Influence of a Concurrent Exercise Training Intervention during Pregnancy on Maternal and Arterial and Venous Cord Serum Cytokines: The GESTAFIT Project

The aim of the present study was to analyze the influence of a supervised concurrent exercise-training program, from the 17th gestational week until delivery, on cytokines in maternal (at 17th and 35th gestational week, and at delivery) and arterial and venous cord serum. Fifty-eight Caucasian pregnant women (age: 33.5 +/- 4.7 years old, body mass index: 23.6 +/- 4.1kg/m(2)) from the GESTAFIT Project (exercise (n = 37) and control (n = 21) groups) participated in this quasi-experimental study (per-protocol basis). The exercise group followed a 60-min 3 days/week concurrent (aerobic-resistance) exercise-training from the 17th gestational week to delivery. Maternal and arterial and venous cord serum cytokines (fractalkine, interleukin (IL)-1 beta, IL-6, IL-8, IL-10, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha) were assessed using Luminex xMAP technology. In maternal serum (after adjusting for the baseline values of cytokines), the exercise group decreased TNF-alpha (from baseline to 35th week, p = 0.02), and increased less IL-1 beta (from baseline to delivery, p = 0.03) concentrations than controls. When adjusting for other potential confounders, these differences became non-significant. In cord blood, the exercise group showed reduced arterial IL-6 and venous TNF-alpha (p = 0.03 and p = 0.001, respectively) and higher concentrations of arterial IL-1 beta (p = 0.03) compared to controls. The application of concurrent exercise-training programs could be a strategy to modulate immune responses in pregnant women and their fetuses. However, future research is needed to better understand the origin and clearance of these cytokines, their role in the maternal-placental-fetus crosstalk, and the influence of exercise interventions on them

A Single Amino Acid Substitution, Found in Mammals with Low Susceptibility to Prion Diseases, Delays Propagation of Two Prion Strains in Highly Susceptible Transgenic Mouse Models

Specific variations in the amino acid sequence of prion protein (PrP) are key determinants of susceptibility to prion diseases. We previously showed that an amino acid substitution specific to canids confers resistance to prion diseases when expressed in mice and demonstrated its dominant-negative protective effect against a variety of infectious prion strains of different origins and characteristics. Here, we show that expression of this single amino acid change significantly increases survival time in transgenic mice expressing bank vole cellular prion protein (PrP C ), which is inherently prone to misfolding, following inoculation with two distinct prion strains (the CWD-vole strain and an atypical strain of spontaneous origin). This amino acid substitution hinders the propagation of both prion strains, even when expressed in the context of a PrP C uniquely susceptible to a wide range of prion isolates. Non-inoculated mice expressing this substitution experience spontaneous prion formation, but showing an increase in survival time comparable to that observed in mutant mice inoculated with the atypical strain. Our results underscore the importance of this PrP variant in the search for molecules with therapeutic potential against prion diseases

Variational Mean Field approach to the Double Exchange Model

It has been recently shown that the double exchange Hamiltonian, with weak antiferromagnetic interactions, has a richer variety of first and second order transitions than previously anticipated, and that such transitions are consistent with the magnetic properties of manganites. Here we present a thorough discussion of the variational Mean Field approach that leads to the these results. We also show that the effect of the Berry phase turns out to be crucial to produce first order Paramagnetic-Ferromagnetic transitions near half filling with transition temperatures compatible with the experimental situation. The computation relies on two crucial facts: the use of a Mean Field ansatz that retains the complexity of a system of electrons with off-diagonal disorder, not fully taken into account by the Mean Field techniques, and the small but significant antiferromagnetic superexchange interaction between the localized spins.Comment: 13 pages, 11 postscript figures, revte

Protective Effect of Val129-PrP against Bovine Spongiform Encephalopathy but not Variant Creutzfeldt-Jakob Disease

Bovine spongiform encephalopathy (BSE) is the only known zoonotic prion that causes variant Creutzfeldt-Jakob disease (vCJD) in humans. The major risk determinant for this disease is the polymorphic codon 129 of the human prion protein (Hu-PrP), where either methionine (Met129) or valine (Val129) can be encoded. To date, all clinical and neuropathologically confirmed vCJD cases have been Met129 homozygous, with the exception of 1 recently reported Met/Val heterozygous case. Here, we found that transgenic mice homozygous for Val129 Hu-PrP show severely restricted propagation of the BSE prion strain, but this constraint can be partially overcome by adaptation of the BSE agent to the Met129 Hu-PrP. In addition, the transmission of vCJD to transgenic mice homozygous for Val129 Hu-PrP resulted in a prion with distinct strain features. These observations may indicate increased risk for vCJD secondary transmission in Val129 Hu-PrP–positive humans with the emergence of new strain features

Radon and material radiopurity assessment for the NEXT double beta decay experiment

The Neutrino Experiment with a Xenon TPC (NEXT), intended to investigate the neutrinoless double beta decay using a high-pressure xenon gas TPC filled with Xe enriched in 136Xe at the Canfranc Underground Laboratory in Spain, requires ultra-low background conditions demanding an exhaustive control of material radiopurity and environmental radon levels. An extensive material screening process is underway for several years based mainly on gamma-ray spectroscopy using ultra-low background germanium detectors in Canfranc but also on mass spectrometry techniques like GDMS and ICPMS. Components from shielding, pressure vessel, electroluminescence and high voltage elements and energy and tracking readout planes have been analyzed, helping in the final design of the experiment and in the construction of the background model. The latest measurements carried out will be presented and the implication on NEXT of their results will be discussed. The commissioning of the NEW detector, as a first step towards NEXT, has started in Canfranc; in-situ measurements of airborne radon levels were taken there to optimize the system for radon mitigation and will be shown too.Comment: Proceedings of the Low Radioactivity Techniques 2015 workshop (LRT2015), Seattle, March 201

