Mecanismos de neurotoxicidad en el circuito corticoestrial : papel protector del receptor CB1 cannabinoide

Los ganglios basales son una serie de núcleos subcorticales interconectados que incluyen el estriado (caudado y putamen en primates), el globo pálido (segmentos internos y externos), el núcleo subtalámico y la sustancia nigra (pars reticulata y pars compacta). Se trata de un nodo fundamental para muchos procesos conductuales y neurobiológicos como el control afectivo, la actividad motora y las funciones cognitivas. La mayoría (~ 95%) de las neuronas del estriado son neuronas GABAérgicas espinosas medianas (del inglés medium spiny neurons, MSNs), que reciben aferencias glutamatérgicas principalmente de la corteza y el tálamo. Está bien establecido que existen dos poblaciones principales de MSNs: las MSNs de la vía directa, que proyectan principalmente a la sustancia nigra pars reticulata y el globo pálido interno, y expresan receptores de dopamina de tipo 1 (D1R-MSNs), y las MSNs de la vía indirecta, que proyectan principalmente al globo pálido externo y expresan receptores de dopamina de tipo 2 (D2RMSNs). Dada su heterogeneidad neuroquímica y funcional, no es de extrañar que el desequilibrio entre la MSNs de la vía directa e indirecta subyazca a la patogenia de diversos trastornos de los ganglios basales como la enfermedad de Huntington (EH) y la enfermedad de Parkinson (EP). Se han descrito cambios notables en la actividad electrofisiológica de las D1R-MSNs, más que de las D2R-MSNs, en modelos de EH durante diferentes etapas de la enfermedad, lo que sugiere un papel importante de esta población neuronal en el desarrollo y progresión de la patología. Por otra parte, en pacientes y modelos animales de EH se ha observado una pérdida selectiva de D2RMSNs. Muchos modelos conceptuales apoyan la hipótesis de que estas dos poblaciones de MSNs son mecánica y funcionalmente opuestas. Sin embargo, la obtención de evidencias empíricas que demuestren sus funciones ha sido difícil, debido a que ambas poblaciones celulares se encuentran físicamente entremezcladas y son morfológicamente indistinguibles..

Sustained Gq-Protein Signaling Disrupts Striatal Circuits via JNK

International audienceThe dorsal striatum is a major input structure of the basal ganglia and plays a key role in the control of vital processes such as motor behavior, cognition, and motivation. The functionality of striatal neurons is tightly controlled by various metabotropic receptors. Whereas the G s /G i-protein-dependent tuning of striatal neurons is fairly well known, the precise impact and underlying mechanism of G q-protein-dependent signals remain poorly understood. Here, using different experimental approaches, especially designer receptor exclusively activated by designer drug (DREADD) chemogenetic technology, we found that sustained activation of G q-protein signaling impairs the functionality of striatal neurons and we unveil the precise molecular mechanism underlying this process: a phospholipase C/Ca 2ϩ /proline-rich tyrosine kinase 2/cJun N-terminal kinase pathway. Moreover, engagement of this intracellular signaling route was functionally active in the mouse dorsal striatum in vivo, as proven by the disruption of neuronal integrity and behavioral tasks. To analyze this effect anatomically, we manipulated G q-protein-dependent signaling selectively in neurons belonging to the direct or indirect striatal pathway. Acute G q-protein activation in direct-pathway or indirect-pathway neurons produced an enhancement or a decrease, respectively , of activity-dependent parameters. In contrast, sustained G q-protein activation impaired the functionality of direct-pathway and indirect-pathway neurons and disrupted the behavioral performance and electroencephalography-related activity tasks controlled by either anatomical framework. Collectively, these findings define the molecular mechanism and functional relevance of G q-protein-driven signals in striatal circuits under normal and overactivated states

Implementación de un plan de mejoramiento del clima organizacional en la empresa producción y comercializadora huevos de codorniz en el segundo semestre del 2022

