CGP37157, an inhibitor of the mitochondrial Na+/Ca2+ exchanger, protects neurons from excitotoxicity by blocking voltage-gated Ca2+ channels

Inhibition of the mitochondrial Na+/Ca2+ exchanger (NCLX) by CGP37157 is protective in models of neuronal injury that involve disruption of intracellular Ca2+ homeostasis. However, the Ca2+ signaling pathways and stores underlying neuroprotection by that inhibitor are not well defined. In the present study, we analyzed how intracellular Ca2+ levels are modulated by CGP37157 (10 mu M) during NMDA insults in primary cultures of rat cortical neurons. We initially assessed the presence of NCLX in mitochondria of cultured neurons by immunolabeling, and subsequently, we analyzed the effects of CGP37157 on neuronal Ca2+ homeostasis using cameleon-based mitochondrial Ca2+ and cytosolic Ca2+ ([Ca2+](i)) live imaging. We observed that NCLX-driven mitochondrial Ca2+ exchange occurs in cortical neurons under basal conditions as CGP37157 induced a decrease in [Ca-2](i) concomitant with a Ca2+ accumulation inside the mitochondria. In turn, CGP37157 also inhibited mitochondrial Ca2+ efflux after the stimulation of acetylcholine receptors. In contrast, CGP37157 strongly prevented depolarization-induced [Ca2+](i) increase by blocking voltage-gated Ca2+ channels (VGCCs), whereas it did not induce depletion of ER Ca2+ stores. Moreover, mitochondrial Ca2+ overload was reduced as a consequence of diminished Ca2+ entry through VGCCs. The decrease in cytosolic and mitochondrial Ca2+ overload by CGP37157 resulted in a reduction of excitotoxic mitochondrial damage, characterized here by a reduction in mitochondrial membrane depolarization, oxidative stress and calpain activation. In summary, our results provide evidence that during excitotoxicity CGP37157 modulates cytosolic and mitochondrial Ca2+ dynamics that leads to attenuation of NMDA-induced mitochondrial dysfunction and neuronal cell death by blocking VGCCs.

Ca2+ Influx and Tyrosine Kinases Trigger Bordetella Adenylate Cyclase Toxin (ACT) Endocytosis. Cell Physiology and Expression of the CD11b/CD18 Integrin Major Determinants of the Entry Route

Humans infected with Bordetella pertussis, the whooping cough bacterium, show evidences of impaired host defenses. This pathogenic bacterium produces a unique adenylate cyclase toxin (ACT) which enters human phagocytes and catalyzes the unregulated formation of cAMP, hampering important bactericidal functions of these immune cells that eventually cause cell death by apoptosis and/or necrosis. Additionally, ACT permeabilizes cells through pore formation in the target cell membrane. Recently, we demonstrated that ACT is internalised into macrophages together with other membrane components, such as the integrin CD11b/CD18 (CR3), its receptor in these immune cells, and GM1. The goal of this study was to determine whether ACT uptake is restricted to receptor-bearing macrophages or on the contrary may also take place into cells devoid of receptor and gain more insights on the signalling involved. Here, we show that ACT is rapidly eliminated from the cell membrane of either CR3-positive as negative cells, though through different entry routes, which depends in part, on the target cell physiology and characteristics. ACT-induced Ca2+ influx and activation of non-receptor Tyr kinases into the target cell appear to be common master denominators in the different endocytic strategies activated by this toxin. Very importantly, we show that, upon incubation with ACT, target cells are capable of repairing the cell membrane, which suggests the mounting of an anti-toxin cell repair-response, very likely involving the toxin elimination from the cell surface.

Intracellular Ca2+ release through ryanodine receptors contributes to AMPA receptor-mediated mitochondrial dysfunction and ER stress in oligodendrocytes

Overactivation of ionotropic glutamate receptors in oligodendrocytes induces cytosolic Ca2+ overload and excitotoxic death, a process that contributes to demyelination and multiple sclerosis. Excitotoxic insults cause well-characterized mitochondrial alterations and endoplasmic reticulum (ER) dysfunction, which is not fully understood. In this study, we analyzed the contribution of ER-Ca2+ release through ryanodine receptors (RyRs) and inositol triphosphate receptors (IP(3)Rs) to excitotoxicity in oligodendrocytes in vitro. First, we observed that oligodendrocytes express all previously characterized RyRs and IP(3)Rs. Blockade of Ca2+-induced Ca2+ release by TMB-8 following alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor-mediated insults attenuated both oligodendrocyte death and cytosolic Ca2+ overload. In turn, RyR inhibition by ryanodine reduced as well the Ca2+ overload whereas IP3R inhibition was ineffective. Furthermore, AMPA-triggered mitochondrial membrane depolarization, oxidative stress and activation of caspase-3, which in all instances was diminished by RyR inhibition. In addition, we observed that AMPA induced an ER stress response as revealed by alpha subunit of the eukaryotic initiation factor 2 alpha phosphorylation, overexpression of GRP chaperones and RyR-dependent cleavage of caspase-12. Finally, attenuating ER stress with salubrinal protected oligodendrocytes from AMPA excitotoxicity. Together, these results show that Ca2+ release through RyRs contributes to cytosolic Ca2+ overload, mitochondrial dysfunction, ER stress and cell death following AMPA receptor-mediated excitotoxicity in oligodendrocytes. Cell Death and Disease (2010) 1, e54; doi:10.1038/cddis.2010.31; published online 15 July 2010

