Modulation of Fas receptor proteins and dynamin during opiate addiction and induction of opiate withdrawal in rat brain

The Fas receptor is involved in the regulation of apoptosis but also can function as a non-apoptotic signal transducer. This study was mainly designed to quantitate Fas proteins in rat brain during heroin addiction and opiate withdrawal. In rat, mouse and human brains, and in SH-SY5Y cells, similar forms of Fas were immunodetected with different antibodies (i.e., 35kDa native Fas and 48- and 51-kDa glycosylated Fas). Acute (2h) treatments with the μ-opioid receptor agonists heroin (10mg/kg) and morphine (30mg/kg) increased the immunodensity of native Fas (124% and 36%) but not that of glycosylated Fas in the cerebral cortex. Chronic (5days) heroin (5-30mg/kg) and morphine (10-100mg/kg) were also associated with increased native Fas (76% and 45%) and with different expressions of glycosylated Fas. In heroin-dependent rats, opiate withdrawal (48h) resulted in a sustained increase in native Fas (107%) and in up-regulation of 51kDa glycosylated Fas (51%). Acute treatments with selective δ-receptor (SNC-80, 10mg/kg) or κ-receptor (U 50488-H, 10mg/kg) agonists did not alter the content of native or glycosylated Fas. Chronic pentazocine (10-80mg/kg, 5days), a mixed opiate drug and σ1 receptor agonist, decreased native (48%) and glycosylated (38-82%) Fas proteins. Similarly, the selective σ1 agonist (+)-SKF 10047 also decreased native Fas (37%) and the effect was blocked by the σ1 antagonist BD 1063. Brain dynamin was up-regulated by acute and/or chronic heroin (30-39%), morphine (47-85%), pentazocine (51%) and heroin withdrawal (74%). The main results indicate that chronic heroin/morphine treatment and heroin withdrawal are associated with up-regulation of 35kDa native Fas (and with different expressions of glycosylated Fas), and also with concomitant increases of dynamin in rat brai

ADBench: benchmarking autonomous driving systems

Driven by the improvements in a variety of domains, autonomous driving is becoming a reality and today, industry aims at moving toward fully autonomous vehicles. High-tech chip manufacturers are designing high-performance and energy-efficient platforms in accordance with safety standard requirements. However, the software used to implement advanced functionalities in autonomous vehicles challenges real-time constraints on those platforms. Hence, there is a clear need for industry-level autonomous driving benchmarks to evaluate platforms and systems. In this paper, we propose ADBench, a benchmarking approach and benchmark suite for state-of-the-art autonomous driving platforms, in accordance with the key modules, structural design and functions of AD systems, building on several industry-level autonomous driving systems. The use of standard benchmarks facilitates the design, verification and validation process of autonomous systems.This work has been partially supported by the Spanish Ministry of Economy and Competitiveness (MINECO) under Grant TIN2015-65316-P, the SuPerCom European Research Council (ERC) project under the European Union’s Horizon 2020 research and innovation programme (Grant Agreement No. 772773), and the HiPEAC Network of Excellence.Peer ReviewedPostprint (author's final draft

Metabolomics and biochemical alterations caused by pleiotrophin in the 6‑hydroxydopamine mouse model of Parkinson’s disease.

Pleiotrophin (PTN) is a cytokine involved in nerve tissue repair processes, neuroinflammation and neuronal survival. PTN expression levels are upregulated in the nigrostriatal pathway of Parkinson’s Disease (PD) patients. We aimed to characterize the dopaminergic injury and glial responses in the nigrostriatal pathway of mice with transgenic Ptn overexpression in the brain (Ptn-Tg) after intrastriatal injection of the catecholaminergic toxic 6-hydroxydopamine (6-OHDA) at a low dose (5 µg). Ten days after surgery, the injection of 6-OHDA induced a significant decrease of the number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra and of the striatal TH contents in Wild type (Wt) mice. In contrast, these effects of 6-OHDA were absent in Ptn-Tg mice. When the striatal Iba1 and GFAP immunoreactivity was studied, no statistical differences were found between vehicle-injected Wt and Ptn-Tg mice. Furthermore, 6-OHDA did not cause robust glial responses neither on Wt or Ptn-Tg mice 10 days after injections. In metabolomics studies, we detected interesting metabolites that significantly discriminate the more injured 6-OHDA-injected Wt striatum and the more protected 6-OHDA-injected Ptn-Tg striatum. Particularly, we detected groups of metabolites, mostly corresponding to phospholipids, whose trends were opposite in both groups. In summary, the data confirm lower 6-OHDA-induced decreases of TH contents in the nigrostriatal pathway of Ptn-Tg mice, suggesting a neuroprotective effect of brain PTN overexpression in this mouse model of PD. New lipid-related PD drug candidates emerge from this study and the data presented here support the increasingly recognized “lipid cascade” in PD.post-print2513 K

Pleiotrophin overexpression regulates amphetamine-induced reward and striatal dopaminergic denervation without changing the expression of dopamine D1 and D2 receptors: Implications for neuroinflammation.

