Amyloid-beta aggregates cause alterations of astrocytic metabolic phenotype: impact on neuronal viability.

Amyloid-beta (Abeta) peptides play a key role in the pathogenesis of Alzheimer's disease and exert various toxic effects on neurons; however, relatively little is known about their influence on glial cells. Astrocytes play a pivotal role in brain homeostasis, contributing to the regulation of local energy metabolism and oxidative stress defense, two aspects of importance for neuronal viability and function. In the present study, we explored the effects of Abeta peptides on glucose metabolism in cultured astrocytes. Following Abeta(25-35) exposure, we observed an increase in glucose uptake and its various metabolic fates, i.e., glycolysis (coupled to lactate release), tricarboxylic acid cycle, pentose phosphate pathway, and incorporation into glycogen. Abeta increased hydrogen peroxide production as well as glutathione release into the extracellular space without affecting intracellular glutathione content. A causal link between the effects of Abeta on glucose metabolism and its aggregation and internalization into astrocytes through binding to members of the class A scavenger receptor family could be demonstrated. Using astrocyte-neuron cocultures, we observed that the overall modifications of astrocyte metabolism induced by Abeta impair neuronal viability. The effects of the Abeta(25-35) fragment were reproduced by Abeta(1-42) but not by Abeta(1-40). Finally, the phosphoinositide 3-kinase (PI3-kinase) pathway appears to be crucial in these events since both the changes in glucose utilization and the decrease in neuronal viability are prevented by LY294002, a PI3-kinase inhibitor. This set of observations indicates that Abeta aggregation and internalization into astrocytes profoundly alter their metabolic phenotype with deleterious consequences for neuronal viability.

Cell viability and noninvasive in vivo MRI tracking of 3D cell encapsulating self-assembled microcontainers.

Several molecular therapies require the implantation of cells that secrete biotherapeutic molecules and imaging the location and microenvironment of the cellular implant to ascertain its function. We demonstrate noninvasive in vivo magnetic resonance imaging (MRI) of self-assembled microcontainers that are capable of cell encapsulation. Negative contrast was obtained to discern the microcontainer with MRI; positive contrast was obtained in the complete absence of background signal. MRI on a clinical scanner highlights the translational nature of this research. The microcontainers were loaded with cells that were dispersed in an extracellular matrix, and implanted both subcutaneously and in human tumor xenografts in SCID mice. MRI was performed on the implants, and microcontainers retrieved postimplantation showed cell viability both within and proximal to the implant. The microcontainers are characterized by their small size, three dimensionality, controlled porosity, ease of parallel fabrication, chemical and mechanical stability, and noninvasive traceability in vivo.

Cilengitide modulates attachment and viability of human glioma cells, but not sensitivity to irradiation or temozolomide in vitro.

Cilengitide is a cyclic peptide antagonist of integrins alphavbeta3 and alphavbeta5 that is currently being evaluated as a novel therapeutic agent for recurrent and newly diagnosed glioblastoma. Its mode of action is thought to be mainly antiangiogenic but may include direct effects on tumor cells, notably on attachment, migration, invasion, and viability. In this study we found that, at clinically relevant concentrations, cilengitide (1-100 microM) induces detachment in some but not all glioma cell lines, while the effect on cell viability is modest. Detachment induced by cilengitide could not be predicted by the level of expression of the cilengitide target molecules, alphavbeta3 and alphavbeta5, at the cell surface. Glioma cell death induced by cilengitide was associated with the generation of caspase activity, but caspase activity was not required for cell death since ectopic expression of cytokine response modifier (crm)-A or coexposure to the broad-spectrum caspase inhibitor zVAD-fmk was not protective. Moreover, forced expression of the antiapoptotic protein marker Bcl-X(L) or altering the p53 status did not modulate cilengitide-induced cell death. No consistent effects of cilengitide on glioma cell migration or invasiveness were observed in vitro. Preliminary clinical results indicate a preferential benefit from cilengitide added to temozolomide-based radiochemotherapy in patients with O(6)-methylguanine DNA methyltransferase (MGMT) gene promoter methylation. Accordingly, we also examined whether the MGMT status determines glioma cell responses to cilengitide alone or in combination with temozolomide. Neither ectopic expression of MGMT in MGMT-negative cells nor silencing the MGMT gene in MGMT-positive cells altered glioma cell responses to cilengitide alone or to cilengitide in combination with temozolomide. These data suggest that the beneficial clinical effects derived from cilengitide in vivo may arise from altered perfusion, which promotes temozolomide delivery to glioma cells.

