Estradiol Meets Notch Signaling in Developing Neurons

The transmembrane receptor Notch, a master developmental regulator, controls gliogenesis, neurogenesis, and neurite development in the nervous system. Estradiol, acting as a hormonal signal or as a neurosteroid, also regulates these developmental processes. Here we review recent evidence indicating that estradiol and Notch signaling interact in developing hippocampal neurons by a mechanism involving the putative membrane receptor G protein-coupled receptor 30. This interaction is relevant for the control of neuronal differentiation, since the downregulation of Notch signaling by estradiol results in the upregulation of neurogenin 3, which in turn promotes dendritogenesis

Estradiol-dependent axogenesis and Ngn3 expression are determined by XY sex chromosome complement in hypothalamic neurons

Hypothalamic neurons show sex differences in neuritogenesis, female neurons have longer axons and higher levels of the neuritogenic factor neurogenin 3 (Ngn3) than male neurons in vitro. Moreover, the effect of 17-β-estradiol (E2) on axonal growth and Ngn3 expression is only found in male-derived neurons. To investigate whether sex chromosomes regulate these early sex differences in neuritogenesis by regulating the E2 effect on Ngn3, we evaluated the growth and differentiation of hypothalamic neurons derived from the “four core genotypes” mouse model, in which the factors of “gonadal sex” and “sex chromosome complement” are dissociated. We showed that sex differences in neurite outgrowth are determined by sex chromosome complement (XX > XY). Moreover, E2 increased the mRNA expression of Ngn3 and axonal length only in XY neurons. ERα/β expressions are regulated by sex chromosome complement; however, E2-effect on Ngn3 expression in XY neurons was only fully reproduced by PPT, a specific ligand of ERα, and prevented by MPP, a specific antagonist of ERα. Together our data indicate that sex chromosomes regulate early development of hypothalamic neurons by orchestrating not only sex differences in neuritogenesis, but also regulating the effect of E2 on Ngn3 expression through activation of ERα in hypothalamic neurons.Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Mir, Franco Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Scerbo, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Arevalo, María Angeles. Instituto de Salud Carlos Iii (isciii); EspañaFil: García-Segura, Luis Miguel. Instituto de Salud Carlos Iii (isciii); EspañaFil: Cambiasso, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

Relación entre el número y horario de comidas, ingesta energética y de nutrientes y composición corporal en adultos jóvenes

Los adultos jóvenes se someten a cambios bruscos en su alimentación, favoreciendo patrones alimentarios irregulares que podrían afectar su composición corporal. El objetivo del presente trabajo fue determinar la relación entre el número y horario de comidas, ingesta energética y denutrientes y composición corporal en adultos jóvenes. Para ello se aplicó un estudio observacional,cuantitativo, transversal con una muestra consistente en 95 estudiantes universitarios de 18 a 35 años. El análisis de los resultados arrojó que sobre la población del 66,3% mujeres con una edad promedio 22,01 ± 3,31 años; el 40% realizó las 4 comidas principales, el 82,1% había desayunado, el 100% había almorzado, el 78,9% había merendado y el 95,8% había cenado. Se identificó una correlación estadísticamente significativa entre el número de comidas y la ingesta energética; la hora del desayuno y la edad, edad corporal y grasa visceral; la hora de la merienda y la grasa visceral. Se concluye que mantener horarios regulares y número adecuado de ingesta son clavespara el buen desempeño del organismo humano, por lo cual en las recomendaciones nutricionales se debería incluirel horario de las comidas.Young adults undergo abrupt changes in their diet, favoring irregular eating patterns that could affect their body composition. The objective of this study was to determine the relationship between the number and timing of meals, energy and nutrient intake, and body composition in young adults. For this, an observational, quantitative, crosssectional study was applied with a sample consisting of 95 university students between 18 and 35 years of age. The analysis of the results showed that 66.3% of the population were women with an average age of 22.01 ± 3.31 years; 40% had the 4 main meals, 82.1% had breakfast, 100% had lunch, 78.9% had a snack and 95.8% had dinner. A statistically significant correlation was identified between the number of meals and energy intake; breakfast time and age, body age, and visceral fat; snack time and visceral fat. It is concluded that maintaining regular schedules and an adequate number of meals are key to the good performance of the human organism, for which the timing of meals should be included in the nutritional recommendations.Fil: Rodríguez, Yamila Elvira. Universidad de la Cuenca del Plata. Secretaria de Politicas del Conocimiento. Instituto de Investigaciones Científicas (sede Goya); ArgentinaFil: Dietz, Rocio Milagros. Universidad de la Cuenca del Plata. Secretaria de Politicas del Conocimiento. Instituto de Investigaciones Científicas (sede Goya); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Química Básica y Aplicada del Nordeste Argentino. Universidad Nacional del Nordeste. Facultad de Ciencias Exactas Naturales y Agrimensura. Instituto de Química Básica y Aplicada del Nordeste Argentino; ArgentinaFil: Spagnolo, Lorena Cecilia. Universidad de la Cuenca del Plata. Secretaria de Politicas del Conocimiento. Instituto de Investigaciones Científicas (sede Goya); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Arevalo, María de los Angeles. Universidad de la Cuenca del Plata. Secretaria de Politicas del Conocimiento. Instituto de Investigaciones Científicas (sede Goya); ArgentinaFil: Mancuello, Rocío Luján. Universidad de la Cuenca del Plata. Secretaria de Politicas del Conocimiento. Instituto de Investigaciones Científicas (sede Goya); Argentin

