Alors que les étapes du cycle du virus de la rage sont plutôt bien décrites, les interactions du virus avec la machinerie cellulaire restent mal connues. Le but de ce projet de thèse a été d’identifier et caractériser les voies de signalisation cellulaires impliquées dans le déroulement du cycle viral. Les kinases cellulaires jouent un rôle majeur dans la régulation de ces voies et certaines protéines rabiques ont déjà été décrites comme cibles de ces enzymes. Afin d’identifier les kinases impliquées dans le déroulement du cycle viral, nous avons réalisé un criblage d’une banque d’inhibiteur de kinases. L’analyse a été effectuée par cytométrie en flux dans des cellules infectées avec un virus rabique recombinant exprimant la protéine fluorescente GFP. Nous avons ainsi pu isoler deux inhibiteurs de kinases bloquant l’infection : La Tyrphostin 9,un inhibiteur de l’autophosphorylation du récepteur au PDGF (platelet-derived growth factor) (PDGF.R), et la Rottlerin, un inhibiteur de la PKCδ et découplant mitochondrial. Nous avons confirmé leur activité anti-virale dans différents types cellulaires (fibroblaste, glioblastome,neuroblastome et neurones primaires) et sur deux souches rabiques (CVS et SAD-B19). Par diverses approches expérimentales, nous avons identifié l’étape du cycle viral ciblée par chacun de ces inhibiteurs. Les résultats obtenus montrent que la Tyrphostin 9 perturbe une étape très précoce de l’infection : la fusion virale et plus particulièrement l’acidification endosomale. Nous avons observé que la Tyrphostin 9 provoquait également une désagrégation de l’appareil de Golgi. L’inhibition de l’acidification endosomale pourrait donc découler de cet effet. En présence de Rottlerin, le cycle viral est également inhibé au niveau d’une étape précoce : la réplication. A l’aide de siRNA, nous avons montré que cet effet de la Rottlerin est indépendant de la PKCδ. Les expériences réalisées avec un découplant mitochondrial bien caractérisé, le CCCP, tendent à montrer que l’effet de la Rottlerin est dû à sa fonction de découplant mitochondrial, qui induit une diminution du niveau d’ATP intracellulaire. Ce travail a permis d’identifier deux inhibiteurs de kinases inhibant des étapes précoces du cycle rabique. Les cibles cellulaires précisément impactées ainsi que l’effet sur le fonctionnement cellulaire lors de l’infection virale restent à déterminer. Des études in vivo pourraient valider leur utilisation en tant qu’agents antiviraux. / However the rabies viral cycle is fairly well described, the interactions with the cellular machinery are not. This thesis project aimed at identifying and characterizing the cellular signaling pathways involved in the establishment and progress of the viral cycle through the study of cellular kinases. Indeed, kinases are the main actors of these pathways and their effects on certain rabies proteins have already been reported. In order to identify kinases involved in the viral cycle, we screened a kinase inhibitor library for anti-viral activity using a recombinant rabies virus expressing the GFP fluorescent protein. This assay allowed us to isolate two kinase inhibitors that block rabies virus infection: Tyrphostin 9, an inhibitor of the receptor tyrosine kinase platelet-derived growth factor receptor (PDGF.R), and Rottlerin, a PKCδ inhibitor and mitochondrial uncoupler. We confirmed their anti-viral action in different cell types (fibroblast, glioblastoma, neuroblastoma, as well as primary neurons) and on different rabies strains (CVS and SAD-B19). Using various experimental approaches, we found that each inhibitor impairs an early stage of the viral cycle: the viral fusion and more specifically the endosomal acidification by Tyrphostin 9 and the viral replication step by Rottlerin. We observed that Tyrphostin 9 also caused disintegration of the Golgi apparatus. The inhibition of endosomal acidification could therefore result from this effect. Seeking for the mechanisms involved in Rottlerin’s effect, we evidenced that it is independent of PKCδ. Experiments with a well characterized mitochondrial uncoupler (CCCP), revealed that the Rottlerin anti-viral effect is rather due to its mitochondrial uncoupling function, which leads to a decrease of the cellular ATP level. This study allowed the identification of two kinase inhibitors with anti-viral effects acting on early stages of the rabies cycle. The cellular targets as well as the effect on the cellular functions during viral infection remain to be determined. In vivo studies could validate their use in therapeutics as anti-rabies agents.

