An ASIC channel for acid chemotransduction

Producción CientíficaSpontaneous breathing requires feedback controls in which detection of blood gas and pH are critical. While O2 detection is performed by pheripheral chemoreceptors, CO2/pH-sensitive chemoreceptors are in the carotid bodies (CBs), but major sites are also within the brain (the central chemoreceptors [CCR]). CO2/pH signals are related to the acid-base status of the blood and reflect the adequacy of breathing to metabolism. Small changes in CO2/pH can affect breathing, so that a rise in Pco2 as small as 1 mm Hg produces an evident change in ventilation.1 Such a high CO2 sensitivity relies in the inherent properties of CO2/pH-sensing molecules present both in CB and CCR cells, as shown in several recent studies on CO2/pH sensing ion channels and receptors.2,3 Functional properties of most proteins can be regulated by changes in pH, as this would only require 1 or a few titratable residues of the molecule, whose protonation can lead to conformation changes that translate into changes in activity. However, to define whether those molecules have a relevant role in CO2/pH chemoreception, some more criteria should be met, including their range of pH sensitivity, their location in chemoreceptor cells, and their functional contribution to the integrated chemoreceptor response. In this regard, the molecular characterization of pH-sensitive channels and transporters has progressed considerably within the last years, but conclusive evidences of their contribution to acid chemotransduction are not so well established for many of them. The main reason for this delay is the fact that the identity of the primary sensory cells constituting CCRs and of their neuronal networks remains elusive. In vitro, neurons from many brain locations are excited or inhibited by CO2/pH changes, but it has been difficult to link this neuronal chemosensitivity to chemoreception in vivo. Moreover, in addition to chemosensitive neurons, CCRs sites may also contain neurons with other integrative functions that are not clearly distinct from chemosensitive ones in their morphological or functional properties, making their experimental study difficult.Ministerio de Sanidad, Consumo y Bienestar Social - Instituto de Salud Carlos III (grants R006/009 and PI041044)Ministerio de Ciencia, Innovación y Universidades (grant BFU2004-05551)Junta de Castilla y León (grant VA011C05

Are Kv channels the essence of O2 sensing?

Producción CientíficaThis report represents a relevant contribution to the study of oxygen sensing for two main reasons. First, it shows an approach adequate for identification of a putative O2-sensitive K+ channel, by moving from the modulation by hypoxia of a recombinant channel back to its physiological context, the role of this channel in the response to low Po2 of the native cells. Second, it demonstrates that hypoxic inhibition of the recombinant Kv3.1 channels is retained in excised membrane patches, pointing to a membrane-delimited mechanism as the origin of hypoxic responses. The importance of this latter finding deserves additional comment

Obtaining the fatigue laws of bituminous mixtures from a strain sweep test: effect of temperature and aging

Fatigue is associated with the deterioration caused by applying repeated loads, and is affected by temperature or aging. Generally, time sweep tests are used to simulate fatigue, in order to obtain the fatigue laws. However, this requires too much time, often preventing its use. A method to estimate the fatigue laws from a strain sweep test is presented. The test was performed on a semi-dense mixture with different types of binder (unconditioned or aged) tested at different temperatures. This test is able to estimate fatigue laws more quickly, allowing the effect of different factors on the mixtures' fatigue life to be studied.Peer ReviewedPostprint (author's final draft

Kvβ1.2 Subunit Coexpression in HEK293 Cells Confers O2 Sensitivity to Kv4.2 but not to Shaker Channels

Voltage-gated K+ (KV) channels are protein complexes composed of ion-conducting integral membrane α subunits and cytoplasmic modulatory β subunits. The differential expression and association of α and β subunits seems to contribute significantly to the complexity and heterogeneity of KV channels in excitable cells, and their functional expression in heterologous systems provides a tool to study their regulation at a molecular level. Here, we have studied the effects of Kvβ1.2 coexpression on the properties of Shaker and Kv4.2 KV channel α subunits, which encode rapidly inactivating A-type K+ currents, in transfected HEK293 cells. We found that Kvβ1.2 functionally associates with these two α subunits, as well as with the endogenous KV channels of HEK293 cells, to modulate different properties of the heteromultimers. Kvβ1.2 accelerates the rate of inactivation of the Shaker currents, as previously described, increases significantly the amplitude of the endogenous currents, and confers sensitivity to redox modulation and hypoxia to Kv4.2 channels. Upon association with Kvβ1.2, Kv4.2 can be modified by DTT (1,4 dithiothreitol) and DTDP (2,2′-dithiodipyridine), which also modulate the low pO2 response of the Kv4.2+β channels. However, the physiological reducing agent GSH (reduced glutathione) did not mimic the effects of DTT. Finally, hypoxic inhibition of Kv4.2+β currents can be reverted by 70% in the presence of carbon monoxide and remains in cell-free patches, suggesting the presence of a hemoproteic O2 sensor in HEK293 cells and a membrane-delimited mechanism at the origin of hypoxic responses. We conclude that β subunits can modulate different properties upon association with different KV channel subfamilies; of potential relevance to understanding the molecular basis of low pO2 sensitivity in native tissues is the here described acquisition of the ability of Kv4.2+β channels to respond to hypoxia

