Increased expression of cystine/glutamate antiporter in multiple sclerosis

Background: Glutamate excitotoxicity contributes to oligodendrocyte and tissue damage in multiple sclerosis (MS). Intriguingly, glutamate level in plasma and cerebrospinal fluid of MS patients is elevated, a feature which may be related to the pathophysiology of this disease. In addition to glutamate transporters, levels of extracellular glutamate are controlled by cystine/glutamate antiporter x(c)(-), an exchanger that provides intracellular cystine for production of glutathione, the major cellular antioxidant. The objective of this study was to analyze the role of the system x(c)(-) in glutamate homeostasis alterations in MS pathology. -- Methods: Primary cultures of human monocytes and the cell line U-937 were used to investigate the mechanism of glutamate release. Expression of cystine glutamate exchanger (xCT) was quantified by quantitative PCR, Western blot, flow cytometry and immunohistochemistry in monocytes in vitro, in animals with experimental autoimmune encephalomyelitis (EAE), the animal model of MS, and in samples of MS patients. -- Results and discussion: We show here that human activated monocytes release glutamate through cystine/glutamate antiporter x(c)(-) and that the expression of the catalytic subunit xCT is upregulated as a consequence of monocyte activation. In addition, xCT expression is also increased in EAE and in the disease proper. In the later, high expression of xCT occurs both in the central nervous system (CNS) and in peripheral blood cells. In particular, cells from monocyte-macrophage-microglia lineage have higher xCT expression in MS and in EAE, indicating that immune activation upregulates xCT levels, which may result in higher glutamate release and contribution to excitotoxic damage to oligodendrocytes. -- Conclusions: Together, these results reveal that increased expression of the cystine/glutamate antiporter system x(c)(-) in MS provides a link between inflammation and excitotoxicity in demyelinating diseases.

Los programas de apoyo a la creación de spin-offs académicas en las universidades españolas: una comparación internacional

XXII,1021 p.

Number of prior episodes and the presence of depressive symptoms are associated with longer length of stay for patients with acute manic episodes

Background: Few studies have analyzed predictors of length of stay (LOS) in patients admitted due to acute bipolar manic episodes. The purpose of the present study was to estimate LOS and to determine the potential sociodemographic and clinical risk factors associated with a longer hospitalization. Such information could be useful to identify those patients at high risk for long LOS and to allocate them to special treatments, with the aim of optimizing their hospital management. Methods: This was a cross-sectional study recruiting adult patients with a diagnosis of bipolar disorder (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) criteria) who had been hospitalized due to an acute manic episode with a Young Mania Rating Scale total score greater than 20. Bivariate correlational and multiple linear regression analyses were performed to identify independent predictors of LOS. Results: A total of 235 patients from 44 centers were included in the study. The only factors that were significantly associated to LOS in the regression model were the number of previous episodes and the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at admission (P < 0.05). Conclusions: Patients with a high number of previous episodes and those with depressive symptoms during mania are more likely to stay longer in hospital. Patients with severe depressive symptoms may have a more severe or treatment-resistant course of the acute bipolar manic episode.

Age-dependent decrease in glutamine synthetase expression in the hippocampal astroglia of the triple transgenic Alzheimer's disease mouse model : mechanism for deficient glutamatergic transmission?

Astrocytes are fundamental for brain homeostasis and the progression and outcome of many neuropathologies including Alzheimer's disease (AD). In the triple transgenic mouse model of AD (3xTg-AD) generalised hippocampal astroglia atrophy precedes a restricted and specific beta-amyloid (A beta) plaque-related astrogliosis. Astrocytes are critical for CNS glutamatergic transmission being the principal elements of glutamate homeostasis through maintaining its synthesis, uptake and turnover via glutamate-glutamine shuttle. Glutamine synthetase (GS), which is specifically expressed in astrocytes, forms glutamine by an ATP-dependent amination of glutamate. Here, we report changes in GS astrocytic expression in two major cognitive areas of the hippocampus (the dentate gyrus, DG and the CA1) in 3xTg-AD animals aged between 9 and 18 months. We found a significant reduction in Nv (number of cell/mm(3)) of GS immunoreactive (GS-IR) astrocytes starting from 12 months (28.59%) of age in the DG, and sustained at 18 months (31.65%). CA1 decrease of GS-positive astrocytes Nv (33.26%) occurs at 18 months. This Nv reduction of GSIR astrocytes is paralleled by a decrease in overall GS expression (determined by its optical density) that becomes significant at 18 months (21.61% and 19.68% in DG and CA1, respectively). GS-IR Nv changes are directly associated with the presence of A beta deposits showing a decrease of 47.92% as opposed to 23.47% in areas free of A beta. These changes in GS containing astrocytes and GS-immunoreactivity indicate AD-related impairments of glutamate homeostatic system, at the advanced and late stages of the disease, which may affect the efficacy of glutamatergic transmission in the diseased brain that may contribute to the cognitive deficiency.

