Azithromycin inhibits IL-1 secretion and non-canonical inflammasome activation

Deregulation of inflammasome activation was recently identified to be involved in the pathogenesis of various inflammatory diseases. Although macrolide antibiotics display well described immunomodulatory properties, presumably involved in their clinical effects, their impact on inflammasome activation has not been investigated. We compared the influence of macrolides on cytokine induction in human monocytes. The role of intracellular azithromycin- accumulation was examined by interference with Ca++-dependent uptake. We have also analysed the signalling cascades involved in inflammasome activation, and substantiated the findings in a murine sepsis model. Azithromycin, but not clarithromycin or roxithromycin, specifically inhibited IL-1α and IL-1β secretion upon LPS stimulation. Interference with Ca++-dependent uptake abolished the cytokine-modulatory effect, suggesting a role of intracellular azithromycin accumulation in the modulatory role of this macrolide. Azithromycin’s inhibiting effects were observed upon LPS, but not upon flagellin, stimulation. Consistent with this observation, we found impaired induction of the LPS-sensing caspase-4 whereas NF-κB signalling was unaffected. Furthermore, azithromycin specifically affected IL-1β levels in a murine endotoxin sepsis model. We provide the first evidence of a differential impact of macrolides on the inflammasome/IL-1β axis, which may be of relevance in inflammasome-driven diseases such as chronic obstructive pulmonary disease or asthma

Estimación del Producto Bruto Geográfico del Partido de General Pueyrredon: pesca (primario e industria) serie 2004-2012 a precios constantes 2004

Se presentan los resultados de la estimación del valor agregado a precios básicos del sector pesquero: pesca (primario e industria) serie 2004-2012 a precios constantes 2004, necesarios para la estimación del Producto Bruto Geográfico del Partido de General Pueyrredon. Este trabajo se inscribe en el programa de asistencia técnica, a efectos de calcular el Producto Bruto Geográfico del sector pesquero del Partido de General Pueyrredon de la Universidad Nacional de Mar del Plata, en el marco del convenio permanente (vigente con renovación automática) con el INIDEP.Fil: Bertolotti, María Isabel. Universidad Nacional de Mar del Plata. Facultad de Ciencias Económicas y Sociales; Argentina.Fil: Pagani, Andrea N. Universidad Nacional de Mar del Plata. Facultad de Ciencias Económicas y Sociales; Argentina.Fil: Gualdoni, Patricia. Universidad Nacional de Mar del Plata. Facultad de Ciencias Económicas y Sociales; Argentina.Fil: Buono, J. J. Instituto Nacional de Investigación y Desarrollo Pesquero (INIDEP); Argentina

Estimación del Producto Bruto Geográfico del Partido de General Pueyrredon

El producto sectorial pesquero es un indicador económico que permite: * Conocer la importancia relativa de la actividad pesquera; * Establecer la participación del producto pesquero en la Provincia y la Nación; * Comparar la información de distintos períodos. Para el sector pesquero la estimación del Producto Sectorial es el primer estadio para establecer los futuros vínculos con la contabilidad del medio ambiente y los recursos naturales; las Naciones Unidas impulsa el método de la cuenta satélite en la contabilidad ambiental, ya que este método amplía la capacidad analítica de las cuentas nacionales sin sobrecargar el marco central del Sistema de Cuentas Nacionales (Naciones Unidas, 1994). Además la estimación del Producto Bruto Pesquero brinda un marco adecuado para sistematizar indicadores de coyuntura y garantizar su coherencia con un conjunto más amplio de variables económicas (BIRF, 1992). Para estimar los principales indicadores se fragmentó la actividad pesquera en: 1) Sector Primario, que comprende a las actividades extractivas de los recursos naturales y 2) Sector Secundario, que incluye las actividades encargadas de transformar las materias primas (recursos pesqueros).Fil: Bertolotti, María Isabel. Universidad Nacional de Mar del Plata. Facultad de Ciencias Económicas y Sociales; Argentina.Fil: Errazti, Elizabeth. Universidad Nacional de Mar del Plata. Facultad de Ciencias Económicas y Sociales; Argentina.Fil: Pagani, Andrea N. Universidad Nacional de Mar del Plata. Facultad de Ciencias Económicas y Sociales; Argentina.Fil: Gualdoni, Patricia. Universidad Nacional de Mar del Plata. Facultad de Ciencias Económicas y Sociales; Argentina.Fil: Buono, J. J. Instituto Nacional de Investigación y Desarrollo Pesquero (INIDEP); Argentina