A Role for DPPX Modulating External TEA Sensitivity of Kv4 Channels

Shal-type (Kv4) channels are expressed in a large variety of tissues, where they contribute to transient voltage-dependent K+ currents. Kv4 are the molecular correlate of the A-type current of neurons (ISA), the fast component of ITO current in the heart, and also of the oxygen-sensitive K+ current (KO2) in rabbit carotid body (CB) chemoreceptor cells. The enormous degree of variability in the physiological properties of Kv4-mediated currents can be attributable to the complexity of their regulation together with the large number of ancillary subunits and scaffolding proteins that associate with Kv4 proteins to modify their trafficking and their kinetic properties. Among those, KChIPs and DPPX proteins have been demonstrated to be integral components of ISA and ITO currents, as their coexpression with Kv4 subunits recapitulates the kinetics of native currents. Here, we explore the presence and functional contribution of DPPX to KO2 currents in rabbit CB chemoreceptor cells by using DPPX functional knockdown with siRNA. Additionally, we investigate if the presence of DPPX endows Kv4 channels with new pharmacological properties, as we have observed anomalous tetraethylammonium (TEA) sensitivity in the native KO2 currents. DPPX association with Kv4 channels induced an increased TEA sensitivity both in heterologous expression systems and in CB chemoreceptor cells. Moreover, TEA application to Kv4-DPPX heteromultimers leads to marked kinetic effects that could be explained by an augmented closed-state inactivation. Our data suggest that DPPX proteins are integral components of KO2 currents, and that their association with Kv4 subunits modulate the pharmacological profile of the heteromultimers

Pautas cíclicas de la economía andaluza en el período 1984-2001: un análisis comparado

In this paper we characterize some cyclical patterns for the Andalusian economy, for the period 1984-2001. Our work is basically an empirical one. Our results show that the Andalusian economy is more volatile than Spain as a whole, although there exist an important degree of coherence between both economies. This result holds at the aggregate level and at the industry level. On average, GDP growth has been higher in Andalusia during expansions, although it has been lower during recessions. The relationship between the fluctuations of income and the fluctuations of the number of unemployed people is shown to be clearly negative, as the theory would predict, but the coefficient of the relation is lower in the case of Andalusia. Moreover, we find the relation not to be symmetric. For a given increase in production, unemployment gets reduced in a larger fraction than the increase that would present in recessions under the same, but negative, increase in production.Business cycles, Unemployment, Asymmetries, Regional Economics

Tratamiento metodológico de la observación indirecta en la gestión de organizaciones deportivas

En el presente trabajo se utilizaron partidos del Campeonato Europeo de la UEFA y del Mundo de la FIFA para evaluar la evolución de los patrones ofensivos de juego entre 1982 y 2010. Para ello se utilizó el instrumento de observación, codificación y registro SoccerEye en la recopilación de 45 partidos, que supuso un total de 6.791 ataques y 73.463 multieventos. Se implementó el análisis secuencial por medio del software SDIS - GSEQ, que permitió conocer los cambios producidos en las últimas tres décadas en la dinámica de los ataques que terminaron en gol. Los goles fueron conseguidos desde la zona central del sector ofensivo, en situaciones de uno contra uno del atacante contra el portero. Además, el equipo atacante mostró más jugadores en el centro del juego que el adversario en el momento en que los goles se anotaron. Con el tiempo, los patrones de ataque con gol realizados por equipos de élite han cambiado desde comportamientos más individuales, como conducción del balón y drible (1x1) en el eje central del terreno de juego, hacia tácticas basadas en el equipo, tales como pases cortos y centros desde las bandas. La comprensión de cómo las dinámicas de juego de los equipos de élite ha cambiado con el tiempo permitirá a los entrenadores desarrollar ejercicios de entrenamiento que tendrán más probabilidades de mejorar el éxito individual y colectivo de los equipo

Complexity of the behaviour of asphalt materials in cyclic testing

This paper compares the results obtained in two types of cyclic tension-compression tests, a time sweep test, constant strain amplitude, and a strain sweep test, increasing strain amplitude every 5000 cycles, called EBADE (standing for the Spanish words for strain sweep test). This comparison has shown that the rapid loss of stiffness during the initial part of cyclic testing is recoverable in bituminous materials. It has been found that reversible phenomena dominate in asphalt binders, while in mixtures are as important as damage. A damage equation has been proposed to describe the evolution of the material distress during the phase II in time sweep tests. In addition, a new methodology to estimate the fatigue law of bituminous mixtures is proposed.Peer ReviewedPostprint (author's final draft

