A community electrification project: combination of microgrids and household systems fed by wind, PV or micro-hydro energies according to micro-scale resource evaluation and social constraints

When electrifying isolated rural communities, usually standardized solutions have been implemented using the same technology at all the points. However these solutions are not always appropriate to the community and its population. This article aims to describe the technical design of the electrification system of the community of Alto Peru (in the region of Cajamarca, Peru), where the adequate technology was used at each area according to micro-scale resource evaluation and the socioeconomic requirements of the population. Specifically four technologies were implemented: wind microgrids in highlands, a micro-hydro power plant in the presence of a waterfall, a PV microgrid in a group of points sheltered from the wind and individual PV systems in scattered points with low wind potential. This project brought electricity to 58 households, a health center, a school, a church, two restaurants and two shops.Peer ReviewedPostprint (author’s final draft

Implantación de sistema GMAO para planta de fabricación ITC Packaging

[ES] Se realizará la implantación de un sistema GMAO, (Gestión del Mantenimiento Asistido por Ordenador) en una planta de fabricación de inyección de plástico. Esta, está constituida de 28 máquinas inyectoras de plástico, robots, sistemas auxiliares del tipo compresores, climatizadoras, maquinas enfriadoras del circuito del agua de refrigeración, etc. Para ello, se utilizará el software escogido por la empresa PGMwin , el cual no solo se limita a la planificación del mantenimiento de los activos de la empresa, también está diseñado, entre otras funciones, para gestionar los almacenes de recambios de una empresa, la gestión de compras de los mismos, recepción de albaranes y facturas, y un asistente documental para gestionar toda la documentación tanto legal, como de productos químicos, PRL, etc. Se mostrarán todas las fases de la implantación de este sistema en una empresa del calibre de ITC Packaging, desde la formación a los técnicos, a la definición de todas las pautas preventivas, recopilación de información del parque de maquinaria de la empresa, etc. Ademas de las mejoras realizadas por el equipo de implantación del software PGMwin para adaptar el programa a la dinámica de trabajo de ITC Packaging.[EN] This Project will explain the implantation of a CMMS system (Computer Aided Maintenance Management) on a plastic injection manufacturing plant. This factory contains 28 plastic injection machines, robots, auxiliary systems such as air compressors, air conditioning or cooling machines of the cooling water circuit. For this purpose, the software chosen by the company is ¿PGMwin¿, which is not only limited to elaborating a maintenance plan of the company assets, but is also designed, among other functions, to manage the spare part warehouses of a company, the management of their purchases, the receipt of delivery notes and invoices, and a record keeper assistant to manage all the documentation, either legal or related to chemical products or health and safety. Each phase of the implementation of this system in a company of the size of ITC Packaging will be revealed, from training to technicians to the definition of every maintenance task, including the compilation of all the information from the company's machinery fleet, as well as the improvements achieved by the PGMwin software implementation team, aimed to adapt the software to ITC Packaging's work dynamic.Vidal Lillo, R. (2020). Implantación de sistema GMAO para planta de fabricación ITC Packaging. http://hdl.handle.net/10251/147885TFG

Gene regulation in activated microglia by adenosine A3 receptor agonists: a transcriptomics study

Most neurodegenerative disorders, including the two most common, Alzheimer’s disease (AD) and Parkinson’s disease (AD), course with activation of microglia, the resident innate immune cells of the central nervous system. A3 adenosine receptor (A3R) agonists have been proposed to be neuroprotective by regulating the phenotype of activated microglia. RNAseq was performed using samples isolated from lipopolysaccharide/interferon-γ activated microglia treated with 2-Cl-IB-MECA, a selective A3R agonist. The results showed that the number of negatively regulated genes in the presence of 2-Cl-IB-MECA was greater than the number of positively regulated genes. Gene ontology enrichment analysis showed regulation of genes participating in several cell processes, including those involved in immune-related events. Analysis of known and predicted protein-protein interactions showed that Smad3 and Sp1 are transcription factors whose genes are regulated by A3R activation. Under the conditions of cell activation and agonist treatment regimen, 2-Cl-IB-MECA did not lead to any tendency to favor the expression of genes related to neuroprotective microglia (M2). Supplementary Information The online version contains supplementary material available at 10.1007/s11302-022-09916-9. Keywords: Alzheimer’s disease, Parkinson’s disease, Neurodegeneration, Adenosine, Receptors, Microglia, Neuroinflammatio

Ghrelin and Cannabinoid Functional Interactions Mediated by Ghrelin/CB1 Receptor Heteromers That Are Upregulated in the Striatum From Offspring of Mice Under a High-Fat Diet

