37 research outputs found
Understanding online business simulation games: the role of flow experience, perceived enjoyment and personal innovativeness
This study aimed to empirically predict the degree of acceptance of an online business simulation game in an educational context. To do so, this study proposed an extended technology acceptance model that includes variables such as perceived enjoyment and flow. In addition, the moderating role of students'' personal imiovativeness in the technology field was analysed. The framework was empirically tested applying partial least squares to a sample of 266 students. Results reveal that perceived enjoyment is a key variable in explaining students'' perceived ease of use, usefulness and attitudes towards the simulation. Perceived ease of use is not significantly related to flow experience. However, this relationship is moderated by personal innovativeness. Indeed, results indicate that the higher the students'' personal innovativeness, the more attenuated the effect of perceived ease of use on the attitude towards the game and on flow experience. The study offers relevant insights for the pedagogical use of competitive digital technologies in university contexts
La influencia de la filosofía del marketing medioambiental en el resultado empresarial: el papel moderador de las características organizacionales
Este trabajo analiza la relación existente entre la filosofía del marketing medioambiental y los resultados empresariales, estudiando los beneficios provenientes desde el lado de la demanda. Además, se explora si dicha influencia está condicionada por la industria en la que la empresa opera y por su posición en la cadena de valor. Para ello, se lleva a cabo un estudio de mercado con empresas españolas del sector industrial. Los resultados evidencian que el marketing medioambiental contribuye a optimizar los rendimientos comerciales y económicos. Además, esta influencia es mayor en empresas de consumo, si bien la industria no modera dicha relación
Oligodendrocyte differentiation from adult multipotent stem cells is modulated by glutamate
We used multipotent stem cells (MSCs) derived from the young rat subventricular zone (SVZ) to study the effects of glutamate in oligodendrocyte maturation. Glutamate stimulated oligodendrocyte differentiation from SVZ-derived MSCs through the activation of specific N-methyl--aspartate (NMDA) receptor subunits. The effect of glutamate and NMDA on oligodendrocyte differentiation was evident in both the number of newly generated oligodendrocytes and their morphology. In addition, the levels of NMDAR1 and NMDAR2A protein increased during differentiation, whereas NMDAR2B and NMDAR3 protein levels decreased, suggesting differential expression of NMDA receptor subunits during maturation. Microfluorimetry showed that the activation of NMDA receptors during oligodendrocyte differentiation elevated cytosolic calcium levels and promoted myelination in cocultures with neurons. Moreover, we observed that stimulation of MSCs by NMDA receptors induced the generation of reactive oxygen species (ROS), which were negatively modulated by the NADPH inhibitor apocynin, and that the levels of ROS correlated with the degree of differentiation. Taken together, these findings suggest that ROS generated by NADPH oxidase by the activation of NMDA receptors promotes the maturation of oligodendrocytes and favors myelination
Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis
Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration.
Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls.
Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected.
Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS
Comparative Genomic Analysis of Human Fungal Pathogens Causing Paracoccidioidomycosis
Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled with a thermally regulated transition from a soil-dwelling filamentous form to a yeast-like pathogenic form. To better understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of Paracoccidioides brasiliensis (Pb03 and Pb18) and one strain of Paracoccidioides lutzii (Pb01). These genomes range in size from 29.1 Mb to 32.9 Mb and encode 7,610 to 8,130 genes. To enable genetic studies, we mapped 94% of the P. brasiliensis Pb18 assembly onto five chromosomes. We characterized gene family content across Onygenales and related fungi, and within Paracoccidioides we found expansions of the fungal-specific kinase family FunK1. Additionally, the Onygenales have lost many genes involved in carbohydrate metabolism and fewer genes involved in protein metabolism, resulting in a higher ratio of proteases to carbohydrate active enzymes in the Onygenales than their relatives. To determine if gene content correlated with growth on different substrates, we screened the non-pathogenic onygenale Uncinocarpus reesii, which has orthologs for 91% of Paracoccidioides metabolic genes, for growth on 190 carbon sources. U. reesii showed growth on a limited range of carbohydrates, primarily basic plant sugars and cell wall components; this suggests that Onygenales, including dimorphic fungi, can degrade cellulosic plant material in the soil. In addition, U. reesii grew on gelatin and a wide range of dipeptides and amino acids, indicating a preference for proteinaceous growth substrates over carbohydrates, which may enable these fungi to also degrade animal biomass. These capabilities for degrading plant and animal substrates suggest a duality in lifestyle that could enable pathogenic species of Onygenales to transfer from soil to animal hosts.National Institute of Allergy and Infectious Diseases (U.S.)National Institutes of Health. Department of Health and Human Services (contract HHSN266200400001C)National Institutes of Health. Department of Health and Human Services(contract HHSN2722009000018C)Brazil. National Council for Scientific and Technological Developmen
