Magnetic Resonance Spectroscopy discriminates the response to microglial stimulation of wild type and Alzheimer's disease models.

Microglia activation has emerged as a potential key factor in the pathogenesis of Alzheimers disease. Metabolite levels assessed by magnetic resonance spectroscopy (MRS) are used as markers of neuroinflammation in neurodegenerative diseases, but how they relate to microglial activation in health and chronic disease is incompletely understood. Using MRS, we monitored the brain metabolic response to lipopolysaccharides (LPS)-induced microglia activation in vivo in a transgenic mouse model of Alzheimers disease (APP/PS1) and healthy controls (wild-type (WT) littermates) over 4 hours. We assessed reactive gliosis by immunohistochemistry and correlated metabolic and histological measures. In WT mice, LPS induced a microglial phenotype consistent with activation, associated with a sustained increase in macromolecule and lipid levels (ML9). This effect was not seen in APP/PS1 mice, where LPS did not lead to a microglial response measured by histology, but induced a late increase in the putative inflammation marker myoinositol (mI) and metabolic changes in total creatine and taurine previously reported to be associated with amyloid load. We argue that ML9 and mI distinguish the response of WT and APP/PS1 mice to immune mediators. Lipid and macromolecule levels may represent a biomarker of activation of healthy microglia, while mI may not be a glial marker

Periconceptional maternal supplement intake and human embryonic growth, development, and birth outcomes:The Rotterdam Periconception Cohort

STUDY QUESTION: Is periconceptional multiple-micronutrient supplement (MMS) use including folic acid (FA) compared to FA use only associated with increased embryonic growth, development, and birth weight in a high-risk population? SUMMARY ANSWER: Women with MMS intake show no significant differences in first-trimester morphological embryo development, but increased first-trimester embryonic growth trajectories and fewer neonates born small for gestational age (SGA), less than the 3rd percentile (&lt;p3), compared to women using only FA. WHAT IS KNOWN ALREADY: Periconceptional maternal FA intake in the general population is associated with increased embryonic and fetal growth, and reduced risks of neural tube defects, other congenital malformations, low birth weight, and neonates born SGA. STUDY DESIGN, SIZE, DURATION: A prospective tertiary hospital-based cohort study (the Rotterdam Periconceptional Cohort) was conducted from January 2010 to December 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 1076 women from the Rotterdam Periconceptional Cohort, before 10 weeks of pregnancy with follow-up until delivery. Embryonic growth was assessed by measurement of crown-rump length (CRL) and embryonic volume (EV), and embryonic morphology was described by Carnegie stages using longitudinal three-dimensional ultrasound scans and virtual reality techniques. Birth outcomes were extracted from medical records. General characteristics and supplement use were extracted from research questionnaires. MAIN RESULTS AND THE ROLE OF CHANCE: This study showed increased embryonic growth trajectories (adjusted models, CRL: β = 0.052, 95% CI 0.012-0.090, EV: β = 0.022, 95% CI 0.002-0.042) in women using MMS compared to those using only FA. Moreover, a 45% reduced risk of a neonate-born SGA (&lt;p3) was shown in women using MMS compared to FA users (adjusted OR = 0.546, 95% CI 0.308, 0.969). Embryonic morphological development (Carnegie stages) and the occurrence of miscarriages did not differ between women using MMS or solely FA. LIMITATIONS, REASONS FOR CAUTION: Following the heterogeneity of the composition and dose of MMS preparations, it is unclear which specific micronutrient, combination, or dose explains the increased embryonic growth trajectory and reduction in risk for SGA. This also hampers the possibility of differentiating between the effects of FA alone or as a component of MMS. WIDER IMPLICATIONS OF THE FINDINGS: Our findings emphasize the importance of periconceptional maternal MMS use as a potential preventative intervention against reduced embryonic growth and neonates born SGA. Therefore, we recommend the periconceptional use of MMS in women at risk of inadequate micronutrient intake. However, awareness of potentially harmful side effects of high doses and combinations of micronutrients is essential, therefore the optimal composition and dose need to be investigated, and careful surveillance is recommended.</p

Extranjeros y diferentes: las formas de la discriminación en la escuela (programa de investigación, docencia y proyección social. inclusión educativa: la mirada en las aulas)

