Adenylate Cyclase Toxin Promotes Internalisation of Integrins and Raft Components and Decreases Macrophage Adhesion Capacity

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Ca2+ Influx and Tyrosine Kinases Trigger Bordetella Adenylate Cyclase Toxin (ACT) Endocytosis. Cell Physiology and Expression of the CD11b/CD18 Integrin Major Determinants of the Entry Route

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.

Crystal structure and characterization of a new μ-oxo bridged iron porphyrin

Comunicacion a congreso: Póster presentado en VIII Reunión Científica de Bioinorgánica – Bioburgos 2013 (Burgos, 7 al 10 de julio de 2013)

The activity view of inner speech

We distinguish two general approaches to inner speech (IS) the "format" and the "activity" views and defend the activity view. The format view grounds the utility of IS on features of the representational format of language, and is related to the thesis that the proper function of IS is to make conscious thinking possible. IS appears typically as a product constituted by representations of phonological features. The view also has implications for the idea that passivity phenomena in cognition may be misat-tributed IS. The activity view sees IS as a speaking activity that does not have a proper function in cognition. It simply inherits the array of functions of outer speech. We argue that it is methodologically advisable to start from this variety of uses, which suggests commonalities between internal and external activities. The format view has several problems; it has to deny "unsymbolized thinking"; it cannot easily explain how IS makes thoughts available to consciousness, and it cannot explain those uses of IS where its format features apparently play no role. The activity view not only lacks these problems but also has explanatory advantages: construing IS as an activity allows it to be integrally constituted by its content; the view is able to construe unsymbolized thinking as part of a continuum of phenomena that exploit the same mechanisms, and it offers a simple explanation for the variety of uses of IS

Hartle's model within the general theory of perturbatiye matchings: the change in mass

Hartle's model provides the most widely used analytic framework to describe isolated compact bodies rotating slowly in equilibrium up to second order in perturbations in the context of General Relativity. Apart from some explicit assumptions, there are some implicit, like the "continuity" of the functions in the perturbed metric across the surface of the body. In this work we sketch the basics for the analysis of the second order problem using the modern theory of perturbed matchings. In particular, the result we present is that when the energy density of the fluid in the static configuration does not vanish at the boundary, one of the functions of the second order perturbation in the setting of the original work by Hartle is not continuous. This discrepancy affects the calculation of the change in mass of the rotating star with respect to the static configuration needed to keep the central energy density unchanged.