuelles observées.

Study of the relationship between academic performance and socioeducative climates in gifted high school students

Il est évalué qu’entre 15 et 40 % des élèves surdoués performent à des niveaux inférieurs à leur potentiel (Seeley, 1994). Récemment, plusieurs chercheurs se sont plongés dans ce phénomène en tentant de l’expliquer. Par contre, une seule équipe de recherche s’est attardé sur l’impact des climats socioéducatifs sur la performance des surdoués, alors que ce lien est bien existant chez les jeunes non-doués. Cette recherche vise à explorer la relation possible entre les climats socioéducatifs, l’environnement familial et la performance scolaire chez les jeunes surdoués, afin de combler ce manque dans la littérature. Afin d’atteindre cet objectif, un échantillon de 1 885 participants de 3e secondaire provenant de la base de donnée de l’évaluation du programme SIAA furent étudiés afin de créer un modèle présentant l’effet des environnements sur la performance des jeunes surdoués, médié par la motivation. Nos résultats suggèrent que l’impact des environnements socioéducatifs et familiaux sur la performance des jeunes surdoués est minime, bien qu’il soit majeur chez les jeunes non-doués.

Arab Women in Translation : the Dynamics of Representation and the Construction of Alterity

Cette recherche examine la traduction et la réception en France, en Grande Bretagne et aux États-Unis de la littérature contemporaine d’expression arabe écrite par des femmes, afin de répondre à deux questions principales: comment les écrivaines provenant de pays arabes perdent-elles leur agentivité dans les processus de traduction et de réception? Et comment la traduction et la réception de leurs textes contribuent-elles à la construction d’une altérité arabe? Pour y répondre, l’auteure examine trois romans présentant des traits thématiques et formels très différents, à savoir Fawḍā al-Ḥawāss (1997) par Ahlem Mosteghanemi, Innahā Lundun Yā ‘Azīzī (2001) par Hanan al-Shaykh et Banāt al-Riyāḍ (2005) par Rajaa Alsanea. L’analyse, basée sur le modèle à trois dimensions de Norman Fairclough, vise à découvrir comment les écrivaines expriment leur agentivité à travers l’écriture, et quelles images elles projettent d’elles-mêmes et plus généralement des femmes dans leurs sociétés respectives. L’auteure se penche ensuite sur les traductions anglaise et française de chaque roman. Elle examine les déplacements qui s’opèrent principalement sur le plan de la texture et le plan pragma-sémiotique, et interroge en quoi ces déplacements ébranlent l’autorité des écrivaines. Enfin, une étude de la réception de ces traductions en France, en Grande Bretagne et aux États-Unis vient enrichir l’analyse textuelle. À cette étape, les critiques éditoriales et universitaires ainsi que les choix éditoriaux relatifs au paratexte sont scrutés de façon à mettre en lumière les processus décisionnels, les discours et les tropes sous-tendant la mise en marché et la consommation de ces traductions. L’analyse des originaux révèle tout d’abord qu’à travers leurs textes, les auteures sont des agentes actives de changement social. Elles s’insurgent, chacune à sa manière, contre les discours hégémoniques tant locaux qu’occidentaux, et (ré-)imaginent leurs sociétés et leurs nations. Ce faisant, elles se créent leur propre espace discursif dans la sphère publique. Toutefois, la thèse montre que dans la plupart des traductions, les discours dissidents sont neutralisés, l’agentivité et la subjectivité des écrivaines minées au profit d’un discours dominant orientaliste. Ce même discours semble sous-tendre la réception des romans en traduction. Dans ce discours réifiant, l’expression de la différence culturelle est inextricablement imbriquée dans l’expression de la différence sexuelle: la « femme arabe » est la victime d’une religion islamique et d’une culture arabe essentiellement misogynes et arriérées. L’étude suggère, cependant, que ce sont moins les interventions des traductrices que les décisions des éditeurs, le travail de médiation opéré par les critiques, et l’intérêt (ou le désintérêt) des universitaires qui influencent le plus la manière dont ces romans sont mis en marché et reçus dans les nouveaux contextes. L’auteure conclut par rappeler l’importance d’une éthique de la traduction qui transcende toute approche binaire et se fonde sur une lecture éthique des textes qui fait ressortir le lien entre la poétique et la politique. Enfin, elle propose une lecture basée sur la reconnaissance du caractère situé du texte traduit comme du sujet lisant/traduisant.