Marcas de distribuidor: análisis del espacio en el lineal por categorías y enseñas

[ES] El objetivo principal de este trabajo es confirmar si la ocupación de espacio por parte de las marcas de distribuidor en los lineales es excesivo, tal y como parecen afirmar los productores de marcas de fabricante. Para ello, se presentan los resultados de una observación del espacio ocupado por estas marcas en una muestra representativa de 40 categorías en 55 establecimientos. Con los datos obtenidos, se muestran las diferencias existentes entre categorías y entre enseñas. Además se observa si los establecimientos han llegado a un punto de lineal máximo y si el espacio ocupado por sus marcas propias es desproporcionado en relación a su cuota de mercado.

Análisis de la satisfacción máxima del consumidor en establecimientos de alimentación: la influencia del folleto publicitario

[ES] Partiendo de la consideración inicial de aquellos atributos del establecimiento comercial que la literatura de marketing ha identificado como fundamentales para que los distribuidores minoristas de alimentación puedan llevar a cabo sus estrategias de diferenciación, este trabajo identifica los principales factores que subyacen a dichos atributos. Todo ello, con objeto de comprender cuáles de estos factores ejercen una mayor influencia sobre el nivel más elevado de satisfacción del consumidor.

Survey of the fatty acid composition of Canadian beef: Backfat and longissimus lumborum muscle

[EN]A survey of Canadian retail beef was undertaken with emphasis on the trans fatty acid (TFA) and conjugated linoleic acid (CLA) isomers, and compared with current health recommendations. Thirty striploin steaks were collected in the winter and summer from major grocery stores in Calgary (Alberta, Canada). Steak fatty acid compositions (backfat and longissimus lumborum muscle analysed separately) showed minor seasonal differences with lower total saturates (PB0.05) and higher total monounsaturates (PB 0.01) in winter, but no differences in total polyunsaturated fatty acids. The ratio of n-6 and n-3 polyunsaturated fatty acid in longissimus lumborum averaged 5.8. The average TFA content in longissimus lumborum was 0.128 g 100 g_1 serving size, and 10t-18:1 was found to be the predominant isomer (32% of total trans), while vaccenic acid was second most abundant (15% of total trans). The CLA content in longissimus lumborum was similar to that of backfat, ranging from 0.43 to 0.60% of total fatty acids and rumenic acid represented 60% of total isomers. Overall, there is still room for improvement in the saturated, mono- and polyunsaturated fatty acid composition of Canadian beef to meet general dietary guidelines for human consumption and additional targets should include reducing 10t-18:1 while increasing both rumenic and vaccenic acids.

Kv7 Channels Can Function without Constitutive Calmodulin Tethering

9 p.

ATP Antagonizes Thrombin-Induced Signal Transduction through 12(S)-HETE and cAMP

15 p.

The Voltage-Gated Sodium Channel Na(v)1.8 Is Expressed in Human Sperm

The role of Na+ fluxes through voltage-gated sodium channels in the regulation of sperm cell function remains poorly understood. Previously, we reported that several genes encoding voltage-gated Na+ channels were expressed in human testis and mature spermatozoa. In this study, we analyzed the presence and function of the TTX-resistant VGSC a subunit Na(v)1.8 in human capacitated sperm cells. Using an RT-PCR assay, we found that the mRNA of the gene SCN10A, that encode Na-v1.8, was abundantly and specifically expressed in human testis and ejaculated spermatozoa. The Na-v1.8 protein was detected in capacitated sperm cells using three different specific antibodies against this channel. Positive immunoreactivity was mainly located in the neck and the principal piece of the flagellum. The presence of Na-v1.8 in sperm cells was confirmed by Western blot. Functional studies demonstrated that the increases in progressive motility produced by veratridine, a voltage-gated sodium channel activator, were reduced in sperm cells preincubated with TTX (10 mu M), the Na-v1.8 antagonist A-803467, or a specific Na-v1.8 antibody. Veratridine elicited similar percentage increases in progressive motility in sperm cells maintained in Ca2+-containing or Ca2+-free solution and did not induce hyperactivation or the acrosome reaction. Veratridine caused a rise in sperm intracellular Na+, [Na+](i), and the sustained phase of the response was inhibited in the presence of A-803467. These results verify that the Na+ channel Na-v1.8 is present in human sperm cells and demonstrate that this channel participates in the regulation of sperm function.

