Effect of the toxic milk mutation (tx) on the function and intracellular localization of Wnd, the murine homologue of the Wilson copperATPase

Wilson disease is an autosomal recessive copper transport disorder resulting from defective biliary excretion of copper and subsequent hepatic copper accumulation and liver failure if not treated. The disease is caused by mutations in the ATP7B (WND) gene, which is expressed predominantly in the liver and encodes a copper-transporting P-type ATPase that is structurally and functionally similar to the Menkes protein (MNK), which is defective in the X-linked copper transport disorder Menkes disease. The toxic milk (tx) mouse has a clinical phenotype similar to Wilson disease patients and, recently, the tx mutation within the murine WND homologue (Wnd) of this mouse was identified, establishing it as an animal model for Wilson disease. In this study, cDNA constructs encoding the wild-type (Wnd-wt) and mutant (Wnd-tx) Wilson proteins (Wnd) were generated and expressed in Chinese hamster ovary (CHO) cells. The fx mutation disrupted the copper-induced relocalization of Wnd in CHO cells and abrogated Wnd-mediated copper resistance of transfected CHO cells. In addition, co-localization experiments demonstrated that while Wnd and MNK are located in the trans-Golgi network in basal copper conditions, with elevated copper, these proteins are sorted to different destinations within the same cell, Ultrastructural studies showed that with elevated copper levels, Wnd accumulated in large multivesicular structures resembling late endosomes that may represent a novel compartment for copper transport. The data presented provide further support for a relationship between copper transport activity and the copper-induced relocalization response of mammalian copper ATPases, and an explanation at a molecular level for the observed phenotype of fx mice.

For Your Freedom and Ours: The Polish Question in Wilson's Peace Initiatives, 1916 - 1917

The first eighteen months of the Great War witnessed an unprecedented awakening of interest in the Polish Question, when worldwide attention was drawn to the prolonged devastation of the Polish territories. Thereafter, a steady increase in media comment and criticism, highlighting Poland's plight, fostered public indignation at the continual stalling of humanitarian relief efforts for Polish refugees. Such burgeoning popular sentiment focused wider political attention upon a growing movement for recognition of Polish claims to independence. This particularly proved to be the case for Woodrow Wilson and his administration's budding interest in Poland. Subsequently, nowhere did the Polish Question assume a greater role in diplomatic efforts to mediate for peace than in America, and at no time more than during the year preceding the President's hesitant decision to intervene in hostilities.

Edward Said Um Intelectual Crítico e Cosmopolita

Edward Said, palestiniano cidadão do mundo, historiador crítico da literatura e da cultura preocupa-se em analisar e desmistificar as representações ideológicas que afirmam a superioridade de uma cultura sobre as outras. Em Orientalismo , publicado originalmente em 1978, demonstra como o colonialismo europeu constrói uma representação do mundo oriental, especialmente do mundo árabe e muçulmano, em que os representados surgem como seres incapazes de autonomia, racionalidade e autogoverno. Como contraponto a esta concepção, desenvolve-se, no período da emancipação e das independências coloniais, uma nova visão em que os povos colonizados de mero objecto de representação se transformam em sujeitos da sua própria história. Em Cultura e Imperialismo , publicado em 1993, Said analisa como os intelectuais e os criadores dos povos dominados elaboram uma nova representação de si próprios e do Outro no âmbito do processo de luta e emancipação colonial. Mas apenas a livre interacção e interdependência das culturas poderá constituir uma síntese superadora do imperialismo e do nacionalismo anticolonial. Dimensão libertadora que se tornará a verdadeira missão e vocação do intelectual sem fronteiras de que Said foi um dos maiores expoentes contemporâneos.

Genealogia de uma operação historiográfica: Edward Palmer Thompson, Michel Foucault e os historiadores brasileiros da década de 1980

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Construção e desconstrução de identidades em a Caverna de José Saramago e Who's afraid of Virginia Woolf ? de Edward Albee

Dissertação apresentada para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Línguas, Literaturas e Culturas, Estudos Ingleses e Norte-Americanos

Edward Tylor e a extraordinária evolução religiosa da humanidade

Cadernos de Campo. Revista dos alunos de pós-graduação em Antropologia Social da USP, ano 19, Jan.-Dez. 2010, pág. 297-308.

Zinc Therapy of Neurological Wilson's Disease in a Woman with Two Foetus with Agenesis of the Corpus Callosum

8A>C>86A G:EDGI: A patient diagnosed Wilson’s disease (WD) 22 years previously, successfully treated initially with zinc, developed neuropsychiatric disease after years of irregular therapy. Reassuming zinc therapy was successful. After a normal pregnancy, she had two therapeutic abortions for corpus callosum agenesis, and a missed abortion. We review the genetics, physiopathology, clinics and imagiologic response to zinc therapy, the problems of pregnancy in WD, advising to maintain therapy. A hypothetic cause for fetus brain anomaly would be hypocupremia due to zinc therapy, confronting with two other possibilities, one related to Wilson’s disease in itself, other due to a congenital syndrome of agenesis of the corpus callosum, impossible to diagnose by our available diagnostic methods.