Categorias objetais : localização ôntica do objeto jurídico / José Wilson Ferreira Sobrinho. --

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Functional expression of the Wilson disease protein reveals mislocalization and impaired copper-dependent trafficking of the common H1069Q mutation

Wilson disease is an autosomal recessive disorder of hepatic copper metabolism caused by mutations in a gene encoding a copper-transporting P-type ATPase. To elucidate the function of the Wilson protein, wild-type and mutant Wilson cDNAs were expressed in a Menkes copper transporter-deficient mottled fibroblast cell line defective in copper export. Expression of the wild-type cDNA demonstrated trans-Golgi network localization and copper-dependent trafficking of the Wilson protein identical to previous observations for the endogenously expressed protein in hepatocytes. Furthermore, expression of the Wilson cDNA rescued the mottled phenotype as evidenced by a reduction in copper accumulation and restoration of cell viability. In contrast, expression of an H1069Q mutant Wilson cDNA did not rescue the mottled phenotype, and immunofluorescence studies showed that this mutant Wilson protein was localized in the endoplasmic reticulum. Consistent with these findings, pulse–chase analysis demonstrated a 5-fold decrease in the half-life of the H1069Q mutant as compared with the wild-type protein. Maintenance of these transfected cell lines at 28°C resulted in localization of the H1069Q protein in the trans-Golgi network, suggesting that a temperature-sensitive defect in protein folding followed by degradation constitutes the molecular basis of Wilson disease in patients harboring the H1069Q mutation. Taken together, these studies describe a tractable expression system for elucidating the function and localization of the copper-transporting ATPases in mammalian cells and provide compelling evidence that the Wilson protein can functionally substitute for the Menkes protein, supporting the concept that these proteins use common biochemical mechanisms to effect cellular copper homeostasis.

The Menkes/Wilson disease gene homologue in yeast provides copper to a ceruloplasmin-like oxidase required for iron uptake.

The CCC2 gene of the yeast Saccharomyces cerevisiae is homologous to the human genes defective in Wilson disease and Menkes disease. A biochemical hallmark of these diseases is a deficiency of copper in ceruloplasmin and other copper proteins found in extracytosolic compartments. Here we demonstrate that disruption of the yeast CCC2 gene results in defects in respiration and iron uptake. These defects could be reversed by supplementing cells with copper, suggesting that CCC2 mutant cells were copper deficient. However, cytosolic copper levels and copper uptake were normal. Instead, CCC2 mutant cells lacked a copper-dependent oxidase activity associated with the extracytosolic domain of the FET3-encoded protein, a ceruloplasmin homologue previously shown to be necessary for high-affinity iron uptake in yeast. Copper restored oxidase activity both in vitro and in vivo, paralleling the ability of copper to restore respiration and iron uptake. These results suggest that the CCC2-encoded protein is required for the export of copper from the cytosol into an extracytosolic compartment, supporting the proposal that intracellular copper transport is impaired in Wilson disease and Menkes disease.

El reto y la oportunidad de acabar con el hambre: reflexiones desde la obra de José María Bengoa Lecanda (1913-2010)

El trabajo aborda, a través de la obra de José María Bengoa Lecanda (1913-2010), la condición de intolerable social que alcanzó, a lo largo del siglo XX, el problema del hambre y la desnutrición. Así mismo, intenta mostrar la oportunidad que comportaba dicho reto, si como parecía razonable, se trataba de corregir los factores condicionantes que estaban detrás del hambre y la desnutrición, en particular la pobreza y la falta de equidad.

La dimensión sociosanitaria del hambre: el testimonio de José María Bengoa Lecanda (1913-2010)

Se analizan algunos de los elementos conceptuales con los que abordó el profesor José María Bengoa Lecanda (1913-2010) la complejidad de factores que están asociados al hambre. Se estudian sus reflexiones sobre la interrelación entre desnutrición, enfermedad y pobreza, así como sus propuestas para romper dicho círculo. Desde los presupuestos de la medicina social, el doctor Bengoa articuló un discurso donde las desigualdades sociales aparecen como uno de los determinantes clave que explican las diferencias socio-sanitarias entre regiones, poblaciones e individuos. El cambio social, con la educación como principal argumento, y la mejora de las condiciones de vida de la población, eran reivindicadas por el doctor Bengoa como las estrategias más adecuadas para abordar la malnutrición en cualquiera de sus manifestaciones.

The International Competitiveness of the Biscayan Iron and Steel Industry (1880-1913)

This study has a double objective: to provide foreign colleagues with an insight into the controversy surrounding the international competitiveness of pig iron produced in Bilbao and also to present previously unpublished documentation regarding the European iron industry, which I have retrieved from the historical archive of Credit Lyonnais of Paris. This information includes the costs of Biscayan, French, British, German and Belgium pig iron broken down into five components (iron ore, coke, flux, labour and other costs), which is useful in determining the reasons why the pig iron from Bilbao became less competitive. The article is made up of three parts. Firstly, I will synthesise the controversy surrounding the competitiveness of the Basque iron and steel industry. Then I will present the itemised costs which provide information to illustrate how Biscayan pig iron was not competitive because it was produced with English coal which was more expensive than that consumed by the European factories located "on top of" or near coal seams. The article will finish with a section that, by way of conclusion, explains the comparative advantage and disadvantage of Bilbao, applying the first model of Alfred Weber's Theory of Industrial Location to three technological advances, occurring between the 1860s and 1913 (malleable iron, Bessemer steel and Thomas steel).

Fauna hawaiiensis; being the land-fauna of the Hawaiian islands. by various authors, 1899-1913.

v. 2

Insecta Saundersiana : or, Charcters of undescribed insects in the collection of William Wilson Saunders.

v.4 (1858) [Homoptera]