The impact of Basic Fibroblast Growth Factor on Photoreceptor function and morphology

To assess the impact of basic fibroblast growth factor (bFGF) on photoreceptor function and morphology. METHODS: Impact was assessed in two models. In one, the endogenous expression of bFGF in photoreceptors was raised by sectioning one optic nerve of rats 3 to 4 weeks before study. In the other, bFGF was injected into the vitreous chamber in rats and cats. Retinal function was assessed from the electroretinogram (ERG), and retinal morphology was studied using DNA dyes, immunolabeling, and in situ hybridization. RESULTS: In both models of bFGF upregulation, the ERG b-wave was suppressed over a wide stimulus range and in light- and dark-adapted conditions. The a-wave was not suppressed by either procedure and at the brightest intensities was enhanced by both procedures. In nerve-sectioned eyes, outer retina appeared normal histologically, but levels of bFGF protein in the inner and outer nuclear layers were raised, whereas bFGF mRNA levels remained unchanged. In both models, levels of synaptophysin in the outer plexiform layer and of cytochrome oxidase in inner segments were raised in association with increases in bFGF protein levels. CONCLUSIONS: bFGF increased the ability of photoreceptors to respond to light but attenuated the transmission of this response to inner retinal cells, presumably by blocking the photoreceptor-bipolar synapse. If the expression of bFGF protein is upregulated in human photoreceptor dystrophies, it may contribute a reversible component to the loss of vision. The relationship between these actions of bFGF and its ability to protect photoreceptors from stress remains to be established

Monoclonal antibodies and antibody fragments: state of the art and future perspectives in the treatment of non-haematological tumors

Introduction: The use of monoclonal antibodies is one of the strategies for targeting the specific key points of the main pathways of cancer growth and survival, but only a few antibodies have offered a clear clinical benefit in the treatment of non-haematological malignancies. Areas covered: This review summarizes the general properties of monoclonal antibodies, including structure, nomenclature and production techniques. The antibodies approved for use in clinical practice for the treatment of non-haematological tumors and those antibodies still being developed in this setting are briefly described. The types of antibody fragments are also reported. Expert opinion: Monoclonal antibodies were initially developed in order to avoid the cytotoxic effects of chemotherapy on healthy tissues. However antibodies have not yet replaced chemotherapy agents, since the combination of both kinds of drugs have usually appeared to achieve higher benefit compared with chemotherapy alone. The research for the development of new monoclonal antibodies aims to identify further targets and to provide innovative antibody constructs

Flow synthesis and biological studies of an analgesic adamantane derivative that inhibits P2X7-evoked glutamate release

We report the biological evaluation of a class of adamantane derivatives, which were achieved via modified telescoped machine-assisted flow procedure. Among the series of compounds tested in this work, 5 demonstrated outstanding analgesic properties. This compound showed that its action was not mediated through direct interaction with opioid and/or cannabinoid receptors. Moreover, it did not display any significant anti-inflammatory properties. Experiments carried out on rat cerebrocortical purified synaptosomes indicated that 5 inhibits the P2X7-evoked glutamate release, which may contribute to its antinociceptive properties. Nevertheless, further experiments are ongoing to characterize the pharmacological properties and mechanism of action of this molecule

Mejoras al Proyecto de Seguimiento y Control de Consumo Eléctrico para Artefactos del Hogar

Este proyecto surge de las conclusiones y propuestas de mejoras del proyecto Seguimiento y Control de Consumo Eléctrico para Artefactos del Hogar, Presentado en el VI Congreso de Microelectrónica Aplicada (uEA 2015) desarrollado en la Universidad Nacional de la Matanza, centrado en la conformación de un sistema de monitoreo y control de consumo energético de hogares. Se mantiene el concepto del desarrollo de una red descentralizada de nodos. Debido a ciertas fallas en la transmisión, la tecnología Bluetooth fue reemplazada por una comunicación ZigBee que otorga mayor alcance y efectividad de la red. Dado que la electrónica de consumo masivo no cuenta con conectividad ZigBee, para no perder la capacidad de manejar el dispositivo remotamente se ha desarrollado un equipo de adquisición de datos, capaz de publicar la información mediante un servidor web embebido. Por otra parte, dado que el tamaño era uno de los problemas principales del prototipo anterior, su reducción se logró gracias al perfeccionamiento del módulo de alimentación del equipo, al rediseño de los circuitos y al desarrollo de un gabinete compacto.Fil: Grupo de Investigación y Desarrollo Electrónico (GIDE). Departamento de Ingeniería Electrónica. Universidad Tecnológica Nacional Facultad Regional San Francisco; ArgentinaPeer Reviewe