Infidelity of clergy has been defined as a culture, by those who believe in polygamous marriage. Women are often controlled by men and very few societies exhibit an equalitarian relationship. One paramount way in which men control women is through sex and sexual power. Infidelity is abuse because the characteristics of the unfaithful are like those of a battered and the symptoms of the victim are like those of the battered. Sitting in on battered women’s group, I heard the same things-women wanting to go back; full of anger and rage, saying they’d rather be beaten than wonder where their partner was sleeping at night. The researcher is ministering among Pondo and Bhaca people who are no strangers to this oppressing practice. Few marriages in these days last beyond few years, because infidelity has become such an accepted alternative way of living and working out marital problems. The problem disturbed author’s ministry as a junior minister. As result I am researching this problem so as to come out with a theory that will help to address this issue. Clergy spouses approach the act of infidelity very painful, they ended up traumatizing their own spouses, children and their ministry. One of my favourite clergy in Pondo even resigned his pastorate about a year ago due to adultery and fathering a child outside of his marriage. All of these high profile ministers have been involved in some form of infidelity. But still the powerful words from Paul in 1 Corinthians 10:13 “no temptation has overtaken you except such as is common to man, but God is faithful, who will not allow you to be tempted beyond what you are able, but with the temptation will also make the way of escape, that you may be able to bear it”. Today, many churches invite unfaithful itinerant clergies to preach to their congregations unaware of the spiritual poison they are injecting directly into the life blood of their congregations and the Christian community. No wonder many churches are so full of infidelity, dishonesty and immorality of the worst kind. Clergy spouses decided to stay in their marriage are taught forgiveness, so that they can move away from their traumatic experience. / Dissertation (MA Theol)--University of Pretoria, 2013. / gm2014 / Practical Theology / unrestricted

At best anger is problematic for most of us and especially an issue for women (and other discriminated groups). True a collaborative craft project focusing on silver objects, I investigate female anger and how it is perceived. Also, how the prevention of acting it out silences our need for change. I use the aesthetics of magic to reference the judging of women acting outside of set rules, and also as a tactic of female liberation.

Aggressive driving is a phenomenon that has taken on tremendous significance in society. While the issue has been studied from perspectives of several disciplines, relatively few comprehensive empirical investigations have been conducted. This may be due, at least in part, to a scarcity of comprehensive theoretical works in the field, from which methodical research hypotheses could be derived. This paper reviews major extant theories of general aggression to offer a rationale for choosing a particular framework to apply to the topic of aggressive driving. The social-cognitive model of aggressive driving is recommended, as it takes into account wide-ranging cognitive, situational, and dispositional factors. Implications for future research are also considered.

Driving anxiety that has developed following crashes has been studied relatively frequently, but anxiety per se and its effects on driving has not as yet garnered much attention in the literature. The current study included 1121 participants and found higher levels of general anxiety were related to a wide variety of dangerous driving behaviors. While there were clear and expected sex differences on many dangerous driving variables, there were still more such differences with regard to anxiety levels and independent of sex, higher levels of anxiety were associated with greater levels of dangerous driving. Of particular import, it was found that the high anxiety group had caused significantly more crashes and engaged in more DUI episodes than the low and/or medium anxiety groups. Taken as a whole, the results suggest there is a tremendous need for more research in the area of anxiety and dangerous driving and that interventions for highly anxious drivers may well be warranted.

