Gz mediates the long-lasting desensitization of brain CB1 receptors and is essential for cross-tolerance with morphine

Abstract Background Although the systemic administration of cannabinoids produces antinociception, their chronic use leads to analgesic tolerance as well as cross-tolerance to morphine. These effects are mediated by cannabinoids binding to peripheral, spinal and supraspinal CB1 and CB2 receptors, making it difficult to determine the relevance of each receptor type to these phenomena. However, in the brain, the CB1 receptors (CB1Rs) are expressed at high levels in neurons, whereas the expression of CB2Rs is marginal. Thus, CB1Rs mediate the effects of smoked cannabis and are also implicated in emotional behaviors. We have analyzed the production of supraspinal analgesia and the development of tolerance at CB1Rs by the direct injection of a series of cannabinoids into the brain. The influence of the activation of CB1Rs on supraspinal analgesia evoked by morphine was also evaluated. Results Intracerebroventricular (icv) administration of cannabinoid receptor agonists, WIN55,212-2, ACEA or methanandamide, generated a dose-dependent analgesia. Notably, a single administration of these compounds brought about profound analgesic tolerance that lasted for more than 14 days. This decrease in the effect of cannabinoid receptor agonists was not mediated by depletion of CB1Rs or the loss of regulated G proteins, but, nevertheless, it was accompanied by reduced morphine analgesia. On the other hand, acute morphine administration produced tolerance that lasted only 3 days and did not affect the CB1R. We found that both neural mu-opioid receptors (MORs) and CB1Rs interact with the HINT1-RGSZ module, thereby regulating pertussis toxin-insensitive Gz proteins. In mice with reduced levels of these Gz proteins, the CB1R agonists produced no such desensitization or morphine cross-tolerance. On the other hand, experimental enhancement of Gz signaling enabled an acute icv administration of morphine to produce a long-lasting tolerance at MORs that persisted for more than 2 weeks, and it also impaired the analgesic effects of cannabinoids. Conclusion In the brain, cannabinoids can produce analgesic tolerance that is not associated with the loss of surface CB1Rs or their uncoupling from regulated transduction. Neural specific Gz proteins are essential mediators of the analgesic effects of supraspinal CB1R agonists and morphine. These Gz proteins are also responsible for the long-term analgesic tolerance produced by single doses of these agonists, as well as for the cross-tolerance between CB1Rs and MORs.</p

Self- vs. External-Regulation Behavior ScaleTM in different psychological contexts:A validation study

The self- vs. external-regulation behavior theory, SR-ER Theory (2021) model has postulated the Self-Regulation /Non or De-Regulation/Dys-regulation (SR-NR-DR) continuum in the person and in their context. The model also generates a behavioral heuristic that allows us to predict and explain the variability of other dependent behavioral variables in a range of scenarios (clinical, educational, health and technology contexts). Consequently, the objective of this study was to validate the different scales prepared on the basis of the theory presented. A total of 469 students voluntarily completed at different times the five questionnaires presented, to give a total of 1,385 completed questionnaires. Using an ex post facto design, descriptive, correlational, confirmatory factorial analysis (CFA), reliability, and concurrent validity analyses were carried out. The scales were analyzed individually and as a whole. The results showed the acceptable structure of scale and consistent levels of reliability. The five levels generated by the SR-NR-DR (personal and contextual) combinatory heuristic that arises from the theoretical model determined significant differences in the levels of the variables analyzed for each psychological context. We discuss the theoretical implications and the implications for the assessment and improvement of the behaviors analyzed in function of the personal and contextual regulation levels evaluated

Applying the SRL vs. ERL Theory to the Knowledge of Achievement Emotions in Undergraduate University Students

The SRL vs.ERL Theory predicts that a student's own self-regulation and the regulatory nature of the context are factors that jointly determine the student's level of motivational-affective variables. However, this principle has not yet been verified in the case of achievement emotions. The aim of this research was to test this prediction, with the hypothesis that students' level of self-regulation (low-medium-high), in interaction with the regulatory nature of the teaching (low-medium-high), would determine positive or negative emotions as well as the degree of burnout/engagement. A total of 440 university students completed validated questionnaires on self-regulation; regulatory teaching; achievement emotions in class, in study and in testing situations; and on burnout/engagement. Using a quasi-experimental design by selection, ANOVAs and MANOVAs (3 × 3; 5 × 1) were carried out. The results confirmed that the level of self-regulation and the level of external regulation jointly determined university students' level of achievement emotions, as well as their level of burnout/engagement. Based on these results, a five-level progressive scale was configured. We conclude that this scale may be useful and adequate as a heuristic technique or model for understanding and analyzing the type of student-teacher interaction that is taking place in the university classroom, and thereby learn the probability of stressful effects and the students' level of emotional health.Fil: de la Fuente, Jesús. Universidad de Almeria; España. Universidad de Navarra; EspañaFil: Martínez-Vicente, José Manuel. Universidad de Almeria; EspañaFil: Peralta-Sánchez, Francisco Javier. Fundacion Universitaria Konrad Lorenz.; ColombiaFil: Garzón-Umerenkova, Angélica. Fundacion Universitaria Konrad Lorenz.; ColombiaFil: Vera, Manuel Mariano. Universidad de Granada; EspañaFil: Paoloni, Paola Veronica Rita. Universidad Nacional de Rio Cuarto. Instituto de Investigaciones Sociales, Territoriales y Educativas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Sociales, Territoriales y Educativas; Argentin

