Three-dimensional growth as multicellular spheroid activates the proangiogenic phenotype of colorectal carcinoma cells via LFA-1-dependent VEGF: implications on hepatic micrometastasis

Background: The recruitment of vascular stromal and endothelial cells is an early event occurring during cancer cell growth at premetastatic niches, but how the microenvironment created by the initial three-dimensional (3D) growth of cancer cells affects their angiogenesis-stimulating potential is unclear. Methods: The proangiogenic profile of CT26 murine colorectal carcinoma cells was studied in seven-day cultured 3D-spheroids of <300 mu m in diameter, produced by the hanging-drop method to mimic the microenvironment of avascular micrometastases prior to hypoxia occurrence. Results: Spheroid-derived CT26 cells increased vascular endothelial growth factor (VEGF) secretion by 70%, which in turn increased the in vitro migration of primary cultured hepatic sinusoidal endothelium (HSE) cells by 2-fold. More importantly, spheroid-derived CT26 cells increased lymphocyte function associated antigen (LFA)-1-expressing cell fraction by 3-fold; and soluble intercellular adhesion molecule (ICAM)-1, given to spheroid-cultured CT26 cells, further increased VEGF secretion by 90%, via cyclooxygenase (COX)-2-dependent mechanism. Consistent with these findings, CT26 cancer cells significantly increased LFA-1 expression in non-hypoxic avascular micrometastases at their earliest inception within hepatic lobules in vivo; and angiogenesis also markedly increased in both subcutaneous tumors and hepatic metastases produced by spheroid-derived CT26 cells. Conclusion: 3D-growth per se enriched the proangiogenic phenotype of cancer cells growing as multicellular spheroids or as subclinical hepatic micrometastases. The contribution of integrin LFA-1 to VEGF secretion via COX-2 was a micro environmental-related mechanism leading to the pro-angiogenic activation of soluble ICAM-1-activated colorectal carcinoma cells. This mechanism may represent a new target for specific therapeutic strategies designed to block colorectal cancer cell growth at a subclinical micrometastatic stage within the liver.

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.

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.

Las deficiencias formativas en la Educación Superior: El caso de las Ingenierías

[ES] El entorno en el que desarrollan sus actividades las instituciones universitarias está poniendo de manifiesto algunas debilidades en la formación impartida a sus egresados. Entre ellas destaca la falta de adecuación entre las competencias potenciadas por las universidades en sus alumnos y las demandadas por las organizaciones. Ante esta situación, este artículo pretende analizar el estado de la cuestión, concretamente centrándonos en el caso de los ingenieros y para el contexto de la Comunidad Autónoma de Aragón. Para ello, se analizan las opiniones manifestadas, a través de un cuestionario, a un grupo de empleadores.

Repercusión económica de la certificación medioambiental ISO 14001

Este trabajo ha sido realizado bajo el marco de objetivos del Grupo de Investigación de Excelencia CREVALOR reconocido por la Diputación General de Aragón.

Los Recursos Humanos en las Pymes: Análisis empírico de la formación, rotación y estructura de propiedad

[ES] Este trabajo tiene como objetivo presentar los principales resultados de un estudio que pretende acercarse a la realidad de las pequeñas y medianas empresas riojanas, tanto familiares como no familiares, ya que son mayoría abrumadora en la Comunidad. Se ha realizado un análisis descriptivo de algunos aspectos relevantes de la gestión de los recursos humanos como la formación y el desarrollo de sus trabajadores y directivos, la estabilidad laboral y la estructura de propiedad. En el presente trabajo ofrecemos los principales resultados con respecto a estas cuestiones, esbozando una descripción y valoración de estas empresas, así como un perfil de sus percepciones principales en relación a las cuestiones analizadas.

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.

Hago click y opero a tu lado: Estrategia de la banca online en España

[ES] La estrategia de la Banca española con respecto a Internet se ha enmarcado entre la modernización del sector y el miedo a la competencia de terceras partes. En el artículo mostramos como, desde la efervescencia inicial, las entidades se han centrado en construir un negocio rentable parte de una estrategia multicanal. Sin embargo todavía las instituciones españolas no han conseguido aprovechar todas las ventajas que presenta Internet a la hora de facilitar la comercialización de productos financieros.

Caso Grúas Ruiz

Las estrategias competitivas son las posibles líneas de actuación de las que dispone la empresa para competir mejor en mercados determinados, con productos o servicios concretos, de tal forma que se genere una posición competitiva ventajosa para la misma. Aunque la empresa se proponga competir en un mercado provincial o regional, para tener éxito en un contexto global, tiene que combinar dos extremos aparentemente irreconciliables. Por un lado tendrá que «pegarse al terreno» para conocer y aportar valor a sus clientes, mientras que, por otro lado, tendrá que conocer y estar presente en las iniciativas de valor en todos los ámbitos. Desde el punto de vista de sus negocios, la empresa deberá plantear su estrategia competitiva de acuerdo con estas premisas.