Encuesta a empleadosEn el presente trabajo se evidencia un estudio que se le realizó a la empresa “producción y comercialización huevos de codorniz” en el municipio de la Primavera Vichada, su principal objetivo es fortalecer el clima organizacional de la empresa por medio de un análisis interno que permita identificar y establecer las posibles causas que afectan el clima organizacional de la compañía; el método empleado para llevar a cabo este estudio es el deductivo, el cual consiste en la recopilación de información por medio de una encuesta diseñada con 14 preguntas claves para la búsqueda de respuestas, involucra directamente al ambiente y desempeño laboral, motivación y capacitación, comunicación e integración, para llevar a cabo esta actividad se tuvo en cuenta a 10 funcionarios y/o empleados que hacen parte tanto del área administrativa como operativa de la empresa. La herramienta que optamos para la recolección de la información se obtuvo mediante el software Google Drive, ya que facilita la visualización y análisis de resultados, estos fueron presentados mediante graficas con porcentaje, dado en opción de pregunta con cinco opciones de respuestas tales como siempre, casi siempre, algunas veces, nunca y casi nunca. Con la información plasmada se permitió identificar de manera cercana la situación actual de la empresa, donde se realizó el análisis a cada una de ítems expuestos, diseño de una propuesta de mejora, recomendaciones y conclusiones de la actividad desarrollada, lo anterior con el fin de mejorar los puntos con mayor grado de dificultad encontrados dentro de la empresa.In the present work, a study is evidenced that was carried out on the company "Production and commercialization of quail eggs" in the municipality of Primavera Vichada, its main objective is to strengthen the organizational climate of the company through an internal analysis that allows identify and establish the possible causes that affect the organizational climate of the company; the method used to carry out this study is deductive, which consists of collecting information through a survey designed with 14 key questions to search for answers, directly involves the environment and work performance, motivation and training, communication and integration, to carry out this activity, 10 officers and/or employees who are part of both the administrative and operational areas of the company were taken into account. The tool that we chose to collect the information was obtained through the Google Drive software, since it facilitates the visualization and analysis of results, these were presented through graphs with percentages, given in multiple response options such as: yes, no, not so much, always, sometimes, almost never, never. With the information captured, it was possible to closely identify the current situation of the company, where the analysis was carried out on each of the exposed items, design of a proposal for improvement, recommendations and conclusions of the activity carried out, the above to improve the points with the greatest degree of difficulty found within the company

Clinical Study Evaluation of the Success Criteria for Zirconia Dental Implants: A Four-Year Clinical and Radiological Study

Objectives. The aim was to evaluate survival and success rates, soft tissue health, and radiographic marginal bone loss (MBL) of zirconia implants placed in the esthetic and posterior areas of the jaws and in association with multiple or single implant restorations after at least 6 months of definitive restoration. Material and Methods. 35 one-piece zirconium implants were utilized for single or partially edentulous ridges rehabilitation. All implants received immediate temporary restorations and six months after surgery were definitively restored. Every 6 months after implant placement, a clinical-radiographic evaluation was performed. For each radiograph, the measurements of MBL were calculated. Results. The results showed that the mean MBL at 48-month followup was 1.631 mm. The mean MBL during the first year of loading was not more significant for implants placed in the first molar regions than for those positioned in other areas. Moreover, no differences in marginal bone level changes were revealed for multiple and single implants, whereas MBL in the first year was observed to be slightly greater for implants placed in the maxilla than for those placed in the mandible. Conclusion. Zirconia showed a good marginal bone preservation that could be correlated with one-piece morphology and characteristics of zirconia implants

Overexpression of CYB5R3 and NQO1, Two NAD\u3csup\u3e+\u3c/sup\u3e-Producing Enzymes, Mimics Aspects of Caloric Restriction

Calorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH‐dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age‐associated diseases. However, it is unclear whether changes in metabolic homeostasis solely through upregulation of these NADH‐dehydrogenases have a positive impact on health and survival. We generated a mouse that overexpresses both metabolic enzymes leading to phenotypes that resemble aspects of CR including a modest increase in lifespan, greater physical performance, a decrease in chronic inflammation, and, importantly, protection against carcinogenesis, one of the main hallmarks of CR. Furthermore, these animals showed an enhancement of metabolic flexibility and a significant upregulation of the NAD+/sirtuin pathway. The results highlight the importance of these NAD+ producers for the promotion of health and extended lifespan

Violencia de género: tratamiento y prevención

Esta publicación ha sido posible gracias a la V Convocatoria de Ayudas para Proyectos de Cooperación al Desarrollo y Apoyo a la Movilidad de la Universidad Carlos III de Madrid.Introducción / Helena Soleto Muñoz (pp. 11-12). -- Rocío Zafra Espinosa de los Monteros / Situación general de la violencia de género en España (pp. 13-35). -- María Ángeles Carmona / Violencia de género: prevención y abordaje en justicia (pp. 37-50). -- Belén Hernández Moura / Protección de las víctimas de violencia de género en la ley 4/2015 (pp. 51-73). -- Cristina Ruiz López / La denuncia del delito de violencia de género: perspectivas interrelacionadas (pp. 75-101). -- Félix Arias / Aproximación a la violencia de género desde una perspectiva psicológica (pp. 103-130). -- Santiago Madrid Liras / Dinámica y aspectos psicológicos en las relaciones de maltrato: la “tela de araña” (pp. 131-158). -- Emiliano Carretero Morales / Utilidad de los ODR en los casos de violencia de género (pp. 159-190). -- Cómic / Helena Soleto Muñoz, Jessica Jullien de Asís y Andrea Ochaita Calvo (pp. 191-212). -- Los autores (pp. 213)

New thilinear hybrid of hard yellow corn for the Peruvian tropic

El objetivo de este estudio es evaluar y comparar el comportamiento agronómico de cinco híbridos trilineales experimentales de maíz amarillo duro y la variedad Marginal 28T, en ocho localidades del trópico peruano. El experimento se realizó en dos fases: de marzo del 2018 a marzo del 2019 en cuatro parcelas de validación en San Martín y de marzo a diciembre del 2019 en cuatro parcelas de adaptabilidad en San Martín, Pucallpa, Loreto y Amazonas. Las variables evaluadas fueron: altura de planta y mazorca, dimensiones y peso de mazorca, acame de raíz, resistencia a roya y rendimiento (t ha-1). Se aplicó el diseño de bloques completos al azar con análisis combinado y la interacción genotipo x ambiente del rendimiento con el modelo efectos aditivos principales y modelos de interacción multiplicativa. Resultados. El híbrido HTE6 fue superior en diámetro de mazorca (4,66 cm), peso de mazorca (190,76 g), número de hileras por mazorca (14,26), granos por hilera (37,45), peso total de grano (156,21 g) y rendimiento de grano (7,21 t ha-1). HTE6 mostró adaptabilidad superior en Iquitos (9,20 t ha-1) y San Martín (8,10 t ha-1). En la interacción genotipo-ambiente alcanzó 7,18 t ha-1 y fue el más estable en las ocho localidades. Conclusión. De los cinco híbridos evaluados y la variedad Marginal 28T, el HTE6 tuvo el mejor desempeño agronómico y el mayor rendimiento en las ocho localidades evaluadas. Por lo que se consideró el híbrido trilineal para su liberación comercial en regiones del trópico peruan

Generalidades de la farmacovigilancia

A través de los últimos años, el uso de medicamentos se volvió algo cotidiano, por lo mismo se crearon diferentes programas, actividades y procesos, para mitigar aquellos sucesos que atentaban contra la calidad de vida de las personas. Entender la importancia de realizar la una serie de mecanismos que lograran comprobar la efectividad y seguridad de los medicamentos, dio origen a la farmacovigilancia, la cual se encarga de detección, prevención y evaluación de los efectos adversos que se pueden presentar a lo largo del tratamiento farmacológico.Over the last few years, the use of medicines has become a daily occurrence, and different programs, activities and processes have been created to mitigate those events that threaten the quality of life of people. Understanding the importance of carrying out a series of mechanisms to verify the effectiveness and safety of medicines, gave rise to pharmacovigilance, which is responsible for detection, prevention and evaluation of adverse effects that may occur during pharmacological treatment

