Structural and functional investigation of the cytoplasmic domain of the Fas death receptor

Activation of the transmembrane death receptor Fas (CD95/APO-1) by a membrane bound ligand (FasL/CD95L) activates the extrinsic pathway of apoptosis. Intracellular Fas death domains (DDs) are induced to oligomerise enabling binding to the adaptor protein FADD, thereby leading to the recruitment of procaspase 8 and other proteins to form the death inducing signalling complex (DISC).This thesis describes an investigation of the structure and function of the cytoplasmic Fas-DD. A model for the solution structure of the Fas-DD was published in 1996, it has since been reported that the death domain can form at least one other conformation when in complex with FADD. As a foundation to the work in this thesis, modern multidimensional NMR techniques have been used to solve the structure of the FasDD, to further probe the potential for alternative conformations. It has previously been reported that Fas can be phosphorylated at Tyr291, providing a platform for the recruitment of binding partners that can affect non-apoptotic signalling. The second part of this thesis details the development of an expressed protein ligation methodology to prepare a Tyr291 phosphorylated Fas DD to provide a basis for in vitro studies of the structural, dynamic and functional effects of phosphorylation. It is widely accepted that Fas is palmitoylated at Cys199 and recognised by the membrane cytoskeletal protein, ezrin. Fas palmitoylation is important for clathrinmediated internalisation of the DISC, and amplification of the caspase cascade. There are multiple reports detailing the binding of ezrin to Fas, but it is not clear whether this interaction occurs in a palmitoylation-dependent manner. Efforts to characterise an interaction between bacterially expressed intracellular Fas and ezrin proteins were carried out using a number of biophysical assays, described in the third part of this thesis. Building upon this, the fourth section explores the preparation of a palmitoylated Fas construct suitable for biophysical analysis by incubating recombinant Fas with palmitoyl-CoA

An American Enforcement Model of Civil Process in a Canadian Landscape

One general perspective from which to view the Anglo-American legal system shared by Canada is that proposed by Charles Darwin to explain the origin and diversity of biologically distinct species. Darwin\u27s theory of evolution places emphasis upon the adjustment or adaptation over time of biological characteristics to environmental factors by the selection of genetically determined features enabling the most suited to their surroundings to better thrive - the so-called survival of the fittest .\u27 Law might usefully be thought of as bearing an analogous relationship to the social environment in which it exists and must operate. As this milieu for various reasons inevitably undergoes a process of change, a process dramatically popularized as the death of permanence by Alvin Toffler2 , so must the legal system in response adapt itself to the needs dictated by current conditions

The relationship context of nonmarital childbearing in the U.S.

Using Early Childhood Longitudinal Study-Birth Cohort data, we update estimates of cohabiting nonmarital births, examine factors associated with relationship context at birth, and assess racial/ethnic differences. We find that 52% of nonmarital births occur within cohabitations – an increase of 33% since the early 1990s. Blacks have shown the greatest increase in cohabiting births over time. We also find that the fertility histories of men and women have opposite influences on nonmarital childbearing. Furthermore, for Whites, a partner of a different race/ethnicity is associated with a higher risk of a nonmarital birth; for Blacks and Hispanics, the opposite is true.cohabitation, non-marital childbearing

Of Herbicides and Humankind: Palmer\u27s Common Law Lessons

In 1982-83 a small group of Cape Breton landowners and two Indian chiefs, with wide-spread public support took the multi-national forest industry to court in Nova Scotia; and lost Their objective was to obtain an injunction to prevent the spraying of a dioxin-contaminated herbicide on forest plantations near their homes and properties and those of their neighbours The case raised important environmental law issues including the use of class actions, reliance upon common law causes of action, and the availability of injunctive remedies Most significantly, the case brought to the fore the question of how the judicial system should handle the deliberate release of toxic chemicals into the environment when uncertainty existed concerning the impact this activity would have. In this article the author provides background to the case and analyzes the Nova Scotia Supreme Court decision. He concludes that future plaintiffs in a similar position should win on existing legal theory. Finally, Professor Wildsmith suggests an alternative approach that judges could and should within an evolving common law system, take to adjust the burden of proof in cases concerning the use of toxic chemicals

The International Law of Pollution: Protecting the Global Environment in a World of Sovereign States

