Studies of intercellular Ca2+ signaling and gap-junction coupling in the developing cochlea of mouse models affected by congenital hearing loss

Connexin 26 (Cx26) and connexin 30 (Cx30) form gap junction channels that allow the intercellular diffusion of the Ca2+ mobilizing second messenger IP3. They also form hemichannels that release ATP from the endolymphatic surface of cochlear supporting and epithelial cells. Released ATP in turn activates G-protein coupled P2Y2 and P2Y4 receptors, PLC-dependent generation of IP3, release of Ca2+ from intracellular stores, permitting the regenerative propagation of intercellular Ca2+ signals. In the course of this work, we found that cochlear non-sensory cells of the greater and lesser epithelial ridge (GER and LER, respectively) share the same PLC- and IP3R-dependent signal transduction cascade activated by ATP. In addition, we demonstrated that ATP-dependent Ca2+ signaling activity in cochlear non-sensory cells is spatially graded from the apex to the base of the cochlea during the first postnatal week. Ca2+ signaling under these conditions depends on inositol-1,4,5-trisphosphate generation from phospholipase C (PLC)-dependent hydrolysis of PI(4,5)P(2). Thus we analyzed mice with defective expression of PIPKIγ and found that (i) this enzyme is essential for the acquisition of hearing; (ii) it is primarily responsible for the synthesis of the receptor-regulated PLC-sensitive PI(4,5)P(2) pool in the cell syncytia that supports auditory hair cells and; (iii) spatially graded impairment of the PIP2-IP3-Ca2+ signaling pathway in cochlear non-sensory cells affects the level of gap junction coupling. Vice versa, we found defective gap junction coupling and intercellular IP3-dependent Ca2+ signaling the cochlea of mice with targeted ablation Cx26 or Cx30, as well as in mice knock in for a point mutation (Cx30T5M) associated with human congenital deafness. Altogether, our findings link bidirectionally defective hearing acquisition to Ca2+ signaling impairment and decreased biochemical coupling in the developing cochlea. Transduction of connexin deficient cochlear cultures with a bovine adeno associated virus vectors encoding Cx26 or Cx30 restored protein expression, rescued both gap junction coupling and Ca2+ signaling. Based on this work, we conclude that in vivo connexin gene delivery to the inner ear is a route worth exploring to rescue hearing function in mouse models of deafness and, in future, may lead to the development of therapeutic interventions in humans

The role of the eucharist in the making of an ecclesiology according to haimo of auxerre’s commentary on I cor

Carolingian biblical exegesis presents itself as a synthesis of exegetical and theological patristic tradition in order to make it affordable to the Christians of that time. The result of that process are interpretations of biblical texts that can be considered new, though based on the texts of the Fathers. Among them it is possible to find images of the Church containing ideas about power or how to govern and to order society. This paper studies Haimo of Auxerre’s commentary on I Cor 12, 12 et seq in order to establish the author’s concept of ’body of Christ’, in the context of the Eucharistic controversy of the ninth century. It also studies the ideological consequences of his exegesis.Fil: Hernandez Rodriguez, Alfonso Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Multidisciplinario de Historia y Ciencias Humanas; Argentina. Universidad de la Defensa Nacional; Argentin

La protesta política: una propuesta para su estudio

El presente documento tiene la intención de desarrollar un marco teórico sustentable, desde la psicología social, para explicar la protesta política, lo que implica conocer los significados, las conductas y los motivos que tienen y llevan a los ciudadanos a participar (como parte de grupos u organizaciones sociales) en este tipo de movilizaciones. Asimismo, se considerará la influencia que tienen los medios de comunicación; la estructura legal en la cual se sustentan los partidos en el poder, y las coyunturas políticas para la construcción de las creencias compartidas.El presente documento tiene la intención de desarrollar un marco teórico sustentable, desde la psicología social, para explicar la protesta política, lo que implica conocer los significados, las conductas y los motivos que tienen y llevan a los ciudadanos a participar (como parte de grupos u organizaciones sociales) en este tipo de movilizaciones. Asimismo, se considerará la influencia que tienen los medios de comunicación; la estructura legal en la cual se sustentan los partidos en el poder, y las coyunturas políticas para la construcción de las creencias compartidas

Poemas

Se incluye los poemas "Qué pasa con las hojas cuando terminan de caer?" y "Dos esencias antes de ti". Ambos se refieren a la relación amorosa: el primero está cargado hacia la melancolía; el segundo, al deseo vehemente.Se incluye los poemas "Qué pasa con las hojas cuando terminan de caer?" y "Dos esencias antes de ti". Ambos se refieren a la relación amorosa: el primero está cargado hacia la melancolía; el segundo, al deseo vehemente

Principles for Consciousness in Integrated Cognitive Control

In this article we will argue that given certain conditions for the evolution of bi- \ud ological controllers, these will necessarily evolve in the direction of incorporating \ud consciousness capabilities. We will also see what are the necessary mechanics for \ud the provision of these capabilities and extrapolate this vision to the world of artifi- \ud cial systems postulating seven design principles for conscious systems. This article \ud was published in the journal Neural Networks special issue on brain and conscious- \ud ness

Tribological behaviour of copper oxide nanoparticle suspension

This work presents and discusses the tribological behaviour of nanoparticle suspensions in a polyalphaolefin (PAO6). CuO nanoparticles were separately dispersed at 0.5, 1.0 and 2.0% wt. in PAO6 using an ultrasonic probe for 2 minutes. AW properties were obtained using a TE53SLIM tribometer with a block-on-ring configuration and EP properties were obtained using a Four-Ball machine according to ASTM D2783. Wear surfaces were analyzed by SEM and EDS after tests. The study led to the following conclusions: nanoparticle suspensions exhibited reductions in friction and wear compared to the base oil; CuO suspensions showed the highest friction coefficient and lowest wear per nanoparticle content of 2%; all concentrations of nanoparticles improved the EP properties of PAO6; CuO showed better results at 0.5% wt. of nanoparticles; and the antiwear mechanism of nanoparticulate additive was produced by tribo-sintering

Viscosity and tribology of copper oxide nanofluids

Nanofluids, a term proposed by Choi in 1995 [1], are composites consisting of solid nanoparticles with sizes varying generally from 1 to 100 nm dispersed in a liquid. Numerous nanoparticles used as oil additives have been investigated in recent years [2-7]. Results show that they deposit on the rubbing surface and improve the tribological properties of the base oil, displaying good friction and wear reduction characteristics even at concentrations below 2%wt. Although the viscosity of the nanofluids is a property of crucial importance for film forming, and hence friction and wear reduction, which are characteristic of lubricants, only Hwang et al. [8] have studied thermal characteristics, kinematic viscosity and tribological properties of nanofluids simultaneously. In this paper, we present measurements of dynamic viscosity of nanofluids formed by copper oxide nanoparticles dispersed in a polyalphaolefin, for temperatures and concentrations varying from 20 to 60ºC and 0.5 to 2% wt., respectively. Dependence of the nanofluid viscosity to the solid fraction and temperature was compared with existing models and its influence on lubrication was also analysed