Las características del boca-oído electrónico y su influencia en la intención de recompra online
Con la creciente expansio´n de Internet, cada vez es ma´s habitual que las empresas incluyan en sus pa´gi- nas de venta online un espacio virtual donde los usuarios compartan informacio´n sobre los productos o servicios ofrecidos. Este estudio explora las caracteri´sticas de las recomendaciones publicadas por los usuarios (cantidad, credibilidad y calidad del boca-oi´do electro´nico) como antecedentes de la intencio´n de recompra a trave´s de su influencia en la actitud y confianza hacia el vendedor online y en la utili- dad percibida de la tienda virtual. Para contrastar las hipo´tesis propuestas se procedio´ al disen ~o de una encuesta online, utiliza´ndose una muestra de conveniencia formada por 252 consumidores. El modelo fue testado mediante ecuaciones estructurales, utilizando la te´cnica Partial Least Squares (PLS). Los resulta- dos muestran que, si bien todas las caracteri´sticas del boca-oi´do electro´nico influyen positivamente en la utilidad percibida de la pa´gina web, solo la calidad de los comentarios influye en la confianza. Asimismo, una mayor cantidad de recomendaciones en la plataforma puede afectar negativamente a la confianza en el vendedor online. Este trabajo pone de manifiesto la importancia de la actitud hacia el vendedor y la utilidad percibida de la pa´gina web como antecedentes de la intencio´n de recompra online
El aprendizaje y la innovación como determinantes del desarrollo de una capacidad de gestión medioambiental proactiva
Este trabajo, a través del enfoque de capacidades dinámicas, plantea y estima un modelo en el que las dimensiones de la orientación al aprendizaje y la predisposición a innovar influyen en la capacidad de gestión medioambiental proactiva. Adicionalmente, analiza el efecto mediador de la predisposición a innovar en la relación entre las dimensiones de la orientación al aprendizaje y la estrategia medioambiental proactiva. Para alcanzar los objetivos se realizó un estudio empírico a 250 establecimientos hoteleros. Los resultados contribuyen a llenar un vacío en la literatura existente, ya que analiza cómo determinadas capacidades organizacionales significativamente explican el desarrollo de una capacidad de gestión medioambiental proactiva. En concreto, estas tienen que ver con los valores asociados a la consideración del aprendizaje como un recurso crítico, la implantación de estructuras que faciliten la acumulación y la diseminación de conocimiento, la existencia de una mentalidad abierta y la predisposición de la empresa a desarrollar innovaciones organizacionales
PET imaging with [18F]FSPG evidences the role of system xc- on brain inflammation following cerebral ischemia in rats
In vivo Positron Emission Tomography (PET) imaging of the cystine-glutamate antiporter (system xc-) activity with [18F]FSPG is meant to be an attractive tool for the diagnosis and therapy evaluation of brain diseases. However, the role of system xc- in cerebral ischemia and its involvement in inflammatory reaction has been scarcely explored. In this work, we report the longitudinal investigation of the neuroinflammatory process following transient middle cerebral artery occlusion (MCAO) in rats using PET with [18F]FSPG and the translocator protein (TSPO) ligand [18F]DPA-714. In the ischemic territory, [18F]FSPG showed a progressive binding increase that peaked at days 3 to 7 and was followed by a progressive decrease from days 14 to 28 after reperfusion. In contrast, [18F]DPA-714 evidenced maximum binding uptake values over day 7 after reperfusion. Ex vivo immnunohistochemistry confirmed the up-regulation of system xc- in microglial cells and marginally in astrocytes. Inhibition of system xc- with sulfasalazine and S-4-CPG resulted in increased arginase (anti-inflammatory M2 marker) expression at day 7 after ischemia, together with a decrease in TSPO and microglial M1 proinflammatory markers (CCL2, TNF and iNOS) expression. Taken together, these results suggest that system xc- plays a key role in the inflammatory reaction underlying experimental stroke. ¸ Ivyspring International Publisher
The expression of glutamate transporter GLT-1 in the rat cerebral cortex is down-regulated by the antipsychotic drug clozapine
We show here that clozapine, a beneficial antipsychotic, down-regulates the expression of the glutamate transporter GLT-1 in the rat cerebral cortex, thereby reducing glutamate transport and raising extracellular glutamate levels. Clozapine treatment (25-35 mg kg(-1) day(-1) orally) reduced GLT-1 immunoreactivity in several brain regions after 3 weeks; this effect was most prominent after 9 weeks and most evident in the frontal cortex. GLT-1 protein levels were reduced in the cerebral cortex of treated rats compared with controls and were more severely affected in the anterior (71.9 +/- 4.5%) than in the posterior (53.2 +/- 15.4%) cortex. L-[H-3]-glutamate uptake in Xenopus laevis oocytes injected with mRNA extracted from the anterior cerebral cortex of rats treated for 9 weeks was remarkably reduced (to 30.6 +/- 8.6%) as compared to controls. In addition, electrophysiological recordings from oocytes following application of glutamate revealed a strong reduction in glutamate uptake currents (46.3 +/- 10.2%) as compared to controls, Finally, clozapine treatment led to increases in both the mean basal (8.1 +/- 0.7 muM) and the KCl-evoked (28.7 +/- 7.7 muM) output of glutamate that were 3.1 and 3.5, respectively, higher than in control rats. These findings indicate that clozapine may potentiate glutamatergic synaptic transmission by regulating glutamate transport