It was previously shown that mice with genetic deletion of the neurotrophic factor pleiotrophin (PTN-/-) show enhanced amphetamine neurotoxicity and impair extinction of amphetamine conditioned place preference (CPP), suggesting a modulatory role of PTN in amphetamine neurotoxicity and reward. We have now studied the effects of amphetamine (10mg/kg, 4 times, every 2h) in the striatum of mice with transgenic PTN overexpression (PTN-Tg) in the brain and in wild type (WT) mice. Amphetamine caused an enhanced loss of striatal dopaminergic terminals, together with a highly significant aggravation of amphetamine-induced increase in the number of GFAP-positive astrocytes, in the striatum of PTN-Tg mice compared to WT mice. Given the known contribution of D1 and D2 dopamine receptors to the neurotoxic effects of amphetamine, we also performed quantitative receptor autoradiography of both receptors in the brains of PTN-Tg and WT mice. D1 and D2 receptors binding in the striatum and other regions of interest was not altered by genotype or treatment. Finally, we found that amphetamine CPP was significantly reduced in PTN-Tg mice. The data demonstrate that PTN overexpression in the brain blocks the conditioning effects of amphetamine and enhances the characteristic striatal dopaminergic denervation caused by this drug. These results indicate for the first time deleterious effects of PTN in vivo by mechanisms that are probably independent of changes in the expression of D1 and D2 dopamine receptors. The data also suggest that PTN-induced neuroinflammation could be involved in the enhanced neurotoxic effects of amphetamine in the striatum of PTN-Tg mice

Transcriptional Changes Common to Human Cocaine, Cannabis and Phencyclidine Abuse

A major goal of drug abuse research is to identify and understand drug-induced changes in brain function that are common to many or all drugs of abuse. As these may underlie drug dependence and addiction, the purpose of the present study was to examine if different drugs of abuse effect changes in gene expression that converge in common molecular pathways. Microarray analysis was employed to assay brain gene expression in postmortem anterior prefrontal cortex (aPFC) from 42 human cocaine, cannabis and/or phencyclidine abuse cases and 30 control cases, which were characterized by toxicology and drug abuse history. Common transcriptional changes were demonstrated for a majority of drug abuse cases (N = 34), representing a number of consistently changed functional classes: Calmodulin-related transcripts (CALM1, CALM2, CAMK2B) were decreased, while transcripts related to cholesterol biosynthesis and trafficking (FDFT1, APOL2, SCARB1), and Golgi/endoplasmic reticulum (ER) functions (SEMA3B, GCC1) were all increased. Quantitative PCR validated decreases in calmodulin 2 (CALM2) mRNA and increases in apolipoprotein L, 2 (APOL2) and semaphorin 3B (SEMA3B) mRNA for individual cases. A comparison between control cases with and without cardiovascular disease and elevated body mass index indicated that these changes were not due to general cellular and metabolic stress, but appeared specific to the use of drugs. Therefore, humans who abused cocaine, cannabis and/or phencyclidine share a decrease in transcription of calmodulin-related genes and increased transcription related to lipid/cholesterol and Golgi/ER function. These changes represent common molecular features of drug abuse, which may underlie changes in synaptic function and plasticity that could have important ramifications for decision-making capabilities in drug abusers

Development of Proteomics-Based Fungicides: New Strategies for Environmentally Friendly Control of Fungal Plant Diseases

Proteomics has become one of the most relevant high-throughput technologies. Several approaches have been used for studying, for example, tumor development, biomarker discovery, or microbiology. In this “post-genomic” era, the relevance of these studies has been highlighted as the phenotypes determined by the proteins and not by the genotypes encoding them that is responsible for the final phenotypes. One of the most interesting outcomes of these technologies is the design of new drugs, due to the discovery of new disease factors that may be candidates for new therapeutic targets. To our knowledge, no commercial fungicides have been developed from targeted molecular research, this review will shed some light on future prospects. We will summarize previous research efforts and discuss future innovations, focused on the fight against one of the main agents causing a devastating crops disease, fungal phytopathogens

Modulation et mécanismes régulateurs du récepteur [mu]-opioïde, des voies de signalisation associées et des neurofilaments dans l'addiction aux opiacés

L'exposition répétée aux opiacés produit des changements des fonctions cérébrales qui peuvent durer un certain temps après l'interruption de l'administration chronique de la drogue. Dans le cortex préfrontal des cerveaux des sujets addicts aux opiacés qui se trouvent dans un état de tolérance/dépendance, le récepteur [mu] ainsi que les protéines régulatrices GRK2/6 et β-arrestine2 sont diminués. La densité de PKA et de CREB n'est pas modifiée dans le même groupe de sujets. Par contre, l'immunoréactivité des ERK1/2 est diminuée chez ces sujets, ainsi que les niveaux du complexe p35/cdk5, dont l'implication est pour la première fois démontrée dans le processus d'addiction aux opiacés. Chez ces mêmes sujets, il existe une diminution des formes non-phosphorylées des neurofilaments accompagnée d'une hyperphosphorylation de ces protéines. Les résultats présentés dans ce travail de thèse indiquent que les opiacés peuvent induire des adaptations et des modifications neuronales importantes dans le cerveau humain

Aula de innovación educativa

Resumen basado en el de la publicaciónTítulo, resumen, palabras clave en español e inglesSe describe cómo las maestras de apoyo a la inclusión (pedagogía terapéutica y audición y lenguaje) del CEIP (Colegio de educación Infantil y Primaria) l’Albea situado en la Vall d’Alba (Castellón) han diseñado el Proyecto Conviu : prácticas de educación emocional e inclusiva para la convivencia y el éxito escolar. Gracias al compromiso y la ayuda del equipo directivo y de todo el claustro ha sido posible su implementación, realizando una docencia compartida desde el corazón que permite caminar juntos hacia una escuela inclusiva.Biblioteca del Ministerio de Educación y Formación Profesional; Calle San Agustín, 5; 28014 Madrid; Tel. +34917748000; [email protected]