Recognition of Membrane-Bound Fusion-Peptide/MPER Complexes by the HIV-1 Neutralizing 2F5 Antibody : Implications for Anti-2F5 Immunogenicity

13 p.

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.

Magnetization reversal and exchange bias effects in hard/soft ferromagnetic bilayers with orthogonal anisotropies

21 p.

Double proximity effect in lateral S-NF-S junctions

We investigate planar Josephson junctions where the intermediate spacer between the two superconductors is an hybrid structure made by a normal metal and a ferromagnet. The different behaviors of the S-N-S junctions with thicknesses of 50 nm in both Cu and Nb layers, and S-N/F-S junctions with 10 nm of Co, 50 nm of Cu and 50 nm of Nb are studied. In this way, we analyze the influence of the ferromagnetic exchange interaction on the proximity effect. A dramatic supression of the josephson critical current of the Nb-(Cu/Co)-Nb junctions is observed. We believe that the reason for this is due to the length scale of the superconducting correlations of the electrons and holes of the weak link is larger than the thickness of Cu/Co bilayer.