Clostridium perfringensepsilon toxin H149A mutant as a platform for receptor binding studies

Clostridium perfringens epsilon toxin (Etx) is a pore-forming toxin responsible for a severe and rapidly fatal enterotoxemia of ruminants. The toxin is classified as a category B bioterrorism agent by the U.S. Government Centres for Disease Control and Prevention (CDC), making work with recombinant toxin difficult. To reduce the hazard posed by work with recombinant Etx, we have used a variant of Etx that contains a H149A mutation (Etx-H149A), previously reported to have reduced, but not abolished, toxicity. The three-dimensional structure of H149A prototoxin shows that the H149A mutation in domain III does not affect organisation of the putative receptor binding loops in domain I of the toxin. Surface exposed tyrosine residues in domain I of Etx-H149A (Y16, Y20, Y29, Y30, Y36 and Y196) were mutated to alanine and mutants Y30A and Y196A showed significantly reduced binding to MDCK.2 cells relative to Etx-H149A that correlated with their reduced cytotoxic activity. Thus, our study confirms the role of surface exposed tyrosine residues in domain I of Etx in binding to MDCK cells and the suitability of Etx-H149A for further receptor binding studies. In contrast, binding of all of the tyrosine mutants to ACHN cells was similar to that of Etx-H149A, suggesting that Etx can recognise different cell surface receptors. In support of this, the crystal structure of Etx-H149A identified a glycan (β-octyl-glucoside) binding site in domain III of Etx-H149A, which may be a second receptor binding site. These findings have important implications for developing strategies designed to neutralise toxin activity

Intractable policy failure: the case of bovine TB and badgers

The failure to eliminate bovine TB from the English and Welsh cattle herd represents a long-term intractable policy failure. Cattle-to-cattle transmission of the disease has been underemphasised in the debate compared with transmission from badgers despite a contested evidence base. Archival evidence shows that mythical constructions of the badger have shaped the policy debate. Relevant evidence was incomplete and contested; alternative framings of the policy problem were polarised and difficult to reconcile; and this rendered normal techniques of stakeholder management through co-option and mediation of little assistance

Mechanism of 2003, 2007 and 2009 earthquakes (S. Vicente Cape) and implications for the 1755 Lisbon earthquake

The San Vicente Cape region (SW Iberia) is of great seismological interest due to its tectonic complexity and for the occurrence of the 1755 Lisbon mega-earthquake. A structure capable of generating such large earthquake has not been convincingly found but authors agree with the possible occurrence in the future of a similar earthquake offshore of San Vicente Cape.We have studied the mechanism of three earthquakes in this area: 29 July 2003 (Mw = 5.3), 12 February 2007 (Mw = 6.1) and 17 December 2009 (Mw = 5.5) which throw light on the dynamics of the region. These earthquakes are the largest occurred in the last 40 years at the western of San Vicente Cape. From inversion of body waves and kinematic slip distribution, we have obtained that the three shocks have similar characteristics (dimensions, maximum slip, stress drop, source time function, focal depth and rupture velocity), but we can observe differences on geometry of the rupture that reflect the great seismotectonics complexity of the zone. The 2003 and 2007 focal mechanisms are similar, corresponding to thrusting motion but the 2009 earthquake has dip-slip motion on a vertical plane. The ruptures planes for the three shocks, deduced from the slip distribution, show ruptures on NE-SW planes, with the released energy propagating to NE direction, compatible with the regional horizontal compression in the NW-SE direction produced by the convergence between the Eurasian and African plates. This direction of faulting may be applied to the generation of the 1755 Lisbon earthquake, in terms of a complex rupture along NE-SW trending thrust faults at the Gorringe Bank, the Horseshoe Scarp and the Marques de Pombal Fault, with rupture propagating in NE direction toward the coast of Portugal and which may explain the large damage at Lisbon city

Seismic source in the Iberian-African plate boundary

The plate boundary between Iberia and Africa has been studied using data on seismicity and focal mechanisms. The region has been divided into three areas: A; the Gulf of Cadiz; B, the Betics, Alboran Sea and northern Morocco; and C, Algeria. Seismicity shows a complex behavior, large shallow earthquakes (h < 30 km) occur in areas A and C and moderate shocks in area B; intermediate-depth activity (30 < h < 150 km) is located in the depth earthquakes (h » 650 km) are located to the south of Granada. Moment rate, slip velocity and b values have been estimated for shallow shocks, and show similar characteristics for the Gulf of Cadiz and Algeria, and quite different ones for the central region. Focal mechanisms of 80 selected shallow earthquakes (8 ‡ mb ‡ 4) show thrust faulting in the Gulf of Cadiz and Algeria with horizontal NNW-SSE compression, and normal faulting in the Alboran Sea with E-W extension. Focal mechanisms of 26 intermediate-depth earthquakes in the Alboran Sea display vertical motions, with a predominant plane trending E-W. Solutions for very deep shocks correspond to vertical dip-slip along N-S trends. Frohlich diagrams and seismic moment tensors show different behavior in the Gulf of Cadiz, Betic-Alboran Sea and northern Morocco, and northern Algeria for shallow events. The stress pattern of intermediate-depth and very deep earthquakes has different directions: vertical extension in the NW-SE direction for intermediate depth earthquakes, and tension and pressure axes dipping about 45 ° for very deep earthquakes. Regional stress pattern may result from the collision between the African plate and Iberia, with extension and subduction of lithospheric material in the Alboran Sea at intermediate depth. The very deep seismicity may be correlated with older subduction processes

What are we teaching with textbooks? Electricity and electronics on technology 3º ESO

Este trabajo trata de dar respuestas al interrogante: ¿Qué estamos enseñando con los libros de texto en Educación Secundaria Obligatoria? En primer lugar, revisamos los trabajos realizados sobre estos materiales en España y, a pesar de la importancia que tienen en nuestro sistema educativo, no hemos encontrado muchos que se hayan ocupado de aquellos que se elaboraron durante la Reforma LOE. Nos centramos en algunos elementos que consideramos fundamentales en estos recursos didácticos: la estructura de las lecciones y los tipos de contenidos (conceptos, procedimientos y actitudes) a través del análisis de las actividades de aprendizaje planteadas por seis libros de texto de editoriales conocidas, relativas al bloque “Electricidad y electrónica” de Tecnología de 3º ESO, y su adecuación o no a la normativa vigente en la CARM. Los resultados muestran algunas de las carencias y deficiencias existentes, y que los libros de texto, en general, no se acomodan a lo que marca el currículum oficial