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Genetics and Epigenetics of the X and Y Chromosomes in the Sexual Differentiation of the Brain

For many decades to date, neuroendocrinologists have delved into the key contribution of gonadal hormones to the generation of sex differences in the developing brain and the expression of sex-specific physiological and behavioral phenotypes in adulthood. However, it was not until recent years that the role of sex chromosomes in the matter started to be seriously explored and unveiled beyond gonadal determination. Now we know that the divergent evolutionary process suffered by X and Y chromosomes has determined that they now encode mostly dissimilar genetic information and are subject to different epigenetic regulations, characteristics that together contribute to generate sex differences between XX and XY cells/individuals from the zygote throughout life. Here we will review and discuss relevant data showing how particular X- and Y-linked genes and epigenetic mechanisms controlling their expression and inheritance are involved, along with or independently of gonadal hormones, in the generation of sex differences in the brain

Regulation of aromatase expression in the anterior amygdala of the developing mouse brain depends on ERβ and sex chromosome complement

During development sex differences in aromatase expression in limbic regions of mouse brain depend on sex chromosome factors. Genes on the sex chromosomes may affect the hormonal regulation of aromatase expression and this study was undertaken to explore that possibility. Male E15 anterior amygdala neuronal cultures expressed higher levels of aromatase (mRNA and protein) than female cultures. Furthermore, treatment with oestradiol (E2) or dihydrotestosterone (DHT) increased Cyp19a1 expression and aromatase protein levels only in female neuronal cultures. The effect of E2 on aromatase expression was not imitated by oestrogen receptor (ER) α agonist PPT or the GPER agonist G1, but it was fully reproduced by DPN, a specific ligand of ERβ. By contrast, the effect of DHT on aromatase expression was not blocked by the anti-androgen flutamide, but completely abrogated by the ERβ antagonist PHTPP. Experiments using the four core genotype model showed a sex chromosome effect in ERβ expression (XY > XX) and regulation by E2 or DHT (only XX respond) in amygdala neurons. In conclusion, sex chromosome complement governs the hormonal regulation of aromatase expression through activation of ERβ in developing mouse brain.Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Universidad Nacional de Córdoba. Facultad de Odontología; ArgentinaFil: Cabrera Zapata, Lucas Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Arevalo, María Angeles. Instituto de Salud Carlos III; EspañaFil: Garcia Segura, Luis Miguel. Instituto de Salud Carlos III; EspañaFil: Cambiasso, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Universidad Nacional de Córdoba. Facultad de Odontología; Argentin

Gestión del conocimiento y aprendizaje organizacional en the New Commercial Company S.A.S TNCC

