Microtubule plus-end tracking proteins:novel modulators of cardiac sodium channels and arrhythmogenesis

The cardiac sodium channel NaV1.5 is an essential modulator of cardiac excitability, with decreased NaV1.5 levels at the plasma membrane and consequent reduction in sodium current (INa) leading to potentially lethal cardiac arrhythmias. NaV1.5 is distributed in a specific pattern at the plasma membrane of cardiomyocytes, with localization at the crests, grooves, and T-tubules of the lateral membrane and particularly high levels at the intercalated disc region. NaV1.5 forms a large macromolecular complex with and is regulated by interacting proteins, some of which are specifically localized at either the lateral membrane or intercalated disc. One of the NaV1.5 trafficking routes is via microtubules (MTs), which are regulated by MT plus-end tracking proteins (+TIPs). In our search for mechanisms involved in targeted delivery of NaV1.5, we here provide an overview of previously demonstrated interactions between NaV1.5 interacting proteins and +TIPs, which potentially (in)directly impact on NaV1.5 trafficking. Strikingly, +TIPs interact extensively with several intercalated disc- and lateral membrane-specific NaV1.5 interacting proteins. Recent work indicates that this interplay of +TIPs and NaV1.5 interacting proteins mediates the targeted delivery of NaV1.5 at specific cardiomyocyte subcellular domains, while also being potentially relevant for the trafficking of other ion channels. These observations are especially relevant for diseases associated with loss of NaV1.5 specifically at the lateral membrane (such as Duchenne muscular dystrophy), or at the intercalated disc (for example, arrhythmogenic cardiomyopathy), and open up potential avenues for development of new anti-arrhythmic therapies.</p

Modified Douglas splitting methods for reaction–diffusion equations

We present modifications of the second-order Douglas stabilizing corrections method, which is a splitting method based on the implicit trapezoidal rule. Inclusion of an explicit term in a forward Euler way is straightforward, but this will lower the order of convergence. In the modifications considered here, explicit terms are included in a second-order fashion. For these modified methods, results on linear stability and convergence are derived. Stability holds for important classes of reaction–diffusion equations, and for such problems the modified Douglas methods are seen to be often more efficient than related methods from the literature

Modified Douglas Splitting Methods for Reaction-Diffusion Equations

We present modifications of the second-order Douglas stabilizing corrections method, which is a splitting method based on the implicit trapezoidal rule. Inclusion of an explicit term in a forward Euler way is straightforward, but this will lower the order of convergence. In the modifications considered here, explicit terms are included in a second-order fashion. For these modified methods, results on linear stability and convergence are derived. Stability holds for important classes of reaction-diffusion equations, and for such problems the modified Douglas methods are seen to be often more efficient than related methods from the literature

Subsistence Strategies in the Lower Magdalenian at El Cierro Cave (Ribadesella, Asturias, Spain)

[EN]El Cierro Cave (Ribadesella, Asturias, Spain) possesses one of the most complete Upper Palaeolithic stratigraphic sequences in northern Spain. Magdalenian occupations, particularly the lower Magdalenian, are well represented in its full sequence. This article presents the zooarchaeological analysis of the levels Cierro G1, Cierro G and Cierro F, dated by 14C to between 20,000 and 17,000 cal BP. The remains correspond to vertebrates (mainly large mammals and to a lesser extent fish and birds) and invertebrates (almost exclusively marine molluscs). The taphonomic analysis of the bones and shells has determined the role that the different animal resources played in the diet of the Magdalenian hunter-gatherers at El Cierro. The results obtained in each level of the sequence are compared and included in their regional context. This study also considers the way in which the Magdalenian groups at El Cierro processed the meat and fat of the different animal species and establishes the operational chain in the strategies of procurement, preparation and consumption of the pre

Estudio tecnológico sobre la prevención y mecanismos de extinción de incendios

El objetivo de dicho proyecto ha sido hacer un balance general y dar a conocer los aspectos más significativos sobre un tema que cada día está más presente en la vida cotidiana de las personas como es la prevención de incendios. El proyecto también ha tratado de englobar aspectos relacionados con el desarrollo y extinción de los incendios en diferentes ámbitos y condicione

Epifisiolisis de cabeza de radio asociadas a luxación de codo y reducción espontánea

Realizamos un estudio retrospectivo de 10 casos de la epifisiolisis de cabeza de radio ocurridas durante el periodo 1992 a 1997, con un desplazamiento mayor de 60º que según los criterios de O'Brien corresponderían a un grado III. De todas las revisadas seleccionamos 6 casos en los que había una angulación mayor de 90º, creemos ocurren después de luxación o reducción espontánea de luxación de codo; por ser las más frecuentes, las que más problemas presentan en el tratamiento y las que producen más secuelas. Nuestro objetivo es valorar los resultados obtenidos con nuestros tratamientos y realizar una revisión bibliográfica.We have done a retrospective study of ten cases of radial head epiphysiolysis occurred between 1992 and 1997, displaced more than 60º. (O'Brien's grade III). Amongst them we have selected those which were displaced more than 90º (six cases) probably occurred after an elbow luxation or after the spontaneous reduction of an elbow luxation; because the are more infrequent, more troublesome and they give more secuelae. Our aim is to evaluate the results obtained with the treatment and to review the literature