Microglial angiotensin type 2 receptors mediate sex-specific expression of inflammatory cytokines independently of circulating estrogen

Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia, Grant/Award Numbers: XUGA, ED431C 2018/10, ED431G/05; Instituto de Salud Carlos III, Grant/Award Numbers: PI20/00385, RD16/0011/0016, CIBERNED; Secretaría de Estado de Investigación, Desarrollo e Innovación, Grant/Award Number: RTI2018-098830-B-I00; Regional European Development Fund (FEDER)There are sex differences in microglia, which can maintain sex-related gene expression and functional differences in the absence of circulating sex steroids. The angiotensin type 2 (AT2) receptors mediate anti-inflammatory actions in different tissues, including brain. In mice, we performed RT-PCR analysis of microglia isolated from adult brains and RNA scope in situ hybridization from males, females, ovariectomized females, orchiectomized males and brain masculinized females. We also compared wild type and AT2 knockout mice. The expression of AT2 receptors in microglial cells showed sex differences with much higher AT2 mRNA expression in females than in males, and this was not dependent on circulating gonadal hormones, as observed using ovariectomized females, brain masculinized females and orchiectomized males. These results suggest genomic reasons, possibly related to sex chromosome complement, for sex differences in AT2 expression in microglia, as the AT2 receptor gene is located in the X chromosome. Furthermore, sex differences in expression of AT2 receptors were associated to sex differences in microglial expression of key anti-inflammatory cytokines such as interleukin-10 and pro-inflammatory cytokines such as interleukin-1β and interleukin-6. In conclusion, sex differences in microglial AT2 receptor expression appear as a major factor contributing to sex differences in the neuroinflammatory responses beyond the effects of circulating steroidsThere are sex differences in microglia, which can maintain sex-related gene expression and functional differences in the absence of circulating sex steroids. The angiotensin type 2 (AT2) receptors mediate anti-inflammatory actions in different tissues, including brain. In mice, we performed RT-PCR analysis of microglia isolated from adult brains and RNA scope in situ hybridization from males, females, ovariectomized females, orchiectomized males and brain masculinized females. We also compared wild type and AT2 knockout mice. The expression of AT2 receptors in microglial cells showed sex differences with much higher AT2 mRNA expression in females than in males, and this was not dependent on circulating gonadal hormones, as observed using ovariectomized females, brain masculinized females and orchiectomized males. These results suggest genomic reasons, possibly related to sex chromosome complement, for sex differences in AT2 expression in microglia, as the AT2 receptor gene is located in the X chromosome. Furthermore, sex differences in expression of AT2 receptors were associated to sex differences in microglial expression of key anti-inflammatory cytokines such as interleukin-10 and pro-inflammatory cytokines such as interleukin-1β and interleukin-6. In conclusion, sex differences in microglial AT2 receptor expression appear as a major factor contributing to sex differences in the neuroinflammatory responses beyond the effects of circulating steroidsS

High-pressure synthesis, structural and complex magnetic properties of the ordered double perovskite Pb2NiReO6

The ordered double perovskite Pb2NiReO6 has been prepared at 6 GPa and temperatures ranging from 1273 to 1373 K. Its crystal structure determined by X-ray powder diffraction and selected area electron diffraction shows monoclinic symmetry with centrosymmetric space group I2/m (a = 5.6021(1) Å, b = 5.6235(1) Å, c = 7.9286(1) Å and β = 90.284°(1)). High angle annular dark field microscopy studies reveal the existence of compositional microdomains. The compound displays a re-entrant spin-glass transition from a ferrimagnetic ordering below TN 37 K between the Re+5 and Ni+3 (high spin configuration) magnetic sublattices to a spin-glass configuration. Magnetic field dependent magnetization measurements revealed wasp-waisted hysteresis loops at 5 K. These shaped features originate from the antiferromagnetic/ferromagnetic (AFM/FM) competing interactions

Human corneal fibroblast migration and ECM synthesis during stromal repair: Role played by PDGF-BB, bFGF, and TGFβ1 (HCFs migration and ECM synthesis during stromal repair: GFs effects)