Seguimiento y control de consumo eléctrico para artefactos del hogar

El aporte de este proyecto está centrado en la conformación de un sistema no sólo basado en el control, sino que considera también poner a disposición del usuario información relevante sobre consumo de energía en un marco temporal, individualizado hacia cada punto de la red, para estudiar las estrategias de control a implementar en aplicaciones que tengan como metas hacer más eficiente la utilización de la energía en los entornos residenciales. El trabajo que se expone forma parte de un proyecto final de Ingeniería Electrónica y consiste en el desarrollo de una red de nodos sensores y actuadores configurables que permitan implementar funciones de control y supervisión de consumo energético de artefactos y dispositivos hogareños. Adicionalmente, para brindar el acceso a la información y a la configuración de los nodos, se realiza una aplicación Android, ya que smartphones y tablets son elementos comunes en el ámbito doméstico. Finalizado el desarrollo del sistema y efectuadas las mediciones podríamos concluir que la red de nodos cumple en principio con los objetivos propuestos en cuanto al alcance de la red y exactitud de los valores medidos y se pretende como paso posterior a futuro reducir el tamaño del prototipo realizado.Fil: Grupo de Investigación y Desarrollo Electrónico - Departamento de Ingeniería Electrónica. Universidad Tecnológica Nacional Facultad Regional San Francisco.Peer Reviewe

Functional characterisation and subcellular localisation of HCN1 channels in rabbit retinal rod photoreceptors

Gating of voltage-dependent conductances in retinal photoreceptors is the first step of a process leading to the enhancement of the temporal performance of the visual system. The molecular components underlying voltage-dependent gating in rods are presently poorly defined. In the present work we have investigated the isoform composition and the functional characteristics of hyperpolarisation-activated cyclic nucleotide-gated channels (HCN) in rabbit rods. Using immunocytochemistry we show the expression in the inner segment and cell body of the isoform I (HCN1). Electrophysiological investigations show that hyperpolarisation-activated currents (I-h) can be measured only from the cell regions where HCN1 is expressed. Half-activation voltage (-75.0 +/- 0.3 mV) and kinetics (t(nu2) of 101 +/- 8 ins at -110 mV and 20degreesC) of the I-h in rods are similar to those of the macroscopic current carried by homomeric rabbit HCN1 channels expressed in HEK 293 cells. The homomeric nature of HCN1 channels in rods is compatible with the observation that cAMP induces a small shift (2.3 +/- 0.8 mV) in the half-activation voltage of I-h. In addition, the observation that within the physiological range of membrane potentials, cAMP does not significantly affect the gain of the current-to-voltage conversion, may reflect the need to protect the first step in the processing of visual signals from changes in cAMP turnover

Vesicular glutamate release from feeder-free hiPSC-derived neurons

Human-induced pluripotent stem cells (hiPSCs) represent one of the main and powerful tools for the in vitro modeling of neurological diseases. Standard hiPSC-based protocols make use of animal-derived feeder systems to better support the neuronal differentiation process. Despite their efficiency, such protocols may not be appropriate to dissect neuronal specific properties or to avoid interspecies contaminations, hindering their future translation into clinical and drug discovery approaches. In this work, we focused on the optimization of a reproducible protocol in feeder-free conditions able to generate functional glutamatergic neurons. This protocol is based on a generation of neuroprecursor cells differentiated into human neurons with the administration in the culture medium of specific neurotrophins in a Geltrex-coated substrate. We confirmed the efficiency of this protocol through molecular analysis (upregulation of neuronal markers and neurotransmitter receptors assessed by gene expression profiling and expression of the neuronal markers at the protein level), morphological analysis, and immunfluorescence detection of pre-synaptic and post-synaptic markers at synaptic boutons. The hiPSC-derived neurons acquired Ca2+-dependent glutamate release properties as a hallmark of neuronal maturation. In conclusion, our study describes a new methodological approach to achieve feeder-free neuronal differentiation from hiPSC and adds a new tool for functional characterization of hiPSC-derived neurons

