Activity dependent therapies modulate the spinal changes that motoneurons suffer after a peripheral nerve injury

Injury of a peripheral nerve not only leads to target denervation, but also induces massive stripping of spinal synapses on axotomized motoneurons, with disruption of spinal circuits. Even when regeneration is successful, unspecific reinnervation and the limited reconnection of the spinal circuits impair functional recovery. The aim of this study was to describe the changes that axotomized motoneurons suffer after peripheral nerve injury and how activity-dependent therapies and neurotrophic factors can modulate these events. We observed a marked decrease in glutamatergic synapses, with a maximum peak at two weeks post-axotomy, which was only partially reversed with time. This decrease was accompanied by an increase in gephyrin immunoreactivity and a disintegration of perineuronal nets (PNNs) surrounding the motoneurons. Direct application of neurotrophins at the proximal stump was not able to reverse these effects. In contrast, activity-dependent treatment, in the form of treadmill running, reduced the observed destructuring of perineuronal nets and the loss of glutamatergic synapses two weeks after injury. These changes were proportional to the intensity of the exercise protocol. Blockade of sensory inputs from the homolateral hindlimb also reduced PNN immunoreactivity around intact motoneurons, and in that case treadmill running did not reverse that loss, suggesting that the effects of exercise on motoneuron PNN depend on increased sensory activity. Preservation of motoneuron PNN and reduction of synaptic stripping by exercise could facilitate the maintenance of the spinal circuitry and benefit functional recovery after peripheral nerve injury

Análisis de Escalamiento Multidimensional del turismo de los países que conforman la APEC

Tourism has strengthened and has become more important for the economy of the countries, providing them a significant income by the foreign exchange they receive, activating employment generation, besides being an engine of development and contribute to povertyalleviation in the emerging countries. This research tests the hypothesis that the 14 factors of the tourism competitiveness, evaluated by the World Economic Forum determined Mexico´s tourism competitiveness in Asia-Pacific region. Therefore, the aim of this study is to determine the incidence of the 14 factors mentioned before in the tourism competitiveness for 20 APEC countries in 2013. To achieve this objective Multidimensional Scaling Analysis (mds) was used. The results highlighted that cultural resources, environmental sustainability and air transport infrastructure were the competitiveness factors that distinguished effectively from the other factors analyzed in the sample countries. In other words, these factors were identified as the most significant in determining the competitiveness of tourism destinations.El turismo ha cobrado una mayor importancia para la economía de los países al aportarles importantes ingresos por el concepto de divisas recibidas, activar la generación de empleo y contribuir a aminorar la pobreza en los países emergentes, siendo un motor de desarrollo. La investigación parte de la hipótesis de que los catorce factores de la competitividad turística evaluados por el Foro Económico determinaron la competitividad turística de México en la región de Asia-Pacífico. El objetivo del presente trabajo es establecer el grado de influencia de los catorce factores mencionados en la competitividad turística de veinte países que conformaron la APEC para el periodo 2013. Para ello se utilizó el Análisis de Escalamiento Multidimensional. Los recursos culturales, la sustentabilidad ambiental y la infraestructura del transporte aéreo son los factores de la competitividad que se distinguen de manera efectiva

Cisplatin-induced peripheral neuropathy is associated with neuronal senescence-like response

Altres ajuts: Departament de Salut, programa CERCA SLT008/18/00028Cisplatin-induced peripheral neuropathy (CIPN) is a frequent serious dose-dependent adverse event that can determine dosage limitations for cancer treatment. CIPN severity correlates with the amount of platinum detected in sensory neurons of the dorsal root ganglia (DRG). However, the exact pathophysiology of CIPN is poorly understood, so the chance of developing neuroprotective treatment is reduced. The aim of this study was to determine the exact mechanisms involved in CIPN development. Methods: By single-cell RNA-sequencing (scRNAseq), we have studied the transcriptomic profile of DRG sensory neurons from a well-characterized neurophysiological mouse model of CIPN. Results :Gene Ontology analysis of the scRNAseq data indicated that cisplatin treatment induces the upregulation of biological pathways related to DNA damage response (DDR) in the DRG neuronal population. Moreover, DRG neurons also upregulated the Cdkn1a gene, confirmed later by the measurement of its protein product p21. While apoptosis activation pathways were not observed in DRG sensory neurons of cisplatin-treated mice, these neurons did express several senescence hallmarks, including senescence-associated β-galactosidase, phospho-H2AX, and nuclear factor kappa B (Nfkb)-p65 proteins. Conclusions:In this study, we determined that after cisplatin-induced DNA damage, p21 appears as the most relevant downstream factor of the DDR in DRG sensory neurons in vivo, which survive in a nonfunctional senescence-like state

Pharmacogenetic Modulation of STEP improves motor and cognitive function in a mouse model of Huntington's disease.

Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an expansion of a CAG repeat in the huntingtin (htt) gene, which results in an aberrant form of the protein (mhtt). This leads to motor and cognitive deficits associated with corticostriatal and hippocampal alterations. The levels of STriatal-Enriched protein tyrosine Phosphatase (STEP), a neural-specific tyrosine phosphatase that opposes the development of synaptic strengthening, are decreased in the striatum of HD patients and also in R6/1 mice, thereby contributing to the resistance to excitotoxicity described in this HD mouse model. Here, we aimed to analyze whether STEP inactivation plays a role in the pathophysiology of HD by investigating its effect on motor and cognitive impairment in the R6/1 mouse model of HD. We found that genetic deletion of STEP delayed the onset of motor dysfunction and prevented the appearance of cognitive deficits in R6/1 mice. This phenotype was accompanied by an increase in pERK1/2 levels, a delay in the decrease of striatal DARPP-32 levels and a reduction in the size of mhtt aggregates, both in the striatum and CA1 hippocampal region. We also found that acute pharmacological inhibition of STEP with TC-2153 improved cognitive function in R6/1 mice. In conclusion, our results show that deletion of STEP has a beneficial effect on motor coordination and cognition in a mouse model of HD suggesting that STEP inhibition could be a good therapeutic strategy in HD patients

Changes with age (from 0 to 37 D) in tibiae bone mineralization, chemical composition and structural organization in broiler chickens

Broiler chickens have an extreme physiology (rapid growth rates) that challenges the correct bone mineralization, being an interesting animal model for studying the development of bone pathologies. This work studies in detail how the mineralization, chemistry, and structural organization of tibiae bone in broiler chickens change with age during the first 5 wk (37 D) from hatching until acquiring the final weight for slaughter. During the early growth phase (first 2 wk), the rapid addition of bone tissue does not allow for bone organic matrix to fully mineralize and mature, and seems to be a critical period for bone development at which bone mineralization cannot keep pace with the rapid growth of bones. The low degree of bone mineralization and large porosity of cortical bone at this period might be responsible of leg deformation and/or other skeletal abnormalities commonly observed in these birds. Later, cortical bone porosity gradually decreases and the cortical bone became fully mineralized (65%) at 37 D of age. At the same time, bone mineral acquires the composition of mature bone tissue (decreased amount of carbonate, higher crystallinity, Ca/P = 1.68)

Un método nuevo y más sensible para integrar la relación entre distancia y desaturación durante la prueba de la marcha de seis minutos en las enfermedades respiratorias crónicas: correlaciones fisiológicas

Case Report

Traducción y subtitulación de un episodio de ficción científica

El objetivo principal de este trabajo es la traducción y la subtitulación del inglés al castellano de un producto de ficción (serie televisiva) de una duración aproximada de una hora. A partir de una reflexión sobre el proceso de subtitulación y las restricciones del mismo, traduciremos el diálogo y subtitularemos el episodio. Además, añadiremos dos tablas de análisis de los problemas encontrados durante estos procesosL'objectiu principal d'aquest treball és la traducció i la subtitulació de l'anglès a l'espanyol d'un producte de ficció (sèrie de televisió) d'una durada aproximada d'una hora. A partir d'una reflexió sobre el procés de subtitulació i les seves restriccions, traduirem el diàleg i subtitularem l'episodi. A més, afegirem dues taules d'anàlisi dels problemes que hem trobat durant aquests processosThe main objective of this project is the translation and subtitling from English to Spanish of a television series, which has a duration of an hour approximately. To translate the dialogue and subtitle the episode, we will first have a few considerations about the subtitling process and its restrictions. We will also add two tables to analyse the problems we found during the processes of translating and subtitlin

Role of Cyclooxygenase-2 on Intermittent Hypoxia-Induced Lung Tumor Malignancy in a Mouse Model of Sleep Apnea

An adverse role for obstructive sleep apnea (OSA) in cancer epidemiology and outcomes has recently emerged from clinical and animal studies. In animals, intermittent hypoxia (IH) mimicking OSA promotes tumor malignancy both directly and via host immune alterations. We hypothesized that IH could potentiate cancer aggressiveness through activation of the cyclooxygenase-2 (COX-2) pathway and the concomitant increases in prostaglandin E2 (PGE2). The contribution of the COX-2 in IH-induced enhanced tumor malignancy was assessed using celecoxib as a COX-2 specific inhibitor in a murine model of OSA bearing Lewis lung carcinoma (LLC1) tumors. Exposures to IH accelerated tumor progression with a tumor associated macrophages (TAMs) shift towards a pro-tumoral M2 phenotype. Treatment with celecoxib prevented IH-induced adverse tumor outcomes by inhibiting IH-induced M2 polarization of TAMs. Furthermore, TAMs isolated from IH-exposed mice treated with celecoxib reduced the proliferation of LLC1 naïve cells, while the opposite occurred with placebo-treated IH-exposed mice. Finally, in vitro IH exposures of murine macrophages and LLC1 cells showed that both cell types increased PGE2 release in response to IH. These results suggest a crucial role for the COX-2 signaling pathway in the IH-exacerbated malignant processes, and designate macrophages and lung adenocarcinoma cells, as potential sources of PGE2