El sistema electoral de les Corts Valencianes: orígens i reforma

[cat] Aquest article vol refutar la hipòtesi que els partits decideixen sistemes electorals majoritaris i que decideixen també mantenir-los invariables, sempre que el sistema de partits s"aproximi al bipartidisme i cap dels dos grans partits pugui perdre la seva posició a favor d"un nou competidor. De manera inversa, els sistemes electorals proporcionals són la conseqüència del multipartidisme, en el qual cap partit té opcions de rebre la majoria dels vots. El cas valencià, però, confirma només parcialment la hipòtesi: els partits van aprovar el 1982 regles proporcionals perquè les eleccions dels parlaments autonòmics eren considerades secundàries, no només pel multipartidisme existent aleshores. En canvi, sí que es confirma que el canvi iniciat el 2006 amb la reforma estatutària manté, de moment, l"status quo per no alterar la formació de majories parlamentàries. Encara queda pendent, però, que es modifiqui la Llei Electoral, de la qual depèn quin mínim de vots per entrar a les Corts s"establirà.

Seed viability constants for Eucalyptus grandis

This work aimed to analyse Eucalyptus grandis W.Hill ex Maiden seed behaviour, under controlled deterioration, and to estimate viability equation constants for the species. Seeds were harvested in the growing season of 1999, and the moisture contents were adjusted from 11.3% to a range between 1.2 and 18.1% at 25ºC. The subsamples were sealed into laminate aluminium-foil packets, for storage in incubators at 40, 50 and 65±0.5ºC. The seeds presented orthodox performance, in which the constants for predicting seed longevity of E. grandis were K E = 9.661, C W = 6.467, C H = 0.03498 and C Q = 0.0002330. The usual and inverse relationship between water content and seed longevity was also observed. The lowest moisture content limit for application of the viability equation at 65ºC was 4.9%, estimated under hygroscopic equilibrium with 23% of relative humidity in the storage environment.

Enhanced-reality video fluorescence: a real-time assessment of intestinal viability.

OBJECTIVE: Our aim was to evaluate a fluorescence-based enhanced-reality system to assess intestinal viability in a laparoscopic mesenteric ischemia model. MATERIALS AND METHODS: A small bowel loop was exposed, and 3 to 4 mesenteric vessels were clipped in 6 pigs. Indocyanine green (ICG) was administered intravenously 15 minutes later. The bowel was illuminated with an incoherent light source laparoscope (D-light-P, KarlStorz). The ICG fluorescence signal was analyzed with Ad Hoc imaging software (VR-RENDER), which provides a digital perfusion cartography that was superimposed to the intraoperative laparoscopic image [augmented reality (AR) synthesis]. Five regions of interest (ROIs) were marked under AR guidance (1, 2a-2b, 3a-3b corresponding to the ischemic, marginal, and vascularized zones, respectively). One hour later, capillary blood samples were obtained by puncturing the bowel serosa at the identified ROIs and lactates were measured using the EDGE analyzer. A surgical biopsy of each intestinal ROI was sent for mitochondrial respiratory rate assessment and for metabolites quantification. RESULTS: Mean capillary lactate levels were 3.98 (SD = 1.91) versus 1.05 (SD = 0.46) versus 0.74 (SD = 0.34) mmol/L at ROI 1 versus 2a-2b (P = 0.0001) versus 3a-3b (P = 0.0001), respectively. Mean maximal mitochondrial respiratory rate was 104.4 (±21.58) pmolO2/second/mg at the ROI 1 versus 191.1 ± 14.48 (2b, P = 0.03) versus 180.4 ± 16.71 (3a, P = 0.02) versus 199.2 ± 25.21 (3b, P = 0.02). Alanine, choline, ethanolamine, glucose, lactate, myoinositol, phosphocholine, sylloinositol, and valine showed statistically significant different concentrations between ischemic and nonischemic segments. CONCLUSIONS: Fluorescence-based AR may effectively detect the boundary between the ischemic and the vascularized zones in this experimental model.

Assessing the viability of cryopreserved coconut zygotic embryos by electrolytic conductivity and potassium leaching

The objective of this work was to adapt the application of electrolytic conductivity and potassium leaching tests to assess the viability of cryopreserved embryos of 'Anão Verde do Brasil de Jiqui' (AVeJBr) coconut. The zygotic embryos were excised, sterilized and subjected to four cryoprotectant treatments combined with three incubation times (12, 16 and 20 hours), totaling 12 treatments. The pre-treatment of mature zygotic embryos of AVeJBr coconut using a cryoprotectant with 1.75 mol L-1 of sucrose + 15% glycerol for 12 and 16 hours promoted lower embryo humidity and increased viability in electrolytic conductivity and potassium leaching tests. Samples with ten embryos are sufficient for electrolytic conductivity analysis in cryopreserved or non-cryopreserved AVeJBr coconut zygotic embryos. The 4 to 8 hour imbibition period of the embryos is promising for the electrolytic conductivity analysis of non-cryopreserved mature zygotic embryos of AVeJBr coconut.

