6 resultados para Underlying determinants

em Archivo Digital para la Docencia y la Investigación - Repositorio Institucional de la Universidad del País Vasco


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Humans infected with Bordetella pertussis, the whooping cough bacterium, show evidences of impaired host defenses. This pathogenic bacterium produces a unique adenylate cyclase toxin (ACT) which enters human phagocytes and catalyzes the unregulated formation of cAMP, hampering important bactericidal functions of these immune cells that eventually cause cell death by apoptosis and/or necrosis. Additionally, ACT permeabilizes cells through pore formation in the target cell membrane. Recently, we demonstrated that ACT is internalised into macrophages together with other membrane components, such as the integrin CD11b/CD18 (CR3), its receptor in these immune cells, and GM1. The goal of this study was to determine whether ACT uptake is restricted to receptor-bearing macrophages or on the contrary may also take place into cells devoid of receptor and gain more insights on the signalling involved. Here, we show that ACT is rapidly eliminated from the cell membrane of either CR3-positive as negative cells, though through different entry routes, which depends in part, on the target cell physiology and characteristics. ACT-induced Ca2+ influx and activation of non-receptor Tyr kinases into the target cell appear to be common master denominators in the different endocytic strategies activated by this toxin. Very importantly, we show that, upon incubation with ACT, target cells are capable of repairing the cell membrane, which suggests the mounting of an anti-toxin cell repair-response, very likely involving the toxin elimination from the cell surface.

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222 p. : il.

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31 p.

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In the middle of the so-called pension crisis, the ageing of population and the sharp decrease in affiliations to Social Security are threatening the well-functioning of the Spanish public pension system. The purpose of this paper is to present the main challenges to be faced by the Spanish pension system, as well as to shed light on the main determinants that will condition the evolution of pension expenditure over GDP along the following decades. This quantitative analysis, which considers the 2011 and 2013 pension reforms, uses the latest data on the Spanish demographic, labor market and institutional factors in order to project the evolution of the system from the expenditure side up to 2060. For the purpose of analyzing the dynamics and the underlying drivers of pension expenditure, the so-called aggregate accounting approach will be utilized. The alternative scenarios proposed allow for exploring the robustness of the results within the baseline scenario, which constitutes the reference point of projections in the exercise. The analysis concludes that, by the end of the projected period, Spain will count on a similar public pension expenditure ratio as the current one.