Producción CientíficaThe development of treatments that modulate corneal wound healing to avoid fibrosis during tissue repair is important for the restoration of corneal transparency after an injury. To date, few studies have studied the influence of growth factors (GFs) on human corneal fibroblast (HCF) expression of extracellular matrix (ECM) proteins such as collagen types I and III, proteoglycans such as perlecan, or proteins implicated in cellular migration such as α5β1-integrin and syndecan-4. Using in vitro HCFs, we developed a mechanical wound model to study the influence of the GFs basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF-BB), and transforming growth factor beta 1 (TGFβ1) on ECM protein production and cellular migration. Our results show that mechanical wounding provokes the autocrine release of bFGF and TGFβ1 at different time points during the wound closure. The HCF response to PDGF-BB was a rapid closure due to fast cellular migration associated with a high focal adhesion replacement and a high expression of collagen and proteoglycans, producing a non-fibrotic healing. bFGF stimulated non-fibrotic ECM production and limited the migration process. Finally, TGFβ1 induced expression of the fibrotic markers collagen type III and α5β1 integrin, and it inhibited cellular migration due to the formation of focal adhesions with a low turnover rate. The novel in vitro HCF mechanical wound model can be used to understand the role played by GFs in human corneal repair. The model can also be used to test the effects of different treatments aimed at improving the healing process

Expression and potential role of apolipoprotein D on the death–survival balance of human colorectal cancer cells under oxidative stress conditions

Producción CientíficaPurpose Inverse correlations of apolipoprotein D (ApoD) expression with tumor growth have been shown, therefore proposing ApoD as a good prognostic marker for diverse cancer types, including colorectal cancer (CRC). Besides, ApoD expression is boosted upon oxidative stress (OS) in many pathological situations. This study aims at understanding the role of ApoD in the progression of human CRC. Methods Samples of CRC and distant normal tissue (n051) were assayed for levels of lipid peroxidation, expression profile of OS-dependent genes, and protein expression. Three single-nucleotide polymorphisms in the ApoD gene were analyzed (n0139), with no significant associations found. Finally, we assayed the effect of ApoD in proliferation and apoptosis in the CRC HT-29 cell line

Direito ao lazer da infância e lazer da família no confinamento: aprendizados e desafios

