Structural and Functional Insights into Endoglin Ligand Recognition and Binding

Endoglin, a type I membrane glycoprotein expressed as a disulfide-linked homodimer on human vascular endothelial cells, is a component of the transforming growth factor (TGF)-β receptor complex and is implicated in a dominant vascular dysplasia known as hereditary hemorrhagic telangiectasia as well as in preeclampsia. It interacts with the type I TGF-β signaling receptor activin receptor-like kinase (ALK)1 and modulates cellular responses to Bone Morphogenetic Protein (BMP)-9 and BMP-10. Structurally, besides carrying a zona pellucida (ZP) domain, endoglin contains at its N-terminal extracellular region a domain of unknown function and without homology to any other known protein, therefore called the orphan domain (OD). In this study, we have determined the recognition and binding ability of full length ALK1, endoglin and constructs encompassing the OD to BMP-9 using combined methods, consisting of surface plasmon resonance and cellular assays. ALK1 and endoglin ectodomains bind, independently of their glycosylation state and without cooperativity, to different sites of BMP-9. The OD comprising residues 22 to 337 was identified among the present constructs as the minimal active endoglin domain needed for partner recognition. These studies also pinpointed to Cys350 as being responsible for the dimerization of endoglin. In contrast to the complete endoglin ectodomain, the OD is a monomer and its small angle X-ray scattering characterization revealed a compact conformation in solution into which a de novo model was fitted

Development and Validation of an Automated High-Throughput System for Zebrafish In Vivo Screenings

The zebrafish is a vertebrate model compatible with the paradigms of drug discovery. The small size and transparency of zebrafish embryos make them amenable for the automation necessary in high-throughput screenings. We have developed an automated high-throughput platform for in vivo chemical screenings on zebrafish embryos that includes automated methods for embryo dispensation, compound delivery, incubation, imaging and analysis of the results. At present, two different assays to detect cardiotoxic compounds and angiogenesis inhibitors can be automatically run in the platform, showing the versatility of the system. A validation of these two assays with known positive and negative compounds, as well as a screening for the detection of unknown anti-angiogenic compounds, have been successfully carried out in the system developed. We present a totally automated platform that allows for high-throughput screenings in a vertebrate organism

Concentration fluctuations in nonisothermal reaction-diffusion systems

In this paper a simple reaction-diffusion system, namely a binary fluid mixture with an association-dissociation reaction between the two components, is considered. Fluctuations at hydrodynamic spatiotemporal scales when a temperature gradient is present in this chemically reacting system are studied. First, fluctuating hydrodynamics when the system is in global equilibrium (isothermal) is reviewed. Comparing the two cases, an enhancement of the intensity of concentration fluctuations in the presence of a temperature gradient is predicted. The nonequilibrium concentration fluctuations are spatially long ranged, with an intensity depending on the wave number q. The intensity exhibits a crossover from a proportional to q(-4) to a proportional to q(-2) behavior depending on whether the corresponding wavelength is smaller or larger than the penetration depth of the reacting mixture. This opens a possibility to distinguish between diffusion- or activation-controlled regimes of the reaction by measuring these fluctuations. In addition, the possible observation of these fluctuations in nonequilibrium molecular dynamics simulations is considered

Nuevas resistencias comunicativas: la rebelión de los ACARP

Introducción. El trabajo pretende ser una aportación en el debate en torno al papel que los medios de comunicación tienen en el cultivo de asunciones sobre la realidad, especialmente a raíz de la emergencia de las nuevas tecnologías de la información y la comunicación (TICs). Objetivos. Se analizarán dos formas específicas y novedosas de disputa comunicativa por parte de los movimientos sociales: los lip dub reivindicativos y las grabaciones ciudadanas de actuaciones policiales. Englobamos a ambas bajo la categoría de Artefacto Cultural Audiovisual de Reivindicación y Protesta (ACARP). Metodología. Se realiza un análisis teórico acerca de las relaciones entre poder, comunicación y resistencias, proponiendo una lectura acerca de los distintos planos en los que resistencias y disputas se articulan. Para el análisis empírico, atendemos a las reflexiones metodológicas en torno a la sociología visual, aplicándolas a seis de estos artefactos audiovisuales en el contexto vasco. Resultados y conclusiones. Los resultados proporcionan una caracterización general de estos artefactos audiovisuales. El análisis del caso vasco permite situar estas innovaciones tácticas y comunicativas, y discutir acerca de la importancia del contexto, la construcción del discurso, las posibles tendencias a la espectacularización y las posibilidades de contrarrestrar estereotipaciones