Programmed 'disarming' of the neutrophil proteome reduces the magnitude of inflammation

The antimicrobial functions of neutrophils are facilitated by a defensive armamentarium of proteins stored in granules, and by the formation of neutrophil extracellular traps (NETs). However, the toxic nature of these structures poses a threat to highly vascularized tissues, such as the lungs. Here, we identified a cell-intrinsic program that modified the neutrophil proteome in the circulation and caused the progressive loss of granule content and reduction of the NET-forming capacity. This program was driven by the receptor CXCR2 and by regulators of circadian cycles. As a consequence, lungs were protected from inflammatory injury at times of day or in mouse mutants in which granule content was low. Changes in the proteome, granule content and NET formation also occurred in human neutrophils, and correlated with the incidence and severity of respiratory distress in pneumonia patients. Our findings unveil a 'disarming' strategy of neutrophils that depletes protein stores to reduce the magnitude of inflammation.We thank members of the Comparative Medicine Unit and Advanced Microscopy Unit at CNIC. This study was supported by Intramural grants from the Severo Ochoa program (IGP-SO), a grant from Fundació La Marató de TV3 (120/C/2015-20153032), grant SAF2015-65607-R from Ministerio de Ciencia, Investigacion y Universidades (MCIU) with cofunding from Fondo Europeo de Desarrollo Regional, grant RTI2018-095497-B-I00 from MCIU and HR17_00527 from Fundación La Caixa (to A.H.), and fellowship BES-2013-065550 from MCIU (to J.M.A.), fellowship from La Caixa Foundation (ID 100010434, code LCF/BQ/DR19/11740022, to A.A.-C.) and fellowship Health-PERIS 2016–2020 (to C.C.) Funds were also obtained from Instituto de Salud Carlos III (FIS PI17/01601, to I.L.) and SAF2015-68632-R from MCIU (to M.A.M.); Wellcome Trust Seed Award in Science (206103/Z/17/Z, to D.R.), SFB1123-A1/A10 from Deutsche Forschungsgemeinschaft and ERC-AdG 692511 (to C.W.); SAF2017-84494-C2-R and Programa Red Guipuzcoana de Ciencia, Tecnología e Información 2018-CIEN-000058-01 (to J.R.-C.). Work at CIC biomaGUNE was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency (MDM-2017-0720). C.W. is a van de Laar professor of atherosclerosis. The CNIC is supported by the MCIU and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505).S

Control of a hippocampal recurrent excitatory circuit by cannabinoid receptor-interacting protein Gap43

The type-1 cannabinoid receptor (CB1R) is widely expressed in excitatory and inhibitory nerve terminals, and by suppressing neurotransmitter release, its activation modulates neural circuits and brain function. While the interaction of CB1R with various intracellular proteins is thought to alter receptor signaling, the identity and role of these proteins are poorly understood.Using a highthroughput proteomic analysis complemented with an array of in vitro and in vivo approaches in the mouse brain, we report that the C-terminal, intracellular domain of CB1R interacts specifically with growth-associated protein of 43 kDa (GAP43). The CB1R-GAP43 interaction occurs selectively at mossy cell axon boutons, which establish excitatory synapses with dentate granule cells in the hippocampus. This interaction impairs CB1R-mediated suppression of mossy cell to granule cell transmission, thereby inhibiting cannabinoidmediated anti-convulsant activity inmice. Thus, GAP43 acts as a synapse typespecific regulatory partner of CB1R that hampers CB1R-mediated effects on hippocampal circuit function