A hot sub-Neptune in the desert and a temperate super-Earth around faint M dwarfs: Color validation of TOI-4479b and TOI-2081b

We report the discovery and validation of two TESS exoplanets orbiting faint M dwarfs: TOI-4479b and TOI-2081b. We have jointly analyzed space (TESS mission) and ground based (MuSCAT2, MuSCAT3 and SINISTRO instruments) lightcurves using our multi-color photometry transit analysis pipeline. This allowed us to compute contamination limits for both candidates and validate them as planet-sized companions. We found TOI-4479b to be a sub-Neptune-sized planet ($R_{p}=2.82^{+0.65}_{-0.63}~\rm R_{\oplus}$) and TOI-2081b to be a super-Earth-sized planet ($R_{p}=2.04^{+0.50}_{-0.54}~\rm R_{\oplus}$). Furthermore, we obtained that TOI-4479b, with a short orbital period of $1.15890^{+0.00002}_{-0.00001}~\rm days$, lies within the Neptune desert and is in fact the largest nearly ultra-short period planet around an M dwarf known to date. These results make TOI-4479b rare among the currently known exoplanet population around M dwarf stars, and an especially interesting target for spectroscopic follow-up and future studies of planet formation and evolution.Comment: Accepted for publication in Astronomy&Astrophysic

The influence of rice husk ash addition on the properties of metakaolin-based geopolymers

This paper investigates the replacement of metakaolin (MK) with rice husk ash (RHA) in the production of alkali-activated binders or geopolymers. The influence of the RHA addition on compressive and flexural strength, as well as water absorption and apparent porosity were determined, in terms of the percentage of RHA in the mixture and molar ratios of the mixes. Fourier Transform Infrared (FTIR) spectroscopy and Energy Dispersive spectroscopy (EDS) were carried out to assess the changes in the microstructure of the geopolymer matrices with the RHA addition. Results have shown that RHA may be a supplementary precursor for geopolymers. The composition of the geopolymer matrices containing 0-40% RHA is very similar, which indicates that the additional Si provided by RHA is not incorporated to the geopolymer matrix. In addition, geopolymers with RHA content higher than 40% present a plastic behavior, characterized by extremely low strength and high deformation, which can be attributed to the formation of silica gel in formulations containing variable Si/Al ratio

iPS cell cultures from a Gerstmann-Sträussler-Scheinker patient with the Y218N PRNP mutation recapitulate tau pathology

Gerstmann-Sträussler-Scheinker (GSS) syndrome is a fatal autosomal dominant neurodegenerative prionopathy clinically characterized by ataxia, spastic paraparesis, extrapyramidal signs and dementia. In some GSS familiar cases carrying point mutations in the PRNP gene, patients also showed comorbid tauopathy leading to mixed pathologies. In this study we developed an induced pluripotent stem (iPS) cell model derived from fibroblasts of a GSS patient harboring the Y218N PRNP mutation, as well as an age-matched healthy control. This particular PRNP mutation is unique with very few described cases. One of the cases presented neurofibrillary degeneration with relevant Tau hyperphosphorylation. Y218N iPS-derived cultures showed relevant astrogliosis, increased phospho-Tau, altered microtubule-associated transport and cell death. However, they failed to generate proteinase K-resistant prion. In this study we set out to test, for the first time, whether iPS cell-derived neurons could be used to investigate the appearance of disease-related phenotypes (i.e, tauopathy) identified in the GSS patien

Mice lacking endoglin in macrophages show an impaired immune response

24 p.-9 fig.-1 tab. Ojeda Fernández, Luisa et al.Endoglin is an auxiliary receptor for members of the TGF-β superfamily and plays an important role in the homeostasis of the vessel wall. Mutations in endoglin gene (ENG) or in the closely related TGF-β receptor type I ACVRL1/ALK1 are responsible for a rare dominant vascular dysplasia, the Hereditary Hemorrhagic Telangiectasia (HHT), or Rendu-OslerWeber syndrome. Endoglin is also expressed in human macrophages, but its role in macrophage function remains unknown. In this work, we show that endoglin expression is triggered during the monocyte-macrophage differentiation process, both in vitro and during the in vivo differentiation of blood monocytes recruited to foci of inflammation in wild-type C57BL/6 mice. To analyze the role of endoglin in macrophages in vivo, an endoglin myeloid lineage specific knock-out mouse line (Engfl/flLysMCre) was generated. These mice show a predisposition to develop spontaneous infections by opportunistic bacteria. Engfl/flLysMCre mice also display increased survival following LPS-induced peritonitis, suggesting a delayed immune response. Phagocytic activity is impaired in peritoneal macrophages, altering one of the main functions of macrophages which contributes to the initiation of the immune response. We also observed altered expression of TGF-β1 target genes in endoglin deficient peritoneal macrophages. Overall, the altered immune activity of endoglin deficient macrophages could help to explain the higher rate of infectious diseases seen in HHT1 patients.This work was funded by: Ministerio de Economía y Competitividad of Spain (SAF2011-23475 to LMB; SAF2013-43421-R and SAF2010- 19222 to CB.Peer reviewe