The Economic Impacts of Biodiversity Policy for Improving the Climate Regulating Services Provided by EU Natura 2000 Habitats

22 p.

Evaluation of Two Alternative Carbon Capture and Storage Technologies: A Stochastic Model

30 p.

Análisis económico-financiero de las empresas del sector de comercio al por menor en el Pais Vasco

El trabajo consiste en realizar un análisis económico-financiero de las empresas del sector del comercio al por menor en establecimientos no especializados, con predominio en productos alimenticios establecidas en el País Vasco, centrándose especialmente en el diagnóstico de su situación actual y la evolución reciente de su liquidez, riesgo y rentabilidad. The work consists of carry out an economic and financial analysis of companies in the retail trade in non-specialized sector, stores with food products based in the Basque Country, especially focusing on the diagnosis of the current situation and recent developments their liquidity, risk and profitability.

2.0 funtsezko tresna bezala informazioaren kudeaketan

[EU]Ezagutzaren gizartean aurkitzen gara eta informazioak enpresa munduan hartu duen garrantziak garapen berriak ekarri ditu bai ikerketan bai informazio eta komunikazio teknologietan (IKT). Beraz, enpresek informazioa era sistematiko batean kudeatu beharra dute ez badute lehiakortasuna galdu nahi. Egoera honetan, zaintza teknologikoak paper garrantzitsu bat betetzen du informazioa lortzeaz, gordetzeaz eta transmititzeaz arduratzen den sistema baita. Baina sistema honen irispena mugatuta egongo da erabiltzen diren baliabideengatik. Gainera, muga hori garrantzi handiagoa hartzen du ETEtan, Euskal Herriko ekonomia-ehunaren oinarria, non baliabideak minimoak diren eta enpresa handiagoekin lehiatu behar diren. Egoera honi aurre egiteko, 2.0 tresnak aurkezten dira, zaintza teknologikorako baliagarriak diren tresnak, kostu eta denbora minimoak eskatzen dituztenak. Horrela, lan hau Euskal Herriko ETEtan zaintza teknologikoaren egoera aztertzera eta bere beharretara egokitzen diren soluzio teknologikoak planteatzera zuzenduta joango da, 2.0 tresnak oinarri moduan daudela.

Aplicando netnografía a la obtención del mapa de posicionamiento para empresas de distribución alimentaria

[ES] Las comunidades online se han convertido en un lugar de encuentro muy popular para los consumidores que les permite compartir información. En este artículo se presenta una técnica de información novedosa como la netnografía, y se aplica para determinar cuál es el posicionamiento de las empresas de distribución alimentaria. Tras la recogida y análisis de 506 mensajes válidos de la comunidad online Ciao, se pudo conocer qué atributos se asociaban a seis establecimientos de alimentación analizados. Mercadona se asocia con la calidad de su marca de distribuidor y una escasa variedad de marcas/productos. Las tiendas discount, Lidl y DIA, destacan por la posibilidad de mejora en la limpieza del establecimiento y la localización de los productos. Los hipermercados, Eroski, Alcampo y Carrefour, son destacados por su variedad de marcas/productos, y alejado del domicilio. También se ha identificado a los competidores más directos de cada empresa, encontrándose una competencia entre los formatos de venta del mismo tipo (intratipo). El uso de la netnografia, técnica relativamente reciente, supone la mayor originalidad del trabajo. Además, las conclusiones obtenidas, que son coincidentes con estudios anteriores, muestran que la netnografía puede ser una fuente de información para determinar cuál es la imagen comercial y el posicionamiento de las empresas.

Brand image and lexicographic analysis: an application to shopping malls

[EN] The concept of image in its different aspects is very important in today s society as well as in the business management field. Some authors reports that most of the studies that measure image do not take into account neither previous theoretical and conceptual models nor other possible empirical evidence alternatives. Given this need, a research regarding the concept of brand image applied to shopping malls was conducted based on the conceptual model of the consumer cognitive response in order to empirically explore and contrast it. For this reason, a survey was applied to 420 consumers in five shopping malls in Bogotá, achieving a database of 3.749 cases. The results show attribute-shopping mall associations expressed in unique, differentiated, and notorious vocabulary obtained applying lexicometric and multivariate analysis techniques. Attribute-shopping mall associations such as spacious , good location , good variety of stores , and the existence of movie theaters . Finally, this research aims to potentially improve the management of shopping malls and increase their attractiveness and customer loyalty by applying the development of service quality systems, integral communication, segmentation, and positioning.