The α5 subunit regulates the expression and function of α4*-containing neuronal nicotinic acetylcholine receptors in the ventral-tegmental area

Human genetic association studies have shown gene variants in the α5 subunit of the neuronal nicotinic receptor (nAChR) influence both ethanol and nicotine dependence. The α5 subunit is an accessory subunit that facilitates α4* nAChRs assembly in vitro. However, it is unknown whether this occurs in the brain, as there are few research tools to adequately address this question. As the α4*-containing nAChRs are highly expressed in the ventral tegmental area (VTA) we assessed the molecular, functional and pharmacological roles of α5 in α4*-containing nAChRs in the VTA. We utilized transgenic mice α5+/+(α4YFP) and α5-/-(α4YFP) that allow the direct visualization and measurement of α4-YFP expression and the effect of the presence (α5+/+) and absence of α5 (-/-) subunit, as the antibodies for detecting the α4* subunits of the nAChR are not specific. We performed voltage clamp electrophysiological experiments to study baseline nicotinic currents in VTA dopaminergic neurons. We show that in the presence of the α5 subunit, the overall expression of α4 subunit is increased significantly by 60% in the VTA. Furthermore, the α5 subunit strengthens baseline nAChR currents, suggesting the increased expression of α4* nAChRs to be likely on the cell surface. While the presence of the α5 subunit blunts the desensitization of nAChRs following nicotine exposure, it does not alter the amount of ethanol potentiation of VTA dopaminergic neurons. Our data demonstrates a major regulatory role for the α5 subunit in both the maintenance of α4*-containing nAChRs expression and in modulating nicotinic currents in VTA dopaminergic neurons. Additionally, the α5α4* nAChR in VTA dopaminergic neurons regulates the effect of nicotine but not ethanol on currents. Together, the data suggest that the α5 subunit is critical for controlling the expression and functional role of a population of α4*-containing nAChRs in the VTA.

semantic oriented ontology cohesion metrics for ontology-based systems

Ontologies play a core role to provide shared knowledge models to semantic-driven applications targeted by Semantic Web. Ontology metrics become an important area because they can help ontology engineers to assess ontology and better control project management and development of ontology based systems, and therefore reduce the risk of project failures. In this paper, we propose a set of ontology cohesion metrics which focuses on measuring (possibly inconsistent) ontologies in the context of dynamic and changing Web. They are: Number of Ontology Partitions (NOP), Number of Minimally Inconsistent Subsets (NMIS) and Average Value of Axiom Inconsistencies (AVAI). These ontology metrics are used to measure ontological semantics rather than ontological structure. They are theoretically validated for ensuring their theoretical soundness, and further empirically validated by a standard test set of debugging ontologies. The related algorithms to compute these ontology metrics also are discussed. These metrics proposed in this paper can be used as a very useful complementarity of existing ontology cohesion metrics.

Philippe II et don Carlos, devant l'histoire

UANL

(Ego)centrismo docente y enseñanza inmadura.

Resumen tomado del autor

Synchronization of two independently moving cameras without feature correspondences

In this work, a method that synchronizes two video sequences is proposed. Unlike previous methods, which require the existence of correspondences between features tracked in the two sequences, and/or that the cameras are static or jointly moving, the proposed approach does not impose any of these constraints. It works when the cameras move independently, even if different features are tracked in the two sequences. The assumptions underlying the proposed strategy are that the intrinsic parameters of the cameras are known and that two rigid objects, with independent motions on the scene, are visible in both sequences. The relative motion between these objects is used as clue for the synchronization. The extrinsic parameters of the cameras are assumed to be unknown. A new synchronization algorithm for static or jointly moving cameras that see (possibly) different parts of a common rigidly moving object is also proposed. Proof-of-concept experiments that illustrate the performance of these methods are presented, as well as a comparison with a state-of-the-art approach.

Heads buried in the sand: member states block solutions to the refugee crisis. EPC Commentary, 15 September 2015

Yesterday’s meeting of Interior Ministers demonstrated that the EU’s asylum and immigration policy remains incomplete. This is mainly due to the member states’ inability to plan ahead, their reluctance to adopt binding common rules – considered as a violation of their sovereignty – and their central position in the implementation of EU rules.