Viability of dourado embryos cooled in different cryoprotectant solutions

The objective of this work was to evaluate the effect of different cryoprotectants on the viability of dourado (Salminus brasiliensis) embryos. Ten cryoprotectant solutions were tested. For each solution, 300 embryos were selected at the closing of the blastopore stage, and 300 more embryos were used as a negative control. After cooling (-8ºC for 6 hours), the embryos were rehydrated directly in the incubator until hatching. The best result is obtained with the cryoprotectant solution containing 9% methanol associated with 17% sucrose, resulting in a larvae hatching rate of 67.06%.

La normativa municipal española a mediados del siglo XIX. Espacio electoral y definición social del modelo liberal en Lleida

El análisis y la comparación de las leyes municipales y, más concretamente, de los censos electorales de Lleida en el periodo liberal que abarcó de 1837 a 1853 muestra como se adoptaron diversos modelos electorales en ese momento según fuese el partido que gobernase. Así, cuando lo hicieron los progresistas elaboraron una ley electoral descentralizada y ampliaron el censo de electores hasta llegar a cubrir las capas medias de la sociedad de Lleida, mientras que los moderados, cuando lo hicieron, legislaron para jerarquizar el poder del Estado del centro a las provincias y recortaron el censo hasta dejar a los 250 mayores contribuyentes de la ciudad. El segundo objetivo del estudio ha mostrado la evolución del electorado municipal del municipio a raíz de la abertura liberal que significó el triunfo de la Revolución Burguesa, que propició que los sectores que vivieron una coyuntura económica favorable, principalmente los dedicados al comercio, se situasen en los primeros lugares entre los mayores contribuyentes en detrimento de otros grupos, el campesinado, que permanecían estancados.

El proceso electoral en España y Cataluña según la Constitución de 1812

En el presente trabajo se analiza la normativa electoral y su aplicación incluida en el articulado de la Constitución de 1812. Para ello en primer lugar se estudia el espíritu del proyecto electoral constitucional. Posteriormente se analiza su aplicación en los comicios para elegir las Cortes Ordinarias de 1813 en las dos realidades que contempla: los territorios de la metrópoli y los de ultramar. Analizada la normativa electoral, establecemos el Parlamento teórico resultante y su aplicación real. Finalmente, realizamos un análisis prosopográfico de los diputados elegidos en España y Cataluña, establecemos la morfología del parlamentario tipo y lo comparamos con los resultados de las dos realidades electorales apuntadas.

Proceso electoral y prosopografía de los diputados de las Cortes Extraordinarias de Cádiz (1810-1813)

En el presente trabajo analizamos el proceso de elección de los diputados españoles en las Cortes Extraordinarias de Cádiz (1810-1813), la sociología de estos parlamentarios y su asistencia en el Parlamento. Después de efectuar el análisis observamos en primer lugar que hubo cuatro modalidades de elección de los diputados y que, una vez escogidos, nunca se cubrieron todos los puestos de diputado otorgados. En segundo lugar, detectamos que los diputados elegidos por los diversos entes que participaron en el proceso electoral fueron en su mayoría de condición social acomodada y representativos de la sociedad española, sobresaliendo en número el grupo de diputados eclesiásticos, de leyes y funcionarios.

El enigma del voto étnico o las tribulaciones del movimiento indígena: reflexiones sobre los resultados de la primera vuelta electoral (2006) en las províncias de la sierra (Coyuntura)

Con toda seguridad, uno de los aspectos que más sorprendieron a la opinión pública ecuato" riana de los resultados de la primera vuelta de las elecciones presidenciales de octubre de 2006, fue el triunfo sin paliativos de la candidatura de Gilmar Gutiérrez en las provincias del callejón interandino y el aparente hundimiento del candidato de Pachakutik en escenarios como los de Cañar; Chimborazo, Bolívar, Cotopaxi o lmbabura, otrora verdaderos baluartes del poder de convocatoria del movimiento indígena.

Los diputados catalanes en las Cortes de Cádiz (1810-1813) : proceso electoral y prosopografía

En el presente trabajo pretendemos analizar el proceso de elección de los diputados catalanes que representaron al Principado de Cataluña en las Cortes de Cádiz (1810-1813), la sociología de los parlamentarios y su comportamiento en el Parlamento según la ideología que manifestaron. Para el estudio hemos cruzado, principalmente, los datos del Diccionario Biográfico de los Parlamentarios Españoles (Madrid, 2010) y la documentación del Archivo del Congreso de los Diputados. Tras el análisis del proceso electoral, primero observamos que nunca se cubrieron todos los puestos otorgados a Cataluña. En segundo lugar, los diputados elegidos fueron, en su mayoría, de condición social acomodada, representativos de la sociedad catalana y acordes con sus homónimos españoles, sobresaliendo en número los grupos de diputados eclesiásticos, abogados y nobles. En tercer lugar, a diferencia del caso global español, destacamos que la adscripción política de la representación catalana fue de mayoría realista y se mostró globalmente contraria a la legislación liberal aprobada en Cádiz.