Este proyecto se desarrolla en el marco del Programa de Investigación, Docencia y Proyección Social denominado Inclusión educativa: La mirada en las aulas; y constituye el germen inicial de la articulación de proyectos que aborden lo educativo como espacio para la inclusión social, cultural, económica, política. La investigación ha avanzado en la identificación de ciertas inconsistencias en el discurso de docentes primarios entre una valoración positiva de los alumnos pertenecientes a comunidades extranjeras y una opinión desfavorable hacia la migración en general. Esa inconsistencia se origina en creencias subyacentes sobre el carácter indeseable de las migraciones desde países vecinos, que son compartidas por fracciones importantes de la sociedad en general, no solo de nuestro país sino también en la mayoría de los centros globales de recepción de migrantes. Estas creencias se corporizan en expresiones abiertas de prejuicio hacia extranjeros ante situaciones puntuales, como aumento del desempleo, de la inseguridad, o bien cuando los medios o figuras públicas ponen el tema en agenda. La identificación a través de entrevistas de estas inconsistencias llevó al diseño de un instrumento estándar para evaluar de manera sistemática las actitudes de los docentes primarios de Córdoba hacia los extranjeros y sus comunidades de pertenencia. Aunque se dispone de una escala que evalúa prejuicio latente y manifiesto (Pettigrew y Meertens, 1995), se trata de un instrumento que aún está en discusión (Espelt, Javaloy y Cornejo, 2006) y que no se adecúa completamente a nuestros interrogantes, por lo que se decidió construir una escala original dirigida a medir aspectos del prejuicio hacia los migrantes, tanto en términos generales como el ámbito de la escuela. Durante el año 2011, ese instrumento fue construido y validado en una muestra de 115 docentes, se observó su estructura factorial (Bologna, Faas y Ergo, 2011) y se alcanzó la versión definitiva. Actualmente (noviembre 2011) se está desarrollando el operativo de campo, que consiste en aplicar un cuestionario que, además de la escala diseñada, incluye ítems sobre creencias acerca de la migración actual hacia Argentina y una pregunta que distingue posiciones más próximas a valores materialistas o postmaterialistas. Esta última pregunta permite comparaciones con otros estudios internacionales, como la encuesta mundial de valores (http://www.worldvaluessurvey.org/). Ademas, el estudio indaga por la existencia de alumnos pertenecientes a comunidades extranjeras y de acciones específicas que la escuela desarrolle. Se ha completado el trabajo de campo en escuelas privadas y se está desarrollando en este momento en provinciales y municipales

Altered expression of immune-associated genes in first-trimester human decidua of pregnancies later complicated with hypertension or foetal growth restriction

During pregnancy the maternal immune system has to coordinate uterine spiral-artery remodelling, trophoblast invasion, and acceptance of the semi-allogenic fetus simultaneously. As dysregulation of the immune system is associated with adverse pregnancy outcomes, we analysed first-trimester deciduas of pregnancies for immune parameters in later complicated pregnancies. Higher IL6 and macrophage mRNA expression, and lower ratios of regulatory macrophages were found in first-trimester deciduas of pregnancies later complicated with pregnancy-induced hypertension. Lower Gata3 (Th2) mRNA expression was found in deciduas of pregnancies with later foetal growth restriction. Our results suggest that adverse pregnancy outcomes are associated with immunological disturbances in first-trimester deciduas. (C) 2012 Elsevier Ltd. All rights reserved

Crossover from Poisson to Wigner-Dyson Level Statistics in Spin Chains with Integrability Breaking

We study numerically the evolution of energy-level statistics as an integrability-breaking term is added to the XXZ Hamiltonian. For finite-length chains, physical properties exhibit a cross-over from behavior resulting from the Poisson level statistics characteristic of integrable models to behavior corresponding to the Wigner-Dyson statistics characteristic of the random-matrix theory used to describe chaotic systems. Different measures of the level statistics are observed to follow different crossover patterns. The range of numerically accessible system sizes is too small to establish with certainty the scaling with system size, but the evidence suggests that in a thermodynamically large system an infinitesimal integrability breaking would lead to Wigner-Dyson behavior.Comment: 8 pages, 8 figures, Revtex

Correlative cryo super-resolution light and electron microscopy on mammalian cells using fluorescent proteins

Sample fixation by vitrification is critical for the optimal structural preservation of biomolecules and subsequent high-resolution imaging by cryo-correlative light and electron microscopy (cryoCLEM). There is a large resolution gap between cryo fluorescence microscopy (cryoFLM), ~400-nm, and the sub-nanometre resolution achievable with cryo-electron microscopy (cryoEM), which hinders interpretation of cryoCLEM data. Here, we present a general approach to increase the resolution of cryoFLM using cryo-super-resolution (cryoSR) microscopy that is compatible with successive cryoEM investigation in the same region. We determined imaging parameters to avoid devitrification of the cryosamples without the necessity for cryoprotectants. Next, we examined the applicability of various fluorescent proteins (FPs) for single-molecule localisation cryoSR microscopy and found that all investigated FPs display reversible photoswitchable behaviour, and demonstrated cryoSR on lipid nanotubes labelled with rsEGFP2 and rsFastLime. Finally, we performed SR-cryoCLEM on mammalian cells expressing microtubule-associated protein-2 fused to rsEGFP2 and performed 3D cryo-electron tomography on the localised areas. The method we describe exclusively uses commercially available equipment to achieve a localisation precision of 30-nm. Furthermore, all investigated FPs displayed behaviour compatible with cryoSR microscopy, making this technique broadly available without requiring specialised equipment and will improve the applicability of this emerging technique for cellular and structural biology. Microscopic imaging and technolog

The matter of the reproductive microbiome

The preconceptional presence of microbiota in the female and male reproductive organs suggests that fertilization is taking place in a nonsterile environment and contributes to reproductive success. The concept of embryonic development in a sterile uterus has also been challenged with recent reports of the existence of a microbiome of the placenta, amniotic fluid

Exploring Pompeii: discovering hospitality through research synergy

Hospitality research continues to broaden through an ever-increasing dialogue and alignment with a greater number of academic disciplines. This paper demonstrates how an enhanced understanding of hospitality can be achieved through synergy between archaeology, the classics and sociology. It focuses on classical Roman life, in particular Pompeii, to illustrate the potential for research synergy and collaboration, to advance the debate on hospitality research and to encourage divergence in research approaches. It demonstrates evidence of commercial hospitality activities through the excavation hotels, bars and taverns, restaurants and fast food sites. The paper also provides an example of the benefits to be gained from multidisciplinary analysis of hospitality and tourism