El objetivo de este trabajo es estudiar la relación entre el ocio y la conciliación de las familias durante el confinamiento, analizando la función desempeñada por las instituciones educativas y los cambios experimentados en el ocio infantil durante la pandemia. Este estudio presenta un carácter exploratorio en el que se utiliza un diseño cualitativo a través de la entrevista en profundidad semiestructurada y se realiza un análisis basado en procesos tanto inductivos como deductivos, mediante el programa para el análisis cualitativo ATLAS.ti. Para la realización del estudio se seleccionó a un grupo de 11 personas expertas (72,7% mujeres) vinculadas al análisis y/o puesta en marcha de servicios de apoyo a las familias y actividades de ocio de la infancia. Los resultados indican que el ocio familiar durante el confinamiento supuso un aumento del tiempo compartido, de la realización de actividades en común y una mejora del conocimiento mutuo, pero también un incremento del uso de pantallas y una mayor conflictividad en la convivencia en las familias con adolescentes. Respecto al ocio de la infancia tras el confinamiento, se detecta una mayor valoración de las actividades al aire libre y en el medio natural y un ocio festivo en grupo más reducidos, pero también un incremento del coste de las actividades y una gran demanda de las familias en cuestiones de apoyo psicológico-emocional a la infancia. La valoración del papel de las instituciones durante la pandemia es negativa, identificándose un sentimiento de abandono de las familias y de las empresas en materia de ocio. Se concluye que durante este periodo tuvieron lugar cambios y aprendizajes en las dinámicas familiares respecto al ocio, lo que nos permite conocer las prioridades y necesidades de las familias abriendo una posible línea de investigación para estudiar si estas modificaciones han venido para quedarseThis paper aims to study the relationship between leisure and family work-life balance during the COVID-19 lockdown, analysing the educational institutions’ role and the changes in children’s leisure experiences during the pandemic. Using the ATLAS.ti software, this exploratory study uses a qualitative design through a semi-structured in-depth interview and an analysis based on inductive and deductive processes. A group of 11 experts (72.7% women) involved in the analysis and/or implementation of family support services and children’s leisure activities were selected for the study. Results show that family leisure during the COVID-19 lockdown involved an increase in time spent together and in shared activities and an improvement in mutual knowledge, but also a rise in screen use and more conflicts in the coexistence of families with adolescents. Concerning children’s leisure time after lockdown, a greater appreciation of outdoor activities and activities in natural settings is detected, as well as festive leisure in smaller groups, but also an increase in the activities’ cost and considerable demand from families of psychological and emotional support for children. Finally, the assessment of institutions’ role during the COVID-19 pandemic was negative, identifying an abandonment feeling by families and companies from the government in leisure. However, it is concluded that during this period, changes and learning took place in leisure family dynamics, which allows us to understand the priorities and needs of families, opening up a possible line of research to study whether these changes are here to stayO objetivo deste trabalho é estudar a relação entre o lazer e a conciliação familiar durante o confinamento, analisando o papel desempenhado pelas instituições de ensino e as mudanças vividas no lazer infantil durante a pandemia. Este estudo apresenta um caráter exploratório em que se utiliza um delineamento qualitativo por meio de entrevista semiestruturada em profundidade e realiza uma análise qualitativa com base em processos indutivos e dedutivos, utilizando o programa ATLAS.ti. Para a realização do estudo, foi selecionado um grupo de 11 especialistas (72,7% mulheres) vinculados à análise e/ou implementação de serviços de apoio às famílias e atividades de lazer para crianças. Os resultados indicam que o lazer familiar durante o confinamento significou um aumento do tempo compartilhado, da realização de atividades em comum e uma melhoria do conhecimento mútuo, mas também um aumento do uso de ecrãs e um maior conflito na convivência em famílias com adolescentes. Em relação ao lazer infantil após o confinamento, consta uma maior valorização das atividades ao ar livre e em ambiente natural, assim como um menor lazer festivo em grupo, mas também um aumento do custo das atividades e uma grande procura das mesmas famílias em matéria de apoio psicológico-emocional para as crianças. A avaliação do papel das instituições durante a pandemia é negativa, identificando-se um sentimento de abandono por parte das famílias e das empresas em termos de lazer. Conclui-se que neste período ocorreram mudanças e aprendizados na dinâmica familiar quanto ao lazer, o que nos permite conhecer as prioridades e as necessidades das famílias, abrindo uma possível linha de pesquisa para estudar se essas modificações vieram para ficarS

Interaction between angiotensin type 1, type 2, and mas receptors to regulate adult neurogenesis in the brain ventricular–subventricular zone

The renin–angiotensin system (RAS), and particularly its angiotensin type-2 receptors (AT2), have been classically involved in processes of cell proliferation and maturation during development. However, the potential role of RAS in adult neurogenesis in the ventricular-subventricular zone (V-SVZ) and its aging-related alterations have not been investigated. In the present study, we analyzed the role of major RAS receptors on neurogenesis in the V-SVZ of adult mice and rats. In mice, we showed that the increase in proliferation of cells in this neurogenic niche was induced by activation of AT2 receptors but depended partially on the AT2-dependent antagonism of AT1 receptor expression, which restricted proliferation. Furthermore, we observed a functional dependence of AT2 receptor actions on Mas receptors. In rats, where the levels of the AT1 relative to those of AT2 receptor are much lower, pharmacological inhibition of the AT1 receptor alone was sufficient in increasing AT2 receptor levels and proliferation in the V-SVZ. Our data revealed that interactions between RAS receptors play a major role in the regulation of V-SVZ neurogenesis, particularly in proliferation, generation of neuroblasts, and migration to the olfactory bulb, both in young and aged brains, and suggest potential beneficial effects of RAS modulators on neurogenesis.This research was funded by Spanish grants from Ministerio de Economía y Competitividad (BFU2015-70523 and SAF2017-86690-R), Instituto de Salud Carlos III (Retic TERCEL RD16/0011/0016, RD16/0011/0017, and CIBERNED), Galician Government (XUGA, ED431C2018/10; ED431G/05), FEDER (Regional European Development Fund), Generalitat Valenciana (Prometeo 2017-030), and Fundación Emilio Botín-Banco SantanderS

Chirp-dependent dual light emission in Na_(0.95)Er_(0.05)Nb_(0.9)Ti_(0.1)O_(3) perovskite