Running Pace Decrease during a Marathon Is Positively Related to Blood Markers of Muscle Damage

Background: Completing a marathon is one of the most challenging sports activities, yet the source of running fatigue during this event is not completely understood. The aim of this investigation was to determine the cause(s) of running fatigue during a marathon in warm weather. Methodology/Principal Findings: We recruited 40 amateur runners (34 men and 6 women) for the study. Before the race, body core temperature, body mass, leg muscle power output during a countermovement jump, and blood samples were obtained. During the marathon (27 uC; 27% relative humidity) running fatigue was measured as the pace reduction from the first 5-km to the end of the race. Within 3 min after the marathon, the same pre-exercise variables were obtained. Results: Marathoners reduced their running pace from 3.5 6 0.4 m/s after 5-km to 2.9 6 0.6 m/s at the end of the race (P,0.05), although the running fatigue experienced by the marathoners was uneven. Marathoners with greater running fatigue (. 15% pace reduction) had elevated post-race myoglobin (1318 6 1411 v 623 6 391 mg L21; P,0.05), lactate dehydrogenase (687 6 151 v 583 6 117 U L21; P,0.05), and creatine kinase (564 6 469 v 363 6 158 U L21; P = 0.07) in comparison with marathoners that preserved their running pace reasonably well throughout the race. However, they did not differ in their body mass change (23.1 6 1.0 v 23.0 6 1.0%; P = 0.60) or post-race body temperature (38.7 6 0.7 v 38.9 6 0.9 uC; P = 0.35). Conclusions/Significance: Running pace decline during a marathon was positively related with muscle breakdown blood markers. To elucidate if muscle damage during a marathon is related to mechanistic or metabolic factors requires further investigation.

Dynamics of Streptococcus pneumoniae Serotypes Causing Acute Otitis Media Isolated from Children with Spontaneous Middle-Ear Drainage over a 12-Year Period (1999–2010) in a Region of Northern Spain

10 p.

Inoculation of Triatoma Virus (Dicistroviridae: Cripavirus) elicits a non-infective immune response in mice

Background: Dicistroviridae is a new family of small, non-enveloped, +ssRNA viruses pathogenic to both beneficial arthropods and insect pests. Little is known about the dicistrovirus replication mechanism or gene function, and any knowledge on these subjects comes mainly from comparisons with mammalian viruses from the Picornaviridae family. Due to its peculiar genome organization and characteristics of the per os viral transmission route, dicistroviruses make good candidates for use as biopesticides. Triatoma virus (TrV) is a pathogen of Triatoma infestans (Hemiptera: Reduviidae), one of the main vectors of the human trypanosomiasis disease called Chagas disease. TrV was postulated as a potential control agent against Chagas' vectors. Although there is no evidence that TrV nor other dicistroviruses replicate in species outside the Insecta class, the innocuousness of these viruses in humans and animals needs to be ascertained. Methods: In this study, RT-PCR and ELISA were used to detect the infectivity of this virus in Mus musculus BALB/c mice. Results: In this study we have observed that there is no significant difference in the ratio IgG2a/IgG1 in sera from animals inoculated with TrV when compared with non-inoculated animals or mice inoculated only with non-infective TrV protein capsids. Conclusions: We conclude that, under our experimental conditions, TrV is unable to replicate inmice. This study constitutes the first test to evaluate the infectivity of a dicistrovirus in a vertebrate animal model.

Enhanced Operation of Electricity Distribution Grids Through Smart Metering PLC Network Monitoring, Analysis and Grid Conditioning

Low Voltage (LV) electricity distribution grid operations can be improved through a combination of new smart metering systems' capabilities based on real time Power Line Communications (PLC) and LV grid topology mapping. This paper presents two novel contributions. The first one is a new methodology developed for smart metering PLC network monitoring and analysis. It can be used to obtain relevant information from the grid, thus adding value to existing smart metering deployments and facilitating utility operational activities. A second contribution describes grid conditioning used to obtain LV feeder and phase identification of all connected smart electric meters. Real time availability of such information may help utilities with grid planning, fault location and a more accurate point of supply management.

Pumped double quantum dot with spin-orbit coupling

We study driven by an external electric field quantum orbital and spin dynamics of electron in a one-dimensional double quantum dot with spin-orbit coupling. Two types of external perturbation are considered: a periodic field at the Zeeman frequency and a single half-period pulse. Spin-orbit coupling leads to a nontrivial evolution in the spin and orbital channels and to a strongly spin-dependent probability density distribution. Both the interdot tunneling and the driven motion contribute into the spin evolution. These results can be important for the design of the spin manipulation schemes in semiconductor nanostructures.

Novel Papillomaviruses in Free-Ranging Iberian Bats: No Virus-Host Co-evolution, No Strict Host Specificity, and Hints for Recombination

Papillomaviruses (PVs) are widespread pathogens. However, the extent of PV infections in bats remains largely unknown. This work represents the first comprehensive study of PVs in Iberian bats. We identified four novel PVs in the mucosa of free-ranging Eptesicus serotinus (EserPV1, EserPV2, and EserPV3) and Rhinolophus ferrumequinum (RferPV1) individuals and analyzed their phylogenetic relationships within the viral family. We further assessed their prevalence in different populations of E. serotinus and its close relative E. isabellinus. Although it is frequent to read that PVs co-evolve with their host, that PVs are highly species-specific, and that PVs do not usually recombine, our results suggest otherwise. First, strict virus-host co-evolution is rejected by the existence of five, distantly related bat PV lineages and by the lack of congruence between bats and bat PVs phylogenies. Second, the ability of EserPV2 and EserPV3 to infect two different bat species (E. serotinus and E. isabellinus) argues against strict host specificity. Finally, the description of a second noncoding region in the RferPV1 genome reinforces the view of an increased susceptibility to recombination in the E2-L2 genomic region. These findings prompt the question of whether the prevailing paradigms regarding PVs evolution should be reconsidered.