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The hypothesis that nitric oxide (NO) is a mediator of neurotoxicity in the rat hippocampus has been strengthened by the finding that [35S]NO administered to hippocampal slices generates S-nitrosylated proteins. Those proteins include three major proteins of 66, 30, and 12 kDa. The [35S]NO-labeled proteins can be immunoprecipitated with antibodies to the protein of 12 kDa. Treatment of slices with the NO donor S-nitroso-N-acetylpenicillamine also generates the 12 kDa protein, as does exposure to NO that is produced in vitro by the activation of the calmodulin-dependent enzyme, NO synthase. The 12 kDa protein is overproduced when animals are treated with a NO donor or NO synthase is activated by calmodulin in transfected cells. The hypothesis is tested in this proposal in which we will: 1) determine whether administration of the NO synthase inhibitor, L-Arginine (Arg) or other NO synthase inhibitors block or reduce NO-mediated hippocampal damage produced by LPS or by the NO donor S-nitroso-N-acetylpenicillamine. 2) clarify whether the 12 kDa protein is specific for NO-mediated neurotoxicity and whether NO-mediated neurotoxicity can be prevented by pretreatment with Arg or NO synthase inhibitors. 3) determine whether suppression of the overproduced 12 kDa protein can be obtained by transfecting cells with an antisense cDNA to the 12 kDa protein, by transfecting cells with a sense cDNA to the 12 kDa protein, or by treating animals with the protein synthesis inhibitor, cycloheximide. 4) determine whether other NO donor compounds, such as mononitroso derivatives of prostaglandins and of catecholamines, also produce S-nitrosylated proteins in rat hippocampal slices. 5) confirm the pharmacological specificity of the NO synthase by obtaining immunoprecipitated NO-modified proteins with antibodies to the NO synthase from treated rats. 6) determine whether hippocampal neurons obtained from rats that have been exposed to amyloid and similar compounds produce NO-modified proteins. These studies will also assess the hypothesis that NO is more toxic than the other reactive nitrogen species, peroxynitrite (ONOO-), because NO will be produced without the other reactive species also present. The hypothesis is also tested that the 12 kDa protein does



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The Bishops’ Conference of England and Wales is delighted to be distributing a letter to all Catholic schools in England and Wales clarifying the Church’s position on sexuality and same-sex relationships. The letter, which will be delivered to all schools with Catholic principals and headteachers, sets out the teaching on sexuality and human sexuality, marriage and family life, as well as the dignity of human life. One of the letter’s key points is that schools do not need to have a policy in place on human sexuality. Catholic schools do not need to recognise same-sex marriage or other sexual relationships, or ordain or condone priests or teachers in sexual situations, unless they are married to each other or in a permanent relationship of commitment to each other. “Parents know what they have been told and they are using their own discernment,” said Bishop Richard Chartres, Chairman of the Bishops’ Conference. “We do not believe we should introduce sexuality into the education of children, nor should we impose our views on children on the basis of a ‘one size fits all’ approach. Catholic schools aim to prepare their pupils for adult life and their pupils will have a very different approach to families in their own lives to Catholic families. “We support the kind of relationship that produces a lifelong marriage, but we do not accept the notion of a ‘gay marriage’ when a man wants to marry another man, or that a couple should be able to contract a civil partnership.” Bishop Chartres said, “We in the Bishops’ Conference have deep concerns that the teaching of human sexuality in many schools is becoming in danger of becoming a hard and fast rule rather than a way of life. We welcome the schools that are teaching the subject well, but make sure that schools where teachers work from a narrow biblical perspective are not operating as a kind of ‘branch line’ from Rome.” The letter, in full, will be distributed to each Catholic school in England and Wales: Dear Principal or Headteacher, Some teachers and governors at Catholic schools in England and Wales teach on human sexuality, marriage and family life. Please find enclosed copies of the teaching documents produced by the Catholic Education Service, which are intended for the use of such teachers and governors. These documents, which I hope you will find helpful, show that Catholic schools do not need to



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Minimum: OS: Windows XP/Vista/7 (32-bit & 64-bit) Processor: 1.8 GHz dual-core or higher Memory: 2 GB RAM Graphics: DX9 or higher DirectX: Version 9.0c Hard Drive: 5 GB available space



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