Histological and histochemical evaluation of human oral mucosa constructs developed by tissue engineering

Reconstruction of large oral mucosa defects is often challenging, since the shortage of healthy oral mucosa to replace the excised tissues is very common. In this context, tissue engineering techniques may provide a source of autologous tissues available for transplant in these patients. In this work, we developed a new model of artificial oral mucosa generated by tissue engineering using a fibrin-agarose scaffold. For that purpose, we generated primary cultures of human oral mucosa fibroblasts and keratinocytes from small biopsies of normal oral mucosa using enzymatic treatments. Then we determined the viability of the cultured cells by electron probe quantitative X-ray microanalysis, and we demonstrated that most of the cells in the primary cultures were alive and had high K/Na ratios. Once cell viability was determined, we used the cultured fibroblasts and keratinocytes to develop an artificial oral mucosa construct by using a fibrin-agarose extracellular matrix and a sequential culture technique using porous culture inserts. Histological analysis of the artificial tissues showed high similarities with normal oral mucosa controls. The epithelium of the oral substitutes had several layers, with desmosomes and apical microvilli and microplicae. Both the controls and the oral mucosa substitutes showed high suprabasal expression of cytokeratin 13 and low expression of cytokeratin 10. All these results suggest that our model of oral mucosa using fibrin-agarose scaffolds show several similarities with native human oral mucosa.This work was supported by the grants FIS 03/0141 and FIS 04/1306 from the Spanish National Ministry of Health (Instituto de Salud Carlos III) and by CM 2005/011 from Junta de Andalucía

Co-planar PET/CT for small animal imaging

Proceeding of: 2005 IEEE Nuclear Science Symposium Conference Record, Puerto Rico, October 23 - 29, 2005A small animal PET/CT system based on a common rotating gantry is proposed. The PET detection subsystem is composed of two detector modules based on MLS arrays and four flat panel type PS PMT. The CT subsystem consists in a micro focus X ray tube and a semiconductor X ray detector. Space for opposed PET detectors and the CT scanner have been allocated on the same plane in such a way that the trans axial and axial centers are common for both systems. Shielding elements have been placed around the detectors to avoid cross modality contamination. The gantry can rotate 370 degrees to provide complete data sets for the CT image reconstruction algorithm that is based on the cone beam geometry. PET image reconstruction is implemented using FBP (2D and 3D) and OSEM. Sequential acquisition protocols minimize the scan duration, and CT information can be used to implement PET imaging corrections. The coplanar configuration of this system provides intrinsically co registered data sets, and it is not necessary to reposition the animal to perform any modality imaging, avoiding undesired animal or additional accessories movements. An additional advantage is the compactness of the system that saves space and allows a direct visual monitoring of the animal during the scanPart of this work is founded by the IM3 network (G03/185 Ministerio de Sanidad), with grants from the Ministerio de Educación y Ciencia, project TEC2004-07052-C02-01, and Ministerio de Industria, Turismo y Comercio project FIT-330101-2004-3. J.J. Vaquero has support from the “Ramón y Cajal” Program, Ministerio de Educación y Cienci

Plan de negocios sistema de gestión de riesgos IOSAFETY

Nuestro plan de negocio fue concebido para cubrir la necesidad que tienen las empresas industriales de velar por el cumplimiento de la seguridad industrial de sus colaboradores, en concordancia con el Decreto Supremo N.° 005-2017-TR. El servicio consistie en un sistema informático distribuido bajo el modelo de Software as a Service (SaaS), es decir, un paquete de software que incluirá múltiples procesos de gestión de riesgos

Development of secretome‑based strategies to improve cell culture protocols in tissue engineering