Tratamiento metodológico de la observación indirecta en la gestión de organizaciones deportivas

Contemplar al usuario/a como elemento clave de la gestión, es una de las tendencias que actualmente ha recibido mucha atención científica. Sin embargo, la evaluación de la calidad de los programas deportivos orientados a la población infantil, es escasa, queda evidenciado en los pocos estudios realizados. Por ello, consideramos necesario realizar un estudio dirigido a la población infantil, como usuarios directos, ya que se trata del grupo social más numeroso a la hora de realizar actividades físicas y, la necesidad de crear y consolidar hábitos deportivos que pueden repercutir en estilos de vida saludables. El objetivo de nuestro trabajo es plantear un desarrollo metodológico de observación indirecta con el fin de profundizar en la evaluación de la calidad en los servicios municipales deportivos orientados a la población infantil. En la actualidad, el desarrollo metodológico ha beneficiado de manera muy notoria a la observación indirecta. Se trata de documentos de los cuales hemos aprendido a extraer información válida y consistente; documentos que pueden tener un alto valor informativo, pero que formalmente requieren de una preparación que los adecúen para alcanzar la necesaria sistematización. Para ello contrastamos las percepciones de los usuarios/as más pequeños/as (de 8 a 12 años) con la de los/as padres/madres y el personal experto de las instalaciones municipales deportivas, para adecuar y mejorar los servicios deportivos orientados a la población infantil. Para la recogida de información se realizaron entrevistas en profundidad y para el tratamiento de los datos, se utilizó el programa Atlas Ti. Los datos aquí presentados forman parte de un trabajo de mayor envergadura.Researchers are paying increasing attention to users as a key component in service management. However, very few studies have sought to examine the quality of sports services for children. This is perhaps surprising when one considers that physical activity is engaged in more by children than by any other social group, not to mention the importance of developing and consolidating children's interest in sport so as to help promote healthy lifestyles. With this in mind the present study uses indirect observation as a means of assessing the quality of municipal sports services for children. In recent years the indirect observational approach has made a notable contribution to the development of research methodologies. Indeed, it has been shown that valid, reliable information can be extracted from documents of various kinds. However, in order to ensure that such information is of high value, these documents need to be prepared in such a way that systematic analyses are possible. This study focuses on the quality of sports services for children and compares the views of children (8-12 years old) with those of parents and of the staff of municipal sports facilities. The aim was to gather information that could help improve such services and tailor them more to children's needs. The information was gathered by means of in-depth interviews, the contents of which were then analysed using Atlas.ti software. The data presented here forms part of a broader research project.Contemplar o usuário/a como elemento-chave da gestão, é uma das tendências que actualmente tem recibido muita atenção científica. Contudo, a avaliação da qualidade dos programas desportivos orientados para a população infantil é escassa, o que se tem verificado pelos poucos estudos realizados. Assim, consideramos necessário realizar um estudo dirigido à população infantil, como usuários directos, já que se trata do grupo social mais numeroso quando se trata de realizar actividades físicas e, a necessidade de criar e consolidar hábitos desportivos que se podem repercutir em estilos de vida saudáveis. O objectivo do nosso trabalho é propor um desenvolvimento metodológico de observação indirecta com a finalidade de aprofundar a avaliação da qualidade dos serviços municipais desportivos orientados para a população infantil. Na actualidade, o desenvolvimento metodológico tem beneficiado de maneira bastante notória, a observação indirecta. Refere-se a documentos dos quais temos aprendido a extrair informação válida e consistente; documentos que podem ter um elevado valor informativo, mas que formalmente requerem uma preparação que os tornem adequados para alcançar a necessária sistematização. Para tal, comparámos as percepções dos usuários/as mais jovens (de 8 a 12 anos) com as dos pais/mães e do pessoal especialista das instalações municipais desportivas, para adequar e melhorar os serviços desportivos orientados para a população infantil. Para a recolha de dados foram realizadas entrevistas estruturadas e para o tratamento de dados foi utilizado o programa Atlas Ti. Os dados aqui apresentados fazem parte de um trabalho de maior envergadura

Analytical Framework for Emergency Remote Education in Universities During Lockdown

Abstract This paper presents a framework based on three dimensions (material, educational, and psychoemotional) to explore the characteristics, processes, and outcomes of emergency remote education introduced by in-person universities during the COVID-19 pandemic. With this aim, two ad hoc questionnaires were designed and administered in April-May to a sample of 220teachers and 548 students in a Spanish university. The most significant findings show digital inequality between students in terms of technological equipment and the quality of connectivity. Remote education was designed as a way to transfer the in-person teaching model to a virtual environment. Both teachers and students experienced an overload of work, which may help to explain the high levels of stress experienced by both groups. The research concludes with proposals to improve the quality and effectiveness of distance learning in any future crises