Financial Information Mediation: A Case Study of Standards Integration for Electronic Bill Presentment and Payment Using the COIN Mediation Technology

Each player in the financial industry, each bank, stock exchange, government agency, or insurance company operates its own financial information system or systems. By its very nature, financial information, like the money that it represents, changes hands. Therefore the interoperation of financial information systems is the cornerstone of the financial services they support. E-services frameworks such as web services are an unprecedented opportunity for the flexible interoperation of financial systems. Naturally the critical economic role and the complexity of financial information led to the development of various standards. Yet standards alone are not the panacea: different groups of players use different standards or different interpretations of the same standard. We believe that the solution lies in the convergence of flexible E-services such as web-services and semantically rich meta-data as promised by the semantic Web; then a mediation architecture can be used for the documentation, identification, and resolution of semantic conflicts arising from the interoperation of heterogeneous financial services. In this paper we illustrate the nature of the problem in the Electronic Bill Presentment and Payment (EBPP) industry and the viability of the solution we propose. We describe and analyze the integration of services using four different formats: the IFX, OFX and SWIFT standards, and an example proprietary format. To accomplish this integration we use the COntext INterchange (COIN) framework. The COIN architecture leverages a model of sources and receivers’ contexts in reference to a rich domain model or ontology for the description and resolution of semantic heterogeneity.

Belonging to a community: the mediation of belonging

This paper introduces the concept of belonging and discusses it in the context of online social networking experience and community experience considering social capital and user’s activities as nuclear concepts to understand collective actions and social relationships mediated by social media. The paper presents an empirical approach based on the study of two local communities and analyses whether interactive social technologies promote greater social involvement and higher production of social capital and participation, that results in a greater sense of belonging within communities. The results indicate a positive relationship between the use of social media and the increase of social capital and sense of belonging. Our work discusses the role and influence of social media in communitarian practices and the relevance social capital theory has as an outcome of media technologies use that result in a greater sense of belonging to a community.

Platonic allusion in Plutarch's Alcibiades 4-7

Plutarch deals with Socrates' relationship with Alcibiades in chs. 4-7 of his Life. He draws heavily here on two Platonic works, the First Alcibiades and the Symposium, but engagement with the Platonic texts is denser and more profound in Alcibiades than a study of just those two texts would suggest. In fact, this part of the Alcibiades contains allusions to several other Platonic texts in which Alcibiades does not occur as a character and in which his name is not mentioned: Republic Books 6 and 8, Charmides, Phaedrus, Apology, and Lysis. These texts function as ‘intertexts’ against which the Alcibiades is to be read.

Does training improve understanding of core concepts in cognitive behaviour therapy by people with intellectual disabilities? A randomized experiment

Background. People with intellectual disabilities (ID) experience similar or even higher rates of mental health problems than the general population and there is a need to develop appropriate treatments. Cognitive behaviour therapy (CBT) is effective for a wide range of disorders in the general population. However, there is some evidence that people with ID may lack the cognitive skills needed to take part in CBT. Aims. To test if people with ID can learn skills required for CBT, specifically the ability to distinguish between thoughts, feelings, and behaviours and to link thoughts and feelings (cognitive mediation). Method. A randomized independent groups design was used to examine the effect of training in CBT on two tasks measuring CBT skills. Thirty-four adults with ID were randomly allocated to the experimental condition ðN ¼ 18Þ or to the control condition ðN ¼ 16Þ. CBT skills were assessed blind at baseline and after the intervention. Results. The training led to significant improvements in participants’ ability to link thoughts and feelings, and this skill was generalized to new material. There was no effect of training on participants’ ability to distinguish amongst thoughts, feelings, and behaviours. People with ID can, therefore, learn some skills required for CBT. This implies that preparatory training for CBT might be useful for people with ID. The results might be applicable to other groups who find aspects of CBT difficult.