We have here assessed, using Δ9-tetrahydrocannabinol (Δ9-THC) for comparison, the effect of Δ9-tetrahydrocannabinolic acid (Δ9-THCA) and of Δ9-tetrahydrocannabivarin (Δ9-THCV) that is mediated by human versions of CB1, CB2, and CB1-CB2 receptor functional units, expressed in a heterologous system. Binding to the CB1 and CB2 receptors was addressed in living cells by means of a homogeneous assay. A biphasic competition curve for the binding to the CB2 receptor, was obtained for Δ9-THCV in cells expressing the two receptors. Signaling studies included cAMP level determination, activation of the mitogen-activated protein kinase pathway and ß-arrestin recruitment were performed. The signaling triggered by Δ9-THCA and Δ9-THCV via individual receptors or receptor heteromers disclosed differential bias, i.e. the bias observed using a given phytocannabinoid depended on the receptor (CB1, CB2 or CB1-CB2) and on the compound used as reference to calculate the bias factor (Δ9-THC, a selective agonist or a non-selective agonist). These results are consistent with different binding modes leading to differential functional selectivity depending on the agonist structure, and the state (monomeric or heteromeric) of the cannabinoid receptor. In addition, on studying Gi-coupling we showed that Δ9-THCV and Δ9-THCA and Δ9-THCV were able to revert the effect of a selective CB2 receptor agonist, but only Δ9-THCV, and not Δ9-THCA, reverted the effect of arachidonyl-2'-chloroethylamide (ACEA 100 nM) a selective agonist of the CB1 receptor. Overall, these results indicate that cannabinoids may have a variety of binding modes that results in qualitatively different effects depending on the signaling pathway that is engaged upon cannabinoid receptor activation

Microglial Adenosine Receptors: From Preconditioning to Modulating the M1/M2 Balance in Activated Cells

Neuronal survival depends on the glia, that is, on the astroglial and microglial support. Neurons die and microglia are activated not only in neurodegenerative diseases but also in physiological aging. Activated microglia, once considered harmful, express two main phenotypes: the pro-inflammatory or M1, and the neuroprotective or M2. When neuroinflammation, i.e., microglial activation occurs, it is important to achieve a good M1/M2 balance, i.e., at some point M1 microglia must be skewed into M2 cells to impede chronic inflammation and to afford neuronal survival. G protein-coupled receptors in general and adenosine receptors in particular are potential targets for increasing the number of M2 cells. This article describes the mechanisms underlying microglial activation and analyzes whether these cells exposed to a first damaging event may be ready to be preconditioned to better react to exposure to more damaging events. Adenosine receptors are relevant due to their participation in preconditioning. They can also be overexpressed in activated microglial cells. The potential of adenosine receptors and complexes formed by adenosine receptors and cannabinoids as therapeutic targets to provide microglia-mediated neuroprotection is here discussed. Keywords: neurodegeneration; aging; Parkinson's disease; Alzheimer's disease; neuroprotection; neuronal survival; cannabinoids; receptor heteromer

N-Methyl-D-aspartate (NMDA) and cannabinoid CB2 receptors form functional complexes in cells of the central nervous system: insights into the therapeutic potential of neuronal and microglial NMDA receptors

Background: The cannabinoid CB2 receptor (CB2R), which is a target to afford neuroprotection, and N-methyl-D-aspartate (NMDA) ionotropic glutamate receptors, which are key in mediating excitatory neurotransmission, are expressed in both neurons and glia. As NMDA receptors are the target of current medication in Alzheimer's disease patients and with the aim of finding neuromodulators of their actions that could provide benefits in dementia, we hypothesized that cannabinoids could modulate NMDA function. Methods: Immunocytochemistry was used to analyze the colocalization between CB2 and NMDA receptors; bioluminescence resonance energy transfer was used to detect CB2-NMDA receptor complexes. Calcium and cAMP determination, mitogen-activated protein kinase (MAPK) pathway activation, and label-free assays were performed to characterize signaling in homologous and heterologous systems. Proximity ligation assays were used to quantify CB2-NMDA heteromer expression in mouse primary cultures and in the brain of APPSw/Ind transgenic mice, an Alzheimer's disease model expressing the Indiana and Swedish mutated version of the human amyloid precursor protein (APP). Results: In a heterologous system, we identified CB2-NMDA complexes with a particular heteromer print consisting of impairment by cannabinoids of NMDA receptor function. The print was detected in activated primary microglia treated with lipopolysaccharide and interferon-γ. CB2R activation blunted NMDA receptor-mediated signaling in primary hippocampal neurons from APPSw/Ind mice. Furthermore, imaging studies showed that in brain slices and in primary cells (microglia or neurons) from APPSw/Ind mice, there was a marked overexpression of macromolecular CB2-NMDA receptor complexes thus becoming a tool to modulate excessive glutamate input by cannabinoids. Conclusions: The results indicate a negative cross-talk in CB2-NMDA complexes signaling. The expression of the CB2-NMDA receptor heteromers increases in both microglia and neurons from the APPSw/Ind transgenic mice, compared with levels in samples from age-matched control mice

5-Hydroxytryptamine, Glutamate, and ATP: Much More Than Neurotransmitters

5-hydroxytryptamine (5-HT) is derived from the essential amino acid L-tryptophan. Although the compound has been studied extensively for its neuronal handling and synaptic actions, serotonin 5-HT receptors can be found extra-synaptically and not only in neurons but in many types of mammalian cells, inside and outside the central nervous system (CNS). In sharp contrast, glutamate (Glu) and ATP are better known as metabolism-related molecules, but they also are neurotransmitters, and their receptors are expressed on almost any type of cell inside and outside the nervous system. Whereas 5-hydroxytryptamine and Glu are key regulators of the immune system, ATP actions are more general. 5-hydroxytryptamine, ATP and Glu act through both G protein-coupled receptors (GPCRs), and ionotropic receptors, i.e., ligand gated ion channels. These are the three examples of neurotransmitters whose actions as holistic regulatory molecules are briefly put into perspective here

Similarities and differences upon binding of naturally occurring Δ9-tetrahydrocannabinol-derivatives to cannabinoid CB1 and CB2 receptors.