[R_SanMillan_Yuso] Documentación geométrica de las excavaciones arqueológicas realizadas en el Monasterio de Yuso (San Millán de la Cogolla, La Rioja)

[ES] El seguimiento arqueológico se realiza sobre las capillas del la nave Norte de la iglesia más la capilla “de las reliquias”, en total 9 capillas de unos 10 x 10 metros cada una. Los elementos a documentar son las unidades estratigráficas exhumadas que, en gran medida corresponden a enterramientos (fosas y los propios esqueletos).

[G_Oñati_Arantzazu] Documentación fotográfica del Apostolado y la Piedad del exterior del Monasterio de Arantzazu (Oñati, Gipuzkoa)

[ES] Conjunto de figuras en piedra de gran porte (unos 4 metros de altura cada una), lo componen 14 figuras en la zona baja del apostolado y un conjunto de 2 personajes más formando la Piedad en la parte superior. Se trata de formas esquemáticas de perfil redondeado que corresponden artísticamente a una de las corrientes más destacadas del siglo XX.

[S_Ambrona_Insitu] Levantamiento fotogramétrico del yacimiento paleontológico “Museo in situ” de Ambrona (Soria)

[ES] Se trata de un área cubierta de unos 8 x 8 metros (la altura del techo es de unos 2,5 metros en la zona más baja) en la que se disponen varios huesos de diferentes especies entre los que destacan, por su porte, varios colmillos de elefante.

[B_Muskiz_Muñatones] Documentación geométrica de la muralla interior del Castillo de Muñatones (Muskiz, Bizkaia)

[ES] Este proyecto corresponde a una continuación del que documenta la torre central y que se realizó en 2005. Dicho trabajo puede consultarse también es este repositorio:

El autoconcepto social y el rendimiento académico en la educación artística escolar del alumnado preadolescente

[EN] This correlational study aims to analyse the relationship of the social dimension of the selfconcept with age, educational level, sex and with the academic performance, understood as qualification and as artistic understanding of a group of primary and secondary students. The results show, generally, negative relationship between social self-concept and demographic variables, while statistically significant, although of opposite sign, of the social self-concept with the qualification in the field and with the artistic understanding respectively.

[A_Vitoria_Mariturri] Registro fotogramétrico de la cisterna del yacimiento arqueológico de Mariturri (Vitoria-Gasteiz, Álava)

[ES] Yacimiento arqueológico a las afueras de la ciudad de Vitora-Gasteiz que han sido afectadas por la urbanización de Zabalgana. Se trata de restos muy arrasados de varios edificios de los que sólo se conserva su interpretación en planta aunque excepcionalmente se conserva algún alzado.

[R_Villoslada_Eras] Generación de una ortoimagen de las eras de Villoslada de Cameros (La Rioja)

[ES] Se trata de una explanada de unos 150 x 50 metros a las afueras del pueblo que antiguamente formaba un conjunto de eras empedradas (círculos de unos 20 metros de diámetro) de las cuales dos se han descubierto.

La internacionalización de la empresa manufacturera española: Efectos del capital humano genérico y específico

[ES] La eficiencia y capacidad competitiva de las organizaciones depende —además de otros factores— de la calidad del capital humano de que disponen. Así, el objetivo de este trabajo es analizar el efecto del capital humano de la empresa tanto en la decisión de entrar en los mercados internacionales como en la intensidad de ventas realizadas en dichos mercados utilizando modelos de regresión logit y tobit. El trabajo empírico se realiza sobre una muestra de empresas manufactureras españolas. El capital humano se evalúa desde una doble óptica, por un lado se considera la formación genérica de los empleados y por otro lado la formación específica de los mismos. Los resultados muestran que la formación genérica y la específica tienen un efecto positivo y significativo tanto sobre la decisión de entrar en los mercados internacionales como en la intensidad de ventas realizadas en dichos mercados.

Comportamiento de las empresas respecto a la formación contínua de sus directivos

Este trabajo ha sido previamente presentado en las XVII Jornadas Luso-Espanholas de Gestao Científica, celebradas en Evora (Portugal) en febrero de 2006.

Un marco para la evaluación de los factores críticos en el proceso de adopción de I+D externa

[ES] En el entorno actual, la obtención de innovaciones en la gestión, en el producto y en el proceso, resulta una herramienta competitiva fundamental para las empresas. Éstas, para garantizarse fuentes de innovación, deben recurrir a mecanismos de captación y generación de conocimiento. Un mecanismo fundamental a este respecto es la captación de conocimientos del exterior, en especial los de tipo científico y tecnológico.

The Metabolic Core and Catalytic Switches Are Fundamental Elements in the Self-Regulation of the Systemic Metabolic Structure of Cells

19 p.