Rac1 and Rac3 GTPases Regulate the Development of Hilar Mossy Cells by Affecting the Migration of Their Precursors to the Hilus

We have previously shown that double deletion of the genes for Rac1 and Rac3 GTPases during neuronal development affects late developmental events that perturb the circuitry of the hippocampus, with ensuing epileptic phenotype. These effects include a defect in mossy cells, the major class of excitatory neurons of the hilus. Here, we have addressed the mechanisms that affect the loss of hilar mossy cells in the dorsal hippocampus of mice depleted of the two Rac GTPases. Quantification showed that the loss of mossy cells was evident already at postnatal day 8, soon after these cells become identifiable by a specific marker in the dorsal hilus. Comparative analysis of the hilar region from control and double mutant mice revealed that synaptogenesis was affected in the double mutants, with strongly reduced presynaptic input from dentate granule cells. We found that apoptosis was equally low in the hippocampus of both control and double knockout mice. Labelling with bromodeoxyuridine at embryonic day 12.5 showed no evident difference in the proliferation of neuronal precursors in the hippocampal primordium, while differences in the number of bromodeoxyuridine-labelled cells in the developing hilus revealed a defect in the migration of immature, developing mossy cells in the brain of double knockout mice. Overall, our data show that Rac1 and Rac3 GTPases participate in the normal development of hilar mossy cells, and indicate that they are involved in the regulation of the migration of the mossy cell precursor by preventing their arrival to the dorsal hilus

Promises of stem cell therapy for retinal degenerative diseases

With the development of stem cell technology, stem cell-based therapy for retinal degeneration has been proposed to restore the visual function. Many animal studies and some clinical trials have shown encouraging results of stem cell-based therapy in retinal degenerative diseases. While stem cell-based therapy is a promising strategy to replace damaged retinal cells and ultimately cure retinal degeneration, there are several important challenges which need to be overcome before stem cell technology can be applied widely in clinical settings. In this review, different types of donor cell origins used in retinal treatments, potential target cell types for therapy, methods of stem cell delivery to the eye, assessments of potential risks in stem cell therapy, as well as future developments of retinal stem cells therapy, will be discussed

Cell replacement and visual restoration by retinal sheet transplants

Retinal diseases such as age-related macular degeneration (ARMD) and retinitis pigmentosa (RP) affect millions of people. Replacing lost cells with new cells that connect with the still functional part of the host retina might repair a degenerating retina and restore eyesight to an unknown extent. A unique model, subretinal transplantation of freshly dissected sheets of fetal-derived retinal progenitor cells, combined with its retinal pigment epithelium (RPE), has demonstrated successful results in both animals and humans. Most other approaches are restricted to rescue endogenous retinal cells of the recipient in earlier disease stages by a ‘nursing’ role of the implanted cells and are not aimed at neural retinal cell replacement. Sheet transplants restore lost visual responses in several retinal degeneration models in the superior colliculus (SC) corresponding to the location of the transplant in the retina. They do not simply preserve visual performance – they increase visual responsiveness to light. Restoration of visual responses in the SC can be directly traced to neural cells in the transplant, demonstrating that synaptic connections between transplant and host contribute to the visual improvement. Transplant processes invade the inner plexiform layer of the host retina and form synapses with presumable host cells. In a Phase II trial of RP and ARMD patients, transplants of retina together with its RPE improved visual acuity. In summary, retinal progenitor sheet transplantation provides an excellent model to answer questions about how to repair and restore function of a degenerating retina. Supply of fetal donor tissue will always be limited but the model can set a standard and provide an informative base for optimal cell replacement therapies such as embryonic stem cell (ESC)-derived therapy

An Improved Representation of Measurement Information Content Via the Distribution of the Kullback-Leibler Divergence

Proper utilization of sensor networks is key in target-dense or measurement-scarce environments, such as in the creation and maintenance of reliable records for space objects in Earth orbit. In recent years, there have been many investigations of utilizing different information-theoretic measures as performance measures in allocating sensor tasks to maximize the information gained. More specifically, information divergences have been considered in sensor tasking schemes to effectively and efficiently utilize the available sensor resources. However, it is typical that only the expected information gain with respect to the measurement likelihood is considered, while the rest of the distribution of the divergence in question is disregarded. This work studies the full distribution of the Kullback-Leibler divergence and if the utilization of this knowledge when committing to an action regarding the acquisition of measurement information is beneficial