We have here assessed, using Δ9 -tetrahydrocannabinol (Δ9 -THC) for comparison, the effect of Δ9 -tetrahydrocannabinolic acid (Δ9 -THCA) and of Δ9 -tetrahydrocannabivarin (Δ9-THCV) that is mediated by human versions of CB1, CB2, and CB1-CB2 receptor functional units, expressed in a heterologous system. Binding to the CB1 and CB2 receptors was addressed in living cells by means of a homogeneous assay. A biphasic competition curve for the binding to the CB2 receptor, was obtained for Δ9 -THCV in cells expressing the two receptors. Signaling studies included cAMP level determination, activation of the mitogen-activated protein kinase pathway and ß-arrestin recruitment were performed. The signaling triggered by Δ9 -THCA and Δ9 -THCV via individual receptors or receptor heteromers disclosed differential bias, i.e. the bias observed using a given phytocannabinoid depended on the receptor (CB1, CB2 or CB1-CB2) and on the compound used as reference to calculate the bias factor (Δ9 -THC, a selective agonist or a non-selective agonist). These results are consistent with different binding modes leading to differential functional selectivity depending on the agonist structure, and the state (monomeric or heteromeric) of the cannabinoid receptor. In addition, on studying Gi-coupling we showed that Δ9 -THCV and Δ9 -THCA and Δ9 -THCV were able to revert the effect of a selective CB2 receptor agonist, but only Δ9-THCV, and not Δ9-THCA, reverted the effect of arachidonyl-2′ -chloroethylamide (ACEA 100 nM) a selective agonist of the CB1 receptor. Overall, these results indicate that cannabinoids may have a variety of binding modes that results in qualitatively different effects depending on the signaling pathway that is engaged upon cannabinoid receptor activatio

Adenosine A2A and A3 Receptors Are Able to Interact with Each Other. A Further Piece in the Puzzle of Adenosine Receptor-Mediated Signaling

The aim of this paper was to check the possible interaction of two of the four purinergic P1 receptors, the A2A and the A3. Discovery of the A2A-A3 receptor complex was achieved by means of immunocytochemistry and of bioluminescence resonance energy transfer. The functional properties and heteromer print identification were addressed by combining binding and signaling assays. The physiological role of the novel heteromer is to provide a differential signaling depending on the pre-coupling to signal transduction components and/or on the concentration of the endogenous agonist. The main feature was that the heteromeric context led to a marked decrease of the signaling originating at A3 receptors. Interestingly from a therapeutic point of view, A2A receptor antagonists overrode the blockade, thus allowing A3 receptor-mediated signaling. The A2A-A3 receptor heteromer print was detected in primary cortical neurons. These and previous results suggest that all four adenosine receptors may interact with each other. Therefore, each adenosine receptor could form heteromers with distinct properties, expanding the signaling outputs derived from the binding of adenosine to its cognate receptors

Adenosine A2A receptor antagonists affects NMDA glutamate receptor function. Potential to address neurodegeneration in Alzheimer's disease

(1) Background. N-methyl d-aspartate (NMDA) ionotropic glutamate receptor (NMDAR), which is one of the main targets to combat Alzheimer's disease (AD), is expressed in both neurons and glial cells. The aim of this paper was to assess whether the adenosine A2A receptor (A2AR), which is a target in neurodegeneration, may affect NMDAR functionality. (2) Methods. Immuno-histo/cytochemical, biophysical, biochemical and signaling assays were performed in a heterologous cell expression system and in primary cultures of neurons and microglia (resting and activated) from control and the APPSw,Ind transgenic mice. (3) Results. On the one hand, NMDA and A2A receptors were able to physically interact forming complexes, mainly in microglia. Furthermore, the amount of complexes was markedly enhanced in activated microglia. On the other hand, the interaction resulted in a novel functional entity that displayed a cross-antagonism, that could be useful to prevent the exacerbation of NMDAR function by using A2AR antagonists. Interestingly, the amount of complexes was markedly higher in the hippocampal cells from the APPSw,Ind than from the control mice. In neurons, the number of complexes was lesser, probably due to NMDAR not interacting with the A2AR. However, the activation of the A2AR receptors resulted in higher NMDAR functionality in neurons, probably by indirect mechanisms. (4) Conclusions. A2AR antagonists such as istradefylline, which is already approved for Parkinson's disease (Nouriast® in Japan and Nourianz® in the US), have potential to afford neuroprotection in AD in a synergistic-like fashion. i.e., via both neurons and microglia