A good book must have focus. This may not be the only criteria for evaluating a book, but it is certainly a sine qua non. A scholarly work such as Professor Springer\u27s is a means of communicating ideas; the sharper its focus the clearer the message of its author and the better it and he communicates. When reading this book I wondered about its focus: was there a central unified objective? Having now completed the book, I can see that the author has painted us a useful, but blurred picture. He has not quite brought into focus his objective; much valuable information and many good ideas are obscured by the lack of a clear thesis. The book is not a repository or summing up of law; it does not provide reform or future-oriented suggestions; it does not argue for a particular point. What it does do is provide much interesting description on the theme of international pollution. But this is not the focus suggested by the author himself

The Mi\u27kmaq and the Fishery: Beyond Food Requirements

The Mi\u27kmaq, the traditional Aboriginal nation in Nova Scotia, are struggling to find their place in the modern fishery. Significant milestones have been achieved, including the Denny, Paul and Sylliboy (N.S.C.A.) case establishing the right of the Mi\u27kmaq to harvest fish for food and the Simon (S.C.C.) case affirming the continuing validityof the Mi\u27kmaq Treatyof 1752, a treaty that contains an express right to sell fish. Though fishing by the Mi\u27kmaq for food no longer appears to be a subject of controversy (assuming the needs of conservation have been met), the spectre of commercial aspects to the Mi\u27kmaq fishery is meeting resistance. This paperexplains the background to these developments andcomments on the future role of the Mi\u27kmaq in the commercial fishery. The author argues that the present collapse in the fishery was not the fault of the Mi\u27kmaq and the Mi\u27kmaq should be accorded a priority in future harvesting. Further, Mi\u27kmaq participation and resource management raise issues of self-government that must resolved through Mi\u27kmaq governmental mechanisms

Reflections on a research initiative aimed at enhancing the role of African languages in education in South Africa

In the South African educational domain, there are an increasing number of initiatives which attempt to address the inequities in the system by providing support in an African language at various levels. Many of these initiatives use translation of texts in various subject areas as a major method of support which necessarily involves terminology development. This article puts forward the argument that although linguistic andconceptual development are inextricably linked, provision of translations, terms and word lists may not be sufficient to encourage ‘deep’ learning of the key concepts in the disciplinary content areas. The challenges arising out of the present educational context in South Africa require a more holistic approach, including language provision and management, professional translation and back translation, more inclusive methodsof terminology development with richer contextualization and the enrichment of teachers’ pedagogic content knowledge. The argument arises out of a re-examination of the findings from research into the development of two multilingual resource books for use by teachers of mathematics and science at secondary school level. These resources were developed in order to facilitate understanding of key concepts in themathematics and science disciplines and will undergo a re-appraisal of the extent of their effectiveness in meeting these aims

Building a knowledge base for language teaching through translanguaging

The aim of the research reported on in this article was to explore the effects on student learning and performance of the use of two languages of instruction, viz. isiZulu and English, in a course on the teaching of isiZulu as an additional language at school level. The course was for third year BA students considering a language teaching career. The content of the course came from the Applied Linguistics field and had not been translated from English into isiZulu. In addition, the discipline content was taught by a non-isiZulu speaking applied linguistics lecturer who had recently joined a three-year major course in isiZulu but was not fluent. The course was team taught by the Applied Linguist and an isiZulu lecturer who made the content accessible to the students through translation of difficult terms and concepts into isiZulu. Students were free to use either language. The research questions focused on how the two languages interacted naturally within a translanguaging framework in order to scaffold learning, and whether and how the use of isiZulu would facilitate understanding of key disciplinary concepts when the terminology had not yet been developed. Class sessions were recorded and transcribed with informed consent. Instances of translanguaging were analyzed in terms of the functions they were fulfilling within a broad discourse analysis framework. Findings revealed that what began as planned and systematic code-switching became, over time, translanguaging. Students appreciated the affordance for meaningful engagement with the subject content as they found it easier to challenge the lecturers and to present their own points of view in isiZulu. The experience also created rich affordances for building an academic discourse in isiZulu. Finally, teaching on the course created learning experiences for the lecturers who increased their knowledge of the languages concerned and the subject content respectively.Keywords: applied linguistics; codeswitching; isiZulu; language learning; languages of learning and teaching (LoLTs); language scaffolding; tertiary level; translanguagin

The development of a sustainability model for the integration and use of an African language as a language of learning and teaching in higher education. Alternation

Abstract This paper discusses the organic development of a Sustainability Model for the implementation of an African language, viz