Papel biológico del diadenosin tetrafosfato en el ojo: efecto sobre la composición lacrimal e implicación en la función de barrera corneal

El Ap4A es una molécula con un amplio papel biológico en el ojo. Se ha descrito su implicación en procesos de secreción lagrimal, cicatrización epitelial, regulación de la presión intraocular, y presenta también un papel neuroprotector sobre los terminales simpáticos que inervan el cuerpo ciliar. El objetivo de este trabajo ha sido analizar la participación del Ap4A en otras posibles funciones a nivel ocular. En concreto se ha estudiado la capacidad de este dinucléotido para estimular la liberación de proteínas lagrimales de acción antibacteriana tales como la lisozima y la lactoferrina. Por otra parte se ha investigado su efecto como modulador de la función de barrera de la córnea a través de la regulación de los niveles de expresión de proteínas constituyentes de las tight junctions (TJ). Dicho efecto sobre la barrera puede tener una importante repercusión en la entrada de fármacos y en la consiguiente eficacia terapéutica de los mismos. Por último, se ha estudiado la posible implicación del dinucleótido en el proceso de edematización descrito en modelos animales glaucomatosos tales como el ratón DBA/2J. Con el objetivo de averiguar si la activación de Ap4A inducía un efecto sobre la producción de dos proteínas antimicrobianas relevantes de la lágrima (lisozima y lactoferrina) se realizaron ensayos en la lágrima de conejos albinos de Nueva Zelanda, mediante las técnicas de agar-agar y ELISA. Los resultados obtenidos demostraron que Ap4A produce un aumento en la concentración de lisozima y de lactoferrina del 93% y 24%, respectivamente, frente a valores basales, y este efecto está mediado por receptores de tipo P2...

Stenosis triggers spread of helical Pseudomonas biofilms in cylindrical flow systems

Biofilms are multicellular bacterial structures that adhere to surfaces and often endow the bacterial population with tolerance to antibiotics and other environmental insults. Biofilms frequently colonize the tubing of medical devices through mechanisms that are poorly understood. Here we studied the helicoidal spread of Pseudomonas putida biofilms through cylindrical conduits of varied diameters in slow laminar flow regimes. Numerical simulations of such flows reveal vortical motion at stenoses and junctions, which enhances bacterial adhesion and fosters formation of filamentous structures. Formation of long, downstream-flowing bacterial threads that stem from narrowings and connections was detected experimentally, as predicted by our model. Accumulation of bacterial biomass makes the resulting filaments undergo a helical instability. These incipient helices then coarsened until constrained by the tubing walls, and spread along the whole tube length without obstructing the flow. A three-dimensional discrete filament model supports this coarsening mechanism and yields simulations of helix dynamics in accordance with our experimental observations. These findings describe an unanticipated mechanism for bacterial spreading in tubing networks which might be involved in some hospital-acquired infections and bacterial contamination of catheters.

High On/Off ratio memristive switching of manganite/cuprate bilayer by interfacial magnetoelectricity

Memristive switching serves as the basis for a new generation of electronic devices. Memristors are two-terminal devices in which the current is turned on and off by redistributing point defects, e.g., vacancies, which is difficult to control. Memristors based on alternative mechanisms have been explored, but achieving both the high On/Off ratio and the low switching energy desirable for use in electronics remains a challenge. Here we report memristive switching in a La_(0.7)Ca_(0.3)MnO_(3)/PrBa_(2)Cu_(3)O_(7) bilayer with an On/Off ratio greater than 103 and demonstrate that the phenomenon originates from a new type of interfacial magnetoelectricity. Using results from firstprinciples calculations, we show that an external electric-field induces subtle displacements of the interfacial Mn ions, which switches on/off an interfacial magnetic “dead” layer, resulting in memristive behavior for spin-polarized electron transport across the bilayer. The interfacial nature of the switching entails low energy cost about of a tenth of atto Joule for write/erase a “bit”. Our results indicate new opportunities for manganite/cuprate systems and other transition-metal-oxide junctions in memristive applications.