This study was supported by the Spanish Plan Nacional de Investigación Científica, Desarrollo e Innovación Tec- nológica (I + D + I) of the Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III), grants FIS PI18/0331, FIS PI21/0980, FIS PI18/0332, FIS PI20/0317, ICI19/00024 and ICI21/00010, and by grants PE-0395- 2019 and PI-0442-2019 from the Consejería de Salud y Familias, Junta de Andalucía, Spain. Additional support was provided through grant B-CTS-450-UGR20 (proyectos de I + D + i en el marco del Programa Operativo FEDER Andalucía 2014–2020, University of Granada and Consejería de Transformación Económica, Industria, Conocimiento y Universidades), and cofinancing was provided from the European Regional Development Fund (ERDF) through the “Una manera de hacer Europa” program.The online version contains supplementary material available at https://doi. org/10. 1038/s41598-022-14115-yAdvances in skin tissue engineering have promoted the development of artificial skin substitutes to treat large burns and other major skin loss conditions. However, one of the main drawbacks to bioengineered skin is the need to obtain a large amount of viable epithelial cells in short periods of time, making the skin biofabrication process challenging and slow. Enhancing skin epithelial cell cultures by using mesenchymal stem cells secretome can favor the scalability of manufacturing processes for bioengineered skin. The effects of three different types of secretome derived from human mesenchymal stem cells, e.g. hADSC‑s (adipose cells), hDPSC‑s (dental pulp) and hWJSC‑s (umbilical cord), were evaluated on cultured skin epithelial cells during 24, 48, 72 and 120 h to determine the potential of this product to enhance cell proliferation and improve biofabrication strategies for tissue engineering. Then, secretomes were applied in vivo in preliminary analyses carried out on Wistar rats. Results showed that the use of secretomes derived from mesenchymal stem cells enhanced currently available cell culture protocols. Secretome was associated with increased viability, proliferation and migration of human skin epithelial cells, with hDPSC‑s and hWJSC‑s yielding greater inductive effects than hADSC‑s. Animals treated with hWJSC‑s and especially, hDPSC‑s tended to show enhanced wound healing in vivo with no detectable side effects. Mesenchymal stem cells derived secretomes could be considered as a promising approach to cell‑free therapy able to improve skin wound healing and regeneration.Spanish Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I + D + I) of the Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III) FIS PI18/0331, FIS PI21/0980, FIS PI18/0332, FIS PI20/0317, ICI19/00024, ICI21/00010Junta de Andalucia PE-0395-2019, PI-0442-2019Proyectos de I + D + i en el marco del Programa Operativo FEDER Andalucia , University of Granada and Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades B-CTS-450-UGR20European Commissio

Satisfaction With the Self-Assessment of University Students Through e-Coping With Academic Stress UtilityTM

The general purpose of this report is: (1) research was to check whether the degree of satisfaction with the self-assessment activity of university students was related to the scores obtained and the degree of different variables, associated with level of Self-Regulation; (2) to present the online utility, e-Coping with Academic StressTM, as a technological development in Educational Psychology; (3) analyze the possibilities of transfer of this technological innovation. A total of 929 university students, coming from a public university, participated in the use of this online utility. University students can use the tool’s online inventories to make self-assessments in the different variables of Studying, Learning and Performing under Stress (SLPS Competency Model). Descriptives, correlational and inferential analyzes (ANOVAs and MANOVAs) were carried out. The results allowed to know the profile of competences of the analyzed university students, in addition to the degree of satisfaction with the self-evaluation. Finally, we communicate possible actions and options available for transfer of this resulting technology, through RD transfer contracts arranged directly or with other universities

EMIR, the GTC NIR multi-object imager-spectrograph

EMIR, currently entering into its fabrication and AIV phase, will be one of the first common user instruments for the GTC, the 10 meter telescope under construction by GRANTECAN at the Roque de los Muchachos Observatory (Canary Islands, Spain). EMIR is being built by a Consortium of Spanish and French institutes led by the Instituto de Astrofísica de Canarias (IAC). EMIR is designed to realize one of the central goals of 10m class telescopes, allowing observers to obtain spectra for large numbers of faint sources in a time-efficient manner. EMIR is primarily designed to be operated as a MOS in the K band, but others a wide range of observing modes, including imaging and spectroscopy, both long slit and multi-object, in the wavelength range 0.9 to 2.5 um. It is equipped with two innovative subsystems: a robotic reconfigurable multi-slit mask and dispersive elements formed by the combination of high quality distraction grating and conventional prisms, both at the heart of the instrument. The present status of development, expected performances, schedule and plans for scientific exploitation are described and discussed. The development and fabrication of EMIR is funded by GRANTECAN and the Plan Nacional de Astronomía y Astrofísica (National Plan for Astronomy and Astrophysics, Spain).Peer ReviewedPostprint (published version