La presente investigación tuvo como objetivo determinar los mecanismos de gestión del conocimiento y estrategias de aprendizaje organizacional en una empresa PYME Colombiana del sector construcción. Mediante el uso de técnicas de recolección de información basadas en metodología cualitativa se logró hacer la descripción de la organización a la luz de las diferentes teorías e investigaciones relacionadas tomando como punto de referencia cuatro sub categorías definidas a partir de los dos temas eje de la investigación: conocimiento implícito, conocimiento explicito, intercambio de conocimiento y aprendizaje individual. Se realizó la aplicación de una entrevista semiestructurada y el análisis documental del sistema de gestión de calidad de la compañía; se encontró que la organización no cuenta con un modelo o proceso de gestión del conocimiento, sin embargo otorga alto valor al conocimiento implícito al interior de la organización.The objective of this research was to determine the mechanisms of knowledge management and organizational learning strategies in a Colombian SME company in the construction sector. Through the use of information gathering techniques based on qualitative methodology it was possible to make the description of the organization in light of the different theories and related research taking as reference point four sub categories defined from the two themes of the research: implicit knowledge, explicit knowledge, knowledge exchange and individual learning. The application of a semi-structured interview and the documentary analysis of the company's quality management system was carried out; It was found that the organization does not have a model or process of knowledge management, however, it gives high value to the knowledge implicit within the organizatio

IGF1 gene therapy in middle-aged female rats delays reproductive senescence through its effects on hypothalamic GnRH and kisspeptin neurons

The process of aging is the result of progressive loss of homeostasis and functional body impairment, including the central nervous system, where the hypothalamus plays a key role in regulating aging mechanisms. The consequences of aging include a chronic proinflammatory environment in the hypothalamus that leads to decreased secretion of gonadotropin-releasing hormone (GnRH) and impairs kisspeptin neuron functionality. In this work, we investigated the effect of insulin-like growth factor 1 (IGF1) gene therapy on hypothalamic kisspeptin/GnRH neurons and on microglial cells, that mediate the inflammatory process related with the aging process. The results show that IGF1 rats have higher kisspeptin expression in the anteroventral periventricular (AVPV) nucleus and higher immunoreactivity of GnRH in the arcuate nucleus and median eminence. In addition, IGF1-treated animals exhibit increased numbers of Iba1+ microglial cells and MHCII+/Iba1+ in the AVPV and arcuate nuclei. In conclusion, IGF1 gene therapy maintains kisspeptin production in the AVPV nucleus, induces GnRH release in the median eminence, and alters the number and reactivity of microglial cells in middle-aged female rats. We suggest that IGF1 gene therapy may have a protective effect against reproductive decline.This research was supported in part by grants #PICT13-1119 from the Argentine Agency for the Promotion of Science and Technology and grant PIP0618 from the Argentine Research Council (CONICET) to MJB, grant BFU2017-82754-R from Agencia Estatal de Investigación and CIBERFES to MAA, and grant MHE 200028 from Programa CSIC de Cooperación Científica para el Desarrollo (Programa EMHE-CSIC 2016) to MAA and MJB

Activation of Casein Kinase II and Inhibition of Phosphatase and Tensin Homologue Deleted on Chromosome 10 Phosphatase by Nerve Growth Factor/p75(NTR) Inhibit Glycogen Synthase Kinase-3β and Stimulate Axonal Growth

Axonal elongation and guidance are controlled by extracellular factors such as the neurotrophins. Indeed, nerve growth factor (NGF) seems to promote axon growth through binding to its p75(NTR) receptor and inactivating RhoA. Furthermore, the local inhibition of glycogen synthase kinase (GSK)-3β by NGF also favors microtubule polymerization and axon extension. Inactivation of GSK-3β may be due to the NGF/TrkA-mediated activation of phosphatidylinositol-3 kinase (PI-3 kinase), which increases the levels of phosphatydilinositol 3-phosphate [PI(3)P]. However, we show here that NGF may inactivate GSK-3β through an alternative mechanism. In cultured hippocampal neurons, the capacity of NGF to promote axon elongation is mostly mediated by p75(NTR), and the activation of this pathway leads to the inactivation of GSK-3β. However, the signaling pathway triggered by NGF/p75(NTR) acts through casein kinase II (CK2). NGF/p75(NTR)-activated CK2 phosphorylates the phosphatase and tensin homologue deleted on chromosome 10 (PTEN), thus rendering this phosphatase inactive. Like activation of the PI-3 kinase, PTEN inactivation allows PI(3)P levels to increase, thus favoring GSK-3β inactivation and axon outgrowth. This newly disclosed mechanism may help to extend the repertoire of pharmacological agents that activate CK2 or that inhibit PTEN to stimulate axon regeneration after trauma or disease