Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets

<div><p>Thrombin-induced platelet activation requires substantial amounts of ATP. However, the specific contribution of each ATP-generating pathway <i>i</i>.<i>e</i>., oxidative phosphorylation (OxPhos) versus glycolysis and the biochemical mechanisms involved in the thrombin-induced activation of energy metabolism remain unclear. Here we report an integral analysis on the role of both energy pathways in human platelets activated by several agonists, and the signal transducing mechanisms associated with such activation. We found that thrombin, Trap-6, arachidonic acid, collagen, A23187, epinephrine and ADP significantly increased glycolytic flux (3–38 times <i>vs</i>. non-activated platelets) whereas ristocetin was ineffective. OxPhos (33 times) and mitochondrial transmembrane potential (88%) were increased only by thrombin. OxPhos was the main source of ATP in thrombin-activated platelets, whereas in platelets activated by any of the other agonists, glycolysis was the principal ATP supplier. In order to establish the biochemical mechanisms involved in the thrombin-induced OxPhos activation in platelets, several signaling pathways associated with mitochondrial activation were analyzed. Wortmannin and LY294002 (PI3K/Akt pathway inhibitors), ristocetin and heparin (GPIb inhibitors) as well as resveratrol, ATP (calcium-release inhibitors) and PP1 (Tyr-phosphorylation inhibitor) prevented the thrombin-induced platelet activation. These results suggest that thrombin activates OxPhos and glycolysis through GPIb-dependent signaling involving PI3K and Akt activation, calcium mobilization and protein phosphorylation.</p></div

Effects of manipulating slowpoke calcium-dependent potassium channel expression on rhythmic locomotor activity in Drosophila larvae

Rhythmic motor behaviors are generated by networks of neurons. The sequence and timing of muscle contractions depends on both synaptic connections between neurons and the neurons’ intrinsic properties. In particular, motor neuron ion currents may contribute significantly to motor output. Large conductance Ca2+-dependent K+ (BK) currents play a role in action potential repolarization, interspike interval, repetitive and burst firing, burst termination and interburst interval in neurons. Mutations in slowpoke (slo) genes encoding BK channels result in motor disturbances. This study examined the effects of manipulating slo channel expression on rhythmic motor activity using Drosophila larva as a model system. Dual intracellular recordings from adjacent body wall muscles were made during spontaneous crawling-related activity in larvae expressing a slo mutation or a slo RNA interference construct. The incidence and duration of rhythmic activity in slo mutants were similar to wild-type control animals, while the timing of the motor pattern was altered. slo mutants showed decreased burst durations, cycle durations, and quiescence intervals, and increased duty cycles, relative to wild-type. Expressing slo RNAi in identified motor neurons phenocopied many of the effects observed in the mutant, including decreases in quiescence interval and cycle duration. Overall, these results show that altering slo expression in the whole larva, and specifically in motor neurons, changes the frequency of crawling activity. These results suggest an important role for motor neuron intrinsic properties in shaping the timing of motor output

GetME: Investigación en Telefonía Celular Aplicada a Ambientes de Aprendizaje en Comunidades Amplias

La presente investigación, tiene como contexto el proyecto: “Access to High Quality Digital Services and Information for Large Communities of Users”. Como sabemos, en una sociedad global, el acceso al conocimiento y a la información, permitirá a los individuos, organizaciones y países, una ventaja competitiva, para hacerle frente al problema llamado “brecha digital” (digital divide), por lo que es necesario, llevar todos los beneficios de las tecnologías de la información, y servicios digitales a amplias comunidades, haciendo hincapié en comunidades marginales, en las que es difícil el acceso a la información, por la existencia de barreras humanas y tecnológicas (comunicaciones). Se propuso una investigación, referente al uso del Protocolo para Aplicación Inalámbrica (WAP), para la obtención del contenido existente en un ambiente de aprendizaje en Internet, a través de dispositivos móviles (teléfonos celulares, wireless enable devices). El trabajo implico, el estudio referente a la aplicación de esta nueva tecnología, y el cómo puede facilitar al estudiante su trabajo, correspondiente a su interacción en la comunidad y la obtención de información de acuerdo a sus intereses. En esta investigación, se busco desarrollar un módulo de software para la lectura de los mensajes del estudiante, que servirá como apoyo, para futuro software de Interfaz basado en el Protocolo para Aplicación Inalámbrico (WAP), para Ambientes de Aprendizaje a Distancia. Palabras Claves: Ambientes de Aprendizaje, Comunidades Amplias, Dispositivos Móviles, Aprendizaje a Distancia, Servicios Inalámbricos, Tecnología WAP

Synaptic signaling in an active central network only moderately changes passive membrane properties

The membrane resistance of mammalian central neurons may be dramatically reduced by synaptic events during network activity, thereby changing their integration properties. We have used the isolated neonatal rat spinal cord to provide measurements of the effect of synaptic signaling on passive membrane properties during network activity. Synaptic signaling could take place during fictive locomotor activity with only modest (on average 35%) reduction of the input resistance (R(in)) and of the cell’s charging time constant (τ(in)). Individual synaptic signals, however, often introduced a peak conductance that was greater than the input conductance (G(in) = 1/R(in)) without synaptic activity. The combination of moderate average synaptic conductance and large conductance of individual synaptic signals suggests that individual presynaptic neurons have large but short-lasting influence on the integration properties of postsynaptic neurons

La producción de cobre en el mundo y sus rasgos territoriales básicos en México a fines del siglo XX

El presente trabajo tiene como finalidad examinar los rasgos territoriales de la producción cuprífera en México. El cobre es un mineral metálico de amplio uso en la industria moderna, las comunicaciones y otros sectores de la economía. Actualmente, a diferencia de otros metales que aparecen asociados con el cobre, este tiene precios atractivos en el mercado internacional y su producción, en un contexto a la baja en la extracción de otros metales, tiende a sostenerse en el ultimo decenio

Voltage-dependent amplification of synaptic inputs in respiratory motoneurones

The role of persistent inward currents (PICs) in cat respiratory motoneurones (phrenic inspiratory and thoracic expiratory) was investigated by studying the voltage-dependent amplification of central respiratory drive potentials (CRDPs), recorded intracellularly, with action potentials blocked with the local anaesthetic derivative, QX-314. Decerebrate unanaesthetized or barbiturate-anaesthetized preparations were used. In expiratory motoneurones, plateau potentials were observed in the decerebrates, but not under anaesthesia. For phrenic motoneurones, no plateau potentials were observed in either state (except in one motoneurone after the abolition of the respiratory drive by means of a medullary lesion), but all motoneurones showed voltage-dependent amplification of the CRDPs, over a wide range of membrane potentials, too wide to result mainly from PIC activation. The measurements of the amplification were restricted to the phase of excitation, thus excluding the inhibitory phase. Amplification was found to be greatest for the smallest CRDPs in the lowest resistance motoneurones and was reduced or abolished following intracellular injection of the NMDA channel blocker, MK-801. Plateau potentials were readily evoked in non-phrenic cervical motoneurones in the same (decerebrate) preparations. We conclude that the voltage-dependent amplification of synaptic excitation in phrenic motoneurones is mainly the result of NMDA channel modulation rather than the activation of Ca(2+) channel mediated PICs, despite phrenic motoneurones being strongly immunohistochemically labelled for Ca(V)1.3 channels. The differential PIC activation in different motoneurones, all of which are Ca(V)1.3 positive, leads us to postulate that the descending modulation of PICs is more selective than has hitherto been believed