This article enhances our knowledge of general strain theory (GST) by applying it to the context of traffic delinquency. It does so by first describing and confirming the development of a social-psychological measure allowing for a test of GST. Structural regression analysis is subsequently employed to test the theory within this context across a range of delinquent driving behaviors. Tests indicate that strain experienced while operating a motor vehicle consists of distinct contexts that when considered separately both enhance our understanding of GST and spell policy implications for state-directed interventions. Implications for future GST testing, measurement, and application are also discussed.

Indiana University-Purdue University Indianapolis (IUPUI) / Damage Associated Molecular Patterns (DAMPs) act largely as endogenous ligands to initiate and maintain the signaling of both inflammatory processes and the acquired immune response. Prolonged action of these endogenous signals are thought to play a significant role sterile inflammation which may be integral to the development of chronic inflammation pathology. HMGB1 (High Mobility Group Box 1) is a highly conserved non-acetylated protein which is among the most important chromatin proteins and serves to organize DNA and regulate transcription. Following stress or injury to the cell, hyperacetylation of lysine residues causes translocation of HMGB1 and eventual release into the extracellular environment where it can take the form of a DAMP and interact with cell types bearing either the Receptor for Advanced Glycation End-products (RAGE) or Toll-Like Receptor 4 (TLR4). Activation of these surface receptors contribute directly to both acute and chronic inflammation. This project investigated the role of HMGB1 through its receptors Receptor for Advanced Glycation End-products (RAGE) and Toll-Like Receptor 4 (TLR4) as it pertained to the development of chronic inflammation and pathology in small diameter, nociceptive sensory neurons. It was demonstrated that the neuronal signaling associated with exposure to HMGB1 is dependent upon the ligands conformational states, as the state dictates its affinity and types of neuronal response. Neuronal activation by bacterial endotoxin or the disulfide state of HMGB1 is dependent on TLR4 and the associated signaling adapter protein, Myeloid differentiation primary response gene 88 (MYD88). Interruption of the receptor-mediated signaling cascade associated with MyD88 was shown to be sufficient to mitigate ligand-dependent neuronal activation and demonstrated significant behavioral findings. Further downstream signaling of HMGB1 in the neuron has yet to be identified, however important steps have been taken to elucidate the role of chronic neuroinflammation with hopes of eventual translational adaptation for clinical therapeutic modalities.

Small-scale animal agriculture is a fruitful site for examining the relationships among humans, animals, and the land. This thesis endeavours to show what practices are constitutive of these relationships and, moreover, that establishing the “right” relationships between them are ethical concerns with both analytical and ecological import. Basing myself on fieldwork consisting of participant observation, informal interviews, and filmmaking on a small farm in Ontario, I argue that: dominion is the position from which the farm is cared for; that maintaining the farm is both reproductive and generative of the ethical subject; and that the indeterminacies involved in this maintenance might be resolved or unresolved depending on one’s position in regard to the local farming tradition.

The aim of this paper is to understand how trans people who write and read fanfiction about gender euphoria create meaningful writing processes, contextualize community, and orientate themselves in the world by telling stories about gender euphoria and related emotional experiences. I have conducted interactive chat interviews with four study participants and have, as a way of using an autoethnographic research method, included my own narratives as part of the material. Thus, the material used in this study consists of transcripts of collective sensemaking and discussions about differences and similarities in the experiences that the study participants and I tell each other about. I have analyzed the material using queer phenomenology and affect theory. I have found that the study participants have both varied and similar experiences of finding representation, of translating their emotions into actions, and of (re)shaping what it is that they, as trans people, can do and what narratives they can tell and experience.

In this essay I expend upon the theoretical background of my project on female rage. Through my work I examine how the anger of women is currently viewed and translated in a patriarchal society. I look at different example as a way to contextualize my work, starting from Artemisia Gentileschi’s Judith Slaying Holofernes. I reflect on representations of anger closely through different time periods, mediums and in collaboration with other women. I analyse the process of creating my final visual work RAGE – Glossary to a Woman’s Anger.