Polar Na_(0.95)Er_(0.05)Nb_(0.9)Ti_(0.1)O_(3) perovskite has been synthesized as a nanostructured material by microwave assisted hydrothermal method. The characterization indicates that erbium is a constituent of the crystal structure and is preferentially located in sodium positions. The compound combines the nonlinear optical properties of the host (NaNb_(0.9)Ti_(0.1)O_(2.95) and the fluorescent properties of the Er^(3+)-dopant. Under excitation by a single femtosecond (< 10 fs) laser in the near-infrared region, simultaneous dual emission signals of second harmonic generation (SHG) and up-converting fluorescence (UCF) are observed and the nonlinear dependencies of the SHG and UCF intensities on the excitation intensity are measured. In addition, both emissions are shown to be sensitive to the chirp of the exciting pulses, and for UCF, it can be explained by means of a simple theoretical model based on the density matrix equations. These nano-structured particles with chirp-dependent dual behavior can be very advantageous when used in biological systems, since they can provide complementary information in different spectral ranges and tissues and are susceptible of coherent control, which can be both useful in optical microscopy and bioimaging

Calendario de vacunaciones de la Asociación Española de Pediatría: recomendaciones 2021

The CAV-AEP annually publishes the immunisation schedule considered optimal for all children and adolescent resident in Spain, taking into account the available evidence. The 2+1 schedule is recommended (2, 4, and 11 months) with hexavalent vaccines (DTPa-VPI-Hib-HB) and with 13-valent pneumococcal conjugate.A 6-year booster is recommended, preferably with DTPa (if available), with a dose of polio for those who received 2+1 schemes, as well as vaccination with Tdpa in adolescents and in each pregnancy, preferably between 27 and 32 weeks. Rotavirus vaccine should be systematic for all infants. Meningococcal B vaccine, with a 2+1 schedule, should be included in routine calendar. In addition to the inclusion of the conjugated tetravalent meningococcal vaccine (MenACWY) at 12 years of age with catch up to 18 years, inclusive, the CAV recommends this vaccine to be also included at 12 months of age, replacing MenC. Likewise, it is recommended in those over 6 weeks of age with risk factors or who travel to countries with a high incidence of these serogroups. Two-dose schedules for triple viral (12 months and 3-4 years) and varicella (15 months and 3-4 years) will be used. The second dose could be applied as a tetraviral vaccine. Universal systematic vaccination against HPV is recommended, regardless of gender, preferably at 12 years, and greater effort should be made to improve coverage. The 9 genotype extends coverage for both genders

Approximate Profile Maximum Likelihood

We propose an efficient algorithm for approximate computation of the profile maximum likelihood (PML), a variant of maximum likelihood maximizing the probability of observing a sufficient statistic rather than the empirical sample. The PML has appealing theoretical properties, but is difficult to compute exactly. Inspired by observations gleaned from exactly solvable cases, we look for an approximate PML solution, which, intuitively, clumps comparably frequent symbols into one symbol. This amounts to lower-bounding a certain matrix permanent by summing over a subgroup of the symmetric group rather than the whole group during the computation. We extensively experiment with the approximate solution, and find the empirical performance of our approach is competitive and sometimes significantly better than state-of-the-art performance for various estimation problems

Recensiones

Óscar Alzaga Villaamil. La conquista de la transición (1960-1978). Memorias documentadas (María Garrote de Marcos) Artemi Rallo Lombarte. Investiduras fallidas y Constitución ignota (Nieves Alonso García) Juan Francisco Sánchez Barrilao. Pluralismo ordinamental y Derecho constitucional: El Derecho como relaciones entre ordenamientos jurídicos (Patricia García Majado) María Salvador Martínez. Partidos políticos. El estatuto constitucional en los partidos y su desarrollo legal (Eva Sáenz Royo) María Garrote De Marcos. El sistema electoral español: memoria, balance y cambio (Carlos Fernández Esquer) María Isabel González Pascual. La salvaguarda de la autonomía política ante las crisis (Andrés Dueñas Castrillo) Ángel Sánchez Navarro y Rosa Fernández Riveira (Dirs.). Reflexiones para una democracia de calidad en una era tecnológica y Jordi Barrat i Esteve y Miguel Pérez Moneo (Eds.). La digitalización de los partidos políticos y el uso del voto electrónico (José Luis Mateos Crespo