ATP Antagonizes Thrombin-Induced Signal Transduction through 12(S)-HETE and cAMP

15 p.

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

10 p.

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.

Calpain-Mediated Processing of Adenylate Cyclase Toxin Generates a Cytosolic Soluble Catalytically Active N-Terminal Domain

Bordetella pertussis, the whooping cough pathogen, secretes several virulence factors among which adenylate cyclase toxin (ACT) is essential for establishment of the disease in the respiratory tract. ACT weakens host defenses by suppressing important bactericidal activities of the phagocytic cells. Up to now, it was believed that cell intoxication by ACT was a consequence of the accumulation of abnormally high levels of cAMP, generated exclusively beneath the host plasma membrane by the toxin N-terminal catalytic adenylate cyclase (AC) domain, upon its direct translocation across the lipid bilayer. Here we show that host calpain, a calcium-dependent Cys-protease, is activated into the phagocytes by a toxin-triggered calcium rise, resulting in the proteolytic cleavage of the toxin N-terminal domain that releases a catalytically active "soluble AC''. The calpain-mediated ACT processing allows trafficking of the "soluble AC'' domain into subcellular organella. At least two strategic advantages arise from this singular toxin cleavage, enhancing the specificity of action, and simultaneously preventing an indiscriminate activation of cAMP effectors throughout the cell. The present study provides novel insights into the toxin mechanism of action, as the calpain-mediated toxin processing would confer ACT the capacity for a space- and time-coordinated production of different cAMP "pools'', which would play different roles in the cell pathophysiology.

Raumfigurationen und Macht in Atemschaukel

[EN] Atemschaukel approaches the falling apart and survival in a historically loaded space, such as a labour camp. This novel offers a relevant research field for the space analysis, focused from the perspective of the Spatial Turn, as not only this theoretical frame but also Herta Müller herself conceive of space as a process, unterstood as a reciprocal interaction with the social practice, thus as a spatial and social construct. The representation of space in Atemschaukel is described in this article as a “swinging movement between boxes and abyss”, where the discourse of Leopold Auberg’s memories oscillates between closed and square spaces, on one hand, and open and giddy spaces, on the other hand. In this oscillating movement it is the open spaces that will most clearly show the process of inner destruction of the subject in such oppressive situations as on labour camps, as well as the permanent damages of deportation.

Hezkuntza emozionalaren munduan murgiltzen, irakasleen tentsioak ikertuz

LABURPENA:Ikerkuntza hau Lehen Hezkuntzako irakasleen konpetentzia emozionalen esparruan kokatzen da. Helburua, irakasleen tentsioa eragiten duten egoerek eta horien aurrean euren erantzunak ezagutzea da. Metodologia kualitatiboa erabili da. Informazioaren bilketarako, irakasleek buruturiko landa oharrak erabili dira. Lorturiko emaitzen artean, autoritatearen galeraren sentsazioak sortzen dituen tentsio eta egonezin egoerak azpimarra daitezke.

Introducción a la Espintrónica

Hoy en día, el campo científico-tecnológico denomin ado espintrónica es cada vez más extenso y aunque haya varias definiciones, la más c ercana a lo que se trata en este trabajo es la que sigue: Denominamos espintrónica a un camp o de la física que explota el grado de libertad adicional que es el espín para guardar, co dificar, acceder, procesar y/o transmitir información de alguna manera. [1] El objetivo de este trabajo es hacer una introducci ón al campo de la espintrónica, exponiendo algunos conceptos básicos y describiendo algunos dispositivos que se usan en la espintrónica. El trabajo se dividirá en dos partes, la primera, a modo de resumen bibliográfico, recoge algunos efectos espintrónicos y dispositivos interesantes basados en los mismos. Para la segunda parte se ha hecho un trabaj o práctico mostrando el modo funcionamiento de uno de estos tipos de dispositivo s en particular, utilizando una simulación por computador

Carta enviada por Juan Bueso Roda a Justo Garate en 1939

1 carta (manuscrita) ; 225x330 mm