Heterodimer of A2A and Oxytocin Receptors Regulating Glutamate Release in Adult Striatal Astrocytes

Background: Roles of astrocytes in the modulatory effects of oxytocin (OT) in central nervous system are increasingly considered. Nevertheless, OT effects on gliotransmitter release have been neglected. Methods: In purified astrocyte processes from adult rat striatum, we assessed OT receptor (OTR) and adenosine A2A receptor expression by confocal analysis. The effects of receptors activation on glutamate release from the processes were evaluated; A2A-OTR heteromerization was assessed by co-immunoprecipitation and PLA. Structure of the possible heterodimer of A2A and OT receptors was estimated by a bioinformatic approach. Results: Both A2A and OT receptors were expressed on the same astrocyte processes. Evidence for A2A-OTR receptor-receptor interaction was obtained by measuring the release of glutamate: OT inhibited the evoked glutamate release, while activation of A2A receptors, per se ineffective, abolished the OT effect. Biochemical and bio-physical evidence for A2A-OTR heterodimers on striatal astrocytes was also obtained. The residues in the transmembrane domains 4 and 5 of both receptors are predicted to be mainly involved in the heteromerization. Conclusions: When considering effects of OT in striatum, modulation of glutamate release from the astrocyte processes and of glutamatergic synapse functioning, and the interaction with A2A receptors on the astrocyte processes should be taken into consideration

Sistema de medición con DSP aplicado a un prototipo de ejes levitantes

Este proyecto se deriva como una etapa fundamental de un proyecto más amplio que involucra el desarrollo de un sistema activo de cojinete magnético. Puntualmente, se enfoca en el estudio del elemento de sensado a utilizar y de los pasos requeridos para el acondicionamiento de señal. El estudio realizado involucra un análisis a priori de las condiciones que serán impuestas por el proyecto global de levitación magnética, teniendo como punto de partida la precisión y velocidad a la que debe responder el circuito de sensado, para poder realizar un control efectivo. Como dispositivo sensor se emplean inductancias, que respondan a las variaciones de posición de un material ferromagnético. La unidad de cálculo utiliza un DSP para generar una onda de referencia y para interpretar los datos de medición, con una serie de sub circuitos encargados de adaptar la señal. Luego de realizar las pruebas pertinentes, se concluye de manera favorable, siendo necesario realizar una contrastación rigurosa para verificar la linealidad de la respuesta del dispositivo desarrollado.Fil: Grupo de Investigación y Desarrollo Electrónico - Departamento de Ingeniería Electrónica. Universidad Tecnológica Nacional Facultad Regional San Francisco.Peer Reviewe

Sistema de control PID aplicado a un prototipo de ejes levitantes

A través del presente trabajo se pretende estudiar e investigar distintas estrategias de control a implementar sobre dispositivos de ejes rotantes levitados magnéticamente. El aporte de este proyecto, se centra en desarrollar un modelo de sistema de control que se adecúe a aplicaciones donde se requiera el giro de piezas con mínimo rozamiento. Los alcances de este proyecto se limitan a un eje ubicado de manera horizontal respecto del suelo. Se desarrollará un sistema experimental de ejes rotantes eléctricamente, sin escobillas (es decir con las características de un motor asíncrono del tipo jaula de ardilla), cuyo eje levitará magnéticamente a través de dos cojinetes magnéticos activos. Para poder evaluar su funcionamiento se realizarán simulaciones en computadora mediante el software Matlab/Simulink con el modelo de planta y las distintas estrategias de control (en este trabajo se propone un control clásico mediante un controlador proporcional-integral-derivativo), previamente a las pruebas en el prototipo.Fil: Grupo de Investigación y Desarrollo Electrónico (GIDE). Departamento de Ingeniería Electrónica. Universidad Tecnológica Nacional Facultad Regional San Francisco; ArgentinaPeer Reviewe